Population pharmacokinetics and pharmacodynamic target attainment analysis of cefazolin using total and unbound serum concentration in patients with prostatectomy or nephrectomy.

The aim of this study was to analyze the population pharmacokinetics of total and unbound concentrations of prophylactic cefazolin (CFZ) in patients with prostatectomy or nephrectomy. We also aimed to calculate a pharmacodynamics target unbound concentration that exceeded the minimum inhibitory concentration (MIC), to design an effective dosing regimen. Briefly, 614 total concentration and 610 unbound concentration samples from 152 individuals were evaluated, using a nonlinear mixed-effects model. The obtained pharmacodynamics index target value reflected the probability of maintaining CFZ unbound trough concentrations exceeding MIC90, 0.5 mg/L, and MIC50, and 1.0 mg/L, to account for methicillin-susceptible Staphylococcus aureus (MSSA) or Escherichia coli. Population pharmacokinetics were estimated using a two-compartment model with nonlinear protein binding. Unbound systemic clearance (CL) was significantly associated with creatinine clearance, while the maximum protein-binding constant was significantly associated with albumin levels. The probability of achieving an unbound concentration exceeding the MIC50 for E. coli or MIC90 for MSSA in a patient with normal renal function following a 1 g CFZ infusion over 15 min was above 90% at 3 h after the initial dose. Our findings indicated that population pharmacokinetic parameters are useful for determining unbound CFZ pharmacokinetics and evaluating intraoperative CFZ redosing intervals.

Comparing the Efficacy of Fosnetupitant, an NK1 Receptor Antagonist in CDDP-Based Regimens, with That of Fosaprepitant and Aprepitant: A Retrospective Observational Study.

Existing antiemetic therapy against emetic-risk agents across malignancies 24 h post-dose in the acute period in cisplatin (CDDP)-based regimens yields a satisfactory complete response (CR) rate of ≥90%. However, the control rate after 24 h in the delayed period is unsatisfactory. This study compared the efficacy of fosnetupitant (F-NTP), a neurokinin 1 receptor antagonist, with that of fosaprepitant (F-APR) and aprepitant (APR) in the treatment of patients with cancer at high emetic risk due to chemotherapy. In this retrospective case-control study involving patients receiving cisplatin-containing regimens and neurokinin 1 receptor antagonists, patients were divided into three groups based on prophylactic antiemetic therapy: F-NTP, F-APR, and APR. The CR rate was evaluated for each period up to 168 h and further subdivided into acute (0-24 h), delayed (24-120 h), overall (0-120 h), and beyond-delayed (120-168 h) periods. Eighty-eight patients were included in the F-NTP group, 66 in the F-APR group, and 268 in the APR group. The CR rates at 0-168 and 120-168 h after cisplatin administration were significantly higher in the F-NTP group than in the F-APR and APR groups. After adjusting for confounding factors, F-NTP use was an independent factor in the multivariate analysis. Prophylactic antiemetic therapy, including F-NTP, was effective and well-tolerated during the delayed period. The efficacy of F-NTP in managing chemotherapy-induced nausea and vomiting was superior to those of F-APR and APR during the study period.

Association between ratio of area under the concentration-time curve to minimum inhibitory concentration of vancomycin and clinical outcomes in Enterococcus faecium bacteremia.

The purpose of this study was to evaluate the relationship between the treatment resolution of Enterococcus faecium bacteremia and the pharmacodynamic targets of vancomycin. This is a retrospective single-center cohort study involving patients with E. faecium bacteremia on vancomycin therapy hospitalized between January 2010 and December 2021. The average vancomycin area under the concentration-time curve (AUC)0 -24 was computed using the Bayesian approach. The minimum inhibitory concentration (MIC) was determined using the broth microdilution method, and The AUC24/MIC value over the initial 24-48 h of therapy was calculated. We assessed 30-day mortality, as the primary outcome. Classification and regression tree analysis (CART) was used to identify the vancomycin AUC24/MIC target associated with 30-day mortality. Eighty-seven patients with E. faecium bacteremia were included in this study, with 14 (16.1%) being non-survivors. In the CART analysis, vancomycin AUC/MIC ≥414.3 was associated with a higher treatment success. In multivariate analysis, an AUC/MIC ≥414.3 was a significant factor for treatment success (adjusted odds ratio = 17.5, 95% confidence interval, 3.7-83.9). Our findings suggest that a target vancomycin AUC/MIC ≥414.3 is a good prognostic indicator and could be useful for treatment monitoring of E. faecium bacteremia.

