Support for a hypothetical sugar-sweetened beverage tax in Taiwan.

Sugar-sweetened beverages (SSBs) are drinks that contain added sugar or sweeteners and provide calories with no additional nutrients, and some countries have imposed additional taxes on the SSBs to reduce consumption, which is considered an SSB tax policy. This study used a cross-sectional online survey to examine the patterns of public support for an SSB tax in Taiwan. The sample included 1617 adults aged ≥ 20 years, who answered the survey questionnaire between May 2020 and April 2021. The respondents were recruited using convenience sampling, but sampling weights were applied to represent the Taiwanese population. Generalized ordered logit models with sampling weights were used to examine the correlates of public support for an SSB tax. Results showed that ~60% of the respondents supported the SSB tax and 47% perceived the tax to be effective. The respondents who were aware of the perceived health risks of SSBs or those who believed that one should be partly responsible for the health impact of SSBs were more likely to show support for the SSB tax. In adjusted regression models, both one's perceived risk and perceived responsibility of SSBs were positively associated with the perceived effectiveness of the SSB tax after sociodemographic characteristics were controlled. These research findings show evidence that there is public support for implementing an SSB tax to reduce SSB consumption in Taiwan.

Association Between Trajectory of Severe Hypoglycemia and Dementia in Patients With Type 2 Diabetes: A Population-based Study.

BACKGROUND: We aimed to investigate associations between exposure to various trajectories of severe hypoglycemic events and risk of dementia in patients with type 2 diabetes. METHODS: In 2002-2003, 677,618 patients in Taiwan were newly diagnosed as having type 2 diabetes. Among them, 35,720 (5.3%) experienced severe hypoglycemic events during the 3-year baseline period following diagnosis. All patients were followed from the first day after baseline period to the date of dementia diagnosis, death, or the end of 2011. A group-based trajectory model was used to classify individuals with severe hypoglycemic events during the baseline period. Cox proportional hazard models with the competing risk method were used to relate dementia risk to various severe hypoglycemia trajectories. RESULTS: After a median follow-up 6.70 and 6.10 years for patients with and without severe hypoglycemia at baseline, respectively, 1,952 (5.5%) individuals with severe hypoglycemia and 23,492 (3.7%) without developed dementia during follow-up, for incidence rates of 109.80 and 61.88 per 10,000 person-years, respectively. Four groups of severe hypoglycemia trajectory were identified with a proportion of 18.06%, 33.19%, 43.25%, and 5.50%, respectively, for Groups 1 to 4. Groups 3 (early manifestation but with later decrease) and 4 (early and sustained manifestation) were associated with a significantly increased risk of dementia diagnosis, with a covariate-adjusted subdistribution hazard ratio of 1.22 (95% confidence interval, 1.14-1.31) and 1.25 (95% confidence interval, 1.02-1.54), respectively. CONCLUSION: Our analysis highlighted that early manifestation of severe hypoglycemic events may contribute more than does late manifestation to the risk of dementia among individuals newly diagnosed as having type 2 diabetes.

Associations of hyperglycemic emergency and severe hypoglycemia incidences with seasonality and ambient temperature among pregnant women with diabetes: a nested case-control study in Taiwan.

