Sex-specific associations of Notch signaling with chronic HBV infection: a study from Taiwan Biobank.

BACKGROUND: Hepatitis B, a liver infection caused by the hepatitis B virus (HBV), can develop into a chronic infection that puts patients at high risk of death from cirrhosis and liver cancer. In this study, we aimed to investigate the difference of reactome pre-Notch expression and processing between males and females by using gene to function analysis in FUMA. METHODS: We analyzed Taiwan Biobank (TWB) data pertaining to 48,874 women and 23,178 men individuals which were collected from 2008 to 2019. According to hepatitis B surface antigen (HBsAg) status in hematology, positive and negative were classified into case and control in the genome-wide association study (GWAS) analysis. RESULTS: We found 4715 women and 2656 men HBV cases. The genomic risk loci were different between males and females. In male, three risk loci (rs3732421, rs1884575 and Affx-28516147) were detected while eight risk loci (Affx-4564106, rs932745, rs7574865, rs34050244, rs77041685, rs107822, rs2296651 and rs12599402) were found in female. In addition, sex also presented different results. In females, the most significant SNPs are gathered in chromosome 6. However, except for chromosome 6, significant HBV infection SNPs also could be found in chromosome 3 among males. We further investigated gene function in FUMA to identify the difference in reactome pre-Notch expression and processing between males and females. We found that POGLUT1 and HIST1H2BC only appeared in men but not in women. CONCLUSION: According to our study, the reactome pre-Notch expression including POGLUT1 and HIST1H2BC was associated with a risk of Hepatitis B in Taiwanese men when compared to women.

Hepatitis B is a serious liver infection caused by the hepatitis B virus (HBV). It can lead to long-term liver damage and cancer. We looked at differences in how the virus affects men and women in Taiwan. We analyzed data from over 72,000 people in the Taiwan Biobank. The study individuals were divided into two groups­those who had the hepatitis B virus (cases) and those who did not (controls). We looked for genetic differences between the two groups and found that the specific genetic risk factors for hepatitis B differed between men and women. We found three genetic risk factors in men and eight in women. This suggests that the way the hepatitis B virus interacts with our genes may differ between the sexes. We found that in women, the most significant genetic risk factors were all located on chromosome 6. However, in men, the significant risk factors were spread across different chromosomes, including chromosome 3. Finally, we looked at how these genetic differences might affect the way the body processes the hepatitis B virus. We found that two specific genes, called POGLUT1 and HIST1H2BC, were only linked to hepatitis B risk in men, not in women. This indicates that the biological pathways involved in hepatitis B infection may differ between males and females. Understanding these differences could lead to more effective, personalized treatment strategies for those affected by the virus.

Prevalence and effects of sleep-disordered breathing on middle-aged patients with sedative-free generalized anxiety disorder: A prospective case-control study.

Objective: Generalized anxiety disorder (GAD) and sleep-disordered breathing (SDB) share similar symptoms, such as poor sleep quality, irritability, and poor concentration during daily activities. This study aims to investigate the proportion of undiagnosed SDB and its impacts on anxiety severity and autonomic function in newly diagnosed, sedative-free GAD patients. Methods: This prospective case-control study included newly diagnosed GAD patients and control participants with matched age, sex, and body mass index (BMI) in Taiwan. All participants completed questionnaires for sleep and mood symptoms and a resting 5-min heart rate variability (HRV) examination during enrollment. The participants also used a home sleep apnea test to detect SDB. An oxygen desaturation index (ODI) ≥ 5 was considered indicative of SDB. Results: In total, 56 controls and 47 newly diagnosed GAD participants (mean age 55.31 ± 12.36 years, mean BMI 23.41 ± 3.42 kg/m2) were included. There was no significant difference in the proportion of undiagnosed SDB in the control and sedative-free GAD groups (46.43 vs. 51.06%). Sedative-free GAD patients with SDB scored significantly higher on Beck Anxiety Inventory (23.83 ± 11.54) than those without SDB (16.52 ± 10.61) (p < 0.001). Both control and sedative-free GAD groups with SDB had worse global autonomic function than the control group without SDB, as evidenced by the HRV results (p < 0.05 for all). Conclusion: Average age 55 years and mean BMI 23 kg/m2 patients with GAD and matched controls had an undiagnosed SDB prevalence of approximately 50%. SDB correlated with worsening anxiety severity and reduced cardiac autonomic function. Moreover, age and BMI were considered major risk factors for predicting undiagnosed SDB.

