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BACKGROUND: The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommended in May 2019 that patients with hepatitis C virus (HCV)...

Background This study examined demographics, comorbidities and healthcare resource use (HCRU) and costs among Japanese patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Methods We conducted a repeated cross-sectional analysis of the Medical Data Vision (MDV) claims database, from January 2011 to March 2018. Demographics were described at index date and by calendar year; a “NASH” subpopulation included patients with ≥ 1 claim for NASH at any time. Prevalence of pre-specified comorbidities of interest and data-emergent top comorbidities were estimated. All-cause HCRU and costs were quantified by calendar year. Outcomes were compared between 2011 and 2017 using partially overlapping t tests. Results 58,958 patients (mean age 61.6 years; 55.5% male) were included. 1139 patients (2%) were in the NASH subpopulation. At baseline, comorbid cardiovascular disease (69.4%), diabetes (62.1%) and hyperlipidaemia (54.4%) were most prevalent; comorbidity prevalence increased with age. Mean outpatient visits decreased from 9.36 per patient in 2011 to 7.80 in 2017; mean inpatient admissions increased (both p p = 0.552), cost burden shifted from the outpatient to inpatient setting between 2011 and 2017. All-cause healthcare resource use/costs were generally higher for the NASH subgroup compared with the overall population. Conclusions There is a high burden of disease among Japanese NAFLD/NASH patients, including a high prevalence of comorbidities which generally increase with age. Accordingly, substantial all-cause HCRU and costs were incurred.

AIMS Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality in Japan. As the treatment of viral hepatitis improves, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are rapidly becoming leading causes of HCC in Japan. This structured review aims to characterize the morbidity and mortality of HCC and other malignant and non-malignant complications among Japanese NAFLD and NASH patients. METHODS An English and Japanese structured search of published works was undertaken in PubMed, Embase, and Ichushi Web databases, identifying 6553 studies, 34 of which met predefined inclusion criteria. RESULTS Hepatocellular carcinoma was the most common incident malignancy among NAFLD/NASH patients, with higher incidence in patients with advanced/severe fibrosis (F3/F4) of 10.5%-20.0%. Although NASH results in a lower HCC cumulative incidence than hepatitis C virus (HCV) (11.3% vs. 30.5%), they have similar impacts on health outcomes, including overall mortality. Among Japanese NASH patients, HCC was found to be the main driver of mortality (40.0% in 2.7 years in NASH-HCC). With longer follow-up, higher mortality rates are observed in F3/4 patients: 25.0% in NASH F3/F4 versus 0.0% in NASH F0/2 over 7.7 years. The NASH-HCC patients also have a higher post-operative mortality than HCV-HCC patients. Additionally, NAFLD/NASH patients had higher rates of cardiovascular disease than non-NAFLD/NASH controls, and slightly higher rates of gastric cancer than HCV patients. CONCLUSION Hepatocellular carcinoma is the most common malignancy and cause of death among NAFLD/NASH patients in Japan, with higher mortality observed among those with advanced disease and complications. Early identification and effective treatments are needed.

BACKGROUND It is controversial whether chronic hepatitis B (CHB) patients have more non-liver comorbidities than non-CHB subjects. AIM To characterise the demographics, comorbidity and health utilisation of CHB patients in South Korea and compare them to matched controls. METHODS Using the Health Insurance Review & Assessment Service (HIRA) 2007-2016 database, adult patients with claims for CHB analysed. CHB cases and non-CHB controls matched in a 1:4 ratio using propensity score matching method. RESULTS The age of CHB patients significantly increased from a mean 46.9 years in 2007 to 52.3 years in 2016. The proportions of persons having both liver-related and non-liver related comorbidities were higher in CHB patients compared to matched controls (dyslipidaemia [37.23% vs 23.77%, P

