Sleep apnea (SA) has been associated with cognitive impairment. However, no data regarding the risk of dementia in patients with SA has been reported in the general population. This retrospective ...matched-control cohort study was designed to estimate and compare the risk of dementia in SA and non-SA patients among persons aged 40 and above over a 5-year period follow-up.
We conducted a nationwide 5-year population-based study using data retrieved from the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan. The study cohort comprised 1414 patients with SA aged 40 years who had at least 1 inpatient service claim or 1 ambulatory care claim. The comparison cohort comprised 7070 randomly selected patients who were matched with the study group according to sex, age, and index year. We performed Cox proportional-hazards regressions to compute the 5-year dementia-free survival rates after adjusting for potentially confounding factors.
The SA patients in this study had a 1.70-times greater risk of developing dementia within 5 years of diagnosis compared to non-SA age- and sex-matched patients, after adjusting for other risk factors (95% confidence interval (CI) = 1.26-2.31; P < .01). For the gender-dependent effect, only females with SA were more likely to develop dementia (adjust HR: 2.38, 95% CI =1.51-3.74; P < .001). For the age-dependent effect of different genders, males with SA aged 50-59 years had a 6.08 times greater risk for developing dementia (95% CI = 1.96-18.90), and females with SA aged ≥ 70 years had a 3.20 times greater risk of developing dementia (95% CI =1.71-6.00). For the time-dependent effect, dementia may be most likely to occur in the first 2.5 years of follow-up (adjusted HR:2.04, 95% CI =1.35-3.07).
SA may be a gender-dependent, age-dependent, and time-dependent risk factor for dementia.
Atopic Dermatitis (AD) is a chronic and relapsing skin disease. The medications for treating AD are still limited, most of them are topical corticosteroid creams or antibiotics. The current study ...attempted to discover potential AD treatments by integrating a gene network and genomic analytic approaches. Herein, the Single Nucleotide Polymorphism (SNPs) associated with AD were extracted from the GWAS catalog. We identified 70 AD-associated loci, and then 94 AD risk genes were found by extending to proximal SNPs based on
> 0.8 in Asian populations using HaploReg v4.1. Next, we prioritized the AD risk genes using
pipelines of bioinformatic analysis based on six functional annotations to identify biological AD risk genes. Finally, we expanded them according to the molecular interactions using the STRING database to find the drug target genes. Our analysis showed 27 biological AD risk genes, and they were mapped to 76 drug target genes. According to DrugBank and Therapeutic Target Database, 25 drug target genes overlapping with 53 drugs were identified. Importantly, dupilumab, which is approved for AD, was successfully identified in this bioinformatic analysis. Furthermore, ten drugs were found to be potentially useful for AD with clinical or preclinical evidence. In particular, we identified filgotinub and fedratinib, targeting gene JAK1, as potential drugs for AD. Furthermore, four monoclonal antibody drugs (lebrikizumab, tralokinumab, tocilizumab, and canakinumab) were successfully identified as promising for AD repurposing. In sum, the results showed the feasibility of gene networking and genomic information as a potential drug discovery resource.
Nephrolithiasis is a common disease affecting almost all populations, with an increasing prevalence over the past decades. Previous studies revealed several functional polymorphisms associated with ...the pathogenesis of nephrolithiasis. However, data on Asian populations are limited. In this study, three candidate polymorphisms were selected from previous studies to investigate the correlations with nephrolithiasis in a Taiwanese population. In total, 454 nephrolithiasis patients were recruited from Kaohsiung Medical University Hospital, with SNP frequency for 1513 subjects of general population from the Taiwan Biobank (TWB) as a genotypic reference. Results revealed that subjects with minor TT genotype at rs1256328 (alkaline phosphatase, liver/bone/kidney (ALPL)) have higher susceptibility to nephrolithiasis (odds ratio (OR) = 2.03, p = 0.0013). In addition, subjects carrying the minor AA genotype at rs12654812 (regulator of G protein signaling 14 (RGS14)) have higher susceptibility to nephrolithiasis (OR = 1.91, p = 0.0017). Among nephrolithiasis patients, subjects with GG at rs7627468 (calcium-sensing receptor (CASR)) have lower pH level in urine (p = 0.0088). Importantly, rs7627468 is associated with the expressions of IQCB1 and EAF2. rs12654812 could influence the expression of RGS14 itself, MXD3, and FGFR4. In summary, this study successfully validated the genetic roles of rs1256328 and rs12654812 in human nephrolithiasis.
