Reversibly switching liquid crystals between three orthogonal orientation states for use in rapid-response THz phase shifters.

Liquid crystal (LC) devices for terahertz phase shifters inevitably use a thick cell gap for the required retardation, severely delaying the LC response. To improve the response, we virtually demonstrate novel LC switching between in-plane and out-of-plane for reversible switching between three orthogonal orientation states, broadening the range of continuous phase shifts. This LC switching is realized using a pair of substrates, each with two pairs of orthogonal finger-type electrodes and one grating-type electrode for in- and out-of-plane switching. An applied voltage generates an electric field that drives each switching process between the three distinct orientation states, enabling a rapid response.

Multiscale architecture for fast optical addressing and control of large-scale qubit arrays.

This paper presents a technique for rapid site-selective control of the quantum state of particles in a large array using the combination of a fast deflector (e.g., an acousto-optic deflector) and a relatively slow spatial light modulator (SLM). The use of SLMs for site-selective quantum state manipulation has been limited due to slow transition times that prevent rapid, consecutive quantum gates. By partitioning the SLM into multiple segments and using a fast deflector to transition between them, it is possible to substantially reduce the average time increment between scanner transitions by increasing the number of gates that can be performed for a single SLM full-frame setting. We analyzed the performance of this device in two different configurations: In configuration 1, each SLM segment addresses the full qubit array; in configuration 2, each SLM segment addresses a subarray and an additional fast deflector positions that subarray with respect to the full qubit array. With these hybrid scanners, we calculated qubit addressing rates that are tens to hundreds of times faster than using an SLM alone.

Warming signals in temperate reef communities following more than a decade of ecological stability.

Ecosystem structure and function are increasingly threatened by changing climate, with profound effects observed globally in recent decades. Based on standardized visual censuses of reef biodiversity, we describe 27 years of community-level change for fishes, mobile macroinvertebrates and macroalgae in the Tasmanian ocean-warming hotspot. Significant ecological change was observed across 94 reef sites (5-10 m depth range) spanning four coastal regions between three periods (1992-95, 2006-07, 2017-19), which occurred against a background of pronounced sea temperature rise (+0.80°C on average). Overall, fish biomass increased, macroinvertebrate species richness and abundance decreased and macroalgal cover decreased, particularly during the most recent decade. While reef communities were relatively stable and warming was slight between the 1990s and mid-2000s (+0.12°C mean temperature rise), increased abundances of warm affinity fishes and invertebrates accompanied warming during the most recent decade (+0.68°C rise). However, significant rises in the community temperature index (CTI) were only found for fishes, invertebrates and macroalgae in some regions. Coastal warming was associated with increased fish biomass of non-targeted species in fished zones but had little effect on reef communities within marine reserves. Higher abundances of larger fishes and lobsters inside reserves appeared to negate impacts of 'thermophilization'.

Efficacy of combining ING4 and TRAIL genes in cancer-targeting gene virotherapy strategy: first evidence in preclinical hepatocellular carcinoma.

Current treatments of hepatocellular carcinoma (HCC) are ineffective and unsatisfactory in many aspects. Cancer-targeting gene virotherapy using oncolytic adenoviruses (OAds) armed with anticancer genes has shown efficacy and safety in clinical trials. Nowadays, both inhibitor of growth 4 (ING4), as a multimodal tumor suppressor gene, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as a potent apoptosis-inducing gene, are experiencing a renaissance in cancer gene therapy. Herein we investigated the antitumor activity and safety of mono- and combined therapy with OAds armed with ING4 (Ad-ΔB/ING4) and TRAIL (Ad-ΔB/TRAIL) gene, respectively, on preclinical models of human HCC. OAd-mediated expression of ING4 or TRAIL transgene was confirmed. Ad-ΔB/TRAIL and/or Ad-ΔB/ING4 exhibited potent killing effect on human HCC cells (HuH7 and Hep3B) but not on normal liver cells. Most importantly, systemic therapy with Ad-ΔB/ING4 plus Ad-ΔB/TRAIL elicited more eradicative effect on an orthotopic mouse model of human HCC than their monotherapy, without causing obvious overlapping toxicity. Mechanistically, Ad-ΔB/ING4 and Ad-ΔB/TRAIL were remarkably cooperated to induce antitumor apoptosis and immune response, and to repress tumor angiogenesis. This is the first study showing that concomitant therapy with Ad-ΔB/ING4 and Ad-ΔB/TRAIL may provide a potential strategy for HCC therapy and merits further investigations to realize its possible clinical translation.

