Blood pressure reduction cut-points for orthostatic hypotension in stroke survivors using a sit-up test: a multicentre cross-sectional study.

OBJECTIVE: The sit-up test is used to assess orthostatic hypotension in stroke survivors who cannot stand independently without using a tilt table. However, no study has identified the optimal cut-points for orthostatic hypotension using the test. Therefore, this study aimed to examine the decrease in SBP and DBP during the sit-up test to detect orthostatic hypotension in individuals with stroke. METHODS: Thirty-eight individuals with stroke, recruited from three convalescent rehabilitation hospitals, underwent the sit-up and head-up tilt tests. Systolic and diastolic orthostatic hypotension was defined as a decrease of at least 20 and 10 mmHg in the SBP and DBP, respectively, during the head-up tilt test. The receiver operator characteristic curve with the Youden Index was used to identify the optimal cut-points. RESULTS: Eight and three participants showed systolic and diastolic orthostatic hypotension, respectively. The optimal cut-points for orthostatic hypotension using the sit-up test were a decrease of 10 mmHg in SBP [sensitivity = 87.5% (95% confidence interval: 47.4-99.7), specificity = 96.7% (82.8-99.9)] and 5 mmHg in DBP [sensitivity = 100.0% (29.2-100.0), specificity = 88.6% (73.3-96.8)]. CONCLUSION: Compared with the conventional cut-points, smaller cut-points of a decrease in SBP and DBP may be better to identify orthostatic hypotension in individuals with stroke using the sit-up test. The findings of this study may provide valuable information for the clinical application of the sit-up test.

Comparison of the sit-up test and head-up tilt test for assessing blood pressure and hemodynamic responses in healthy young individuals.

OBJECTIVE: The sit-up test is used to assess orthostatic hypotension, without the use of a tilt table, in populations who are unable to stand. The primary objective of this study was to determine the differences in blood pressure and hemodynamic responses between the sit-up and head-up tilt tests. The secondary objective was to determine the hemodynamic responses related to changes in blood pressure during each test. METHODS: Nineteen healthy volunteers (nine males, aged 24.3 ± 2.4 years) underwent the sit-up and head-up tilt tests. Systolic and diastolic blood pressure, heart rate, stroke volume, cardiac output, and total peripheral resistance were measured. RESULTS: The increase in systolic blood pressure (15 ± 9 vs. 8 ± 8 mmHg) was greater, while the increase in heart rate (8 ± 5 vs. 12 ± 8 bpm) and reduction in stroke volume (-17 ± 10 vs. -21 ± 10 ml) were smaller during the sit-up test than during the head-up tilt test (P < 0.05). Additionally, the increases in blood pressure variables were significantly associated with the increase in total peripheral resistance (P < 0.05), but not with changes in other hemodynamic variables in both tests. CONCLUSION: Although the magnitudes of changes in systolic blood pressure, heart rate, and stroke volume differed between the tests, the hemodynamic variable related to changes in blood pressure was the same for both tests. These results may contribute to the clinical application of the sit-up test for identifying the presence and hemodynamic mechanisms of orthostatic hypotension.

A Single Bout of Constant-Load Exercise Test for Estimating the Time Constant of Oxygen Uptake Kinetics in Individuals With Stroke.

OBJECTIVE: To examine the relationship between the time constant of oxygen uptake kinetics during the onset of exercise (τVO2) estimated from a single exercise bout and that obtained from three averaged exercise bouts in individuals with stroke. METHODS: Twenty participants with stroke performed three bouts of a constant-load pedaling exercise at approximately 80% of the workload corresponding to the ventilatory threshold to estimate τVO2. The VO2 data from the first trial of three bouts were used to estimate τVO2 for a single bout. Additionally, data collected from three bouts were ensemble-averaged to obtain τVO2 for three averaged bouts as the criterion. RESULTS: There was a very high correlation between τVO2 for a single bout (34.8±14.0 seconds) and τVO2 for three averaged bouts (38.5±13.4 seconds) (r=0.926, p<0.001). However, τVO2 for a single bout was smaller than that for three averaged bouts (p=0.006). CONCLUSION: τVO2 for a single bout could reflect the relative difference in τVO2 for three averaged bouts among individuals with stroke. However, it should be noted that τVO2 for a single bout may be underestimated compared to τVO2 for three averaged bouts.

