Effective situation-based delirium simulation training using flipped classroom approach to improve interprofessional collaborative practice competency: a mixed-methods study.

BACKGROUND: Interprofessional collaborative practice competency (ICPC) is key to providing safe, high-quality, accessible, patient-centred care. Effective delirium management, particularly, requires a multi-component intervention, including the use of interprofessional teams at care point. This research aims to investigate the effectiveness of the flipped classroom approach for improving ICPC in simulation-based delirium case management. METHOD: An embedded mixed-methods study was designed to investigate the effects of the flipped classroom approach on health professionals' performance in delirium management. The study population comprised nine health professionals (three physicians, nurses, and pharmacists each). They used pre-class study materials about delirium management via a digital learning platform before a simulation case training session. A readiness assurance process test was conducted on key concepts, covered in the pre-class study material. Participants were randomly assigned to three teams, each of which included health professionals. Each team participated in a simulation case scenario. For the quantitative outcome measures, the Chiba Interprofessional Competency Scale (CICS29), a validated scale for measuring competencies of interprofessional practice, was used before, after, and three months after the educational intervention. The qualitative component consisted of a post-training questionnaire and semi-structured focused group interviews about the impact of the flipped classroom approach. RESULT: The CICS29 measured after the intervention and three months after was noted to be significantly higher than before the intervention. Three semi-structured focused group interviews were conducted (n=9), which, upon analysis revealed that the flipped classroom approach effected on four stages of Bloom's taxonomy level. A total of nine categories and 17 subcategories were identified corresponding to four levels of the revised Bloom's taxonomy: remember (1), understand (12), apply (23), and analyse (3). CONCLUSION: The simulation-based skill training using flipped classroom approach can be an effective method for improving ICPC for health professionals. In this approach, an elevated level of cognitive activity is practiced in the Bloom's taxonomy, and the participants worked on an application-based case simulation that promoted higher level learning and engagement in interprofessional collaborative practice. This approach also established a basic common language of delirium assessment and management, thus facilitating communication among health professionals and improving ICPC.

Development of an intraoperative breast cancer margin assessment method using quantitative fluorescence measurements.

Breast-conserving surgery has become the preferred treatment method for breast cancer. Surgical margin assessment is performed during surgery, as it can reduce local recurrence in the preserved breast. Development of reliable and lower-cost ex vivo cancer detection methods would offer several benefits for patient care. Here, a practical and quantitative evaluation method for the ex vivo fluorescent diagnosis of breast lesions was developed and confirmed through a three-step clinical study. Gamma-glutamyl-hydroxymethyl rhodamine green (gGlu-HMRG) has been reported to generate fluorescence in breast lesions. Using this probe, we constructed a reliable and reproducible procedure for the quantitative evaluation of fluorescence levels. We evaluated the reliability of the method by considering reproducibility, temperature sensitivity, and the effects of other clinicopathological factors. The results suggest that the fluorescence increase of gGlu-HMRG is a good indicator of the malignancy of breast lesions. However, the distributions overlapped. A 5 min reaction with this probe could be used to distinguish at least part of the normal breast tissue. This method did not affect the final pathological examination. In summary, our results indicate that the methods developed in this study may serve as a feasible intraoperative negative-margin assessment tool during breast-conserving surgery.

Reliability and validity of the Japanese version of the 4A's Test for delirium screening in the elderly patient.

Although many screening tools for delirium are available, delirium is still occasionally overlooked or misdiagnosed. One of the reasons for this is the lack of brief screening tools that do not require specialized training to use. The 4 'A's test (the 4AT) is a validated screening tool for delirium that can be administered in a very short time without specialized training. Herein, we evaluated the reliability and validity of the Japanese version of the 4AT (the 4AT-J). A total of 150 patients aged ≥ 65 years were enrolled. Their demographics and clinical characteristics were obtained within 24 hr of their hospitalization. On each patient's high-risk day of developing delirium, the 4AT-J was administered by a nurse, and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-Ⅴ) and the Japanese version of Delirium Rating Scale-Revised-98 (DRS-98-J) were administered by a psychiatrist. Our analyses revealed that when a cut-off score of 4, the 4AT-J showed high sensitivity and specificity. The Cronbach's α-coefficient was similar to that of the original version. A receiver operating curve analysis showed sufficient power of the 4AT-J to discriminate delirium. The 4AT-J showed adequate reliability and validity for delirium screening in elderly patients.