BACKGROUND: Associations of acute glycemic complications with season and ambient temperature have been reported in general population with diabetes. However, little is known about the risks of acute glycemic complications in relation to season and ambient temperature in pregnant women, who are likely to be even more vulnerable. This work aimed to investigate the associations of season and ambient temperature with pregnancies complicated with hyperglycemia emergency or severe hypoglycemia. METHODS: Two separate case-control studies were nested within 150,153 pregnancies by women with type 1, type 2, or gestational diabetes between 2009 and 2014 in Taiwan. Hyperglycemia emergency (mainly diabetic ketoacidosis and hyperosmolar hyperglycemic state) and severe hypoglycemia occurred in 77 and 153 diabetic pregnancies (cases), respectively. Ten control pregnancies were randomly selected for each case by matching each case pregnancy on type of diabetes (i.e., T1DM, T2DM, or GDM), maternal age on the date of acute glycemic complication occurrence (i.e., index date), and "length of gestation at risk" (i.e., period between conception and index date). Meteorological parameters were retrieved from 542 meteorological monitoring stations across Taiwan during 2008-2014. Conditional logistic regression analysis with generalized estimation equation was separately performed to estimate the covariate adjusted odds ratios (ORs) of each of the two acute glycemic complications in association with season and ambient temperature within 30 days prior to the index date. RESULTS: Compared to summer, winter season was associated with a significantly elevated risk of severe hypoglycemia with an OR of 1.74 (95% confidence interval (CI) 1.08-2.79). The OR of hyperglycemic emergency was also elevated in winter season at OR of 1.88, but the significance is only marginal (95% CI 0.97-3.64, p = 0.0598). Subgroup analyses further noted that such seasonal variation was also observed in pregnancies with pre-pregnancy type 1 diabetes and gestational diabetes. On the other hand, ambient temperature was not significantly associated with the two acute glycemic complications. CONCLUSIONS: A moderately but significantly elevated risk of severe hypoglycemia was found in pregnant women with diabetes during winter season, and such increased risk was more evident in pregnancies with T1DM.

Overall and Cause-Specific Mortality in Patients With Type 1 Diabetes Mellitus: A Population-Based Cohort Study in Taiwan From 1998 Through 2014.

BACKGROUND: To investigate all-cause and cause-specific mortality in Taiwanese patients with type 1 diabetes. METHODS: A cohort of 17,203 patients with type 1 diabetes were identified from Taiwan's National Health Insurance claims in the period of 1998-2014. Person-years were accumulated for each individual from date of type 1 diabetes registration to date of death or the last day of 2014. Age, sex, and calendar year standardized mortality ratios (SMRs) were calculated with reference to the general population. RESULTS: In up to 17 years of follow-up, 4,916 patients died from 182,523 person-years. Diabetes (30.15%), cancer (20.48%), circulatory diseases (13.14%), and renal diseases (11.45%) were the leading underlying causes of death. Mortality rate (26.93 per 1,000 person-years) from type 1 diabetes in Taiwan was high, the cause of death with the highest mortality rate was diabetes (8.12 per 1,000 person-years), followed by cancer (5.52 per 1,000 person-years), and circulatory diseases (3.54 per 1,000 person-years). The all-cause SMR was significantly elevated at 4.16 (95% confidence interval, 4.04-4.28), with a greater all-cause SMR noted in females than in males (4.62 vs 3.79). The cause-specific SMR was highly elevated for diabetes (SMR, 16.45), followed by renal disease (SMR, 14.48), chronic hepatitis and liver cirrhosis (SMR, 4.91) and infection (SMR, 4.59). All-cause SMRs were also significantly increased for all ages, with the greatest figure noted for 15-24 years (SMR, 8.46). CONCLUSIONS: Type 1 diabetes in both genders and all ages was associated with significantly elevated SMRs for all-cause and mostly for diabetes per se and renal disease.

Dual-wavelength fiber-optic technique to assist needle cricothyroidotomy.

The traditional needle cricothyroidotomy procedure is performed blindly without any medical equipment. Complications including posterior tracheal wall perforation, accidental vessel puncture, and missed tracheal puncture are reported. Therefore, we proposed a dual-wavelength fiber-optic technique based on the technique of near-infrared spectroscopy to assist operators performing needle cricothyroidotomy in a swine model. We embedded optical fibers in a 16-gauge intravenous needle catheter. Real-time data were displayed on an oscilloscope, and we used the program to analyze the data immediately. The change of optical density corresponding to 690-nm and 850-nm wavelengths and hemoglobin parameters (HbO2 and Hb concentrations) was analyzed immediately using the program in the laptop. Unique and significant optical differences were presented in this experiment. We could easily identify every different tissue by the change of optical density corresponding to 690-nm and 850-nm wavelengths and hemoglobin parameters (HbO2 and Hb concentrations). Statistical method (Kruskal-Wallis H test) was used to compare differences in tissues at each time-point, respectively. The p values in every tissue in optical density change corresponding to 690 nm and 850 nm were all < 0.001. Furthermore, the p values in every tissue in Hb and HbO2 were also all < 0.001. The results were statistically significant. This is the first and novel study to introduce a dual-wavelength embedded fibers into a standard cricothyroidotomy needle. This proposed system might be helpful to provide us real-time information of the advanced needle tip to decrease possible complications.

