Sodium-glucose cotransporter-2 inhibitors increase urinary tract infections?-a cross sectional analysis of a nationwide Japanese claims database.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of antidiabetic drugs. Guidelines for the proper use of SGLT2 inhibitors recommend caution regarding urinary tract infections (UTIs). However, little evidence has been reported on the relationship between SGLT2 inhibitors and UTIs in large epidemiological studies. We investigated (1) the relationship between diabetes mellitus (DM) and UTIs and (2) the relationship between SGLT2 inhibitor prescriptions and the likelihood of developing UTIs in patients with DM, using a nationwide Japanese health insurance claims database by MDV analyzer®. We found that the incidence of UTIs was significantly higher among patients with DM than among those without DM (odds ratio (OR), 1.71; 95% confidence interval (CI), 1.69-1.72, for male; OR, 1.90; 95% CI, 1.89-1.92 for female). In contrast, in male patients with DM, the prescription of SGLT2 inhibitors was negatively associated with the likelihood of developing UTIs (OR, 0.74; 95% CI, 0.72-0.75). Among female patients with DM, there was no significant difference in the incidence of UTIs with or without an SGLT2 inhibitor prescription (OR, 0.99; 95% CI, 0.96-1.01). Subgroup analyses by age confirmed similar relationships between SGLT2 inhibitor prescriptions and UTIs, except for female patients aged ≤39 years, in whom SGLT2 inhibitor prescription was negatively associated with the likelihood of developing UTIs. In conclusion, our analysis of a nationwide claims database found no evidence that SGLT2 inhibitors increase UTIs in Japanese patients with DM, regardless of sex or age.

Intestinal Perforation in a Patient with Colon Cancer during Treatment with Regorafenib: A Case Report and Review of the Literature.

The multikinase inhibitor, regorafenib, is known to exert its antitumor effects by targeting several kinases, inhibiting interstitial intracellular signaling and suppressing tumor cell proliferation. Regorafenib causes gastrointestinal perforation and gastrointestinal fistula as adverse events, and discontinuation is recommended if these adverse events occur during administration. However, there are no prescribed standards for re-administration after discontinuation and for administration in patients with a history of gastrointestinal perforation. Herein, we report a case of gastrointestinal perforation in a patient, with a history of gastrointestinal microperforation, undergoing bevacizumab therapy, within a few days of starting regorafenib; this had a significant effect on the prognosis. The site of gastrointestinal perforation was consistent with previously reported sites around the tumor and at the anastomotic site. Based on a review of literature and our experience with the case presented here, we recommend that administration of regorafenib to patients with a history of gastrointestinal perforation should be avoided to the extent possible. Moreover, in case of prior administration of a drug reported to cause gastrointestinal perforation, such as an anti-VEGFR drug, the risk of gastrointestinal perforation should be considered during the administration of regorafenib. In the event of complaints, such as abdominal pain, gastrointestinal perforation should be considered as a differential diagnosis and appropriate tests and treatments should be initiated at an early stage.

[A Case of Long-Term Survival in a Patient with Colorectal Liver Metastasis Treated with Multidisciplinary Therapy].

A-71-year-old man underwent right hemicolectomy combined with partial resection of the small intestine and duodenum for an ascending colon carcinoma in July 2009. He presented with a liver metastasis adjacent to the inferior vena cava in November 2009. He received 6 courses of FOLFOX4, but the therapeutic effect was SD, so he underwent an extended posterior sectionectomy combined with partial S8 resection, inferior vena cava resection, and cholecystectomy. He developed remnant liver recurrence in February 2011 and another partial S8 resection was performed. He presented with remnant liver recurrence in October 2011, and radiofrequency ablation and systemic chemotherapy were performed, but were not effective. In June 2013, we performed an extended S8 segmentectomy combined with median hepatic vein and diaphragm resection. He is alive 2 years after the third hepatectomy without any recurrence. Although non-anatomical resection is often performed in repeat liver resections for colorectal liver metastases, sometimes detection of recurrent lesions in the same segment indicates Glisson invasion; therefore, anatomic resection may prolong long-term survival.

A retrospective study examining the association between polypharmacy and complications after laparoscopic surgery for colorectal cancer.