Risk analysis of COVID-19 hospitalization and critical care by race and region in the United States: a cohort study.

BACKGROUND: This study aimed to identify the current risk factors for coronavirus disease 2019 severity and examine its association with medication use. METHODS: We used data from a large United States electronic health record database to conduct an anonymized cohort study of 171,491 patients with coronavirus disease 2019. The study was conducted from January 1, 2020, to August 27, 2021. Data on age, race, sex, history of diseases, and history of medication prescriptions were analyzed using the Cox proportional hazards model analysis to calculate hazard ratios for hospitalization and severe risk. RESULTS: Factors that increased the risk of hospitalization and critical care were age ≥ 65 years, male sex, type 2 diabetes, hypertension, interstitial pneumonia, and cardiovascular disease. In particular, age ≥ 65 years significantly increased the risk of hospitalization (hazard ratio, 2.81 [95% confidence interval, 2.58-3.07]; P < 0.001) and critical care (hazard ratio, 3.45 [2.88-4.14]; P < 0.001). In contrast, patients with hyperlipidemia had a reduced risk. However, patients with hyperlipidemia who were not taking statins had a significantly increased risk of hospitalization (hazard ratio, 1.24 [1.16-1.34]; P < 0.001). Sodium-glucose cotransporter-2 inhibitors, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, glucocorticoids, and statins significantly reduced the risk of hospitalization and critical care. The risk of hospitalization and critical care increased in patients of all ethnicities with type 2 diabetes. The factors that significantly increased the risk of hospitalization in all regions were older age, hypertension, chronic obstructive pulmonary disease, and cardiovascular disease. CONCLUSION: This study identified factors that increase or reduce the risk of severe coronavirus disease. The provision of appropriate drug treatment and modification of lifestyle-related risk factors may reduce coronavirus disease severity.

Investigating effective methods of clinical pharmacy training on oncology for community pharmacists: An observational study.

INTRODUCTION: Kitasato University Hospital offers a training course for community pharmacists that focus on advanced pharmacy management care in outpatient cancer chemotherapy. The objective of this training program is to facilitate the transition from general to oncology certification for community pharmacists with limited experience in outpatient oncology to support the acquisition of an oncology specialty. AIM: To evaluate the relationship between the changes in awareness, knowledge, and self-assessment that advanced pharmacy management care traineeship in an outpatient oncology unit for community pharmacists brings to trainees and the duration of training. METHODS: A quantitative text analysis was conducted of the daily training reports of six community pharmacists who had participated previously in the training course and had received in-service training in oncology for at least 30 days. The pre- and post-training results of the knowledge tests and self-assessments of confidence, understanding, and performance were compared. This study was approved by the Research Ethics Committee of Kitasato Institute Hospital in October 2019 (Study No. 19044). RESULTS: The terms Prescription, Recommendation were extracted from the daily report after the 21st day of oncology in-service training. Furthermore, factors such as knowledge of cancer pharmacotherapy, confidence in patient education regarding the side effects of chemotherapy, and understanding of the work of pharmacists in outpatient cancer chemotherapy significantly increased at the end of the training. CONCLUSIONS: Community pharmacists with limited experience in outpatient oncology could improve their knowledge, understanding, and awareness of outpatient oncology patient care through 30 days of in-service oncology training in a hospital setting. The issues that emerged included training pharmacists to send follow-up documents on the patients' side effects and medication status as well as developing the literature search environment in community pharmacies.