Non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH) represent a growing unmet medical need and an increasingly prevalent cause of cirrhosis, hepatocellular carcinoma (HCC), and death in Japan. The aim of this review was to characterize the epidemiology of NAFLD and NASH in Japan. An English and Japanese literature search was conducted in PubMed, Embase, and ICHUSHI Web, identifying 6553 studies, 67 of which were included. Prevalence of NAFLD in the Japanese population rose from the early 1990s (12.6–12.9%) to the early 2000s (24.6–34.7% of the population). Japanese NASH prevalence is estimated to be 1.9–2.7%. NAFLD and NASH are more common among males than females; however, females experience more severe disease than males. While obese patients had higher prevalence of NAFLD/NASH, nonobese individuals (body mass index [BMI] 35% of NAFLD and NASH patients. The evidence shows that, despite obesity being linked with worse disease stages, “lean‐NASH” also plays an important role in NASH epidemiology. Besides obesity, diabetes and metabolic syndrome appeared to be reliably associated with disease severity. The prevalence of advanced fibrosis or cirrhotic disease was the highest in patients with NASH‐HCC (44–80% with stage F3/F4 disease), while 21–50% of patients with NASH had F3/F4 disease. NAFLD/NASH is common in the Japanese population, and the prevalence of these conditions has tripled in the last two decades. Furthermore, these NAFLD/NASH patients have a high comorbidity burden. Early and efficient identification of safe and effective treatments for NAFLD/NASH patients is urgently needed., This review characterizes the epidemiology and morbidity of NAFLD and NASH in Japan. The prevalence of both conditions has been increasing in the past three decades and the disease progression is associated with the presence of obesity, diabetes mellitus and metabolic syndrome. The prevalence of advanced fibrosis or cirrhotic disease was highest in patients with NASH‐HCC compared with regular NASH patients: 44%‐80% versus 21%–50%.

About 10 million people in China are infected with hepatitis C virus (HCV), with the seroprevalence of anti-HCV in the general population estimated at 0.6%. Delaying effective treatment of chronic hepatitis C (CHC) is associated with liver disease progression, cirrhosis, hepatocellular carcinoma, and liver-related mortality. The extrahepatic manifestations of CHC further add to the disease burden of patients. Managing CHC-related advanced liver diseases and systemic manifestations are costly for both the healthcare system and society. Loss of work productivity due to reduced well-being and quality of life in CHC patients further compounds the economic burden of the disease. Traditionally, pegylated-interferon plus ribavirin (PR) was the standard of care. However, a substantial number of patients are ineligible for PR treatment, and only 40%-75% achieved sustained virologic response. Furthermore, PR is associated with impairment of patient-reported outcomes (PROs), high rates of adverse events, and poor adherence. With the advent of direct acting antivirals (DAAs), the treatment of CHC patients has been revolutionized. DAAs have broader eligible patient populations, higher efficacy, better PRO profiles, fewer adverse events, and better adherence rates, thereby making it possible to cure a large proportion of all CHC patients. This article aims to provide a comprehensive evaluation on the value of effective, curative hepatitis C treatment from the clinical, economic, societal, and patient experience perspectives, with a focus on recent data from China, supplemented with other Asian and international experiences where China data are not available.

Chronic hepatitis B demographics and comorbidity data are limited in China. Materials & methods: The China Health Insurance Association claims database from 2013 and 2016 was used to augment the existing data: the proportion of patients aged >45 years increased significantly from 40.3% in 2013 to 49% in 2016 (p Results: Significant increases in multiple comorbidities were observed, including hypertension (9.4–14.5%), hyperlipidemia (4.7–7.0%) and cardiovascular disease (5.7–10%; p Conclusion: Careful selection of treatment options and comorbidity monitoring should be considered when managing adult Chinese patients with chronic hepatitis B.

