Impact of an antimicrobial stewardship in a 126-bed community hospital with close communication between pharmacists working on post-prescription audit, ward pharmacists, and the antimicrobial stewardship team.

BACKGROUND: Antimicrobial stewardship (AS) is defined as coordinated interventions to improve and measure the appropriate use of antimicrobial agents. However, available resources for AS differ depending on the size of the clinical setting. Therefore, AS programs based on guidelines need to be selected in order to implement AS in small- to medium-sized hospitals. The present study compared the impact of AS in a 126-bed community hospital between pre- and post-AS periods. METHODS: The present study was retrospectively performed by selecting data on eligible patients from electronic medical records stored in the central database of the hospital. The roles of the AS team included weekly rounds and recommendations on the appropriate use of antimicrobials, and pharmacists working on post-prescription audits and pharmaceutical care at the bedside closely communicated with the AS team to assist with its implementation. As process measurements, the order rate of culture examinations, the conducting rate of de-escalation, antimicrobial use density (AUD), days of therapy (DOT), and the AUD/DOT ratio of carbapenems and tazobactam-piperacillin (TAZ/PIPC) were measured. Thirty-day mortality and recurrence rates were examined as clinical outcomes. RESULTS: A total of 535 patients (288 in the pre-AS period and 247 in the post-AS period) were enrolled in the present study. The recommendation rate to prescribers significantly increased (p < 0.01) from 10.4% in the pre-AS period to 21.1% in the post-AS period. The order rate of culture examinations increased from 56.3 to 73.3% (p < 0.01). The conducting rate of de-escalation increased from 10.2 to 30.8% (p < 0.05). The AUD of carbapenems and TAZ/PIPC significantly decreased (p < 0.05). The DOT of carbapenems (p < 0.01) and TAZ/PIPC (p < 0.05) also significantly decreased. The AUD/DOT ratio of carbapenem significantly increased from 0.37 to 0.60 (p < 0.01). Thirty-day mortality rates were 11.2 and 14.2%, respectively, and were not significantly different. The 30-day recurrence rate significantly decreased (p < 0.05) from 14.7 to 7.5%. CONCLUSIONS: The implementation of AS in this hospital improved the appropriate use of antimicrobials without negatively affecting clinical outcomes. These results may be attributed to close communication between pharmacists working on post-prescription audits and pharmaceutical care at the bedside and the AS team.

Relativistic Rational Extended Thermodynamics of Polyatomic Gases with a New Hierarchy of Moments.

A relativistic version of the rational extended thermodynamics of polyatomic gases based on a new hierarchy of moments that takes into account the total energy composed by the rest energy and the energy of the molecular internal mode is proposed. The moment equations associated with the Boltzmann-Chernikov equation are derived, and the system for the first 15 equations is closed by the procedure of the maximum entropy principle and by using an appropriate BGK model for the collisional term. The entropy principle with a convex entropy density is proved in a neighborhood of equilibrium state, and, as a consequence, the system is symmetric hyperbolic and the Cauchy problem is well-posed. The ultra-relativistic and classical limits are also studied. The theories with 14 and 6 moments are deduced as principal subsystems. Particularly interesting is the subsystem with 6 fields in which the dissipation is only due to the dynamical pressure. This simplified model can be very useful when bulk viscosity is dominant and might be important in cosmological problems. Using the Maxwellian iteration, we obtain the parabolic limit, and the heat conductivity, shear viscosity, and bulk viscosity are deduced and plotted.

Rational extended thermodynamics of dense polyatomic gases incorporating molecular rotation and vibration.

