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Abstract We sought to evaluate the topographic risk factors for early myopic regression after small-incision lenticule extraction (SMILE). A retrospective case‒control study was conducted, and individuals who underwent SMILE surgery were enrolled. Among them, 406 and 14 eyes were categorized into the nonregression and regression groups, respectively. The preoperative and postoperative parameters in the two groups were collected, including spherical refraction (SE), axial length (AXL) and topographic data. A generalized linear model was adopted to analyze the difference in each parameter between the two groups. After 6 months, UCVA decreased in the regression group, and SE increased in the regression group (both P

BackgroundWe aim to evaluate lifestyle and nutritional factors that lead to dry eye disease (DED) in a depressed population using data from the Taiwan BioBank (TWB).MethodsA retrospective case–control study was conducted, and patients with depression based on a questionnaire were selected as the depression group. Each patient in the depression group was matched by age and sex to two individuals without depression, and a total of 3,754 and 7,508 patients constituted the depression and non-depression groups, respectively. Based on the questionnaire, the primary outcome was the presence of DED. Additionally, the chi-square test and interaction test were applied to survey the effect of lifestyle and nutritional factors on DED in the depression and non-depression groups.ResultsThere were 822 (21.90%) and 958 (12.76%) DED patients in the depression and non-depression groups, respectively, and the incidence of DED was significantly higher in the depression group (p

Abstract Background To evaluate the possible topographic and surgical risk factors for high postoperative residual astigmatism in patients who undergo small-incision lenticule extraction (SMILE) surgery and have different myopia degrees. Methods A retrospective cohort study was conducted, and patients who underwent SMILE surgery were enrolled. A total of 80 and 150 eyes from 40 to 75 individuals, respectively, were selected as the low myopia and high myopia groups. The demographic data, visual acuity, refraction, topographic parameters and surgical settings were recorded. Multiple linear regression with interaction tests were performed to survey the risk factors for high postoperative residual astigmatism in each group. Results Five (6.25%) and 9 (6.00%) eyes presented with high postoperative residual astigmatism in the low myopia and high myopia groups, respectively, but these differences were not significant (P = 0.569). A steep corneal curvature was correlated with a greater risk of high postoperative residual astigmatism in the low myopia group (P = 0.015), while a higher degree of cycloplegic cylinder power, steeper corneal curvature, greater topographic cylinder power, smaller optic zone and longer incision length were associated with a high rate of postoperative residual astigmatism in the high myopia group (all P

The aim of this study is to survey the effectiveness of preservative-free artificial tears containing hyaluronic acid (HA) on post-cataract surgery dry eye disease (DED) prevention. A retrospective cohort study was performed, and patients that received cataract surgeries were divided into either an HA group or non-HA group depending on the artificial tear they used. A total of 37 and 74 eyes were enrolled into the HA and non-HA groups, respectively, after the selection. The primary outcomes are postoperative superficial keratitis and multiple (>3) DED symptoms. The generalized linear model was utilized to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of primary outcomes between the two groups. There were 10 and 2 episodes of superficial keratitis in the non-HA group and HA group, respectively, and the HA group demonstrated a significantly lower incidence of superficial keratitis (p < 0.001). Moreover, 13 and 5 patients developed multiple DED symptoms in the non-HA and HA groups, and the HA group illustrated fewer multiple DED symptoms (p = 0.024). The lower preoperative tear break-up time (TBUT) was correlated with superficial keratitis in the HA group (p = 0.043), while old age, low preoperative TBUT and ocular surface staining were associated with superficial keratitis in the non-HA group (all p < 0.05). Lower preoperative TBUT was correlated with multiple DED symptoms in the HA group (p = 0.020), while female sex, low preoperative TBUT and any DED symptoms were associated with multiple DED symptoms in the non-HA group (all p < 0.05). In conclusion, the usage of preservative-free artificial tears containing HA is associated with lower postoperative DED events.

We aimed to survey the potential correlation between biometric parameters and postoperative outcomes after implanting extended depth-of-focus (EDOF) intraocular lenses (IOLs) and trifocal IOLs. A retrospective cohort study was conducted, and patients receiving EDOF or trifocal IOL implantations were included. In total, 36 and 26 eyes were enrolled in the EDOF and trifocal groups, respectively. The primary outcomes of this study were the postoperative uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), and spherical equivalent (SE). The generalized linear model was applied to evaluate the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) of primary outcomes in patients with different biometric characters. The final UDVA of the EDOF group was significantly better than that of the trifocal group (p = 0.020), and the UNVA and SE did not show significant differences between the two groups throughout the postoperative period (all p > 0.05). In a multivariable analysis, the UDVA was significantly better in the EDOF group than in the trifocal group (p = 0.038). For the subgroup analysis, the high axial length (AXL) value correlated to a lower postoperative UDVA in the EDOF group (both p < 0.05). Additionally, a large white-to-white (WTW) diameter was related to worse postoperative UNVA in the trifocal group (p = 0.042), and a high AXL was associated with higher SE in both the EDOF and trifocal groups (both p < 0.05). In conclusion, a high AXL correlates to worse postoperative outcomes in both the EDOF and trifocal IOLs, and trifocal IOL outcomes could be affected by large WTW diameters.

