Menarche-a journey into womanhood: age at menarche and health-related outcomes in East Asians.

STUDY QUESTION: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY: Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION: We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION: Our findings were specific to Han Taiwanese individuals, with genetic correlation analyses conducted in East Asians. Further research in other ethnic groups is necessary. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides insights into the genetic architecture of AAM and its health-related outcomes in East Asians, highlighting causal links between BMI/T2D and earlier AAM, which may suggest potential prevention strategies for early puberty. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by China Medical University, Taiwan (CMU110-S-17, CMU110-S-24, CMU110-MF-49, CMU111-SR-158, CMU111-MF-105, CMU111-MF-21, CMU111-S-35, CMU112-SR-30, and CMU112-MF-101), the China Medical University Hospital, Taiwan (DMR-111-062, DMR-111-153, DMR-112-042, DMR-113-038, and DMR-113-103), and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-039-063-MY3, MOST 111-2314-B-039-064-MY3, MOST 111-2410-H-039-002-MY3, and NSTC 112-2813-C-039-036-B). The funders had no influence on the data collection, analyses, or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Association of scrub typhus with the risk of venous thromboembolism and long-term mortality: a population-based cohort study.

BACKGROUND: The existing literature lacks studies examining the epidemiological link between scrub typhus and deep vein thrombosis (DVT) or pulmonary embolism (PE), and the long-term outcomes. The objective of this study is to explore the potential association between scrub typhus and the subsequent risk of venous thromboembolism, and long-term mortality. METHOD: This nationwide cohort study identified 10,121 patients who were newly diagnosed with scrub typhus. Patients with a prior DVT or PE diagnosis before the scrub typhus infection were excluded. A comparison cohort of 101,210 patients was established from the general population using a propensity score matching technique. The cumulative survival HRs for the two cohorts were calculated by the Cox proportional hazards model. RESULT: After adjusting for sex, age, and comorbidities, the scrub typhus group had an adjusted HR (95% CI) of 1.02 (0.80-1.30) for DVT, 1.11 (0.63-1.93) for PE, and 1.16 (1.08-1.25) for mortality compared to the control group. The post hoc subgroup analysis revealed that individuals younger than 55 years with a prior scrub typhus infection had a significantly higher risk of DVT (HR: 1.59; 95% CI: 1.12-2.25) and long-term mortality (HR: 1.75; 95% CI, 1.54-1.99). CONCLUSION: The scrub typhus patients showed a 16% higher risk of long-term mortality. For those in scrub typhus cohort below 55 years of age, the risk of developing DVT was 1.59 times higher, and the risk of mortality was 1.75 times higher. Age acted as an effect modifier influencing the relationship between scrub typhus and risk of new-onset DVT and death.

Relative and absolute inequalities in cerebrovascular disease mortality rates: exploring the influence of socioeconomic status and urbanization levels in Taiwan.

BACKGROUND/OBJECTIVE: Limited evidence exists regarding the socioeconomic inequalities in cerebrovascular disease (CBD) mortality at different urbanization levels. Therefore, this study was conducted to assess the socioeconomic inequalities and urbanization levels in township-based CBD mortality in Taiwan. METHODS: Socioeconomic variables, including the percentages of low-income households, individuals with a university education and above, and tax payments, were measured at the township level from 2011 to 2020. Urbanization was also determined by the national survey and divided into seven levels. Age-standardized mortality rate (ASMR) of CBD was calculated using a Geographic Information System (GIS) in 358 townships. The effects of socioeconomic variables and urbanization levels on relative and absolute inequalities in township-based CBD mortality rates were examined. RESULTS: Significant differences in ASMR of CBD were observed across all socioeconomic status indicators over the years. Higher proportions of low-income households were associated with higher ASMR of CBD. Conversely, there were negative correlations between higher proportions of individuals with a university education and above and tax payments with ASMR of CBD. The regression analysis indicated significant impacts of relative and absolute socioeconomic inequalities on ASMR of CBD. Additionally, a moderation effect of socioeconomic variables and urbanization on CBD mortality rates was observed, with rural areas showing sensitivity to these factors. CONCLUSION: Although ASMR of CBD showed significant decreases over time, socioeconomic inequalities in CBD mortality rates persist. Interventions targeting socioeconomic inequalities in health outcomes, especially in rural areas, are needed to address this issue.