Association of Dysfunction of Vascular Access for Hemodialysis With Major Adverse Cardiovascular Events　- A Group-Based Trajectory Model Analysis.

BACKGROUND: An unconventional risk factor, "dysfunction of hemodialysis vascular access", was demonstrated to be associated with subsequent major adverse cardiovascular events (MACE) in our previous study. However, applying this suggestion in a clinical scenario may be not intuitive. A group-based trajectory model was applied to further recognize those patients with the highest risks for MACE.Methods and Results:In a cohort of patients who received hemodialysis from 2001 to 2010, we identified 9,711 cases that developed MACE in the stage of stable maintenance dialysis, and 19,422 randomly selected controls matched to cases on age, gender and duration of dialysis. Events of vascular access dysfunction in the 6-month period before MACE for cases and index dates for controls were evaluated. By group-based trajectory modeling, patients according to their counts of vascular access dysfunction in each month over the 6-month period prior to MACE or index dates were categorized. There were 26,744 patients in group 1 (no dysfunction), 650 in group 2 (escalating dysfunction) and 1,739 in group 3 (persistent dysfunction). Logistic regression analysis indicated that patients in group 3 had the highest chance of subsequent MACE (odds ratio 2.47, in comparison with group 1) after controlling for all the available potential confounders. CONCLUSIONS: Uninterrupted clusters of vascular access dysfunction are associated with a higher risk of subsequent MACE.

Urban-rural disparity in lower extremities amputation in patients with diabetes after nearly two decades of universal health Insurance in Taiwan.

BACKGROUND: To assess the prevalence of urban-rural disparity in lower extremities amputation (LEA) among patients with diabetes and to explore whether patient-related or physician-related factors might have contributed to such disparity. METHODS: This was a population-based study including patients with diabetes aged ≥55 years from 2009 to 2013. Among them, 9236 received LEA. Data were retrieved from Taiwan's National Health Insurance (NHI) claims. A multiple Poisson regression model was also employed to assess the urban-rural difference in LEA prevalence by simultaneously taking into account socio-demographic variables and density of practicing physicians. RESULTS: Between 2009 and 2013, the annual prevalence of LEA declined from 30.4 to 20.5 per 10,000 patients. Compared to patients from urban areas, those who lived in sub-urban and rural areas suffered from a significantly elevated prevalence of LEA, with a prevalence rate ratio (PRR) of 1.47 (95% CI, 1.39-1.55) and 1.68 (95% CI, 1.56-1.82), respectively. The density of physicians who presumably provided diabetes care can barely explain the urban-rural disparity in LEA prevalence. CONCLUSIONS: Although the universal health insurance has largely removed financial barriers to health care, the urban-rural disparity in LEA prevalence still exists in Taiwan after nearly two decades of the NHI program.

A Population-Based Study of Secondary Prostate Cancer Risk after Radiotherapy in Male Patients with Rectal Cancer: A Retrospective Cohort Study.

Background and objective: Risk of secondary prostate cancer after radiation therapy among patients with rectal cancer remains undetermined. Given an increased incidence of rectal cancer in younger people and improved survival for rectal cancer patients who received radiation therapy, the potential risk of secondary prostate cancer needs to be further investigated. Materials and Methods: Male patients (n = 11,367) newly diagnosed rectal cancer and who underwent abdominoperineal resection (APR) or low anterior resection (LAR) from 1 January, 1998 to 31 December, 2010 were identified from Taiwan National Health Insurance Research Database. The incidence and relative risk of secondary prostate cancer in study patients with (n = 1586) and without (n = 9781) radiotherapy within one year after rectal cancer diagnosis were compared using a competing-risks analysis. Results: Rectal cancer patients with radiotherapy were at a significantly decreased risk of developing prostate cancer, with a hazard ratio (HR) of 0.41 (95% confidence interval = 0.20⁻0.83) after adjustment for age. Analysis of the risk estimated for various follow-up lengths suggested that a decreasing HR was seen through the period followed-up and that there was a trend of decreasing prostate cancer risk with time after radiotherapy. Conclusions: Radiotherapy was significantly associated with decreased risk of secondary prostate cancer among rectal cancer patients, by a magnitude of 59%.