Asthma is a common and heterogeneous disease characterized by chronic airway inflammation. Currently, the two main types of asthma medicines are inhaled corticosteroids and long-acting ...β2-adrenoceptor agonists (LABAs). In addition, biological drugs provide another therapeutic option, especially for patients with severe asthma. However, these drugs were less effective in preventing severe asthma exacerbation, and other drug options are still limited. Herein, we extracted asthma-associated single nucleotide polymorphisms (SNPs) from the genome-wide association studies (GWAS) and phenome-wide association studies (PheWAS) catalog and prioritized candidate genes through five functional annotations. Genes enriched in more than two categories were defined as "biological asthma risk genes." Then, DrugBank was used to match target genes with FDA-approved medications and identify candidate drugs for asthma. We discovered 139 biological asthma risk genes and identified 64 drugs targeting 22 of these genes. Seven of them were approved for asthma, including reslizumab, mepolizumab, theophylline, dyphylline, aminophylline, oxtriphylline, and enprofylline. We also found 17 drugs with clinical or preclinical evidence in treating asthma. In addition, eleven of the 40 candidate drugs were further identified as promising asthma therapy. Noteworthy,
is considered a target for asthma drug repurposing based on its high target scores. Through in silico drug repurposing approach, we identified sarilumab and satralizumab as the most promising drug for asthma treatment.
Intravenous immunoglobulin (IVIG) is the treatment of choice in Kawasaki disease (KD). IVIG is used to prevent cardiovascular complications related to KD. However, a proportion of KD patients have ...persistent fever after IVIG treatment and are defined as IVIG resistant.
To develop a risk scoring system based on genetic markers to predict IVIG responsiveness in KD patients, a total of 150 KD patients (126 IVIG responders and 24 IVIG nonresponders) were recruited for this study. A genome-wide association analysis was performed to compare the 2 groups and identified risk alleles for IVIG resistance. A weighted genetic risk score was calculated by the natural log of the odds ratio multiplied by the number of risk alleles. Eleven single-nucleotide polymorphisms were identified by genome-wide association study. The KD patients were categorized into 3 groups based on their calculated weighted genetic risk score. Results indicated a significant association between weighted genetic risk score (groups 3 and 4 versus group 1) and the response to IVIG (Fisher's exact
value 4.518×10
and 8.224×10
, respectively).
This is the first weighted genetic risk score study based on a genome-wide association study in KD. The predictive model integrated the additive effects of all 11 single-nucleotide polymorphisms to provide a prediction of the responsiveness to IVIG.
Association between endometriosis and ovarian cancer has been well established. Nonetheless, endometriosis may also be associated with endometrial cancer because of shared etiological mechanisms of ...both estrogen stimulation and chronic inflammation; however, the association between these 2 disorders has rarely been investigated.
The National Health Insurance Research Databases in Taiwan were retrieved and analyzed. The case cohort consisted of patients with a diagnosis of endometriosis between January 1997 and December 2000 (N = 15,488). For the construction of control cohort, 8 age- and sex-matched control patients for every patient in the case cohort were selected using a random sampling method (n = 123,904). All subjects were tracked for 10 years from the date of entry to identify whether they had developed endometrial cancer. The Cox proportional hazards regression model was used to evaluate 10-year event occurrence of endometrial cancer.
During the 10-year follow-up period, 392 participants developed endometrial cancer, with 104 (0.7%) distributed in the case cohort and 288 (0.2%) in the control cohort. Multivariable Cox regression modeling demonstrates a higher risk for developing endometrial cancer in the case cohort than in the control cohort (adjusted hazard ratio aHR, 2.83; 95% confidence interval CI, 1.495.35; P < 0.01). Age at diagnosis of endometriosis shows a moderator effect: when 40 years or younger, the risk for developing endometrial cancer was comparable between the case cohort and the control cohort (aHR, 1.42; 95% CI, 0.55-3.70; P = 0.226), whereas when older than 40 years, the risk for developing endometrial cancer was higher in the former group than in the latter group (aHR, 7.08; 95% CI, 2.33-21.55; P = 0.007).
Patients diagnosed with endometriosis may harbor an increased risk for developing endometrial cancer in their later life. Closer monitoring is advised for this patient population.
Kawasaki disease (KD) is characterized by systemic vasculitis with unknown etiology. Previous studies from Japan indicated that a gene polymorphism of ITPKC (rs28493229) is responsible for ...susceptibility to KD. We collected DNA samples from 1,531 Taiwanese subjects (341 KD patients and 1,190 controls) for genotyping ITPKC. In this study, no significant association was noted for the ITPKC polymorphism (rs28493229) between the controls and KD patients, although the CC genotype was overrepresented. We further combined our data with previously published case/control KD studies in the Taiwanese population and performed a meta-analysis. A significant association between rs28493229 and KD was found (Odds Ratio:1.36, 95% Confidence Interval 1.12-1.66). Importantly, a significant association was obtained between rs28493229 and KD patients with aneurysm formation (P = 0.001, under the recessive model). Taken together, our results indicated that C-allele of ITPKC SNP rs28493229 is associated with the susceptibility and aneurysm formation in KD patients in a Taiwanese population.