Your height affects your health: genetic determinants and health-related outcomes in Taiwan.

BACKGROUND: Height is an important anthropometric measurement and is associated with many health-related outcomes. Genome-wide association studies (GWASs) have identified hundreds of genetic loci associated with height, mainly in individuals of European ancestry. METHODS: We performed genome-wide association analyses and replicated previously reported GWAS-determined single nucleotide polymorphisms (SNPs) in the Taiwanese Han population (Taiwan Biobank; n = 67,452). A genetic instrument composed of 251 SNPs was selected from our GWAS, based on height and replication results as the best-fit polygenic risk score (PRS), in accordance with the clumping and p-value threshold method. We also examined the association between genetically determined height (PRS251) and measured height (phenotype). We performed observational (phenotype) and genetic PRS251 association analyses of height and health-related outcomes. RESULTS: GWAS identified 6843 SNPs in 89 genomic regions with genome-wide significance, including 18 novel loci. These were the most strongly associated genetic loci (EFEMP1, DIS3L2, ZBTB38, LCORL, HMGA1, CS, and GDF5) previously reported to play a role in height. There was a positive association between PRS251 and measured height (p < 0.001). Of the 14 traits and 49 diseases analyzed, we observed significant associations of measured and genetically determined height with only eight traits (p < 0.05/[14 + 49]). Height was positively associated with body weight, waist circumference, and hip circumference but negatively associated with body mass index, waist-hip ratio, body fat, total cholesterol, and low-density lipoprotein cholesterol (p < 0.05/[14 + 49]). CONCLUSIONS: This study contributes to the understanding of the genetic features of height and health-related outcomes in individuals of Han Chinese ancestry in Taiwan.

The effectiveness of acupressure for managing postoperative pain in patients with thoracoscopic surgery: A randomized control trial.

PURPOSE: More than 86% patients experience moderate to severe pain after thoracoscopic surgery. A combination of diverse nonpharmacological pain relief methods is a developing trend for pain management. The purpose of this study was to explore the effect of acupressure in reducing pain after thoracoscopic surgery. DESIGN: A Randomized controlled study with purpose sampling was used for this study. Patients who underwent thoracoscopic surgery at a medical center in central Taiwan were enrolled. Study data was collected from September 2020 to April 2021 after the approval of the institutional review board. A total of 100 participants were randomized into two groups (49 and 51 in the experimental and control groups, respectively). METHODS: Participants in the experimental group received acupressure at the Neiguan (PC6) and Shenmen (HT7) acupoints thrice a day for 2 days, whereas those in the control group received routine treatment and did not receive acupressure. The measurement included questionnaires for the collection of general information, physiological information, and disease rating scale. The Visual Analogue Scale-Pain (VAS-P) was used to measure the severity of pain. SPSS statistical software was used for data analysis. Independent sample t-test and chi-squared test were used for descriptive statistics, and paired t-test and linear mixed model were used to examine the effect of acupressure in alleviating pain. FINDINGS: After acupressure intervention, the pain score of the experimental group was lower than that of the control group, and this difference was significant ß = 17.76, p < 0.001 on day 1 after intervention; ß = 19.80, p < 0.001 on day 2 after intervention. The postoperative pain score in the experimental group on day 2 after intervention was significantly lower than that in the control group (t = 2.039, p = 0.044). After the subjects received acupressure, pain index significantly decreased after considering the interaction between time and group (p < 0.001). Regardless of the type of surgery, there were significant differences in pain index when the interaction between time and group was considered (p < 0.001). CONCLUSIONS: This study provided an experimental basis that acupressure can help in pain management in patients after thoracoscopic surgery, and the pain relief results become more significant as the duration of intervention increases. CLINICAL RELEVANCE: Acupressure is effective in relieving postoperative pain in any type of thoracoscopic surgery. Nurses can use acupressure to help control pain in patients after thoracoscopic surgery.