Background: Remdesivir is approved by the US Food and Drug Administration for the treatment of patients hospitalized with coronavirus disease 2019 (COVID-19) and has been shown to shorten time to recovery and improve clinical outcomes in randomized trials. Methods: This was the final day 28 comparative analysis of data from a phase 3, randomized, open-label study comparing 2 remdesivir regimens (5 vs 10 days, combined for this analysis [remdesivir cohort]) and a real-world retrospective longitudinal cohort study of patients receiving standard-of-care treatment (nonremdesivir cohort). Eligible patients, aged ≥18 years, had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), oxygen saturation ≤94% on room air or required supplemental oxygen, with pulmonary infiltrates. Propensity score matching (up to 1:10 ratio) was used to ensure comparable populations. We assessed day 14 clinical recovery (determined using a 7-point ordinal scale) and day 28 all-cause mortality (coprimary endpoints). Results: A total of 368 (remdesivir) and 1399 (nonremdesivir) patients were included in the matched analysis. The day 14 clinical recovery rate was significantly higher among the remdesivir versus the nonremdesivir cohort (65.2% vs 57.1%; odds ratio [OR], 1.49; 95% confidence interval [CI], 1.16-1.90; P=0.002). The day 28 mortality rate was significantly lower in the remdesivir cohort versus the nonremdesivir cohort (12.0% vs 16.2%; OR, 0.67; 95% CI, 0.47-.95; P=.03). Conclusions: Remdesivir was associated with significantly higher rates of day 14 clinical recovery, and lower day 28 mortality, compared with standard-of-care treatment in hospitalized patients with COVID-19. These data, taken together, support the use of remdesivir to improve clinical recovery and decrease mortality from SARS-CoV-2 infection., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction: Advancing age, comorbidity, and financial burden have been observed in chronic hepatitis B (CHB) patients globally. As Japan is leading the world in aging demographics, similar real-world data are urgently needed for its CHB population to inform all stakeholders. Methods: This cross-sectional study characterized the demographics, comorbidities, and healthcare costs of a large Japanese real-world adult (≥18 years) CHB patient (ICD-10: B18.1) population from the Medical Data Vision database from January 01, 2012, to December 31, 2016. Comorbidities were identified by ICD-10 codes, and the annual point prevalence and Charlson Comorbidity Index (CCI) score were calculated. Annual mean and median all-cause healthcare utilization and costs per patient were calculated. Comparison tests were conducted for CCI scores, prevalence of comorbidities, and healthcare resource utilization and costs. Results: We identified 11,125 CHB patients. Between 2012 and 2016, the mean age increased from 62.0 to 65.2 years, and the percentage of those aged ≥65 years increased from 45.6% to 60.7%. The prevalence of cirrhosis remained similar (5.8% in 2012 and 5.6% in 2016, p = 0.69) while hepatocellular carcinoma decreased from 6.3% to 4.5% (p < 0.01). The prevalence of nonliver comorbidities increased (40.9–52.0% for cancer [p < 0.01], 12.1–17.7% for osteoporosis [p < 0.01], and 10.7–15.0% for renal impairment [p < 0.01]). Healthcare resource utilization and costs also increased, with a 119.3% increase in median total healthcare costs from JPY 229,143 in 2012 to 502,467 in 2016 (p < 0.01). Conclusions: The CHB population of Japan is predominantly elderly and carry a high nonliver comorbidity burden, while incurring increasing healthcare costs.

Background We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care. Methods GS-US-540–5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540–5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. Results After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34–3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22–.68, P = .001). Conclusions In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19. Clinical Trials Registration NCT04292899 and EUPAS34303.

Background: Cervical cancer is caused by the human papillomavirus and is a leading cause of cancer death among young Korean women. Current screening programmes could benefit from the addition of HPV vaccination into their schedule to help reduce disease burden. Two-dose vaccination schedules targeting HPV types 16 and 18, which are responsible for most cervical cancer cases, have recently been approved. Of the two available vaccines, AS04-adjuvanted HPV16/18 vaccine (AS04-HPV16/18v) provides greater protection against non-vaccine oncogenic HPV, while HPV-6/11/16/18 vaccine (4vHPVv) provides protection against genital warts. Methods: The health and economic consequences of introducing a two-dose HPV vaccination programme in 12-year-old girls together with screening were assessed in the Korean healthcare setting using a previously-published Markov model. Results: Compared with screening alone, AS04-HPV16/18v was cost-effective (incremental cost-effectiveness ratio below and within the Korean Won [KRW] 20-30 million treshold). When comparing the two vaccines, at 3% discount rate, AS04-HPV16/18v dominated 4vHPVv (i.e., provided 174 more quality-adjusted life-years (QALYs), 304 more life-years (LYs) and cost-savings of KRW 980 million). At a 5% discount rate, AS04-HPV16/18v provided comparable QALYs (albeit 5 fewer), 105 more LYs and cost-savings of KRW 292 million compared with 4vHPVv. Results were particularly sensitive to the discount rate used, as the health benefits of preventing cervical cancer are observed much later than those of preventing genital warts. Conclusion: For the Korean setting, HPV vaccination with a two-dose schedule is a cost-effective option, and AS04-HPV16/18v is likely to offer better health outcomes at a cost-saving compared with 4vHPVv.

