Clinical and economic burden of bacteremia due to multidrug-resistant organisms in Korea: a prospective case control study.

OBJECTIVES: The socioeconomic and clinical burden of multidrug-resistant organisms (MDRO), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) have not yet been adequately addressed. METHODS: We prospectively searched for MDRO bacteremia cases with matched controls from 10 hospitals across Korea during a 6-month period in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had been selected according to predefined criteria. We collected clinical information and estimated the total additional medical cost due to MDRO infections using the multistate model. RESULTS: During the 6-month period, a total of 486 MDRO bacteremia cases (260, 87, 18, 20, and 101 cases of MRSA, MRAB, MRPA, CRE, and VRE, respectively) were identified. The 90-d mortality rates were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. The additional costs caused by bacteremia were $15 768, $35 682, $39 908, $72 051, and $33 662 per MDRO type, respectively. Based on these 6-month data, the estimated annual number of bacteremia cases due to these five MDRO in Korea were 7979 (4070, 1396, 218, 461, and 1834 cases, respectively). Overall, this caused an estimated 3280 (1237, 882, 36, 254, and 871, respectively) deaths and cost $294 505 002 ($84 707 359, $74 387 364, $10 344 370, $45 850 215, and $79 215 694, respectively) (range $170,627,020-$416,094,679) in socioeconomic loss. CONCLUSIONS: A tremendous clinical and economic burden is caused by MDRO bacteremia compared with antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed.

Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trial.

Background: Vaccination has helped to mitigate the COVID-19 pandemic. Ten traditional and novel vaccines have been listed by the World Health Organization for emergency use. Additional alternative approaches may better address ongoing vaccination globally, where there remains an inequity in vaccine distribution. GBP510 is a recombinant protein vaccine, which consists of self-assembling, two-component nanoparticles, displaying the receptor-binding domain (RBD) in a highly immunogenic array. Methods: This randomised, placebo-controlled, observer-blinded phase 1/2 study was conducted to evaluate the safety and immunogenicity of GBP510 (2-doses at a 28-day interval) adjuvanted with or without AS03 in adults aged 19-85 years at 14 hospital sites in Korea. This study was consisted of two stages (stage I, healthy adults aged 19-55 years; stage II, 240 healthy adults aged 19-85 years). Healthy participants who did not previously receive any vaccine within 4 weeks (2 weeks for flu vaccine) prior to the study, no history of COVID-19 vaccination/medication, and were naïve to SARS-CoV-2 infection at screening were eligible for the study enrollment. Participants were block-randomized in a 2:2:1 ratio to receive 2 doses of 10 µg GBP510 adjuvanted with AS03 (group 1), 10 µg unadjuvanted GBP510 (group 2) or placebo intramuscularly in stage I, while they were block-randomized in a 2:2:1:1 ratio to receive 10 µg GBP510 adjuvanted with AS03 (group 1), 25 µg GBP510 adjuvanted with AS03 (group 3), 25 µg unadjuvanted GBP510 (group 4) or placebo in stage II. The primary safety outcomes were solicited and unsolicited adverse events, while primary immunogenicity outcomes included anti-SARS-CoV-2 RBD IgG antibodies; neutralizing antibody responses; and T-cell immune responses. Safety assessment included all participants who received at least 1 dose of study intervention (safety set). Immunogenicity assessment included all participants who completed the vaccination schedule and had valid immunogenicity assessment results without any major protocol deviations (per-protocol set). This study was registered with ClinicalTrials.gov (NCT04750343). Findings: Of 328 participants who were enrolled between February 1 and May 28, 2021, 327 participants received at least 1 dose of vaccine. Each received either 10 µg GBP510 adjuvanted with AS03 (Group 1, n = 101), 10 µg unadjuvanted GBP510 (Group 2, n = 10), 25 µg GBP510 adjuvanted with AS03 (Group 3, n = 104), 25 µg unadjuvanted GBP510 (Group 4, n = 51), or placebo (n = 61). Higher reactogenicity was observed in the GBP510 adjuvanted with AS03 groups compared to the non-adjuvanted and placebo groups. The most frequently reported solicited local adverse event (AE) was injection site pain after any vaccination: (88·1% in group 1; 50·0% in group 2; 92·3% in group 3; 66·7% in group 4). Fatigue and myalgia were two most frequently reported systemic AEs and more frequently reported in GBP510 adjuvanted with AS03 recipients (79·2% and 78·2% in group 1; 75·0% and 79·8% in group 3, respectively) than in the unadjuvanted vaccine recipients (40·0% and of 40·0% in group 2; 60·8% and 47·1% in group 4) after any vaccination. Reactogenicity was higher post-dose 2 compared to post-dose 1, particularly for systemic AEs. The geometric mean concentrations of anti-SARS-CoV-2-RBD IgG antibody reached 2163·6/2599·2 BAU/mL in GBP510 adjuvanted with AS03 recipients (10 µg/25 µg) by 14 days after the second dose. Two-dose vaccination of 10 µg or 25 µg GBP510 adjuvanted with AS03 induced high titres of neutralizing antibody via pseudovirus (1369·0/1431·5 IU/mL) and wild-type virus (949·8/861·0 IU/mL) assay. Interpretation: GBP510 adjuvanted with AS03 was well tolerated and highly immunogenic. These results support further development of the vaccine candidate, which is currently being evaluated in Phase 3. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investment ID OPP1148601. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Volumetric assessment and clinical predictors of cirrhosis in patients undergoing hepatectomy for hepatocellular carcinoma with presumed normal liver function.

