Genetic and Phenotypic Spectrum of KMT2D Variants in Taiwanese Case Series of Kabuki Syndrome.

Kabuki syndrome (KS) is a rare genetic disorder characterized by distinct facial features, intellectual disability, and multiple congenital anomalies. We conducted a comprehensive analysis of the genetic and phenotypic spectrum of KS in a Taiwanese patient group of 23 patients. KMT2D variants were found in 22 individuals, with missense (26.1%), nonsense (21.7%), and frameshift (17.4%) variants being the most prevalent. One patient had a KMT2D variant of uncertain significance. The most common clinical characteristics included distinct facial features (100%), intellectual disability (100%), developmental delay (95.7%), speech delay (78.3%), hypotonia (69.6%), congenital heart abnormalities (69.6%), and recurrent infections (65.2%). Other abnormalities included hearing loss (39.1%), seizures (26.1%), cleft palate (26.1%), and renal anomalies (21.7%). This study broadens the mutational and phenotypic spectrum of KS in the Taiwanese population, highlighting the importance of comprehensive genetic testing and multidisciplinary clinical evaluations for diagnosis and treatment.

Application of whole exome sequencing in the diagnosis of muscular disorders: a study of Taiwanese pediatric patients.

Background: Muscular dystrophies and congenital myopathies encompass various inherited muscular disorders that present diagnostic challenges due to clinical complexity and genetic heterogeneity. Methods: This study aimed to investigate the use of whole exome sequencing (WES) in diagnosing muscular disorders in pediatric patients in Taiwan. Out of 161 pediatric patients suspected to have genetic/inherited myopathies, 115 received a molecular diagnosis through conventional tests, single gene testing, and gene panels. The remaining 46 patients were divided into three groups: Group 1 (multiplex ligation-dependent probe amplification-negative Duchenne muscular dystrophy) with three patients (6.5%), Group 2 (various forms of muscular dystrophies) with 21 patients (45.7%), and Group 3 (congenital myopathies) with 22 patients (47.8%). Results: WES analysis of these groups found pathogenic variants in 100.0% (3/3), 57.1% (12/21), and 68.2% (15/22) of patients in Groups 1 to 3, respectively. WES had a diagnostic yield of 65.2% (30 patients out of 46), detecting 30 pathogenic or potentially pathogenic variants across 28 genes. Conclusion: WES enables the diagnosis of rare diseases with symptoms and characteristics similar to congenital myopathies and muscular dystrophies, such as muscle weakness. Consequently, this approach facilitates targeted therapy implementation and appropriate genetic counseling.

A simple scoring algorithm based on intrinsic capacity for functional ability in community-dwelling older adults in Taiwan.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of the overall well-being of older adults, and assessing of IC can help identify early stage of disability and tailor intervention to individual needs. However, there is a lack of effective and simple IC assessment tools. This study aimed to establish predictive scoring algorithms of IC to identify older adults at high risk of impaired functional ability. METHODS: We conducted a cross-sectional study in Southern Taiwan, measuring IC using 7 subitems: cognition, locomotion, vitality, vision, hearing, psychological well-being, and medication usage were measured. Functional ability outcomes included frailty, basic activities of daily living, and instrumental activities of daily living (IADL). The capability of 7 domains of IC in predicting functional ability was assessed by multivariable logistic regression. The prediction of capability of scoring algorithms was indicated by receiver operating characteristic (AUC) curves and measures of sensitivity and specificity. RESULTS: A total of 1,152 older adults were recruited and analyzed. Locomotion emerged as a significant predictor of IADL disability and worsening frailty. The IC-based weighted scoring algorism for predicting IADL demonstrated satisfactory capability (AUC: 0.80), as did the algorithm for predicting worsening frailty (AUC: 0.90). The optimal cutoff points for predicting IADL disability and frailty worse were estimated respectively at 13 and 16, with sensitivity/specificity values of 0.74/0.75 for the IADL prediction algorithm and 0.92/0.77 for the frailty prediction algorithm. CONCLUSION: Our 7-domain IC screening tool proves to be sensitive and practical for early identification of functional disability and frailty among community-dwelling older adults in Taiwan.

Illuminating the Genetic Basis of Congenital Heart Disease in Patients with Kabuki Syndrome.