Population-Based Cohort Study on Dementia Risk in Patients with Type 1 Diabetes Mellitus.

BACKGROUND: The risk of dementia increases by 15-28% in patients with type 2 diabetes mellitus (DM). However, studies on dementia risk in type 1 DM have been neither comprehensive nor conclusive. METHODS: We carried out a cohort study involving 1,077 patients registered to have type 1 DM from 1998 to 2009 and 32,310 matched non-DM controls who were selected from Taiwan National Health Insurance Claims. These participants were followed up from their first clinical appearance for type 1 DM treatment in 1998-2009 to the date of dementia diagnosis or the last day of 2011. The Cox proportional hazard model was employed to estimate the hazard ratio (HR) of dementia incidence. RESULTS: The incidence rates of dementia reached 42.8 and 13.1 per 104 person-years for the type 1 DM and control groups respectively. The adjusted HR of dementia in patients with type 1 DM was estimated at 3.01 (95% CI 2.18-4.14) after adjustment for demographics, comorbidity, urbanization, monthly income, and annual frequency of ambulatory care visits. No significant difference in sex-specific HR was observed. CONCLUSIONS: The relative risk of developing dementia (118-314%) in patients with type 1 DM was much higher than the -previously reported relative risk (15-28%) associated with type 2 DM.

Risk of Recurrence After Surviving Severe Sepsis: A Matched Cohort Study.

OBJECTIVES: To examine the risk of recurrence in adults who survived first-episode severe sepsis for at least 3 months. DESIGN: A matched cohort study. SETTING: Inpatient claims data from Taiwan's National Health Insurance Research Database. SUBJECTS: We analyzed 10,818 adults who survived first-episode severe sepsis without recurrence for at least 3 months in 2000 (SS group; mean age, 62.7 yr; men, 54.7%) and a group of age/sex-matched (1:1) population controls who had no prior history of severe sepsis. All subjects were followed from the study entry to the occurrence of end-point, death, or until December 31, 2008, whichever date came first. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary end-point was severe sepsis that occurred after January 1, 2001 (the study entry). Relative risk of the end-point was assessed using competing risk regression model. During the follow-up period, severe sepsis and death occurred in 35.0% and 26.5% of SS group and in 4.3% and 18.6% of controls, respectively, representing a covariate-adjusted sub-hazard ratio of 8.89 (95% CI, 8.04-9.83) for the risk of recurrence. In stratified analysis by patient characteristics, the sub-hazard ratios ranged from 7.74 in rural area residents to 23.17 in young adults. In subgroup analysis by first-episode infection sites in SS group, the sub-hazard ratios ranged from 4.82 in intra-abdominal infection to 9.99 in urinary tract infection. CONCLUSIONS: Risk of recurrence after surviving severe sepsis is substantial regardless of patient characteristics or infection sites. Further research is necessary to find underlying mechanisms for the high risk of recurrence in these patients.

Risk of Diabetes Mellitus after First-Attack Acute Pancreatitis: A National Population-Based Study.

