Fu Wen Liang

The temporal trends of incidence, treatment, and in-hospital mortality of acute myocardial infarction over 15 years in a Taiwanese population

BACKGROUNDnThe study was conducted to examine the nationwide temporal trends of incidence, treatment, and short-term outcomes for acute myocardial infarction (AMI) over a 15-year period in Taiwan.nnnMETHODSnWe identified patients who were hospitalized for incident AMI between 1997 and 2011 from the inpatient medical claim dataset of the National Health Insurance Research Database. Age- and sex-adjusted incidence and in-hospital mortality rates were calculated for AMI, and separately for ST-segment elevation and non-ST-segment elevation myocardial infarction (STEMI and NSTEMI).nnnRESULTSnA total of 144,634 patients were identified. The incidence rates (per 100,000 population) of AMI increased from 30 in 1997 to 42 in 2011, which was mainly driven by the increase of NSTEMI. The in-hospital mortality rate after AMI decreased from 9.1% in 1997 to 6.5% in 2011, which was also driven by the case mortality rate for NSTEMI. Although the in-hospital mortality rates significantly decreased from 7.3% to 5.1% between 1997 and 2003 for STEMI, it did not change significantly from 2004 to 2011. Moreover, AMI patients undergoing revascularization treatment, particularly PCI, was the most important independent predictor for improved in-hospital survival.nnnCONCLUSIONnThe results of this study demonstrated a recent dramatic increase in the incidence rates and a decrease in short-term mortality in patients with NSTEMI; while the incidence and in-hospital morality of STEMI only modestly changed over time in Taiwan. Further quality improvement approaches for AMI prevention and treatment to favorably affect the incidence and outcomes from both major types of AMI are highly recommended.

Trends in Unintentional Fall-Related Traumatic Brain Injury Death Rates in Older Adults in the United States, 1980–2010: A Joinpoint Analysis

Unintentional fall-related traumatic brain injury (TBI) death rate is high in older adults in the United States, but little is known regarding trends of these death rates. We sought to examine unintentional fall-related TBI death rates by age and sex in older adults from 1980 through 2010 in the United States. We used multiple-cause mortality data from 1980 through 2010 (31 years of data) to identify fall-related TBI deaths. Using a joinpoint regression program, we determined the joinpoints (years at which trends change significantly) and annual percentage changes (APCs) in mortality trends. The fall-related TBI death rates (deaths per 100,000 population) in older adults ages 65-74, 75-84, and 85 years and above were 2.7, 9.2, and 21.5 for females and 8.5, 18.2, and 40.8 for males, respectively, in 1980. The rate was about the same in 1992, yet increased markedly to 5.9, 23.4, and 68.9 for females and 11.6, 41.2, and 112.4 for males, respectively, in 2010. For males all 65 years years of age and above, we found the first joinpoint in 1992, when the APC for 1980 through 1992, -0.8%, changed to 6.2% for 1992-2005. The second joinpoint occurred in 2005, when the APC decreased to 3.7% for 2005-2010. For all females 65 years of age and above, the first joinpoint was in 1993 when the APC for 1980 through 1993, -0.2%, changed to 7.6% from 1993 to 2005. The second joinpoint occurred in 2005 when the APC decreased to 3.8% for 2005-2010. This descriptive epidemiological study suggests increasing fall-related TBI death rates from 1992 to 2005 and then a slowdown of increasing trends between 2005 and 2010. Continued monitoring of fall-related TBI death rate trends is needed to determine the burden of this public health problem among older adults in the United States.

