The impact of earlier intervention by an antimicrobial stewardship team for specific antimicrobials in a single weekly intervention.

OBJECTIVE: The objective of this study was to evaluate the effects of earlier intervention by an antimicrobial stewardship team (AST) on antimicrobial use, antimicrobial resistance rates, and the clinical outcomes, without changing the weekly intervention schedule. METHODS: A retrospective study was conducted at Fukuoka University Hospital between April 2013 and March 2016. The effects were compared among three study periods (SP): SP1 (patients receiving anti-methicillin-resistant Staphylococcus aureus agents and carbapenems for ≥14 days), SP2 (patients receiving specific antimicrobials for ≥14 days), and SP3 (patients receiving specific antimicrobials regardless of the duration of treatment). RESULTS: The timing of AST intervention was shortened from an average of 15.5days after administration in SP1 to 4.2 days in SP3. The antimicrobial use density (AUD) of carbapenems and piperacillin-tazobactam decreased significantly (SP2 vs. SP3, p<0.05), and the costs of specific antimicrobials decreased (SP1, US$ 1080000; SP2, US$ 944000; SP3, US$ 763000). The rates of carbapenem resistance among Pseudomonas aeruginosa isolates showed a significant reduction from 16.2% in SP2 to 8.7% in SP3 (p<0.05). The mortality rate and length of stay did not change during the study period. CONCLUSIONS: Earlier intervention by an AST could contribute to the proper use of antimicrobials without adversely affecting patient outcomes.

Quality of life, depression, and psychosocial characteristics of patients awaiting liver transplants.

BACKGROUND: The identification of the psychological issues that impair the quality of life and the adherence to treatment in transplant candidates are important. OBJECTIVE: This study evaluated the presence of symptoms of depression and the quality of life of liver transplant candidates. METHODS: One hundred liver transplant candidates underwent a psychological analysis using the following instruments: the short form-36 (SF-36) quality of life questionnaire, the Beck depression inventory (BDI), and Structured Interviews for liver transplant candidates. RESULTS: Seventy-three (73%) of the patients were males. Interestingly, 63% of the patients were in a domestic partnership. At the time of the evaluation, 55 patients were not working due to illness, 27 patients were actively working, and 11 patients were retired. Importantly, fears related to the transplant (e.g., fear the surgery and of death) were identified in 38% of the patients. The data from this study demonstrated a significant negative correlation between depressive scores (BDI) and seven of the eight areas of quality of life (SF-36), such as functional capacity (r = .317, P = .0013), social aspects (r = -.469, P < .0001), economic aspects (r = -.319, P = .0012), and mental health (r = -.3832, P < .0001). CONCLUSION: The data indicated that the psychological aspects related to transplants require psychological intervention because they can affect the recuperation process, the quality of life, and the adherence to treatment for potential transplant patients.

Evaluating measles surveillance: comparison of sentinel surveillance, mandatory notification, and data from health insurance claims.

Inadequate notification is a recognized problem of measles surveillance systems in many countries, and it should be monitored using multiple data sources. We compared data from three different surveillance sources in 2007: (1) the sentinel surveillance system mandated by the Act on Prevention of Infectious Diseases and Medical Care for Patients Suffering Infectious Diseases, (2) the mandatory notification system run by the Aichi prefectural government, and (3) health insurance claims (HICs) submitted to corporate health insurance societies. For each dataset, we examined the number of measles cases by month, within multiple age groups, and in two categories of diagnostic test groups. We found that the sentinel surveillance system underestimated the number of adult measles cases. We also found that HIC data, rather than mandatory notification data, were more likely to come from individuals who had undergone laboratory tests to confirm their measles diagnosis. Thus, HIC data may provide a supplementary and readily available measles surveillance data source.

Patients on the waiting list for liver transplantation: caregiver burden and stress.

Over the last few decades, informal caregivers of patients with chronic diseases have received more attention, and there is a growing volume of studies demonstrating high rates of burden, stress, and mental disorders in this group of individuals. The objective of this study was to evaluate the burden, stress, and psychosocial characteristics of informal caregivers of liver transplantation candidates. Participants were assessed by individual evaluations with the following instruments: a semistructured interview, the Caregiver Burden Scale, the Inventário de Sintomas de Stress para Adultos de Lipp, and the Beck Depression Inventory. The Mann-Whitney test was used for statistical analysis with a significance level of 0.05. The characteristics of the study group (n = 61) were similar to those of groups in other studies with respect to gender (82% were women), kinship (64% were spouses), and age (the mean age was 47.6 years). The main stressors identified by the participants were as follows: doubts about ways to react in a crisis or in emergency situations (42.6%), mood swings of the patient (29.5%), and care involving food and medications (27.9%). Approximately 25% of the caregivers reported that they felt unprepared to adequately perform their roles. Data analysis indicated a greater burden overall on caregivers when the patient's Model for End-Stage Liver Disease score was greater than or equal to 15 points (P = 0.041). Furthermore, caregivers of patients with alcoholic liver disease showed higher depression (P = 0.034) and overall burden scores (P = 0.031) versus caregivers of patients with liver disease due to other etiologies. In conclusion, the participants showed significantly high levels of burden, stress, and depression. Support measures and caregiver preparation should be implemented by health care providers.