OBJECTIVES: Population-based data on the risk of diabetes mellitus onset after acute pancreatitis (AP) are lacking. We assessed the incidence of diabetes in AP survivors compared with matched controls. METHODS: The study cohort, drawn from Taiwan National Health Insurance claims data, included 2,966 first-attack AP patients and 11,864 non-AP general controls individually matched on age and sex, with an AP/non-AP ratio of 1:4. Incidence rate was estimated under Poisson assumption. Relative risks of diabetes were indicated by hazard ratios (HRs) estimated from Cox proportional hazard regression models with a partitioning of time at 3 months to account for proportionality. RESULTS: In the first partition of time (<3 months), the incidences of diabetes were 60.8 and 8.0 per 1,000 person-years in AP and control groups, respectively; representing a covariate-adjusted HR of 5.90 (95% confidence interval (CI) 3.37-10.34). In the second partition (≥3 months), the incidences of diabetes were 22.5 and 6.7 per 1,000 person-years in AP and control groups, respectively (adjusted HR 2.54, 95% CI 2.13-3.04). In the second partition, the risk of diabetes was greater in men than in women (HR 3.21 vs. 1.58, P=0.0004). When the analyses were stratified by severity of AP, the results for mild AP were similar to those for all AP. CONCLUSIONS: The risk of diabetes increases by twofold after AP; therefore, a long-term screening is necessary to evaluate diabetes after an attack regardless of severity. Further research should be conducted to develop cost-effective follow-up strategies, and to elucidate the underlying mechanisms of the relationship between diabetes and AP.

A 15-Year Nationwide Epidemiological Analysis of Guillain-Barré Syndrome in Taiwan.

BACKGROUND: Guillain-Barré syndrome (GBS) is a potentially life-threatening disease that typically occurs after a preceding infectious disease. An accurate estimation of GBS incidence would be useful for investigating the potential causal relationships between risk factors and GBS. Here we described the nationwide incidence of GBS in Taiwan. METHODS: The cases of GBS were obtained from all admission records of the National Health Insurance Research Database. We identified all of the first-admitted GBS patients by a code of ICD-9-CM 357.0 presented at the discharge diagnoses in admission records between 1997 and 2011. Calendar year, age, and sex-specific incidence, and seasonal variation were estimated. RESULTS: A total of 5,998 patients were identified. The male-to-female rate ratio was 1.54. The crude incidence rate was 1.65 per 100,000 person-years. The incidence of GBS was lowest in people aged less than 20 and increased with age, especially in people older than 50 years. In spring, the incidence was 10% higher than in other seasons. CONCLUSIONS: The overall incidence is in line with previous large-scale studies. A significant higher rate in spring is also shown. The potential reasons for the seasonality and higher incidence among older patients should be further investigated.

Cyproheptadine significantly improves the overall and progression-free survival of sorafenib-treated advanced HCC patients.

OBJECTIVE: Sorafenib is a recommended treatment for advanced hepatocellular carcinoma. The study is to evaluate the efficacy of sorafenib plus cyproheptadine compared with sorafenib alone in patients with advanced hepatocellular carcinoma. METHODS: A retrospective cohort study reviewed all consecutive advanced hepatocellular carcinoma cases with Child-Pugh Class A disease starting sorafenib treatment at our hospital from August 2012 to March 2013. They were followed up until 31 December 2013. A total of 52 patients were enrolled: 32 patients in the combination (sorafenib-cyproheptadine) group and 20 patients in the control (sorafenib alone) group. The response to treatment, overall survival and progression-free survival were compared. RESULTS: The median overall survival was 11.0 months (95% confidence interval: 6.8-15.1 months) in the combination group compared with 4.8 months (95% confidence interval: 3.1-6.6 months) in the control group (crude hazard ratio = 0.45, 95% confidence interval: 0.22-0.82). The median progression-free survival time was 7.5 months (95% confidence interval: 5.1-10.0 months) in the combination group compared with 1.7 months (95% confidence interval: 1.4-2.1 months) in the control group (crude hazard ratio = 0.43, 95% confidence interval: 0.22-0.86). Kaplan-Meier survival analysis revealed that both overall survival and progression-free survival in the combination group were significantly longer than that in the control group. The multivariate model found patients in the combination group were 76% less likely to die (adjusted hazard ratio = 0.24, 95% confidence interval: 0.10-0.58) and 82% less likely to have progression (adjusted hazard ratio = 0.18, 95% confidence interval: 0.08-0.44) during the 17 months of follow-up. CONCLUSION: Cyproheptadine may significantly improve survival outcomes of sorafenib-treated advanced hepatocellular carcinoma patients.

Perinatal and childhood risk factors for early-onset type 1 diabetes: a population-based case-control study in Taiwan.