Short- and Long-term Risks of Highly Active Antiretroviral Treatment with Incident Opportunistic Infections among People Living with HIV/AIDS.

Highly active antiretroviral therapy (HAART) causes a rapid increase of CD4 + T cells counts during the first 3-6 months of treatment and may enhance the development of opportunistic infections (OIs). However, the short- and long-term effects of HAART exposure on the development of incident OIs has not been extensively studied. This nationwide longitudinal study followed up a total of 26,258 people living with HIV/AIDS (PLWHA) to ascertain the short- and long-term effects of HAART on incident OIs. During 150,196 person-years of follow-up, 6,413 (24.4%) PLWHA had new onset of OIs. After adjusting for demographics, comorbidities, and AIDS status, PLWHA who received HAART were more likely to develop OIs than those who did not receive HAART. Considering the short- and long-term effects of HAART on the development of OIs, HAART was found to be a risk factor for developing OIs during the first 90 days of treatment, but a protective factor against OIs after 180 days of HAART use. The risk for the development of active OIs significantly decreased as the duration of HAART increased (P < 0.001). Our study suggests that HAART is a risk factor for developing OIs in the short term, but is a protective factor in the long term.

Molecular epidemiology of HIV-1 infection among men who have sex with men in Taiwan from 2013 to 2015.

Men who have sex with men (MSM) is the major risk population of HIV-1 infection in Taiwan, and its surveillance has become critical in HIV-1 prevention. We recruited MSM subjects from 17 high-risk venues and 4 community centers in northern and southern Taiwan for anonymous HIV-1 screening during 2013-2015. Blood samples were obtained for genotyping and phylogenetic analysis, and a questionnaire survey covering demographic variables and social behavior was conducted. In total, 4,675 subjects were enrolled, yielding a HIV-1 prevalence rate of 4.3% (201/4675). Eight risk factors including subjects who did not always use condoms (OR = 1.509, p = 0.0123), those who used oil-based lubricants (OR = 1.413, p = 0.0409), and those who used recreational drugs (OR = 2.182, p = < .0001) had a higher risk of HIV-1 infection. The annual prevalence and incidence of HIV-1 showed a downward trend from 2013 to 2015 (6.56%, 5.97 per 100 person-years in 2013; 4.53%, 3.97 per 100 person-years in 2014; 1.84%, 2.08 per 100 person-years in 2015). Factors such as always using condoms, water-based lubricant use, correct knowledge of lubricating substitutes, and recreational drug use were significantly associated with the trend of incidence. Phylogenetic tree analysis showed that the cross-regional and international interaction of the local MSM population may have facilitated transmission of HIV. This survey of high-risk venues showed decreased prevalence and incidence of HIV-1 infection in Taiwan from 2013 to 2015, and this may be related to changes in behavioral patterns. Moreover, cross-regional interaction and recreational drug use need to be considered in future surveillance.

Risk of Diffuse Infiltrative Lymphocytosis Syndrome in HIV-Infected Patients: A Nationwide Population-Based Cohort Study.

OBJECTIVE: Diffuse infiltrative lymphocytosis syndrome (DILS) is the term used for sicca syndrome in HIV patients and has similar clinical manifestations as Sjögren syndrome. In this nationwide population-based study, we aimed to determine the association between HIV infection and DILS in the Taiwanese population. METHODS: The National Health Insurance Research Database was searched for cases of DILS in HIV-infected individuals diagnosed between January 1, 2000, and December 31, 2012. The incidence of DILS and the factors associated with DILS in people living with HIV/AIDS (PLWHA) were determined. RESULTS: A total of 20,364 PLWHA were followed, and 57 (0.28%) individuals had new-onset DILS. The incidence rate of DILS in PLWHA was 0.56/1000 person-years. One (0.11%) female HIV patient with highly active antiretroviral therapy (HAART) and 24 (2.99%) without HAART had incident DILS, whereas 22 (0.17%) male HIV patients with HAART and 10 (0.17%) without HAART had incident DILS. Hypertension increased the risk of incident DILS. HAART decreased the risk of DILS, but this relationship somewhat attenuated in an adjusted model. None of the patients taking emtricitabine, raltegravir, darunavir, enfuvirtide, or tipranavir developed DILS. Lopinavir was associated with a decreased risk of DILS (adjusted hazard ratio = 0.10, 95% confidence interval: 0.01 to 0.84), whereas zalcitabine was associated with an increased risk of DILS (adjusted hazard ratio = 13.7, 95% confidence interval: 2.18 to 85.9). CONCLUSIONS: DILS is a rare disease found in PLWHA. Hypertension is a risk factor for incident DILS, and HAART could affect the pathogenesis of DILS. Zalcitabine was the only antiretroviral agent found to increase the risk of DILS.