Assessment of lower-back muscle fatigue using electromyography, mechanomyography, and near-infrared spectroscopy.

We have investigated the etiology of lower-back muscle fatigue using simultaneous recordings of electromyography (EMG), mechanomyography (MMG), and near-infrared spectroscopy (NIRS) in an attempt to shed some light on the electrophysiological, mechanical, and metabolic characteristics, respectively. Eight male subjects performed isometric back extensions at an angle of 15 degrees with reference to the horizontal plane, for a period of 60 s. Surface EMG, MMG and NIRS signals were recorded simultaneously from the center of the erector spinae at the level of L3. NIRS was measured to determine the level of muscle blood volume (BV) and oxygenation (Oxy-Hb). The root mean square amplitude value (RMS) of the EMG signal was significantly increased at the initial phase of contraction and then fell significantly, while mean power frequency (MPF) of the EMG signal decreased significantly and progressively as a function of time. There were also significant initial increases in RMS-MMG that were followed by progressive decreases at the end of fatiguing contractions. MPF-MMG remained unchanged. Muscle BV and Oxy-Hb decreased dramatically at the onset of the contraction and then remained almost constant throughout the rest of the contraction. These results, obtained by simultaneous recordings of EMG, MMG, and NIRS, demonstrate that the restriction of blood flow due to high intramuscular mechanical pressure is one of the most important factors in muscle fatigue in the lower-back muscles. In addition, the simultaneous recording system described here can be used to obtain more reliable information regarding the mechanism(s) of lower-back muscle fatigue.

Bioavailability assessment of disopyramide using pharmacokinetic-pharmacodynamic (PK-PD) modeling in the rat.

The relationship between the serum concentration and the pharmacological effect of disopyramide was investigated quantitatively to estimate the extent of its oral bioavailability (EBA(p.o.) and to evaluate the drug interaction with miconazole, a CYP3A4 inhibitor. An integrated pharmacokinetic-pharmacodynamic (PK-PD) model was used to describe the relationship between the serum concentrations and changes in QT interval (pharmacological data) of disopyramide after intra-vascular infusion for 15 min (i.v. short-term infusion) to rats. A two-compartment model was applied to the pharmacokinetics of disopyramide. The pharmacological data after short-term infusion were well explained using a PK-PD link model. To validate the present PK-PD model. disopyramide was administered intra-vascularly in separate experiments, and the doses were predicted only from the pharmacological data. The model predicted doses were identical to the actual doses, regardless of the dosing rates. This result indicates that the PK-PD model used in the present study is appropriate, and that the relationship between the serum concentrations and changes in QT intervals is independent of the dosing (input) rate. When miconazole was co-administered orally 1 h before disopyramide infusion, the serum disopyramide concentrations were significantly higher than that following disopyramide alone. The raised serum concentrations under miconazole co-administration were well explained by nonlinear elimination clearance. The pharmacological effects of disopyramide under miconazole co-administration, were also greater than those following disopyramide alone. The results of the PK-PD analysis indicated that the enhanced pharmacological response under miconazole co-administration was simply caused by a pharmacokinetic change. The EBA(p.o.) values estimated from the pharmacological effects predicted the observed values reasonably well. In conclusion, we demonstrated following: (1) the pharmacological effect after intra-vascular administration of disopyramide is related quantitatively to the serum concentrations using a PK-PD model; (2) miconazole affects only the elimination clearance of disopyramide to enhance the pharmacological effect; (3) the EBA of disopyramide can estimated reasonably only well from the pharmacological data using the PK-PD model; (4) there is no dosing-rate-dependent or dosing-route-dependent pharmacological effect of disopyramide.

Bioavailability assessment of arginine-vasopressin (AVP) using pharmacokinetic-pharmacodynamic (PK-PD) modeling in the rat.