Genetic risk score constructed from common genetic variants is associated with cardiovascular disease risk in type 2 diabetes mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) experience a two-fold increased risk of cardiovascular diseases. Genome-wide association studies (GWAS) have identified T2DM susceptibility genetic variants. Interestingly, the genetic variants associated with cardiovascular disease risk in T2DM Han Chinese remain to be elucidated. The present study aimed to investigate the genetic variants associated with cardiovascular disease risk in T2DM. METHODS: We performed bootstrapping, GWAS and an investigation of genetic variants associated with cardiovascular disease risk in a discovery T2DM cohort and in a replication cohort. The discovery cohort included 326 cardiovascular disease patients and 1209 noncardiovascular disease patients. The replication cohort included 68 cardiovascular disease patients and 317 noncardiovascular disease patients. The main outcome measures were genetic variants for genetic risk score (GRS) in cardiovascular disease risk in T2DM. RESULTS: In total, 35 genetic variants were associated with cardiovascular disease risk. A GRS was generated by combining risk alleles from these variants weighted by their estimated effect sizes (log odds ratio [OR]). T2DM patients with weighted GRS ≥ 12.63 had an approximately 15-fold increase in cardiovascular disease risk (odds ratio = 15.67, 95% confidence interval [CI] = 10.33-24.00) compared to patients with weighted GRS < 10.39. With the addition of weighted GRS, receiver-operating characteristic curves showed that area under the curve with conventional risk factors was improved from 0.719 (95% CI = 0.689-0.750) to 0.888 (95% CI = 0.866-0.910). CONCLUSIONS: These 35 genetic variants are associated with cardiovascular disease risk in T2DM, alone and cumulatively. T2DM patients with higher levels of weighted genetic risk score have higher cardiovascular disease risks.

Association of health checkups with health-related quality of life among public servants: a nationwide survey in Taiwan.

BACKGROUND: Preventive health checkups have gained in importance over the last decade. The association of health checkups and the number of diseases with health-related quality of life (HRQoL), including physical and mental health, remains unclear. We sought to investigate the aforementioned association among Taiwanese public servants. METHODS: A cross-sectional survey was conducted using randomized and multistage stratified cluster sampling based on proportional probabilistic sampling. The questionnaires addressed demographics, job characteristics, health behaviors, health status, 3 types of health checkups during the preceding 3 years (government-paid health checkup [GPHC], self-paid health checkup [SPHC], and no health checkup [NOHC]), and physical component summary (PCS) and mental component summary (MCS) scores of the Short-Form Health Survey. In total 11,454 middle-aged public servants were analyzed. A multivariate general linear model (GLM) was used to estimate PCS and MCS scores by using least square means. RESULTS: Health checkup types were associated with a significant difference in PCS scores among the public servants. Scores of PCS and MCS were both significantly higher in the GPHC group than in the NOHC group for those with no chronic diseases (51.20 vs. 50.66 [P = 0.008] and 46.23 vs. 45.58 [P = 0.02], respectively). Compared with the NOHC group, both scores of GPHC and SPHC groups were significantly associated with higher PCS scores for public servants with ≥ 2 chronic diseases (46.93 vs. 45.13 [P = 0.002] and 46.52 vs. 45.13 [P = 0.009], respectively). CONCLUSION: In Taiwan, public servants undergoing GPHCs are more likely to report higher PCS scores than are those undergoing SPHCs. It is crucial that encourage periodically using the health checkup to improve health status and HRQoL.

Primary hemiarthroplasty after unstable trochanteric fracture in elderly patients: mortality, readmission and reoperation.