Long-term prediction of hepatocellular carcinoma using serum autotaxin levels after antiviral therapy for hepatitis C.

INTRODUCTION AND OBJECTIVES: Continuous monitoring for hepatocellular carcinoma is necessary following treatment with direct-acting antivirals in patients with hepatitis C virus infection. We investigated whether the long-term follow-up of serum autotaxin levels could predict the development of hepatocellular carcinoma. PATIENTS AND METHODS: This prospective observational study enrolled adult patients with chronic hepatitis C virus infection who presented to the study center from January 2016 to March 2021. Among the patients who achieved a sustained viral response, the relationship between the development of hepatocellular carcinoma and serum autotaxin levels was assessed before treatment with direct-acting antivirals; at the end of therapy; at 12 and 24 weeks; and at 12, 24, 36, and 48 months after treatment. RESULTS: Data were analyzed for 139 patients. Thirteen patients developed hepatocellular carcinoma 48 months after treatment. The cut-off serum autotaxin values that predicted hepatocellular carcinoma after 24 weeks were 1.22 (men) and 1.92 (women) mg/L. The area under the curve for serum autotaxin was 0.83 (95% confidence interval [CI]:0.71-0.95) in men and 0.90 (95% CI: 0.82-0.99) in women. The positive predictive value of serum autotaxin was 0.208 (95% CI: 0.139-0.248), and the negative predictive value was 0.971 (95% CI: 0.939-0.990). The cumulative incidence of hepatocellular carcinoma was significantly higher when serum autotaxin levels were above the cut-off value after 24 weeks (p < 0.0001). CONCLUSIONS: Serum autotaxin is a candidate biomarker for predicting hepatocellular carcinoma during the long-term follow-up of patients with a sustained viral response following treatment with direct-acting antivirals.

Tolerability of Erythrocyte Ribavirin Triphosphate Concentrations Depends on the ITPA Genotype.

BACKGROUND: Ribavirin (RBV) is an antiviral drug that is part of the current standard therapy for chronic hepatitis C (CHC). It is enzymatically converted to ribavirin triphosphate (RTP) that inhibits the activity of viral RNA polymerase, thereby preventing viral replication. However, one of its adverse effects includes hemolytic anemia that limits its application. The variant of ITPA (inosine triphosphatase), which dephosphorylates inosine triphosphate to inosine monophosphate, is a protective factor for RBV-induced anemia. RTP is an important metabolite required for ribavirin action. This study evaluated the time-dependent association of RTP concentrations in erythrocytes, RBV-induced toxicity, and virological response to RBV treatment for hepatitis C. METHODS: A total of 28 Japanese patients with CHC were treated with RBV/peg-interferon/simeprevir or RBV/sofosbuvir and were genotyped for ITPA variants (rs1127354 and rs7270101). We measured RTP concentrations in erythrocytes in a total of 76 samples collected at 4, 8, and 12 weeks from the initiation of treatment. RESULTS: The ITPA rs1127354 variant was found in 7 patients. This was associated with significantly higher RTP concentrations in erythrocytes than in the wild-type patients (P < 0.001). Moreover, a significant correlation was observed between RTP concentrations and decline in hemoglobin (Hb) levels from baseline values in ITPA wild type and rs1127354 variant 12 weeks after treatment initiation (P < 0.01; r = -0.618 and -0.967, respectively). Multiple regression analysis revealed that ITPA genotype and erythrocyte RTP concentrations were major factors associated with reduced Hb levels in RBV therapy for CHC. However, we did not find any association between erythrocyte concentrations and virological response. CONCLUSIONS: The increased tolerability to RTP concentrations in erythrocytes in the ITPA variant rs1127354 plays a role in preventing RBV-induced severe anemia in this ITPA variant.

Evaluation of Measures against Exposure during Administration of Hazardous Drugs through a Feeding Tube.