A novel method of assessing the extent of oral bioavailability of arginine-vasopressin (AVP) from pharmacological data was presented. After intravascular administration (i.v. bolus or short-term infusion) of AVP to rats, the relationship between blood concentrations and its effect on both mean arterial pressure (hemodynamic effect) and urinary sodium concentration (anti-diuretic effect) was described on the basis of an integrated pharmacokinetic-pharmacodynamic (PK-PD) model. A direct model was used for the hemodynamic response, while an indirect response model, rather than a hypothetical link model was used for the anti-diuretic response. A sigmoid Emax model was applied to describe the drug-receptor interaction. Pharmacological responses after intravascular administration of AVP were reasonably described by the PK-PD model. However, PD parameters estimated by the PK-PD analysis suggested that apparent receptor affinity rather than efficacy in i.v. bolus study was significantly higher than that in the short-term infusion study. This fact indicated that PK-PD relationship was influenced by the intravascular input rate of AVP. We then investigated the relationship between plasma concentration and amount of AVP bound to the V2 receptors in the kidney. The result indicated that the amount of AVP bound to the receptors after i.v. bolus injection was always greater than that after short-term infusion. Since the PK-PD relationship after oral administration was almost identical with that after short-term infusion, the PK-PD model obtained in the short-term infusion study was used to assess the extent of oral bioavailability (EBAPp.o.). The EBAp.o. values, estimated from pharmacological effects (hemodynamic effect and anti-diuretic effect) after oral administration of 5 microg/kg of AVP were 0.68% to 0.93% and were almost identical with the actual EBAPp.o. value (0.81%). From these results, we concluded that oral bioavailability of AVP was reasonably predicted by the PK-PD model, provided that appropriate pharmacological effects and appropriate intravascular dosing rate as a reference formulation are available. The method may be an alternative to methods based on plasma concentrations, when drug concentration cannot be measured and when appropriate pharmacological data are available.

Interobserver and intraobserver variation in endoscopic assessment of GERD using the "Los Angeles" classification.

BACKGROUND: A new endoscopic classification of gastroesophageal reflux disease (GERD) has been proposed, and the term mucosal break has been introduced to describe mucosal damage. This new classification was evaluated by endoscopists with different levels of experience. METHODS: Fifty endoscopic photographs for each of 20 randomly selected patients with GERD were assessed retrospectively by three groups of seven endoscopists classified by experience: group 1 (100 to 500 procedures), group 2 (500 to 3000), and group 3 (more than 3000). The new classification was modified by adding grade 0 to describe healed mucosal breaks, so that there were five grades. All photographs were assessed twice at an interval of more than 1 week, and kappa statistics were used to determine observer variation. RESULTS: Interobserver variation within group 3 (kappa = 0.39, n = 21) and between groups 3 and 2 (kappa = 0.36, n = 49) was significantly different (p < 0.01) from that between groups 3 and 1 (kappa = 0.26, n = 49). Intraobserver variation in group 1 (kappa = 0.39, n = 7) was significantly different (p < 0.01) from that in group 2 (kappa = 0.51, n = 7) and group 3 (kappa = 0.54, n = 7). CONCLUSIONS: Observer variation depends on level of endoscopic experience. Only experienced endoscopists should use the new classification for grading of GERD.

Norms and validity of the DriVR: a virtual reality driving assessment for persons with head injuries.

This article presents the results of two studies of a new driving simulator called "DriVR." The first, normative study examined the performance of an uninjured driving population on the simulator. The driving ability of 148 participants in eight age categories was assessed using DriVR. The second, discriminative validity study examined DriVR's ability to discriminate between the performance of head-injured and uninjured adults. We administered the DriVR assessment to 17 head-injured adults. The performance of this group was compared to that of a subgroup of uninjured participants that matched the brain-injured participants in age, gender, and years of education. In general, DriVR's measures showed age-related changes in participant performance and were able to discriminate between head-injured and uninjured participants. These results suggested that age norms would be useful for analyzing the performance of head-injured clients who are being assessed with DriVR. It should be noted, however, that these studies did not examine DriVR's ability to predict performance in real, on-the-road tests.

Substituted 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase.

A series of 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives have been synthesized and evaluated for their ability to selectively inhibit human heart chymase. The structure-activity relationship studies on these compounds gave the following results. The 1-phenyl moiety participates in a hydrophobic interaction where an optimum size is required. At this position, 3,4-dimethylphenyl is the best moiety for inhibiting chymase and showed high selectivity compared with chymotrypsin and cathepsin G. A 3-phenylsulfonyl moiety substituted with hydrogen-bond acceptors such as nitrile and methoxycarbonyl enhances its activity. Molecular-modeling studies on the interaction of 3-[(4-chlorophenyl)sulfonyl]-1-(4-chlorophenyl)-imidazolidine-2,4-dione (29) with the active site of human heart chymase suggested that the 1-phenyl moiety interacts with the hydrophobic P1 pocket, the 3-phenylsulfonyl moiety resides in the S1'-S2' subsites, and the 4-carbonyl of the imidazolidine ring and sulfonyl group interact with the oxyanion hole and the His-45 side chain of chymase, respectively. The complex model is consistent with the structure-activity relationships.