The paper aims to construct a rational extended thermodynamics (RET) theory of dense polyatomic gases by taking into account the experimental evidence that the relaxation time of molecular rotation and that of molecular vibration are quite different from each other. For simplicity, we focus on gases with only one dissipative process due to bulk viscosity. In fact, in some polyatomic gases, the effect of bulk viscosity is much larger than that of shear viscosity and heat conductivity. The present theory includes the previous RET theory of dense gases with six fields as a particular case, and it also includes the RET theory of rarefied polyatomic gases with seven fields in the rarefied-gas limit. The closure is carried out by using the universal principles, that is, Galilean invariance and objectivity, entropy principle, and thermodynamic stability (convexity of entropy), where the duality principle connecting rarefied gases to dense gases also plays an important role. A detailed discussion is devoted to the expression of the production terms in the system of balance equations. As typical examples, we study a gas with virial equations of state and a van der Waals gas. Lastly the dispersion relation of a linear wave is derived, and its comparison with experimental data is made. This article is part of the theme issue 'Fundamental aspects of nonequilibrium thermodynamics'.

Extended Thermodynamics of Rarefied Polyatomic Gases: 15-Field Theory Incorporating Relaxation Processes of Molecular Rotation and Vibration.

After summarizing the present status of Rational Extended Thermodynamics (RET) of gases, which is an endeavor to generalize the Navier-Stokes and Fourier (NSF) theory of viscous heat-conducting fluids, we develop the molecular RET theory of rarefied polyatomic gases with 15 independent fields. The theory is justified, at mesoscopic level, by a generalized Boltzmann equation in which the distribution function depends on two internal variables that take into account the energy exchange among the different molecular modes of a gas, that is, translational, rotational, and vibrational modes. By adopting the generalized Bhatnagar, Gross and Krook (BGK)-type collision term, we derive explicitly the closed system of field equations with the use of the Maximum Entropy Principle (MEP). The NSF theory is derived from the RET theory as a limiting case of small relaxation times via the Maxwellian iteration. The relaxation times introduced in the theory are shown to be related to the shear and bulk viscosities and heat conductivity.

Rational extended thermodynamics of a rarefied polyatomic gas with molecular relaxation processes.

We present a more refined version of rational extended thermodynamics of rarefied polyatomic gases in which molecular rotational and vibrational relaxation processes are treated individually. In this case, we need a triple hierarchy of the moment system and the system of balance equations is closed via the maximum entropy principle. Three different types of the production terms in the system, which are suggested by a generalized BGK-type collision term in the Boltzmann equation, are adopted. In particular, the rational extended thermodynamic theory with seven independent fields (ET_{7}) is analyzed in detail. Finally, the dispersion relation of ultrasonic wave derived from the ET_{7} theory is confirmed by the experimental data for CO_{2}, Cl_{2}, and Br_{2} gases.

Thermodynamic theory of the shock wave structure in a rarefied polyatomic gas: beyond the Bethe-Teller theory.

The structure of a shock wave in a rarefied polyatomic gas is studied on the basis of the theory of extended thermodynamics. Three types of the shock wave structure observed in experiments, that is, the nearly symmetric shock wave structure (type A, small Mach number), the asymmetric structure (type B, moderate Mach number), and the structure composed of thin and thick layers (type C, large Mach number), are explained by the theory in a unified way. The theoretical prediction of the profile of the mass density agrees well with the experimental data. The well-known Bethe-Teller theory of the shock wave structure in a polyatomic gas is reexamined in the light of the present theory.

Synchronous bilateral breast cancer in a male patient following hormone therapy for prostate cancer.

We report an unusual case of bilateral, synchronous breast cancer in a male patient who had a history of estrogen therapy for prostate cancer. A 64-year-old Japanese man was diagnosed with T1N0M0 prostate cancer and received a total prostatectomy. Twenty months after the resection, the patient developed multiple bone metastases, and received radiation therapy, systemic chemotherapy, and hormone therapy for 15 months. After completing this treatment, he was diagnosed with T1N0M0 primary breast cancer in his left breast and underwent a modified mastectomy. Five months after the mastectomy he received systemic chemotherapy followed by estrogen therapy because of the progression of prostate cancer. Three months after this treatment, he was diagnosed with T1N0M0 primary breast cancer in his right breast. To the best of our knowledge, this is a rare case of synchronous bilateral male breast cancer following hormone therapy for prostate cancer.

A phase I/II trial of TAC-101, an oral synthetic retinoid, in patients with advanced hepatocellular carcinoma.