In this study, we aim to evaluate the risk factors of myopia undercorrection in recipients of second-generation keratorefractive lenticule extraction (KLEx) surgery. A retrospective case–control study was performed, and patients who received second-generation KLEx surgery were enrolled. The cases with myopia undercorrection were matched to non-myopia undercorrection cases with a 1:4 ratio according to age, and a total of 22 and 88 eyes were categorized into the undercorrection and control groups, respectively. Demographic, refractive, topographic, and surgical data were collected preoperatively. A generalized linear model was operated to evaluate the potential risk factors for myopia undercorrection. The uncorrected distance visual acuity (UDVA) at three months postoperation was significantly better in the control group (p = 0.006), and residual myopia and SE were significantly higher in the undercorrection group during the whole follow-up period (all p < 0.001). The UDVA value showed a trend of improvement in the control group (p < 0.001), and the changes to SE and residual myopia were significantly lower in the control group (both p < 0.001). Regarding the risk factors for myopia undercorrection in the whole population and the high-myopia population, a higher manifest sphere power, higher steep keratometry (K), higher topographic cylinder, lower central corneal thickness (CCT) at apex, higher CCT difference and lower residual stromal thickness (RST) correlated to myopia undercorrection (all p < 0.05). In the low-myopia population, only higher myopia and lower RST correlated to myopia undercorrection (both p < 0.05). In conclusion, a high-sphere power and irregular topographic pattern correlated to myopia undercorrection after the second KLEx surgery, especially for individuals with high myopia.

We aim to investigate the potential risk factors for undercorrection in those who have received extend depth-of-focus (EDOF) intraocular lens (IOL) implantation. A retrospective case-control study was conducted in which patients who had received one type of EDOF IOL implantation were included. The patients were divided into the residual group and non-residual group according to the final postoperative sphere power. The preoperative data include the refractive, topographic, endothelial, and biometric parameters obtained. A generalized linear model was generated to yield the adjusted odds ratio (aOR) and 95% confidence interval (CI) of each parameter of the residual myopia. One month postoperatively, the UDVA was better in the non-residual group than in the residual group (p = 0.010), and the final SE was significantly higher in the residual group than in the non-residual group (p < 0.001). In the multivariable analysis, the high preoperative cycloplegia sphere power, higher TCRP, higher corneal cylinder power, and longer AXL significantly correlated to the presence of postoperative residual myopia (all p < 0.05). Furthermore, the higher preoperative cycloplegia sphere power, higher TCRP, higher corneal cylinder power, longer AXL, larger ACD, and larger WTW were significantly associated with postoperative residual myopia in the high-myopia population (all p < 0.001), while the higher preoperative cycloplegia sphere power, higher TCRP, and longer AXL were related to postoperative residual myopia in the low-myopia population (all p < 0.05). In conclusion, high preoperative myopia and corneal refractive power correlate to high risk of residual myopia after EDOF IOL implantation, especially in the high-myopia population.

We aimed to evaluate the postoperative visual and refractive outcomes between the first- and second-generation keratorefractive lenticule extraction (KLEx) surgeries. A retrospective cohort study was conducted and patients who had received first- and second-generation KLEx surgeries were enrolled. A total of 80 and 80 eyes were categorized into the first and second KLEx groups after exclusion, respectively. The primary outcomes were the postoperative uncorrected distance visual acuity (UDVA), spherical equivalent (SE), and safety indexes. An independent t-test and generalized estimate equation were implemented to compare the primary outcomes between the two groups. After the KLEx surgery, the UDVA showed no significant difference between the two groups throughout the study period (all p > 0.05), and the postoperative SE and safety index were also statistically identical between the two groups during the follow-up interval (all p > 0.05). There was a similar trend of visual recovery between the two groups (aOR: 0.967; 95% CI: 0.892–1.143; p = 0.844), while the amplitude of the SE change was significantly lower in the second KLEx group (aOR: 0.760; 95% CI: 0.615–0.837; p = 0.005). Nine and two unintended initial dissection of the posterior plane (UIDPP) occurred intraoperatively in the first and second KLEx groups, respectively, and the second group showed a lower risk of UIDPP (p = 0.032). In conclusion, the efficiency, predictability, and safety are similar between first- and second-generation KLEx surgeries.

Our objective was to evaluate the topographic and surgical factors of early myopic regression between laser in situ keratomileusis (LASIK) and small-incision lenticule extraction (SMILE). A retrospective case–control study was conducted, and 368 and 92 eyes were enrolled in the LASIK and SMILE groups via propensity score matching (PSM). Visual acuity, refractive status, axial length, and topographic/surgical parameters were collected. Multiple linear regression was applied to the yield coefficient and the 95% confidence interval (CI) of the parameters. The cumulative incidence of early myopic regression was higher in the LASIK group (p < 0.001). In the SMILE group, a lower central corneal thickness (CCT) thinnest value and a higher corneal cylinder associated with early myopic regression were observed; meanwhile, in the LASIK group, a lower CCT thinnest value, a higher steep corneal curvature, a larger optic zone, and a lower flap thickness related to early myopic regression were observed (all p < 0.05). In the SMILE group, a higher CCT difference correlated with early myopic regression was observed compared to the LASIK group (p = 0.030), and higher steep corneal curvature and lower cap/flap thickness (both p < 0.05) correlated with early myopic regression were observed in the LASIK group compared to the SMILE group. In conclusion, CCT differences significantly influence early myopic regression in the SMILE group; meanwhile, corneal curvature and flap thickness affect early myopic regression principally in the LASIK group.

The increase in both the frequency and magnitude of natural disasters, coupled with recent advancements in artificial intelligence, has introduced prospects for investigating the potential of new technologies to facilitate disaster response processes. Preliminary Damage Assessment (PDA), a labor-intensive procedure necessitating manual examination of residential structures to ascertain post-disaster damage severity, stands to significantly benefit from the integration of computer vision-based classification algorithms, promising efficiency gains and heightened accuracy. Our paper proposes a Vision Transformer (ViT)-based model for classifying damage severity, achieving an accuracy rate of 95%. Notably, our model, trained on a repository of over 18,000 ground-level images of homes with damage severity annotated by damage assessment professionals during the 2020–2022 California wildfires, represents a novel application of ViT technology within this domain. Furthermore, we have open sourced this dataset—the first of its kind and scale—to be used by the research community. Additionally, we have developed a publicly accessible web application prototype built on this classification algorithm, which we have demonstrated to disaster management practitioners and received feedback on. Hence, our contribution to the literature encompasses the provision of a novel imagery dataset, an applied framework from field professionals, and a damage severity classification model with high accuracy.