BACKGROUND: Most unstable trochanteric fractures are treated with internal fixation and often with high complication rates. Hemiarthroplasty might be an alternative method in difficult condition, especially in unstable comminuted fracture in fragile bone. However, few have investigated the long-term outcomes after hemiarthroplasty for unstable trochanteric fracture. We conducted a population-based retrospective cohort study of trochanteric fracture after primary hemiarthroplasty using competing risk analysis on their long-term outcomes, including mortality, readmission and reoperation. METHODS: We studied a total of 2798 patients over 60 years old, with a mean age of 79 years, of which 68% are females and 67.23% have at least one comorbidity. They underwent a hemiarthroplasty for unstable trochanteric fracture during the period between January 1, 2000 and December 31, 2010 and were follow-up until the end of 2012, or death. Survival analysis and Cox model were used to characterize mortality. Competing risk analysis and Fine and Gray model were used to estimate the cumulative incidences of the first readmission and the first reoperation. RESULTS: The follow-up mortality rate for 1-year was 17.94%; 2-year, 29.76%; 5-year, 56.8%; and 10-year, 83.38%. The cumulative incidence of the first readmission was 16.4% for 1-year and 22.44% for 3-year. The cumulative incidence of the first reoperation was 13.87% for 1-year, 18.11% for 2-year, 25.79% for 5-year, and 38.24% for 10-year. Male gender, older age, higher Charlson Comorbidity Index (CCI) and lower insured amount were all risk factors for the overall mortality. Older age and higher CCI were risk factors for the first readmission. Older age was a protective factor for reoperation, which is likely due to the competing death. CONCLUSIONS: The mortality and revision rates after hemiarthroplasty for unstable trochanteric fracture are acceptable as a salvage procedure for this fragile sub-population.

KCNQ1 variants associate with hypertension in type 2 diabetes and affect smooth muscle contractility in vitro.

KCNQ1 encodes a potassium voltage-gated channel and represents a susceptibility locus for type 2 diabetes mellitus (T2DM). Here, we explored the association between KCNQ1 polymorphisms and hypertension risk in individuals with T2DM, as well as the role of KCNQ1 in vascular smooth muscle cell contraction in vitro. To investigate the relationship between KCNQ1 and the risk of developing hypertension in patients with T2DM, we divided the T2DM cohort into hypertension (n = 452) and non-hypertension (n = 541) groups. The Mann-Whitney U test, chi-square test, and multivariate regression analyses were used to assess the clinical characteristics and genotypic frequencies. In vitro studies utilized the rat aortic smooth muscle A10 cell line. Patients in the hypertension group were significantly older at the time of enrollment and had higher levels of body mass index, waist-to-hip ratio, and triglyceride than those in the non-hypertension group. The KCNQ1 rs3864884 and rs12576239 genetic variants were associated with hypertension in T2DM. KCNQ1 expression was lower in the individuals with the CC versus the CT and TT genotypes. Smooth muscle cell contractility was inhibited by treatment with a KCNQ1 inhibitor. These results suggest that KCNQ1 might be associated with hypertension in individuals with T2DM.

The association between continuous positive airway pressure therapy and liver disease development in obstructive sleep apnea/hypopnea syndrome patients: a nationwide population-based cohort study in Taiwan.

PURPOSE: Studies on the association between continuous positive airway pressure (CPAP) treatment and liver diseases such as non-alcoholic fatty liver disease (NAFLD) and cirrhosis in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) are limited. To the best of our knowledge, none exists that makes use of a national database in an Asian population. This study aims to evaluate the effects of CPAP treatment on patients with these two disorders in a retrospective, population-based study in Taiwan. METHODS: Using the Taiwan National Health Insurance claims database, this study collected the data of OSAHS patients diagnosed between 2000 and 2008 and divided them into CPAP treatment and non-CPAP treatment groups. All subjects were followed up until 2010. Liver disease incidence and risk were calculated. RESULTS: The CPAP group had a lower cumulative incidence rate of developing liver disease than the non-CPAP group within the observation periods (p < 0.001). After adjusting for age, gender, urbanization level, and comorbidities, the CPAP treatment group showed a lower risk of developing liver disease compared with the non-CPAP treatment group (sub-aHR of 0.66 (95% CI 0.55-0.80), p < 0.001). CONCLUSIONS: Our observations suggest that CPAP treatment may play an important role to delay the progression of liver disease in OSAHS patients and decreases the incidence of liver disease among OSAHS patients. Thus, CPAP therapy may be a feasible way to decrease the risk of liver disease among patients with OSAHS.

Validating the Quality of Life After Brain Injury Through Rasch Analysis.

