Pharmacological Investigation of Hypoalbuminemia on the Prolonged and Potentiated Action of Midazolam in Rats.

Midazolam (MDZ) is clinically used for its sedative and anticonvulsant properties. However, its prolonged or potentiated effects are sometimes concerning. The main binding protein of MDZ is albumin, and reduced serum albumin levels could lead to MDZ accumulation, thereby potentiating or prolonging its effects. Previous investigations have not thoroughly examined these phenomena from a behavioral pharmacology standpoint. Consequently, this study aimed to evaluate both the prolonged and potentiated effects of MDZ, as well as the effects of serum albumin levels on the action of MDZ in low-albumin rats. Male Wistar rats were classified into control (20% protein diet), low-protein (5% protein), and non-protein groups (0% protein diet) and were fed the protein-controlled diets for 30 d to obtain low-albumin rats. The locomotor activity and muscle relaxant effects of MDZ were evaluated using the rotarod, grip strength, and open-field tests conducted 10, 60, and 120 min after MDZ administration. Serum albumin levels decreased significantly in the low-protein and non-protein diet groups compared with those in the control group. Compared with the control rats, low-albumin rats demonstrated a significantly shorter time to fall, decreased muscle strength, and a significant decrease in the distance traveled after MDZ administration in the rotarod, grip strength, and open-field tests, respectively. Decreased serum albumin levels potentiated and prolonged the effects of MDZ. Hence, serum albumin level is a critical parameter associated with MDZ administration, which should be monitored, and any side effects related to decreased albumin levels should be investigated.

Relationship between the phase angle from bioelectrical impedance analysis and daily physical activity in patients with rheumatoid arthritis.

OBJECTIVES: This study aimed to examine the relationship between daily physical activity and the phase angle (PhA) obtained by bioelectrical impedance analysis in rheumatoid arthritis (RA) patients. METHODS: Data from a prospective cohort study of RA patients who were surveyed every year were analysed. The PhA was assessed by the bioelectrical impedance analysis method, and physical activity was assessed as the amount of time of exercise in metabolic equivalents (METs) per day using a triaxial accelerometer for 7 consecutive days. The association between physical activity and the PhA was evaluated using the isotemporal substitution model in multiple regression analysis. RESULTS: Seventy-six RA patients were included in the analysis (81% female and age 66.2 ± 13.1 years). On cross-sectional analysis, the isotemporal substitution model in multiple regression analysis showed that the PhA was 0.05 points higher every 10 minutes when activities with intensity of 1 ≤ METs < 2 were replaced by activities with intensity of ≥3 METs (P = .01). Over 1 year, the rate of change in the PhA was 0.69% higher every 10 minutes when activities with intensity of 1 ≤ METs < 2 were replaced by activities with intensity of ≥3 METs (P = .037). CONCLUSION: The PhA in RA patients may be related to physical activity level.

Hospital pharmacist interventions for the management of oral mucositis in patients with head and neck cancer receiving chemoradiotherapy: a multicenter, prospective cohort study.

PURPOSE: Oral mucositis is a severe adverse event in patients with head and neck cancer (HNC) receiving chemotherapy and radiotherapy that may cause the termination of cancer treatment. In this study, we aimed to reveal the benefits of pharmacist interventions in oral health care for patients with HNC receiving concurrent chemoradiotherapy (CCRT). METHODS: We conducted a multicenter, prospective cohort study on 173 patients from September 2019 to August 2022. We evaluated the association between the occurrence of oral mucositis during CCRT and various factors in the absence or presence of direct medication instructions from hospital pharmacists. RESULTS: Sixty-eight patients received medication instructions from pharmacists (the pharmacist intervention group), whereas 105 patients did not receive instructions (the control group). Logistic regression analysis showed that grade 2 (Gr 2) oral mucositis was significantly lower in patients receiving pharmacist interventions than in patients in the control group (adjusted odds ratio [aOR], 0.42; 95% confidence interval [CI], 0.18-0.96; P = 0.04). The time to onset of Gr 2 oral mucositis was significantly longer in the pharmacist intervention group than in the control group (hazard ratio, 0.53; 95% CI, 0.29-0.97; P = 0.04). CONCLUSION: Direct intervention, especially when provided by hospital pharmacists, can have a real effect in supporting patients with HNC experiencing severe side effects of treatments. Moreover, the integration of pharmacists into the oral healthcare team is becoming even more essential to reduce the severity of side effects.

