The Epidemiology of Entamoeba histolytica Infection and Its Associated Risk Factors among Domestic and Imported Patients in Taiwan during the 2011-2020 Period.

Background and Objectives: Amebiasis remains an important public health problem worldwide, and immigration and increased international travel have affected incident disease cases. This study assesses the prevalence of Entamoeba histolytica in Taiwan between 2011 and 2020 by analyzing data from surveillance programs conducted by the Centers for Disease Control of Taiwan (TCDC) on laboratory-confirmed cases. Materials and Methods: The E. histolytica infection-related data reported to the National Infectious Diseases Statistics System at the TCDC from 1 January 2011 to 31 December 2020 were collected, including age, gender, place of residence, and the geographic season of exposure for each case. Results: In total, 3066 cases with E. histolytica infections were included in our analysis. Among them, 1735 (57%) cases were imported, and 1331 (43%) were locally acquired. The average annual incidence rate of E. histolytica infections in Taiwan between 2011 and 2020 was 10.6 and 16.1 per 1,000,000 patients. There were statistical differences in gender, age group, and place of residence (p < 0.001) by the source distribution of cases. Also, these differences were found every year (p < 0.05). There were statistical differences in gender and age group (p < 0.001) by place of residence (p < 0.001). The only difference between the distribution of cases and age group was in gender (p < 0.001). Eight patients with amebiasis died, and the fatality rate was 0.3% (8/3066), of whom 75% (6/8) were male, and 75% (6/8) were over 45 years old. This study demonstrates that multiple linear regression analysis shows positive associations between NO2 concentration and amebiasis cases (B value = 2.569, p = 0.019), O3 concentration and amebiasis cases (B value = 0.294, p = 0.008), and temperature and amebiasis cases (B value = 1.096, p = 0.046). Conclusions: This study is the first report of confirmed E. histolytica cases from TCDC surveillance data between 2011 and 2020. This study showed the importance of long periods, air pollutants, and geographically comprehensive analysis for estimating the effect of amebiasis transmission in Taiwan's populations.

Carbon Monoxide Poisoning and Chronic Kidney Disease Risk: A Nationwide, Population-Based Study.

INTRODUCTION: Patients with carbon monoxide poisoning (COP) commonly have long-term morbidities. However, it is not known whether patients with COP exhibit an increased risk of developing chronic kidney disease (CKD) and whether hyperbaric oxygen therapy (HBOT) alters this risk. METHODS: This study identified 8,618 patients who survived COP and 34,464 propensity score-matched non-COP patients from 2000 to 2013 in a nationwide administrative registry. The primary outcome was the development of CKD. The association between COP and the risk of developing CKD was estimated using a Cox proportional hazards regression model; the cumulated incidence of CKD among patients stratified by HBOT was evaluated using a Kaplan-Meier analysis. RESULTS: After adjusting for covariates, the risk of CKD was 6.15-fold higher in COP patients than in non-COP controls. Based on the subgroup analyses, regardless of demographic characteristics, environmental factors, and comorbidities, the COP cohort exhibited an increased risk of developing CKD compared with the controls. The cumulative incidence of CKD in COP patients did not differ between the HBOT and non-HBOT groups (p = 0.188). CONCLUSIONS: COP might be an independent risk factor for developing CKD. Thus, clinicians should enhance the postdischarge follow-up of kidney function among COP patients.

Risk factors for in-hospital mortality and acute kidney injury in neonatal-pediatric patients receiving extracorporeal membrane oxygenation.

