Assessing the Quality of Cause-of-Death Reporting Before and During the COVID-19 Pandemic.

This study assessed the quality of cause-of-death reporting in the US before and during the COVID-19 pandemic. We used the selection rate and the adjusted odds ratio (aOR) to analyze each cause identified by the National Center for Health Statistics as unsuitable for the underlying cause of death (UCOD). The selection rate was defined as the proportion of deaths with mention of a particular unsuitable UCOD on the death certificate where that cause was ultimately selected as the UCOD. Out of 36 unsuitable UCODs, 33 exhibited a significant decline in selection rates from 2019 to 2021. However, when deaths with mention of COVID-19 on the death certificate were excluded, only 19 causes revealed a significant decline. In analyses that controlled for the age of decedents, aORs in 2021 were significantly lower compared with 2019 for 26 causes, and this number decreased to 17 causes in analyses that excluded COVID-19-related deaths. In conclusion, the overall quality of COD reporting improved during the COVID-19 pandemic, attributable mainly to the fact that over one-tenth of the deaths were related to COVID-19. Yet, for deaths that did not involve COVID-19, improvements in the quality of COD reporting were less prominent for certain causes.

Effects of an integrated ambulatory care program on healthcare utilization and costs in older patients with multimorbidity: a propensity score-matched cohort study.

BACKGROUND: Population aging has increased the prevalence of multimorbidity, jeopardizing the sustainability and efficiency of healthcare systems. This study aimed to evaluate the effects of an integrated ambulatory care program (IACP) on healthcare utilization and costs among older patients with multimorbidity while accounting for the confounding effects of frailty. METHODS: A retrospective cohort study using propensity matching including patients aged 65 or older with two or more chronic conditions attending the outpatient clinic at our hospital between June 1 and December 31, 2019, was conducted. Exposure was defined as receipt of IACP care. Patients not undergoing the IACP comprised the unexposed group and were matched at a ratio of 1:4 to patients undergoing the IACP group according to sex, age, Charlson Comorbidity Index score, multimorbidity frailty index score, and number of outpatient visits within 6 months before the index date. Outcomes were changes in healthcare utilization and related costs between 6 months before and after receiving IACP care. Multivariate regression analyses were used for data analysis and the Generalized Estimation Equation method was used to fit the regression models. RESULTS: A total of 166 (IACP) and 664 (non-exposed) patients were analyzed. The mean participant baseline ages were 77.15 ± 7.77 (IACP) and 77.28 ± 7.90 years (unexposed). In univariate analyses, the IACP group demonstrated greater reductions than the unexposed group in the frequency of outpatient visits (-3.16 vs. -1.36, p < 0.001), number of physicians visited (-0.99 vs. -0.17, p < 0.001), diagnostic fees (-1300 New Taiwan Dollar [NTD] vs. -520 NTD, p < 0.001), drug prescription fees (-250 NTD vs. -70 NTD, p < 0.001), and examination fees (-1620 NTD vs. -700 NTD, p = 0.014). Multivariate analyses demonstrated that patients in the IACP group experienced significant reduction in the frequency of outpatient visits (95% CI: -0.357 to -0.181, p < 0.001), number of physicians visited (95% CI: -0.334 to -0.199, p < 0.001), and overall outpatient costs (95% CI: -0.082 to -0.011, p = 0.01). However, emergency department utilization, hospitalization, and costs did not differ significantly. CONCLUSIONS: Expanding IACPs may help patients with multimorbidity reduce their use of outpatient clinics at the 6-month follow-up, reduce care fragmentation, and promote sustainability of the healthcare system.

International Variations in Dementia and Alzheimer Disease Diagnosis and Certification Habits and Their Associations With Dementia and Alzheimer Disease Mortality: A Cross-Sectional Study of 38 Countries.