Congenital Palmar Duplication of the Index Finger: Ventral Polydactyly With Ventral Dimelia.

This report describes the case of a 10-month-old boy who presented with a duplicated index finger enveloped by palmar skin on the palmar side of the first web of the left hand. He was healthy without any other abnormalities except the hand anomaly. Surgical resection of the extra finger was performed with triangular flap at 15 months of age. The resected finger was composed of only palmar components: skin without nail or hair; flexor tendons; and digital nerves branching from the median nerve. Histological examination of the specimen demonstrated similar structures on both palmar and dorsal sides, that is, ridged, hairless, and glabrous skin with a high number of epithelial layers and thick corneous stratum and similar shaped tendons inserted into the symmetrical phalanx. This appears to be the first report in literature of an ectopic palmar index finger, a ventral polydactyly with ventral dimelia.

Computed Tomography Evaluation of Distal Screw Penetration in Volar Locking Plate Fixation for Intra-Articular Distal Radius Fractures.

PURPOSE: Volar locking plate fixation for distal radius fractures (DRFs) is a technically demanding procedure with a risk of distal screw penetration through the dorsal cortex or the articular surface. This study aimed to investigate the incidence and details of distal screw penetration after volar locking plate fixation for intra-articular DRFs using a CT scan and to evaluate the relationship between the incidence of screw penetration and fracture comminution severity and the clinical complications of screw penetration. METHODS: This was a retrospective case series of 91 adult patients (mean age, 63 years; 27 men) who underwent volar locking plate fixation for intra-articular DRFs from 2015 to 2018. The positioning of the distal screws was evaluated using a postoperative CT scan, and radiological outcomes were compared between the AO C1 and C3 groups. At the final follow-up, tendon rupture and arthritis severity were assessed as clinical complications of dorsal and intra-articular screw penetration. RESULTS: Distal screw penetration was observed in 44 wrists (48%), dorsal cortex screw penetration in 34, intra-articular screw penetration in 13, and both dorsal cortex and intra-articular screw penetration in three. The incidence of intra-articular screw penetration was significantly higher in the C3 group than in the C1 group. No tendon rupture was observed. Multivariable analysis revealed that intra-articular screw penetration was significantly related to high severity of arthritis. CONCLUSIONS: Approximately half of the study patients with intra-articular DRFs had distal screw penetration. The incidence of intra-articular screw penetration was associated with the severity of fracture comminution, and the intra-articular screw penetration was associated with the incidence of early radiocarpal arthritis. Intra-articularly penetrating screws should be replaced as soon as they are discovered, regardless of the length of penetrated screw or absence of patients' subjective symptoms. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The bioimpedance phase angle may be associated with frailty in rheumatoid arthritis patients: Results from a prospective, cohort study.

OBJECTIVES: This study investigated whether the phase angle (PhA) on bioelectrical impedance analysis is related to frailty in rheumatoid arthritis (RA) patients. METHODS: Data from a prospective cohort study of RA patients were analysed. The PhA was assessed by the bioelectrical impedance analysis method, and frailty was assessed by the Kihon Check List (KCL) annually. The cut-off value of the PhA for frailty was calculated by receiver-operating characteristic analysis. The relationships between the PhA and frailty were evaluated by logistic regression analysis. The relationships between the change in PhA and frailty status and the KCL score were evaluated by analysis of covariance and multiple regression analysis. RESULTS: A total of 170 patients (81.2% female, 66.2 ± 13.1 years) were included in the analysis. A PhA of less than the cut-off for frailty was significantly associated with frailty (odds ratio: 4.75, 95% confidence interval: 1.86, 12.17). The change in the PhA was significantly associated with the change in the KCL score (ß = -0.15). In robust patients, there was a significant difference in the rate of change of the PhA between the group that became pre-frail in the next year and the group that remained robust. CONCLUSIONS: The PhA may be associated with frailty in RA patients.

[Development and Verification of an irAEs Self-Reported Interview System(ISRIS)].

