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A low-cost subsurface irrigation system can generate benefits for small-scale farmers who have scarce water resources. A ring-shaped emitter made from a standard rubber hose has been developed and introduced for subsurface irrigation in Indonesia. It is a low-cost irrigation technology based on indigenous materials and skills. To build a ring-shaped emitter of the original design, a rubber hose is bent into a ring shape with a diameter of about 20 cm, and then five 5-mm holes are drilled into it at even intervals. Next, the entire ring-shaped hose is covered with a permeable textile so that water can infiltrate in all directions around the buried emitter. Water is applied from a water tank connected to the emitter by adjusting the pressure head imposed at the inlet of the emitter. Although it has been successfully used in practice, the performance of the ring-shaped emitter has not been evaluated in detail. Additionally, because the ring-shaped hose is fully covered with the textile, it may be difficult to detect any malfunctions or repair it. To promote the ring-shaped emitter for subsurface irrigation among small-scale farmers in arid or semi-arid regions, it is important to design an emitter that is easy to maintain. This study proposes a reduction in the number of holes and a change of covering method. Because the number of experiments that can be carried out to evaluate the performance of alternative ring-shaped emitters is usually limited, numerical simulations can be performed in addition to experiments. The main objectives of this study thus were 1) to experimentally investigate the water movement around a buried ring-shaped emitter and 2) to numerically evaluate the effect of modifying the design of the ring-shaped emitter on soil water dynamics around the emitter. Numerical simulations were carried out using HYDRUS, one of the most complete packages for simulating variably-saturated water flow in two- or three-dimensional domains. HYDRUS simulations in a fully three-dimensional domain were performed using the soil hydraulic parameters that were optimized against experimental data collected during experiments with the original ring-shaped emitter. Simulation results confirmed that reducing the number of holes does not significantly affect the water availability in silt for model plants, such as tomato and strawberry, and that covering the entire emitter is not necessary. Partially covering the emitter allows one to maintain the emitter much more easily compared to the original fully-covered emitter.

An artificial capillary barrier (CB), which consists of two layers of gravel and coarse sand, was used to improve the soil water retention capacity of the root zone of sandy soil for the cultivation of Japanese spinach (Brassica rapa var. perviridis). The performance of a CB under specific conditions can be evaluated using numerical simulations. However, there have been relatively few numerical studies analyzing soil water dynamics in CB systems during crop growth. The objectives of this study were (i) to evaluate the performance of a CB during the cultivation of Japanese spinach irrigated at different rates and (ii) to investigate the effect of the irrigation schedule on root water uptake. Numerical analysis was performed using HYDRUS-1D after the soil hydraulic properties of the CB materials were determined. In most cases, the HYDRUS-1D results agreed well with the experimental soil water content data without any calibration when the dual-porosity model describing soil hydraulic properties was used for gravel and coarse sand. We found that the dual-porosity model was able to attenuate the unrealistically steep reduction in the unsaturated hydraulic conductivity predicted by the single-porosity model. The numerical simulations also showed that the CB played an important role in maintaining plant-available water in the root zone while maximizing the water use efficiency. The numerical simulations revealed that the irrigation frequency could be reduced by half during the early growth stage, and the water use efficiency could be greatly improved with the CB layer installed.