A Large Pure Uterine Lipoma: Its Diagnosis by Pelvic MRI and Histopathology.

The patient is a 74-year-old female previously diagnosed with an ovarian tumor at age 55. No changes were noted for one year; however, she was lost to follow-up. Eighteen years later, she presented to a local clinic complaining of diffuse abdominal and flank pain. Abdominal and pelvic ultrasound, CT, and gynecological examination showed a fatty pelvic tumor of approximately 12 cm in diameter. A left ovarian teratoma was suspected, and per the patient's request, she was transferred to Kobe Adventist Hospital for further evaluation and treatment. Pelvic MRI revealed no ovarian enlargement; however, a mass in the uterine body was appreciated with a high signal on T1 and T2 images and signal dropout in the fat suppression images, a finding most consistent with a uterine lipoma. A total hysterectomy and bilateral salpingo-oophorectomy was performed, and histopathological examination confirmed the preliminary diagnosis. No complications were observed during the postoperative period. A pure uterine lipoma is an extremely rare tumor with only a few cases reported worldwide. It is a benign tumor; however, it can sometimes be misdiagnosed as a malignant neoplasm. Pelvic MRI appears to be a useful tool in order to make the correct diagnosis preoperatively.

Rapid diagnosis of lymph node metastasis in breast cancer using a new fluorescent method with γ-glutamyl hydroxymethyl rhodamine green.

Sentinel lymph node biopsy is performed as a standard procedure in breast cancer surgery, and the development of quick and simple methods to detect metastatic lesions is in high demand. Here, we validated a new fluorescent method using γ-glutamyl hydroxymethyl rhodamine green to diagnose metastatic lymph nodes in breast cancer. One hundred and forty-nine lymph nodes from 38 breast cancer patients were evaluated in this study. Comparison of fluorescent and pathological images showed that this fluorescent method was successful for visualizing breast cancer cells in lymph nodes. This method had a sufficiently high sensitivity (97%), specificity (79%) and negative predictive value (99%) to render it useful for an intraoperative diagnosis of cancer. These preliminary findings suggest that this novel method is useful for distinguishing non-cancerous specimens from those in need of careful examination and could help save time and cost for surgeons and pathologists.

Rapid intraoperative visualization of breast lesions with γ-glutamyl hydroxymethyl rhodamine green.

We previously developed γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) as a tool to detect viable cancer cells, based on the fact that the enzyme γ-glutamyltranspeptidase (GGT) is overexpressed on membranes of various cancer cells, but is not expressed in normal tissue. Cleavage of the probe by GGT generates green fluorescence. Here, we examined the feasibility of clinical application of gGlu-HMRG during breast-conserving surgery. We found that fluorescence derived from cleavage of gGlu-HMRG allowed easy discrimination of breast tumors, even those smaller than 1 mm in size, from normal mammary gland tissues, with 92% sensitivity and 94% specificity, within only 5 min after application. We believe this rapid, low-cost method represents a breakthrough in intraoperative margin assessment during breast-conserving surgery.

Successful reduction of acute puerperal uterine inversion with the use of a bakri postpartum balloon.

Uterine inversion is a state wherein the endometrial surface is inverted. Although this condition may be observed in nonpregnant women, it most commonly develops at the time of delivery. In the present case, a 37-year-old woman without any remarkable history developed acute puerperal uterine inversion after the successful induction of labor. Following the delivery, she complained twice of severe lower abdominal pain; subsequently, hemorrhage was noted at the site of partial detachment of the placenta. These findings led to a diagnosis of placenta accreta, and the patient developed a state of shock. A Bakri postpartum balloon was inserted into the uterine cavity under ultrasonographic guidance and was filled with physiological saline for treatment of this condition. With this procedure, the uterine inversion was completely reduced and the hemorrhage was stopped. Moreover, no reinversion was observed in the postoperative period. These findings suggest that a Bakri postpartum balloon can be used to noninvasively reduce uterine inversion and prevent its recurrence.