A variety of immune-related adverse events(irAEs)occur during the use of immune checkpoint inhibitors, and delayed detection may make it difficult to continue treatment. To detect irAEs as early as possible, we have been administering an irAEs self-reported interview system(ISRIS)to all outpatients using a tablet device. We conducted a retrospective study of outpatients who received pembrolizumab, nivolumab, atezolizumab, ipilimumab, and durvalumab and utilized the ISRIS from June 2019 to May 2020. The survey items were the primary disease, initial symptoms of irAEs, and detected irAEs. The total number of patients was 140, and the total number of interviews was 1,095. Overall, 42 irAEs occurred. The ISRIS is useful for detecting subjective skin disorders. However, its detection rate of myocarditis and thyroid, hepatic, and renal dysfunction was low, and there is room for improvement. We are currently developing an ISRIS application that maintains sensitivity and increases specificity to allow for early detection of irAEs at home.

Renin-Angiotensin-Aldosterone System Inhibitors Prevent the Onset of Oxaliplatin-Induced Peripheral Neuropathy: A Retrospective Multicenter Study and in Vitro Evaluation.

Oxaliplatin (OXA) is used in chemotherapy for various cancer types and is associated with acute and chronic neurotoxicity. However, a preventive strategy for OXA-induced peripheral neuropathy (OIPN) and its underlying mechanism remain unclear. We examined the effects of renin-angiotensin-aldosterone system inhibitors (RAASIs) on OIPN by performing a retrospective multicenter study and an in vitro assay. We retrospectively evaluated electronic medical records of 976 patients who underwent one or more courses of OXA-containing regimens at Ehime, Okayama, and Tokushima University Hospitals. The primary endpoint was the incidence of OIPN during or after OXA administration. The effects of RAASIs and OXA on the neurite length in PC12 cells were determined. The combined administration of an OXA-containing regimen and RAASI significantly inhibited the cumulative incidence grade-2 or higher OIPN (log-rank test; p = 0.0001). RAASIs markedly suppressed the development of both acute and chronic OIPN (multivariate analysis; p = 0.017 and p = 0.011). In an in vitro assay, 10 µM OXA suppressed the neurite length; treatment with 1 µM aliskiren, spironolactone, 10 µM candesartan, and enalapril significantly restored neurite length to the control level. Moreover, 1 µM SCH772984 (a selective inhibitor of extracellular signal-regulated kinase, ERK1/2) and 500 µM SQ22536 (a cell-permeable adenylate cyclase (AC) inhibitor) markedly abolished neurite-extending effects of candesartan and enalapril. These results indicate that RAASIs possess preventive or therapeutic effects in acute and chronic OIPN, candesartan and enalapril may increase in the activity of ERK1/2 and AC in PC12 cells.

Degradation and inactivation efficacy of ozone water for antineoplastic drugs in hospital settings.

PURPOSE: Occupational exposure to antineoplastic drugs in hospital settings is recognized to be hazardous, and as such environmental decontamination including degradation and inactivation of such drugs is recommended. To data, although various agents such as oxidants have been reported to be useful for decontamination, simpler, safer, and more convenient methods are required. In this study, the degradation and inactivation efficacy of ozone water, which has newly been introduced for decontamination of antineoplastic drugs in spills, was investigated for formulations of gemcitabine, irinotecan, and paclitaxel. METHODS: Antineoplastic formulations (medicinal ingredient: ∼1.5 µmol) were mixed with 50 mL of ozone water (>4 mg/L). The reactions were monitored by high-performance liquid chromatography, and the degradation mixtures were analyzed by 1H nuclear magnetic resonance spectroscopy in order to obtain the structural information of the degradation products. The formulations of gemcitabine and irinotecan and those degradation mixtures were evaluated for their mutagenicity using the Ames test and cytotoxicity against human cancer cells. RESULTS: gemcitabine and irinotecan were found to be readily degraded by the ozone treatment, and their active sites were suggested to be degraded. In contrast, paclitaxel was hard to be decomposed, possibly owing to the consumption of ozone by the polyoxyethylene castor oil added as a pharmaceutical additive of the formulation. No significant mutagenic changes of Salmonella typhimurium strains used for the Ames test were observed for the samples within the concentration ranges examined. The ozone treatment showed obvious increases in cell viability for gemcitabine formulation, and mild increases for irinotecan formulation. CONCLUSIONS: Ozone water was shown to be effective as a decomposition agent for the antineoplastic drug formulations examined, although the efficacy depends on the chemical structures of the drugs and the pharmaceutical additives. It was also suggested that ozone treatment has a tendency to decrease the toxicity of the antineoplastic drug formulations. As such, further studies are required in order to clarify the effects and application limitations of ozone water.