OBJECTIVE: The Quality of Life after Brain Injury (QOLIBRI), a cross-cultural instrument, has been validated in several languages; however, traditional psychometric approaches have critical limitations. Therefore, we applied the Rasch model for validating the 37-item QOLIBRI scale among a Chinese population with traumatic brain injury. PARTICIPANTS AND SETTING: In total, 587 participants (mean age: 44.2 ± 15.4 years; women, 46.3%) were surveyed in neurosurgery departments at 6 hospitals in Taipei, Taiwan. MAIN OUTCOME MEASURE: The QOLIBRI. RESULTS: Of the 6 subscales of the QOLIBRI, 4 (cognition, self, daily life and autonomy, and social relationships) were unidimensional, valid, and reliable, whereas the remaining 2 (emotions and physical problems) exhibited poor unidimensionality, item and person reliability, and person-item targeting. Five items (energy, concentrating, getting out and about, sex life, and achievements) showed considerable differential item functioning among age groups, disability levels, and time since traumatic brain injury. CONCLUSION: According to item response theory, we identified psychometric issues in the emotions and physical problems subscales of the QOLIBRI as well as several differential item functioning items. Future research is required to determine whether similar results are observed in other language versions of the QOLIBRI or in other countries.

Mortality, readmission, and reoperation after hip fracture in nonagenarians.

BACKGROUND: Osteoporotic hip fractures are associated with high mortality and morbidity in people of advanced age; however, few studies have investigated the complication rates in nonagenarians. In this study, we applied a competing risk analysis to estimate the mortality, readmission, and reoperation rates after surgery for hip fracture among nonagenarians. METHODS: A total of 11,184 nonagenarians (aged ≥ 90) who received surgery for hip fracture during the period 1 January 1997 and 31 December 2010 were selected from Taiwan's National Health Insurance (NHI) database. Nonagenarians were followed up until the end of 2012, death, or the date they left the NHI program. Cumulative mortality was estimated using the Kaplan-Meier analysis and risk factors for mortality were investigated using a Cox proportional hazards model. Competing risk analysis was used to estimate cumulative incidence rates and to assess the risk factors for reoperation and readmission. RESULTS: The mortality rates were 29.5% at 1 year, 45.0% at 2 years and 78.1% at 5 years. The cumulative incidence rates of reoperation were 7.3% at 1 year, 9.2% at 2 years and 11.6% at 5 years whereas those of readmission were 18.9% at 1 month and 24.1% at 3 months. Significant risk factors for death included age, male gender, trochanteric fracture, and higher Charlson comorbidity index (CCI) whereas those for reoperation were age, cervical fracture and higher CCI. Furthermore, age, male gender, and higher CCI were risk factors for readmission. CONCLUSIONS: The overall 2-years mortality rate among nonagenarians in Taiwan was around 45%, the 2-years reoperation rate was around 9% and the 90-days medical complication rate was around 24%. High complication rates are associated with increased risk for death. Postoperative care to prevent medical complications is likely the most effective strategy to reduce mortality rates among nonagenarians with hip fracture.

The effects of surface neuromuscular electrical stimulation on post-stroke dysphagia: a systemic review and meta-analysis.

OBJECTIVE: In this study, we intended to evaluate whether swallow treatment with neuromuscular electrical stimulation is superior to that without neuromuscular electrical stimulation, and whether neuromuscular electrical stimulation alone is superior to swallow therapy. METHODS: We searched the PubMed and Scopus databases from their earliest record to 31 December 2014 for randomized and quasi-randomized controlled trials that used neuromuscular electrical stimulation to treat post-stroke dysphagia. The Jadad scale was used to assess the quality of the included studies. We extracted the mean differences and standard deviation (SD) between baseline and posttreatment or posttreatment mean and SD for selected outcomes measured in the experimental and control groups for subsequent meta-analyses. RESULTS: Eight studies were identified. For the comparison "swallow treatment with neuromuscular electrical stimulation vs. swallow treatment without neuromuscular electrical stimulation," we found a significant standardized mean difference (SMD) of 1.27 (95% confidence interval (CI) = 0.51-2.02, P = 0.001) with significant heterogeneity (I(2) = 85%). The meta-analysis for the comparison of neuromuscular electrical stimulation alone and swallow therapy demonstrated a non-significant SMD of 0.25 (95% CI = -0.16-0.65, P = 0.23) without significant heterogeneity (I(2) = 16%). CONCLUSION: Swallow treatment with neuromuscular electrical stimulation seems to be more effective than that without neuromuscular electrical stimulation for post-stroke dysphagia in the short term considering the limited number of studies available. Evidence was insufficient to indicate that neuromuscular electrical stimulation alone was superior to swallow therapy.