Abstract Background and purpose The implantation of carotid artery stents prevents recurrent ischemic stroke in patients with carotid stenosis. This study aimed to investigate associations between change of ophthalmic artery flow (COAF) post carotid stenting and recurrent ischemic stroke, as well as the link toward the anterior and posterior circulations and patients’ prognosis after carotid stenting. Methods This retrospective, longitudinal cohort study recruited 87 left side carotid stenosed ischemic stroke patients undergoing left side carotid stenting between year of 2009 and 2013, and patients were followed up to 9 years after carotid procedures. Clinical data were derived from medical records. The primary outcome was stroke recurrence. Predictive factors were stenosis > 50% in one intracranial artery and ROAF. Kaplan–Meier and Cox regression analyses were used to identify risk factors associated with stroke recurrence. Results Among 87 included patients undergone left side carotid stent treatment, 44 had stroke recurrence within 3 years after carotid stenting. The recurrence group had significantly greater proportions of COAF after stenting (p = 0.001), and middle cerebral artery (MCA) and basilar artery or vertebral artery (BA/VA) stenosis > 50% (all p 50% (100%), followed by left MCA stenosis > 50% plus BA/VA stenosis > 50% (83.33%) or COAF (82.14%). Patients with bilateral MCA stenosis 50%, BA/VA stenosis > 50% and/or COAF. Carotid duplex and magnetic resonance angiography provide definitive information for prognosis prediction.

We aim to investigate the myopic control effect of high-concentration atropine (ATR) and dual-focus contact lenses (DFCLs). A retrospective cohort study was conducted. A total of 182 eyes in 91 individuals who used high-concentration ATR (0.125%) and another 70 eyes in 35 individuals who used DFCLs were enrolled in the ATR and DFCL groups, respectively. The primary outcomes were spherical equivalent refraction (SER) progression and axial length (AXL) elongation. The generalized estimate equation was utilized to yield the adjusted odds ratio (aOR) and 95% confidence interval (CI) of cycloplegic SER progression and AXL elongation between groups. According to the multivariable analysis, the change in cycloplegic SER progression was similar between the DFCL and ATR groups (aOR: 1.305, 95% CI: 0.247–2.515, p = 0.803). The DFCL group demonstrated a numerically higher rate of AXL elongation compared to the ATR group (aOR: 1.530, 95% CI: 0.980–1.894, p = 0.051). In the subgroup analysis, cycloplegic SER progression was insignificant between ATR and DFCL users in different subgroups (all p > 0.05). The DFCL patients with moderate astigmatism and high AXL (both p < 0.001) presented a high risk of AXL elongation. In conclusion, DFCL usage demonstrated similar myopic control of cycloplegic SER and AXL compared to high-concentration ATR, while DFCLs showed lower AXL control, mainly in patients with moderate astigmatism and high AXL.

Background: Ischemic stroke poses a major threat to human beings, and a prompt intravenous thrombolytic management remains the gold standard protocol for stroke sufferers. Although the role of thrombolytic therapy (r-tPA) for ischemic stroke patients and those with underlying impaired renal function has been advocated as effective treating strategy, there is still a lack of investigation as to finding out baseline important variables that are capable of early outcome prediction. Objectives: In this project, we hypothesize that the change of clinical chronic kidney disease (CKD) staging (delta stage = CKD stage after 3-month follow-up – CKD stage at admission) could serve as a crucial predictor of the prognosis of patients. Design: This is a cohort longitudinal retrospective study. Sources and Methods: A total of 765 cerebral artery ischemic stroke patients with impaired renal function were recruited and followed up for 1 year. Among them, 116 had received the thrombolytic treatment (r-tPA) after being evaluated at the triage in the emergency department and the rest had not (non-r-tPA). Propensity-matching was applied to compare the mortality between the r-tPA and non-r-tPA groups. Multiple logistic regression (LR) and decision tree (DT) algorithm were used to identify important prediction factors for mortality as well as the improvement in neurological function. Results: The 1-year mortality rates for r-tPA and non-r-tPA groups were 32.8% and 44.4%, respectively. The propensity-matched odds ratio of mortality for the r-tPA group compared with the non-r-tPA group is 0.469, with p = 0.003. Logistic regressions suggest that age, Hct, diabetes mellitus type 2, coronary artery disease, and delta stage are important factors for mortality for the non-r-tPA group, whereas age, diabetes mellitus type 2, chronic heart failure, hospital day, and delta stage are important factors for the r-tPA group. On the usage of antihypertensive drugs, ACEI/ARB was not associated with mortality ( p = 0.198), whereas the diuretic was, with odds ratio at 1.619 ( p = 0.025), indicating higher mortality after administration. Both LR and DT analyses indicate that delta stage is the most important predictor. For the r-tPA group, patients with delta stage ⩽0 had a 24% mortality, while that for delta stage >0 the mortality is 75%. For non-r-tPA patients, the corresponding mortalities were 30.9 and 66.3, respectively. Delta stage is also useful for predicting patients’ improvement of neurological function, assessed by NIHSS, mRS, and Barthel Index. The areas under the curve for the three assessments are 0.83, 0.835, and 0.663, respectively. Conclusion: Large-artery ischemic stroke patients who received thrombolytic treatment had significantly lower mortality, even when presenting underlying impaired renal function. The change of CKD staging (delta stage) is capable of acting as a powerful clinical baseline surrogate for both r-tPA and non-r-tPA patients in terms of early outcome prediction. Long-term use of diuretics could be potentially harmful to this group of patients. Moreover, delta stage correlates well with clinical long-term neurological functionality assessment (NIHSS, mRS, and Barthel index), which is helpful in aiding urgent clinical decision-making