Congenital heart defects (CHDs) affect a substantial proportion of patients with Kabuki syndrome. However, the prevalence and type of CHD and the genotype-phenotype correlations in Asian populations are not fully elucidated. This study performed a retrospective analysis of 23 Taiwanese patients with molecularly confirmed Kabuki syndrome. Twenty-two patients presented with pathogenic variants in the KMT2D gene. Comprehensive clinical assessments were performed. A literature review was conducted to summarize the spectrum of CHDs in patients with Kabuki syndrome. In total, 16 (73.9%) of 22 patients with pathogenic KMT2D variants had CHDs. The most common types of CHD were atrial septal defects (37.5%), ventricular septal defects (18.8%), coarctation of the aorta (18.8%), bicuspid aortic valve (12.5%), persistent left superior vena cava (12.5%), mitral valve prolapse (12.5%), mitral regurgitation (12.5%), and patent ductus arteriosus (12.5%). Other cardiac abnormalities were less common. Further, there were no clear genotype-phenotype correlations found. A literature review revealed similar patterns of CHDs, with a predominance of left-sided obstructive lesions and septal defects. In conclusion, the most common types of CHDs in Taiwanese patients with Kabuki syndrome who presented with KMT2D mutations are left-sided obstructive lesions and septal defects.

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.

Late creation of vascular access increased post-hemodialysis mortality, hospitalization, and health-care expenditure: A population-based cohort study in Taiwan.

BACKGROUND/PURPOSE: The optimal timing of vascular access (VA) creation for hemodialysis (HD) and whether this timing affects mortality and health-care utilization after HD initiation remain unclear. Thus, we conducted a population-based study to explore their association. METHODS: We used Taiwan's National Health Insurance Research Database to analyze health-care outcomes and utilization in a cohort initiating HD during 2003-2013. We stratified patients by the following VA creation time points: >180, 91-180, 31-90, and ≤30 days before and ≤30 days after HD initiation and examined all-cause mortality, ambulatory care utilization/costs, hospital admission/costs, and total expenditure within 2 years after HD. Cox regression, Poisson regression, and general linear regression were used to analyze mortality, health-care utilization, and costs respectively. RESULTS: We identified 77,205 patients who started HD during 2003-2013. Compared with the patients undergoing VA surgery >180 days before HD initiation, those undergoing VA surgery ≤30 days before HD initiation had the highest mortality-15.92 deaths per 100-person-years, crude hazard ratio (HR) 1.56, and adjusted HR 1.28, the highest hospital admissions rates- 2.72 admission per person-year, crude rate ratio (RR) 1.48 and adjusted RR 1.32, and thus the highest health-care costs- US$31,390 per person-year, 7% increase of costs and 6% increase with adjustment within the 2-year follow-up after HD initiation. CONCLUSION: Late VA creation for HD can increase all-cause mortality, hospitalization, and health-care costs within 2 years after HD initiation. Early preparation of VA has the potential to reduce post-HD mortality and healthcare expenses for the ESKD patients.

Quantitative DNA Methylation Analysis and Epigenotype-Phenotype Correlations in Taiwanese Patients with Silver-Russell Syndrome.

Background: Silver-Russell syndrome (SRS; OMIM #180860) is a clinically and genetically heterogeneous imprinting disorder characterized by prenatal and postnatal growth failure. The aim of this study was to identify the epigenotype-phenotype correlations in these patients using quantitative DNA methylation analysis. Methods: One hundred and eighty-three subjects clinically suspected of having SRS were referred for diagnostic testing by the methylation profiling of H19-associated imprinting center (IC) 1 and imprinted PEG1/MEST regions using methylation-specific high-resolution melting analysis and methylation quantification with the MassARRAY assay. Correlations between quantitative DNA methylation status and clinical manifestations of the subjects according to the Netchine-Harbison (N-H) clinical scoring system for SRS were analyzed. Results: Among the 183 subjects, 90 had a clinical diagnosis of SRS [N-H score ≥ 4 (maximum = 6)] and 93 had an SRS score < 4. Molecular lesions were detected in 41% (37/90) of the subjects with a clinical diagnosis of SRS, compared with 3% (3/93) of those with an N-H score < 4. The IC1 methylation level was negatively correlated with the N-H score. The molecular diagnosis rate was positively correlated with the N-H score. Thirty-one subjects had IC1 hypomethylation (IC1 methylation level <35% by the MassARRAY assay), seven had maternal uniparental disomy 7, and two had pathogenic copy number variants. Among the 90 subjects with an N-H score ≥ 4, the IC1 methylation level was significantly different between those with or without some clinical SRS features, including birth length ≤ 10th centile, relative macrocephaly at birth, normal cognitive development, body asymmetry, clinodactyly of the fifth finger, and genital abnormalities. Conclusions: This study confirmed the suitability of the N-H clinical scoring system as clinical diagnostic criteria for SRS. Quantitative DNA methylation analysis using the MassARRAY assay can improve the detection of epigenotype-phenotype correlations, further promoting better genetic counseling and multidisciplinary management for these patients.