Chronic rhinosinusitis (CRS) can cause an obstruction of the tubal orifice and thereby compromise ventilation of the middle ear. The resulting negative pressure in the middle ear may, in turn, lead ...to the formation of an eardrum retraction pocket and subsequent acquired cholesteatoma. This study hypothesizes that CRS may increase the risk of cholesteatoma.
To evaluate the risk of cholesteatoma in patients with CRS.
This study used a nationwide, population-based claims database to test the hypothesis that CRS may increase the risk of cholesteatoma. The Longitudinal Health Insurance Database of Taiwan was used to compile data from (1) 12 670 patients with newly diagnosed CRS between January 1, 1997, and December 31, 2002, and (2) a comparison cohort of 63 350 matched individuals without CRS, resulting in a CRS vs control ratio of 1:5. Data analysis was performed from June 1 to October 27, 2015. Each patient was followed up for 8 years to identify those in whom cholesteatoma subsequently developed. The Kaplan-Meier method was used to determine the cholesteatoma-free survival rate, and the log-rank test was used to compare survival curves. Cox proportional hazards regression models were used to compute the 8-year hazard ratios (HRs).
Diagnosis of cholesteatoma.
Among the 76 020 patients enrolled in this study, 35 220 (46.3%) were female; mean (SD) age was 27.57 (22.03) years. A total of 209 patients developed cholesteatoma, 66 (101 084 person-years) individuals from the CRS cohort and 143 (506 540 person-years) from the comparison cohort were diagnosed with cholesteatoma during the 8-year follow-up period. The incidence of cholesteatoma per 1000 person-years was more than twice as high among patients with CRS (0.65; 95% CI, 0.50-0.81 person-years) than among those without CRS (0.28; 95% CI, 0.24-0.33). The absolute difference in the incidence density between CRS and non-CRS group was 0.37 (95% CI, 0.21-0.53) per 1000 patient-years. After adjusting for potential confounders, patients with CRS had a 69% increased risk of cholesteatoma within 8 years, compared with those without CRS (HR, 1.69; 95% CI, 1.23-2.32). Patients with CRS presented a significantly lower 8-year cholesteatoma-free survival rate than did those in the comparison group. The absolute difference in the 8-year cholesteatoma-free survival rate between the CRS and non-CRS groups was 0.0029 (95% CI, 0.0016-0.0043).
This is the first large-scale study, to date, to demonstrate a prospective link between CRS and the subsequent development of cholesteatoma within a follow-up period of 8 years. The purpose of the study was to draw attention to the possibility of development of cholesteatoma among patients with CRS. Because that possibility exists, clinicians should keep this association in mind as well as the importance of a thorough head and neck examination.
Single-nucleotide polymorphisms (SNPs) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC, rs28493229) and caspase-3 (CASP3, rs113420705) are associated with susceptibility to KD in Japanese and ...Taiwanese populations. This study was conducted to investigate the involvement of these 2 SNPs in the risk for intravenous immunoglobulin (IVIG) resistance and coronary artery lesion (CAL) in Taiwanese population. A total of 340 KD patients were subjected to assess by the identification of 2-locus genes model. A combinatorial association between ITPKC (rs28493229) and CASP3 (rs113420705) was found in CAL formation (P = 0.0227, OR: 3.06). KD patients with high-risk genotype had a trend of overrepresentation in IVIG resistance compared with individual SNPs. Our findings suggest the existence of genetic factors affecting patients' risk for CAL formation and IVIG responsiveness in a Taiwanese population.
This study aims to evaluate the relationship between traumatic brain injury (TBI) and sleep disorders (SDs). We first initiated a questionnaire-based clinical survey to assess sleep problems in the ...early stage after a TBI, followed by a population-based cohort study to evaluate the long-term risk of SDs in TBI patients. For short-term clinical survey, mild (m)TBI patients and healthy controls were recruited to evaluate the sleep quality and daytime sleepiness using the Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) within two weeks after a TBI. For long-term observation, a 5-year nationwide population-based cohort study that utilized a large administrative database was conducted. In the short-term survey, 236 mTBI patients and 223 controls were analyzed. Total scores of the PSQI and ESS were significantly higher in mTBI patients than in the controls. In the long-term cohort study, 6932 TBI cases and 34,660 matched controls were included. TBI cases had a 1.36-fold greater risk of SDs compared to the non-TBI controls during the 5-year follow-up period. Results showed that patients with TBI had a significantly higher risk of SDs than did controls both in the early stage and during a 5-year follow-up period.
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