BACKGROUND: Acute kidney injury (AKI) is the most frequent complication in critically ill neonatal and pediatric patients receiving extracorporeal membrane oxygenation (ECMO) support. This study analyzed risk factors for in-hospital mortality and the incidence of AKI in neonatal and pediatric patients received ECMO support. METHODS: We reviewed the medical records of 105 neonatal and 171 pediatric patients who received ECMO support at the intensive care unit (ICU) of a tertiary care university hospital between January 2008 and December 2015. Demographic, clinical, and laboratory data were retrospectively collected as survival and AKI predictors, utilizing the Kidney Disease Improving Global Outcome (KDIGO) consensus definition for AKI. RESULTS: In the 105 neonatal and 171 pediatric patients, the overall in-hospital mortality rate were 58% and 55% respectively. The incidence of AKI at post-ECMO 24 h were 64.8% and 61.4%. A greater KDIGO24-h severity was associated with a higher in-hospital mortality rate (chi-square test; p < 0.01) and decreased survival rate (log-rank tests, p < 0.01). In univariate logistic regression analysis of in-hospital mortality, the CVP level at post ECOMO 24-h increased odds ratio (OR) (OR = 1.27 [1.10-1.46], p = 0.001) of in-hospital mortality in neonatal group; as for pediatric group, elevated lactate (OR = 1.12 [1.03-1.20], p = 0.005) and PT (OR = 1.86 [1.17-2.96], p = 0.009) increased OR of in-hospital mortality. And the KDIGO24h stage 3 had the strongest association with in-hospital mortality in both neonatal (p = 0.005) and pediatric (p = 0.001) groups. In multivariate OR of neonatal and pediatric groups were 4.38 [1.46-13.16] (p = 0.009) and 3.76 [1.70-8.33] (p = 0.001), respectively. CONCLUSION: AKI was a significant risk factor for in-hospital mortality in the neonatal and pediatric patients who received ECMO support. A greater KDIGO24-h severity was associated with higher mortality rates and decreased survival rate in both neonatal and pediatric groups. Of note, KDIGO24h can be an easy and early tool for the prognosis of AKI in the neonatal and pediatric patients.

Association between hypertensive pregnancy disorders and future risk of stroke in Taiwan: a Nationwide population-based retrospective case-control study.

BACKGROUND: The incidence of female stroke has increased gradually and has begun occurring at a younger age in recent years. Given that women live longer than men, stroke would cause more negative and longer-term impacts on the rest of the lives of women. There are few related studies on Asian women. We aimed to evaluate stroke risk in Asian women following hypertensive pregnancy disorders. METHODS: Using the Taiwan National Health Insurance database, we designed a retrospective study that included pregnant women between 2000 and 2013. We selected an age-matched control group of women without hypertensive pregnancy disorders at a 1:3 ratio. The endpoint was any episode of stroke; otherwise, the patients were tracked until December 31, 2013. After the index date until the end of 2013, Cox proportional hazards analysis was used to compare the risk of incident stroke. The risk factors for stroke were determined using Cox proportional regression to calculate the hazard ratio (HR) compared with the control group. RESULTS: During the follow-up period, the Kaplan-Meier analysis indicated that patients with hypertensive pregnancy disorders had a significantly higher risk of developing stroke than did patients without hypertensive pregnancy disorders (log-rank test P < 0.001). Multivariate Cox regression analysis demonstrated that the case group had a 2.134-fold increased risk of stroke (HR = 2.134; 95% CI = 1.817-2.505; P < 0.001). CONCLUSION: Our study provided evidence of an increased risk of stroke in patients with hypertensive pregnancy disorders. Compared with those without such disorders, the patients who had experienced the disorders had a 2.134-fold (P < 0.001) higher risk of developing stroke in the future.

Tuberculosis increases the risk of peripheral arterial disease: A nationwide population-based study.

BACKGROUND AND OBJECTIVE: According to several studies, tuberculosis (TB) may be involved in the pathogenesis of cardiovascular disease. However, the relationship between TB and peripheral arterial disease (PAD) has not been studied. The aim of this study was to investigate whether patients with TB exhibit an increased risk of developing PAD. METHODS: The data assessed in this national population-based cohort study were obtained from the Taiwan National Health Insurance Database from 2000 to 2010. Patients with newly diagnosed TB were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. The non-TB cohort was randomly frequency-matched to the TB cohort at a ratio of 2:1 according to age, sex and index year. Cox's proportional hazards regression models were used to analyse the risk of PAD. RESULTS: We enrolled 14 350 patients with TB and 28 700 controls in this study. The risk of PAD was 3.93-fold higher in the patients with TB than in the non-TB controls after adjusting for age, sex, co-morbidities and socio-economic status. Based on the subgroup analysis, the TB cohort exhibited an increased risk of developing PAD compared with the non-TB cohort, regardless of age, sex, co-morbidities and socio-economic status. Patients with TB had a higher risk of developing PAD than healthy control subjects after 1 year of follow-up. CONCLUSION: Patients with TB have a significantly higher risk of developing PAD than patients without TB. TB should be considered when evaluating a patient's risk of developing PAD.