Background: Previous studies suggested that vasomotor symptoms were associated with an increasing risk of coronary heart diseases (CHD) but not clear with menopausal symptoms other than vasomotor symptoms. Given the heterogeneity and interrelationship among menopausal symptoms, it is not easy to make causal inferences based on observational studies. We performed a Mendelian randomization (MR) to investigate the association of individual non-vasomotor menopausal symptoms and the risk of CHDs. Methods: A sample of 177,497 British women aged ≥51 years old (average age at menopause) without related cardiovascular diseases from the UK biobank is selected as our study population. Non-vasomotor menopausal symptoms, including anxiety, nervous, insomnia, urinary tract infection, fatigue, and vertigo, were selected as exposures based on the modified Kupperman index. Outcome variable is CHD. Results: In total, 54, 47, 24, 33, 22, and 81 instrumental variables were selected for anxiety, insomnia, fatigue, vertigo, urinary tract infection and nervous respectively. We conducted MR analyses of menopausal symptoms and CHD. Only insomnia symptoms increased the lifetime risk of CHD with OR 1.394 (p = 0.0003). There were no significant causal relationships with CHD and other menopausal symptoms. Insomnia near menopause age (45–50 years) does not increase the risk of CHD. However, postmenopausal (over 51) insomnia increases the risk of CHD. Conclusion: MR analyses support that among non-vasomotor menopausal symptoms, only insomnia symptoms may increase the lifetime risk of CHD. Insomnia at different ages near menopause has differential impacts on CHD risk.

Abstract Aims Women with menopausal symptoms show evidence of accelerated epigenetic ageing, vascular aging and low‐grade systemic inflammation status. However, data are limited regarding menopausal symptoms and risk of heart failure (HF). We aimed to explore the impact of menopausal symptoms on risk of HF. Methods We included 14 340 symptomatic menopausal women without a history of coronary heart disease (CHD) or HF from the Taiwan National Health Insurance Research Database as the experimental cohort. We included 14 340 asymptomatic women matched for age and comorbidities as controls. We surveyed possible comorbidity‐attributable risks of HF and assessed whether menopausal symptoms play a role in risk of HF. Additional analyses were conducted to ascertain the association of CHD and HF in different risk factor burdens categories in both cohorts and CHD was applied as a sensitivity analysis. Results The incidence of HF was not significantly lower in the experimental than in the control cohort (4.87 vs. 5.06 per 1000 person‐years, P = 0.336). Participants with a higher comorbidity burden had a proportionally increased risk of HF and CHD in both cohorts. The burden of risk factors had a greater impact on risk of HF in the control than in the experimental cohort (≥five risk factors, adjusted hazard ratio 25.69 vs. 14.75). Participants undergoing hormone therapy had no significant effect on the risk of HF, regardless of the presence or absence of menopausal symptoms. Subgroup analysis revealed that compared with the control cohort, the risk of HF in the experimental cohort did not increase significantly in all subgroups. Conclusions Menopausal symptoms were associated with CHD risk but not with risk of HF. Traditional risk factors rather than menopausal symptoms play important roles in the HF risk among middle‐aged women.

BackgroundDue to the affordability of whole-genome sequencing, the genetic association design can now address rare diseases. However, some common statistical association methods only consider homozygosity mapping and need several criteria, such as sliding windows of a given size and statistical significance threshold setting, such as P-value < 0.05 to achieve good power in rare disease association detection.MethodsOur region-specific method, called expanded maximal segmental score (eMSS), converts p-values into continuous scores based on the maximal segmental score (MSS) (Lin et al., 2014) for detecting disease-associated segments. Our eMSS considers the whole genome sequence data, not only regions of homozygosity in candidate genes. Unlike sliding window methods of a given size, eMSS does not need predetermined parameters, such as window size or minimum or maximum number of SNPs in a segment. The performance of eMSS was evaluated by simulations and real data analysis for autosomal recessive diseases multiple intestinal atresia (MIA) and osteogenesis imperfecta (OI), where the number of cases is extremely small. For the real data, the results by eMSS were compared with a state-of-the-art method, HDR-del (Imai et al., 2016).ResultsOur simulation results show that eMSS had higher power as the number of non-causal haplotype blocks decreased. The type I error for eMSS under different scenarios was well controlled, p < 0.05. For our observed data, the bone morphogenetic protein 1 (BMP1) gene on chromosome 8, the Violaxanthin de-epoxidase-related chloroplast (VDR) gene on chromosome 12 associated with OI, and the tetratricopeptide repeat domain 7A (TTC7A) gene on chromosome 2 associated with MIA have previously been identified as harboring the relevant pathogenic mutations.ConclusionsWhen compared to HDR-del, our eMSS is powerful in analyzing even small numbers of recessive cases, and the results show that the method can further reduce numbers of candidate variants to a very small set of susceptibility pathogenic variants underlying OI and MIA. When we conduct whole-genome sequence analysis, eMSS used 3/5 the computation time of HDR-del. Without additional parameters needing to be set in the segment detection, the computational burden for eMSS is lower compared with that in other region-specific approaches.

BACKGROUND:Invoices had been used in food product traceability, however, none have addressed the automated alarm system for food safety by utilizing electronic invoice big data. In this paper, we present an alarm system for edible oil manufacture that can prevent a food safety crisis rather than trace problematic sources post-crisis. MATERIALS AND METHODS:Using nearly 100 million labeled e-invoices from the 2013‒2014 of 595 edible oil manufacturers provided by Ministry of Finance, we applied text-mining, statistical and machine learning techniques to "train" the system for two functions: (1) to sieve edible oil-related e-invoices of manufacturers who may also produce other merchandise and (2) to identify suspicious edible oil manufacture based on irrational transactions from the e-invoices sieved. RESULTS:The system was able to (1) accurately sieve the correct invoices with sensitivity >95% and specificity >98% via text classification and (2) identify problematic manufacturers with 100% accuracy via Random Forest machine learning method, as well as with sensitivity >70% and specificity >99% through simple decision-tree method. CONCLUSION:E-invoice has bright future on the application of food safety. It can not only be used for product traceability, but also prevention of adverse events by flag suspicious manufacturers. Compulsory usage of e-invoice for food producing can increase the accuracy of this alarm system.