Maiko Kadowaki,1,* Koichi Sato,2,* Hisashi Kamio,3 Makoto Kumagai,3 Rikishi Sato,3 Takafumi Nyui,3 Yukihiro Umeda,1 Yuko Waseda,1 Masaki Anzai,1 Haruka Aoki-Saito,4 Yasuhiko Koga,4 Takeshi Hisada,5 Hideaki Tomura,6 Fumikazu Okajima,3 Tamotsu Ishizuka1 1Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193, Japan; 2Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebeshi, 371-8512, Japan; 3Laboratory of Signal Transduction, Faculty of Pharmaceutical Sciences, Aomori University, Aomori, 030-0943, Japan; 4Department of Respiratory Medicine, Gunma University Graduate School of Medicine, Maebeshi, 371-8511, Japan; 5Gunma University Graduate School of Health Sciences, Maebeshi, 371-8514, Japan; 6Laboratory of Cell Signaling Regulation, Division of Life Science, School of Agriculture, Meiji University, Kawasaki, 214-8571, Japan*These authors contributed equally to this workCorrespondence: Tamotsu IshizukaThird Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui, 910-1193, JapanTel +81-776-61-8355Fax +81-776-61-8111Email tamotsui@u-fukui.ac.jpPurpose: Human bronchial smooth muscle cells (BSMCs) contribute to airway obstruction and hyperresponsiveness in patients with bronchial asthma. BSMCs also generate cytokines and matricellular proteins in response to extracellular acidification through the ovarian cancer G protein-coupled receptor 1 (OGR1). Cobalt (Co) and nickel (Ni) are occupational agents, which cause occupational asthma. We examined the effects of Co and Ni on interleukin-6 (IL-6) secretion by human BSMCs because these metals may act as ligands of OGR1.Methods: Human BSMCs were incubated in Dulbecco’s Modified Eagle Medium (DMEM) containing 0.1% bovine serum albumin (BSA) (0.1% BSA-DMEM) for 16 hours and stimulated for the indicated time by exchanging the medium with 0.1% BSA-DMEM containing any of the metals or pH-adjusted 0.1% BSA-DMEM. IL-6 mRNA expression was quantified via reverse transcription polymerase chain reaction (RT-PCR) using the real-time TaqMan technology. IL-6 was measured using an enzyme-linked immunosorbent assay. Dexamethasone (DEX) was added 30 minutes before each stimulation. To knock down the expression of OGR1 in BSMCs, small interfering RNA (siRNA) targeting OGR1 (OGR1-siRNA) was transfected to the cells and non-targeting siRNA (NT-siRNA) was used as a control.Results: Co and Ni both significantly increased IL-6 secretion in human BSMCs at 300 μM. This significant increase in IL-6 mRNA expression was observed 5 hours after stimulation. BSMCs transfected with OGR1-siRNA produced less IL-6 than BSMCs transfected with NT-siRNA in response to either Co or Ni stimulation. DEX inhibited Co- and Ni-stimulated IL-6 secretion by human BSMCs as well as pH 6.3-stimulated IL-6 secretion in a dose-dependent manner. DEX did not decrease phosphorylation of ERK1/2, p38 MAP kinase, and NF-κB p65 induced by either Co or Ni stimulation.Conclusion: Co and Ni induce secretion of IL-6 in human BSMCs through activation of OGR1. Co- and Ni-stimulated IL-6 secretion is inhibited by DEX.Keywords: cobalt, nickel, proton, cytokine, glucocorticoid, asthma

Hiroshi Saito,1 Yuya Nakamura,2,3 Masahiro Inagaki,2,4 Shiho Yamadera,5 Hideo Misawa,2,3 Naoki Sato,2,6 Tatsunori Oguchi,2 Takae Inagaki,7 Yuya Tsuji,2 Mayumi Tsuji,2 Isao Ohsawa,3 Hiromichi Gotoh,3 Yuji Kiuchi2 1JA Hiroshima Genneral Hospital, Hatsukaichi City, Hiroshima, Japan; 2Department of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan; 3Saiyu Soka Hospital, Soka City, Saitama, Japan; 4Faculty of Arts and Sciences at Fujiyoshida, Showa University, Fujiyoshida City, Yamanashi, Japan; 5Department of Hospital Pharmaceutics, Showa University School of Pharmacy, Shinagawa-ku, Tokyo, Japan; 6Department of Research Center, Tanabe Pharmacy Inc., Chuo-ku, Tokyo, Japan; 7Graduate School of Nursing and Rehabilitation Science, Yokohama City, Kanagawa, JapanCorrespondence: Yuya Nakamura Email y.nakamura@med.showa-u.ac.jpPurpose: Lipopolysaccharides (LPS) induce inflammation by binding to the Toll-like receptor (TLR) 4 complex, including LPS-binding protein (LBP). The anti-inflammatory effects of linagliptin in LPS-induced inflammation in the TLR4-independent pathway have not been examined before. We examined the anti-inflammatory effects of linagliptin in the TLR4- and the LBP-independent pathway.Methods: U937 cells were cultured in the medium supplemented with 10% fetal bovine serum (FBS) and treated with 100 nM phorbol myristate acetate for 48 h. Cells were then left untreated or were treated with 10 μg/mL anti-TLR4 antibodies alone or in combination with linagliptin for 1 h in media supplemented with or without 10% FBS. The cells were divided into 5 groups: a) control cells (untreated) b) cells treated with LPS c) cells treated with 10 μg/mL anti-TLR4 antibodies d) cells treated with LPS and 10 μg/mL anti-TLR4 antibodies and e) cells treated with LPS, 10 μg/mL anti-TLR4 antibodies, and linagliptin. The LPS concentrations used were 50 pg/mL or 100 pg/mL for cells treated in the presence of 10% FBS and 100 pg/mL or 1 μg/mL for cells treated in the absence of FBS. Linagliptin concentrations of 1 nM, 10 nM, and 100 nM were used for treatment. The supernatants were analyzed for interleukin (IL)-6 production after 24 h of various treatments.Results: LPS increased IL-6 production compared to the untreated control cells, and anti-TLR4 antibody suppressed LPS-induced increased IL-6 levels. Linagliptin suppressed LPS-induced IL-6 production in a concentration-dependent manner in the presence of FBS. However, only 100 nM linagliptin could suppress LPS-induced IL-6 production in the absence of FBS.Conclusion: Concentration-dependent and -independent inflammatory suppression was observed following linagliptin treatment after LPS induction in an experimental model of TLR4 inhibition by anti-TLR4 antibodies. Our results showed that linagliptin may inhibit inflammation through multiple mechanisms centered around the TLR-4-mediated pathway.Keywords: lipopolysaccharide, U937 cells, fetal bovine serum, anti- toll-like receptor 4 antibody, interleukin-6

Yoshihisa Ohashi,1 Kensuke Fukushima,1 Kentaro Uchida,1 Tomohisa Koyama,1 Maho Tsuchiya,1 Hiroki Saito,1 Katsufumi Uchiyama,2 Naonobu Takahira,3 Gen Inoue,1 Masashi Takaso1 1Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan; 2Department of Patient Safety and Healthcare Administration, Kitasato University School of Medicine, Sagamihara City, Kanagawa, 252-0374, Japan; 3Department of Rehabilitation, Kitasato University School of Allied Health Sciences, Sagamihara City, Kanagawa, 252-0374, JapanCorrespondence: Kensuke FukushimaDepartment of Orthopaedic Surgery, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara City, Kanagawa, 252-0374, JapanTel +81-42-778-9343Fax +81-42-778-5850Email kenfu@r4.dion.ne.jpBackground: In patients with hip osteoarthritis (OA), pain at rest, unlike pain on activity, is due to pain mechanisms that cannot be explained by nociceptive pain. However, it remains unclear whether central sensitization (CS) is one of the causes of exacerbated pain at rest in patients with hip OA. Therefore, we investigated the differences in causative factors and postoperative course of total hip arthroplasty (THA) between preoperative pain at rest and on activity in patients with hip OA.Methods: In total, 120 patients (125 hips, 22 men and 98 women, aged 64.5± 1.0 years) with hip OA were included. Preoperative pain at rest and on activity and CS were assessed using the visual analog scale (VAS) and CS Inventory (CSI), respectively. Postoperative assessments were evaluated using the Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ); pain, satisfaction, function, and mental scores were evaluated 6 and 12 months after THA.Results: Multivariate regression analysis indicated the CSI score as affecting VAS for pain at rest (β=0.067, P=0.002) but not VAS for pain on activity (β=0.036, P=0.073). VAS for pain at rest