A functional polymorphism in the promoter region of TLR3 is associated with susceptibility to end-stage renal disease.

BACKGROUND/AIMS: End-stage renal disease (ESRD) is simultaneously associated with immune activation, systemic inflammation and immune deficiency. Toll-like receptor 3 (TLR3), a receptor for viral double-stranded RNA, is involved in immune cell activation in renal diseases and may contribute to chronic inflammatory disease progression. To date, effects of TLR3 polymorphisms on ESRD remain unknown. Therefore, we determined the predictive value of TLR3 polymorphisms and further functionally studied ESRD. METHODS: We performed a case-control association study and genotyped 616 ESRD patients and 813 healthy controls. Patients were genotyped for -7C/A, 1377C/T and 1234C/T polymorphisms of TLR3 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The Haplotype association analysis was performed using the Haploview package. A luciferase reporter assay and real-time PCR were used to test the function of the -7C/A promoter polymorphism in TLR3 expression in human embryonic kidney 293 (HEK293) cells. RESULTS: Genotype distributions of -7C/A and 1377C/T in TLR3 were significantly different in ESRD patients and healthy controls. The ATC haplotype of TLR3 was associated with a decreased risk of ESRD. We also found significant differences in TLR3 expression by dexamethasone treatment between various genotypes of -7C/A (p = 0.02). TLR3 transcriptional activity of the variant -7 C allele was higher than that of the -7 A allele after dexamethasone treatment. CONCLUSION: RESULTS indicate that, in our population, the presence of the C allele of -7C/A in TLR3 increases the susceptibility to ESRD. In vitro studies demonstrated that -7C/A may be involved in ESRD development through transcriptional modulation of TLR3.

Increased levels of circulating advanced glycation end-products in menopausal women with osteoporosis.

BACKGROUND: Advanced glycation end-products (AGEs) can accumulate in organs and tissues during ageing and diabetes. Increased levels of AGEs are found in the bone tissue of patients with osteoporosis. The purpose of this study was to evaluate circulating AGEs in patients with osteoporosis. METHODS: We evaluated plasma AGEs, osteoporosis-related biomarkers, and bone mass in 82 menopausal women with osteoporosis or osteopenia, 16 young women with osteopenia, and 43 healthy women without osteoporosis or osteopenia. RESULTS: Higher levels of serum AGEs were found in the osteoporosis or osteopenia group compared to healthy women (P < 0.0001). A negative correlation was observed between serum AGEs and lumbar spine bone density (BMD of lumbar spine, r = -0.249, P = 0.028; T-score of lumbar spine, r = -0.261, P = 0.021). Women with a increased level of serum AGEs (> 8.12 U/mL) had a 5.34-fold risk of osteopenia regarding lumbar spine T-score and a 3.31-fold risk of osteopenia regarding the hip T-score. CONCLUSION: Serum AGEs could be used to monitor the severity and progression of osteoporosis. An increased serum level of AGEs was associated with impaired bone formation and was a risk factor for the development of osteoporosis. Targeting AGEs may represent a novel therapeutic approach for primary or secondary osteoporosis.

Investigation of corneal epithelial thickness and irregularity by optical coherence tomography after transepithelial photorefractive keratectomy.