Sex-based differences in ischemic cardiovascular and bleeding outcomes following implantation of drug-eluting stent in patients at high bleeding risk.

BACKGROUND: Patients with high bleeding risk (HBR) may exhibit uncertain adherence to dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) implantation. The current population-based cohort study aimed to investigate the sex-based differences in adverse outcomes among the HBR population by analyzing the National Health Insurance Research Database in Taiwan. METHODS: Patients who had HBR features defined by the Academic Research Consortium (ARC) and received DES implantation between January 1, 2007, and December 31, 2017, were enrolled. Propensity score matching was adopted to select 3,981 pairs with similar clinical cardiovascular risks but different sexes. A competing risk model was performed to evaluate the risk of adverse ischemic events (cardiac death, nonfatal myocardial infarction, and ischemic stroke) and any bleeding events in both sexes. Noncardiac death was considered a competing risk. RESULTS: Within a 5-year follow-up, the incidence rates (per 1,000 person-year (95% confidence interval (CI)) of composite ischemic events and any bleeding events in males were respectively 44.09 (40.25-48.30) and 42.55 (38.79-46.68), while those in females were respectively 40.18 (36.51-44.23) and 42.35 (38.57-46.51). After adjustment for clinical variables, male patients had a marginally increased risk in the composite ischemic events (adjusted subdistribution hazard ratio (SHR) = 1.15 (1.00-1.31), p = 0.045) and a similar risk of any bleeding events (adjusted SHR = 1.00 (0.88-1.15), p = 0.946) compared with female patients. CONCLUSIONS: Of the HBR population, males had an increased risk of ischemic outcomes but a similar risk of bleeding compared with females following DES implantation.

Development and validation of a Chinese version chronic wound health-related quality of life instrument: A methodological study.

AIMS AND OBJECTIVES: To develop a Chinese version of a chronic wound health-related quality of life (QoL) instrument and to examine the psychometric properties of this instrument. BACKGROUND: Existing QoL instruments are not tailored to the linguistic and cultural characteristics of Chinese-speaking patients; a version addressing this gap will increase clinical understanding of their healthcare experience and may help guide chronic wound care. DESIGN: A methodological study. METHODS: The method advanced by DeVellis (2017) was used to develop the instrument. An initial pool of 38 items was created. To optimize scale length and test reliability and validity, exploratory and confirmatory factor analyses were conducted. A total of 23 items formed the final pool. After two rounds of expert discussions, the average content validity index of the final 23 items was .89. RESULTS: A total of 226 patients completed the instrument and were divided into two groups for further analysis. Exploratory factor analysis revealed that 15 items remained in four factors (social activity restrictions, physical and psychological disturbance, wound burden and daily life limitation), which accounted for 64.87% of the variance. Confirmatory factor analysis revealed an acceptable fit of the hypothesized factor structure and the convergent and discriminant validities were achieved. Cronbach's α coefficients for each factor were .807, .773, .799 and .713, respectively. CONCLUSION: The Chinese version of a chronic wound health-related QoL instrument consists of 15 items in four subscales and demonstrates good reliability and validity. RELEVANCE TO CLINICAL PRACTICE: This instrument can be used intermittently or continuously to evaluate the treatment effect of chronic wounds by assessing health-related QoL. Scholars in Chinese-speaking regions may find this culturally compatible instrument useful when conducting studies related to chronic wounds. PATIENT OR PUBLIC CONTRIBUTION: Two hundred twenty-six participants provided their perspectives on health-related QoL.

Pregnancy is associated with more severe injuries from motor vehicle crashes.