Hazardous drugs (HD), which need to be handled with care, may be administered through a feeding tube using the simple suspension method. However, instrument contamination during HD administration with the simple suspension method remains unclear. Therefore, to minimize such contamination during the simple suspension method using an injector, we propose the following exposure countermeasures method: (1) Wear two layers of gloves. (2) Prepare injectors for administration and flushing. (3) Use caps. (4) Replace outer gloves after the removal of tablets from the press-through package (PTP) sheet. (5) Handle drugs on a tray. (6) Inject while wrapping the connection site between the injector for administration and the tube with gauze. (7) Wrap the connection site between the injector and tube with gauze. (8) Do not point the injector downward. To establish whether these countermeasures method are effective, 16 ward nurses who routinely administer drugs via a feeding tube were enrolled as subjects. By visual evaluation, we compared differences in instrument contamination between a suspension using a medicine cup and administration via a feeding tube (the conventional method) and the exposure countermeasures method. Exposure with the countermeasures method under our instruction was markedly lower than that with the conventional method. Furthermore, after implementing the exposure countermeasures method, most nurses noted that caution and awareness of exposure countermeasures increased. Thus, to minimize exposure, we recommend the implementation of the exposure countermeasures method and increasing knowledge and awareness of measures against exposure.

Risk Factors for Non-Adherence to Pharmacist or Non-Pharmacist Explanations on Preoperative Medication Discontinuation: A Retrospective Japanese Study.

Purpose: The risk factors for non-adherence to pharmacist or non-pharmacist explanations of preoperative medication discontinuation are unknown. The primary outcome of this study was to determine whether the final explainer's occupation was a risk factor for non-adherence. The secondary outcomes were to determine the risk factors for non-adherence after limiting the departments or adjusting for age. Patients and Methods: We retrospectively examined the data (including patient age, sex, prescription medications, comorbidities, presence of roommate, and number of days between receiving explanation and surgery) of 1132 patients on medications that could affect surgery at a Japanese university hospital between April 1, 2017, and March 31, 2020. The primary endpoint was whether the occupation of the last person explaining medication discontinuation to the patient was an independent risk factor for non-adherence (age ≥65 years vs <65 years). Secondary endpoints included subgroup analyses in urological, gastrointestinal, and otolaryngological areas, as well as a sensitivity analysis (age as a continuous variable) to confirm the validity of the primary endpoint results. A multivariate binary logistic regression identified independent non-adherence risk factors. Results: The main analysis showed that discontinuing two or more medications was a risk factor for non-adherence (adjusted odds ratio (AOR): 1.67; 95% confidence interval (CI): 1.13-2.47; p = 0.01). However, in analyses coordinated by department (urological, gastrointestinal, and otolaryngological), ≥65 (versus <65) years of age was determined as a risk factor for increased nonadherence (AOR: 2.27, 95% CI: 1.11-4.63; p=0.024). Age-adjusted analysis (continuous variables) showed similar results to the primary endpoint (AOR: 1.68, 95% CI: 1.14-2.49, p = 0.009). Conclusion: Two or more medications, and not the final explainer's occupation, were associated with pre-surgery medication non-adherence. To prevent non-adherence, pharmacists and non-pharmacists should educate patients about preoperative medication discontinuation. These findings could help identify high-risk non-adherence patients.

Frequency of missed doses and its effects on the regulation of glucose levels in patients with type 2 diabetes: A retrospective analysis.