Genetic influence of dopamine receptor, dopamine transporter, and nicotine metabolism on smoking cessation and nicotine dependence in a Japanese population.

BACKGROUND: This study investigated whether polymorphisms of the ankyrin repeat and kinase domain containing 1 gene (ANKK1), which is adjacent to the dopamine D2 receptor gene (DRD2), and the dopamine transporter (SLC6A3) and cytochrome P450 2A6 (CYP2A6) genes influence smoking cessation and nicotine dependence in a Japanese population. In 96 current and former smokers, genotyping frequencies for the ANKK1/DRD2 TaqIA, SLC6A3 VNTR, and CYP2A6 polymorphisms were subjected to chi-square analysis, and regression analyses were used to determine the association of the genotypes of current smokers with a Heavy Smoking Index, in addition to evaluating the effect of the subjects' smoking history on the association. RESULTS: Genotyping results suggested that nicotine dependence among current smokers homozygous for the SLC6A3 10r allele was lower than that of smokers carrying the minor alleles, and that the CYP2A6 polymorphism might mediate this association. Furthermore, the age at which current smokers began smoking might moderate the association between their genetic polymorphisms and nicotine dependence. CONCLUSIONS: This study provides preliminary findings on the influence of genetic variants on the smoking phenotypes in a Japanese population.

Successful management of a cesarean scar defect with dehiscence of the uterine incision by using wound lavage.

Cesarean scar defects (CSDs) that can be visualized using transvaginal ultrasonography (TVUS) may cause prolonged menstruation, irregular genital bleeding, and secondary infertility; surgical repair is sometimes necessary. We present a case of CSD, with dehiscence of the uterine incision, which was managed using wound lavage. A 38-year-old woman (gravida 4, para 4) had delivered her third and fourth children by cesarean section. Upon the resumption of menstruation, 9 months after her second cesarean section, she demonstrated prolonged menstruation and the presence of a menstrual fistula due to dehiscence of the cesarean section incision from the myometrium to the serosa. We treated the defect by lavaging with a physiological saline solution. After lavaging the wound 3 times, spontaneous healing of the dehiscent muscle layer was successfully achieved. The treatment was complication-free and the healing of the muscle layer has been maintained for more than 8 months.

Relationship of α-fetoprotein levels and development of hepatocellular carcinoma in hepatitis C patients with liver cirrhosis.

α-fetoprotein (AFP) is a tumor marker of hepatocellular carcinoma (HCC) and has also been reported to reflect the effectiveness of long-term low-dose interferon (IFN) therapy in hepatitis C virus (HCV)-infected patients with chronic liver disease. The correlation between AFP levels and the incidence of HCC has been discussed over a long period. We investigated whether high levels of AFP at the time of diagnosis were associated with an increased incidence of HCC in patients with HCV. A total of 107 HCV patients with liver cirrhosis without other risks were evaluated for the predictive value of non-invasive risk factors for HCC, including age, gender, alcohol intake, aspartate and alanine aminotransferase levels, bilirubin, albumin, platelet count and AFP levels at study entry, as well as the IFN therapy received. During the follow-up period, HCC developed in 68 (63.6%) patients. Kaplan-Meier estimates were made to assess the cumulative risk of HCC. The 10-year cumulative incidence rate of HCC was 80%. Cox regression analysis was performed on several variables, including age, gender, alcohol consumption, experience of IFN therapy and biochemical parameters. The following factors were identified as exhibiting an increased risk of HCC by univariate analysis: aspartate transaminase (AST) ≥71 IU/l, alanine transaminase (ALT) ≥60 IU/l, AFP ≥6 ng/ml and IFN therapy. Multivariate analysis identified that the AFP level [6-19 ng/ml: hazard ratio (HR), 2.22; P=0.006 and ≥20 ng/ml: HR, 2.09; P=0.003] was an independent and significant risk factor for the development of HCC. A slightly elevated (6-19 ng/ml) AFP level may be a risk factor for HCC in certain cases. By contrast, AFP levels <6 ng/ml indicate a low risk of HCC development in HCV patients with liver cirrhosis.