Hepatocellular carcinoma–related cyclin D1 is selectively regulated by autophagy degradation system

Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We previously reported that autophagy preferentially recruits and degrades the oncogenic microRNA (miR)‐224 to prevent HCC. Therefore, in the present study, we attempted to clarify whether cyclin D1 is another oncogenic factor selectively regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse correlation between low autophagic activity and high cyclin D1 expression in tumors of 147 HCC patients and three murine models, and these results taken together revealed a correlation with poor overall survival of HCC patients, indicating the importance of these two events in HCC development. We found that increased autophagic activity leads to cyclin D1 ubiquitination and selective recruitment to the autophagosome (AP) mediated by a specific receptor, sequestosome 1 (SQSTM1), followed by fusion with lysosome and degradation. Autophagy‐selective degradation of ubiquitinated cyclin D1 through SQSTM1 was confirmed using cyclin D1/ubiquitin binding site (K33‐238R) and phosphorylation site (T286A) mutants, lentivirus‐mediated silencing autophagy‐related 5 (ATG5), autophagy‐related 7 (ATG7), and Sqstm1 knockout cells. Functional studies revealed that autophagy‐selective degradation of cyclin D1 plays suppressive roles in cell proliferation, colony, and liver tumor formation. Notably, an increase of autophagic activity by pharmacological inducers (amiodarone and rapamycin) significantly suppressed tumor growth in both the orthotopic liver tumor and subcutaneous tumor xenograft models. Our findings provide evidence of the underlying mechanism involved in the regulation of cyclin D1 by selective autophagy to prevent tumor formation. Conclusion: Taken together, our data demonstrate that autophagic degradation machinery and the cell‐cycle regulator, cyclin D1, are linked to HCC tumorigenesis. We believe these findings may be of value in the development of alternative therapeutics for HCC patients. (Hepatology 2018;68:141‐154).

Underreporting of maternal mortality in Taiwan: A data linkage study

OBJECTIVEnThis study examined the extent to which maternal mortality in Taiwan is underreported in officially published mortality statistics.nnnMATERIALS AND METHODSnWe used National Health Insurance claims data collected from two million samples, which were linked with the officially published mortality data, to identify women aged 15-49 years, who were admitted to a hospital with pregnancy-related diagnoses during 2000-2009 and died during the pregnancy or within 42 days after the termination of pregnancy.nnnRESULTSnBased on these linked data, we identified 26 maternal deaths, only nine of which were reported in the original officially published mortality data; thus, the rate of underreporting was 65% [(26 - 9)/26]. The revised maternal mortality ratio was 14.1 deaths per 100,000 live births (95% confidence interval: 8.7-19.5), which was approximately three times higher than the official reported ratio of 4.9 (95% confidence interval: 1.7-8.1). The most common cause of maternal deaths was amniotic fluid embolism (n = 10), followed by eclampsia and preeclampsia (n = 4).nnnCONCLUSIONnApproximately two-thirds of the maternal deaths in Taiwan were unreported in the officially published mortality data. Hence, routine nationwide data linkage is essential to monitor maternal mortality in Taiwan accurately.

Maternal Mortality in Taiwan: A Nationwide Data Linkage Study

Background To examine the changes in the maternal mortality ratio (MMR) and causes of maternal death in Taiwan based on nationwide linked data sets. Methods We linked four population-based data sets (birth registration, birth notification, National Health Insurance inpatient claims, and cause of death mortality data) to identify maternal deaths for 2004–2011. Subsequently, we calculated the MMR (deaths per 100,000 live births) and the proportion of direct and indirect causes of maternal death by maternal age and year. Findings Based on the linked data sets, we identified 236 maternal death cases, of which only 102 were reported in officially published mortality data, with an underreporting rate of 57% [(236−102) × 100 / 236]. The age-adjusted MMR was 18.4 in 2004–2005 and decreased to 12.5 in 2008–2009; however, the MMR leveled off at 12.6 in 2010–2011. The MMR increased from 5.2 in 2008–2009 to 7.1 in 2010–2011 for patients aged 15–29 years. Women aged 15–29 years had relatively lower proportion in dying from direct causes (amniotic fluid embolism and obstetric hemorrhage) compared with their counterpart older women. Conclusions Approximately two-thirds of maternal deaths were not reported in officially published mortality data. Routine surveillance of maternal mortality by using enhanced methods is necessary to monitor the health status of reproductive-age women. Furthermore, a comprehensive maternal death review is necessary to explore the preventability of these maternal deaths.

Risk of end-stage renal disease after cancer nephrectomy in Taiwan: a nationwide population-based study.