CLINICAL RELEVANCE: Corneal epithelial healing after refractive surgery is a clinically significant issue, especially for surface ablation procedures, and this can be monitored using optical coherence tomography (OCT). BACKGROUND: The aim of this work is to investigate the corneal epithelial thickness and irregularity by OCT after transepithelial photorefractive keratectomy (t-PRK) and analyse its correlation with visual and refractive outcomes. METHODS: Patients aged ≥18 years with myopia, with or without astigmatism, who underwent t-PRK between May 2020 and August 2021 were included. All participants were subjected to complete ophthalmic examinations and OCT pachymetry at every follow-up visit. Patients were followed up at 1 week and 1, 3, and 6 months postoperatively. RESULTS: A total of 67 patients (126 eyes) were enrolled in this study. One month postoperatively, spherical equivalent refraction and visual acuity achieved preliminary stability. However, central corneal epithelial thickness (CCET) and standard deviation of the corneal epithelial thickness (SDcet) took 3-6 months to progressive recovery. Patients with higher baseline spherical equivalent refraction were associated with slower epithelial recovery. At every follow-up time point, a significant superior-inferior difference in the minimum corneal epithelial thickness area was observed. Higher stromal haze was correlated with higher spherical equivalent refraction (both baseline and residual) but had no relation with visual outcomes. There was a significant correlation between higher CCET with a better uncorrected distance visual acuity and lower corneal epithelial thickness irregularity. CONCLUSIONS: CCET and SDcet measured by OCT seem to be a good auxiliary indicator for reflecting the status of corneal wound recovery after t-PRK surgery. However, a well-designed randomised control study is needed to confirm the study results.

Do patients with nephrotic syndrome have an increased risk of osteoporosis? A nationwide population-based retrospective cohort study in Taiwan.

OBJECTIVES: To evaluate whether nephrotic syndrome (NS) and further corticosteroid (CS) use increase the risk of osteoporosis in Asian population during the period January 2000-December 2010. DESIGN: Nationwide population-based retrospective cohort study. SETTING: All healthcare facilities in Taiwan. PARTICIPANTS: A total of 28 772 individuals were enrolled. INTERVENTIONS: 26 614 individuals with newly diagnosed NS between 2000 and 2010 were identified and included in out study. 26 614 individuals with no NS diagnosis prior to the index date were age matched as controls. Diagnosis of osteoporosis prior to the diagnosis of NS or the same index date was identified, age, sex and NS-associated comorbidities were adjusted. PRIMARY OUTCOME MEASURE: To identify risk differences in developing osteoporosis among patients with a medical history of NS. RESULTS: After adjusting for covariates, osteoporosis risk was found to be 3.279 times greater in the NS cohort than in the non-NS cohort, when measured over 11 years after NS diagnosis. Stratification revealed that age older than 18 years, congestive heart failure, hyperlipidaemia, chronic kidney disease, liver cirrhosis and NS-related disease including diabetes mellitus, hepatitis B infection, hepatitis C infection, lymphoma and hypothyroidism, increased the risk of osteoporosis in the NS cohort, compared with the non-NS cohort. Additionally, osteoporosis risk was significantly higher in NS patients with CS use (adjusted HR (aHR)=3.397). The risk of osteoporosis in NS patients was positively associated with risk of hip and vertebral fracture (aHR=2.130 and 2.268, respectively). A significant association exists between NS and subsequent risk for osteoporosis. CONCLUSION: NS patients, particularly those treated with CS, should be evaluated for subsequent risk of osteoporosis.

The epidemiology of patients with toxoplasmosis and its associated risk factors in Taiwan during the 2007-2020 period.

BACKGROUND: Toxoplasmosis is a zoonotic parasitic disease caused by the protozoan Toxoplasma gondii (T. gondii), and may cause miscarriage and birth defects during pregnancy. This study aimed to assess the epidemiological features, epidemic trends, and correlations between the before number of confirmed toxoplasmosis cases in Taiwan from 2007 to 2020 in gender, age, season, and residential area, and hypothesized the environmental and climate factors also might affect the disease in Taiwan. METHODS: This study reviewed publicly available annual summary data on reported toxoplasmosis cases in the Taiwan Centers for Diseases Control (TCDC) between 2007 and 2020. RESULTS: This study collected 150 confirmed domestic and nine patients with imported toxoplasmosis. There was an increasing trend in the incidence of toxoplasmosis, 0.09-0.89 cases per 1,000,000 people, peaking in 2017. The average annual toxoplasmosis incidence was 4.4, 13, and 18 during 2007-2011, 2012-2016, and 2017-2020, respectively. Comparing sex, age, season, and place of residence, the incidence rate was highest in male, 20-39 years-old patients, summer, and the eastern region, with 1.02, 1.72, 0.38, and 3.63 cases per million population, respectively. Additionally, comparing the distribution of cases by age group in Taiwan, there were significant differences between 40-59 years-old in the northern region (odds ratio (OR) = 0.343, 95% confidence interval (CI) = 0.167-0.705, p = 0.004) and 40-59 years-old in the southern region (OR = 4.488, and 95% CI = 2.149-9.374, p< 0.001), respectively. Linear regression analysis also showed that PM (particulate matter) 2.5 (µg/m3) concentration was positively associated with toxoplasmosis (ß = 0.095, p = 0.037). CO concentration was negatively correlated with toxoplasmosis (ß = -14.001, p = 0.021). CONCLUSIONS: This study is the first to report domestic and confirmed cases of imported toxoplasmosis from the surveillance data of the TCDC between 2007 and 2020. It identified that residence and age were associated with an increased risk of toxoplasmosis in Taiwan. This study confirmed that toxoplasmosis remains a prevalent infectious disease in Taiwan, its epidemic is gradually increasing and becoming more severe. These findings might be useful for policy-makers and clinical experts to direct prevention and control activities to patients with T. gondii, which causes the most severe illness and greatest burden to Taiwanese people.