Ginkgo biloba extract attenuates warfarin-mediated anticoagulation through induction of hepatic cytochrome P450 enzymes by bilobalide in mice.

Ginkgo biloba extract (GBE) is a popular herbal ingredient used worldwide, but it is reported to induce bleeding as a serious adverse event. In this study we examined whether GBE induced spontaneous bleeding or accelerated warfarin anticoagulation via herb-drug interaction. Mice were given GBE or various active components of GBE orally for 5 days and blood coagulation parameters and hepatic cytochrome P450 enzymes (CYPs) were measured. Mice also received warfarin (racemate, (S)- or (R)-enantiomer) for the last 3 days of the 5-day regimen to examine GBE-warfarin interactions. Neither GBE (up to 1000 mg/kg) nor ginkgolide B (up to 140 mg/kg), a platelet-activating factor antagonist, influenced blood coagulation parameters. In contrast, GBE attenuated the anticoagulant action of warfarin. Bilobalide, a component of GBE that markedly induced hepatic CYPs including (S)-warfarin hydroxylase, showed similar effects. For (S)-warfarin, the anticoagulation action and the interaction with GBE was clear, while the influence on metabolism was greater for (R)-warfarin than for (S)-warfarin, which corresponded to the CYP types induced by GBE. These results suggest that GBE and ginkgolide B have no influence on blood coagulation in vivo, and that GBE attenuates the anticoagulation action of warfarin via induction of hepatic CYPs by bilobalide.

Effect of vanadate on ATP-induced increase in intracellular calcium ion levels in human umbilical vein endothelial cells.

We investigated the effect of ammonium vanadate (vanadate) on ATP-induced increases in intracellular calcium ion level ([Ca(2+)](i)) of human umbilical vein endothelial cells (HUVEC) by fluorescence confocal microscopic imaging using the Ca(2+)-sensitive probe Calcium Green 1/AM. The ATP analogue 2-methylthio-ATP (2meS-ATP), at 10 microM, significantly increased the [Ca(2+)](i) of HUVEC, and this was abolished by 1 microM thapsigargin (a calcium pump inhibitor), whereas extracellular free calcium had no effect. Vanadate at 10 microM also significantly increased the [Ca(2+)](i) of HUVEC, which was abolished by 1 microM thapsigargin. However, vanadate at 1 microM did not exert such a significant effect. We thus examined the influence of < or =1 microM vanadate for 24 h on 2meS-ATP-induced increase in [Ca(2+)](i). Vanadate significantly reduced the action of 2meS-ATP at 1 microM but not at 0.1 microM. Endogenously released ATP is known to induce various actions on endothelial cells. The present results suggest that vanadate exerts a regulatory influence on the function of vascular endothelial cells.

Long-term feeding of Ginkgo biloba extract impairs peripheral circulation and hepatic function in aged spontaneously hypertensive rats.

We previously demonstrated that Ginkgo biloba extract (GBE) produces an anti-hypertensive effect via enhanced vasodilation responses in young spontaneously hypertensive rats (SHR) and hepatic hypertrophy occurs with increased cytochrome P450 (CYP) mRNA expression in young rats. In the present study, to clarify whether these actions of GBE are observed in older rats, we investigated cardiovascular functions and hepatic CYP protein expressions in aged SHR fed a control diet or a diet containing 0.5% GBE for 4 weeks. In aged SHR, GBE feeding significantly increased liver weight per 100 g body weight without changing the body weight. Furthermore, significant increases in alanine aminotransferase level in serum and marked increase in CYP2B protein expression in the liver were observed in aged SHR fed GBE. On the other hand, GBE feeding did not affect blood pressure, but significantly reduced heart rate and blood flow velocity in tail arteries of aged SHR. Furthermore, GBE feeding did not affect contractile response to phenylephrine, relaxation responses to not only sodium nitroprusside but also acetylcholine, and protein levels of endothelium nitric oxide synthase and soluble guanylate cyclase in aortas of aged SHR. These results suggested that long-term GBE feeding impairs peripheral circulation due to bradycardia and hepatic function in aged SHR. Thus, in the elderly population with hypertension, the use of GBE may need to be assessed for effects on heart rate and liver function.

p53 antibodies in the serum of patients with prostate cancer.