OBJECTIVE: To examine international variations in national diagnosis and certification habits prefer recording dementia (D) versus Alzhiemer disease (AD) as the underlying cause of death (UCOD) and their associations with mortality rates of dementia and AD. METHODS: We calculated proportions of D/D+AD and AD/D+AD deaths as proxies of national diagnosis and certification habits. Pearson correlation coefficients (r) were estimated to assess the associations of proportions with the mortality rates of dementia or AD among adults aged 75 to 84 years across 38 countries. RESULTS: The countries with a high preference for recording dementia as the UCOD were Taiwan and Latvia with proportion of D/D+AD deaths of 92% and 88%, respectively, and those with a high preference for recording AD as the UCOD were Slovenia, Turkey, and Poland with proportion of AD/D+AD deaths of 100%, 99%, and 89%, respectively. The r values for the proportions and mortality rate for dementia and AD were 0.67 (95% CI: 0.44-0.81) and 0.46 (95% CI: 0.16-0.68), respectively. CONCLUSION: We identified a small number of countries with obvious natonal diagnosis and certification habits preferring dementia or AD and had moderate effects on international variations in the mortality rates of dementia and AD.

Maternal outcomes in association with motor vehicle crashes during pregnancy: a nationwide population-based retrospective study.

BACKGROUND: Limited studies have assessed the association of motor vehicle crashes (MVCs) during pregnancy with adverse maternal outcomes using a population-based nationwide dataset that covers all MVCs. METHODS: A total of 20 844 births from women who had been involved in MVCs during pregnancy were obtained from the National Birth Notification (BN) Database in Taiwan. We randomly selected 83 274 control births from women in the BN matched on age, gestational age and crash date. All study subjects were linked to medical claims and the Death Registry to identify the maternal outcomes after crashes. Conditional logistic regression models were used to estimate the adjusted odds ratio (aOR) and 95% CI of adverse outcomes associated with MVCs during pregnancy. RESULTS: Pregnant women involved in MVCs had significantly higher risks of placental abruption (aOR=1.51, 95% CI 1.30 to 1.74), prolonged uterine contractions (aOR=1.31, 95% CI 1.11 to 1.53), antepartum haemorrhage (aOR=1.19, 95% CI 1.12 to 1.26) and caesarean delivery (aOR=1.05, 95% CI 1.02 to 1.09) than the controls. Such elevated risks tended to be higher in the MVCs with greater severity. Scooter riders had higher ORs of various adverse maternal outcomes than car drivers. CONCLUSIONS: Women involved in MVCs during pregnancy were at increased risk of various adverse maternal outcomes, especially in those with severe MVCs and riding scooters at MVCs. These findings suggest that clinicians should be aware of these effects, and educational materials that include the above information should be provided as part of prenatal care.

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.

Refracture risk and all-cause mortality after vertebral fragility fractures: Anti-osteoporotic medications matter.

BACKGROUND: Osteoporotic vertebral fractures may predict the future occurrence of fractures and increase mortality. Treating underlying osteoporosis may prevent second fractures. However, whether anti-osteoporotic treatment can reduce the mortality rate is not clear. The aim of this population study was to identify the degree of decreased mortality following the use of anti-osteoporotic medication after vertebral fractures. METHODS: We identified patients who had newly diagnosed osteoporosis and vertebral fractures from 2009 to 2019 using the Taiwan National Health Insurance Research Database (NHIRD). We used national death registration data to determine the overall mortality rate. RESULTS: There were 59,926 patients with osteoporotic vertebral fractures included in this study. After excluding patients with short-term mortality, patients who had previously received anti-osteoporotic medications had a lower refracture rate as well as a lower mortality risk (hazard ratio (HR): 0.84, 95% confidence interval (CI): 0.81-0.88). Patients receiving treatment for more than 3 years had a much lower mortality risk (HR: 0.53, 95% CI: 0.50-0.57). Patients who used oral bisphosphonates (alendronate and risedronate, HR: 0.95, 95% CI: 0.90-1.00), intravenous zoledronic acid (HR: 0.83, 95% CI: 0.74-0.93), and subcutaneous denosumab injections (HR: 0.71, 95% CI: 0.65-0.77) had lower mortality rates than patients without further treatment after vertebral fractures. CONCLUSION: In addition to fracture prevention, anti-osteoporotic treatments for patients with vertebral fractures were associated with a reduction in mortality. A longer duration of treatment and the use of long-acting drugs was also associated with lower mortality.