AIM: Indocyanine green retention rate at 15 min (ICGR15) is a frequently used indicator of liver function. Herein, clinicopathological characteristics of cirrhotic patients with normal ICGR15 value (< 10%) were investigated, as these patients have risk of postoperative liver insufficiency when receiving a major hepatic resection. METHODS: Patients undergoing hepatectomy for hepatocellular carcinoma were divided into three groups: non-cirrhotic livers (Group A, n = 112): cirrhotic livers with ICGR15 < 10% (Group B, n = 71): and cirrhotic livers with ICGR15 > 10% (Group C, n = 296). Background characteristics and surgical outcomes were compared between groups. Functional liver volume (FLV) was computed using total liver volume and signal intensity ratio. Liver parenchymal cell volume ratio was measured in non-cancerous tissue obtained from resected specimens. Univariate and multivariate analyses were performed to detect clinical characteristics correlating with cirrhotic liver pathology with normal ICGR15. RESULTS: There was no significant difference between groups in TLV. FLV was gradually reduced from Group A toward Group C. Liver parenchymal cell volume ratio was also gradually reduced from Group A toward Group C. Multivariate analysis revealed that platelet count (< 12 × 104/mm3) (p = 0.001) and prothrombin time (< 80%) (p = 0.025) were significantly associated with cirrhotic liver pathology among patients with normal ICGR15. CONCLUSION: Our results suggested that cirrhotic liver pathology despite normal liver function was characterized by slightly decreasing liver parenchyma as well as slight degree of fibrosis. Platelet count and PT% are useful for predicting liver cirrhosis with normal ICGR15.

Correlation of breast cancer incidence with the number of motor vehicles and consumption of gasoline in Korea.

While several reproductive and lifestyle-related factors are already well-known as established risk factors for breast cancer, environmental factors have attracted attention only recently. The objective of the current study was to assess the association between the breast cancer incidences in females, the mortality rate and the number of motor vehicles on the one side and the consumption of gasoline which could work as a major source of air pollution at the other side. The breast cancer incidences and the mortality trends were compared with various indices of westernization like dietary patterns or industrialization with 10 years lag of time. Geographical variations with 10, 15 and 20 years lag of time were assessed between the breast cancer incidence in 2010 and the number of motor vehicles as well as the consumption of gasoline. The upward trend of motor vehicle numbers proved to be comparable to those of breast cancer incidence and mortality. However, the consumption of gasoline started to decrease since the mid-1990s. The geographic distribution of motor vehicle numbers and gasoline consumption in 1990 is in a positive correlation with the breast cancer incidence rates in 2010 and the 20-year lag time (R2 0.379 with the number of motor vehicles and 0.345 with consumption of gasoline). In a linear relationship between the breast cancer incidences in 2010 and the log transformed number of motor vehicles, the log transformed consumption of gasoline in 2000 also showed a positive relationship (R2 0.367 with the number of motor vehicles and 0.329 with consumption of gasoline). The results of the current study indicate that there may be a positive relation between the number of vehicles, gasoline consumption and the incidence of breast cancer from the aspects of long-term trends and geographical variation.

Clinical and economic burden of invasive pneumococcal disease in adults: a multicenter hospital-based study.

BACKGROUND: Streptococcus pneumoniae causes a broad spectrum of illnesses ranging from mild upper respiratory tract infections to invasive pneumococcal disease (IPD). Quantitative data on the burden of pneumococcal disease, important for the establishment of appropriate vaccination strategies, is currently lacking in adults. METHODS: This multicenter, retrospective cohort study was designed to estimate the clinical and economic burden of IPD in adults over the last decade. Data were collected from patients with IPD at 10 university hospitals in South Korea. We estimated the proportion of IPD among all hospitalized patients, the case fatality rate, and the direct medical costs of IPD. Data were further analyzed according to age and risk groups. RESULTS: During the study period, 970 patients with IPD were identified. The mean age for all patients was 60.9 years; patients aged 50-64 years (33.0%) were most numerous, followed by those aged 65-74 years (27.4%). Overall, the proportion of IPD was 0.36 cases/1000 hospitalized patients and the case fatality rate was 30.9%, which increased significantly with age (p < 0.01). The mean direct medical costs were estimated to be US $7,452 without a difference between age and risk groups. On multivariate analysis, old age, advanced ECOG performance status, bacteremic pneumonia, and nosocomial infection were independent risk factors of 30-day case fatality. CONCLUSIONS: The clinical disease burden of IPD increased significantly with age and direct medical costs from IPD were substantial, regardless of age and co-morbid conditions. The current age-based vaccination strategy appears to be appropriate.

Impact of Physician's Education on Adherence to Tuberculosis Treatment for Patients of Low Socioeconomic Status in Bangladesh.

Successful tuberculosis control depends on good adherence to treatment. Yet, limited data are available on the efficacy of methods for improving the adherence of patients of low socioeconomic status. We evaluated the impact of physician-provided patient education on adherence to anti-tuberculosis medication in a low socioeconomic status and resource-limited setting. A pre-/post-intervention study was conducted at a suburban primary health care clinic in Bangladesh where an intensive education strategy was established in May 2006. Treatment outcomes of tuberculosis patients from March 2005 to April 2006 (pre-intervention) and from May 2006 to December 2007 (post-intervention) were compared. Among 354 patients, 198 (56%) were treated before intervention and 156 (44%) were treated after intervention. Cumulative adherence to anti-tuberculosis medication was significantly greater in the intervention group than in the control group in univariate and multivariate analyses. Physician's education can contribute to increasing the adherence of patients in resource-limited settings.