Incidence and excess mortality of hip fracture in young adults: a nationwide population-based cohort study.

BACKGROUND: This study assessed the incidence and excess mortality of hip fractures among inpatients aged 20-40 years in a nationwide population database in Taiwan. METHODS: Subjects were selected from Taiwan's National Health Insurance Research Database for the period 2001-2008 and were followed up until the end of 2010. A total of 4,523 subjects were admitted for the first time with primary diagnosis of hip fracture and treated with operation. RESULTS: The overall annual incidence, mortality, and standardized mortality ratio (SMR) decreased from 7.68 to 7.23 per 100,000, from 1.37 % to 0.94 %, and from 9.06 to 6.71, respectively, from 2001 to 2008. The 1-year, 2-year, 3-year, 5-year, and 10-year mortality rates were 1.28 %, 2.44 %, 3.54 %, 5.32 %, and 10.50 %, respectively for the whole cohort. The 1-year, 2-year, 3-year, 5-year, and 10-year SMRs were 8.33, 7.59, 7.28, 6.39, and 5.82, respectively, for the whole cohort. Risk factors for overall death were male gender, trochanteric fracture, hemiarthroplasty, and higher Charlson comorbidity index (CCI) scores. CONCLUSIONS: The high SMRs found in the present study suggest that young adults with former hip fracture should be closely followed up to prevent early mortality.

Responder Definition of a Patient-Reported Outcome Instrument for Laryngopharyngeal Reflux Based on the US FDA Guidance.

BACKGROUND: Different end-point measures may contribute to inconsistent therapeutic responses in relief of laryngopharyngeal reflux (LPR) symptoms. OBJECTIVES: We aimed to determine an a priori responder definition for a patient-reported outcome instrument, the Reflux Symptom Index (RSI), using an anchor-based method, to interpret individual treatment benefit in patients with LPR, on the basis of the US Food and Drug Administration guidance. METHODS: Patients with chronic laryngeal symptoms suggestive of LPR underwent twice-daily 40 mg esomeprazole treatment for 12 weeks. We used a 50% or more reduction in the primary laryngeal symptom at week 12, an empirical criterion, as an anchor to dichotomize the participants into two groups, and to establish a responder definition of the RSI score change. The optimal cutoff point of the RSI score change was determined on the basis of the maximal Youden index of the receiver operating characteristic analysis. RESULTS: The mean reduction in the RSI score was significantly greater in subjects with a 50% or more reduction in the primary laryngeal symptom than in those without (-11.0 ± 7.8 vs. -3.1 ± 8.3, P < 0.0001). A reduction of six points or more in the RSI score at week 12 was considered to be the responder definition with a sensitivity of 0.79 and a specificity of 0.70. CONCLUSIONS: We propose an a priori responder definition derived from an empirical criterion according to the Food and Drug Administration guidance: a reduction of six points or more in the RSI score at week 12. This preliminary estimate provides a clinically meaningful change at an individual level, although additional studies and validations across various languages are required.

A psychometric assessment of the St. George's respiratory questionnaire in patients with COPD using Rasch model analysis.