Validation of coding algorithms for identifying people with viral hepatitis using claims data according to different standard references.

BACKGROUND: To assess the performance of various coding algorithms for identifying people with hepatitis B virus (HBV) and hepatitis C virus (HCV) using claims data according to different reference standards (RSs) and study periods (SPs). METHODS: A proportional random sampling of 10,000 patients aged ≥ 20 years in a health care system in Southern Taiwan were enrolled as study participants. We used three hierarchical RSs (RS1: having positive results of laboratory tests; R2: having RS1 or having prescriptions of anti-HBV or anti-HCV medications; R3: having R1 or R2 or having textual diagnosis recorded in electrical medical records) with three SPs (4-, 8-, and 12-years) to calculate positive predictive value (PPV) and sensitivity (Sen) of 6 coding algorithms using HBV- and HCV-related International Classification of Disease Tenth Revision Clinical Modification (ICD-10-CM) codes in Taiwan National Health Insurance claims data for years 2016-2019. RESULTS: Of 10,000 enrolled participants, the number of participants had confirmed HBV and HCV was 146 and 165, respectively according to RS1 with 4-years SP and increased to 729 and 525, respectively according to RS3 with 12-years SP. For both HBV and HCV, the PPV was lowest according to RS1 and highest according to RS3. The longer the SP, the higher the PPV. However, the Sen was highest according to RS2 with 4-years SP. For both HBV and HCV, the coding algorithm with highest PPV and Sen was " ≥ 3 outpatient codes" and " ≥ 2 outpatient or ≥ 1 inpatients codes," respectively. CONCLUSIONS: In conclusion, using different RSs with different SPs would result in different estimation of PPV and Sen. To achieve the best yield of both PPV and Sen, the optimal coding algorithm is " ≥ 2 outpatients or ≥ 1 inpatients codes" for identifying people with HBV or HCV.

Changes in the rankings of leading causes of death in Japan, Korea, and Taiwan from 1998 to 2018: a comparison of three ranking lists.

BACKGROUND: The ranking lists used by most countries for leading causes of death (CODs) comprise broad category such as cancer, heart disease, and accidents. To provide more specific information, the World Health Organization (WHO) and the Institute of Health Metrics and Evaluation (IHME) proposed lists that splitting broad categories into specific categories. We examined the changes in rankings of leading CODs according to different lists in Japan, Korea, and Taiwan from 1998 to 2018. METHODS: We obtained the number of deaths for three countries from the WHO mortality database for 1998, 2008, and 2018. Age-standardized death rates were calculated for rankings 10 leading CODs using WHO 2000 age structure as standard. RESULTS: The first leading COD was cancer in Japan, Korea, and Taiwan from 1998 to 2018 based on government list; nevertheless, became stroke based on WHO list, and was stroke and ischemic heart disease based on IHME list. In the WHO and IHME lists, cancer is categorized based on cancer site. The number of cancer sites included in the 10 leading CODs in 2018 was 4, 4, and 3 in Japan, Korea, and Taiwan, respectively according to the WHO list and was 4, 4, and 2, respectively according to IHME list. The only difference was the rank of liver cancer in Taiwan, which was 6th according to WHO list and was 18th according to IHME list. The ranking and number of deaths for some CODs differed greatly between the WHO and IHME lists due to the reallocation of "garbage codes" into relevant specific COD in IHME list. CONCLUSIONS: Through the use of WHO and the IHME lists, the relative importance of several specific and avoidable causes could be revealed in 10 leading CODs, which could not be discerned if the government lists were used. The information is more relevant for health policy decision making.

Which ICD-9 codes were assigned for malignant mesothelioma in the mortality data in the United States before the ICD-10 was introduced?