UNLABELLED: We assessed the potential clinical utility of levels of p53-specific antibodies as a novel serum biomarker of prostate cancer that could be used in conjunction with level of PSA. MATERIAL AND METHODS: Serum levels of p53-specific antibodies in patients with relapsed, newly diagnosed prostate cancer and in patients with benign prostate hyperplasia were quantified by an enzyme-linked immunoabsorbent assay. RESULT: There was no significant difference (P=0.96) between the serum levels of p53-specific antibodies in patients with newly diagnosed prostate cancer and with benign prostatic hyperplasia. In the newly diagnosed prostate cancer group, stage T1c (n=8) showed the lowest p53-specific antibody level. However, the difference between T1c group and benign prostatic hyperplasia group was not significant (P=0.686). The relapsed cancer group tended to have low levels of the antibodies, and, there was no significant difference between the relapsed prostate cancer group and the benign prostatic hyperplasia group (P=0.14). The serum levels of p53-specific antibodies in patients with metastatic and with localized prostate cancer showed no significant difference (P=0.68). CONCLUSION: The use of titers of p53-specific antibodies to make differential diagnosis between prostate cancer and benign prostatic hyperplasia might have no role, and the antibodies should not be used as a marker of prostate cancer by itself. Because our study is based on small number of patients, further studies are necessary before its absolute validity can be determined.

Peroxynitrite is Involved in the dysfunction of vasorelaxation in SHR/NDmcr-cp rats, spontaneously hypertensive obese rats.

SHR/NDmcr-cp (SHR-cp) rats display typical symptoms and features of the metabolic syndrome. We previously reported that endothelium-dependent relaxation decreases in the thoracic aortas of SHR-cp rats, despite increased nitric oxide (NO) production from the endothelium. In the present study, to search for the reasons for this contradiction, we investigated whether vascular abnormality could be reduced by treatment of SHR-cp rats with antihypertensive drugs; a calcium channel blocker (amlodipine), an alpha 2 and imidazoline receptor agonist (moxonidine), and an angiotensin II type 1 (AT1) receptor antagonist (telmisartan). Telmisartan but not amlodipine and moxonidine ameliorated the impairment of relaxation in response to acetylcholine and the increased protein expression of endothelium NO synthase in thoracic aortas. All three drugs significantly lowered the blood pressure. Telmisartan decreased the serum levels of lipid peroxide and 8-hydroxy-2'-deoxyguanosine, oxidative stress markers, and also the aortic levels of the protein expression of gp91, a component of NADPH oxidase, and 3-nitrotyrosine, a biomarker of peroxynitrite. These findings suggest that NADPH oxidase-derived superoxide, probably produced due to stimulation of AT1 receptors, reacts with NO to form peroxynitrite, and consequently decreases active NO, leading to attenuation of endothelium-dependent relaxation. Angiotensin receptor antagonists may be effective for preventing endothelial dysfunction in metabolic syndrome.

ATP modulates the release of noradrenaline through two different prejunctional receptors on the adrenergic nerves of rat prostate.

1. The effects of adenosine and ATP receptor agonists on the release of endogenous noradrenaline from electrically stimulated (2 Hz, 0.1 msec) rat prostate were examined in order to clarify the pharmacological properties of prejunctional receptors for adenosine and ATP on the adrenergic nerve varicosities in the prostate. Noradrenaline was quantified by HPLC coupled with electrochemical detection techniques. 2. Both adenosine and ATP receptor agonists (1 micromol/L) inhibited noradrenaline release and the relative order of inhibitory effect was N(6)-cyclopentyl-adenosine (CPA) > 5'-N-ethylcarboxamidoadenosine > 2-chloroadenosine > adenosine > 2-methylthio-ATP (2mSATP) > AMP > ATP. 3. The adenosine receptor agonist CPA (1 nmol/L-1 micromol/L) and the ATP receptor agonist 2mSATP (100 nmol/L-100 micromol/L) inhibited the stimulation-induced release of noradrenaline in a concentration-dependent manner. The concentrations of CPA and 2mSATP that produced 50% inhibition of noradrenaline release were 9.6 nmol/L and 1.4 micromol/L, respectively. 4. 1,3-Dipropyl-8-cyclopentylxanthine, an adenosine A(1) receptor antagonist, significantly reduced the inhibitory effects of not only CPA, but also 2mSATP. 5. Suramin, an ATP receptor antagonist, significantly reduced the inhibitory effects of 2mSATP, but not those of CPA. 6. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, another ATP receptor antagonist, had no effect on the inhibitory action of either agonist. 7. These results suggest that, in the sympathetic nerve terminals of rat prostate, adenosine and ATP induce inhibition of noradrenaline release via the activation of adenosine A(1) and/or xanthine-sensitive ATP receptors, which play an inhibitory regulatory role in adrenergic neurotransmission in the prostate.