BACKGROUND: The St. George's Respiratory Questionnaire (SGRQ) was a widely used tool to assess disease impact on patients with obstructive airways disease. Although traditional methods have generally supported construct validity and internal consistency reliability of SGRQ, such methods cannot facilitate the evaluation of whether items are equivalent to different individuals. The purpose of this study is to rigorously examine the psychometric properties of the SGRQ in patients with chronic obstructive pulmonary disease (COPD) using Rasch model analysis. METHODS: A methodological research was conducted on SGRQ in a sample of 240 male patients with COPD recruited from the outpatient services in Central Taiwan. The psychometric properties of the SGRQ were examined using Rasch model analysis with a mixed rating scale and partial credit mode by Winsteps software. The level of matching between the item's difficulty and person's ability was analyzed by item-person targeting as well as ceiling and floor effects. Item-person maps were also examined for checking the location of the item's difficulty and person's measures along the same scale. Finally, the differential item functioning (DIF) was examined to measure group equivalence associated with age and disease's severity. RESULTS: Each of the three domains (Symptom, Activity, Impact) of the SGRQ was found to be unidimensionality. The person separation index ranged from 1.21 (Symptom domain) to 2.50 (Activity domain). There was a good targeting for the SGRQ domains, except the Impact domain (1.36). The percentage of ceiling and floor effects were below 10%, except the ceiling effect in the Impact domain (26.25%). From item-person maps, gaps of location of item corresponded to patient's ability were identified. The results have also showed that many items in SGRQ revealed age or severity related DIF. CONCLUSIONS: Except the Symptom domain of SGRQ, the others have a reliabile internal consistency and a good hierarchical structure. The results of Rasch model analysis can highlight aspects for scale improvement, such as gap, duplicate items or scale responses. There was some age or severity related DIF indicating somewhat unstable across different characteristics of group. IRB No.: DMR94-IRB-179.

Mortality and complications after hip fracture among elderly patients undergoing hemodialysis.

BACKGROUND: Osteoporotic hip fractures cause high mortality and morbidity in elderly adults. Compared to the general population, subjects with end-stage renal disease and hemodialysis often develop mineral bone disorders and have a higher risk for hip fractures. METHODS: We conducted a matched cohort study design and used competing risk analysis to estimate the cumulative incidence of the complication rate. Subjects aged greater than 60 years with hip fracture were selected from Taiwan's National Health Insurance Research Database covering a period from 1997 to 2007, and these subjects were followed up until 2009. We used the Kaplan-Meier method to estimate the overall survival and used the log-rank test and multiple Cox proportional hazards model to explore the risk factors for survival. The cumulative incidence of the first complication was estimated using competing risk analysis. RESULTS: Among hemodialysis subjects, the three-month, one-year, two-year and five-year mortality rates were 17.3 %, 37.2 %, 51.5 %, and 80.5 %, respectively; the one-year and five-year cumulative incidences of the first surgical complication were 14.2 % and 20.6 %, respectively; and the three-month cumulative incidence of the first medical complication was 24.1 %. Hemodialysis subjects presented a 2.32 times (95 % CI: 2.16-2.49) higher hazard ratio of overall death, 1.15 times (95 % CI: 1.01-1.30) higher sub-hazard ratio (sub-HR) of surgical complications, and 1.35 times (95 % CI: 1.21-1.52) higher sub-HR of the first medical complication than non-hemodialysis controls. CONCLUSIONS: The overall mortality and complication rates of hemodialysis subjects after surgery for hip fracture were significantly higher than those of non-hemodialysis subjects. Further prospective studies which include important risk factors are necessary to more precisely quantify the adjusted effect of hemodialysis.

Outcomes after fixation for undisplaced femoral neck fracture compared to hemiarthroplasty for displaced femoral neck fracture among the elderly.

BACKGROUND: This study compared the rates of mortality, medical complication, and reoperation after fixation surgery for displaced femoral neck fracture with those after hemiarthroplasty surgery for undisplaced femoral neck fracture using competing risk analysis in inpatients aged 60 years and above from a population database in Taiwan. METHODS: We identified 13,772 subjects who underwent fixation for undisplaced cervical fracture and 13,772 matched controls who underwent hemiarthroplasty for displaced cervical fracture from 1998 to 2007, and followed them up until the end of 2009. The outcomes of patients who received internal fixation for undisplaced fracture and those of patients who received hemiarthroplasty for displaced fracture were compared. RESULTS: The 3-month, 2-year, and 10-year mortality rates were 4.9%, 22.1%, and 67.1% for fixation, and 5.6%, 23.8%, and 71.0% for hemiarthroplasty, respectively. The 3-month, 2-year, and 10-year cumulative incidence rates of the first reoperation were 7.4%, 18.1%, and 27.7% for fixation and 6.3%, 12.0%, and 22.3% for hemiarthroplasty, respectively. The 3-month cumulative incidence rates of the first medical complication were 14.4% for fixation and 15.4% for hemiarthroplasty, respectively. Hemiarthroplasty had a 1.09 times (95% CI: 1.05-1.12) higher hazard ratio for overall death than fixation. However, fixation had a 1.36 times (95% CI: 1.29-1.43) higher subdistribution hazard ratio for first reoperation than hemiarthroplasty after adjusting for gender, age, and comorbidities. CONCLUSIONS: The short-term overall mortality and medical complication rate of fixation for undisplaced fracture were slightly lower than those of hemiarthroplasty for displaced fracture. However, the short-term cumulative incidence of first reoperation after fixation was significantly higher than that for hemiarthroplasty. Further prospective studies or clinical trials based on the competing risk model, and which include important risk factors, are necessary to quantify the adjusted effects more precisely.