The knee position at tourniquet inflation does not affect the gap balancing during total knee arthroplasty.

INTRODUCTION: The relationship between gap balancing and clinical outcome of total knee arthroplasty (TKA) has been researched. Tourniquet is widely used by most surgeons; however, there are little quantitative data about the gap depending on the tourniquet usage. We aimed to investigate whether the knee position at tourniquet inflation affected the gap measurement intra-operatively. METHODS: TKA was performed for 104 knees and the tourniquet was inflated with the knee at full flexion and extension. The gap was measured in each static knee flexion status (0°, 30°, 45°, 60°, 90°, 120°, and in full flexion) using a tensor. We measured the gap twice; under the tourniquet inflation and release. The gap difference at each static knee flexion status was calculated by subtracting the gap under release from that under inflation. RESULTS: When the tourniquet was inflated with the knee at full flexion, the mean gap differences were < 1 mm and < 1° in each static knee flexion status. When the tourniquet was inflated with the knee at full extension, the mean gap differences were < 1 mm and < 1°, respectively. All values of the gap difference were minimum, and were not affected by the tourniquet, whether the knee position at the tourniquet inflation was flexed or extended. CONCLUSIONS: We postulated that the knee position at tourniquet inflation would affect the gap, which was refuted by our results. This shows that we can measure the gap without considering the knee position at tourniquet inflation.

Impact of urinary albumin excretion on the onset of adverse reactions to vancomycin hydrochloride.

OBJECTIVE: Vancomycin dose needs to be reduced for decreased kidney function; however, impact of urinary albumin excretion (UAE) on serum vancomycin level is unknown. In this study, we examined the factors associated with the onset of renal impairment induced by vancomycin by focusing on UAE. MATERIALS AND METHODS: The study included 52 patients who received vancomycin for methicillin-resistant Staphylococcus aureus at Ehime University Hospital between April 2010 and March 2015. To determine the presence of renal impairment, patients whose common terminology criteria for adverse-events (CTCAE) grade worsened by 1 or more comprised the renal impairment group, and multivariate logistic regression analysis was performed. RESULTS: 13 patients (25%) had renal impairment as indicated by a CTCAE grade change by 1 or more. The results of multivariate logistic regression analysis only of UAE (OR = 18.03; 95% CI = 1.97 - 164.89) was identified as a significant factor. CONCLUSION: We investigated the factors associated with the onset of renal impairment induced by vancomycin and identified UAE as a potential risk factor.

Patients with a quadriceps tendon shorter than 60 mm require a patellar bone plug autograft in anterior cruciate ligament reconstruction.

PURPOSE: To assess the length and thickness of the quadriceps tendon (QT) and anterior cruciate ligament (ACL) to predict the required QT length for individual ACL reconstruction. METHODS: Thirty patients (9 females, 21 males; mean age 24.5 years; mean height 169.3 cm) who underwent ACL reconstruction using the QT with a bone plug autograft were enrolled. The length and thickness of the QT on preoperative magnetic resonance imaging (MRI) were compared with those measured under direct visualization. The ACL length was measured on preoperative MRI and three-dimensional computed tomography after ACL reconstruction. The QT length on MRI was compared with the required graft length, and the factors related to an adequate QT length were assessed. RESULTS: The mean QT length on MRI was 60.8 ± 1.3 mm and was significantly positively correlated with the QT length under direct visualization (P < 0.01). On MRI, the mean ACL length was 30.8 ± 1.2 mm and the mean QT thickness was 6.3 ± 0.2 mm. Although the mean QT was 0.1 mm longer than the mean required graft length, the QT on MRI was shorter than the required graft length in 37% of patients (11/30). Adequate QT length was related to a QT length of more than 60 mm, but not to age, sex, height, or ACL length. CONCLUSION: Although preoperative MRI predicted the required QT length for ACL reconstruction, 37% of patients lacked an adequate QT length, and a QT shorter than 60 mm required the addition of patellar bone. LEVEL OF EVIDENCE: III.

