Impact of Invasive Escherichia Coli Disease on Clinical Outcomes and Medical Resource Utilization Among Asian Patients in the United States.

INTRODUCTION: Invasive Escherichia coli disease (IED) can lead to sepsis and death and is associated with a substantial burden. Yet, there is scarce information on the burden of IED in Asian patients. METHODS: This retrospective study used US hospital data from the PINC AI™ Healthcare database (October 2015-March 2020) to identify IED cases among patients aged ≥ 60 years. IED was defined as a positive E. coli culture in blood or other normally sterile body site (group 1 IED) or positive culture of E. coli in urine with signs of sepsis (group 2 IED). Eligible patients with IED were classified into Asian and non-Asian cohorts based on their reported race. Entropy balancing was used to create cohorts with similar characteristics. Outcomes following IED were descriptively reported in the balanced cohorts. RESULTS: A total of 646 Asian and 19,127 non-Asian patients with IED were included (median age 79 years; 68% female after balancing). For both cohorts, most IED encounters had community-onset (> 95%) and required hospitalization (Asian 96%, mean duration 6.9 days; non-Asian 95%, mean duration 6.8 days), with frequent admission to intensive care (Asian 35%, mean duration 3.3 days; non-Asian 34%, mean duration 3.5 days), all standardized differences [SD] < 0.20. Compared to non-Asian patients, Asian patients were more likely to be discharged home (54% vs. 43%; SD = 0.22), and less likely to be discharged to a skilled nursing facility (24% vs. 31%; SD = 0.16). In-hospital fatality rates during the IED encounter were similar across cohorts (Asian 9%, non-Asian 10%; SD = 0.01). Most E. coli isolates showed resistance to ≥ 1 antibiotic (Asian 61%; non-Asian 64%) and 36% to ≥ 3 antibiotic classes (all SD < 0.20). CONCLUSION: IED is associated with a substantial burden, including need for intensive care and considerable mortality, in Asian patients in the USA that is consistent with that observed for non-Asian patients.

Real-World Epidemiology, Clinical and Economic Burden of Chronic Hepatitis B in Japan: A Retrospective Study Using JMDC Claims Database.

INTRODUCTION: Chronic hepatitis B (CHB) is one of the world's major healthcare problems, especially in the Western Pacific regions. This study describes the prevalence, incidence, treatment profiles and clinical and economic burden of chronic hepatitis B patients in Japan using the Japan Medical Data Center (JMDC) Claims Database. METHODS: This is a retrospective observational study. Prevalence cases were identified as patients with ≥ 1 inpatient or ≥ 2 outpatient CHB diagnoses and ≥ 2 records for hepatitis B tests or ≥ 1 prescription for CHB treatment between January 2010 and December 2019. Newly diagnosed CHB patients were defined as patients diagnosed from 2010 to 2018 with no history of the disease up to 2 years prior to the diagnosis. The index date is defined as the first CHB diagnosis day. We only used patients' data with ≥ 1-year post-index date. RESULTS: We identified 13,061 CHB prevalent cases (2010-2019), yielding a crude period prevalence of 0.32%. Newly diagnosed CHB patients (n = 1973; median age 52 years) were followed for a median period of 3.1 years, during which 15% received a CHB treatment. Entecavir was the most common first treatment (66%). During this period, 3.4% of the patients developed compensated cirrhosis (CC), 1.5% decompensated cirrhosis (DC) and 3.0% hepatocellular carcinoma (HCC). Around 43.3% of CHB patients were hospitalized at least once. Hospitalizations, treatment rates, serologic testing and screening for liver diseases increased as the severity of the disease progressed. The average total healthcare cost was 870,568 JPY (7779 USD) per person per year. DC and HCC resulted in the highest management costs. CONCLUSIONS: Chronic hepatitis B represents a high clinical and economic burden for patients and caregivers, given its morbidity and associated costs.

Targeted literature review of the burden of extraintestinal pathogenic Escherichia Coli among elderly patients in Asia Pacific regions.