AIDS incidence trends at presentation and during follow-up among HIV-at-risk populations: a 15-year nationwide cohort study in Taiwan.

BACKGROUND: Although Taiwan has implemented several important interventions for various HIV-at-risk populations to combat the HIV epidemic, little is known regarding AIDS incidence at presentation and during follow-up among the various HIV-at-risk populations in Taiwan. A better understanding of AIDS incidence trends would help improve patient care and optimize public health strategies aimed at further decreasing HIV-related morbidity and mortality. METHODS: Data from Taiwan Centers for Disease Control-operated Notifiable Diseases Surveillance System and Taiwan National Health Insurance Research Database (1998-2012) was divided into five cohort periods (consecutive 3-year groups). Logistic regression was employed to identify factors associated with AIDS incidence at presentation. Time-dependent Cox regression was used to identify factors associated with AIDS incidence during the follow-up period. RESULTS: Of 22,665 patients [mean age: 32 years; male (93.03%)], 6210 (27.4%) had AIDS incidence over 2 (1.16) [median (interquartile range)] years of follow-up. AIDS developed in ≤3 months of HIV diagnosis in 73.6% AIDS patients. AIDS incidence trends at presentation and during follow-up differed according to HIV transmission routes over the five periods: AIDS at presentation increased in the sexual contact groups (P < 0.001 for homosexuals/heterosexuals; 0.648 for bisexuals) but decreased to a nadir in period 3 and then increased slightly in period 5 (P < 0.001) in people who injected drugs (PWIDs). AIDS incidence during the follow-up period increased from period 1 to a peak in period 3 or 4, before declining slightly in period 5, in the sexual contact groups (P < 0.001 for homosexuals/heterosexuals; 0.549 for bisexuals). However, it increased throughout the five periods in PWIDs (P < 0.001). Older age, sexual contact group versus PWIDs, high versus low income level, cohort periods, and HIV diagnosis regions helped predict AIDS at presentation and during follow-up. CONCLUSIONS: Disparities in AIDS incidence trends in various HIV-at-risk populations reflect different sociodemographic variables of HIV exposure and the adopted HIV prevention strategies. This study suggests the urgent need for tailored strategies aimed at specific populations at presentation and during follow-up.

Association of highly active antiretroviral treatment with incident tuberculosis in people living with HIV/AIDS.

PURPOSE: To determine the short-term and long-term effects of highly active antiretroviral therapy (HAART) on incident tuberculosis (TB) in people living with HIV/AIDS (PLWHA). METHODS: From 2000 to 2012, we identified adult PLWHA from Taiwan Centers for Disease Control HIV Surveillance System. All PLWHA were followed up until December 31, 2012, and observed for TB occurrence. Time-dependent Cox proportional hazards models were used to determine the short-term and long-term effects of HAART on incident TB. RESULTS: Of 20,072 PLWHA, 628 (3.13%) had incident TB, corresponding to an incident rate of 701/100,000 person-years. After adjusting for potential confounders, PLWHA receiving HAART were more likely to develop TB than those not receiving the drugs (adjusted hazard ratio [AHR] 1.56; 95% confidence interval [CI] 1.18-2.05). While the short-term and long-term effects of HAART on incident TB were considered, HAART was a risk factor for TB development within the first 90 days (AHR 6.06; 95% CI 4.58-8.01) and between 90 and 180 days of treatment (AHR 1.80; 95% CI 1.11-2.94) but was a protective factor after 180 days of HAART use (AHR 0.51; 95% CI 0.39-0.66). CONCLUSIONS: HAART is a risk factor for the development of TB in the short term but a protective factor in the long term.