BACKGROUND: Malignant mesothelioma (MM) is rare and fatal; survival in most cases is only about one year. Mortality rate is, therefore, a good proxy measure of incidence rate. However, the specific International Classification of Diseases (ICD) code for MM was not available until the Tenth Revision ICD (ICD-10). Little is known on which Ninth Revision ICD (ICD-9) codes were assigned for MM in the ICD-9 era. METHODS: We used a 1996 double-coded mortality file compiled by the National Center for Health Statistics to calculate the detection rate (DR) and confirmation rate (CR) of selected ICD-9 codes. RESULTS: Of 2386 decedents whose underlying cause of death was MM (ICD-10 code C45), the DR (deaths) of corresponding ICD-9 code was 57% (1365) for code 199 "malignant neoplasm without specification of site;" 19% (448) for code 162.9 "malignant neoplasm of trachea, bronchus, and lung, unspecified;" 13% (310) for code 163 "malignant neoplasm of pleura;" and 11% (271) for other codes. The CR (deaths) for the aforementioned three ICD-9 codes were 4.0% (1365/33,942), 0.3% (448/150,342), and 70.8% (310/438), respectively. CONCLUSIONS: The three ICD-9 codes (199, 162.9, and 163) were the most commonly used codes for MM and composed nine-tenths of all MM deaths in the years before the ICD-10 was introduced. Using only ICD-9 code 163, the code most often used as the surrogate measure of MM in mortality studies in the ICD-9 era, capture may have been only 13% of all MM deaths in the US, and the estimated number of MM deaths missed in 1996 would be 2086.

Hepatitis C virus infection mortality trends according to three definitions with special concern for the baby boomer birth cohort.

We examined mortality trends of hepatitis C virus (HCV) infection in the United States in 1999-2018 according to the following definitions: HCV as the underlying cause of death (UCOD), HCV mentioned anywhere on the death certificate (mentioned), and HCV recorded in Part 1 of the death certificate. By using entity axis information in mortality multiple-cause files, we ascertained the position of HCV on the death certificate. Joinpoint regression analysis was used to evaluate changes in HCV mortality rates according to the definitions. The age-standardized HCV mortality rates (deaths per 100,000 people) in terms of UCOD, mentioned, and Part 1 were, respectively, 1.36, 2.87 and 1.94, in 1999; increased to 1.90, 5.09 and 2.96 in 2013; and declined to 0.98, 3.77 and 2.29 in 2018. The mentioned/UCOD mortality ratio was 2.11 in 1999 and increased to 3.86 in 2018. The mentioned/Part 1 ratio was almost identical (ie 1.48 in 1999 and 1.65 in 2018). The extent of decline from 2014 to 2018 differed according to the definitions; the annual per cent changes for UCOD, mentioned, and Part 1 were -14.6%, -7.1% and -9.8%, respectively. For the same age group, the baby boomer subcohort 1950-1954 had the highest mortality rates among the subcohorts (1945-1949, 1955-1959 and 1960-1964). HCV mortality according to HCV in Part 1 of the death certificate-the explicit opinion of a certifying physician that HCV played a substantial role and directly caused death-differed from that according to HCV as UCOD and HCV mentioned.

Age differences in secular trends in black-white disparities in mortality from systemic lupus erythematosus among women in the United States from 1988 to 2017.

OBJECTIVE: To examine the age differences in secular trends in black-white disparities in mortality from systemic lupus erythematosus (SLE) among women in the United States from 1988 to 2017. METHODS: We used mortality data to calculate age-specific SLE and all-causes (as reference) mortality rates and black/white mortality rates ratios among women from 1988 to 2017. Annual percent change was estimated using joinpoint regression analysis. RESULTS: We identified 10,793 and 4,165,613 black women and 19,455 and 31,129,528 white women who died between 1988 and 2017 from SLE and all-causes, respectively. The black/white SLE mortality rate ratio according joinpoint regression model was 6.6, 7.2, 4.4, and 1.4 for decedents aged 0-24, 25-44, 45-64, and 65+ years in 1988 and was 7.2, 5.9, 4.1, and 1.9, respectively in 2017. No significant decline trend was noted and the annual percent change was 0.3%, -0.7%, -0.2%, and 1.0%, respectively. On the contrast, the black/white all-causes mortality rate ratio was 2.0, 2.5, 1.8, and 1.0, respectively in 1988 and was 1.7, 1.3, 1.5, and 0.9, respectively in 2017, a significant decline trend was noted in each age group. CONCLUSIONS: Black adults, youths and adolescents had four to seven times higher SLE mortality rates than their white counterparts and the black-white disparities persisted during the past three decades. On the contrast, black women had less than two times higher all-causes mortality rates than their white counterparts and black-white disparities significantly diminish during the past three decades.