This study aimed to investigate the association between medication adherence to oral hypoglycemic agents (OHAs) and HbA1c levels in patients with type 2 diabetes mellitus (T2DM) for more than 48 weeks, as well as the factors affecting long-term adherence to OHAs. This retrospective study included 83 patients who had been receiving OHAs for T2DM for ≥48 weeks. Medication adherence values (MAVs) were calculated using the following formula: (total prescription days - prescription days of OHAs brought at admission)/(days from the initiation of OHAs to hospitalization). We assessed the association between HbA1c and MAVs using the Jonckheere-Terpstra test. Furthermore, we examined the association between patient- and medication-related factors and MAVs affecting HbA1c levels. Based on the results, MAVs were categorized as MAV ≤0.86 and MAV >0.86, and factors affecting MAVs were analyzed. Logistic regression analysis revealed that the total number of medications, the number of nonhypoglycemic agents, and a family history of diabetes were independent determinants of MAV ≤0.86 (P < .05). Multiple regression analyses indicated that the number of dosages per day and the timing of OHA administration at lunch were independent determinants of lower MAVs (P < .05). Our findings suggest that poor medication adherence is associated with elevated HbA1c levels in T2DM patients. Independent factors contributing to poor adherence include a lower number of prescribed medications, fewer nonhypoglycemic agents, no family history, a higher daily dosage frequency, and the administration of OHAs at lunch.

Matrix metalloproteinase­1 and microRNA­486­5p in urinary exosomes can be used to detect early lung cancer: A preliminary report.

The present study describes a novel molecular-genetic method suitable for lung cancer (LC) screening in the work-place and at community health centers. Using urinary-isolated exosomes from 35 patients with LC and 40 healthy volunteers, the expression ratio of MMP-1/CD63, and the relative expression levels of both microRNA (miRNA)-21 and miRNA-486-5p were measured. MMP-1/CD63 expression ratio was significantly higher in patients with LC than in the healthy controls {1.342 [95% confidence interval (CI): 0.890-1.974] vs. 0.600 (0.490-0.900); P<0.0001}. The relative expression of miRNA-486-5p in male healthy controls was significantly different from that in female healthy controls, whereas there was no significant difference in miRNA-21. Receiver operating characteristic curve (ROC) analysis of MMP-1/CD63 showed 92.5% sensitivity and 54.3% specificity, whereas miRNA-486-5p showed 85% sensitivity and 70.8% specificity for men, and 70.0% sensitivity and 72.7% specificity for women. The logistic regression model used to evaluate the association of LC with the combination of MMP-1/CD63 and miRNA-486-5p revealed that the area under the ROC curve was 0.954 (95% CI: 0.908-1.000), and the model had 89% sensitivity and 88% specificity after adjusting for age, sex and smoking status. These data suggested that the combined analysis of MMP-1/CD63 and miRNA-486-5p in urinary exosomes may be used to detect patients with early-stage LC in the work-place and at community health centers, although confirmational studies are warranted.

Efficacy of the bleeding risk scoring system for optimal prophylactic anticoagulation therapy of venous thromboembolism in trauma patients: a single-center, retrospective, observational cohort study.

BACKGROUND: We developed a bleeding risk scoring system (BRSS) using prophylactic anticoagulation therapy to comprehensively assess the risk of venous thromboembolism (VTE) in trauma patients. This study evaluated the usefulness of this system in trauma patients, with a focus on minimizing the rate of bleeding events associated with prophylactic anticoagulation therapy. METHODS: We retrospectively evaluated the efficacy of BRSS in trauma patients who received prophylactic anticoagulation therapy for VTE at the Kitasato University Hospital Emergency and Critical Care Center between April 1, 2015, and August 31, 2020. To compare the incidence of bleeding events, patients were divided into two groups: one group using the BRSS (BRSS group) and another group not using the BRSS (non-BRSS group). RESULTS: A total of 94 patients were enrolled in this study, with 70 and 24 patients assigned to the non-BRSS and BRSS groups, respectively. The major bleeding event rates were not significantly different between the two groups (BRSS group, 4.2%; non-BRSS group, 5.7%; p = 1.000). However, minor bleeding events were significantly reduced in the BRSS group (4.2% vs.27.1%; p = 0.020). Multivariate logistic regression analysis showed that BRSS was not an independent influencing factor of major bleeding events (odds ratio, 0.660; 95% confidence interval: 0.067-6.47; p = 0.721). Multivariate logistic regression analysis showed that BRSS was an independent influencing factor of minor bleeding events (odds ratio, 0.119; 95% confidence interval: 0.015-0.97; p = 0.047). The incidence of VTE did not differ significantly between groups (BRSS group, 4.2%; non-BRSS group, 8.6%; p = 0.674). CONCLUSIONS: BRSS may be a useful tool for reducing the incidence of minor bleeding events during the initial prophylactic anticoagulation therapy in trauma patients. There are several limitations of this study that need to be addressed in future research.