Background/Purpose: Chromium and nickel are important soil pollutants in Taiwan. Previously, we showed that blood chromium levels correlated strongly with soil chromium levels. Our observation that many patients with dry eyes or a dry mouth came from areas where soils contain high chromium levels prompted us to investigate whether incidence and prevalence of SS are higher in areas where soils contain high levels of heavy metals. Methods: We used a database from national health insurance (NHI) to study the epidemiology of SS. It was ascertained by at least 3 hospital visits with the diagnosis within 12 months. We then compared the results with the information about heavy metal contents in farm soils. Results: The incidence of SS was significantly increased (3.6 fold) in the areas where soils contained high levels of chromium and nickel. In contrast, lead, copper, or arsenic did not show such a strong association. Conclusion: Both the prevalence and incidence of SS are significantly increased in areas where soils contain high levels of chromium and nickel. Whether heavy metal, particularly chromium or nickel is a novel environmental risk factor for sicca syndrome needs more studies to confirm. Keywords: Sicca syndrome, Chromium, Nickel, Epidemiology

Heavy metal pollution in farm soils is a problem in some parts of Taiwan. Copper can be a factor associated with increased disease activities of rheumatoid arthritis (RA). Thus, the aim of this study was to investigate whether copper pollution in farm soils is associated with worsened RA. Methods: Clinical parameters from 122 RA patients were collected from a medical center in central Taiwan. Levels of heavy metals in the blood were measured using inductively coupled plasma mass spectrometry. Levels of copper in farm soils were retrieved from a national survey. These data were analyzed to find the factors related to RA disease activities. Results: RA patients living where farm soils contained high levels of copper had increased white blood cell counts, erythrocyte sedimentation rate, and disease activity score 28, compared with patients living where copper levels were low. Among the nine types of heavy metal measured in the study, blood levels of copper and nickel correlated with erythrocyte sedimentation rate. Conclusion: Our cross-sectional data suggest a correlation between RA disease activity and the level of copper at township farm soils samples. Further longitudinal studies using more rigorous methodologies are warranted to examine whether this correlation is causal.

Traumatic brain injury (TBI) is an important cause of death and disability worldwide. The relationship between TBI and kidney diseases is largely unknown.We aimed to determine whether TBI is associated with long-term adverse renal outcomes. We performed a nationwide, population-based, propensity score-matched cohort study of 32,152 TBI patients and 128,608 propensity score-matched controls. Data were collected by the National Health Insurance Research Database of Taiwan from 2000 to 2012. Our clinical outcomes were chronic kidney disease (CKD), end-stage renal disease (ESRD) and the composite endpoint of ESRD or all-cause mortality.The incidence rate of CKD was higher in the TBI than in the control cohort (8.99 vs. 7.4 per 1000 person-years). The TBI patients also showed higher risks of CKD (adjusted hazard ratio [aHR] 1.14, 95% confidence interval [CI] 1.08-1.20; P < 0.001) and composite endpoints (aHR 1.08, 95% CI 1.01-1.15; P = 0.022) than the control groups, but the ESRD was not significantly different between the groups. In subgroup analyses, the risks of incident CKD and composite endpoints were significantly raised in TBI patients aged < 65 years and/or without comorbidities. However, the risks of both CKD and composite outcome were little affected by the severity of TBI.TBI has a modest but significant effect on incident CKD and composite endpoint, but not on ESRD alone. TBI patients under 65 are at greater risk of CKD and composite outcome than their older counterparts.

There is little information about the association between stroke and kidney diseases. We aimed to investigate the impact of stroke on long-term renal outcomes.In this large population-based retrospective cohort study, we identified 100,353 subjects registered in the National Health Insurance Research Database of Taiwan from January 1, 2000, through December 31, 2012, including 33,451 stroke patients and 66,902 age-, sex- and Charlson's comorbidity index score-matched controls.The incidence rate of chronic kidney disease (CKD) was higher in the stroke than in the control cohort (17.5 vs. 9.06 per 1000 person-years). After multivariate adjustment, the risk of developing CKD was significantly higher in patients with stroke (adjusted hazard ratio [aHR] 1.43, 95% confidence interval [CI] 1.36-1.50, P

This study aimed to elucidate whether or not high-risk clusters of oral cancer (OC) incidence spatially correlate with the prevalence rates of betel quid chewing (BQC) and cigarette smoking (CS) in Taiwan. The spatial autocorrelation and potential clusters of OC incidence among the 307 townships and heavy metal content of soil throughout Taiwan were identified using the Anselin’s local Moran test. Additionally, the spatial correlations among the incidence of OC, the prevalence of BQC and CS and heavy metal content of soil were determined based on a comparison of spatial clusters. High-risk OC (Moran’s I = 0.638, P