A Population-Based Cohort Study of the Association between Visual Loss and Risk of Suicide and Mental Illness in Taiwan.

The psychosocial and health consequences of ocular conditions that cause visual impairment (VI) are extensive and include impaired daily activities, social isolation, cognitive impairment, impaired functional status and functional decline, increased reliance on others, increased risk of motor vehicle accidents, falls and fractures, poor self-rated health, and depression. We aimed to determine whether VI increases the likelihood of a poor prognosis, including mental illness, suicide, and mortality over time. In this large, location, population-based, nested, cohort study, we used data from 2000 to 2015 in the Taiwan National Health Insurance Research Database (NHIRD), which includes diagnoses of all the patients with VI. Baseline features, comorbidities, and prognostic variables were evaluated using a 1:4-matched cohort analysis. Furthermore, comparisons were performed using Cox regression and Bonferroni-correction (for multiple comparisons) to study the association between VI and poor prognosis (mental illness, suicide). The study outcome was the cumulative incidence of poor prognosis among the visually impaired and controls. A two-tailed Bonferroni-corrected p < 0.001 was considered statistically significant. Among the 1,949,101 patients enlisted in the NHIRD, 271 had been diagnosed with VI. Risk factors for poor prognosis and the crude hazard ratio was 3.004 (95% confidence interval 2.135-4.121, p < 0.001). Participants with VI had an increased risk of poor prognosis according to the sensitivity analysis, with a poor prognosis within the first year and first five years. VI was associated with suicide and mental health risks. This study revealed that patients with VI have a nearly 3-fold higher risk of psychiatric disorders, including anxiety, depression, bipolar, and sleep disorders, than the general population. Early detection through comprehensive examinations based on increased awareness in the clinical context may help maintain visual function and avoid additional complications.

The efficacy and safety of combined GLP-1RA and basal insulin therapy among inadequately controlled T2D with premixed insulin therapy.

This study investigated the effect of a combination of glucagon-like peptide-1 receptor agonist (GLP-1 RA) and basal insulin (BI) in poorly controlled type 2 diabetes mellitus previously treated with premixed insulin. The possible therapeutic benefit of the subject is mainly hoped to provide a direction for optimizing treatment options to reduce the risk of hypoglycemia and weight gain. A single-arm, open-label study was conducted. The antidiabetic regimen was switched to GLP-1 RA plus BI to replace previous treatment with premixed insulin in type 2 diabetes mellitus subjects. After 3 months of treatment modification, GLP-1 RA plus BI was compared for superior outcomes by continuous glucose monitoring system. There were 34 subjects at the beginning, 4 withdrew due to gastrointestinal discomfort, and finally 30 subjects completed the trial, of which 43% were male; the average age was 58 ± 9 years old, and the average duration of diabetes was 12 ± 6 years, the baseline glycated hemoglobin level was 8.6 ± 0.9 %. The initial insulin dose of premixed insulin was 61 ± 18 units, and the final insulin dose of GLP-1 RA + BI was 32 ± 12 units (P < .001). Time out of range (from 59%-42%), time-in-range (from 39%-56%) as well as glucose variability index including standard deviation also improved, mean magnitude of glycemic excursions, mean daily difference and continuous population in continuous glucose monitoring system, continuous overall net glycemic action (CONGA). Also noted was a decrease in body weight (from 70.9 kg-68.6 kg) and body mass index (all P values < .05). It provided important information for physicians to decide to modify therapeutic strategy as individualized needs.

