Comparative analysis of genetic testing utilization rates among people with and without disabilities in South Korea from 2016 to 2019, focusing on malignant neoplasms: A national population-based study.

INTRODUCTION: Oncogene testing is widely used to detect or direct cancer treatments. Compared to people without disabilities, people with disabilities in Korea have a lower cancer incidence rate but a fivefold higher cancer mortality rate, implying delayed detection. METHODS: We used an administrative database combining disability status and care utilization to analyze every case of cancer-related genetic testing paid for by the National Health Insurance Services of Korea between 2016 and 2019. We first compared percentages of individuals who had taken a registered genetic test by their disability statuses. We then compared the most frequently utilized tests between individuals with and without disabilities. RESULTS: Korean citizens, 175,000 in total, underwent at least one of the 192 registered cancer-related genetic tests between 2016 and 2019. People with disabilities utilized these genetic tests at higher rates than those without disabilities, regardless of sex or age. Among people aged ≥40 years, lung and colorectal cancer-related tests were most frequently utilized, regardless of disability status. CONCLUSION: Although the cancer-related genetic test uptake rate is higher among people with disabilities than among those without disabilities, it is still possible that information on these tests is not as readily available to people with disabilities. Therefore, it is imperative for the government to actively devise strategies to enhance national cancer screening rates among people with disabilities.

Design, synthesis, and evaluation of purine and pyrimidine-based KRAS G12D inhibitors: Towards potential anticancer therapy.

Oncogenic RAS mutations, commonly observed in human tumors, affect approximately 30% of cancer cases and pose a significant challenge for effective cancer treatment. Current strategies to inhibit the KRAS G12D mutation have shown limited success, emphasizing the urgent need for new therapeutic approaches. In this study, we designed and synthesized several purine and pyrimidine analogs as inhibitors for the KRAS G12D mutation. Our synthesized compounds demonstrated potent anticancer activity against cell lines with the KRAS G12D mutation, effectively impeding their growth. They also exhibited low toxicity in normal cells, indicating their selective action against cancer cells harboring the KRAS G12D mutation. Notably, the lead compound, PU1-1 induced the programmed cell death of KRAS G12D-mutated cells and reduced the levels of active KRAS and its downstream signaling proteins. Moreover, PU1-1 significantly shrunk the tumor size in a pancreatic xenograft model induced by the KRAS G12D mutation, further validating its potential as a therapeutic agent. These findings highlight the potential of purine-based KRAS G12D inhibitors as candidates for targeted cancer therapy. However, further exploration and optimization of these compounds are essential to meet the unmet clinical needs of patients with KRAS-mutant cancers.

Pre-pandemic physical activity as a predictor of infection and mortality associated with COVID-19: Evidence from the National Health Insurance Service.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, many populations have experienced reduced physical activity (PA) levels, weight gain, and increased anxiety and depression. However, according to a previous study, engaging in PA has a positive effect on damages caused by COVID-19. Therefore, this study aimed to investigate the association between PA and COVID-19 using the National Health Insurance Sharing Service Database in South Korea. Methods: Logistic regression analysis was used to analyze the association of PA with COVID-19 and mortality. The analysis was adjusted for body mass index, sex, age, insurance type, comorbidity, and region of residence at baseline. Disability and lifestyle (weight, smoking, and drinking status) were adjusted consecutively. Results: The results indicated that engaging in insufficient PA as per the WHO guidelines predicts a higher risk of COVID-19 when controlling for personal characteristics, comorbidity, lifestyle, disability, and mortality. Discussion: This study revealed the need to engage in PA and manage weight to reduce the risk of infection and mortality associated with COVID-19. Because engaging in PA is an important component of weight management and can help restore physical and mental health after the COVID-19 pandemic, it should be emphasized as a pillar of recovery after COVID-19.

Measuring Trends in the Socioeconomic Burden of Disease in Korea, 2007-2015.