Cardiorespiratory responses to exercise related to post-stroke fatigue severity.

Physical deconditioning after stroke may induce post-stroke fatigue. However, research on this association is limited. Our primary objective was to investigate the associations of post-stroke fatigue severity with oxygen uptake ([Formula: see text]O2) at peak exercise and the time constant of [Formula: see text]O2 kinetics (τ[Formula: see text]O2) at exercise onset. The secondary objective was to examine the associations between fatigue and cardiorespiratory variables potentially affecting [Formula: see text]O2 during exercise. Twenty-three inpatients from a subacute rehabilitation ward were enrolled in this study. The median (interquartile range) Fatigue Severity Scale (FSS) score, as a measure of fatigue, was 32 (range 27-42) points. The FSS score was not associated with [Formula: see text]O2 at peak exercise during a symptom-limited graded exercise test (rho = - 0.264; p = 0.224), whereas it was significantly associated with τ[Formula: see text]O2 during a submaximal constant-load exercise test (rho = 0.530; p = 0.009). A higher FSS score also significantly correlated with a longer time constant of cardiac output (CO) kinetics (rho = 0.476; p = 0.022). Our findings suggest that severe post-stroke fatigue is associated with delayed increases in [Formula: see text]O2 and CO at the onset of exercise. Our findings can contribute to the development of an appropriate rehabilitation programme for individuals with post-stroke fatigue.

Cardiorespiratory mechanisms underlying the impaired oxygen uptake kinetics at exercise onset after stroke.

BACKGROUND: Oxygen uptake (V˙O2) kinetics at the onset of exercise is slower in patients with stroke than in healthy adults. However, little is known about the cardiorespiratory mechanisms underlying the impaired V˙O2 kinetics. OBJECTIVES: This study aimed to investigate the relative effect of impaired oxygen delivery and utilisation on V˙O2 kinetics at the onset of submaximal exercise in patients with stroke by comparing the time constants of cardiac output (τCO) and V˙O2 (τV˙O2). In addition, we aimed to examine the association between the kinetics of cardiorespiratory variables and functional outcomes. METHODS: We included 21 patients with stroke (15 males, mean [SD] age 58.7 [9.5] years, mean days post-stroke 67.9 [30.9]). A submaximal constant-load exercise test was performed to measure τV˙O2, τCO, and the time constant of arterialvenous oxygen difference (τAVO2diff). The ratio of τCO to τV˙O2 was calculated to assess the matching of oxygen delivery and consumption. Fugl-Meyer lower-extremity motor scores, comfortable gait speeds, and Functional Independence Measure motor scores were used as functional variables. RESULTS: Mean (SD) τAVO2diff was markedly shorter than τV˙O2 and τCO (26.1 [7.1] vs. 38.7 [10.2] and 46.6 [23.2 s], P<0.05), with no significant difference between τV˙O2 and τCO (P=0.444). The greater ratio of τCO to τV˙O2 was related to poorer motor function (rho=-0.484, P=0.026) and slower comfortable gait speed (r=-0.482, P=0.027). CONCLUSIONS: An increase in CO was slower than that in AVO2diff in patients with stroke. Therefore, V˙O2 kinetics in patients with stroke appears to be affected by a delayed increase in CO rather than AVO2diff. Furthermore, these patients with motor and gait impairments may have a poor matching of oxygen delivery and consumption during exercise onset.

Cardiorespiratory factors related to the increase in oxygen consumption during exercise in individuals with stroke.