OBJECTIVE: Whether pregnancy is associated with severe injuries from motor vehicle crashes (MVCs) remains unclear. This study aimed to investigate the potential relationship between pregnancy and severity of injuries from MVCs. METHODS: We identified a total of 23,559 pregnant women victims who encountered MVCs during pregnancy as well as 94,236 age- and calendar year-at MVC matched non-pregnant women victims that are also involved in MVCs. Injury severity was assessed using the Maximum Abbreviated Injury Scale (MAIS) based on the diagnosis of medical claims after MVCs. Multinomial logistic regression models were used to estimate the odds ratio and corresponding 95 % CI of injury severity levels associated with pregnancy. RESULTS: Pregnant women had a significantly higher risk of both severe (adjusted odds ratio, aOR = 1.79, 95 % CI = 1.54-2.08) and mild injuries (aOR = 8.63, 95 % CI = 8.21-9.07) following MVCs as compared to non-pregnant women victims. Particularly, pregnant women who were riding scooters had an increased risk of severe injury (aOR = 4.25, 95 % CI = 3.58-5.04). In addition, pregnant women who experienced MVC but without any injury were more likely to visit a clinic than non-pregnant MVC victims. CONCLUSION: Pregnant women victims, particularly those who were riding scooters involved in MVCs suffered from a higher risk of severe injury as compared to their non-pregnant counterparts. Our findings suggest that women should consider avoiding riding a scooter and must use restrictive devices during pregnancy, which would help reduce the severity of injuries sustained following an MVC.

Profiles of pregnant women encountering motor vehicle crashes in Taiwan, 2008-2017.

BACKGROUND: Understanding demographic profiles is essential to the assessment of health burden imposed by motor vehicle crashes (MVCs) on pregnant women. However, Asian studies that have examined it are lacking. The study aimed to describe the demographic characteristics and prevalence of MVCs involving pregnant women in Taiwan. METHODS: A cross-sectional study conducted by the Taiwan Birth Notification dataset from 2008 to 2017 was linked with the police-reported traffic collision registry to identify pregnant women involved in MVCs. The pregnant women were categorized according to their gestational age, age at delivery, the role of road user (driver, passenger, or pedestrian), and vehicle types (car, two-wheeled motor vehicle, or others). A chi-square test was performed for the significance test. RESULTS: A total of 22,134 (1.13%) pregnant women were involved in MVCs in the study period. Two-wheeled motor vehicle (47.9%) and driver (81.4%) were the mainly reported vehicle type and road user at the crash scenes, respectively. The majority of MVCs occurred in pregnant women aged 28-34 years. The number of MVCs rapidly declined after 37 weeks of gestation, especially two-wheeled motor vehicle or car crashes. However, the number of pedestrian victims climbed up during the third trimester. CONCLUSION: Pregnant women are susceptible to MVCs regardless of their gestational age, role of a road user, or type of vehicle. The findings of this study emphasize the need for increased awareness of traffic collision prevention among pregnant women aged 28-34. In addition, improving pedestrian safety is essential for the reduction of pregnant victims.

Dynamical characteristics of AC-driven hybrid WSe2 monolayer/AlGaInP quantum wells light-emitting device.

The exploration of functional light-emitting devices and numerous optoelectronic applications can be accomplished on an elegant platform provided by rapidly developing transition metal dichalcogenides (TMDCs). However, TMDCs-based light emitting devices encounter certain serious difficulties, such as high resistance losses from ohmic contacts or the need for complex heterostructures, which restricts the device applications. Despite the fact that AC-driven light emitting devices have developed ways to overcome these challenges, there is still a significant demand for multiple wavelength emission from a single device, which is necessary for full color light emitting devices. Here, we developed a dual-color AC-driven light-emitting device by integrating the WSe2 monolayer and AlGaInP-GaInP multiple quantum well (MQW) structures in the form of capacitor structure using AlOx insulating layer between the two emitters. In order to comprehend the characteristics of the hybrid device under various driving circumstances, we investigate the frequency-dependent EL intensity of the hybrid device using an equivalent RC circuit model. The time-resolved electroluminescence (TREL) characteristics of the hybrid device were analyzed in details to elucidate the underlying physical mechanisms governing its performance under varying applied frequencies. This dual-color hybrid light-emitting device enables the use of 2-D TMDC-based light emitters in a wider range of applications, including broad-band LEDs, quantum display systems, and chip-scale optoelectronic integrated systems.

22q11.2 Deletion Syndrome in Taiwan: Clinical Presentation and Immune System Status of Patients.