This study estimated the direct and indirect socioeconomic costs of 238 diseases and 22 injuries from a social perspective in Korea from 2007 to 2015. The socioeconomic cost of each disease group was calculated based on the Korean Standard Disease Classification System. Direct costs were estimated using health insurance claims data provided by the National Health Insurance Service. The numbers of outpatients and inpatients with the main diagnostic codes for each disease were selected as a proxy indicator for estimating patients' medical use behavior by disease. The economic burden of disease from 2007 to 2015 showed an approximately 20% increase in total costs. From 2007 to 2015, communicable diseases (including infectious, maternal, pediatric, and nutritional diseases) accounted for 8.9-12.2% of the socioeconomic burden, while non-infectious diseases accounted for 65.7-70.7% and injuries accounted for 19.1-22.8%. The top 5 diseases in terms of the socioeconomic burden were self-harm (which took the top spot for 8 years), followed by cirrhosis of the liver, liver cancer, ischemic heart disease, and upper respiratory infections in 2007. Since 2010, the economic burden of conditions such as low back pain, falls, and acute bronchitis has been included in this ranking. This study expanded the scope of calculating the burden of disease at the national level by calculating the burden of disease in Koreans by gender and disease. These findings can be used as indicators of health equality and as useful data for establishing community-centered (or customized) health promotion policies, projects, and national health policy goals.

Health-related factors leading to disabilities in Korea: Survival analysis.

The purpose of this study is to analyze (a) population and socioeconomic factors affecting disability, excluding the occurrence of disability due to accidents and congenital diseases, and (b) health-related behavioral factors and factors that can prevent and reduce the cause of disability due to disease in Korea. This study was a longitudinal research. Data were obtained from The 2018 Korean Health Panel (KHP) is a survey jointly conducted by the Korea Institute of Health and Social Affairs and the National Health Insurance Service. A total of 7, 372 (Mage = 52.14, SD = 21.39; Male = 47.52%) were analyzed in this study. People with Higher education attainments and more income levels were associated with lower hazard of developing new disabilities (all p < 0.05). In this study, the health factors that could be related to the occurrence of new disabilities were smoking, alcohol consumption, physical activity, and stress (all p < 0.0001). However, physical activity was negatively associated with the risk of developing a disability at all follow-ups (p < 0.05). Higher scores on the number of chronic diseases (valid scores = 0, 1, 2, 3, or more) represented a greater level of newly developing disability present at all follow-ups (all p < 0.0001). This longitudinal study confirmed the relationship between health-related factors and specific chronic diseases. Its findings can be used as a crucial foundation for establishing healthcare policies and services that can lower and prevent disability by preventing and reducing specific negative health behaviors and unhealthy behavioral factors, and alleviating chronic diseases in Korea.

Characteristics and trends of PCSK9 inhibitor prescription fills in the United States.

BACKGROUND: PCSK9 inhibitors were approved by the Food and Drug Administration in 2015 to lower low-density lipoprotein cholesterol (LDL-C) levels. In the years following, additional research findings, changes in national guideline recommendations, and price reductions have occurred. OBJECTIVE: The goal of the study is to describe the characteristics and trends in PCSK9 inhibitor prescription fills and price, from initial FDA approval in Quarter 3 2015 through Quarter 4 2019, at the national and state levels. METHODS: Cross-sectional study of fills obtained using the IQVIA National Prescription Audit®, Extended Insights, New to Brand, and Regional databases. Prescription fills included injections that provided cholesterol-lowering therapy from 14 to 90 days for the two PCSK9 inhibitors: alirocumab (75 mg/mL and 150 mg/mL) or evolocumab (140 mg/mL and 420 mg/3.5 mL). Quarterly prescription fills obtained nationally for Quarter 3 2015 through Quarter 4 2019, by sex, age, and state during 2019. RESULTS: Over the time period examined, 2.75 million PCSK9 inhibitor prescriptions were filled nationally (alirocumab: 38%; evolocumab: 62%), and the average retail price per fill (unadjusted $US) from retail pharmacies decreased by 40% from $1502 to $896 per fill. Year-over-year percent change in new PCSK9 inhibitor users increased throughout the observation period, with 9611 new alirocumab users and 25,381 new evolocumab users in Q4 2019. PCSK9 inhibitor fill rates ranged from 5.6 per 1000 in the Northeast to 3.4 per 1000 in the West in 2019, with the highest rate per 1000 in Louisiana (9.1), and lowest in Wyoming (1.3). CONCLUSIONS: PCSK9 inhibitor prescriptions have increased nationally since 2015, coinciding with additional evidence supporting their use for LDL-C lowering and cardiovascular event reduction. Although the retail price has decreased since introduction, cost and delivery mode likely continue as barriers.