Clinical experience using cadaveric skin for wound closure in taiwan.

UNLABELLED: Taiwan's skin banking program was initially set up to provide a ready source of cadaveric skin for patients with severe burns. However, human cadaveric skin may offer a useful alternative to conventional dressings in other wounds as well. METHODS: In this retrospective review, cadaveric skin transplantation was used as temporary coverage in 145 patients with chronic ulcers, diabetic foot ulcers (DFU), necrotizing fasciitis, and acute traumatic wounds. Sex, age, number of debridements, and number of cadaveric skin transplantations were analyzed using statistical methods. RESULTS: After clinical determination of engraftment 1 week after cadaveric skin allograft, skin samples harvested for histology in 15 cases revealed migration of epithelia from patient's skin to the surface of cadaver skin and the presence of granulation tissue in the base of the cadaver skin. All wounds exhibited good wound-bed preparation after cadaveric skin transplantation, and could eventually be resurfaced with a skin autograft. CONCLUSION: Human cadaveric skin, in addition to being the mainstay in burn therapy, is a good biological dressing for chronic ulcers, DFUs, necrotizing fasciitis, and acute traumatic wounds. .

Epidemiological features and risk factors for measles and rubella in Taiwan during 2011 to 2020.

The risk of geographic transmission of infectious diseases due to air travel varies greatly. Our aim is to survey empirical data that provide a retrospective historical perspective on measles and rubella. This study used the open data website provided by the Taiwan Centers for Disease Control (TCDC) to extract the reported numbers of measles and rubella case between 2011 and 2020. There were 306 cases of measles and 135 cases of rubella. The incidence of measles and rubella per million population were 0 to 6.0 and 0 to 2.6, respectively. There was a gradual increase in the numbers of cases in those aged 20-39 years, and distinct duration patterns. It indicated that the risk of contracting rubella has significantly decreased in the last 5 years. Measles cases aged 20 to 39 years accounted for 72.5% of all cases. Rubella cases aged 20 to 39 years accounted for 59.3% of all cases. The male and residency in the Taipei metropolitan area or northern area were identified as potential risk factors for measles and rubella. Coverage with the first dose of the measles, mumps and rubella (MMR) vaccine in Taiwan increased from 97.31% to 98.86%, and the uptake rate of the second dose of the MMR vaccine increased from 95.73% to 98.39% between 2010 and 2020. Furthermore, the numbers of imported cases of measles (n = 0) and rubella (n = 0) reported during the coronavirus disease 2019 (COVID-19) pandemic were lower than those from 2011 to 2019. Measles and rubella cases were imported most frequently from Cambodia and Vietnam. This study represents the first report of confirmed cases of acquired measles and rubella from surveillance data of the TCDC between 2011 and 2020, also demonstrates that the numbers of cases of measles and rubella significantly decreased in Taiwan during the COVID-19 pandemic.

Risk of cardiovascular disease in patients with alcohol use disorder: A population-based retrospective cohort study.

The complex effects of alcohol consumption on the cardiovascular system vary with mean daily consumption and duration of intake. This population-based retrospective cohort study aimed to explore the risk of cardiovascular disease (CVD) in patients with alcohol use disorder (AUD). Data was collected from the Taiwan National Health Insurance Research Database from 2000 to 2013. A total of 7,420 patients with AUD were included in our study group, and 29,680 age- and sex-matched controls without AUD in the control group. Cox proportional hazard regression analysis was used to investigate the effects of AUD on the risk of CVD. Most patients were men aged 25-44 years. At the end of the follow-up period, the AUD group had a significantly higher incidence of CVD (27.39% vs. 19.97%, P<0.001) and more comorbidities than the control group. The AUD group also exhibited a significantly higher incidence of CVD than the control group based on the Cox regression analysis and Fine and Gray's competing risk model (adjusted hazard ratio [AHR] = 1.447, 95% confidence interval [CI] = 1.372-1.52 5, P<0.001). Furthermore, male sex, diabetes mellitus, hypertension, hyperlipidemia, chronic kidney disease, chronic obstructive pulmonary disease, anxiety, depression, and a high Charlson Comorbidity Index were also associated with an increased risk of CVD. Patients with AUD in different CVD subgroups, such as those with CVD, ischemic heart disease (IHD), and stroke, were at a significantly higher risk of disease than those without AUD; CVD (AHR = 1.447, 95% CI = 1.372-1.525, P<0.001), IHD (AHR = 1.304, 95% CI = 1.214-1.401, P<0.001), and stroke (AHR = 1.640, 95% CI = 1.519-1.770, P<0.001). The risk also significantly differed among patients in the different CVD subgroups. We observed an association between AUD and development of CVD even after adjusting for several comorbidities and medications in our nationwide population cohort.