Changes in liver-related mortality by etiology and sequelae: underlying versus multiple causes of death.

BACKGROUND: The expanded definition of liver-related deaths includes a wide range of etiologies and sequelae. We compared the changes in liver-related mortality by etiology and sequelae for different age groups between 2008 and 2018 in the USA using both underlying and multiple cause of death (UCOD and MCOD) data. METHODS: We extracted mortality data from the CDC WONDER. Both the absolute (rate difference) and relative (rate ratio and 95% confidence intervals) changes were calculated to quantify the magnitude of change using the expanded definition of liver-related mortality. RESULT: Using the expanded definition including secondary liver cancer and according to UCOD data, we identified 68,037 liver-related deaths among people aged 20 years and above in 2008 (29 per 100,000) and this increased to 90,635 in 2018 (33 per 100,000), a 13% increase from 2008 to 2018. However, according to MCOD data, the number of deaths was 113,219 (48 per 100,000) in 2008 and increased to 161,312 (58 per 100,000) in 2018, indicating a 20% increase. The increase according to MCOD was mainly due to increase in alcoholic liver disease and secondary liver cancer (liver metastasis) for each age group and hepatitis C virus (HCV) and primary liver cancer among decedents aged 65-74 years. CONCLUSION: The direction of mortality change (increasing or decreasing) was similar in UCOD and MCOD data in most etiologies and sequelae, except secondary liver cancer. However, the extent of change differed between UCOD and MCOD data.

Incidence and characteristics of paediatric abusive head trauma in Taiwan, 2006-2015: a nationwide population-based study.

OBJECTIVES: To examine the incidence rate and characteristics of paediatric abusive head trauma (PAHT) among children under age 5 years in Taiwan. METHODS: The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) was used to identify broad and narrow definitions of children aged under 5 years with PAHT from 2006 to 2015 in Taiwan using a representative national insurance research database. Medical resource utilisation was also analysed. Incidence rates per 100 000 person-years were calculated and presented with 95% CI. Joinpoint regression analysis was used to detect the changes in trends and calculate the annual percentage change in PAHT incidence over time. RESULTS: From 2006 to 2015, 479 (narrow definition) and 538 (broad definition) PAHT cases were identified. Incidence rates of PAHT by narrow and broad definitions among children under 1 year of age (18.7/100 000 and 20.0/100 000) were nearly 10-fold or 20-fold higher than for children aged 1-2 (1.7/100 000 and 2.1/100 000) and 3-5 (0.9/100 000 and 1.2/100 000) years. The PAHT incidence significantly increased since 2012, with trends varying by age and gender. Our results suggest that over 40% of the children with PAHT experienced serious injury and nearly 13% were fatal cases. For 87% (n=57) of fatal cases, this was their first ever hospitalisation. The number of fatal cases among infants was fourfold higher than that of children aged 1-5 years. CONCLUSIONS: This study provides a robust national estimate of PAHT and identifies infants as the most vulnerable group for PAHT in Taiwan. Education to enhance healthcare profession's sensitivity and competence for the early identification and diagnosis of PAHT is critical.

Mortality, morbidity, and risk factors in Taiwan, 1990-2017: findings from the Global Burden of Disease Study 2017.