A National Study of Life-Sustaining Treatments in South Korea: What Factors Affect Decision-Making?

PURPOSE: This cross-sectional study investigated the status of life-sustaining treatment (LST) practices and identified characteristics and factors influencing decision-making practices. MATERIALS AND METHODS: The National Agency for Management of Life-sustaining Treatment retains records provided by doctors regarding patients subject to LST implementation. A total of 71,327 patients receiving LST were identified. We analyzed all nationally reported data between February 2018 and October 2019. Indicators such as the proportion of deaths, records for decision to terminate LST, implementation of LST records, and registration of Advance Statements on LST were analyzed. RESULTS: A total of 67,252 (94.3%) end-of life decisions were implemented in South Korea. The proportion of deaths preceded by a LST plan, non-self-determination LST decision, and any advance statements was 33.5% (23,891/71,327), 66.5% (47,436/71,327), and 1.2% (890/71,327), respectively. The logistic regression model revealed that self-determination to terminate LST was more frequent for men than for women and higher for those aged 30-69. Disability (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.56 to 0.61), living in non-metropolitan areas (OR, 0.84; 95% CI, 0.81 to 0.86), and disease comorbidity was independently associated with a low level of self-determination. CONCLUSION: After the implementation of the new LST Act, about a third of patients in end-of-life process made decisions regarding their medical LST. However, family members still play a major role in LST decisions where the patient's intention cannot be verified. Decisions related to LST are predominantly made when death is imminent. Thus, it is necessary to increase awareness of end-of-life LST decision-making among medical staff and the public.

Characteristics of US Adults Who Would Be Recommended for Lifestyle Modification Without Antihypertensive Medication to Manage Blood Pressure.

BACKGROUND: The 2017 American College of Cardiology / American Heart Association Guideline for blood pressure (BP) management newly classifies millions of Americans with elevated BP or stage 1 hypertension for recommended lifestyle modification alone (without pharmacotherapy). This study characterized these adults, including their cardiovascular disease risk factors, barriers to lifestyle modification, and healthcare access. METHODS: This cross-sectional study examined nationally representative National Health and Nutrition Examination Survey data, 2013-2016, on 10,205 US adults aged ≥18, among whom 2,081 had elevated BP or stage 1 hypertension and met 2017 ACC/AHA BP Guideline criteria for lifestyle modification alone. RESULTS: An estimated 22% of US adults (52 million) would be recommended for lifestyle modification alone. Among these, 58% were men, 43% had obesity, 52% had low-quality diet, 95% consumed excess sodium, 43% were physically inactive, and 8% consumed excess alcohol. Many reported attempting lifestyle changes (range: 39%-60%). Those who reported receiving health professional advice to lose weight (adjusted prevalence ratio 1.21, 95% confidence interval 1.06-1.38), reduce sodium intake (2.33, 2.00-2.72), or exercise more (1.60, 1.32-1.95) were significantly more likely to report attempting changes. However, potential barriers to lifestyle modification included 28% of adults reporting disability, asthma, or arthritis. Additionally, 20% had no health insurance and 22% had no healthcare visits in the last year. CONCLUSIONS: One-fifth of US adults met 2017 ACC/AHA BP Guideline criteria for lifestyle modification alone, and many reported attempting behavior change. However, barriers exist such as insurance gaps, limited access to care, and physical impairment.

Transfer Is Associated with a Higher Mortality Rate in Necrotizing Soft Tissue Infections.