The Most Common Location of Schools with Viral Upper Respiratory Tract Infection Clusters in Taiwan, 2011-2019.

Clusters of acute upper respiratory tract infections are mainly caused by type A or B influenza virus. Numerous factors modify the risk of upper respiratory tract infection (URTI) cluster transmission. The purpose of this study was to investigate the epidemiological characteristics, differences, and epidemic trends in influenza viruses and in non-influenza respiratory pathogens, and the distribution of the sites of URTI cluster events in Taiwan from 2011 to 2019. We examined the publicly available annual summary data on 1864 confirmed URTI clusters in the Taiwan Centers for Disease Control (Taiwan CDC) from 2011 to 2019. URTI clusters were mainly divided into 1295 clusters of influenza virus infections, 149 clusters of non-influenza respiratory pathogen infections, 341 clusters of pathogens not detected by routine tests, and 79 clusters of unchecked samples. There were statistically significant differences (p < 0.001) in the event numbers of URTI clusters among influenza and non-influenza respiratory pathogens between 2011 and 2019. There were statistically significant differences (p = 0.01) in instances of URTI clusters among non-influenza respiratory pathogens between 2011 and 2019. There were also statistically significant differences (p < 0.001) in instances of URTI clusters in different locations between 2011 and 2019. In all the pathogens of URTI clusters (odds ratio (OR) = 1.89−2.25, p = 0.002−0.004), most single infections were influenza A viruses (64.9%, 937/1444). Respiratory syncytial virus single infections were most numerous (43.0%, 64/149) among the non-influenza respiratory pathogens of URTI clusters. Of the institutions where URTI clusters occurred, schools had the most cases (50.1%, 933/1864) (OR = 1.41−3.02, p < 0.001−0.04). After the categorization of isolated virus strains by gene sequencing, it was found that, of the seasonal influenza A viruses, the H1N1 subtype viruses were predominantly A/California/07/2009, A/Michigan/45/2015, and A/Brisbane/02/2018, and the H3N2 subtype viruses were predominantly A/Hong Kong/4801/2014, A/Singapore/INFIMH-16−0019/2016, and A/Switzerland/8060/2017, during 2017−2019. Of the influenza B viruses, B/Brisbane/60/2008 (B/Vic) was the dominant type, and some were B/Massachusetts/02/2012 (B/Yam) and B/PHUKET/3073/2013 (B/Yam). This study is the first report of confirmed events of URTI clusters from surveillance data provided by the Taiwan CDC (2011−2019). This study highlights the importance of long-term, geographically extended studies, particularly for highly fluctuating pathogens, for understanding the implications of the transmission of URTI clusters in Taiwanese populations. Knowledge gaps and important data have been identified to inform future surveillance and research efforts in Taiwan.

Circulating protein disulfide isomerase family member 4 is associated with type 2 diabetes mellitus, insulin sensitivity, and obesity.