[Significant Prolongation of the International Normalized Ratio Associated with COVID-19 Treatment: Possible Drug Interaction with Remdesivir].

A 55-year-old man with hypertrophic cardiomyopathy and a pacemaker was admitted with coronavirus disease 2019 (COVID-19). Before admission, the patient's medications included amiodarone, diltiazem, bisoprolol, atorvastatin, etizolam, and warfarin (WF). After admission, dexamethasone (DXM) and remdesivir (RDV) were initiated for treating COVID-19. The international normalized ratio (INR) on admission was 1.8, which increased to 3.4 on day 5 and to 6.9 on day 10 after admission. Although there have been reports that RDV may occasionally prolong prothrombin time and that the degree of prolongation is often less severe, the mechanism of action has not been elucidated till date. There are reports of prolonged INR when WF is co-administered with RDV and DXM, suggesting that drug interactions may be a potential cause for the prolongation. A similar drug interaction may have potentially occurred in the case reported here. In addition, this case used amiodarone (AMD), and it has been reported that the RDV concentration increases when used in combination with AMD. Further investigations are needed to elucidate the cause of INR prolongation. Thus, close monitoring of the patient is recommended when RDV is co-administered with high-risk agents to avoid unnecessary side effects.

Smoking cessation in the elderly as a sign of susceptibility to symptomatic COVID-19 reinfection in the United States.

Background: We aimed to clarify the relationship between coronavirus disease 2019 (COVID-19) reinfection and basic disease and smoking status. Methods: The electronic health records of 165,320 patients with COVID-19 from January 1, 2020, to August 27, 2021, were analyzed. Data on age, race, sex, smoking status (never, current, former), and basic disease were analyzed using Cox proportional hazard models. Results: In total, 6,133 patients (3.7%) were reinfected. The overall reinfection rate for never, current, and former smokers was 4.2, 3.5, and 5.7%, respectively. Although the risk of reinfection was highest among former smokers aged ≥65 years (7.7% [422/5,460]), the reinfection rate among current smokers aged ≥65 years was 6.2% (341/5,543). Among reinfected patients, the number of basic diseases was higher in former smokers (2.41 ± 1.16) than in current (2.28 ± 1.07, P = 0.07) and never smokers (2.07 ± 1.05, P < 0.001). Former smokers who are older may have been exposed to factors that increase their risk of symptomatic COVID-19 reinfection.

[Two Cases at Community Pharmacies of Mercaptopurine Removal from a Disk-type Powder-packaging Machine by Wiping It with Water].

"Leukerin® powder 10%" containing mercaptopurine (6-MP) is an oral anticancer drug that requires careful handling. As a powder formulation, there are risks of exposure due to scattering during dispensing and possible 6-MP contamination to other drugs due to adhesion to the packaging machine. We previously reported that wiping with an alcohol-containing towel is useful for removing scattered powder after dispensing. However, it is recommended to wipe disk-type powder-packaging machines with water instead of cleaning with the alcohol-containing towel. Hence, we scattered 6-MP powder 100 mg (total amount of 6-MP: 10 mg), and then wiped with water three times using different types of cloth each time. We confirmed that third time wiping cloth did not have any 6-MP. Furthermore, we confirmed that the adhering 6-MP could be removed by wipe-cleaning (water-wiping twice and dry-wiping once) after dispensing 6-MP powder at two pharmacies that routinely dispensed 6-MP powder using a disk-type powder-packaging machine. In addition, we confirmed the adhesion of 6-MP in parts of the machine not cleaned by wipe-cleaning and also in parts that were washed only with water, in both the pharmacies. Based on the above observations, we recommend the following steps for cleaning disk-type powder-packaging machines after dispensing 6-MP powder: (1) wipe-cleaning that includes water-wiping twice and then dry-wiping once, (2) cleaning all areas of the packaging machine, and (3) wipe-cleaning with water before washing with water.