BACKGROUND: Extraintestinal Pathogenic Escherichia coli (ExPEC) is a leading cause of invasive disease, including bacteremia and sepsis. Invasive ExPEC disease (IED) has the potential to complicate the clinical treatment of other conditions and is associated with an increased mortality, hospitalization, and worse outcomes. Older adults and individuals with comorbid conditions are at higher risk of IED. ExPEC is of particular concern in the Asia Pacific region due to aging populations and rising antimicrobial resistance. OBJECTIVES: This study aimed to synthesize most recent data on the epidemiology, clinical and economic burden of IED in the elderly/high risk populations in China, Japan, South Korea, Taiwan, and Australia. METHODS: A targeted literature review was conducted using Embase, Medline, as well as local scientific databases. We included studies published in English and local languages published from January 1, 2010 to October 7, 2020 that were relevant to the research objectives. Studies were narratively synthesized. RESULTS: A total of 1,047 studies were identified and 34 of them were included in this review. ExPEC accounted for 46.0% (1,238/2,692) of bacteria-related invasive diseases in patients aged above 60 years in South Korea, followed by China (44.4% (284/640)), Taiwan (39.0% (1,244/3,194)), and Japan (18.1% (581/3,206)), while Australia reported ExPEC out of all pathogens (54.7% (4,006/7,330)) in general adults. Comorbidities such as diabetes or cancer were common in these patients. Studies reported increases in length-of-stay, and in-hospital 30-day all-cause mortality related to ExPEC associated bacteremia was between 9% to 12%. From a cost perspective, a 3-fold increase in sepsis-associated cost was reported in South Korea between 2005 and 2012. In Australia, antimicrobial resistance contributed to an additional cost of AUD $5.8 million per year (95% uncertainty interval [UI], $2.2-$11.2 million) in the treatment of bloodstream infections (BSIs). CONCLUSION: ExPEC was a major cause of blood stream infection across China, Japan, South Korea, Taiwan, and Australia. Both the clinical and economic burden associated to ExPEC infections as well as the antimicrobial resistance observed in the elderly call for preventive and curative actions in these regions.

Extraintestinal Pathogenic Escherichia coli (ExPEC) is a leading cause of invasive disease, including bacteremia and sepsis.A targeted literature review included the most recent data from 34 published studies on the epidemiology and clinical and economic burden of IED in the elderly/high risk populations in China, Japan, South Korea, Taiwan, and Australia.ExPEC accounted for 46.0% (1,238/2,692) of bacteria-related invasive diseases in patients aged above 60 years in South Korea, followed by China (44.4% (284/640)), Taiwan (39.0% (1,244/3,194)), and Japan (18.1% (581/3,206)), while Australia reported ExPEC out of all pathogens (54.7% (4,006/7,330)) in general adults. Studies reported increases in length-of-stay and in-hospital 30-day all-cause between 9% to 12%. These factors, along with antimicrobial resistance observed in the elderly, call for preventive and curative actions in these regions.Data for costs associated with ExPEC induced BSI or sepsis in this region are limited, but evidence shows increasing expenditures.

Distribution of extraintestinal pathogenic Escherichia coli O-serotypes and antibiotic resistance in blood isolates collected from patients in a surveillance study in Japan.

INTRODUCTION: Invasive extraintestinal pathogenic Escherichia coli (ExPEC) disease (IED), characterised by sepsis and bacteraemia, is a major global healthcare concern worsened by emerging multidrug resistant (MDR) strains. The development of multivalent prophylactic vaccines targeting E. coli strains of IED-associated O-serotypes could address this. A better understanding of O-serotype distribution is required for this purpose. Here, we characterised O-serotype prevalence and drug resistance among ExPEC bacteraemia isolates in Japan. METHODS: E. coli blood isolates from patients aged ≥60 years with bacteraemia were obtained from a retrospective surveillance study in Japan (2015-2017). O-serotyping was performed by agglutination; for isolates non-typeable by agglutination, O-genotyping was performed. Antimicrobial susceptibility was evaluated by broth microdilution using a 21-antibiotic panel. The frequency of drug resistant (DR) isolates was evaluated by antimicrobial susceptibility testing. RESULTS: Of 401 ExPEC bacteraemia isolates evaluated, the most prevalent O-serotype (≥1%) was O25 (28.7% [n = 115]), followed by O1 (14.2% [n = 57]), O2 (8.5% n = 34]), O6 (5.5% [n = 22]), O75, O18, O13, O16, O15, O4, O46/O134, O86, O8 and O83 (each <5% prevalence). These 14 O-serotypes accounted for 81.5% of isolates collected. In total, 19% (n = 77) of isolates were DR ≥ 3, of which 59.7% were O25. Fluoroquinolone-resistance among all and O25 isolates was most prevalent (35.7% and 84.3%, respectively). Almost all (98%) isolates identified as O25 were of subtype O25B. CONCLUSIONS: E. coli serotype O25B showed the highest prevalence and highest multidrug resistance among ExPEC bacteraemia isolates from patients ≥60 years in Japan. Our data may inform development of multivalent glycoconjugate vaccines to prevent IED.