Impaired effect of salt loading on nitric oxide-mediated relaxation in aortas from stroke-prone spontaneously hypertensive rats.

1. The present study was designed to characterize the effects of salt on vasorelaxation via the nitric oxide (NO)/cGMP pathway in stroke-prone spontaneously hypertensive rats (SHRSP), which are highly salt sensitive. 2. Male 8-week-old SHRSP were given 1% NaCl solution as drinking water for 4 weeks, whereas control animals were given water only. 3. In aortic rings from salt-loaded SHRSP, relaxations in response to acetylcholine and sodium nitroprusside were significantly impaired compared with those in the control. In the presence of zaprinast, a cGMP-specific cyclic nucleotide phosphodiesterase (PDE)-5 inhibitor, the cGMP levels induced by these drugs were significantly reduced by salt loading, but remained unchanged in the absence of zaprinast. The protein levels of endothelial NO synthase, soluble guanylate cyclase (sGC) and cGMP-dependent protein kinase (PKG) remained unchanged with salt loading, but those of PDE-5 decreased significantly and those of phosphorylated PKG tended to decrease, although the change was not statistically significant. Salt loading significantly impaired the relaxation in response to 8-bromo-cGMP. 4. These results indicate that, in aortas from SHRSP, salt loading causes impairment of relaxation in response to NO, which may be due to a decrease in cGMP production by sGC and impairment of the relaxation pathway downstream of cGMP, which, in turn, probably causes a decrease in PKG activity. Reduced PDE-5 protein expression may act, in part, as a compensatory response to impairment of cGMP-mediated relaxation.

Absence of Bcl-2 expression favors response to the short-term administration of diethylstilbestrol diphosphate in prostate Cancer.

BACKGROUND: Neoadjuvant hormone therapy remains a controversial issue in spite of multiple studies having been performed. METHODS: We performed short-term (10 days) treatment with diethylstilbestrol (DES) in 30 patients with stages T2 or T3 prostate cancer (PCa). All the patients underwent needle core prostate biopsy before and radical prostatectomy within a month after the start of the endocrine therapy. The histological effects in PCa and the changes in morphological and clinical parameters and their association were elucidated. RESULTS: Serum PSA (P < 0.001), Ki-67 PI (P = 0.022), and AR (P = 0.002) expression decreased after the treatment. An obvious effect (Grade 1-3) of endocrine treatment was seen in 11 of 30 patients and was associated with a prominent PSA decrease (P = 0.0274) and with older age (P = 0.0026). Pre-treatment specimens from a group without any effects of endocrine therapy had a higher frequency of Bcl-2 positivity (57.9%) compared to the group of Grade 1-3 effects (27.3%). Prostatectomy specimens presented with significantly higher AI in Bcl-2 negative cases (P = 0.0029) and pre treatment Bcl-2 was associated with a higher AI in Grade 1-3 patients (P = 0.0393). CONCLUSIONS: Older age is a predictor of histological effects in short-term hormone treatment of PCa. A lower Bcl-2 in biopsy specimens presented more frequently in the patients who experienced a prominent effect of endocrine therapy, and it was also useful to predict a significantly higher AI in Grade 1-3 patients. Histological effects are also associated with the PSA decrease, reflecting the clinically meaningful shrinkage of tumors and a decrease of tumor burden.