Oral cancer is one of the fastest increasing malignancies in Taiwan. Among the counties on the island, Changhua has been ranked in the top three in the list of oral cancer incidence. This study was performed to better characterize the epidemiology of oral cancer in Changhua county. Methods: We used the complete registered records of oral cancer from the Department of Health data bank, and studied the trends in incidence rate, age of distribution, and anatomic sites of oral cancer in Taiwan. In addition, we correlated the incidence rate with known risk factors (betel quid chewing, smoking, and alcohol drinking) by regression analysis. Results: Among neoplasms, oral cancer is one of the fastest increasing malignancies in Taiwan. In the past two decades from 1982 to 2001, Taiwan had an alarming 5.3-fold increase in the incidence of male oral cancer. Among the 23 counties, Changhua has ranked top in oral cancer incidence in recent years. The incidence of male oral cancer in Changhua is also among the highest in the world (45.07/105/year in 2001). The most common site was the buccal mucosa, while it was the tongue in other counties. Finally, Changhua was the only outlier in our regression model, indicating that possible interference factors may interact with oral cancer incidence and prevalence of betel quid chewing in Changhua. Conclusion: We conclude that the high incidence and buccal mucosa preponderance of oral cancer in Changhua may have an exceptionally close relation with patients' betel quid chewing habit, and other unknown etiologic factors may also be present locally. [J Formos Med Assoc 2007;106(3):225-233]

Third-party payer systems are consistently associated with health care cost escalation. Taiwan’s single-payer, universal coverage National Health Insurance (NHI) adopted global budgeting (GB) to achieve cost control. This study captures ophthalmologists’ response to GB, specifically service volume changes and service substitution between low-revenue and high-revenue services following GB implementation, the subsequent Bureau of NHI policy response, and the policy impact. De-identified eye clinic claims data for the years 2000, 2005, and 2007 were analyzed to study the changes in Simple Claim Form (SCF) claims versus Special Case Claims (SCCs). The 3 study years represent the pre-GB period, post-GB but prior to region-wise service cap implementation period, and the post-service cap period, respectively. Repeated measures multilevel regression analysis was used to study the changes adjusting for clinic characteristics and competition within each health care market. SCF service volume (low-revenue, fixed-price patient visits) remained constant throughout the study period, but SCCs (covering services involving variable provider effort and resource use with flexibility for discretionary billing) increased in 2005 with no further change in 2007. The latter is attributable to a 30% cap negotiated by the NHI Bureau with the ophthalmology association and enforced by the association. This study demonstrates that GB deployed with ongoing monitoring and timely policy responses that are designed in collaboration with professional stakeholders can contain costs in a health insurance–financed health care system.

BACKGROUND:Despite dengue dynamics being driven by complex interactions between human hosts, mosquito vectors and viruses that are influenced by climate factors, an operational model that will enable health authorities to anticipate the outbreak risk in a dengue non-endemic area has not been developed. The objectives of this study were to evaluate the temporal relationship between meteorological variables, entomological surveillance indices and confirmed dengue cases; and to establish the threshold for entomological surveillance indices including three mosquito larval indices [Breteau (BI), Container (CI) and House indices (HI)] and one adult index (AI) as an early warning tool for dengue epidemic. METHODOLOGY/PRINCIPAL FINDINGS:Epidemiological, entomological and meteorological data were analyzed from 2005 to 2012 in Kaohsiung City, Taiwan. The successive waves of dengue outbreaks with different magnitudes were recorded in Kaohsiung City, and involved a dominant serotype during each epidemic. The annual indigenous dengue cases usually started from May to June and reached a peak in October to November. Vector data from 2005-2012 showed that the peak of the adult mosquito population was followed by a peak in the corresponding dengue activity with a lag period of 1-2 months. Therefore, we focused the analysis on the data from May to December and the high risk district, where the inspection of the immature and mature mosquitoes was carried out on a weekly basis and about 97.9% dengue cases occurred. The two-stage model was utilized here to estimate the risk and time-lag effect of annual dengue outbreaks in Taiwan. First, Poisson regression was used to select the optimal subset of variables and time-lags for predicting the number of dengue cases, and the final results of the multivariate analysis were selected based on the smallest AIC value. Next, each vector index models with selected variables were subjected to multiple logistic regression models to examine the accuracy of predicting the occurrence of dengue cases. The results suggested that Model-AI, BI, CI and HI predicted the occurrence of dengue cases with 83.8, 87.8, 88.3 and 88.4% accuracy, respectively. The predicting threshold based on individual Model-AI, BI, CI and HI was 0.97, 1.16, 1.79 and 0.997, respectively. CONCLUSION/SIGNIFICANCE:There was little evidence of quantifiable association among vector indices, meteorological factors and dengue transmission that could reliably be used for outbreak prediction. Our study here provided the proof-of-concept of how to search for the optimal model and determine the threshold for dengue epidemics. Since those factors used for prediction varied, depending on the ecology and herd immunity level under different geological areas, different thresholds may be developed for different countries using a similar structure of the two-stage model.

Globally, influenza infection is a major cause of morbidity and mortality in the elderly, who are suggested to be the major target group for trivalent influenza vaccine (TIV) vaccination by World Health Organization. In spite of an increasing trend in vaccine coverage rates in many countries, the effect of vaccination among the elderly in reducing hospitalization and mortality remains controversial. In this study, we conducted a historical cohort study to evaluate the temporal pattern of influenza-associated morbidity among persons older than 64 years over a decade. The temporal patterns of influenza-associated morbidity rates among the elderly older than 64 years indicated that Taiwan's elderly P&I outpatient visits have been decreasing since the beginning of the 1999-2000 influenza season; however, hospitalization has been increasing despite significant increases in vaccine coverage. The propensity score logistic regression model was implemented to evaluate the source of bias and it was found that the TIV-receiving group had a higher propensity score than the non-receiving group (P

Advances in biotechnology have resulted in large-scale studies of DNA methylation. A differentially methylated region (DMR) is a genomic region with multiple adjacent CpG sites that exhibit different methylation statuses among multiple samples. Many so-called "supervised" methods have been established to identify DMRs between two or more comparison groups. Methods for the identification of DMRs without reference to phenotypic information are, however, less well studied. An alternative "unsupervised" approach was proposed, in which DMRs in studied samples were identified with consideration of nature dependence structure of methylation measurements between neighboring probes from tiling arrays. Through simulation study, we investigated effects of dependencies between neighboring probes on determining DMRs where a lot of spurious signals would be produced if the methylation data were analyzed independently of the probe. In contrast, our newly proposed method could successfully correct for this effect with a well-controlled false positive rate and a comparable sensitivity. By applying to two real datasets, we demonstrated that our method could provide a global picture of methylation variation in studied samples. R source codes to implement the proposed method were freely available at http://www.csjfann.ibms.sinica.edu.tw/eag/programlist/ICDMR/ICDMR.html.