Background: Necrotizing soft tissue infections (NSTI) are a surgical emergency with significant morbidity and mortality rates. It has been thought that NSTIs are best treated in large tertiary centers. However, the effect of transfer has been under-studied. We examined whether transfer status is associated with a higher mortality rate in NSTIs. Methods: We conducted a retrospective review of patients with an International Classification of Disease (ICD) code associated with NSTI seen from 2012-2015 at two tertiary care institutions. Patients transferred to a tertiary center (T-NSTI) were compared with those who were treated initially at a tertiary center (P-NSTI). The primary endpoint was in-hospital death. Results: A total of 138 patients with NSTI met our study criteria, 39 transfer patients (28.0%) and 99 (72.0%) who were treated primarily at our institutions. The mortality rate was significantly higher for T-NSTI patients than P-NSTI patients (35.9% versus 14.1%; p < 0.01) with an adjusted odds ratio of 5.33 (95% confidence interval 1.02-28.30; p = 0.04). The need for hemodialysis was an independent predictor of in-hospital death. Treatment at a Level 1 trauma center and current smoking status were independent protectors???? of in-hospital death. For the transfer patients, the timing of transfer and debridement status were not different in survivors and non-survivors. However, there was a trend toward a lower in-hospital mortality rate if patients were transferred early without prior debridement than in all other transfers (21.4% versus 40.0%; p = 0.21). The in-hospital mortality rate was significantly lower at the Level 1 trauma center than at the non-trauma tertiary center (15.5% versus 34.3%; p = 0.02). Conclusion: Transfer status is an independent predictor of in-hospital death in patients with NSTI. Larger, multi-institutional studies are needed to elucidate further what factors contribute to the higher mortality rate in these patients.

HIV Screening and Early Referral in the Trauma Population: The Experience of a Large Safety Net Hospital.

BACKGROUND: While the prevalence of HIV infection in the population is 0.5%, it is higher among trauma patients as are rates of unknown seropositivity. Routine HIV screening for all trauma evaluations was implemented at our urban level I center in 2009. We aimed to evaluate use and results of the program in our trauma population. METHODS: This was a retrospective analysis of all trauma evaluations between July 2015 and February 2018. After passage of legislation rescinding the requirement for consent to perform HIV testing, our trauma service instituted an order set which automatically tested for HIV unless the ordering physician opted out. Patients found to be infected with HIV were to be counseled and referred to specialty care. RESULTS: Of 6175 consecutive trauma evaluations during the study period, 449 (7.3%) patients had been screened within the prior year and were excluded. Of the remaining cohort, 2024 (35.3%) patients were screened with 27 (1.3%) testing positive. Among those testing positive for infection, 100% were male, 77% white, 63% non-Hispanic, and 70% lacked insurance. Twenty-five (92.6%) patients received counseling and 19 were referred to specialty care. Age, gender, race, ethnicity, Injury Severity Score, trauma activation level, and payor type were not significant predictors for positive HIV screen on logistic regression analysis. CONCLUSIONS: Despite a significantly higher rate of HIV in the trauma population, only a third of patients are screened. Such high infection rates justify the existence of this screening program but steps must be taken to increase screening rate. LEVEL OF EVIDENCE: Level 3.

Latent Profiles Based on Light Physical Activity, Sedentary Behavior, Perceived Body Shape, and Body Mass Index in Patients with Dyslipidemia Influence Their Quality of Life.

Despite the increasing prevalence and economic burden of dyslipidemia in South Korea, we have little data on the physical activity of patients. Thus, we aimed to investigate how quality of life among patients with dyslipidemia is influenced by a combination of the following variables: light physical activity (PA), sedentary behavior (SB), perceived body shape, and body mass index (BMI). We examined data from the Sixth Korean National Health and Nutrition Examination Survey (KNHANES VI 2015), collected in 2015 by the Korean Centers for Disease Control and Prevention. The analysis included 534 individuals with dyslipidemia out of 7380 survey participants. Latent profile analysis identified three latent classes of individuals based on their physical profiles. Class 1 patients (active; n = 48) were more active, possessed more positive views of their body shape, were less sedentary, and had a lower BMI than Class 3 patients (inactive; n = 154). Class 2 patients (moderate; n = 331) had profiles in between the other two classes. Additionally, Class 1 and 2 patients had better quality of life than Class 3 patients. Our results suggest that promoting light PA and altering perceived body shape through counselling may improve quality of life in patients with dyslipidemia.

Factors of Physical Activity and Sedentary Behavior in Elderly Koreans.