had a weak negative correlation with satisfaction and pain scores at both 6 and 12 months after THA (satisfaction, r=− 0.309, − 0.278; pain, r=− 0.202, − 0.22). VAS for pain on activity was not correlated with JHEQ. The CSI score had a weak or moderate negative correlation with three scores other than the function score at both 6 and 12 months after THA (satisfaction, r=− 0.266, − 0.213; pain, r=− 0.332, − 0.203, mental, r=− 0.427, − 0.370). The function score was weakly correlated with the CSI score only 6 months after THA (function, r=− 0.231, − 0.190).Conclusion: A higher level of preoperative pain at rest, a CS-related symptom, may affect postoperative pain persistence and dissatisfaction in patients with hip OA.Keywords: central sensitization, pain at rest, postoperative pain, hip osteoarthritis, total hip arthroplasty

Hironi Makita,1,2,* Masaru Suzuki,1,* Satoshi Konno,1 Kaoruko Shimizu,1 Yasuyuki Nasuhara,1 Katsura Nagai,1,3 Yasushi Akiyama,3 Satoshi Fuke,4 Hiroshi Saito,5 Takeshi Igarashi,5 Kimihiro Takeyabu,6 Masaharu Nishimura1,2 1Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 2Hokkaido Medical Research Institute for Respiratory Diseases, Sapporo, Japan; 3Center for Respiratory Diseases, JCHO Hokkaido Hospital, Sapporo, Japan; 4Department of Internal Medicine, KKR Sapporo Medical Center, Sapporo, Japan; 5Department of Internal Medicine, Hokkaido Chuo Rosai Hospital, Iwamizawa, Japan; 6Department of Respiratory Medicine, Otaru Kyokai Hospital, Otaru, Japan*These authors contributed equally to this workCorrespondence: Masaharu NishimuraDepartment of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanTel +81 11 706 5911Fax +81 11 706 7899Email ma-nishi@med.hokudai.ac.jpPurpose: Causes of death may be unique and different in Japanese patients with COPD because they are generally older, thinner, experience fewer exacerbations, and live longer than those in other countries. We investigated the detailed mortality profile in the Hokkaido COPD cohort study, which completed a 10-year follow-up with a very low dropout rate.Patients and Methods: We prospectively examined the 10-year natural history in 279 Japanese patients with COPD (GOLD 1, 26%; GOLD 2, 45%; GOLD 3, 24%; and GOLD 4, 5%). The majority of patients were male, and the average age at baseline was 69 years old. About 95% of all patients had accurate mortality data. The risk factors for mortality were also analyzed.Results: During the 10 years, 112 patients (40%) died. Their median survival time was 6.1 years (interquartile range: 4.7– 7.9 years), and age at death was 79 ± 6 years old (mean ± SD). Respiratory diseases, including pneumonia, were the leading causes of death in 45 (40%), followed by lung cancer in 24 (21%), other cancers in 18 (16%), and cardiovascular diseases in 12 (11%). In particular, lung cancer-related death was equally distributed across all COPD stages, with a higher proportion of lung cancer in the relatively younger generation (< 64 years old). Older age at baseline, lower BMI, and severer emphysema were significant risk factors for all-cause mortality.Conclusion: The unique mortality profile observed in this study should be considered when designing strategies for the management of patients with COPD in any geographic region.Keywords: chronic obstructive pulmonary disease, mortality, cause of death, cohort study

Yuka Ohe, Sachio Fushida, Takahisa Yamaguchi, Jun Kinoshita, Hiroto Saito, Koichi Okamoto, Keishi Nakamura, Hidehiro Tajima, Itasu Ninomiya, Tetsuo Ohta Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, JapanCorrespondence: Sachio FushidaDepartment of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa 920-8641, JapanTel +8176-265-2362Email fushida@staff.kanazawa-u.ac.jpIntroduction: Platelets are one factor promoting tumor development. Conversely, lymphocytes are one factor for immune protection. The peripheral blood platelets–lymphocyte ratio (PLR) is useful as an inflammation/immune indicator to