Objective: Renal transplantation is a risk factor for premalignant and malignant changes of the endometrium. Thus, prompt and aggressive treatment of postoperative complications remains a major issue. We report the case of an asymptomatic postmenopausal woman with a history of renal transplantation who underwent surgery for uterine serous carcinoma (USC). Case report: An asymptomatic 59-year-old woman who had undergone renal transplantation presented with elevated serum CA-125 levels. Cancer screening revealed uterine serous carcinoma, for which she underwent total hysterectomy and bilateral salpingo-oophorectomy. Unfortunately, the postoperative course was complicated by cardiogenic shock and decompensated heart failure. The complexities of the cardiac problems and renal transplantation required a multidisciplinary approach involving different specialists. She was successfully discharged 48 days after the surgery. Conclusion: Gynecologic cancer screening in asymptomatic postmenopausal women after renal transplantation is warranted. If postoperative complications occur in this population, a multidisciplinary approach is recommended. Keywords: Multidisciplinary approach, Renal transplant, Uterine serous carcinoma

Early dissemination is a unique characteristic and a detrimental process of pancreatic ductal adenocarcinoma (PDAC); however, the underlying mechanism remains largely unknown. Here, we investigate the role of dual-specificity phosphatase-2 (DUSP2)-vascular endothelial growth factor-C (VEGF-C) axis in mediating PDAC lymphangiogenesis and lymphovascular invasion. Expression of DUSP2 is greatly suppressed in PDAC, which results in increased aberrant expression of extracellular vesicle (EV)-associated VEGF-C secretion. EV-VEGF-C exerts paracrine effects on lymphatic endothelial cells and autocrine effects on cancer cells, resulting in the lymphovascular invasion of cancer cells. Tissue-specific knockout of Dusp2 in mouse pancreas recapitulates PDAC phenotype and lymphovascular invasion. Mechanistically, loss-of-DUSP2 enhances proprotein convertase activity and vesicle trafficking to promote the release of the mature form of EV-VEGF-C. Collectively, these findings represent a conceptual advance in understanding pancreatic cancer lymphovascular invasion and suggest that loss-of-DUSP2-mediated VEGF-C processing may play important roles in early dissemination of pancreatic cancer. Abbreviations: DUSP2: dual-specificity phosphatase-2; VEGF-C: vascular endothelial growth factor-C; EV: extracellular vesicles; PDAC: pancreatic ductal adenocarcinoma; KD: knockdown

Cervical cancer (CC) is the second leading cause of cancer death among Filipino women. Human papillomavirus (HPV) vaccination protects against CC. Two vaccines (AS04-HPV-16/18 and 4vHPV) are approved in the Philippines; they were originally developed for a 3-dose (3D) administration and have recently been approved in a 2-dose schedule (2D). This study aims to evaluate the cost-effectiveness of HPV vaccination of 13-year-old Filipino girls, in addition to current screening, in the new 2D schedule. An existing static lifetime, one-year cycle Markov cohort model was adapted to the Philippine settings to simulate the natural history of low-risk and oncogenic HPV infection, the effects of screening and vaccination of a 13-year-old girls cohort vaccinated with either the 2D-AS04-HPV-16/18 or 2D-4vHPV assuming a 100% vaccination coverage. Incremental cost, quality-adjusted life year (QALY) and cost-effectiveness were derived from these estimates. Input data were obtained from published sources and Delphi panel, using country-specific data where possible. Sensitivity analyses were performed to assess the robustness of the model. The model estimated that 2D-AS04-HPV-16/18 prevented 986 additional CC cases and 399 CC deaths (undiscounted), as well as 555 increased QALY (discounted), and save 228.1 million Philippine pesos (PHP) compared with the 2D-4vHPV. In conclusion, AS04-HPV-16/18 is shown to be dominant over 4vHPV in the Philippines, with greater estimated health benefits and lower costs.

Policy makers and advocates are increasingly encouraging child-serving organizations to work together. The current study examined how child welfare agency ties with substance abuse treatment providers and schools correlated with substance abuse treatment for adolescents receiving child protective services. A sample of adolescents with substance use risk was extracted from a national survey of families engaged with child welfare. Logistic regressions with adjustments for complex survey design used child welfare agency ties to substance abuse treatment providers and schools to predict treatment. As expected, adolescents were more likely to report treatment when child protective services and substance abuse treatment were in the same agency and when child welfare agency directors reported joint planning with schools. However, child welfare agency agreements with substance abuse treatment providers were negatively associated with treatment. This unexpected finding implies that agencies may sometimes cooperate to address problems as well as to improve service utilization.

