Association between the Co-administration of Histamine H2 Receptor Antagonists and the Effectiveness of Capecitabine in Patients with Colorectal Cancer: Propensity Score Analysis.

Background: The association between the effectiveness of capecitabine and the concomitant administration of gastric acid suppressants remains controversial. We aimed to clarify whether the effectiveness of capecitabine is affected by the co-administration of histamine H2 receptor antagonists (H2RAs) in early-stage colorectal cancer (CRC) patients using real-world data. Methods: This multicenter, retrospective, observational study included consecutive patients with stage II-III CRC who received either capecitabine monotherapy or the CapeOX regimen (capecitabine and oxaliplatin) as adjuvant therapy between January 2009 and December 2014 in Japan. Relapse-free survival (RFS) and overall survival were estimated using the Kaplan-Meier method. Additionally, multivariable Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting analyses were performed. Results: In total, 552 patients were included in this study, of which 30 were co-administered H2RAs. RFS at five years was 76.7% (95% confidence interval [CI]: 57.2-88.1%) and 79.8% (95% CI: 76.0-83.0%) in the H2RA and non-H2RA groups, respectively. Multivariable Cox proportional hazards model and propensity score-adjusted analyses showed that the co-administration of H2RAs was associated with a poor RFS among those receiving capecitabine monotherapy (hazard ratio [HR], 2.01; 95% CI: 0.86-4.70 and HR, 1.81; 95% CI: 0.77-4.22, respectively). In contrast, these results were inconsistent with the group receiving the CapeOX regimen. Conclusions: The study findings suggest that the co-administration of H2RAs may not reduce the effectiveness of capecitabine therapy in patients with early-stage CRC. To confirm this relationship, a prospective study with a pharmacokinetic approach is needed.

Using an online journal club to improve Asian speakers' comfort in using English to discuss and understand research papers written in English.

INTRODUCTION: This study aimed to evaluate the participants' comfort in understanding research papers written in English and discussing such research in English via an Asian online journal club. METHODS: A self-administered online survey was delivered to seven journal club meeting attendees from July 2020 to July 2021. A customer satisfaction analysis was performed to assess the association between the participants' perspectives on program logistics and satisfaction. RESULTS: The recovery rate was 37.0% (44/119). After participating in the journal club, the median scores of critical appraisal skills, knowledge and/or pharmaceutical care skills in clinical practice, and discussion skills in English (assessed using a seven-point Likert scale) improved significantly (compared to pre-participation median scores) from 4 (interquartile range [IQR]: 3-5) to 5 (IQR: 4-6), 5 (IQR: 4-5) to 5 (IQR: 5-6), and 4 (IQR: 2-5) to 5 (IQR: 3-5), respectively (P < 0.0001). The respondents also expressed great appreciation for the benefits and overall qualities of the journal club. Additionally, regarding patient care behavior after participation in the journal club, 34 (77.3%), 17 (38.6%), 16 (36.4%), and 14 (31.8%) respondents reported improvement in "drug information services," "patient assessments," "patient counseling," and "multidisciplinary rounds," respectively. Customer satisfaction analysis revealed that sharing information, mutual discussion, a shift system of presenters and co-chairs, and session duration should be improved as a matter of highest priority. CONCLUSION: The findings suggest that our program could be helpful for Asian pharmacists, pharmacy students, and faculty members of the department of pharmacy.

Proton pump inhibitors affect capecitabine efficacy in patients with stage II-III colorectal cancer: a multicenter retrospective study.

The association between capecitabine efficacy and proton pump inhibitors (PPIs) is controversial. Here, we determined whether co-administration of PPIs affects the real-world effectiveness of capecitabine. This retrospective observational study included consecutive patients with stage II-III colorectal cancer (CRC) who received adjuvant capecitabine monotherapy or CapeOX (capecitabine and oxaliplatin) between January 2009 and December 2014 at nine participating institutions. The primary endpoint was the difference in relapse-free survival (RFS) between patients who received PPIs and those who did not and was estimated using the Kaplan-Meier method. Overall survival (OS) was the secondary endpoint. Multivariable analysis of RFS and OS was performed using a Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting (IPTW) analyses. Data from 606 patients were evaluated, 54 of whom had received a PPI. PPI-treated patients tended to have poorer RFS and OS than patients treated without PPIs. The hazard ratio for RFS with capecitabine monotherapy was 2.48 (95% confidence interval: 1.22-5.07). These results were consistent with sensitivity analyses performed using propensity score adjustment and IPTW methods. Co-administration of PPIs may reduce the effectiveness of capecitabine and negatively impact patients with stage II-III CRC.

The efficacy and safety of high-dose arbekacin sulfate therapy (once-daily treatment) in patients with MRSA infection.