BACKGROUND: Understanding the cardiorespiratory factors related to the increase in oxygen consumption ([Formula: see text]) during exercise is essential for improving cardiorespiratory fitness in individuals with stroke. However, cardiorespiratory factors related to the increase in [Formula: see text] during exercise in these individuals have not been examined using multivariate analysis. This study aimed to identify cardiorespiratory factors related to the increase in [Formula: see text] during a graded exercise in terms of respiratory function, cardiac function, and the ability of skeletal muscles to extract oxygen. METHODS: Eighteen individuals with stroke (aged 60.1 ± 9.4 years, 67.1 ± 30.8 days poststroke) underwent a graded exercise test for the assessment of cardiorespiratory response to exercise. The increases in [Formula: see text] from rest to first threshold and that from rest to peak exercise were measured as a dependent variable. The increases in respiratory rate, tidal volume, minute ventilation, heart rate, stroke volume, cardiac output, and arterial-venous oxygen difference from rest to first threshold and those from rest to peak exercise were measured as the independent variables. RESULTS: From rest to first threshold, the increases in arterial-venous oxygen difference (ß = 0.711) and cardiac output (ß = 0.572) were significant independent variables for the increase in [Formula: see text] (adjusted R2 = 0.877 p < 0.001). Similarly, from rest to peak exercise, the increases in arterial-venous oxygen difference (ß = 0.665) and cardiac output (ß = 0.636) were significant factors related to the increase in [Formula: see text] (adjusted R2 = 0.923, p < 0.001). CONCLUSION: Our results suggest that the ability of skeletal muscle to extract oxygen is a major cardiorespiratory factor related to the increase in [Formula: see text] during exercise testing in individuals with stroke. For improved cardiorespiratory fitness in individuals with stroke, the amount of functional muscle mass during exercise may need to be increased.

Development and evaluation of a formula for predicting introduction of medication self-management in stroke patients in the Kaifukuki rehabilitation ward.

BACKGROUND: Medication self-management in stroke patients is important to prevent further progression of disease and incidence of side effects. The purpose of this study was to create a formula for predicting medication self-management introduction in stroke patients using functional independence measure items and patient data, including medication-related information. METHODS: This was a retrospective analysis of 104 patients (cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage) discharged from the Kaifukuki rehabilitation ward at Showa University Fujigaoka Rehabilitation Hospital from January to December 2012. Multivariate analysis was performed to develop a formula for predicting achievement of medication self-management. RESULTS: Of the 104 patients, 39 (37.5%) achieved medication self-management. In the logistic regression analysis, number of drugs, age, walk/wheelchair mobility FIM, and memory FIM were extracted as significant factors independently contributing to achievement of medication self-management (p < 0.05). The prediction formula was [4.404 - 0.229 × number of drugs at admission + 0.470 × walk/wheelchair mobility FIM at admission + 0.416 × memory FIM at admission - 0.112 × age]. CONCLUSIONS: In the future, this formula may be used as an index to predict success of medication self-management in stroke patients.

Real-world cost analysis of chemotherapy for colorectal cancer in Japan: detailed costs of various regimens during the entire course of chemotherapy.

BACKGROUND: Various chemotherapy regimens for advanced colorectal cancer have been introduced to clinical practice in Japan over the past decade. The cost profiles of these regimens, however, remain unclear in Japan. To explore the detailed costs of different regimens used to treat advanced colorectal cancer during the entire course of chemotherapy in patients treated in a practical setting, we conducted a so-called "real-world" cost analysis. METHOD: A detailed cost analysis was performed retrospectively. Patients with advanced colorectal cancer who had received chemotherapy in a practical healthcare setting from July 2004 through October 2010 were extracted from the ordering system database of Showa University Hospital. Direct medical costs of chemotherapy regimens were calculated from the hospital billing data of the patients. The analysis was conducted from a payer's perspective. RESULTS: A total of 30 patients with advanced colorectal cancer were identified. Twenty patients received up to second-line treatment, and 8 received up to third-line treatment. The regimens identified from among all courses of treatment in all patients were 13 oxaliplatin-based regimens, 31 irinotecan-based regimens, and 11 regimens including molecular targeted agents. The average (95% confidence interval [95% CI]) monthly cost during the overall period from the beginning of treatment to the end of treatment was 308,363 (258,792 to 357,933) Japanese yen (JPY). According to the type of regimen, the average monthly cost was 418,463 (357,413 to 479,513) JPY for oxaliplatin-based regimens, 215,499 (188,359 to 242,639) JPY for irinotecan-based regimens, and 705,460 (586,733 to 824,187) JPY for regimens including molecular targeted agents. Anticancer drug costs and hospital fees accounted for 50 to 77% and 11 to 25% of the overall costs of chemotherapy, respectively. CONCLUSION: The costs of irinotecan-based regimens were lower than those of oxaliplatin-based regimens and regimens including molecular targeted agents in Japan. Using a lower cost regimen for first-line treatment can potentially reduce the overall cost of chemotherapy. The main cost drivers were the anticancer drug costs and hospitalization costs.