predict postoperative recurrence and prognosis of a variety of malignancies. The peripheral blood neutrophil–lymphocyte ratio (NLR) has also been reported as a useful inflammation/immune indicator. However, there are few studies evaluating the relationship between these peripheral blood indicators and the effectiveness of chemotherapy. Thus, we examined these relationships in gastric cancer patients.Patients and Methods: Between 2005 and 2018, 41 gastric cancer patients treated with preoperative DCS therapy (docetaxel, cisplatin, and S-1) therapy followed by gastrectomy were evaluated. Data for peripheral blood tests prior to the initiation of chemotherapy were used. The effectiveness of chemotherapy was determined using Response Evaluation Criteria in Solid Tumors (RECIST) and the pathological response of primary lesions (Ef grade). The relationship between the blood test results and the effectiveness of chemotherapy was evaluated.Results: Each optimal cut-off value of peripheral inflammation/immune indicators was calculated through ROC curves. Although the pathological responder (Ef grade 2 or 3) revealed significantly better prognosis than the non-responder (Ef grade 0-1b), no relationship was found between responder according to RECIST and prognosis (P=0.014, P=0.992). In univariate analysis, a low PLR (< 180, P=0.005), low NLR (< 2.6, P=0.019), high lymphocyte (≥ 1.43, P=0.019) and high PNI (≥ 40, P=0.032) were identified as prognostic markers, whereas PLR was the only marker correlated with pathological response (P=0.031).Conclusion: PLR obtained prior to chemotherapy might be a useful indicator for predicting chemosensitivity owing to the simplicity of its procedure.Keywords: gastric cancer, preoperative chemotherapy, chemosensitivity, platelet-lymphocyte ratio

Naoki Sato,1,2 Yuya Nakamura,1,3 Shiho Yamadera,4 Masahiro Inagaki,1,5 Sachiyo Kenmotsu,5 Hiroshi Saito,4,6 Tatsunori Oguchi,1 Mayumi Tsuji,1 Hirokazu Chokki,1 Isao Ohsawa,3 Hiromichi Gotoh,3 Shinichi Iwai,6 Yuji Kiuchi1 1Department of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan; 2Department of Research Center, Tanabe Pharmacy Inc., Tokyo, Japan; 3Department of Nephrology, Saiyu Soka Hospital, Soka City, Saitama-ken, Japan; 4Department of Hospital Pharmaceutics, Showa University School of Pharmacy, Shinagawa-ku, Tokyo, Japan; 5Fuculty of Arts and Sciences at Fujiyoshida, Showa University, Fujiyoshida City, Yamanashi-ken, Japan; 6Department of Healthcare and Regulatory Sciences, Showa University School of Pharmacy, Shinagawa-ku, Tokyo, JapanCorrespondence: Yuya NakamuraDepartment of Pharmacology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, JapanTel +81-3-3784-8125Fax +81-3-3787-4790Email y.nakamura@med.showa-u.ac.jpPurpose: Dipeptidyl peptidase-4 inhibitors, including linagliptin, prevent inflammation. However, the in vitro effects of linagliptin are unclear. Moreover, although linagliptin inhibits lipopolysaccharide (LPS)-induced inflammation, the anti-inflammatory effects of linagliptin in this context are not concentration-dependent. In the absence of LPS-binding protein (LBP), the pro-inflammatory effects of LPS involve pathways other than the Toll-like receptor (TLR) 4 pathway. Here, we aimed to determine the anti-inflammatory mechanisms of linagliptin in an experimental model in which LBP was added to the medium.Methods: Human U937 monocytes were cultured at 1 × 106 cells/mL in Roswell Park Memorial Institute medium and differentiated into macrophages using phorbol myristate acetate. All processes were carried out in medium containing 10% fetal bovine serum (FBS). After 48 hrs of culture, we replaced the medium and pretreated the cells with 100, 250, 500, or 2500 nM linagliptin for 1 hr. We exchanged the medium again, and the cells were treated with 1 ng/mL LPS with or without 100, 250, 500, or 2500 nM linagliptin. Interleukin (IL)-6 and LBP in the supernatant, nuclear factor (NF)-κB/p65 in the nucleus, and reactive oxygen