The efficacy and safety of once-daily high-dose arbekacin sulfate therapy for methicillin-resistant Staphylococcus aureus (MRSA) infection were evaluated, with analysis of their relationship to blood drug levels. The study was conducted in patients with pneumonia or sepsis, the cause of which was suspected to be MRSA, who were admitted to the Nagasaki University Hospital or its affiliated hospitals between January 2009 and December 2010. The initial drug dose was set at a level expected to yield the goal peak of 20 µg/ml and a trough level of less than 2 µg/ml, using the Habekacin Therapeutic Drug Monitoring analysis software. Thirteen patients were enrolled: 10 patients had pneumonia and 3 patients had sepsis. Patient mean age was 72.0 years; mean initial drug dose was 269.2 mg. Clinical efficacy at completion of treatment and bacterial eradication-reduction were achieved in 66.7% (6/9) and 62.5% (5/8) of patients, respectively. Incidence of adverse reactions was 38.5% (5/13). In analysis of efficacy in relationship to serum drug levels, the peak drug level was 22.7 ± 5.50 µg/ml, on average, and 15 µg/ml or higher in all 6 responders. Also, in patients with renal dysfunction, it seemed to be essential to ensure a certain peak drug level and to control the trough level appropriately. Although the number of patients was limited, once-daily high-dose arbekacin sulfate therapy may be highly effective, without posing any major safety problems. Further larger-scale studies are needed.

Effect of anionic and cationic n-butylcyanoacrylate nanoparticles on NO and cytokine production in Raw264.7 cells.

CONTEXT: Research on drug delivery carriers that use nanoparticles is currently attracting a great deal of attention. In order to evaluate the safety of these drug carriers for clinical applications, a full assessment of their toxicity and bioactivity is required. Although it is well-known that the surface charge of nanoparticles influences their bioactivity, most of the published studies on n-butylcyanoacrylate (NBCA) nanoparticles as a potential drug delivery carrier are restricted to analyzing the anionic form. OBJECTIVE: We compared biological responses of cyanoacrylate anionic nanoparticles with cationic nanoparticles in cultured murine macrophages for assessing cytotoxicity and inflammatory responses. MATERIALS AND METHODS: The cytotoxicity was evaluated with the MTS and LDH leakage assays. Inflammatory responses were evaluated by measurement of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The interaction of the nanoparticle and the macrophage was assessed by fluorescence microscopy. RESULT: Anionic and cationic NP showed no detectable cytotoxicity at a concentration of 10 µg/mL or less. At concentrations greater than 10 µg/mL, cationic NP displayed lower cytotoxicity by comparison with anionic NP. NO, IL-6, and TNF-α production were not induced by anionic or cationic nanoparticles alone. In contrast, both types of nanoparticles decreased NO, IL-6, and TNF-α productions induced by LPS. However, the anti-inflammatory effect of anionic nanoparticles was significantly greater than that of cationic nanoparticles. Nanoparticles were presumed to be either internalized or attached to the cell membranes. DISCUSSION AND CONCLUSION: NBCA nanoparticles are not only important as potential drug carriers but also as promising anti-inflammatory agents that may have therapeutic properties.

Magic wavelength to make optical lattice clocks insensitive to atomic motion.

In a standing wave of light, a difference in spatial distributions of multipolar atom-field interactions may introduce atomic-motion dependent clock uncertainties in optical lattice clocks. We show that the magic wavelength can be defined so as to eliminate the spatial mismatch in electric dipole, magnetic dipole, and electric quadrupole interactions for specific combinations of standing waves by allowing a spatially constant light shift arising from the latter two interactions. Experimental prospects of such lattices used with a blue magic wavelength are discussed.

[Study on the blood concentration and clinical efficacy of ceftazidime, a cephem antibiotic at dose of one gram q.i.d, for adult hospital-acquired pneumonia patients].

Ceftazidime (CAZ), a cephem antibiotic for injection, was administered at dose of one gram q.i.d. to adult hospital-acquired pneimonia patients, and the clinical efficacy and blood concentration of CAZ was studied in five cases. The assessment of clinical efficacy was "efficacy" in all cases, and early improvement of examination value including body temperature, the value of CRP, and white blood cell counts were obtained. Abnormality of hepatic function as adverse effect was noted in two cases. However, the severity was mild and didn't affect the treatment in both cases. The maximum drug concentration immediately after the end of infusion was 72.1-176.5 microg/mL (median, 82.7 microg/mL) and the trough level was 5.1-72.1 microg/mL (median, 26.6 microg/mL), therefore the blood concentration was maintained a higher level than the MIC of bacteria estimated to be causative. From these results, administration method of ceftazidime one gram q.i.d. was considered to be a good way with increase of drug efficacy by maintaining highly blood concentration over prolonged period, and expected to be a good effect for hospital-acquired pneumonia.

Interstitial pneumonia caused by inhalation of fumes of nickel and chrome.

Two male industrial painters were admitted to hospital with dry cough and dyspnoea on exertion following a tank coating operation using a high-temperature spray paint consisting of a nickel-chromium alloy. Both patients showed hypoxaemia, peripheral leukocytosis, high levels of serum cytokines and bilateral ground-glass opacities on a chest CT scan. They were diagnosed with interstitial pneumonia caused by inhalation of nickel and chrome fumes and successfully treated with corticosteroid. These are rare cases of interstitial pneumonia associated with nickel/chromium inhalation.