Clinical effectiveness of switching between DPP-4 inhibitors in patients with type 2 diabetes mellitus
.

OBJECTIVES: Dipeptidyl peptidase-4 inhibitors (DPP-4Is) can be classified into three categories according to their binding subsites. We wished to clarify the efficacy of switching between DPP-4Is according to their binding subsites. MATERIALS AND METHODS: We undertook a retrospective study of the medical records of patients who switched from one DPP-4I to another. RESULTS: Among 62 patients eligible for study inclusion, the mean change in the glycated hemoglobin (HbA1c) level between different categories of DPP-4I was -0.35 (95% CI, -0.12 to -0.58; n = 59). The mean change in the HbA1c level between each class of DPP-4I was calculated. From class 3 to class 2 it was -0.45 (n = 25); from class 3 to class 1 it was -0.36 (n = 17); from class 1 to class 2 it was -0.24 (n = 7); from class 1 to class 3 it was 0.33 (n = 4); from class 2 to class 1 it was -0.30 (n = 5); from class 2 to class 3 it was -1.30 (n = 1). CONCLUSIONS: When switching DPP-4Is because of insufficient efficacy, consideration of their DPP-4 binding site may be beneficial.

Changes in postoperative extension angle after total knee arthroplasty: Effect of polyethylene insert thickness.

BACKGROUND: Flexion contracture is a serious complication after total knee arthroplasty (TKA). Polyethylene insert (PE) thicker than the extension gap during surgery causes flexion contracture. The purpose of this study was to identify the changes over time in postoperative extension angle and the correlation between extension gap and PE thickness. METHODS: Overall, 127 knees were analyzed to evaluate the changes in extension angle over time. "Gap difference" was defined as the distance obtained by subtracting the extension gap from the PE thickness. Patients were divided into four groups according to gap difference (0-3 or greater mm). We evaluated the correlation of gap difference and changes in postoperative extension angle over time. RESULTS: The extension angles of all knees were -4.2 ± 3.9 (deg. mean ± s.d.) at surgery, -5.9 ± 5.7 at 3 months, -3.4 ± 5.4 at 6 months, and -1.3 ± 5.4 at 2 years. Gap difference was negatively correlated with the extension angle at surgery and at 2 years (r = 0.40, r = 0.36). The extension angles at 2 years in each group (groups 0, 1, 2, 3 or greater) were 2.0°±4.7°, -0.8°±5.3°, -3.4°±5.3°, -4.0°±4.1° (p < 0.05), respectively. CONCLUSIONS: The extension angle became worse at 3 months compared to that at surgery (p = 0.01) and then improved until 2 years. The correlation between gap difference and extension angle was maintained at 2 years, and thicker PE caused flexion contracture even after 2 years. Hence, PE selection considering the extension gap is important.

Toward a unified understanding of drug-drug interactions: mapping Japanese drug codes to RxNorm concepts.

OBJECTIVES: Linking information on Japanese pharmaceutical products to global knowledge bases (KBs) would enhance international collaborative research and yield valuable insights. However, public access to mappings of Japanese pharmaceutical products that use international controlled vocabularies remains limited. This study mapped YJ codes to RxNorm ingredient classes, providing new insights by comparing Japanese and international drug-drug interaction (DDI) information using a case study methodology. MATERIALS AND METHODS: Tables linking YJ codes to RxNorm concepts were created using the application programming interfaces of the Kyoto Encyclopedia of Genes and Genomes and the National Library of Medicine. A comparative analysis of Japanese and international DDI information was thus performed by linking to an international DDI KB. RESULTS: There was limited agreement between the Japanese and international DDI severity classifications. Cross-tabulation of Japanese and international DDIs by severity showed that 213 combinations classified as serious DDIs by an international KB were missing from the Japanese DDI information. DISCUSSION: It is desirable that efforts be undertaken to standardize international criteria for DDIs to ensure consistency in the classification of their severity. CONCLUSION: The classification of DDI severity remains highly variable. It is imperative to augment the repository of critical DDI information, which would revalidate the utility of fostering collaborations with global KBs.

