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Background Current guidelines recommend early termination of triple therapy and the use of direct oral anticoagulants (DOAC) for non-valvular atrial fibrillation (NVAF) patients who undergo percutaneous coronary intervention (PCI), due to safety concerns. However, to date, real-world medication usage and safety outcomes (specifically bleeding) in NVAF patients with stent implantation have not been well assessed. Methods This was a retrospective, observational, medical database cohort study in Japanese ischemic heart disease (IHD) patients with NVAF who underwent PCI between 2012 and 2017. The primary outcome was clinically relevant bleeding; secondary outcomes included individual bleeding events. A multivariate analysis was conducted to identify risk factors affecting the occurrence of clinically relevant bleeding events. Results The analysis population comprised 5695 patients [3530 received DOACs and 2165 received vitamin K antagonists (VKAs)]. The incidence of primary outcome events (clinically relevant bleeding/100 patient-years) was 6.05 in the DOAC group and 8.42 in the VKA group, resulting in a nonsignificant 21% lower risk in the DOAC group. The DOAC group also had a nonsignificant 24%, 24%, and 34% lower risk of bleeding requiring transfusion, intracranial bleeding, and lower gastrointestinal bleeding, respectively, compared with the VKA group. A multivariate analysis of the primary outcome showed a significantly higher risk of bleeding among older patients and those with lower body weight and abnormal renal function. Conclusions In this retrospective real-world evaluation of IHD patients with NVAF and PCI, DOAC-treated patients had a lower risk of developing clinically relevant bleeding compared with the VKA group.

Background: ETNA-VTE-Japan is a prospective, observational study conducted as part of a postmarketing study regarding the safety and effectiveness of edoxaban in Japanese patients with venous thromboembolism (VTE). The results of the final analysis of data collected at 1 year are presented. Methods and Results: A total of 1,732 patients were included in this study. The safety and effectiveness were evaluated in 1,702 patients (safety analysis set; SAS) and in 1,698 patients (effectiveness analysis set). In the SAS, 39.4% of patients were aged ≥75 years, 58.2% had body weight ≤60 kg, and 22.2% had creatinine clearance

To evaluate scoring systems to predict Legionella pneumonia and therapeutic efficacy against Legionella pneumonia, the Japanese Society of Chemotherapy Legionella committee has collected data on cases of Legionella pneumonia from throughout Japan. We analyzed 176 patients with Legionella pneumonia and compared them with 217 patients with Streptococcus pneumoniae pneumonia and 202 patients with Mycoplasma pneumoniae pneumonia. We evaluated four scoring systems, the Winthrop-University Hospital score, Community-Based Pneumonia Incidence Study Group score, and Japan Respiratory Society score, but they demonstrated limited sensitivity and specificity for predicting Legionella pneumonia. Using six clinical and laboratory parameters (high fever, high C-reactive protein, high lactate dehydrogenase, thrombocytopenia, hyponatremia, and unproductive cough) reported by Fiumefreddo and colleagues, only 6% had Legionnella pneumonia when less than 2 parameters were present. The efficacy rates of antibiotics at the time of termination were 94.6% for intravenous antibiotics, including ciprofloxacin and pazufloxacin, and 95.5% for oral antibiotics, including ciprofloxacin, levofloxacin, garenoxacin, moxifloxacin, and clarithromycin. Our results suggested that the previously reported clinical scoring systems to predict Legionnella pneumonia are not useful, but 6 simple diagnostic score accurately ruled out Legionnella pneumonia, which may help to optimize initial empiric therapy. Quinolones and clarithromycin still showed good clinical efficacy against Legionella pneumonia.