AIMS: Endoplasmic reticulum (ER) stress is associated with obesity and type 2 diabetes mellitus (T2DM) and increasing evidence demonstrates that some ER stress markers can represent the severity of metabolic dysfunction in either cellular or animal models. However, no appropriate molecule has been identified to demonstrate these relationships in clinical practice. METHODS: To determine whether the serum level of the ER chaperone, protein disulfide isomerase family A, member 4 (PDIA4), is associated with type 2 diabetes mellitus, obesity, and insulin sensitivity, we conducted a cross-sectional study for which a total of 553 adults, including 159 with normal glucose tolerance (NGT), 169 with prediabetes (Pre-DM), and 225 with newly diagnosed T2DM, were recruited. RESULTS: Serum PDIA4 levels were significantly higher in patients with T2DM than in those with NGT (P < 0.001), even after adjustment for potential confounders. These levels correlated positively with fasting plasma glucose, BMI, waist circumference as well as high-sensitivity C-reactive protein levels, and negatively and strongly correlated with insulin sensitivity. In a multivariate logistic regression analysis, higher serum PDIA4 concentration was observed to be significantly associated with an increased risk of T2DM. CONCLUSIONS: Our findings provide new mechanistic insights linking ER stress, T2DM, insulin sensitivity, and obesity, which may, in part, account for the ER chaperone properties associated with PDIA4. The results suggest that PDIA4 may serve as a potential instigator of and a putative therapeutic target for T2DM.

PDIA4, a new endoplasmic reticulum stress protein, modulates insulin resistance and inflammation in skeletal muscle.

Introduction: Endoplasmic reticulum (ER) stress has emerged as a key player in insulin resistance (IR) progression in skeletal muscle. Recent reports revealed that ER stress-induced the expression of protein disulfide isomerase family a member 4 (PDIA4), which may be involved in IR-related diseases. A previous study showed that metformin modulated ER stress-induced IR. However, it remained unclear whether metformin alleviated IR by regulating PDIA4 expression in skeletal muscle. Methods: Herein, we used palmitate-induced IR in C2C12 cells and a high-fat diet-induced IR mouse model to document the relations between metformin, IR, and PDIA4. Results: In C2C12 cells, palmitate-induced IR increased inflammatory cytokines and PDIA4 expression. Besides, knocking down PDIA4 decreased palmitate-induced IR and inflammation in C2C12 cells. Furthermore, metformin modulated PDIA4 expression and alleviated IR both in vitro and in vivo. In addition, serum PDIA4 concentrations are associated with IR and inflammatory cytokines levels in human subjects. Discussion: Thus, this study is the first to demonstrate that PDIA4 participates in the metformin-induced effects on skeletal muscle IR and indicates that PDIA4 is a potential novel therapeutic target for directly alleviating IR.

Epidemiology and risk factors for notifiable Clostridium botulinum infections in Taiwan from 2003 to 2020.

Botulinum toxin is produced by Clostridium botulinum, a gram-positive anaerobic bacterium. This study aimed to examine the epidemiological characteristics, including sex, age, season in which infection occurred, place of residence, and epidemiological trends, of confirmed botulism cases in Taiwan from 2003 to 2020. This study examined the annual summary data on reported botulism in Taiwan' s Center for Disease Control from 2003 to 2020 available to the public on the internet. We found that there were 50 confirmed domestic cases of botulism. The incidence of botulism ranged from 0 to 0.48 per 1000,000 from 2003 to 2020 and peaked in 2008 and 2010. During the 18-year investigation period in which 6-year intervals were used, the study results showed a decreasing trend (2003-2008, 2009-14, and 2015-2020, had 22, 19, 9 cases each). In terms of patients' gender, age, and place of residence, most of the patients were females (56%), were aged ≥ 50 years (48%), and resided in Taipei and northern Taiwan (44%). The number of botulism cases in Taiwan from 2012 to 2020 compared with other years (from 2003 to 2011) found that there were significant differences among patients within an age group of <20 years (P = .003, odds ratio = 18.500, and 95% confidence interval = 3.287-104.111), and there were significant differences among patients whose place of residence was Taipei metropolitan area (P = .025, odds ratio = 5.667, and 95% confidence interval = 1.248-25.734). During 2003 to 2009, there was no case of botulism among those aged <20 years. Over the last 10 years, botulism in children showed an increasing trend. A total of 9 children were found to have botulism during 2010 to 2020; most of these children were male (66.7%) and were infected during spring and summer (66.7%). This study is the first to report the number of confirmed domestic cases with botulism from surveillance data from Taiwan's Center for Disease Control during 2003 to 2020. This study also found that the place of residence and age were associated with an increased risk of botulism in Taiwan. This information may be useful for policymakers and clinical experts to direct prevention- and control-based activities regarding botulism that result in the most severe illness and the greatest burden on Taiwanese.