Human Immunodeficiency Virus Infection Increases the Risk of Incident Autoimmune Hemolytic Anemia: A Population-Based Cohort Study in Taiwan.

Background: Currently, the association between human immunodeficiency virus (HIV) infection and subsequent development of autoimmune hemolytic anemia (AIHA) remains unclear. This nationwide population-based cohort study aimed to determine the association between incident AIHA and HIV infection in Taiwan. Methods: During 2000-2012, we identified people aged ≧15 years living with HIV (PLWH) from the Taiwan Centers for Disease Control HIV Surveillance System. Individuals were considered to be infected with HIV on the basis of positive results of an HIV type 1 Western blot. Age- and sex-matched controls without HIV infection were selected from the Taiwan National Health Insurance Research Database for comparison. All patients were followed until 31 December 2012 and observed for occurrence of AIHA. Results: Of 171468 subjects (19052 PLWH and 152416 controls), 30 (0.02%) had incident AIHA during a mean follow-up of 5.45 years, including 23 PLWH (0.12%) and 7 controls (0.01%). After adjustment for age, sex, and comorbidities, HIV infection was found to be an independent risk factor of incident AIHA (adjusted hazard ratio, 20.9; 95% confidence interval, 8.34-52.3). Moreover, PLWH who were receiving highly active antiretroviral therapy were more likely to develop AIHA than those who were not receiving these drugs (adjusted hazard ratio, 16.2; 95% confidence interval, 3.52-74.2). Conclusions: Our study suggests that HIV infection is an independent risk factor for incident AIHA.

HIV Infection Increases the Risk of Incident Psoriasis: A Nationwide Population-Based Cohort Study in Taiwan.

BACKGROUND: HIV can cause an imbalance of T lymphocytes, which may contribute to the onset of psoriasis. However, the association of HIV with incident psoriasis has not been extensively studied. OBJECTIVES: The aim of this nationwide population-based cohort study was to determine the association of HIV with incident psoriasis. METHODS: Since January 1, 2000, we identified adult people living with HIV/AIDS (PLWHA) from the Taiwan National Health Insurance Research Database. A control cohort without HIV infection, matched for age and sex, was selected for comparison. All patients were followed until December 31, 2012, and observed for the occurrence of psoriasis. The time-dependent Cox proportional hazards model was used to determine the association of HIV with incident psoriasis, while considering death as a competing risk event. RESULTS: Of the 102,070 patients (20,294 PLWHA and 81,776 matched controls), 248 (0.24%) had incident psoriasis during a mean follow-up period of 5.53 years, including 81 (0.40%) PLWHA and 171 (0.21%) controls. After adjusting for age, sex, and comorbidities, HIV infection was found to be an independent risk factor for incident psoriasis (adjusted hazard ratio, 1.80; 95% confidence interval: 1.38 to 2.36). CONCLUSIONS: The population of PLWHA is living longer; clinicians need to be aware of their higher risk of psoriasis.

Incidence of autoimmune diseases in a nationwide HIV/AIDS patient cohort in Taiwan, 2000-2012.