Legionella species are consistently identified as some of the most common causative agents of severe community-acquired pneumonia (CAP) or nosocomial pneumonia. Although the number of reported Legionella infection cases is gradually increasing in Japan, most cases are diagnosed by a urinary antigen test, which identifies only L. pneumophila serogroup 1. Therefore, assessment of pneumonia-causing Legionella species and serogroups would be important. The Japan Society for Chemotherapy Legionella committee has collected the isolates and clinical information on cases of sporadic community-acquired Legionella pneumonia throughout Japan. Between December 2006 and March 2019, totally 140 sporadic cases were identified, in which L. pneumophila was the most frequently isolated species (90.7%) followed by L. bozemanae (3.6%), L. dumofii (3.6%), L. micdadei (1.4%), and L. longbeachae (0.7%). Among 127 isolates of L. pneumophila, 111 isolates were of serogroup 1, two of serogroup 2, four of serogroup 3, one of serogroup 4, one of serogroup 5, seven of serogroup 6, and one was of serogroup 10. We also assessed in vitro activity of antibiotics against these isolates and showed that quinolones and macrolides have potent anti-Legionella activity. Our study showed that pneumonia-causing Legionella species and serogroup distribution was comparable to that reported in former surveillances. L. pneumophila was the most common etiologic agent in patients with community-acquired Legionella pneumonia, and L. pneumophila serogroup 1 was the predominant serogroup.

BACKGROUND ETNA-VTE-Japan is an ongoing prospective observational study conducted as part of a postmarketing observational study to investigate the safety and effectiveness of edoxaban in Japanese patients for whom the drug has been newly prescribed to treat venous thromboembolism (VTE) and prevent VTE recurrence. The results of an interim analysis of data collected at 3 months are presented.Methods and Results:A total of 1,732 patients were enrolled. The safety and effectiveness analyses included data from 1,703 and 1,699 patients, respectively. In the safety analysis set, 39.4% of patients were aged ≥75 years, 58.2% had body weight ≤60 kg, and 22.2% had creatinine clearance

In vitro activities of sitafloxacin (STFX) along with fluoroquinolones (levofloxacin (LVFX), moxifloxacin (MFLX), garenoxacin (GRNX)) and macrolides (azithromycin, clarithromycin) against atypical bacteria (Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia trachomatis, Chlamydophila pneumoniae) recovered from clinical specimens from 2009 to 2014 at different healthcare facilities in Japan were investigated. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC₉₀) against M pneumoniae (n= 14) was 0.03μg/mL which was comparable to GRNX, 4- and 16-fold more active than MFLX and LVFX, respectively. Reduced susceptibilities of M pneumoniae (9/14 isolates) to macrolides were observed. MIC₉₀ of STFX against L. pneumophila (n =15) was 0.004μg/mL which was 2- and 4-fold more active than GRNX/LVFX and MFLX, respectively. The minimum inhibitory concentration range of STFX against C. trachomatis (n=5) and C. pneumoniae (n=5) were from 0.015 to 0.03 and from 0.03 to 0.06μg/mL, respectively. Furthermore, differences between the activities of STFX against various clinical isolates in 2009 and those in 2012, which were already published in two articles (Jpn. J. Antibiotics 63:411- 430, 2010, 66:311-330, 2013), were also evaluated. The MIC90s of STFX against methicillin- susceptible Staphylococcus aureus (MSSA), Streptococcus spp. and Enterococcus faecalis isolated in 2012 were 4 or 8 times higher than those in 2009, however there was no difference between STFX activities against other species in 2009 and those in 2012. In conclusion, STFX showed potent activity against atypical bacteria (M pneumoniae, L. pneumophila, C. trachomatis, C. pneumoniae) and no tendency for emergence resistance to Gram- positive cocci, Gram-negative bacteria and anaerobes except MSSA, Streptococcus spp. andt. faecalis.

The activities of various antibiotics against 58 clinical isolates of Legionella species were evaluated using two methods, extracellular activity (minimum inhibitory concentration [MIC]) and intracellular activity. Susceptibility testing was performed using BSYEα agar. The minimum extracellular concentration inhibiting intracellular multiplication (MIEC) was determined using a human monocyte-derived cell line, THP-1. The most potent drugs in terms of MICs against clinical isolates were levofloxacin, garenoxacin, and rifampicin with MIC90 values of 0.015 μg/ml. The activities of ciprofloxacin, pazufloxacin, moxifloxacin, clarithromycin, and azithromycin were slightly higher than those of levofloxacin, garenoxacin, and rifampicin with an MIC90 of 0.03–0.06 μg/ml. Minocycline showed the highest activity, with an MIC90 of 1 μg/ml. No resistance against the antibiotics tested was detected. No difference was detected in the MIC distributions of the antibiotics tested between L. pneumophila serogroup 1 and L. pneumophila non-serogroup 1. The MIECs of ciprofloxacin, pazufloxacin, levofloxacin, moxifloxacin, garenoxacin, clarithromycin, and azithromycin were almost the same as their MICs, with MIEC90 values of 0.015–0.06 μg/ml, although the MIEC of minocycline was relatively lower and that of rifampicin was higher than their respective MICs. No difference was detected in the MIEC distributions of the antibiotics tested between L. pneumophila serogroup 1 and L. pneumophila non-serogroup 1. The ratios of MIEC:MIC for rifampicin (8) and pazufloxacin (2) were higher than those for levofloxacin (1), ciprofloxacin (1), moxifloxacin (1), garenoxacin (1), clarithromycin (1), and azithromycin (1). Our study showed that quinolones and macrolides had potent antimicrobial activity against both extracellular and intracellular Legionella species. The present data suggested the possible efficacy of these drugs in treatment of Legionella infections.