BACKGROUND: Certain factors originating from the perinatal and childhood periods are suspected of contributing to the recent increasing trend of childhood type 1 diabetes (T1D) incidence. This study sought to investigate the relationships between various perinatal and childhood risk factors and T1D incidence in young children (<10 years). METHODS: We used a nested case-control design based on 1,478,573 live births born in 2000-05 in Taiwan. Cases were 632 incident cases of T1D between 2000 and 2008. Ten matched controls for each case were randomly selected. Information on various perinatal risk factors was also identified from claim data. Multiple conditional logistic regression was employed to estimate odds ratio (OR) and 95 confidence interval (CI) of T1D. RESULTS: Childhood infection was significantly associated with an increased risk of T1D (OR = 1.46, 95% CI = 1.23-1.73). Increased risk of T1D was also noted in children born to younger mothers (<25 years) (OR = 1.94, 95% CI = 1.34-2.81), older fathers (>30 years) (OR = 1.56 (95% CI = 1.16-2.10) to 1.57 (95% CI = 1.19-2.05), mothers with Caesarean section (CS) (OR = 2.35, 95% CI = 1.52-3.64), and mothers with gestational diabetes mellitus (OR = 4.36, 95% CI = 2.76-7.77). Fathers with T1D (OR = 7.36, 95% CI = 1.02-57.21) or type 2 diabetes (OR = 1.54, 95% CI = 1.04-2.26) were observed to substantially increase the risk of offspring T1D. CONCLUSIONS: Certain modifiable perinatal factors such as infection and CS may predispose incidence of T1D in young children.

Do physicians have lower risk of severe sepsis and associated mortality? A matched cohort study*.

OBJECTIVES: Physicians generally have higher disease awareness and easier access to medical care, which may help them reduce risk of developing severe sepsis and associated mortality when they suffer from acute infection. However, the opposite situation may occur due to the presence of potential barriers to healthcare in physicians. We aim to examine the risk of severe sepsis and associated mortality in physicians. DESIGN: A matched cohort study. SETTING: Registry of medical professionals and inpatient and outpatient claims data from Taiwan's National Health Insurance Research Database. SUBJECTS: Physicians (n = 29,697) in Taiwan and a group of persons who were demographically and socioeconomically matched (1:1 ratio) and without any medical education and background. All subjects were followed from the index date (January 1, 2000) to the occurrence of endpoint, withdrawal, or December 31, 2008, whichever date came first. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was development of severe sepsis. Secondary outcome was 90-day mortality following severe sepsis. The overall incidence density of severe sepsis was lower in physicians than in controls (3.25 vs 3.90 per 1,000 person-years, p < 0.001). According to the Cox regression model, severe sepsis develops in physicians 24% less likely than controls after baseline covariates were adjusted (adjusted hazard ratio, 0.76; 95% CI, 0.68-0.85). The 90-day mortality rates were similar between physicians and controls with severe sepsis (46.5% vs 45.7%, p = 0.72). However, after controlling for the baseline and additional covariates, the risk of death was significantly lower in physicians than in controls (adjusted hazard ratio, 0.82; 95% CI, 0.71-0.95). CONCLUSIONS: These findings support the hypothesis that physicians are less likely than controls to develop or die of severe sepsis, implying that medical knowledge, higher disease awareness, and easier healthcare access in physicians may help reduce their risk of severe sepsis and associated mortality.

Higher hospital caseload is associated with better treatment outcomes of patients with pleural infection.