Serum hyaluronate in the assessment of liver endothelial cell function after orthotopic liver transplantation in the rat.

This study was designed to evaluate the use of serum hyaluronate as a marker of liver endothelial cell function after liver transplantation. We performed orthotopic liver transplantation in both isogeneic and allogeneic rejector models. After transplantation, hepatocyte function was assessed on the basis of serum ALT and total bilirubin levels, and liver endothelial cell function was judged on the basis of serum hyaluronate levels. Significant increase of hyaluronate in the rejector model, compared with the isogeneic model, was seen before any significant results could be obtained from conventional liver function tests. The impaired metabolism of hyaluronate in the rejector model was observed after intravenous injection of trace amounts of radioactive material. Serial studies demonstrate that the endothelial cell is a more susceptible target for the immune response than the hepatocyte. Serum hyaluronate concentration may be a better indicator in the early assessment of graft function. We also examined serum hyaluronate levels to evaluate cold ischemia-reperfusion injury to the liver endothelial cells in the isogeneic model. At 2 hr after reperfusion, hyaluronate levels in the 6-hr cold ischemia (nonviable allograft) group were significantly higher than in the 1-hr and 3-hr cold ischemia (viable allograft) groups. However, there was little difference between the viable allograft groups. After an intravenous injection of 1 mg/kg hyaluronate, the hyaluronate elimination rate in the 3-hr group was distinctly slower than that in the 1-hr group. These data indicate that the hyaluronate elimination rate may be a more sensitive marker of liver endothelial cell function in viable liver after a short period of ischemia.

Assessment of lymphokine-activated killer activity and gamma-interferon production in patients with small hepatocellular carcinomas.

We have previously reported depressed gamma-interferon production and depressed lymphokine-activated killer and natural killer activity in patients with relatively large hepatocellular carcinomas. These parameters were normal in cirrhosis. Some evidence had suggested a gamma-interferon production defect as the main cause of depressed lymphokine-activated killer activity in hepatocellular carcinoma, (i.e., gamma-interferon enhances lymphokine-activated killer and natural killer activity and gamma-interferon antibody inhibits lymphokine-activated killer induction). However, we were unable to clinically define the precise mechanism operating here because gamma-interferon production and lymphokine-activated killer activity were both defective in advanced hepatocellular carcinoma. In recent years, it has become possible to detect even small hepatocellular carcinomas on ultrasonography and to confirm them by fine-needle biopsy. In this study, we assessed those immune parameters in 48 patients with hepatocellular carcinomas less than 2 cm in diameter to confirm depressed immune function and to clarify the mechanism of these defects. Lymphokine-activated killer activity was defective in 31 patients (64.6%), whereas gamma-interferon production was defective in only 1 of these patients (2.1%). This observation argues against the hypothesis that defective gamma-interferon production is the primary defect and provides new insight into the mechanism of progression of defective immune function in hepatocellular carcinoma. Thirty-one of the 48 hepatocellular carcinoma patients were treated surgically, and these immune parameters were followed for 6 mo. The recovery of lymphokine-activated killer activity in all hepatocellular carcinoma patients with low lymphokine-activated killer activity suggests the tumor burden as the cause of defective lymphokine-activated killer activity.

Development of the brainstem: assessment by MR imaging.

The morphological development of the brainstem was studied by means of MR imaging. The subjects were 74 cases ranging in age from 4 months to 16 years, and 6 adult cases. The brainstem development was rapid until 4-6 years of age and thereafter it slowed down. That is the brainstem showed exponential growth (w', t', v and u). The relationship between brainstem growth and the cranium size was divided into 4 types as follows: 1) linear increase with development (s/T-O), 2) plateau (w/T-I and v/RTP-LTP), 3) down and up (u/RTM-LTM and z/RTM-LTM) and 4) exponential (t/T-P). In the values of v, z (the size of the brainstem in axial view) and t/T-P (the ratio of the midbrain and the cranium size in sagittal view), there were significant sex differences for cases of 10-16 years old. These values in male subjects were greater than those in female subjects (v, p less than 0.05, z, p less than 0.01, and t/T-P, p less than 0.05). That is the brainstem in male subjects was greater than that in female subjects.