Objectives: Metabolic factors are major risk factors for non-alcoholic fatty liver disease although other factors may also contribute to development of fatty liver disease. We explored the association between exposure to soil heavy metals and prevalence of fatty liver disease. Methods: We retrospectively analysed data from patients diagnosed with fatty liver disease in 2014 at the Health Evaluation Centre of Chang-Hua Christian Hospital (n=1137). We used residency data provided in the records of the Health Evaluation Centre and data for soil metal concentrations from a nationwide survey conducted by the Environmental Protection Administration of Taiwan. We studied the correlations between the severity of fatty liver disease and concentrations of soil heavy metals (arsenic, mercury, cadmium, chromium, copper, nickel, lead and zinc). Results: The prevalence of moderate to severe fatty liver disease in our study was 26.5%. Using univariate and multivariate analysis, we demonstrated that the presence of soil heavy metals was a significant risk factor for fatty liver disease in men (OR 1.83, 95% CI 1.161 to 2.899, p=0.009). With stratification by body mass index (BMI) and gender, lean men with a BMI <24 kg/m² were the most susceptible to soil heavy metals (OR 5.059, 95% CI 1.628 to 15.728, p<0.05). Conclusions: Our study suggested a significant association between exposure to soil heavy metals and fatty liver disease in lean men. [ABSTRACT FROM AUTHOR]

Purpose To estimate the incidence and clinical characteristics of rhegmatogenous retinal detachment (RRD) in Taiwan. Methods This was a nationwide, population-based retrospective study of patients with RRD. Data from the Taiwan National Health Insurance Research Database (2000-2012), which represents 4% of the total population in Taiwan, were analysed. The incidence of RRD and its associations with age, gender and high myopia were analysed. Results A total of 2359 patients with RRD (1336 men and 1023 women) were identified from 2000-2012. The age-standardised incidence rate of RRD over the 13-year period was 16.40±1.06 per 105 person-years (18.89 and 13.93 for men and women, respectively, p<0.0001) and an average age of 47.76±0.67 years. The incidence in both genders had an obvious peak at 50-69 years of age, and a secondary peak at 20-29 years in women. Concomitant high myopia was noted in 10.51% of the patients, with an average of 39.72±1.95 years. Prior cataract extraction was noted in 11.06% of the patients, including 17.64% in the patients RRD aged ≥50 years and 4.04% in those younger than 50 years. The average age of the patients with pseudophakic or aphakic RRD was 61.85 ±1.60 years. Conclusions The annual incidence of RRD in Taiwan is comparable to most Western countries, with a relatively younger mean age. The male patients were more susceptible to retinal detachment in almost all age groups. Retinal detachment in patients with high myopia was associated with a younger age at onset. [ABSTRACT FROM AUTHOR]

Background Genome-wide association studies have been successful in identifying common genetic variants for human diseases. However, much of the heritable variation associated with diseases such as Parkinson's disease remains unknown suggesting that many more risk loci are yet to be identified. Rare variants have become important in disease association studies for explaining missing heritability. Methods for detecting this type of association require prior knowledge on candidate genes and combining variants within the region. These methods may suffer from power loss in situations with many neutral variants or causal variants with opposite effects. Results We propose a method capable of scanning genetic variants to identify the region most likely harbouring disease gene with rare and/or common causal variants. Our method assigns a score at each individual variant based on our scoring system. It uses aggregate scores to identify the region with disease association. We evaluate performance by simulation based on 1000 Genomes sequencing data and compare with three commonly used methods. We use a Parkinson's disease case-control dataset as a model to demonstrate the application of our method. Our method has better power than CMC and WSS and similar power to SKAT-O with wellcontrolled type I error under simulation based on 1000 Genomes sequencing data. In real data analysis, we confirm the association of α-synuclein gene (SNCA) with Parkinson's disease (p = 0.005). We further identify association with hyaluronan synthase 2 (HAS2, p = 0.028) and kringle containing transmembrane protein 1 (KREMEN1, p = 0.006). KREMEN1 is associated with Wnt signalling pathway which has been shown to play an important role for neurodegeneration in Parkinson's disease. Conclusions Our method is time efficient and less sensitive to inclusion of neutral variants and direction effect of causal variants. It can narrow down a genomic region or a chromosome to a disease associated region. Using Parkinson's disease as a model, our method not only confirms association for a known gene but also identifies two genes previously found by other studies. In spite of many existing methods, we conclude that our method serves as an efficient alternative for exploring genomic data containing both rare and common variants. [ABSTRACT FROM AUTHOR]