[Expected Duties of Pharmacists and Potential Needs of Physicians and Nurses on a Kaifukuki Rehabilitation Ward].

This study investigated the required duties of pharmacists in a kaifukuki rehabilitation ward from the viewpoint of the ward physicians and nurses. A questionnaire survey was distributed to 27 facilities with kaifukuki rehabilitation wards. The questionnaire examined which duties the physicians and nurses expected from pharmacists while on the ward (4 areas, 10 items), as well as the time required for pharmacists to carry out those duties. Multivariate analysis was used to investigate which types of work took the most time for pharmacists on kaifukuki rehabilitation wards. Responses were received from 43 physicians and 184 nurses who worked on the kaifukuki rehabilitation wards of 19 facilities. The results revealed that the essential duties performed by pharmacists were the management of medical supplies, instruction on the use of self-medicating drugs at the time of introduction, and monitoring drug side effects. Furthermore, some duties, such as the distribution of medicines and changing or suggesting new drugs, required pharmacists to spend extended time on the ward. The responses indicated that physicians and nurses recognized the necessity for pharmacists to perform ward duties along with their routine work. This study shows that physicians and nurses working in kaifukuki rehabilitation wards demand proactive participation from pharmacists in appropriate medical therapy, such as instruction in the administration of medications and assessment at the time of prescription changes.

Mizoribine requires individual dosing due to variation of bioavailability.

BACKGROUND: Mizoribine (MZR) is an immunosuppressant used for the treatment of glomerular diseases, but there are few reports on the pharmacokinetics of MZR in children. METHODS: First, we performed a pharmacokinetic study on nine childhood-onset glomerular disease patients. The MZR dosages ranged from 1.8 to 14.5 mg/kg/dose. Pharmacokinetic parameters were analyzed using 38 MZR concentration-time curves. Second, nine patients who were newly treated with MZR were enrolled to validate the findings obtained from prior investigation. RESULTS: In the prior study, peak serum MZR concentration (C(max) ) was dose-dependent in each patient. Although proportionality between dosage and C(max) was observed in each patient, the regression coefficient was in a wide range from 0.075 to 1.04 and was specific to each patient. This variability was likely caused by individual variation of bioavailability. When the optimal time-point to monitor C(max) was investigated, the time-to-reach peak serum MZR concentration (T(max)) was similar among all the patients, which was from 2.5 to 3.5 h after administration of MZR. T(max) was most frequently observed at 3 h and the serum MZR concentration ratio relative to C(max) at 3 h was also highest (0.93 ± 0.07). In the following study, it was validated that monitoring C(3) is reproducible and reliable after adjusting the dosage of MZR to obtain target serum concentration. CONCLUSION: Individual dosing is required to optimize C(max) in childhood-onset glomerular disease patients. The safe dosage of MZR for each patient could be predicted by evaluating the serum MZR concentration 3 h after administration.

[Examination of factors affecting adverse reactions and dosage reduction in UGT1A1 genotyped patients: a retrospective survey of irinotecan].