Measurement equivalence and feasibility of the EORTC QLQ-PR25: paper-and-pencil versus touch-screen administration.

OBJECTIVE: We assessed the measurement equivalence and feasibility of the paper-and-pencil and touch-screen modes of administration of the Taiwan Chinese version of the EORTC QLQ-PR25, a commonly used questionnaire to evaluate the health-related quality of life (HRQOL) in patients with prostate cancer in Taiwan. METHODS: A cross-over design study was conducted in 99 prostate cancer patients at an urology outpatient clinic. Descriptive exact and global agreement percentages, intraclass correlation, and equivalence test based on minimal clinically important difference (MCID) approach were used to examine the equity of HRQOL scores between these two modes of administration. We also evaluated the feasibility of computerized assessment based on patients' acceptability and preference. Additionally, we used Rasch rating scale model to assess differential item functioning (DIF) between the two modes of administration. RESULTS: The percentages of global agreement in all domains were greater than 85% in the EORTC QLQ-PR25. All results from equivalence tests were significant, except for Sexual functioning, indicating good equivalence. Only one item exhibited DIF between the two modes. Although nearly 80% of the study patients had no prior computer-use experience, the overall proportion of acceptance and preference for the touch-screen mode were quite high and there was no significant difference across age groups or between computer-use experience groups. CONCLUSIONS: The study results showed that the data obtained from the modes of administration were equivalent. The touch-screen mode of administration can be a feasible and suitable alternative to the paper-and-pencil mode for assessment of patient-reported outcomes in patients with prostate cancer.

Validation of the quality of life after brain injury in Chinese persons with traumatic brain injury in Taiwan.

OBJECTIVE: To determine the psychometric properties of the Quality of Life After Brain Injury (QOLIBRI) in Chinese persons with traumatic brain injury (TBI) in Taiwan. PARTICIPANTS: Three hundred one patients with TBI were interviewed face-to-face at baseline; of these, 132 completed a follow-up assessment 1 year later. SETTINGS: Neurosurgery clinics of 6 teaching hospitals in northern Taiwan. MEASURE: The 37-item QOLIBRI, including 6 domains of Cognition, Self, Daily Life and Autonomy, Social Relationships, Emotions, and Physical Problems. RESULTS: A small percentage (<1%) of responses were missing, except the Sex Life item under the Social domain (5.9%). The QOLIBRI achieved adequate percentages for the floor value (0%-4%), ceiling value (1%-3.3%), internal consistency (0.79-0.95), and test-retest reliability (0.81-0.89). For construct validity, correlation coefficients (rs) for the QOLIBRI domains and selected clinical measures conceptually related to that domain were all 0.4 or more, except rs for QOLIBRI Cognition and Mini-Mental State Examination scores. A principal components analysis found that one item (Loneliness) of the Emotions domain did not converge with its corresponding domain of the original QOLIBRI (loading score <0.4). Effect sizes of responsiveness to changes in the Glasgow Outcome Scale-Extended over the 1-year period were clinically meaningful for all the QOLIBRI domains except the Emotions domain. CONCLUSION: With modifications to the Emotions domain, the QOLIBRI would be suitable for use with Chinese people in Taiwan who have TBI.