Recommendations for the Nomenclature of Cognitive Change Associated with Anaesthesia and Surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines (Diagnostic and Statistical Manual for Mental Disorders, fifth edition [DSM-5] and National Institute for Aging and the Alzheimer Association [NIA-AA]) are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions. Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Recommendations for the Nomenclature of Cognitive Change Associated With Anaesthesia and Surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Utility of the laryngeal handshake method for identifying the cricothyroid membrane.

BACKGROUND: The cricothyroid membrane is the most commonly accessed location for invasive surgical airway. Although the laryngeal handshake method is recommended for identifying the cricothyroid membrane, there is no clinical data regarding the utility of the laryngeal handshake method in cricothyroid membrane identification. The objective of this study was to compare the accuracy of cricothyroid membrane identification between the laryngeal handshake method and simple palpation. METHODS: After anaesthesia induction, the otorhinolaryngology resident and anaesthesia resident identified and marked the needle insertion point for cricothyroidotomy using simple palpation and the laryngeal handshake method, respectively. The cricothyroid membrane was confirmed with ultrasonography. Identification was determined successful if the marked point was placed within the longitudinal area of the cricothyroid membrane and within 5 mm from midline transversely. The accuracy of cricothyroid membrane identification using the laryngeal handshake method and simple palpation was compared. RESULTS: A total of 123 patients were enrolled. The cricothyroid membrane was correctly identified in 87 (70.7%, 95% confidence interval 61.8-78.6%) patients using the laryngeal handshake method compared to 78 (63.4%, 95% confidence interval 54.3-71.9%) patients using simple palpation (P = .188). The time required to identify the cricothyroid membrane was longer when using the laryngeal handshake method (15 [3-48] seconds vs 10.9 [3-55] seconds, P = .003). CONCLUSION: The success rate of identifying the cricothyroid membrane was similar among the anesthesiologists who performed the laryngeal handshake method and also among otorhinolaryngologists who used simple palpation.

Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Influence of head and neck position on ventilation using the air-Q® SP airway in anaesthetized paralysed patients: a prospective randomized crossover study.

Background: The influence of different head and neck positions on the effectiveness of ventilation with the air-Q® self-pressurizing airway remains unevaluated. This study aimed to evaluate the influence of different head and neck positions on ventilation with the air-Q® SP airway. Methods: In this prospective, randomized crossover study, we enrolled 51 female patients who were to undergo elective gynaecological or breast surgery under general anaesthesia. An air-Q® SP airway was placed in all patients, and mechanical ventilation was performed using a volume-controlled mode with a tidal volume of 10 ml kg−1 and a respiratory rate of 12 bpm. The expiratory tidal volume, peak inspiratory pressure, oropharyngeal leak pressure, and ventilation score were assessed first for the neutral head position and then for the extended, flexed, and rotated head positions in a random order. Results: All parameters were similar for the rotated head and neck position and the neutral position. Compared with the neutral position, the oropharyngeal leak pressure and peak inspiratory pressure decreased in the extended position but increased significantly in the flexed position (P<0.001). However, the expiratory tidal volume and ventilation score decreased significantly in only the extended position (P<0.001) but were similar in the flexed and neutral positions. Conclusions: Ventilation was not adversely affected in the rotated or flexed head and neck positions, whereas head and neck extension negatively influenced ventilation. Clinically, it is better to avoid head and neck extension during ventilation with an air-Q® SP airway. Clinical trial registration: NCT02402387.

Multiparametric approach with diffusion-weighted imaging and dynamic contrast-enhanced MRI: a comparison study for differentiating between benign and malignant bone lesions in adults.

AIM: To evaluate and compare the diagnostic performance of quantitative parameters derived from diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in differentiating benign and malignant bone tumours. MATERIALS AND METHODS: Fifty-five patients (age range, 21-82 years; mean age, 55 years) underwent pretreatment MRI. Apparent diffusion coefficient (ADC) values were calculated by DWI. The DCE-MRI data were analysed for the volume transfer constant (Ktrans), extravascular extracellular volume fraction (Ve), and volume rate constant (Kep), and Ktrans/ADC ratio. Each parameter's performance was evaluated using the area under the receiver operating characteristic (ROC) curv (AUC), and their AUCs were compared. ROC curves were analysed and each parameter's optimal cut-off value was determined, from which each parameter was evaluated for sensitivity, specificity, accuracy, and positive and negative predictive values. The odds ratio (OR) with 95% confidence interval for detecting malignant bone lesions after adjusting the age factor of each parameter was estimated. RESULTS: All parameter values (except Ve) were significantly different between benign and malignant bone tumours (p<0.05). The Ktrans had a significantly greater AUC than Ve (p=0.03). The Ktrans/ADC and Kep had the best sensitivity (0.917) and specificity (0.632), respectively. The Kep and Ktrans/ADC had the best positive (0.811) and negative (0.769) predictive values, respectively. The OR was highest for Ktrans/ADC (17.38; p=0.0013). CONCLUSION: The Ktrans, Kep, ADC, and Ktrans/ADC could help to detect malignant lesions from bone tumours and Ktrans/ADC appears to be the superior variable among them.