Our aim was to clarify the side effects of irinotecan which occurred in patients admitted to Showa University Hospital to investigate whether the UGT1A1 genetic polymorphism status was reflected in the discontinuation or dose reduction of irinotecan. We retrospectively investigated UGT1A1 genetic polymorphisms, irinotecan dosage, dose discontinuance or reduction, and laboratory results from May 1 2009 to April 30 2010. The analysis of UGT1A1 genetic polymorphisms in 23 patients showed that frequencies of the UGT1A1*6 and UGT1A1*28 polymorphisms were 35% (eight patients) and 22% (five patients), respectively, and 17% (three patients) were UGT1A1*6/UGT1A1*28 compound heterozygotes. Of all patients who received irinotecan, dose reduction occurred in six patients (38%) and discontinuance in two patients (13%) due to neutropenia and other factors. Of these eight patients, seven (88%) had the UGT1A1*6 and/or *28 polymorphism. The most common irinotecan dose reduction was about 25% of the initial dose. Grade 4 neutropenia was observed in two patients who had the UGT1A1*6 and/or *28 mutation (13%), and one patient was a compound heterozygote. Our investigation confirmed that the UGT1A1 genetic polymorphism status of the patients was reflected in the discontinuance or dose reduction of irinotecan. Our results suggest that Grade 4 neutropenia may occur in patients who are compound heterozygotes and that these patients may need careful selection of treatment regimens possibly involving discontinuance or reduction in irinotecan dosage.

[Effect of the active adult learning/patient oriented clerkship on affective reaction of students ∼ from the results of student survey].

We have previously reported the efficacy of the Patient Oriented Clerkship (POC) in the clinical clerkship in Showa University Hospitals, by a trial with old four-year pharmacy program students. In the unique clerkship, each student has a patient in charge, and follows his/her clinical conditions throughout the rotation. The aim of the POC is that having the students learn spontaneously (Active Learning) and actively (Adult Learning) promoted by student's commitment and responsibility by communicating with patients and health professionals in a team. As the POC requires students both Active Learning and Adult Learning, we define the POC as Active Adult Learning (AAL). Having a patient in charge for each student gives them many opportunities to participate in the medical team and foster their problem solving skills. Our previous study eventually showed positive results of the POC in the one-month short clerkship in the four-year program. On the other hand, the effect of the unique hospital clerkship in the new six-year program is not known. We conducted a student survey to clarify the learning effect in the new six-year education system which was revised and 2.5 month clinical clerkship was scheduled according to the model core clerkship curriculum. This report is the first report to show a challenge of the AAL/POC clerkship in the new six-year pharmacy education program.

Development of a novel fluorometric assay for nitric oxide utilizing sesamol and its application to analysis of nitric oxide-releasing drugs.

Nitric oxide (NO) is related to various physiological effects as well as to numerous diseases caused by accentuation of NO production. Measurement of NO in cells and tissues is difficult as NO readily reacts with other molecules; furthermore, its half-life as a radical is fleeting. Currently, many NO pharmaceuticals are marketed as therapeutic agents for ischemic disease. Consequently, the identification of NO radicals and determination of generation rate from pharmaceuticals is very important when the effect of the medicinal supply is estimated. In this study, we developed a fluorometric assay for NO employing sesamol (3,4-methylenedioxyphenol) as a fluorometric substrate. Sesamol is converted to a fluorescent derivative (ex. 365 nm, em. 447 nm), which is dimmer in the presence of NO. The detection limit of NO with this method is 400 fmol; moreover, NO generated from drugs can be measured.

[Utility-based evaluation of the quality of life of patient's with gastric cancer who receive chemotherapy--comparison of patients' quality of life between oral TS-1 and conventional injectable combination therapy].

We tried to clarify the applicability of "utility" for the evaluation of patient's QOL with gastric cancer after chemotherapy and attempted to compare differences in QOL after treatment with the oral antitumor agent TS-1 or with a conventional injectable combination. Three items, moving activity, pain, and gastrointestinal symptoms, were employed as indicators of patient QOL, and then the assessment of utility was compared based on the expected outcomes that 9 pharmacists working on a ward, 9 nurses working on a neurosurgery ward, and 9 nurses working on a gastrointestinal surgery ward estimated directly using the three methods of standard gamble, time trade-off, and rating scale according to predictive scenarios based on each scenario. The QOL of patients who received the two different types of chemotherapy were also compared as the average utilities from the direct estimation depending on patient conditions as used for chart review. Furthermore, the average utilities were compared with the utility of the mapping method, which can be estimated by applying a utility-converting table defined in the EQ-5D survey. The average utility from each practitioner using the direct estimation revealed that the assessed utility from nurses working on a neurosurgery ward was higher than those of the pharmacists. The average utility obtained using the standard gamble method was higher than those using the rating scale and time trade-off methods. The average utility in the TS-1 therapy group was 0.84-0.94, and that in the conventional injectable therapy group was 0.52-0.79 (p<0.05). The result suggests that utility is applicable for estimation of gastric cancer patient QOL after chemotherapy, and that TS-1 therapy is superior to the traditional injectable combination therapy.