Pill Counting in the Determination of Factors Affecting Medication Adherence in Patients with Type 2 Diabetes: A Retrospective Observational Study.

INTRODUCTION: For medication adherence, pill counting has higher accuracy in objective assessment. However, previous reports have shown that factors such as psychological bias and other people's involvement in managing and helping patients take their medications may influence the outcomes. In Japan, all prescription medicines of patients are checked by medical reconciliation, and a pill count is performed during hospitalization. This study investigated factors affecting the medication adherence of patients with type 2 diabetes mellitus (T2DM), including patient- and medication-related factors, by pill counting using medical reconciliation in a situation where the patient's psychological bias is low. METHODS: This study included 103 patients with T2DM who had been treated with oral hypoglycemic agents (OHAs) for at least 24 weeks. Patients whose OHAs were managed by another person were excluded. We calculated medication adherence values (MAVs) according to the following formula: MAV = (total prescription days - prescription days of OHAs brought when admitted)/(days from the start of OHAs to hospitalization). The relationship between MAVs and patient- and medication-related factors was analyzed. RESULTS: On multiple linear regression analysis of patient-related factors with P < 0.10 in the univariate analysis as explanatory variables, a lower number of chronic diseases (ß = 0.017; P < 0.001) and higher number of OHAs (ß = - 0.021; P = 0.04) were independent factors for lower MAV. Medication-related factors were not found to be independent factors. CONCLUSIONS: Our findings suggest that poor adherence was independently associated with lower number of chronic diseases and higher number of OHAs in patients with T2DM.

Impact of overlapping risks of type 2 diabetes and obesity on coronavirus disease severity in the United States.

The impact of overlapping risk factors on coronavirus disease (COVID-19) severity is unclear. To evaluate the impact of type 2 diabetes (T2D) and obesity on COVID-19 severity, we conducted a cohort study with 28,095 anonymized COVID-19 patients using data from the COVID-19 Research Database from January 1, 2020 to November 30, 2020. The mean age was 50.8 ± 17.5 years, and 11,802 (42%) patients were male. Data on age, race, sex, T2D complications, antidiabetic medication prescription, and body mass index ≥ 30 kg/m2 (obesity) were analysed using Cox proportional hazard models, with hospitalization risk and critical care within 30 days of COVID-19 diagnosis as the main outcomes. The risk scores were 0-4 for age ≥ 65 years, male sex, T2D, and obesity. Among the participants, 11,294 (61.9%) had obesity, and 4445 (15.8%) had T2D. T2D, obesity, and male sex were significantly associated with COVID-19 hospitalization risk. Regarding hospitalization risk scores, compared with those for hospitalization risk score 0 and critical care risk score 0, hazard ratios [95% confidence intervals] were 19.034 [10.470-34.600] and 55.803 [12.761-244.015] (P < 0.001) (P < 0.001), respectively, for risk score 4. Complications from diabetes and obesity increased hospitalization and critical care risks for COVID-19 patients.

[Safe Handling Method for Splitting Azathioprine Tablets].