Background: 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome exhibiting significant clinical phenotype variability. This study aimed to investigate the clinical features, immune profiles, and cognitive abilities of 22q11.2DS patients receiving treatment at MacKay Memorial Hospital in Taipei, Taiwan. Methods: This is a cross-sectional analysis between January 2001 and December 2022. We recruited 27 patients with 22q11.2DS using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). Our evaluation included patient history, physical examination, laboratory analysis, and cardiac and cognitive assessment. Results: We included 27 patients with 22q11.2DS, 7 (25.9%) of whom were female. The median age of the patients was 17.9 yr. Ninety-three percent of the patients exhibited the characteristic facial features associated with the syndrome. A family history of 22q11.2DS was found in 11.1% of the patients. Furthermore, 74.1% of the patients had a congenital heart defect, the most common of which was tetralogy of Fallot (40.7%). Hypocalcemia was observed in 40.7% of the patients. A low T-cell count was observed in 66.7% of the patients, whereas 18.5% had low immunoglobulin levels. Cognitive assessments revealed that four out of six evaluated patients (66.7%) had an intellectual disability, as evidenced by intellectual quotient scores less than 70. The remaining two patients (33.3%) had a borderline intellectual function. Conclusion: Tetralogy of Fallot, hypocalcemia, immunologic defects, and cognitive impairment were common among our patients. To address the potential multisystem involvement, we recommend that all affected individuals undergo a comprehensive evaluation by a multidisciplinary care team.

Risks of motor vehicle crash before and during pregnancy: A population-based controlled study in Taiwan.

BACKGROUND: Changes in risk of motor vehicle crashes (MVCs) during pregnancy are less known, and very few studies have assessed this issue by using unselected population-based datasets and adopting a before-and-during design. The study aimed to address the risk of MVC events in association with pregnancy using a national pregnant women cohort in Taiwan. METHODS: We conducted a self-matched design in which each woman served as a driver before and during pregnancy. A total of 1,372,664 pregnant women with live birth(s) at 18-50 years of age between 2008 and 2017 were identified from the Birth Notification dataset. MVC events as a driver were ascertained from the Police-reported Traffic Accident Registry dataset. We calculated the rate ratio (RR) with a 95 % confidence interval (CI) using the conditional Poisson regression model to compare the MVC event rates between pre-pregnancy and pregnancy periods. RESULTS: The overall rate of MVC events was significantly reduced during pregnancy (RR = 0.69, 95 % confidence interval (CI) = 0.68-0.71). Mothers with alcoholism during pregnancy were associated with an increased RR at 2.00 but with a very wide CI. Reduction in RR was primarily attributed to the reduced MVC event rate involving scooter crashes (0.60, 95 % CI = 0.58-0.62). CONCLUSION: Although MVC event rates decreased during women became pregnant, many women drivers were still involved in MVCs during pregnancy. Their potential maternal and perinatal conditions along with their offspring's health outcomes need further investigations.

SUMO-Activating Enzyme Subunit 1 Is Associated with Poor Prognosis, Tumor Progression, and Radio-Resistance in Colorectal Cancer.

Concurrent chemoradiotherapy is an effective treatment option for patients with low-grade colorectal cancer (CRC) in the local disease stage. At present, the principle of the Taiwan Medical Center is to treat CRC patients with combination radiotherapy and chemotherapy (high-dose 5-FU) for a period of about five weeks prior to surgery. Radical resection of the tumor is performed at least six to eight weeks after concurrent chemoradiotherapy (CCRT). However, this approach fails to produce the desired therapeutic effect in approximately 20% to 30% of patients, and such patients are unnecessarily exposed to the risks of radiation and drug toxicity posed by this therapy. Therefore, it is crucial to explore new biomarkers to predict the prognosis of CRC. SUMO-activating enzyme subunit 1 (SAE1) plays an important role in SUMOylation, a post-translational modification involved in cellular functions, such as cell proliferation, cell cycle, and apoptosis. In our study, to explore the clinical-pathological role of SAE1 protein in CRC, we evaluated the clinical data and paraffin sections from CRC patients. The expression of SAE1 was evaluated using immunohistochemical analysis, and clinical parameters were analyzed using chi-square and Kaplan-Meier survival tests. The results of in vitro proliferation and radiosensitive assays were compared between control groups and SAE1 siRNA groups. Western blotting was also used to detect the expressions of the SAE1, PARP, cyclin D1, p-NF-κB, and NF-κB proteins. Flow cytometry and colony formation assays were used to detect the effect of SAE-1 on radiosensitivity. In vivo, we detected the growth curve in a mouse xenograft model. The results showed that SAE-1 was revealed to be an independent prognostic biomarker of CRC. SAE1 knockdown inhibited CRC proliferation in vitro and in vivo, and led to the cleavage of PARP, downregulation of cyclin D1 protein expression, and downregulation of p-NF-κB/NF-κB. Additionally, SAE1 knockdown promoted radiosensitivity in CRC cells. Therefore, it was inferred that SAE1 may be used as a potential therapeutic target in CRC treatment.