species (ROS) in the cells, as important markers of the mechanism of inflammation induction by LPS, were measured using enzyme-linked immunosorbent assay kits.Results: Linagliptin significantly prevented LPS-stimulated IL-6 production and intranuclear NF-κB/p65 levels in a concentration-dependent manner. LPS-induced intracellular ROS levels were significantly decreased by linagliptin at all concentrations. LBP levels were markedly higher in FBS-containing medium than in medium without FBS. However, LBP levels did not change following administration of linagliptin and/or LPS.Conclusion: Concentration-dependent and -independent inflammatory suppression was observed following linagliptin treatment in the context of LPS-induced pro-inflammatory responses. Thus, our findings suggested that linagliptin induced two different mechanisms to repress inflammation, i.e., TLR4-dependent and -independent mechanisms.Keywords: linagliptin, lipopolysaccharide-binding protein, interleukin-6, intranuclear subunit of nuclear factor-κB/p65, reactive oxygen species

Hitoki Saito,1 Momoko Ebashi,2 Masaru Kushimoto,3 Jin Ikeda,3 Fujiko Egashira,1 Suguru Yamaguchi,1 Kentaro Watanabe1 Katsuhiko Ogawa,2,4 Yutaka Suzuki,3,4 Hisamitsu Ishihara,1 Midori Fujishiro1,4 1Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Tokyo, Japan; 2Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; 3Division of General Medicine, Department of Internal Medicine, Nihon University, Tokyo, Japan; 4Department of Internal Medicine, Nihon University Hospital, Tokyo, Japan Abstract: Patients with diabetes mellitus (DM) are at increased risk of infections, with the urinary tract being the most frequent infection site. Incomplete bladder emptying, frequent urination and abdominal distension are typical symptoms of urinary tract infections (UTIs). A 68-year-old female with a long history of poorly controlled type 2 DM (T2DM) visited our hospital complaining of urinary retention, which was initially diagnosed as cystitis by another doctor. The urologist at our hospital identified a skin rash extending from the left hip to her genital area. A dermatologist was consulted. She was clinically diagnosed with herpes zoster (HZ) involving the left sacral dermatome area. As Elsberg syndrome (ES) was suspected, a lumbar puncture was performed, revealing aseptic meningitis associated with varicella zoster virus (VZV) infection. Intravenous acyclovir with urinary catheterization in combination with methylprednisolone pulse therapy resulted in a good clinical course. HZ very uncommonly involves sacral dermatomes, but it can develop in patients with prolonged poorly controlled DM. Furthermore, early diagnosis can be difficult when patients have diabetic peripheral neuropathy, which may mask symptoms related to skin lesions. Because this disease is potentially severe, detailed examination is important for clinicians managing patients with DM who have complaints indicative of urinary tract disorders. Keywords: herpes zoster, urinary retention, diabetic neuropathy

Daisuke Kobayashi,1,2 Yuichiro Shindo,2 Ryota Ito,2,3 Mai Iwaki,4,5 Junya Okumura,2,6 Toshihiro Sakakibara,2,7 Ikuo Yamaguchi,8 Tetsuya Yagi,9 Tomohiko Ogasawara,4 Yasuteru Sugino,6 Hiroyuki Taniguchi,7 Hiroshi Saito,10 Hideo Saka,11 Takashi Kawamura,1 Yoshinori Hasegawa2 On behalf of the Central Japan Lung Study Group 1Kyoto University Health Service, Kyoto, Japan; 2Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan; 3Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 4Department of Respiratory Medicine, Nagoya Daini Red Cross Hospital, Nagoya, Japan; 5Department of Respiratory Medicine, Kasugai Municipal Hospital, Kasugai, Japan; 6Department of Respiratory Medicine, Toyota Memorial Hospital, Toyota, Japan; 7Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan; 8Department of Central Laboratory, Toyohashi Municipal Hospital, Toyohashi, Japan; 9Department of Infectious Diseases, Nagoya University