Medical Economic Effect of Pharmaceutical Interventions by Board-Certified Pharmacists in Palliative Pharmacy for Patients with Cancer Using Medical Narcotics in Japan: A Multicenter, Retrospective Study.

BACKGROUND: The Japanese Society for Pharmaceutical Palliative Care and Sciences specializes in pharmacology in the field of palliative medicine. More than 700 board-certified pharmacists in palliative pharmacy (BCPPP) are actively involved in palliative pharmacotherapy at various hospitals and pharmacies. The purpose of this study was to determine the economic effect of pharmaceutical interventions by BCPPPs. METHODS: This multicenter retrospective study included 27 medical centers and analyzed the medical economic effect of interventions by BCPPPs (17 pharmacists) and non-BCPPPs (24 pharmacists) on patients using medical narcotics for cancer pain in September 2021. RESULTS: The percentage of patients who received a pharmaceutical intervention and whose drug costs were reduced by pharmacist intervention was significantly higher in the BCPPP group than in the non-BCPPP group. Although there was no significant difference between the two groups in drug cost reduction per patient per month (BCPPP group: $0.89 [-$64.91 to $106.76] vs. non-BCPPP group $0.00 [-$1,828.95 to $25.82]; P = 0.730), the medical economic benefit of pharmacist intervention in avoiding or reducing adverse drug reactions was higher in the BCPPP group ($103.18 [$0.00 to $628.03]) than in the non-BCPPP group ($0.00 [$0.00 to $628.03]) (P = 0.070). The total medical economic benefit-the sum of these-was significantly higher in the BCPPP group ($88.82 [-$14.62 to $705.37]) than in the non-BCPPP group ($0.66 [-$1,200.93 to $269.61]) (P = 0.006). CONCLUSION: Pharmacological intervention for patients with cancer using medical narcotics may have a greater medical economic benefit when managed by BCPPPs than by non-certified pharmacists in Japan.

Diagnostic imaging for elbow TRASH lesions in children and usefulness of ultrasonography using standard planes.

Fractures around the elbow in children should be carefully evaluated because the main portion is cartilaginous, and radiographs are not completely reliable. This study aimed to assess the diagnostic imaging for pediatric elbow fractures that require special attention and consider the usefulness of ultrasonography with seven standard planes for the diagnosis. Patients diagnosed with elbow fractures wherein TRASH (The Radiographic Appearance Seemed Harmless) lesions were evaluated retrospectively. The diagnoses on initial radiographs, final diagnoses, additional imaging excluding radiographs, and the treatments were investigated. The standard planes for ultrasonography to detect elbow fractures included an anterior transverse scan at the level of the capitellum and proximal radioulnar joint, an anterior longitudinal scan at the level of the humeroradial and humeroulnar joints, a longitudinal scan along the lateral and medial border of the distal humerus, and a posterior longitudinal scan at the level of the distal humerus. A total of 107 patients with an average age of 5.8 years (range, 0-12 years) at the time of diagnosis were included. Of 46 (43.0%) patients misdiagnosed at the initial radiograph, 19 (17.8%) needed additional treatments due to inappropriate initial management. Ultrasonography using the standard planes was useful for prompt diagnosis and appropriate treatment. Prompt and appropriate evaluation with ultrasonography can prevent the mismanagement of pediatric elbow injuries. Level of evidence: Level IV-retrospective case series.

Lifestyle and body composition changes in patients with rheumatoid arthritis during the COVID-19 pandemic: A retrospective, observational study.

Objectives: Behavioral restrictions and staying at home during the COVID-19 pandemic have affected lifestyles. It was hypothesized that patients with rheumatoid arthritis (RA) decreased their activities of daily living (ADL) and exercise during the pandemic. The aim of this study is to investigate the changes in lifestyle and body composition. Methods: Data were obtained from an observational study (CHIKARA study). Of 100 RA patients, 70 (57 women, 13 men) were followed-up with measurements of grip strength, as well as muscle mass, fat mass, and basal metabolic rate by a body composition analyzer. Changes in ADL and exercise were evaluated using a visual analog scale. The relationships between changes in ADL or exercise and body composition were investigated. Results: Muscle mass and grip strength were significantly lower after behavioral restrictions compared to the periods before restrictions (34.0 vs 34.7 kg, P < 0.001; 16.2 vs 17.2 kg, P = 0.013, respectively). Fat mass was significantly greater after behavioral restrictions compared to the periods before restrictions (16.2 vs 15.5 kg, P = 0.014). The mean decrease in ADL was 44%, whereas that of exercise was 20%.The change in muscle mass (ß = -0.335, P = 0.007) was the only independent factor for the change in exercise on multivariate analysis. Conclusions: Muscle mass and grip strength decreased and fat mass increased in RA patients with the behavioral restrictions of the COVID-19 pandemic. Muscle mass decreased in patients without exercise. Maintenance of muscle mass may be important during the COVID-19 pandemic.