Associations of maternal motor vehicle crashes during pregnancy with offspring's neonatal birth outcomes.

BACKGROUND: Adverse events in fetuses are well researched but studies on the follow-up health outcomes of infants exposed to maternal motor vehicle crashes (MVCs) during pregnancy have yielded inconsistent results. This study aimed to investigate the association of maternal exposure to MVCs during pregnancy with the risk of adverse neonatal outcomes. METHODS: This population-based cohort study used data from birth notifications in Taiwan. A total of 19 277 offspring with maternal exposure to MVCs during pregnancy and 76 015 randomly selected comparison offspring without such exposure were selected. Neonatal adverse outcomes were identified from National Health Insurance medical claims data. Conditional logistic regression was used to estimate the unadjusted and adjusted odds ratios (aORs) of neonatal adverse outcomes. RESULTS: Offspring exposed to maternal MVCs during pregnancy had a higher risk of birth defects (aOR, 1.21; 95% CI, 1.04-1.41) than offspring without such exposure. This positive association was sustained with exposure to an MVC during the first or second trimester. A dose-response relationship (P = 0.0023) was observed between the level of injury severity and the risk of birth defects. CONCLUSIONS: In the early stages of pregnancy, maternal exposure to MVCs may entail a risk of birth defects in the offspring. The potential mechanisms for the associations of maternal exposure to MVCs with birth defects need further investigation.

Different levels of hypoglycemia in patients with type 2 diabetes, their achieved mean HbA1c vs. all-cause and cardiovascular mortality.

AIM: In patients with type 2 diabetes (T2D), levels of hypoglycemia and their risk of mortality are not well understood. The aim of this study was to ascertain the correlation among disparate levels of hypoglycemia and patients with T2D's achieved mean glycated hemoglobin A1c (HbA1c) with all-cause and cardiovascular mortality. METHODS: 27,932 T2D patients taking hypoglycemic medications at outpatient visits for more than 6 months between 2008 and 2018 were linked to Taiwan's National Death Registry. We determined the respective mortality rates with Poisson assumption, and explored the relative risks of all-cause and cardiovascular mortality according to dissimilar levels of hypoglycemia with their achieved mean HbA1c by Cox proportional hazard regression model with adjustment of potential confounders. RESULTS: T2D patients with level 3 hypoglycemia had the highest rates of all-cause and cardiovascular mortality. Compared with those who never encountered hypoglycemia, study subjects with level 1 and level 2 hypoglycemia did not show excessive risks of either all-cause or cardiovascular mortality. Only those with level 3 hypoglycemia revealed marginal risk of all-cause (Hazard ratio [HR]: 1.18; 95% Confidence Interval [CI] 1.04-1.33) but not cardiovascular mortality (HR: 1.16; 95% CI 0.88-1.53). In T2D patients with hypoglycemia, only those with mean HbA1c ≥9.0% increased all-cause mortality in level 3 hypoglycemia, and cardiovascular mortality in level 1 hypoglycemia. CONCLUSIONS: Elevated risk of all-cause mortality was exclusively found in patients with level 3 hypoglycemia. In T2D patients with hypoglycemia, mean HbA1c ≥ 9% increased all-cause or cardiovascular mortality. Aggressive treatment of accompanying serious illness in severe hypoglycemia may help reduce mortality in patients with T2DM.

Listening and attitude change.

We review research on the role of high-quality listening behavior in attitude change. We examine how listening behaviors can impact attitudes and the mechanisms underlying these effects. The article discusses research that explicitly examines high-quality listening, as well as research that examines behaviors that may indicate high-quality listening or that incorporates high-quality listening into larger interventions. The reviewed research suggests that receiving high-quality listening increases psychological safety and open-minded self-reflection, leading people to consider perspectives they otherwise would not. This in turn leads to less extreme, clearer, and more nuanced views on the topic of conversation. Finally, we highlight the need for further research to better understand the role of listening in attitude change, particularly in non-western cultures.