The relationship between hospital caseload or volume and the outcome of various surgical procedures has been well documented. However, such hospital caseload-outcome relationship (HCOR) has been seldom addressed in rare medical conditions, such as pleural infection, which is usually associated with pneumonia and may progress to systemic inflammation and severe sepsis. Pleural infection can be treated with medical or surgical pleural space drainage, but the treatment is still unstandardized. This population-based study, using Taiwan's medical claim data, investigated the HCOR in patients with pleural infection. A total of 24,876 patients with pleural infection (median age of 65 years; men, 76.6%) were identified between 1997 and 2008. Hospital caseload was calculated with the average number of cases per hospital annually. The primary outcome is hospital mortality, and the secondary outcomes include hospital length of stay and charges. The risk of mortality among patients treated in hospitals with the highest caseload quartile (≥ 14 cases per hospital annually) is less than those treated in hospitals with the lowest caseload (1 case per hospital annually) by 27% (adjusted odds ratio = 0.73, 95% confidence interval = 0.55 to 0.96). Such beneficial effect disappeared after adjustment for therapeutic procedures. Hospital caseload explained only a small portion of variation in hospital mortality (-2 log likelihood % = 0.26%). These findings suggest that higher hospital caseload is associated with better outcomes of patients with pleural infection. The difference in therapeutic procedures for pleural infection contributes to the observed effect of hospital caseload on hospital mortality.

Urinary non-albumin protein-creatinine ratio is an independent predictor of mortality in patients with type 2 diabetes: a retrospective cohort study.

Albuminuria is a well-known predictor of chronic kidney disease in patients with type 2 diabetes mellitus (DM). However, proteinuria is associated with chronic complications in patients without albuminuria. In this retrospective cohort study, we explored whether non-albumin proteinuria is associated with all-cause mortality and compared the effects of non-albumin proteinuria on all-cause mortality between patients with and without albuminuria. We retrospectively collected data from patients with type 2 DM for whom we had obtained measurements of both urinary albumin-to-creatinine ratio (UACR) and urinary protein-to-creatinine ratio (UPCR) from the same spot urine specimen. Urinary non-albumin protein-creatinine ratio (UNAPCR) was defined as UPCR-UACR. Of the 1809 enrolled subjects, 695 (38.4%) patients died over a median follow-up of 6.4 years. The cohort was separated into four subgroups according to UACR (30 mg/g) and UNAPCR (120 mg/g) to examine whether these indices are associated with all-cause mortality. Compared with the low UACR and low UNAPCR subgroup as the reference group, multivariable Cox regression analyses indicated no significant difference in mortality in the high UACR and low UNAPCR subgroup (hazard ratio [HR] 1.189, 95% confidence interval [CI] 0.889-1.589, P = 0.243), but mortality risks were significantly higher in the low UACR and high UNAPCR subgroup (HR 2.204, 95% CI 1.448-3.356, P < 0.001) and in the high UACR with high UNAPCR subgroup (HR 1.796, 95% CI 1.451-2.221, P < 0.001). In the multivariable Cox regression model with inclusion of both UACR and UNAPCR, UNAPCR ≥ 120 mg/g was significantly associated with an increased mortality risk (HR 1.655, 95% CI 1.324-2.070, P < 0.001), but UACR ≥ 30 mg/g was not significantly associated with mortality risk (HR 1.046, 95% CI 0.820-1.334, P = 0.717). In conclusion, UNAPCR is an independent predictor of all-cause mortality in patients with type 2 DM.

Hepatitis C virus antibody seropositivity is associated with albuminuria but not peripheral artery disease in patients with type 2 diabetes.

Hepatitis C virus (HCV) infection is prevalent in patients with type 2 diabetes mellitus (DM). We aimed to investigate whether HCV antibody (Ab) seropositivity is associated with diabetic micro- and macro-vascular diseases. In this hospital-based cross-sectional study, we retrospectively collected data from patients who participated in the diabetes pay-for-performance program and underwent HCV Ab screening in the annual comprehensive assessment between January 2021 and March 2022. We examined the relationships of HCV Ab seropositivity with the spot urinary albumin-to-creatinine ratio (UACR) and ankle-brachial index (ABI) in patients aged ≥ 50 years with type 2 DM. A total of 1758 patients were enrolled, and 85 (4.83%) of the enrolled patients had HCV Ab seropositivity. Multivariable regression analyses revealed that albuminuria showed a dose-dependent association with HCV Ab seropositivity (UACR [30-299 mg/g]: odds ratio [OR] = 1.463, 95% confidence interval [CI] 0.872‒2.456); UACR [≥ 300 mg/g]: OR = 2.300, 95% CI 1.160‒4.562; P for trend = 0.015) when compared with normal albuminuria (UACR < 30 mg/g). However, the proportion of patients with peripheral arterial disease, defined as an ABI ≤ 0.9, was not significantly different between the groups with and without HCV Ab seropositivity (3.5% vs. 3.9%, P = 0.999). In conclusion, severely increased albuminuria, but not the ABI, showed a significant association with HCV Ab seropositivity in patients aged ≥ 50 years with type 2 DM.