[Clinical pathway based on evidence-based medicine (EBM) for chemotherapy for lung cancer].

Recently, combination treatment with cisplatin has been recommended as chemotherapy for lung cancer. However, no clinical pathway for safe and efficient use of anticancer agents has been established. We devised a clinical pathway satisfying evidence-based medicine (EBM) criteria by analyzing case records and the relevant literature. We analyzed 73 case records of hospitalized patients who had undergone chemotherapy for lung cancer on the internal medicine ward of the Showa University Hospital. Grade 3 or higher toxicities of leukopenia, thrombocytopenia, anemia, vomiting, and diarrhea occurred in 30%, 51%, 14%, 5%, 8%, and 1% of patients, respectively. Therefore the checklists for these toxicities were included in the clinical pathway. The National Cancer Institute Common Toxicity Criteria were used for the evaluation of toxicities. According to the guidelines of the American Society of Clinical Oncology and the US Infection Society, the indicated agents and criteria for their use were chosen for supportive cancer treatment. Pharmacists, physicians, and nurses collaborated in making the clinical pathway safe and sufficiently easy for practical use. The final version of the clinical pathway is compatible with EBM and includes items required for safe chemotherapy, which could be helpful in risk management.

Concentrations of atmospheric sulfur compounds in an extremely snowy region, the Hokuriku District, Japan.

The diurnal and seasonal characteristics in gaseous sulfur dioxide and sulfate in aerosol particles, as well as the concentrations of sulfate in rain and snow, were measured in the Hokuriku District, Japan in order to investigate the spatial spread pattern of sulfur compounds and identify the origin of sulfur. The concentration of sulfur dioxide showed a distinct diurnal pattern, while the concentrations of nss-SO4(2-) in precipitation and aerosol particles did not. These results implied that the sulfur dioxide might originate in local emissions and did not affect the concentration of nss-SO4(2-) in precipitation, while nss-SO4(2-) in aerosol particles seemed to be widespread and might result from long-range transportation. The deposition of nss-SO42- in precipitation increased in winter, while the concentration of nss-SO4(2-) in aerosol particles decreased. This could be attributed to the lower cloud base often observed in this district in winter associated with a higher washout ratio.

[Pharmacoeconomic study of chemotherapy for gastric cancer: analysis of medical costs for oral fluoropyrimidine TS-1 and conventional i.v therapy].

To evaluate the economic impact of TS-1, an oral fluoropyrimidine, on the treatment of gastric cancer, the medical costs required for TS-1 treatment were compared with those for the conventional chemotherapy employed before the launch of TS-1 in patients with advanced and recurrent gastric cancer. The medical costs for 13 patients receiving TS-1 and 10 patients undergoing the conventional chemotherapy were extracted from the ordering system data, and the costs were compared using the fee schedule of the Japanese national health insurance. The monthly medical costs for the TS-1 group and conventional chemotherapy group were 327, 640 +/- 47,647 (mean +/- SE) yen and 852,874 +/- 62,412 yen, respectively. Medical costs appeared to have decreased because TS-1 is an oral preparation, permitting an easy transfer from inpatient treatment to ambulatory treatment, and because only small amounts of medication and blood transfusion were used for supportive care. Consequently, the medical costs for the TS-1 group were significantly lower than for the conventional chemotherapy group. Therefore, the administration of TS-1 leads to a reduction in medical costs.