Objectives: In this study, we examined factors of moderate-to-vigorous physical activity (MVPA) and sedentary behavior (SB) in elderly Koreans. Methods: We used 2015 data from the Sixth National Health and Nutrition Examination Survey. To analyze physical activity (PA), we categorized participants were into those who met MVPA recommendations (150 minutes/week of moderate PA or 75 minutes/week of vigorous PA) or those who did not. We also categorized them into high SB (620-1200 minutes/day of sitting) and low SB (30-600 minutes/day). Results: Final analyses included 1501 adults over 60 years old (mean: 69.2 ± 6.2). We performed multiple logistic regressions examining impacts of grip strength and body mass index, along with self-reports of perceived health, sleep duration, and demographics on PA and SB. We found positive associations between meeting MVPA guidelines and self-perceived health and urban living, but negative associations with sleep duration and education. A strong grip, high self-perceived health, long sleep duration (8-14 hours), and living with a partner were factors of being less sedentary. High annual income was a factor of being more sedentary. Conclusion: Our findings support efforts that develop interventions promoting active lifestyles among elderly Koreans.

Comparative Research for the Healthcare Budget and Burden of Disease in Perspective Resource Allocation.

BACKGROUND: Burden of disease can be used to prioritize the healthcare budget allocation. We analyzed the research and development (R&D) budget of the Ministry of Health and Welfare (MOHW) in 2018 and compared the results with those of the 2015 Korean National Burden of Disease (KNBD) study. METHODS: The 2018 MOHW R&D Project integrated implementation plan was used to analyze the R&D budget of the MOHW. The budget was allocated according to the KNBD disease group and according to the budget lines. The allocated budget was compared with the economic burden and the disability adjusted life years (DALYs) in 2015. Also, for budget targets for risk factors, DALYs of attributable risk factors were compared with corresponding budgets. RESULTS: In 2018, the MOHW major R&D budget of USD 435.1 million accounted for 3% of the total government budget. Within the disease specific R&D budget, 35.9% was allocated to communicable disease groups, 64.1% to non-communicable diseases, and 0% to injury and violence. Among level 2 disease groups, neoplasm was ranked first. Among risk factors, climate change and behavioral risk were targeted for R&D. CONCLUSIONS: It would be difficult to say that current R&D allocations focus to minimize the burden of disease. A mismatch was observed between the R&D budget and the burden of disease in terms of economic burden and DALYs. There was a similar finding for risk factors R&D. A novel approach for allocating government R&D funding that is based on the goal of minimizing the disease burden in the Korean population should be considered.

Modeled state-level estimates of hypertension prevalence and undiagnosed hypertension among US adults during 2013-2015.

Hypertension affects about one in three US adults, from recent surveillance, or four in nine based on the 2017 ACC/AHA Hypertension Guideline; about half of them have their blood pressure controlled, and nearly one in six are unaware of their hypertension status. National estimates of hypertension awareness, treatment, and control in the United States are traditionally based on measured BP from National Health and Nutrition Examination Survey (NHANES); however, at the state level, only self-reported hypertension awareness and treatment are available from BRFSS. We used national- and state-level representative samples of adults (≥20 years) from NHANES 2011-2014 and BRFSS 2013 and 2015, respectively. The authors generated multivariable logistic regression models using NHANES to predict the probability of hypertension and undiagnosed hypertension and then applied the fitted model parameters to BRFSS to generate state-level estimates. The predicted prevalence of hypertension was highest in Mississippi among adults (42.4%; 95% CI: 41.8-43.0) and among women (42.6%; 41.8-43.4) and highest in West Virginia among men (43.4%; 42.2-44.6). The predicted prevalence was lowest in Utah 23.7% (22.8-24.6), 26.4% (25.0-27.7), and 21.0% (20.0-22.1) for adults, men, and women, respectively. Hypertension predicted prevalence was higher in most Southern states and higher among men than women in all states except Mississippi and DC. The predicted prevalence of undiagnosed hypertension ranged from 4.1% (3.4-4.8; Kentucky) to 6.5% (5.5-7.5; Hawaii) among adults, from 5.0% (4.0-5.9; Kentucky) to 8.3% (6.9-9.7; Hawaii) among men, and from 3.3% (2.5-4.1; Kentucky) to 4.8% (3.4-6.1; Vermont) among women. Undiagnosed hypertension was more prevalent among men than women in all states and DC.