Sitafloxacin (STFX, Gracevit 50 mg, fine granules 10%), an oral quinolone antibacterial agent, was approved additionally for administration at a dose of 100 mg once a day in August 2011. A use-results survey on STFX 100 mg/day was performed from December 2011 to May 2013. In total, 1,186 case cards were collected from 226 medical institutions and 1,089 cases were subjected to a safety evaluation and 1,069 were subjected to an efficacy evaluation. The incidence of adverse drug reactions (ADRs) was 2.11% (23/1,089 cases) and no serious ADRs were observed. The major ADR was diarrhea at 1.10% (12/1,089 cases). Of these 12 cases, 10 cases developed symptoms within 4 days of treatment. All of them, except one case that could not be followed up, either recovered or improved. Nonsteroidal anti-inflammatory drugs of the phenyl acetate and propionate types, which require caution when coadministered with STFX, were used concomitantly by 17.6% (192/1,089 cases) of patients but no central nervous system ADRs were observed. The overall efficacy rate was 96.4% (1,030/1,069 cases) and by types of infections, it was 97.0% (387/399 cases) for respiratory tract infections, 96.7% (353/365 cases) for urinary tract infections, 94.7% (36/38 cases) for gynecological infections, 92.3% (132/143 cases) for otorhinolaryngological infections, 98.4% (122/124 cases) for dental and oral surgical infections. The efficacy rate in every category of site of infection exceeded 90%. The overall eradication rate was 94.4% (185/196 strains) including Gram-positive bacteria at 95.4% (62/65 strains), Gram-negative bacteria at 92.2% (94/102 strains), anaerobes at 100.0% (11/11 strains) and atypical bacteria at 100.0% (18/18 strains). In conclusion, this use-results survey confirmed that STFX 100 mg/day is an effective administration with no serious problems in its safety profile and efficacy rate of over 90% in every category of site of infection.

Sitafloxacin (STFX, Gracevit 50mg, fine granules 10%), a new quinolone antibacterial agent, was approved in January 2008, and the use-results survey was carried out over the 2 years between December 2008 and November 2010. We studied the efficacy and safety of STFX in 1,452 patients with urinary tract infections (cystitis, pyelonephritis, urethritis). The total efficacy rate for urinary tract infections was 91.4% (1,235/1,351 patients). Efficacy rates, classified by the type of infection, were: uncomplicated cystitis 95.9% (466/486 patients), complicated cystitis 87.2% (511/586 patients), uncomplicated pyelonephritis 96.1% (49/51 patients), complicated pyelonephritis 93.5% (145/155 patients), and urethritis 87.7% (64/73 patients). Efficacy rates were 86.0% (49/57 patients) for non-responders to cephems and 77.4% (48/62 patients) for non-responders to quinolones. The eradication rate of indicated strains was 90.5% (545/602 strains). The eradication rates of major causative bacteria were; Escherichia coli 92.7% (294/317 isolates), Enterococcus faecalis 86.0% (43/50 isolates), Pseudomonas aeruginosa 66.7% (16/24 isolates), Klebsiella pneumoniae 95.2% (20/21 isolates), and Chlamydia trachomatis 88.9% (8/9 isolates). The incidence of adverse drug reactions (ADRs) was 2.71% (37/1,365 cases). Major ADRs were diarrhoea (0.88%, 12 cases) and hepatic function disorders (0.51%, 7 cases). A serious ADR (hepatic function abnormality) was observed in 1 case, and the hepatic function in this patient returned to normal after treatment with STFX was discontinued. In conclusion, these results suggest that STFX is a useful antibacterial agent with an efficacy rate of 91.4% against urinary tract infections, with a minimum efficacy rate of 87.2% (against complicated cystitis), and has no serious problems in its safety profile.