Effects of clarithromycin on the pharmacokinetics of evogliptin in healthy volunteers.

WHAT IS KNOWN AND OBJECTIVE: Evogliptin (DA-1229), a novel dipeptidyl peptidase (DPP)-4 inhibitor with high potency and selectivity, was approved in Korea for the treatment of type 2 diabetes. Preclinical studies suggest that it is metabolized by cytochrome (CYP) P450 isozymes. Based on these findings, a clinical study was designed to investigate the pharmacokinetic (PK) interaction of evogliptin with a CYP inhibitor, clarithromycin. METHODS: An open-label, two-phase, crossover study was conducted with 12 healthy subjects. On day 1, a single dose of evogliptin 5 mg was administered alone to assess the reference PK profile of evogliptin. On day 10, after a 2-day pretreatment with clarithromycin, evogliptin 5 mg was administered again to evaluate the effect of CYP inhibition on the PK profile of evogliptin. Administration of clarithromycin continued until day 14. Blood sampling in the reference and test phases was performed until 96 and 168 hours after dosing, respectively for PK assays. RESULTS: Eleven of the 12 subjects completed the study, and their data were analysed. In the presence of clarithromycin, exposure to evogliptin increased without any serious adverse events and the geometric mean peak plasma concentration (Cmax ) and area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-∞ ) of evogliptin increased by 116.5% and 89.6%, respectively. WHAT IS NEW AND CONCLUSION: Administration of clarithromycin significantly increased exposure to evogliptin in healthy subjects.

Application of anti-DFS70 antibody and specific autoantibody test algorithms to patients with the dense fine speckled pattern on HEp-2 cells.

OBJECTIVES: Whereas antinuclear antibodies (ANAs) detected by indirect immunofluorescence (IIF) have diagnostic significance, the dense fine speckled (DFS) pattern on HEp-2 cells may be an exclusionary marker for ANA-associated rheumatic disease (AARD). The aim of this study was to evaluate a new algorithm considering anti-DFS70 antibodies for routine ANA testing. METHOD: From ANA requested sequential 10 528 sera, 181 sera samples showing the DFS pattern were additionally tested for anti-DFS70 antibodies by an enzyme-linked immunosorbent assay (ELISA-DFS70) and for specific-ANAs. Specific-ANAs(+)/IIF-DFS(-) control sera samples (n = 50) were also tested. RESULTS: Of the 181 IIF-DFS-positive sera samples, 82.9% (n = 150) were from non-AARD patients and 112 (61.9%) patients had non-rheumatic diseases (NRD), including the most common clinical feature of dermatitis (18.2%). The ELISA-DFS70 was positive in 109 (60.2%) sera and was negative in all control sera. Specific-ANAs were similarly detected as 25.7% (28/109) and 22.2% (16/72) of ELISA-DFS70(+) and ELISA-DFS70(+) patients, respectively (p > 0.05). The prevalence of non-AARD was 95.1% and 25.1% in the ELISA-DFS70(+)/specific-ANAs(-) and ELISA-DFS70(-)/specific-ANAs (+) groups, respectively. CONCLUSIONS: In patients with a HEp-2 DFS pattern, the additional ELISA-DFS70 and specific-ANAs test could improve the efficiency of diagnosing AARD. The detection of anti-DFS70 antibodies should be included in test algorithms for ANA testing.

A combination of excimer laser treatment and topical tacrolimus is more effective in treating vitiligo than either therapy alone for the initial 6 months, but not thereafter.

BACKGROUND: There are insufficient data on the long-term outcome of a combination therapy that comprises phototherapy and topical administration of tacrolimus. AIM: To evaluate the clinical efficacy according to the duration of treatment and in vitro results of a combination therapy involving topical tacrolimus and an excimer laser in the treatment of vitiligo. METHODS: In total, 276 patients with nonsegmental vitiligo were treated with an excimer laser twice weekly, or with tacrolimus ointment twice daily, or both. The melanin contents and levels of melanogenic enzymes were measured in cultured human melanocytes treated with tacrolimus and/or excimer laser. RESULTS: After adjusting for potential confounders, the combination of tacrolimus plus excimer laser was significantly more effective than either tacrolimus or excimer laser alone (P < 0.001 and P < 0.01, respectively) for the first 6 months. However, this superiority was not observed after the initial 6 months of treatment. In vitro, the combination of tacrolimus plus excimer laser led to a higher level of melanogenesis than with either treatment alone. CONCLUSIONS: A combination treatment with topical tacrolimus and an excimer laser may be useful as an induction therapy for up to 6 months, but continuation of this therapy for > 6 months might not provide a better final outcome than monotherapy.