BACKGROUND: Taiwan has implemented a national health insurance system since 1995 with high coverage and utilization rate. However, the health care system in Taiwan is facing immense challenges due to rapid population ageing. We have evaluated the landscape of population health by revisiting the results of GBD 2017 study. METHODS: Taiwan vital registration data (1980-2016) and Taiwan national health insurance database (2016) were used. We also conducted benchmarking comparisons with selected countries in East Asia from 1990 to 2017. RESULTS: The age-standardized disability-adjusted life-year (DALY) rates decreased by one-quarter from 1990 to 2017; however, progress was relatively slow compared to the comparator countries and has been stagnant recently. The Social-demographic Index (SDI) level in Taiwan in 2017 was 0.86, which is similar to Japan, Singapore, and South Korea in 2017, while the SDI level of China in 2017 was similar to that of Taiwan (0.69) in 1990. Although Taiwan's SDI reached the same level as those in Japan, Singapore, and South Korea in 2017, modifiable risk factors still contributed to nearly half of Taiwan's total disease burden. Five leading risk factors (high fasting plasma glucose, high body-mass index, alcohol use, illicit drug use, and impaired kidney function) accounted for a higher DALY rate in Taiwan than comparator countries in 2017. CONCLUSION: Taiwan made marked progress in health from 1990 to 2017. However, interventions targeted on major modifiable disease risk factors should be prioritized to realize the full potential of heath improvement in the process of rapid socioeconomic development.

Improving the Use of Mortality Data in Public Health: A Comparison of Garbage Code Redistribution Models.

Objectives. To describe and compare 3 garbage code (GC) redistribution models: naïve Bayes classifier (NB), coarsened exact matching (CEM), and multinomial logistic regression (MLR).Methods. We analyzed Taiwan Vital Registration data (2008-2016) using a 2-step approach. First, we used non-GC death records to evaluate 3 different prediction models (NB, CEM, and MLR), incorporating individual-level information on multiple causes of death (MCDs) and demographic characteristics. Second, we applied the best-performing model to GC death records to predict the underlying causes of death. We conducted additional simulation analyses for evaluating the predictive performance of models.Results. When we did not account for MCDs, all 3 models presented high average misclassification rates in GC assignment (NB, 81%; CEM, 86%; MLR, 81%). In the presence of MCD information, NB and MLR exhibited significant improvement in assignment accuracy (19% and 17% misclassification rate, respectively). Furthermore, CEM without a variable selection procedure resulted in a substantially higher misclassification rate (40%).Conclusions. Comparing potential GC redistribution approaches provides guidance for obtaining better estimates of cause-of-death distribution and highlights the significance of MCD information for vital registration system reform.

Physician code creep after the initiation of outpatient volume control program and implications for appropriate ICD-10-CM coding.

BACKGROUND: Most studies on the physician code creep (i.e., changes in case mix record-keeping practices to improve reimbursement) have focused on episodes (inpatient hospitalizations or outpatient procedures). Little is known regarding changes in diagnostic coding practices for better reimbursement among a fixed cohort of patients with chronic diseases. METHODS: To examine whether physicians in tertiary medical centers changed their coding practices after the initiation of the Outpatient Volume Control Program (OVCP) in Taiwan, we conducted a retrospective observational study of four patient cohorts (two interventions and two controls) from January 2016 to September 2017 in Taiwan. The main outcomes were the number of outpatient visits with four coding practices: 1) OVCP monitoring code recorded as primary diagnosis; 2) OVCP monitoring code recorded as secondary diagnosis; 3) non-OVCP monitoring code recorded as primary diagnosis; 4) non-OVCP monitoring code recorded as secondary diagnosis. RESULTS: The percentage change of the number of visits with coding practice 1 between 2016Q1 and 2017Q3 was - 74% for patients with hypertension and - 73% with diabetes in tertiary medical centers and - 23% and - 17% in clinics, respectively. By contrast, the percentage changes of coding practice 3 were + 73% for patients with hypertension and + 46% for patients with diabetes in tertiary medical centers and - 19% and - 2% in clinics, respectively. CONCLUSIONS: Physician code creep occurred after the initiation of the OVCP. Education regarding appropriate outpatient coding for physicians will be relatively effective when proper coding is related to reimbursement.

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 (K33-238 R) 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).

Changes in drowning mortality rates and quality of reporting from 2004-2005 to 2014-2015: a comparative study of 61 countries.