The immunosuppressant azathioprine (AZA) is classified as a hazardous drug. AZA contamination during tablet-splitting increases exposure risk. However, there is no study on contamination and exposure during AZA tablet splitting and dispensing. AZA tablet splitting and dispensing methods were classified based on whether tweezers are used during splitting and packaging. In Dispensing Method (1), no tweezers were used in either step. In Dispensing Method (2), no tweezers were used during tablet splitting, but were used during packaging. In Dispensing Method (3), tweezers were used in both steps. After AZA half-tablet split-dispensing, we quantified the adherent AZA removed from the tools, packaging machines, and dispensing counters by three consecutive wipings with water-dampened polypropylene cloths. A large amount of AZA adhered to the gloves used in Dispensing Methods (1) and (2), wherein tablets were placed with gloved hands, compared with Dispensing Method (3), wherein tablets were held with tweezers. Thus, the gloves must be replaced before touching the packaging paper during the final step. After three consecutive wipings, AZA was not detected at most of the sites in the third round. Thus, we recommend that (1) AZA tablet splitting should be performed while wearing gloves, (2) the gloves should be changed before packaging the half tablets, and (3) the tools, packaging machines, and dispensing counters should be wiped twice or thrice with a water-dampened cloth after dispensing.

Mixture of clopidogrel bisulfate and magnesium oxide tablets reduces clopidogrel dose administered through a feeding tube.

BACKGROUND: In clinical practice, a mixed suspension of clopidogrel bisulfate and magnesium oxide (MgO) tablets is administered frequently via a feeding tube. However, there is no report on the changes occurring when suspensions of these two drugs are combined, including the effects or potential decrease in dose following tube administration. Thus, the purpose of our study was to investigate the (i) changes caused by mixing clopidogrel bisulfate (ion form) and MgO tablets and (ii) effects on the administered clopidogrel dose after passing through a feeding tube. METHODS: The molecular structure of clopidogrel generated in a mixture of clopidogrel bisulfate and a basic compound, such as sodium bicarbonate or MgO tablet, was determined by 1H-NMR after extraction and purification. The suspension of clopidogrel bisulfate tablet alone and the mixed suspension of clopidogrel bisulfate tablet and MgO tablet were passed through a feeding tube. We compared the yield of the molecular form of clopidogrel from each passed fraction. RESULTS: The substance obtained from the mixture of clopidogrel bisulfate tablet and sodium bicarbonate or MgO tablet was identified as the molecular form of clopidogrel, and chemical degradation did not occur under these conditions. In the tube passage test, the yield of clopidogrel (molecular form) from the mixture of clopidogrel bisulfate and MgO tablets was lower than that from the suspension of clopidogrel bisulfate tablet alone. CONCLUSIONS: The mixture of clopidogrel bisulfate and MgO tablets caused a considerable reduction in the administered dose passed through the feeding tube. Therefore, it is recommended to administer the suspensions of clopidogrel bisulfate and MgO tablets separately for safe and effective pharmacotherapy.

Determining whether the effect of liraglutide on non-alcoholic fatty liver disease depends on reductions in the body mass index.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) initially presents as steatosis, which can progress to non-alcoholic steatohepatitis (NASH), and often presents clinically alongside metabolic syndromes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are regularly utilized to treat type 2 diabetes mellitus. The GLP-1 RA-liraglutide-ameliorates liver enzymes, histological features, and liver fat content of patients with NASH. However, few studies have examined whether the effect of GLP-1 RAs depends on changes in the patient's body mass index (BMI). Therefore, this retrospective study aimed to investigate whether the efficacy of liraglutide depended on the baseline BMI or a reduction in BMI. METHODS: Fifty-five Japanese patients with type 2 diabetes mellitus and NAFLD who received liraglutide treatment for 24 weeks were assessed. The association between BMI and liver function or fibrosis was evaluated based on the aspartate aminotransferase, alanine aminotransferase, and fibrosis-4 indices. RESULTS: We found that 24 weeks of liraglutide treatment improved liver function and fibrosis in patients with type 2 diabetes mellitus and NAFLD, regardless of BMI changes or obesity status. CONCLUSIONS: Our findings provide important insight into the impact of BMI on liver function and fibrosis in patients with type 2 diabetes mellitus and NAFLD who are treated with liraglutide.