A study on the chemical stability of cholesterol-lowering drugs in concomitant simple suspensions with magnesium oxide.

BACKGROUND: Difficulty in taking solid medicines is a common issue particularly for the elderly because of a decline in swallowing function, also known as dysphagia. For patients with such a dysfunction, a simple suspension method, in which solid medicines are disintegrated and suspended using warm water, has been developed and widely used in Japanese clinical settings. However, there is little information on drug stability in the simple co-suspension of multiple formulations especially including acidic or alkaline ones. In this study, the chemical stability of typical cholesterol-lowering drugs was investigated in a simple co-suspension with alkaline magnesium oxide (MgO) which is frequently used as a laxative or antacid in Japan. METHODS: A cholesterol-lowering drug (one tablet) was soaked with or without MgO in warm water (55°C), and the vessel was left at room temperature for 10 min or 5 h. The suspensions prepared were then analyzed by high-performance liquid chromatography. Degradation products were analyzed by nuclear magnetic resonance spectroscopy and mass spectrometry for the structural elucidation. RESULTS: In the simple co-suspension with MgO, no significant degradation was observed for atorvastatin or pravastatin, while a significant decrease of the recovery from the co-suspension was observed for rosuvastatin after 5 h. On the other hand, simvastatin and ezetimibe co-suspended with MgO were partially degraded to simvastatin acid and a pyran compound, respectively. CONCLUSIONS: A simple co-suspension with MgO is feasible for atorvastatin, pravastatin, and rosuvastatin, although the rosuvastatin tablet should not be left soaking for a long time. Further it is inadvisable to suspend simvastatin or ezetimibe together with MgO because of their partial degradation.

Study on the Use of Ozone Water as a Chemical Decontamination Agent for Antineoplastic Drugs in Clinical Settings.

The exposure of healthcare workers to antineoplastic drugs in hospitals has been recognized to be harmful. To minimize the risk of exposure, the removal of these drugs from work environments, such as compounding facilities, has been recommended. In our previous paper, the degradation and inactivation efficacy of ozone water, which is being introduced into Japanese hospitals as a chemical decontamination agent, was reported for its effects on typical antineoplastic drugs (gemcitabine, irinotecan, paclitaxel). This article aims to further investigate the efficacy of ozone water for eight antineoplastic drugs to clarify its application limitations. A small amount (medicinal ingredient: typically ca. 1.5 µmol) of formulation containing 5-fluorouracil, pemetrexed, cisplatin, oxaliplatin, cyclophosphamide, ifosfamide, doxorubicin, or docetaxel was mixed with 50 mL of ozone water (~8 mg/L), and the resulting solutions were analyzed by high-performance liquid chromatography over time to observe the degradation. Consequently, the ozonation was overall effective for the degradation of the drugs, however this varied depending on the chemical structures of the drugs and additives in their formulations. In addition, after the parent drugs were completely degraded by the ozonation, the degradation mixtures were subjected to 1H nuclear magnetic resonance spectroscopy and evaluated for mutagenicity against Salmonella typhimurium strains and cytotoxicity against human cancer cells. The degradation mixtures of cisplatin and ifosfamide were mutagenic while those of the other drugs were non-mutagenic. Further, the ozonation resulted in clear decreases of cytotoxicity for 5-fluorouracil, oxaliplatin, and doxorubicin, but increases of cytotoxicity for pemetrexed, cisplatin, cyclophosphamide, and ifosfamide. These results suggest that the ozone water should be restrictedly used according to the situation of contamination in clinical settings because the ozonation enhances toxicity depending on the drug even if degradation is achieved.