Vitamin D deficiency in Parkinson's disease patients with orthostatic hypotension.

OBJECTIVES: The purpose of our study was to investigate the associations between serum vitamin D3 levels and orthostatic hypotension (OH) in patients with Parkinson's disease (PD). MATERIALS AND METHODS: Fifty-five patients with PD were enrolled in this study. Blood pressure (BP) measurements were gathered while the patients were in the supine position and while standing up. Then, the patients were divided into two groups: PD patients with and without OH. We compared the levels of serum 25-hydroxyvitamin D3 and 1, 25-dihydroxyvitamin D3 (calcitriol) between the two groups. RESULTS: Serum 25-hydroxyvitamin D and calcitriol levels were significantly decreased in patients with OH compared with those without OH. The systolic and diastolic BPs and symptom severities significantly negatively correlated with the serum 25-hydroxyvitamin D and calcitriol levels. CONCLUSIONS: Although the underlying mechanism for this association is not fully understood, our results suggest that low vitamin D status is associated with OH in patients with PD.

Enhanced oxidative damage to DNA, lipids, and proteins and levels of some antioxidant enzymes, cytokines, and heat shock proteins in patients infected with influenza H1N1 virus.

Overweight and obesity is becoming widespread enough to generate an acceptable and misleading social status. By 2030, in the USA up to 86 % of adults will be overweight or obese. Some selected statistical data based on the body mass index (BMI) indicated that overweight was not associated with increased mortality, this provoked a conceivable interest. Added to this is the observation that while the prevalence of obesity is dramatically increasing, the cardiovascular mortality and life expectancy in the European Union and USA has improved. When more sensitive indicators of body adiposity and its distribution than the BMI, like the waist-thigh ratio in both sexes and the waist-hip ratio in women are projected on mortality, it becomes obvious that even overweight is associated with an increased health risk. Gaining excessive body fat is a continuous, frequently progressive process. Present obesity epidemic in childhood will manifest with deleterious consequences only in future years when adolescents reach adulthood. Prevention is thus essential even before the overweight sets in. Improved life expectancy observed in large populations despite obesity epidemic, is a favourable medical success in the management of hypertension, of serum lipid disorders and diabetes. While encouraging, when it is observed in large population, it does not take away the potential health risk of a metabolic disorder in an individual who is overweight (Fig. 7, Ref. 25).

Clinical significance of CD151 overexpression in subtypes of invasive breast cancer.

BACKGROUND: CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated. METHODS AND RESULTS: The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (P<0.001) and disease-free survival (P=0.02), and stage II and III patients with CD151 overexpression demonstrated substantially poorer OS (P=0.0474 and 0.0169). In the five subtypes analyses, CD151 overexpression retained its adverse impact on OS in the Luminal A (P=0.0105) and quintuple-negative breast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer. CONCLUSION: CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer.

Evaluation of individual risk in nonvariceal gastrointestinal bleeding patients with NSAID administration: a multicenter study in Japan.

BACKGROUNDS: Gastrointestinal (GI) toxicity is an undesirable effect of nonsteroidal anti-inflammatory drugs (NSAIDs). We conducted a multicenter study in Japan to clarify the GI risk grade in patients with NSAID-induced GI bleeding. METHODS: Patients with emergent endoscopic hemostasis by nonvariceal bleeding were registered from 36 hospitals in Hiroshima. In cases with NSAID use, the GI risk grade (low, moderate, or high) was evaluated, and concomitant drugs were investigated. We asked 79 gastroenterologists and 234 orthopedists what concomitant drugs they would prescribe to 3 simulated patients. RESULTS: A total of 1,350 patients were registered. NSAIDs were used in 278 cases (21%). Concerning the risk grade in each patient, the largest group was the moderate-risk group (203 patients; 73%), while the high-risk group comprised 10% of all NSAID users with bleeding. A proton pump inhibitor (PPI) or misoprostol was administrated to only 20 patients (7%). A small number of the gastroenterologists and orthopedists who responded to the questionnaire would prescribe PPI or misoprostol to simulated patients with short-term loxoprofen use. CONCLUSIONS: In NSAID users with GI bleeding, the moderate-risk group was the largest group for GI toxicity in Japan. In these cases, PPI or misoprostol was not commonly medicated in clinical practice.