Serum alanine aminotransferase level and liver-related mortality in patients with chronic hepatitis B: A large national cohort study.

BACKGROUND: The serum alanine aminotransferase (ALT) level has been used to identify at-risk patients with chronic hepatitis B (CHB) who need antiviral therapy. However, the level associated with increased liver-related mortality requiring active treatment is still unclear. METHODS: We used a Health Examination Cohort of the National Health Insurance Service of Korea that included approximately 0.5 million individuals aged 40-79 years. In total, 12 486 patients with CHB and no other concurrent liver disease were enrolled, and patients' liver-related mortality, including that owing to liver cancer, was investigated over 9 years. RESULTS: The serum ALT level was correlated positively with liver-related mortality. The rates in men were 0.14, 0.17, 0.24, 0.57, 0.63 and 0.85 per 100 person-years (%) for serum ALT levels of <20, 20-29, 30-39, 40-49, 50-79 and ≥80 U/L, respectively, and the corresponding liver-related mortality rates in women were 0.03%, 0.09%, 0.12%, 0.63%, 0.65% and 0.32%. In patients with ALT levels of 40-79 U/L, the liver-related mortality rates were 0.60% in men and 0.64% in women, which were similar to the overall mortality rate of age- and sex-matched subjects without CHB (0.69%). The best cut-off values for liver-related mortality prediction were >34 U/L in men and >30 U/L in women. CONCLUSIONS: The liver-related mortality rate increased significantly, even in CHB patients with relatively low serum ALT levels. Careful monitoring or earlier antiviral therapy should be considered for patients aged >40 years with serum ALT levels above the upper limit of normal.

Treatment duration for uncomplicated Staphylococcus aureus bacteremia to prevent relapse: analysis of a prospective observational cohort study.

Practice guidelines recommend at least 14 days of antibiotic therapy for uncomplicated Staphylococcus aureus bacteremia (SAB). However, these recommendations have not been formally evaluated in clinical studies. To evaluate the duration of therapy for uncomplicated SAB, we analyzed data from our prospective cohort of patients with SAB. A prospective observational cohort study was performed in patients with SAB at a tertiary-care hospital in Korea between August 2008 and September 2010. All adult patients with SAB were prospectively enrolled and observed over a 12-week period. Uncomplicated SAB was defined as follows: negative results of follow-up blood cultures at 2 to 4 days, defervescence within 72 h of therapy, no evidence of metastatic infection, and catheter-related bloodstream infection or primary bacteremia without evidence of endocarditis on echocardiography. Of 483 patients with SAB, 111 met the study criteria for uncomplicated SAB. Fifty-three (47.7%) had methicillin-resistant SAB. When short-course therapy (<14 days) and intermediate-course therapy (≥14 days) were compared, the treatment failure rates (10/38 [26.3%] versus 16/73 [21.9%]) and crude mortality (7/38 [18.4%] versus 16/73 [21.9%]) did not differ significantly between the two groups. However, short-course therapy was significantly associated with relapse (3/38 [7.9%] versus 0/73; P = 0.036). In multivariate analysis, primary bacteremia was associated with a trend toward increased treatment failure (P = 0.06). Therefore, in the treatment of uncomplicated SAB, it seems reasonable to consider at least 14 days of antibiotic therapy to prevent relapse, as practice guidelines recommend. Because of its poor prognosis, primary bacteremia, even with a low risk of complication, should not be treated with short-course therapy.

Efficacy and safety of low-dose ganciclovir preemptive therapy in allogeneic haematopoietic stem cell transplant recipients compared with conventional-dose ganciclovir: a prospective observational study.