BACKGROUND: This study assessed international variations in changes in drowning mortality rates and the quality of reporting specific information in death certificates over the past decade. METHODS: Drowning mortality data of 61 countries were extracted from the World Health Organization Mortality Database. We calculated the percentage change (PC) in age-standardized drowning mortality rates and percentage of drowning deaths reported with unspecified codes between 2004 and 2005 and 2014-2015. RESULTS: Of the 61 countries studied, 50 exhibited a reduction in drowning mortality rates from 2004 to 2005 to 2014-2015. Additionally, five countries-Lithuania, Moldova, Kyrgyzstan, Romania, and El Salvador-with a high mortality rate in 2004-2005 (> 40 deaths per 100,000) showed improvement (PC < - 32%). By contrast, four countries-South Africa, Guyana, Morocco, and Guatemala-exhibited a more than twofold increase in mortality rates. Regarding the quality of reporting, 34 countries exhibited a decrease in the percentage of unspecified codes. Additionally, three countries-Paraguay, Serbia, and Croatia-with moderate and high percentages of unspecified codes (> 40%) exhibited a marked reduction (PC < - 60%), whereas three countries-Malaysia, Belgium, and Nicaragua-exhibited a notable increase. CONCLUSIONS: Large international variations in the extent of changes in drowning mortality rates and the quality of reporting specific information on the death certificate were observed during the study period.

Trends in proportions of hospitals and operators not meeting minimum percutaneous coronary intervention volume standards in Taiwan, 2001-2013.

OBJECTIVE: To examine trends in proportions of hospitals and operators not meeting the minimum percutaneous coronary intervention (PCI) volume standards in Taiwan during 2001-2013. BACKGROUND: The 2013 Clinical Competence Statement recommends that operators perform a minimum of ≥50 PCIs annually (averaged over a 2-year period) in hospitals conducting ≥200 PCIs annually. METHODS: Taiwan National Health Insurance claims data from 2001 to 2013 are used to determine the annual numbers of PCIs performed by each hospital and operator. RESULTS: The percentage of hospitals conducting annual PCI volumes of <200 decreased from 57% (26/46) in 2001 to 39% (29/74) in 2007 and 33% (33/91) in 2013; the percentage of operators conducting PCI volumes <50 annually remained relatively constant at 60% (146/243) in 2001, 60% (270/452) in 2007, and 58% (354/611) in 2013; and the percentage of operators conducting low volumes (<50) in low-volume hospitals (<200) decreased from 24% (57/243) in 2001 to 15% (66/452) in 2007 and 12% (76/611) in 2013. CONCLUSIONS: Approximately one-third of hospitals and three-fifths of operators in Taiwan failed to meet minimum PCI volume standards. Further research examining patient outcomes from PCIs performed by low-volume hospitals and operators is recommended.

When high-volume PCI operators in high-volume hospitals move to lower volume hospitals-Do they still maintain high volume and quality of outcomes?

OBJECTIVES: The aim of this quasi-experimental study was to examine whether high-volume percutaneous coronary intervention (PCI) operators still maintain high volume and quality of outcomes when they moved to lower volume hospitals. BACKGROUND: Systematic reviews have indicated that high-volume PCI operators and hospitals have higher quality outcomes. However, little is known on whether high PCI volume and high quality outcomes are mainly due to operator characteristics (i.e., skill and experience) and is portable across organizations or whether it is due to hospital characteristics (i.e., equipment, team, and management system) and is less portable. METHODS: We used Taiwan National Health Insurance claims data 2000-2012 to identify 98 high-volume PCI operators, 10 of whom moved from one hospital to another during the study period. We compared the PCI volume, risk-adjusted mortality ratio, and major adverse cardiovascular event (MACE) ratio before and after moving. RESULTS: Of the 10 high-volume operators who moved, 6 moved from high- to moderate- or low-volume hospitals, with median annual PCI volumes (interquartile range) of 130 (117-165) in prior hospitals and 54 (46-84) in subsequent hospitals (the hospital the operator moved to), and the remaining 4 moved from high to high-volume hospitals, with median annual PCI volumes (interquartile range) of 151 (133-162) in prior hospitals and 193 (178-239) in subsequent hospitals. No significant differences were observed in the risk-adjusted mortality ratios and MACE ratios between high-volume operators and matched controls before and after moving. CONCLUSIONS: High-volume operators cannot maintain high volume when they moved from high to moderate or low-volume hospitals; however, the quality of care is maintained. High PCI volume and high-quality outcomes are less portable and more hospital bound.