Hospital, Nagoya, Japan; 10Department of Respiratory Medicine, Aichi Cancer Center Aichi Hospital, Okazaki, Japan; 11Department of Respiratory Medicine, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan Background: Appropriate initial antibiotic treatment and avoiding administration of unnecessary broad-spectrum antibiotics are important for the treatment of pneumonia. To achieve this, assessment of risk for drug-resistant pathogens (DRPs) at diagnosis is essential.Purpose: The aim of this study was to validate a predictive rule for DRPs that we previously proposed (the community-acquired pneumonia drug-resistant pathogen [CAP-DRP] rule), comparing several other predictive methods.Patients and methods: A prospective observational study was conducted in hospitalized patients with community-onset pneumonia at four institutions in Japan. Pathogens identified as not susceptible to ceftriaxone, ampicillin–sulbactam, macrolides, and respiratory fluoroquinolones were defined as CAP-DRPs.Results: CAP-DRPs were identified in 73 (10.1%) of 721 patients analyzed. The CAP-DRP rule differentiated low vs high risk of CAP-DRP at the threshold of ≥3 points or 2 points plus any of methicillin-resistant Staphylococcus aureus specific factors with a sensitivity of 0.45, specificity of 0.87, positive predictive value of 0.47, negative predictive value of 0.87, and accuracy of 0.79. Its discrimination performance, area under the receiver operating characteristic curve, was 0.73 (95% confidence interval 0.66–0.79). Specificity of the CAP-DRP rule against CAP-DRPs was the highest among the six predictive rules tested.Conclusion: The performance of the predictive rules and criteria for CAP-DRPs was limited. However, the CAP-DRP rule yielded high specificity and could specify patients who should be treated with non-broad-spectrum antibiotics, eg, a non-pseudomonal β-lactam plus a macrolide, more precisely. Keywords: antibiotic resistance, algorithms, community-acquired pneumonia, healthcare-associated pneumonia

Yuka Hasebe,1 Kenji Kashiwagi,1 Toyoaki Tsumura,2 Yasuyuki Suzuki,3 Keiji Yoshikawa,4 Hirotaka Suzumura,5 Toshine Maeda,6 Ryuji Takeda,7 Hitomi Saito,8 Makoto Araie8 1Department of Ophthalmology, University of Yamanashi, Yamanashi, Japan; 2Department of Ophthalmology, Fussa Hospital, Tokyo, Japan; 3Department of Ophthalmology, Tokai University, Kanagawa, Japan; 4Yoshikawa Eye Clinic, Tokyo, Japan; 5Suzumura Eye Clinic, Tokyo, Japan; 6Maeda Eye Clinic, Tokyo, Japan; 7Faculty of Agriculture, Kinki University, Nara, Japan; 8Department of Ophthalmology, Kanto Central Hospital of the Mutual Aid Association of Public School, Tokyo, Japan Purpose: We investigated patient adherence and factors related to a newly introduced prostaglandin analog and timolol fixed-combination eye drops (PGTFC).Patients and methods: The Glaucoma Research on Adherence to fixed-Combination Eye drops in Japan (GRACE) study group performed a nationwide prospective questionnaire survey. Participants in this study were patients with glaucoma who were scheduled to receive any type of PGTFC for the first time. The participants answered a questionnaire on the day of PGTFC introduction and again at a return visit 4–6 weeks after PGTFC introduction. The physicians in charge were asked to complete a separate questionnaire on the day of PGTFC introduction. One of two leaflets was randomly delivered to each participant before the description of the PGTFC. One leaflet explained how to correctly instill the eye drops, and the other explained the clinical meaning of intraocular pressure reduction in addition to explaining how to correctly instill the eye drops. Nonadherence was defined as forgetting to instill the eye drops one or more times during the week before the return visit.Results: In total, 3,597 patients (age, 68.4±12.2 years) met the study protocol requirements. PGTFC introduction significantly reduced the number of antiglaucoma eye drops from 1.93±0.78 to 1.34±0.54 (P