Background The conclusions of population-based studies examining the risk of developing end-stage renal disease (ESRD) after nephrectomy among patients with renal cell carcinoma (RCC) remain inconclusive. In this study, we sought to examine whether patients with RCC undergoing radical nephrectomy (RN) have higher risk of ESRD compared to those undergoing partial nephrectomy (PN). Methods Nationwide population-based retrospective cohort of 7670 patients with RCC who underwent RN or PN between 2000 and 2011 as recorded in the Taiwan National Health Insurance in-patient claims data were analyzed. The primary outcome of interest was the occurrence of ESRD requiring regular renal hemodialysis. Multivariable Cox proportional hazard regression model was performed to assess the risk. Findings The median follow-up for the post-propensity matched cohort (1212 PN and 2424 RN) was 48 months. Seventy patients (2.9%) developed ESRD among those who underwent RN, for an incidence rate of 6.9 cases per 1000 person-years. In contrast, only 23 patients (1.9%) developed ESRD among patients who underwent PN, for an incidence rate of 5.5 cases per 1000 person-years. Despite the higher incidence rate of ESRD among RN, the aIRR (RN/PN) was 1.26 (95% CI 0.78-2.01), which was not statistically significant. Conclusions This Taiwan nationwide population-based study suggests that patients with RCC undergoing RN do not have significantly higher risk of developing ESRD compared to those undergoing PN.

Characteristics of Early and Late Adopting Hospitals Providing Percutaneous Coronary Intervention in Taiwan

Background Studies in the United States suggested that the characteristics of hospitals providing percutaneous coronary intervention (PCI) differed from those not providing PCI. However, little is known on the differences between the characteristics of early‐adopting hospitals and those of late‐adopting hospitals, and on their potential impacts on PCI volume and access. Methods and Results We used inpatient claims data from 1997 to 2012 from the Taiwan National Health Insurance program to identify the hospitals offering PCI. Geographic information systems (GIS) were used to determine the population access to PCI hospital. As of 2012, 88 hospitals were capable of providing PCI. On the basis of the year that the hospitals started providing PCI, 32 hospitals were designated as early adopters (before 1998), 23 as early majority (1998–2002), 24 as late majority (2003–2007), and 16 as laggards (2008–2012). Hospitals that adopted PCI later were smaller in size and closer to an existing PCI hospital and had lower PCI volumes performed and less bypass surgery support. The median PCI volumes in 2012 were n=706, 330, 138, and 81 in early adopters, early majority, late majority, and laggards, respectively. Despite the low volume of PCI performed in laggard hospitals, the percentage with ST‐elevation myocardial infarction and acute myocardial infarction as principal discharge diagnosis was higher than their early‐adopting hospital counterparts. The percentage of the Taiwanese population living within 40 km of PCI hospitals (appropriate access defined in this study) was 95.7% in 1997 and 98.0% in 2002, and this has remained unchanged since 2002. Conclusions The characteristics of early‐adopting hospitals differed from those of late‐adopting hospitals. Despite lower PCI volume performed in late‐adopting hospitals, many of them are in remote areas and provide needed and timely services for patients with acute myocardial infarction.

Cognitively-Related Basic Activities of Daily Living Impairment Greatly Increases the Risk of Death in Alzheimers Disease