Sitafloxacin (STFX, Gracevit 50 mg, fine granules 10%), a new quinolone antibacterial agent, was approved in January 2008, and the use-results survey was performed for 2 years from December 2008 to November 2010. In total, 3558 case cards were collected from 287 medical institutions and 3331 cases were subjected to a safety evaluation and 3225 were subjected to an efficacy evaluation. Incidence of adverse drug reactions (ADRs) was 4.44% (148/3331 cases). Major ADRs were diarrhea (55 cases) and hepatic function disorders (39 cases), and the incidences were 1.65% and 1.17%, respectively. Serious ADRs were observed in 5 cases (7 episodes); gastrointestinal haemorrhage, hepatic function abnormal, white blood cell count decreased, drug eruption, hypoglycemia, pneumonia, and superinfection in one case each. Efficacy rate was 92.9% (2997/3225 patients) in total with a range of 91.4 to 97.8% by type of infection such as respiratory tract and urinary tract. Eradication rate of indicated strains was 91.5% (808/883 strains) including Gram-positive bacteria at 92.3% (310/336 strains), Gram-negative bacteria at 90.7% (458/505 strains), anaerobes at 100.0% (28/28 strains) and atypical bacteria at 85.7% (12/14 strains). In conclusion, this use-results survey confirmed that STFX is a useful antibacterial agent with no serious problems in its safety profile and efficacy rates of over 90% against all infections.

The appropriate administration method of levofloxacin in relation to symptoms was investigated by following up 2,353 patients prescribed either levofloxacin (300 mg divided into 3 doses) or 400 mg (divided into 2 doses) for the treatment of acute upper respiratory tract infection accompanied by fever (temperature (or = 38 degrees C) of suspected bacterial infection. 1) The cure rate based on body temperature as an index was significantly higher in the group administered 400 mg/day compared with the group administered 300 mg/day. No significant difference between the two regimens was observed in patients with a temperatureor = 38.5 degrees C at the start of administration, but patients with a temperatureor = 38.6 degrees C showed a significantly higher cure rate when administered 400 mg/day compared with 300 mg/day. 2) No significant difference between the groups was observed with respect to the improvement of quality of life (QOL), assessed using a VAS. In patients with a temperatureor = 38.6 degrees C, however, significantly higher improvement rates were demonstrated on days 3, 5 and 6 of treatment at 400 mg/day compared with 300 mg/day. 3) The reconsultation rate was significantly lower in the group administered 400 mg/day compared with the group administered 300 mg/day. No significant difference between the groups was observed in patients with a temperatureor = 38.5 degrees C. However, in the patients with a temperatureor = 38.6 degrees C, treatment at 400 mg/day achieved a significantly lower reconsultation rate compared with 300 mg/day. 4) Nonsteroidal anti-inflammatory drugs (NSAIDs) were concomitantly administered to 64.3% of the patients, but no significant difference in the cure rate was observed between patients with or without concomitant use of NSAIDs. 5) Among all of the patients, 12.7% were positive for the influenza virus, and anti-influenza drugs were concomitantly administered to 41.3% of them. However, no significant difference in the cure rate was observed between the group administered levofloxacin alone and the group concomitantly administered anti-influenza drugs. 6) The incidence of adverse drug reactions was 0.84% in the group administered 400 mg/day and 0.50% in the group administered 300 mg/day. No significant difference was observed between these groups and no serious adverse drug reactions occurred. In conclusion, for treating patients with acute upper respiratory tract infection accompanied by fever (or = 38.6 degrees C) and suspected bacterial infection, levofloxacin dosage of 400 mg/day (divided into 2 doses) was superior to 300 mg/day (divided into 3 doses) in terms of therapeutic effect, QOL, and the reconsultation rate. This was considered to be an administration method worth recommending, including its safety. In patients with a temperature of 38.0 degrees C to 38.5 degrees C, administration of levofloxacin at 300 mg/day was confirmed to demonstrate a sufficient therapeutic effect.