Prenatal phthalate exposure and sex steroid hormones in newborns: Taiwan Maternal and Infant Cohort Study.

BACKGROUND: Newborn anogenital distance (AGD) has been associated with prenatal exposure of phthalates. The association between prenatal phthalate exposure and sex steroid hormones in newborns is unclear. OBJECT: This study aimed to examine whether cord-blood sex hormone levels were associated with prenatal phthalate exposure and newborn anogenital distance (AGD). METHODS: In the Taiwan Maternal and Infant Cohort Study, we recruited 1,676 pregnant women in their third trimester in 2012-2015 in Taiwan. We determined 11 urinary phthalate metabolites in pregnant women, three maternal and five cord-blood steroid sex-hormone concentrations. Five hundred and sixty-five mother-infant pairs with sufficient data were included. Trained neonatologists measured 263 newborns' AGD. We examined the associations of prenatal phthalate metabolite levels with AGD and hormones using linear regression models and evaluated correlations between maternal and cord-blood sex hormone levels and AGD. RESULTS: Compared with the male newborns exposed to maternal phthalate metabolites at the first tertile, AGD was -3.75, -3.43, and -3.53 mm shorter among those exposed at the median tertile of di-2-ethylhexyl phthalate (DEHP) metabolites, monobenzyl phthalate (MBzP), and monomethyl phthalate (MMP), respectively. Compared with those who had exposed at the first tertile, cord-blood follicle-stimulating hormone (FSH) decreased among male newborns exposed at higher levels of MMP, mono-n-butyl phthalate (MnBP), MBzP and DEHP, and among female newborns exposed at higher levels of MMP, MBzP and mono(2-ethyl-5-hydroxyhexyl) phthalate. However, we did not observe significant correlations of maternal or cord-blood sex steroid hormones with newborns' AGDs. CONCLUSIONS: Alterations in cord-blood sex steroid hormone levels were associated with prenatal phthalate exposures, particularly in male newborns. Women aspiring to be pregnant should be alerted of the need of reducing phthalate exposure.

Follicular lymphoma in Taiwan: a low frequency of t(14;18), with grade 3A tumours more closely related to grade 3B than to low-grade tumours.

AIMS: To investigate t(14;18)/IGH-BCL2 in follicular lymphoma (FL) cases from Taiwan. METHODS AND RESULTS: We retrospectively studied 93 consecutive cases, using immunohistochemistry and fluorescence in-situ hybridization (FISH). Fifty-nine (63%) tumours were low-grade (LG) and 34 (37%) were high-grade (HG; 24% FL3A and 13% FL3B). FISH showed IGH, BCL2 and BCL6 rearrangements in 59%, 47% and 11% of cases, respectively, and MYC rearrangement in 5% of FL3A tumours and 25% of FL3B tumours. The translocation partner of all BCL2 rearrangements was IGH, with IGH-BCL2 fusion in 63% of LG tumours and 18% of HG tumours. LG tumours were enriched with a CD10+/bcl-2+/MUM1- phenotype, and were frequently associated with BCL2 rearrangement but less commonly with BCL6 rearrangement. FL3A tumours were more closely related to FL3B tumours than to LG tumours in immunophenotype and genetic aberrations. There was no statistically significant difference between grade 1 and two tumours, between FL3A and FL3B tumours or between nodal and extranodal tumours in immunophenotypic or FISH findings. The cumulative survival rate was higher in LG FL patients with IGH-BCL2 translocation than in those without rearrangement. CONCLUSIONS: In Taiwan, FL3A tumours were more closely related to FL3B tumours than to LG tumours, and a literature review showed that the frequency of t(14;18)/IGH-BCL2 in FL in Taiwan is among the lowest in the world.