Introduction Some Alzheimer’s disease (AD) patients die without ever developing cognitively impaired basic activities of daily living (basic ADL), which may reflect slower disease progression or better compensatory mechanisms. Although impaired basic ADL is related to disease severity, it may exert an independent risk for death. This study examined the association between impaired basic ADL and survival of AD patients, and proposed a multistate approach for modeling the time to death for patients who demonstrate different patterns of progression of AD that do or do not include basic ADL impairment. Methods 1029 patients with probable AD at the Baylor College of Medicine Alzheimer’s Disease and Memory Disorders Center met the criteria for this study. Two complementary definitions were used to define development of basic ADL impairment using the Physical Self-Maintenance Scale score. A weighted Cox regression model, including a time-dependent covariate (development of basic ADL impairment), and a multistate survival model were applied to examine the effect of basic ADL impairment on survival. Results As expected decreased ability to perform basic ADL at baseline, age at initial visit, years of education, and sex were all associated with significantly higher mortality risk. In those unimpaired at baseline, the development of basic ADL impairment was also associated with a much greater risk of death (hazard ratios 1.77–4.06) over and above the risk conferred by loss of MMSE points. A multi-state Cox model, controlling for those other variables quantified the substantive increase in hazard ratios for death conferred by the development of basic ADL impairment by two definitions and can be applied to calculate the short term risk of mortality in individual patients. Conclusions The current study demonstrates that the presence of basic ADL impairment or the development of such impairments are important predictors of death in AD patients, regardless of severity.

Association of maternal chronic disease with risk of congenital heart disease in offspring

Background: Information about known risk factors for congenital heart disease is scarce. In this population-based study, we aimed to investigate the relation between maternal chronic disease and congenital heart disease in offspring. Methods: The study cohort consisted of 1 387 650 live births from 2004 to 2010. We identified chronic disease in mothers and mild and severe forms of congenital heart disease in their offspring from Taiwan’s National Health Insurance medical claims. We used multivariable logistic regression analysis to assess the associations of all cases and specific types of congenital heart disease with various maternal chronic diseases. Results: For mothers with the following chronic diseases, the overall prevalence of congenital heart disease in their children was significantly higher than for mothers without these diseases: diabetes mellitus type 1 (adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 1.66–3.25), diabetes mellitus type 2 (adjusted OR 2.85, 95% CI 2.60–3.12), hypertension (adjusted OR 1.87, 95% CI 1.69–2.07), congenital heart defects (adjusted OR 3.05, 95% CI 2.45–3.80), anemia (adjusted OR 1.31, 95% CI 1.25–1.38), connective tissue disorders (adjusted OR 1.39, 95% CI 1.19–1.62), epilepsy (adjusted OR 1.37, 95% CI 1.08–1.74) and mood disorders (adjusted OR 1.25, 95% CI 1.11–1.41). The same pattern held for mild forms of congenital heart disease. A higher prevalence of severe congenital heart disease was seen only among offspring of mothers with congenital heart defects or type 2 diabetes. Interpretation: The children of women with several kinds of chronic disease appear to be at risk for congenital heart disease. Preconception counselling and optimum treatment of pregnant women with chronic disease would seem prudent.

Regional and hospital variations in the extent of decline in the proportion of percutaneous coronary interventions performed for nonacute indications – a nationwide population-based study

BackgroundThe volume and percentage of percutaneous coronary interventions (PCIs) performed for nonacute indications have declined in the United States since 2007. However, little is known if similar trends occurred in Taiwan.MethodsWe used data from Taiwan National Health Insurance inpatient claims to examine the regional and hospital variations in the extent of decline in the percentage of nonacute indication PCIs from 2007 to 2012.ResultsThe volume of total PCIs persistently increased from 29,032 in 2007 to 35,811 in 2010 and 37,426 in 2012. However, the volume of nonacute indication PCIs first increased from 7916 in 2007 to 9143 in 2009 and then decreased to 8666 in 2012. The percentage of nonacute indication PCIs steadily decreased from 27% in 2007 to 26% in 2009 and then to 23% in 2012, axa0−xa015% change. The extent of decline was largest in the North region (from 27% to 21ufeff%, axa0−xa022% change) and least in Kaopin region (from 20% to 18%, axa0−xa013% change). Of the 71 hospitals studied, 14 did not show a decreasing trend. Five of the 14 hospitals even showed an increasing trend, with a percentage change >10% between 2007 and 2012. In 2012, 6 hospitals had a nonacute indication PCI percentagexa0>35%.ConclusionsIn Taiwan, four-fifths of the hospitals showed a decline in the percentage of nonacute indication PCIs from 2007 to 2012. It is plausible that Taiwanese cardiologists would have been influenced by the recommendations of crucial US trials and guidelines.