In the simple suspension method for feeding tube administration, tablets are left to stand in 20 mL of hot water (55℃) for 10 min. However, the method is not applicable to heat-labile drugs, and tube obstruction occurs when large, uncrushed tablet particles are mixed in the suspension. In this study, we developed a method of tube administration using the zirconia ball and rotation-revolution mixer (RRM) method. Tablets were placed in 20 mL of water (≦20℃) and suspended by RRM with an 8 mm-zirconia ball. The recovery rate of Ubidecarenone Tablet with a low melting point was low according to the conventional method, although the content of ubidecarenone was not reduced under an ordinary temperature by the RRM method. Moreover, the particle distribution of the Ubidecarenone Tablets treated by the RRM method was smaller than that by the conventional method, and all the particles passed through a feeding tube. We also examined whether RRM is applicable to various commercial tablets (17 tablets). These 17 tablets were disintegrated and suspended easily by the RRM method, and various tablets were crushed more efficiently with the RRM method in comparison with the conventional method. In addition, the RRM method improved the tube obstruction of Mercazole^® and Riluzole Tablets. These results show that the RRM method could disintegrate and suspend various tablets easily without using hot water, and the suspension could pass through a feeding tube.

The maximum cefazolin dosage for pediatric patients is 100 mg/kg/day according to the medical package insert. When cefazolin is used on surgical site infection (SSI) for prophylaxis, clinical practice guidelines state that the cefazolin dosage for antimicrobial prophylaxis is 30 mg/kg/time. However, the dosage of cefazolin exceeds 100 mg/kg/day from the beginning of administration to 24 hours later due to the long operation time during which cefazolin administration is repeated every 4 hours. The effects of exceeding cefazolin doses in pediatric patients have not been reported. We investigated the relationship between the cefazolin dosage and organ derangement in pediatric patients undergoing spinal fusion.

This study included 49 pediatric patients who underwent spinal fusion from April 2014 to March 2019. We used aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as markers of liver function and serum creatinine (Scr) as a marker of renal function; the SSI rate, number of days of hospital stay and clinical symptoms such as diarrhea and epilepsy were also analyzed.

The average cefazolin doses were 21.8 mg/kg/time and 110 mg/kg/day, and an SSI rate of 6.1% was reported. When we compared AST, ALT, Scr, SSI rate, the number of days of hospital stay, diarrhea and epilepsy between the high dose group and the standard dose group, there were no significant differences.

This study did not identify any dose-dependent side effects of cefazolin. The results suggest that a dose exceeding 100 mg/kg/day is safe under the guidelines for reducing the incidence of SSI.

Adequate caution against immune related adverse events (irAE) is required for patients using immune checkpoint inhibitors. A relationship between tumor proportion score (TPS) and therapeutic outcomes has been reported; however, there are few reports on the relationship between TPS and the onset of irAE. This multicenter study retrospectively investigated the incidence of irAE with respect to TPS in patients treated with pembrolizumab monotherapy for unresectable recurrent non-small-cell lung cancer. The subjects included patients who started and completed pembrolizumab treatment between March 2017 and December 2019 at Hiroshima City Hiroshima Citizens Hospital, Hiroshima City Asa Citizens Hospital, and Iwakuni Clinical Center. We retrospectively investigated the onset of irAE, TPS expression, and patient background using electronic medical records. The patients (n = 104) were divided into two groups based on TPS expression: 1 - 49％ in Group A (n = 28) and 50 - 100％ in Group B (n = 76). irAE occurred in 10 patients (35.7％) in Group A and 45 patients (59.2％) in Group B, showing a significantly higher incidence in Group B. The median numbers of days until the initial onset of an irAE were 49.5 days in Group A and 35.0 days in Group B, showing a significantly shorter period in Group B. Therefore, when pembrolizumab monotherapy is administered in patients with unresectable recurrent non-small-cell lung cancer, maintaining safe treatment and appropriate management is crucial because irAE may have a higher incidence and appear early in patients with higher TPS (≧50％).

It is essential to understand the risk factors for developing proteinuria because the development of ramucirumab-induced proteinuria can interrupt the treatment. Although several previous studies of ramucirumab-induced proteinuria have been reported, there is little evidence on time-dependent risk factors for developing proteinuria. The study subjects were 86 patients with cancer treated with ramucirumab at Ako City Hospital or Okayama University Hospital. We retrospectively evaluated the predictive factors for the development of ramucirumab-induced proteinuria ≥ 2+, which is a more important criterion for interrupting ramucirumab treatment in clinical practice. Sixty-five (75.6％) and 21 (24.4％) patients developed proteinuria ≤ 1+ and ≥ 2+. The incidence of proteinuria ≥ 2+ was significantly higher in patients who were previously treated with bevacizumab than those who were not (41.4％ vs 15.8％, P = 0.016). Multivariate Cox proportional hazards model revealed that previous bevacizumab treatment was significantly associated with the development of proteinuria ≥ 2+ (hazard ratio, 2.74; 95％ confidence interval, 1.06 - 7.19; P = 0.038). These results suggest that patients who have previously been treated with bevacizumab should be monitored carefully for the development of proteinuria after ramucirumab treatment.