PURPOSE: Preclinical models showed TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid), an oral synthetic retinoid, has anti-tumor activity in hepatocellular carcinoma (HCC). A phase I/II study was performed in advanced HCC patients (pts). PATIENTS AND METHODS: Thirty-three patients were enrolled. During Phase I, pts received 40 mg daily for 14 days q3 weeks; 2 of 5 patients developed DLT so dose was reduced to 20 mg/day. Twenty-eight patients received 20 mg/day. RESULTS: No pt had a CR or PR, but 12 of 21 (57%) had SD. Two pts (9.5%) had late PR after discontinuing TAC-101. Median survival (MS) for all 28 pts treated with 20 mg/day was 12.7 months (95% CI 8.8-22.7); MS for 21 evaluable pts was 19.2 months (95% CI 10.4-27.6). CONCLUSIONS: 20 mg of TAC- was well tolerated. Significant disease stabilization (12/21 pts, 57%), 2 late PRs, and prolonged MS (19.2 months) suggest that TAC-101 provides meaningful patient benefit.

Nuclear translocation of ADAM-10 contributes to the pathogenesis and progression of human prostate cancer.

A disintegrin and metalloproteases (ADAM) are cell membrane-anchored proteins with potential implications for the metastasis of human cancer cells via cell adhesion and protease activities. In prostate cancer (PC), the ADAM-10 protein showed a nuclear localization whereas in benign prostate hypertrophy (BPH) it was predominantly bound to the cell membrane. We hypothesized that the pathogenesis and progression of PC are attributable to the nuclear translocation of ADAM-10. Immunoblotting revealed that after 5alpha-dihydrotestosterone treatment, a 60-kDa active form of ADAM-10 was increased in the nuclear fraction but decreased in the cell membrane and cytoplasmic fractions of human androgen-dependent PC cells. Immunocytochemistry revealed that after 5alpha-dihydrotestosterone treatment, the ADAM-10 protein was translocated from the cell membrane to the nucleus. Coimmunoprecipitation of androgen receptor and ADAM-10 was detected in the nuclear fraction but not in the cell membrane and cytoplasmic fractions. Immunohistochemical study of 64 PC and 20 BPH samples showed that the intensity of ADAM-10 staining was significantly higher in the nuclei of PC cells than in the nuclei of BPH cells (P < 0.0001). It was also significantly lower in the cell membrane of PC cells than in the cell membrane of BPH cells (P = 0.0017). Nuclear staining intensity was significantly correlated with the clinical T-factor (P = 0.004), the Gleason score (P < 0.0001) and preoperative prostate-specific antigen levels (P = 0.0061). ADAM-10 small interfering RNA transfectants showed a significant decrease in cell growth compared to the controls. Our results suggest that in human PC, the nuclear translocation of ADAM-10 coupled with the androgen receptor is involved in tumor growth and progression.

[Efficacy of smoking prevention education by dentists].

PURPOSE: At the same time as generating a clear picture of high school students' smoking habits, we examined how effective it was for dentists to provide them with smoking prevention education. METHOD: We chose one high school in Hiroshima City and asked 1003 of its students to fill in questionnaires anonymously before and after a lecture given by dental faculty on smoking. On a different day the students' oral health was examined by dentists. FINDINGS: The higher the year of the students the higher the percentage of those who had smoked at some time or smoking now. Among students not participating in any club activities, the higher the year the greater the number of smokers. Among the effects of smoking the one known to the largest number of students was found to be lung cancer, followed by oral disease. The questionnaires showed the percentage of students thinking that their family should give up smoking had increased by 6.3% from 55.9% to 62.2% by the end of the lecture, indicating that it was effective. Among the contents of the lecture which had impressed, photographs of cancer, dental damage and features Buerger's disease were mentioned in particular. CONCLUSION: It is advisable to show some photographs of cancer and Buerger's disease as well as talk about how smoking damages teeth when we embark on smoking prevention education. Our study confirmed the need for dentists to provide this kind of education.