Background: Combining data from different ethnic populations in a study can increase efficacy of methods designed to identify expression quantitative trait loci (eQTL) compared to analyzing each population independently. In such studies, however, the genetic diversity of minor allele frequencies among populations has rarely been taken into account. Due to the fact that allele frequency diversity and population-level expression differences are present in populations, a consensus regarding the optimal statistical approach for analysis of eQTL in data combining different populations remains inconclusive. Results: In this report, we explored the applicability of a constrained two-way model to identify eQTL for combined ethnic data that might contain genetic diversity among ethnic populations. In addition, gene expression differences resulted from ethnic allele frequency diversity between populations were directly estimated and analyzed by the constrained two-way model. Through simulation, we investigated effects of genetic diversity on eQTL identification by examining gene expression data pooled from normal quantile transformation of each population. Using the constrained two-way model to reanalyze data from Caucasians and Asian individuals available from HapMap, a large number of eQTL were identified with similar genetic effects on the gene expression levels in these two populations. Furthermore, 19 single nucleotide polymorphisms with inter-population differences with respect to both genotype frequency and gene expression levels directed by genotypes were identified and reflected a clear distinction between Caucasians and Asian individuals. Conclusions: This study illustrates the influence of minor allele frequencies on common eQTL identification using either separate or combined population data. Our findings are important for future eQTL studies in which different datasets are combined to increase the power of eQTL identification. [ABSTRACT FROM AUTHOR]

Background: To explore if exposures to specific heavy metals in the environment is a new risk factor of oral cancer, one of the fastest growing malignancies in Taiwan, in addition to the two established risk factors, cigarette smoking and betel quid chewing. Methods: This is an observational study utilized the age-standardized incidence rates of oral cancer in the 316 townships and precincts of Taiwan, local prevalence rates of cigarette smoking and betel quid chewing, demographic factors, socio-economic conditions, and concentrations in farm soils of the eight kinds of heavy metal. Spatial regression and GIS (Geographic Information System) were used. The registration contained 22,083 patients, who were diagnosed with oral cancer between 1982 and 2002. The concentrations of metal in the soils were retrieved from a nation-wide survey in the 1980s. Results: The incidence rate of oral cancer is geographically related to the concentrations of arsenic and nickel in the patients' residential areas, with the prevalence of cigarette smoking and betel quid chewing as controlled variables. Conclusions: Beside the two established risk factors, cigarette smoking and betel quid chewing, arsenic and nickel in farm soils may be new risk factors for oral cancer. These two kinds of metal may involve in the development of oral cancer. Further studies are required to understand the pathways via which metal in the farm soils exerts its effects on human health. [ABSTRACT FROM AUTHOR]

Background: Betel quid chewing and cigarette smoking are two of the risk factors for some dental diseases as well as oral cavity cancer in Taiwan. The aim of the study was to quantify these factors in oral cavity cancer patients and compare the prevalence of these factors in patients and the general population. Methods: A questionnaire was designed to evaluate betel quid chewing, cigarette smoking and alcohol drinking in 254 patients, who had squamous cell carcinoma of the oral cavity, and had received surgical excision at the Changhua Christian Hospital in Taiwan between 2005 and 2008. The results were compared with those of population of Taiwan, based on a nation-wide survey with sample of 26 744 people. Results: We found that more than 80% of the male patients were both betel quid chewers and smokers. Few women in the survey practiced betel quid chewing, cigarette smoking or alcohol drinking. Chewers and smokers usually started the habits in their 20s. On average, a chewer patient consumed 12 508 betel quid pieces per year, for 23.3 years before the diagnosis of oral cavity cancer, making the total amount of betel quid consumed nearly 310 000 pieces; and a smoker patient consumed 469 packs per year, for 28.5 years before diagnosis, making the total number of about 14 000 packs. Patients with both habits had the age at diagnosis 4 years earlier than the smoker-only patients, 5 years earlier than the chewer-only patients, and 6 years earlier than those with neither. Conclusions: On average, it took two decades of betel quid chewing and cigarette smoking before oral cavity cancer diagnosis, making the life-time consumption of these substances an astonishing amount. Betel quid chewing and cigarette smoking patients are more likely to be diagnosed with oral cavity cancer at a younger age than those who have just one habit or none. Patients that smoke more are not only more likely to be diagnosed at a younger age, but also at an advanced stage. [ABSTRACT FROM AUTHOR]

Background: Association testing is a powerful tool for identifying disease susceptibility genes underlying complex diseases. Technological advances have yielded a dramatic increase in the density of available genetic markers, necessitating an increase in the number of association tests required for the analysis of disease susceptibility genes. As such, multiple-tests corrections have become a critical issue. However the conventional statistical corrections on locus-specific multiple tests usually result in lower power as the number of markers increases. Alternatively, we propose here the application of the longest significant run (LSR) method to estimate a region-specific p-value to provide an index for the most likely candidate region. Results: An advantage of the LSR method relative to procedures based on genotypic data is that only p-value data are needed and hence can be applied extensively to different study designs. In this study the proposed LSR method was compared with commonly used methods such as Bonferroni's method and FDR controlling method. We found that while all methods provide good control over false positive rate, LSR has much better power and false discovery rate. In the authentic analysis on psoriasis and asthma disease data, the LSR method successfully identified important candidate regions and replicated the results of previous association studies. Conclusion: The proposed LSR method provides an efficient exploratory tool for the analysis of sequences of dense genetic markers. Our results show that the LSR method has better power and lower false discovery rate comparing with the locus-specific multiple tests. [ABSTRACT FROM AUTHOR]

The primary objective of a Phase I cancer clinical trial is to determine the maximum tolerated dose of a drug. The “failure probability” was proposed and used as a constraint to help identify a suitable initial dose range. The maximum tolerated dose was then determined based on a 3 + 3 cohort-based escalation scheme. Multiple simulations were conducted, and the method was evaluated according to the required sample size and accuracy and precision of maximum tolerated dose estimate. The results indicated that the median of the initial dose range suggested using a failure probability is a suitable initial dose regardless of the dose escalation sequence used for a cancer Phase I study. This initial dose required a smaller sample size and resulted in less bias of the estimated maximum tolerated dose compared with a commonly used initial dose, that is, 10% of the lethal dose. We tested our approach using real dose and toxicity outcome data from two published Phase I studies. These results indicate that adding a failure probability constraint into the calculation of the initial dose range will improve the efficiency of Phase I cancer trials. [ABSTRACT FROM AUTHOR]