Enactment of the self-medication tax deduction system is expected to lead to changes in the public’s behavior towards self-medication and contribute to the optimization of medical expenses. In this study, we rolled out an anonymous self-administered questionnaire on “awareness,” “understanding,” and “interest” about the self-medication tax deduction system to 246 participants of a health promotion seminar to extract and identify challenges towards future revisions to the tax system, so as to clarify the public’s current stance about the tax system and elucidate future issues and challenges in the system prior to termination of the Act on Special Measures Concerning Taxation (December 31, 2021). As a result, more than 60％ of the respondents were aware of this tax system, but in general the public had little understanding about its details. Furthermore, only 14％ of respondents who were purchasing more than 12,000 JPY worth of switch medicines annually had applied for deductions because of the lower limit of application being too high and the current medical cost deductions being higher. On the other hand, many of the respondents who were not aware about this tax system showed interest in it and said that they would like to use the system if they fulfilled the requirements for application. In order to optimize medical costs, we believe it is necessary to relax the requirements for application to the tax system, and to make the public more aware about medicines that are covered as well as the details of the system.

We experienced two cases with mild to moderate renal dysfunction in which amantadine hydrochloride (amantadine) intoxication was followed by increases in its blood levels. Case 1 was a patient with mild to moderate renal dysfunction [estimated glomerular filtration rate (eGFRcreat): 48.9 mL/min/1.73m²; glomerular filtration rate (GFR) category: G3a] taking amantadine 300 mg daily. In Case 1, the blood level of amantadine at 13 hours and 30 mins after administration was 2,368 ng/mL, pyrexia, myoclonus, and psychological symptoms were observed. After discontinuing amantadine, the patient’s myoclonus improved, but he died of acute respiratory distress syndrome. Case 2 was a patient with mild to moderate renal dysfunction [eGFRcreat: 55.6 mL/min/1.73m²; GFR category: G3a] taking amantadine 100 mg daily. In the patient, pyrexia, myoclonus, and consciousness disorder were observed. The blood level of amantadine 88 hours after the last dose was 265 ng/mL, and the blood level that was collected 24 hours after the end of administration was estimated to be about 2,600 to 4,200 ng/mL. In all cases, the clinical features were consistent with the common symptoms of amantadine intoxication, and improved by discontinuing amantadine. Taken together, these findings suggest that the patients were intoxicated with amantadine. These results indicate that amantadine intoxication due to elevated blood levels also occurs in patients with mild to moderate renal dysfunction during the administration of the usual dose of amantadine. In addition, the measurement of amantadine blood levels may be useful in avoiding amantadine intoxication.

Trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis is used to prevent pneumocystis pneumonia (PCP) in patients with autoimmune diseases who usually receive corticosteroid therapy for longer than 4 weeks. However, patients with intraocular inflammation often receive corticosteroids for several weeks without TMP/SMX prophylaxis. Therefore, we investigated the frequency of TMP/SMX prophylaxis use and the incidence of PCP.

Overall, 192 patients received corticosteroids in the departments of ophthalmology and oculoplastic surgery at the Aichi Medical University Hospital from August 11, 2011 to May 6, 2019. The total corticosteroid dose was calculated. We collected patients' clinical data such as underlying disease, infection events, and risk factors of immunodeficiency.

All patients received ≥ 560 mg total prednisolone (PSL) dose during the treatment period; 38.6％ patients received higher corticosteroid dose (PSL > 20 mg/day for 28 days), and 5.2％ patients used TMP/SMX. Among the study population, 74 and 118 patients received corticosteroids at higher or lower doses of the PCP prophylaxis dose (PSL 20 mg/day ≥ 28 day), but 98.6％ (n = 73) and 98.3％ (n = 116) patients did not show respiratory infections, even though they had immunodeficiency risk factors. Additionally, no patient showed symptoms of PCP.

In conclusion, no patients developed PCP caused by corticosteroid therapy despite most patients not receiving TMP/SMX prophylaxis. Therefore, stereotypical TMP/SMX prophylaxis, only based on the steroid dosage and immunodeficiency data, is not recommended for intraocular inflammatory disease patients receiving corticosteroids.