OBJECTIVES: We performed a prospective observational study comparing the efficacy and safety of low-dose ganciclovir (5 mg/kg/day) as initial preemptive therapy in allogeneic haematopoietic stem cell transplantation (HSCT) recipients with conventional-dose ganciclovir (10 mg/kg/day). METHODS: All adult patients undergoing allogeneic HSCT were enrolled at a transplant centre over a 24 month period. The decision to use low-dose or conventional-dose ganciclovir was at the discretion of each attending haematologist. A logistic regression model with inverse probability of treatment weighting (IPTW) using propensity scores was performed to reduce the effect of the selection bias in assignment for ganciclovir preemptive therapy. RESULTS: Of the 252 HSCT recipients, 97 (38%) received preemptive ganciclovir therapy. Of these, 53 (55%) and 44 (45%) received low-dose and conventional-dose ganciclovir, respectively. The viral clearance rate was higher in the low-dose ganciclovir group [98% (52/53)] than in the conventional-dose ganciclovir group [86% (38/44), P = 0.04], while the low-dose ganciclovir group exhibited a longer viral clearance time (median 21.0 days) than the conventional-dose ganciclovir group (median 14.0 days, P = 0.05). The rate of discontinuation of therapy due to neutropenia or nephrotoxicity was similar in the two groups, although conventional-dose ganciclovir was changed to another regimen more frequently than low-dose ganciclovir. There were three cases of cytomegalovirus (CMV) disease in each group after the initial preemptive therapy. The logistic regression models using propensity scores also revealed that there were no significant differences in viral clearance, secondary episodes of CMV infection, CMV disease and overall mortality between the two groups. CONCLUSIONS: Low-dose ganciclovir appears to be safe, and to be at least as effective as conventional-dose ganciclovir for CMV viraemia in allogeneic HSCT recipients.

Paradoxical rising cytomegalovirus antigenemia during preemptive ganciclovir therapy in hematopoietic stem cell transplant recipients: incidence, risk factors, and clinical outcomes.

Preemptive ganciclovir (GCV) therapy is adopted increasingly in hematopoietic stem cell transplant (HCT) recipients, but occasional cases of increasing cytomegalovirus (CMV) antigenemia levels occur during preemptive GCV therapy. This prospective study investigated the incidence, risk factors, and clinical outcomes of paradoxical responses during GCV therapy. Adult patients receiving allogeneic HCTs during a 24-month period were enrolled. Patients were prospectively monitored for CMV antigenemia once a week until 3 months after engraftment. Paradoxical responders were defined as patients exhibiting CMV antigenemia levels elevated from the baseline after the first week of preemptive GCV therapy. Of 252 HCT recipients, 97 (38%) received preemptive GCV therapy due to CMV infection. Of these 97 patients, 23 (24%) were classified as paradoxical responders. Risk factors for paradoxical response were a low white blood cell (WBC) count (P = 0.02) and a prolonged duration of CMV antigenemia (P = 0.04) before preemptive therapy. There were no significant differences in rates of successful viral clearance and secondary episodes of CMV infection between paradoxical responders (87% [20/23] and 26% [6/23]) and nonparadoxical responders (95% [70/74] and 23% [17/74], respectively). However, breakthrough CMV disease during preemptive GCV therapy was significantly more frequent in paradoxical responders (17% [4/23]) than in nonparadoxical responders (3% [2/74], P = 0.03). Paradoxical responses occurred in one-quarter of the HCT recipients receiving preemptive GCV therapy. A low WBC count and a long duration of CMV antigenemia before GCV therapy were associated with paradoxical responses, and breakthrough CMV disease during preemptive GCV therapy occurred more frequently in paradoxical responders.

Screening and identification of a novel esterase EstPE from a metagenomic DNA library.

Esterases represent a large family of hydrolases with broad substrate specificity and functional sequence space. Although many attempts to screen new esterases have been conducted, there have been few reports conducted to discriminate unique enzymes from typical ones based on novel structure and function. In this study, we discovered an esterase and a novel family through a successive assay of whole cells and crude lysates (oxidative open condition). The screened putative esterases from the metagenomic DNA of salted shrimp consisted of 753 bp encoding 27 kDa of polypeptide, namely PE esterase. Sequence analyses revealed that an identical gene was reported from whole genome sequencing of Stenotrophomonas maltophilia K279a. However, its biochemical and phylogenetic characteristics have not yet been evaluated. PE esterase was overexpressed only by the MBP fusion state in E. coli and was easily purified using an affinity column. This enzyme showed a typical spectrum of substrate specificity and possessed the consensus motifs, Ser-Asp-His and GXSXG, which are essential for most esterase/lipase superfamilies. Interestingly, the entire organization of the ORF and consensus sequence around the active site were distinct from the related enzymes, and its structure could be affected by a reducing agent, DTT.