Incidence, economic burden, and treatment of acute respiratory tract infection in hematopoietic stem cell transplantation recipients using real world data in Japan: a retrospective claims data analysis.

AIMS: Acute respiratory tract infections (ARTIs) are common in hematopoietic stem cell transplantation (HSCT) recipients, however, data is limited regarding epidemiology and economic burden of ARTI in HSCT recipients in Japan. We evaluated the incidence of ARTI in HSCT recipients, associated economic burden, and ARTI-related treatments post-HSCT. MATERIALS AND METHODS: Patients receiving HSCT between July 2017 and December 2018, and those enrolled in the JMDC Claims Database for ≥6 months before index month (month when latest medical procedure code of HSCT recorded) were included. The outcomes included demographics, ARTI incidence, healthcare resource utilization (HCRU), direct costs, and ARTI-related treatments. RESULTS: In 330 analyzed patients, the ARTI incidence rate was 85.5% during total follow-up, consisting of post-HSCT hospitalization of mean 2.1 months and post-discharge periods of mean 17.6 months (post-HSCT hospitalization: 44.8%; post-discharge: 77.6%). For ARTI vs non-ARTI patients during post-HSCT hospitalization, length of hospitalization was significantly longer (mean [SD] months; 2.40 [1.73] vs 1.84 [1.09]; p = 0.0004), and median cost was significantly higher (JPY; 6,250,120.00 vs 4,774,570.00; p = 0.0096). The cost of outpatient visits during post-discharge periods, drug-related and non-drug-related costs of outpatient visits were generally higher for ARTI vs non-ARTI patients. In ARTI vs non-ARTI patients, utilization of any symptom relievers (decongestants, antitussives, and antipyretics), bronchodilators, immunoglobulin G, antibiotics, antivirals, and oxygen supply were numerically higher during post-HSCT hospitalization and post-discharge periods. The proportion of patients and mean prescription days for immunosuppressants during post-HSCT hospitalization were higher in ARTI vs non-ARTI patients. LIMITATIONS: This administrative claims study lacks clinical data and contains only direct medical costs. Patients were retained if they had at least 1 month of enrollment post-HSCT. CONCLUSIONS: In HSCT recipients, ARTI leads to substantial incremental HCRU and direct costs for management in real-world settings in Japan.

People receiving hematopoietic stem cell transplantation (HSCT) commonly suffer from acute respiratory infections (ARTIs). The real-world data on its incidence and economic impact in Japan is limited. In this study, using the JMDC Claims Database 330 HSCT recipients were identified during July 2017 and December 2018. Of these patients, 85.5% developed ARTI either during post-HSCT hospitalization (44.8%, within mean 2.1 months) or post-discharge period (77.6%, within mean 17.6 months). Patients with ARTI had longer hospital stays (2.40 months vs 1.84 months) and higher in-patient treatment costs (6,250,120.00 JPY vs 4,774,570.00 JPY) than those without ARTI. The costs associated with out-patient treatment, both drug-related and non-drug-related, were also higher for ARTI patients than non-ARTI patients. The use of medicines for stuffy nose (decongestants), dry cough (antitussives), and fever (antipyretics), and other medicines to treat respiratory infections (such as bronchodilators, immunoglobulin G, antibiotics, antivirals, and oxygen supply) was generally high with ARTI patients both during post-HSCT hospitalization and during post-discharge periods. The use of immunosuppressants was also more in patients who acquired ARTI as compared with non-ARTI patients during post-HSCT hospitalization. This study demonstrates the significant impact of ARTI in terms of economic and healthcare resource utilization in HSCT recipients in Japan.

Comparison of Current Regulatory Status for Gene-Based Vaccines in the U.S., Europe and Japan.

Gene-based vaccines as typified by plasmid DNA vaccines and recombinant viral-vectored vaccines are expected as promising solutions against infectious diseases for which no effective prophylactic vaccines exist such as HIV, dengue virus, Ebola virus and malaria, and for which more improved vaccines are needed such as tuberculosis and influenza virus. Although many preclinical and clinical trials have been conducted to date, no DNA vaccines or recombinant viral-vectored vaccines expressing heterologous antigens for human use have yet been licensed in the U.S., Europe or Japan. In this research, we describe the current regulatory context for gene-based prophylactic vaccines against infectious disease in the U.S., Europe, and Japan. We identify the important considerations, in particular, on the preclinical assessments that would allow these vaccines to proceed to clinical trials, and the differences on the regulatory pathway for the marketing authorization in each region.

Bilateral bipartite carpal scaphoid: a case report and literature review.