Mastoparan has been reported to induce a wide variety of cellular actions by activating GTP-binding proteins (G proteins) in various cells. Here, we demonstrate that mastoparan is able to stimulate the secretion of PRL from rat anterior pituitary tumor GH3 cells in dose- and time-dependent manners. Mastoparan had no effect on the accumulation of intracellular cAMP; however, it induced a rapid increase in the intracellular Ca2+ concentration in GH3 cells. Extracellular Ca2+ was required for mastoparan-induced PRL secretion, which was inhibited by nifedipine, an L-type Ca2+ channel blocker. Incubation of mastoparan with myo-[3H]inositol-labeled GH3 cells also resulted in the increased formation of inositol phosphates (InsPs) compared with control cells. Neomycin sulfate and U73122, both phospholipase C inhibitors, suppressed mastoparan-induced PRL secretion. Guanosine 5'-1beta-thioldiphosphate (GDPbetaS) encapsulated in GH3 cells by reversible electropermeabilization suppressed the response to mastoparan. However, pretreatment with pertussis toxin had no effect on the stimulation of PRL secretion by mastoparan, and both Mas7 (a highly active analogue of mastoparan) and Mas17 (an inactive analogue) enhanced the secretion of PRL to a similar level to that of mastoparan-induced GH3 cells. In contrast, the substance P-related peptide GPant-2A, a Gq antagonist, inhibited mastoparan-induced PRL release, whereas GPant-2, a G(i/o) antagonist, did not in electropermeabilized GH3 cells. Moreover, a specific G(q/11) antibody against the carboxyl terminus of the G(q/11) alpha-subunit blocked the stimulatory effect of mastoparan on secretion and mastoparan-stimulated InsPs production in digitonin-permeabilized GH3 cells. These results indicate that mastoparan induces the Ca2+-regulated secretion of PRL from GH3 cells by activating G(q/11) and the phospholipase C pathway.

Iron oxides can be reduced in a scale by batch annealing treatment in a reducing atmosphere of 7 vol% H2+93 vol% N2 at 1123 K for hot-rolled coils of type430 stainless steel. The heating processes cause cracks, a Cr2O3 layer in the scale and a Cr depleted layer on the substrate. It is possible to produce a large number of cracks in the scale by employing a scale breaker. The ease of descaling is positively related to the amount of bending elongation. Similarly with shot blasting, descaling becomes easier as the projection energy of the shot blasting increases. The pickling solution penetrates the scale through cracks on the surface of the strip, and its acid dissolves the stainless steel coil and part of the scale. The scale peels from the stainless steel coil in island-like exfoliation until the scale has been removed from the entire surface of the stainless steel coil.

重金属除去法としてのフェライト法は, 最近その除去性能および生成汚泥管理の面から注目を集めているが, 重金属の除去機構と条件, 微細粒子の固液分離法, 重金属の溶出特性などについては明らかでない点も多い。本研究では, カドミウム水溶液を例として, 温度, pH, 中和・酸化条件などの各種操作因子について実験的検討を加えてフェライト生成に最適と思われる条件をもとめ, カドミウムの除去効果を調べた。また生成フェライトは通常は安定といわれるが, その安定度合を確認するためにカドミウムの溶出試験を行うとともに, 操作条件と生成物の安定性について検討した。さらに生成フェライトは効率的に固液分離を行う必要があるが, 廃水の質あるいは操作条件によっては微細かつ低磁化の粒子が生成し固液分離に困難をきたす。ここでは, このような粒子についても高効率の除去が期待できる高勾配磁気分離法の適用性と限界についても検討を加えた。

The proton NMR absorption spectra from 1.3 to 77 K in two organic free radicals, BDPA–Bz and p-Cl-BDPA, have been measured on powder samples which undergo a magnetic phase transition from a paramagnetic to an antiferromagnetic state at the temperatures of 1.695 and 3.25 K respectively. The behavior of the NMR absorption spectra associated with the magnetic phase transition has been studied for the first time in the organic free radicals and interpreted in terms of the hyperfine interaction. These results are then compared with those of the TANOL radical, which is a linear antiferromagnet with no magnetic phase transition down to 1.3 K.