Contact burns caused by the exhaust pipe of motorcycles are rarely reported. We performed retrospective studies of such cases in 78 patients with complete records. The majority of victims were unmarried (75.7%), young (25 years, 70.5%), and female (69.3%), dressed mostly in short pants or mini skirts (75.7%). The burn accident occurred mostly in late spring and early summer (52.7%), during rush hours (57.7%), and during parking the motorcycles (65.4%). The burn wounds located mostly on the lateral aspect (46.2%) of the lower leg, usually took 3-4 weeks for complete healing. Continuous monitoring of the exhaust pipe and its outside cover on moving motorcycles showed that the temperature reached 170-250 and 40-60 degrees C, respectively. For the prevention of these injuries, our suggestions include well-designed external shield with adequate separation from the exhaust pipe, motorcycle parking lots of adequate width (120cm), the wearing of trousers by motorcyclists, decrease of the density of motorcycle traffic, and development of the electric assisted cycle in place of the fuel-driven motorcycle.

This study is based on the effects on human joint angles caused by the different form of hand controls used by emergency nurses, using the evaluation methods of bad joint angles, come up with a reasonable height and angle range of controls. This study is divided into mainly two sections, in section one we used filming, to group the postures shown by ten emergency medics operating the common seen hand controls, and take the common seen posture to be the basis of the second section experiment. In section two, using 3D motion analysis system, to study the change of height and angle of control panels while fifteen women operate the five common seen hand controls in emergency (push button, big rotation knob, detent positioning knob, small rotation knob and toggle switch), and the effects on the body bending angle, elbow angle and wrist angle. At last using ANOVA analysis and regression function analysis to conclude a suitable control panel height and angle.

Labor-intensive work is often a way of life for women living in rural areas of developing countries. The physical exertion involved in such work may result in poor health outcomes for mothers and infants when continued through pregnancy. Using longitudinal data from China, Mexico, and Tanzania, we examine the relationship between pregnancy and four time-use outcomes, measured as hours spent in the past week on: (1) housework, (2) caregiving, (3) agricultural work, and (4) self-employment or nonagricultural work outside the home. An individual fixed-effects approach is adopted to overcome the potential time-invariant woman-level endogeneity of pregnancy status. With few exceptions, we do not find significantly different time-use patterns between pregnant and nonpregnant women. The assumption that women decrease labor-intensive work in developing countries during pregnancy needs revisiting and may have implications for both women's livelihood programming and assistance during childbearing periods.

Standardized patient placement criteria such as those developed by the American Society of Addiction Medicine are increasingly common in substance abuse treatment, but it is unclear what factors are associated with their use or with treatment units’ provision of related services. This study examined these issues in the context of a national survey of outpatient substance abuse treatment units. Regressions using 2005 data revealed that both public and private managed care were associated with a greater likelihood of using American Society of Addiction Medicine criteria to develop client treatment plans. However, only public managed care was associated with a greater likelihood of offering more resource-intensive services. Associations between client population severity and resource-intensive service provision were sparse but positive.

Objective: The federal government boosted support for community health centers in medically underserved areas in 2002–2007. This investigation compared trends in behavioral health services provided by community health centers nationwide during the first several years of that initiative with immediately prior trends. Methods: Data were extracted from the Health Resources and Services Administration’s Uniform Data System on community health centers for 1998–2007 (2007, N=1,067). Regression analyses revealed trends in individual community health centers’ likelihood of providing on-site specialty mental health care, crisis services, and substance abuse treatment. Aggregate data were used to show national trends in numbers of behavioral health encounters, patients, and encounters per patient. Results: The number of federally funded community health centers increased 43% between 2001 and 2007, from 748 to 1,067, over twice the annual growth rate between 1998 and 2001. However, trends in individual community health centers’ likelihood of providing different types of behavioral health care were generally consistent across the two time periods. In 2007, 77% of community health centers offered specialty mental health services, 20% offered 24-hour crisis intervention services, and 51% offered substance abuse treatment. The mean number of mental health encounters per mental health patient at community health centers in 2007 was 2.9. Conclusions: The behavioral health care safety net has widened through rapid recent growth in the number of community health centers as well as a continuing increase in the proportion offering specialty mental health services. (Psychiatric Services 61:759–764, 2010)