Congenital bipartite carpal scaphoid has been reported as an extremely rare congenital anomaly. We report a case of a 47-year-old man who was found with bilateral bipartite carpal scaphoids with no history of injury. Radiographs demonstrated symmetric findings of the distinct bipartition of the scaphoid without obvious degenerative change in both wrists. The patient complained of no other symptoms. The diagnostic differentiation of scaphoid bipartition from the pseudarthrosis of the scaphoid could be important in avoiding unnecessary surgery and inappropriate assessment in compensation cases.

Thermal/electron irradiation assisted coalescence of Sc3N@C80 fullerene in carbon nanotube and evidence of charge transfer between pristine/coalesced fullerenes and nanotubes.

Sc3N@C80 fullerenes are inserted inside carbon nanotubes (CNTs). The results show that the thermal stability of Sc3N@C80 fullerenes is around 1200 °C for the fullerenes resting on the wall of CNTs. Internal fullerenes show stability up to 1300 °C, which portrays them as one of most stable types of fullerenes. Electron irradiation of the peapods at 90 kV leads to the formation of capsules inside the CNTs at 5 × 10(9) e nm(-2) electron dosage. This value is an order of magnitude higher than the threshold of electron-induced damage in C60 molecules. Electron energy loss spectroscopy confirms the presence of Sc atoms in capsules. Encapsulation of fullerenes and capsule formation changes the oxidation state of Sc atoms from +2.5 towards +3. This is an evidence of charge transfer between the fullerene/capsule cage and CNT walls.

Site-specific attachment of a protein to a carbon nanotube end without loss of protein function.

Establishing a nanobiohybrid device largely relies on the availability of various bioconjugation procedures which allow coupling of biomolecules and inorganic materials. Especially, site-specific coupling of a protein to nanomaterials is highly useful and significant, since it can avoid adversely affecting the protein's function. In this study, we demonstrated a covalent coupling of a protein of interest to the end of carbon nanotubes without affecting protein's function. A modified Staudinger-Bertozzi ligation was utilized to couple a carbon nanotube end with an azide group which is site-specifically incorporated into a protein of interest. We demonstrated that Ca(2+)-sensor protein, calmodulin, can be attached to the end of the nanotubes without affecting the ability to bind to the substrate in a calcium-dependent manner. This procedure can be applied not only to nanotubes, but also to other nanomaterials, and therefore provides a fundamental technique for well-controlled protein conjugation.

Fluorescence labeling of carbon nanotubes and visualization of a nanotube-protein hybrid under fluorescence microscope.

Biological applications of carbon nanotubes have been hampered by the inability to visualize them using conventional optical microscope, which is the most common tool for the observation and measurement of biological processes. Recently, a number of fluorescence labeling methods for biomolecules and various fluorescence probes have been developed and widely utilized in biological fields. Therefore, labeling carbon nanotubes with such fluorophores under physiological conditions will be highly useful in their biological applications. In this Article, we present a method to fluorescently label nanotubes by combining a detergent and a fluorophore commonly used in biological experiments. Fluorophores carrying an amino group (Texas Red hydrazide or BODIPY FL-hydrazide) were covalently attached to the hydroxyl groups of Tween 20 using carbonyldiimidazole. Fluorescence microscopy demonstrated that nanotubes were efficiently solubilized and labeled by this fluorescently labeled detergent. By using this technique, we also demonstrated multicolor fluorescence imaging of a nanotube-protein hybrid.

Controlling atomic joints between carbon nanotubes by electric current.

Using a transmission electron microscope and a nanomanipulator, we explored the early head-to-head coalescence of two capped carbon nanotubes (CNTs) under induction of electric current. We measured detaching forces for coalesced CNTs, showing discrete identifiable values attributable to van der Waals interaction, single sp2-like bonds, and double sp3-like bonds by comparing them with forces obtained using molecular dynamics simulations. Our results underscore the feasibility of atomically controlled junctions of CNTs tuned by the amount of the electrical current.

A molecular linear motor consisting of carbon nanotubes.

We experimentally investigated a "molecular-linear-motor" system consisting of a capsule-like carbon nanotube (CNT) in the interior space of a host CNT. Transmission electron microscopy revealed the capsule traveled back and forth between both ends of the hollow space along the axial direction and rotated simultaneously. The mechanism was well explained with molecular dynamics simulation by considering the driving force supplied from thermal energy. The present system operates around room temperature and this opens up the possibility of designing novel nanodevices such as oscillators and switching memory devices.

Correlation between the mechanical and electrical properties of carbon nanotubes.