OBJECTIVES: It is not known if the incidences of autoimmune diseases are higher in individuals living with HIV infection or AIDS. Our study investigated the incidences of autoimmune diseases among people living with HIV/AIDS (PLWHA) in Taiwan during 2000-2012. METHODS: The Taiwan National Health Insurance Research Database was used to identify PLWHA. The incidence densities of systemic and organ-specific autoimmune diseases were calculated, and age-adjusted, sex-adjusted and period-adjusted standardised incidence rates (SIRs) were obtained by using two million people from the general population as controls. To examine the effects of highly active antiretroviral therapy (HAART) on the incidence of autoimmune diseases, the incidence densities and SIRs of autoimmune diseases were calculated after stratifying PLWHA by HAART status. RESULTS: Of the 20 444 PLWHA identified, the overall mean (SD) age was 30.1 (11.0) years; 67.2% of the subjects received HAART. As compared with the general population, SIRs were higher for incident Sjögren syndrome (SIR=1.64; 95% CI 1.24 to 2.13), psoriasis (SIR=2.05; 95% CI 1.67 to 2.48), systemic lupus erythematosus (SLE) (SIR=2.59; 95% CI 1.53 to 4.09), autoimmune haemolytic anaemia (SIR=35.06; 95% CI 23.1 to 51.02) and uveitis (SIR=2.50; 95% CI 2.05 to 3.02), but were lower for incident ankylosing spondyloarthritis (SIR=0.70; 95% CI 0.48 to 0.99). When the effect of HAART on incident autoimmune diseases was considered, PLWHA who received HAART had higher SIRs for psoriasis, autoimmune haemolytic anaemia and uveitis, but had lower risks of rheumatoid arthritis (RA) and ankylosing spondyloarthritis. In contrast, PLWHA who did not receive HAART had higher SIRs for Sjögren syndrome, psoriasis, RA, SLE, scleroderma, polymyositis, autoimmune haemolytic anaemia and Hashimoto's thyroiditis. CONCLUSIONS: PLWHA had higher risks of incident Sjögren syndrome, psoriasis, SLE, autoimmune haemolytic anaemia and uveitis.

Effects of periodontal therapy on metabolic control in patients with type 2 diabetes mellitus and periodontal disease: a meta-analysis.

Epidemiologic studies have reported increased incidence, prevalence and acuity of periodontitis in adults with diabetes and some have also suggested that treating periodontal disease may improve glycemic control in diabetic patients. This meta-analysis was conducted to evaluate the effects of different periodontal therapies on metabolic control in patients with type 2 diabetes mellitus (T2DM) and periodontal disease. We searched the Medline, EMBASE and Cochrane Library (Central) databases up to January 2014 for relevant studies pertaining to periodontal treatments and glycemic control in adults with T2DM. The search terms were periodontal treatment/periodontal therapy, diabetes/diabetes mellitus, periodontitis/periodontal and glycemic control. The primary outcome measure taken from the included studies was glycated hemoglobin (HbA1c). We compared differences in patients' pre- and post-intervention HbA1c results between a treatment group receiving scaling and root planing (SRP) combined with administration of oral doxycycline (n=71) and controls receiving SRP alone or SRP plus placebo (n=72). Meta-analysis was performed using Comprehensive Meta Analysis software. Nineteen randomized controlled trials (RCTs) were identified. Four trials involving a total of 143 patients with T2DM and periodontal disease were determined to be eligible for analysis. Data of 1 study were not retained for meta-analysis because HbA1c results were recorded as median with IQR. Meta-analysis of the included 3 studies revealed no significant differences in HbA1c results between the periodontal treatment group (n=71) and control group (n=72) (HbA1c SMD=-0.238, 95% CI=-0.616 to 0.140; P=0.217). Systemic doxycycline added to SRP does not significantly improve metabolic control in patients with T2DM and chronic periodontitis. Current evidence is insufficient to support a significant association between periodontal therapy and metabolic control in this patient population. However, evidence suggests that periodontal therapy itself improves metabolic control and reinforces that T2DM is a risk factor for periodontitis.

Community-based study on summer-winter differences of component of metabolic syndrome in Kinmen, Taiwan.

BACKGROUND: A community-based study was conducted to investigate summer-winter differences of component of metabolic syndrome in Kinmen, Taiwan. METHODS: A total of 8251 residents aged 40 and over were enrolled in the mass survey in Kinmen. They were investigated while on summer (July and August) and winter vacation (January and February) during 2000-2003. Demographics, physical examination findings, lifestyle variables and biochemical data were collected. RESULTS: After controlling for age, body mass index, diet, lifestyle and other risk factors for component of metabolic syndrome, there were independent and significant relationships between summer-winter difference and component of metabolic syndrome. Winter season was positively correlated with blood pressure, fasting plasma glucose level, high-density lipoprotein-cholesterol (HDL-C) and waist circumference, but was negatively associated with fasting triglycerides and metabolic syndrome. CONCLUSIONS: Summer season is positively associated with hypertriglyceridemia, low HDL-C and metabolic syndrome. These findings imply that cross-sectional, experimental and cohort studies of component of metabolic syndrome or metabolic syndrome should take season into account as possible confounding effects.