Correlation between the maximum allowable currents and the Young's moduli of the same individual carbon nanotubes was investigated in terms of current-voltage characteristics and the resonant frequencies of the cantilevered nanotubes. The maximum allowable current increases with increasing Young's modulus and saturates around 3 microA nm(-1) at Young's modulus higher than 1 TPa, indicating that electrical conduction is related to the defect density on the defective nanotube.

Postoperative change of the cross-sectional area of back musculature after 5 surgical procedures as assessed by magnetic resonance imaging.

Many investigators have reported that persistent low back pain may occur after posterior surgical intervention, and studies have investigated the histologic and histochemical changes in back muscle after posterior lumbar spine surgery. The purpose of the current study is to compare the pre- and postoperative cross-sectional area of the back musculature among 5 surgical groups including anterior lumbar interbody fusion, which has no direct invasion of the back musculature, using magnetic resonance imaging, and to correlate the clinical results with the degree of atrophy. The cross-sectional area of the back musculature was measured before and after surgery in T2-weighted axial magnetic resonance images using a computer-linked digitizer. The degree of atrophy (atrophy ratio) was calculated as a ratio of the postoperative cross-sectional area to the preoperative cross-sectional area. Clinical results were evaluated using the Japanese Orthopaedic Association's scores for the management of low back pain. Atrophy of the back musculature was confirmed in each group. However, no significant difference was seen in the atrophy ratio between the groups. Back musculature atrophy occurred even in anterior lumbar interbody fusion, which does not involve any direct surgery of the back muscle. A positive correlation was noted between the atrophy ratio and operation time only in posterior surgery, especially in nonfusion surgery. In conclusion, the current study suggests that a shorter operation time may minimize back muscle injury, and shows that factors inducing back musculature atrophy include not only direct invasion of the back muscle via a posterior approach, but also postoperative external fixation.

Structured water layers adjacent to biological membranes.

Water amid the restricted space of crowded biological macromolecules and at membrane interfaces is essential for cell function, though the structure and function of this "biological water" itself remains poorly defined. The force required to remove strongly bound water is referred to as the hydration force and due to its widespread importance, it has been studied in numerous systems. Here, by using a highly sensitive dynamic atomic force microscope technique in conjunction with a carbon nanotube probe, we reveal a hydration force with an oscillatory profile that reflects the removal of up to five structured water layers from between the probe and biological membrane surface. Further, we find that the hydration force can be modified by changing the membrane fluidity. For 1,2-dipalmitoyl-sn-glycero-3-phosphocholine gel (Lbeta) phase bilayers, each oscillation in the force profile indicates the force required to displace a single layer of water molecules from between the probe and bilayer. In contrast, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine fluid (Lalpha) phase bilayers at 60 degrees C and 1,2-dioleoyl-sn-glycero-3-phosphocholine fluid (Lalpha) phase bilayers at 24 degrees C seriously disrupt the molecular ordering of the water and result predominantly in a monotonic force profile.

Synthesis of carbon tubule nanocoils using Fe-In-Sn-O fine particles as catalysts.

We have developed Fe-In-Sn-O fine particle or powder catalysts for synthesizing carbon nanocoils by catalytic thermal chemical vapor deposition. The coprecipitation technique was used to produce the powder catalysts. By optimizing the composition ratios of Fe, In (between 10 and 33% of Fe), and Sn (less than 3.3% of Fe), carbon nanocoils could be grown in high yield. From the study of optimizing the compositions of In and Sn and the study of crystal structures of the catalysts using X-ray diffraction measurements, it was also found that Sn in the catalysts was required to grow carbon nanocoils and that In plays roles in increasing the yield of carbon nanocoils and controlling the coil diameters. This study will lead to the mass production of carbon nanocoils and therefore widen their applications.

Scanning probe microscopy installed with nanotube probes and nanotube tweezers.

We have developed well-controlled processes for the growth and manipulation of carbon nanotubes. The relatively thin multiwalled nanotubes were prepared with high purity by arc discharge with a high gas temperature. In the manipulation of nanotubes, the first crucial process is to prepare a nanotube array, so-called nanotube cartridge. We have found the alternated current electrophoresis of nanotubes by which nanotubes are aligned at the knife-edge of a disposal razor. The second important process is to transfer a nanotube from the nanotube cartridge onto a substrate in a scanning electron microscope. Using this method, we have developed nanotube probes and nanotube tweezers that operate in a scanning probe microscope (SPM). The nanotube probes have been applied for observation of biological samples and industrial samples to clarify their advantages. The nanotube tweezers have been demonstrated for their motion in scanning electron microscope and operated to carry a nanomaterial in a SPM.