BACKGROUND: Polypharmacy is an escalating public health concern across various healthcare settings worldwide. We aimed to comprehensively investigate postoperative complications after laparoscopic surgery for colorectal cancer and explore their association with polypharmacy. As laparoscopic surgery is widespread, clarifying the association between polypharmacy and postoperative complications is clinically important. METHODS: We retrospectively surveyed the medical charts of adult inpatients who underwent laparoscopic surgery for colorectal cancer at Tohoku Medical and Pharmaceutical University Hospital between April 2019 and March 2023. Postoperative complications were determined using the Clavien-Dindo classification. We explored the factors related to postoperative complications and calculated the cut-off values for the number of medication ingredients. RESULTS: Among the 236 patients, 32 (13.6%) developed postoperative complications. On multivariable logistic regression analysis, the number of regularly used medication ingredients (odds ratio = 1.160, 95% confidence interval 1.050-1.270, p = 0.002) was identified as a factor related to postoperative complications. The identified cut-off value for complications was 10 ingredients. Patients using 10 or more ingredients had approximately 3.5 times higher occurrence of postoperative complications than those using fewer than 10 ingredients (33.3% vs. 9.3%, p < 0.001, Fisher's exact test). CONCLUSIONS: Our study comprehensively investigated postoperative complications and examined their association with polypharmacy. We found that the number of regularly used medication ingredients may be linked to complications following laparoscopic surgery for colorectal cancer. These findings have important implications for perioperative management and patient care, providing valuable insights that may influence clinical practices and enhance patient outcomes.

Assessing the stability of daptomycin in icodextrin-based peritoneal dialysis solution.

BACKGROUND: The stability of antimicrobials in peritonitis during peritoneal dialysis (PD) solutions is a critical factor influencing treatment success. This study investigated the stability of daptomycin (DAP) when combined with icodextrin-based PD solution, by measuring DAP concentrations and observing any structural changes. METHODS: A dose of DAP (350 mg) was dissolved in 7 mL of saline in a clean bench. The solution was then injected into the large compartment (1,260 mL) of NICOPELIQ® Peritoneal Dialysis Solution and thoroughly mixed. Samples were collected at intervals ranging from 0 to 336 h (7 points in total). The concentration of DAP was quantified using high-performance liquid chromatography (HPLC). The structure of any unidentified peaks was determined using HPLC coupled with electrospray ionization tandem mass spectrometry. RESULTS: DAP maintained 90% of the initial concentration in NICOPELIC® for 72 h at room temperature and 12 h at 37 °C. Unidentified peaks, distinct from DAP, were detected during analysis. Further investigation indicated that these peaks corresponded to anhydrated DAP. CONCLUSIONS: The findings from this stability study are expected to enhance the effectiveness of outpatient management and preparation for treating peritonitis using DAP.

A Case of Esophagogastric Junction Cancer Treated with Pain Control by Administering Methadone Tablets Through a Gastrostomy.

Introduction: Methadone is used to treat intractable cancer pain when other opioid analgesics are ineffective. Methadone tablets may be difficult to administer in cases of gastrointestinal passage obstruction. However, changing the route of methadone tablet administration is possible. Case Description: The patient, diagnosed with esophagogastric junction cancer with multiple metastases, continued to receive methadone tablets even after not being longer able to take oral medication. Method: Methadone tablets were administered using a simple suspension method via gastrostomy. We measured the respiratory rate during sleep daily. We also measured weekly QTc values using a 12-lead electrocardiogram and methadone blood concentration periodically. No side effects were observed. Conclusion: Using a simple suspension method to administer methadone is a safe pain management method when accompanied by careful monitoring. To date, no study has examined the tube administration safety of methadone tablets. Thus, this case report is of important clinical significance.

Trends in Anti-Influenza Drug Prescription and Adverse Drug Reaction Reporting After the Lifting of Oseltamivir Prescribing Restrictions in Pediatric Outpatients: An Ecological Study Using the MDV Analyzer® And the Japanese Adverse Drug Event Report Database.

BACKGROUND: Abnormal behavior after oseltamivir administration has been reported in the media; in 2007, the package insert for oseltamivir phosphate was revised to restrict its administration to individuals aged over 10 years. However, in 2018, the age limitation specified in the package insert was removed. Here, we evaluated the trends in anti-influenza drug prescription and adverse drug reactions (ADRs) reported in pediatric outpatients after revising the oseltamivir package insert as an ecological study. METHODS: Anti-influenza drug prescriptions for pediatric outpatients with influenza aged 0-19 years were downloaded from the acute Diagnosis Procedure Combination hospital databases using the MDV analyzer®. ADR reports on anti-influenza drug prescription among patients aged 0-20 years in the Japanese Adverse Drug Event Report database were downloaded from the Pharmaceutical and Medical Devices Agency website. Data were collected during the 2016/2017 and 2019/2020 influenza seasons. RESULTS: During the influenza epidemic season (January-March), the percentage of oseltamivir prescriptions for patients with influenza aged 10-19 years tripled after the revision of the oseltamivir package insert (9.3% during the 2016/2017 season and 29.2% during the 2019/2020 season); however, reports of abnormal behavior did not increase (two during the 2016/2017 season and none during the 2019/2020 season). CONCLUSIONS: The number of oseltamivir-related ADR reports among minors over 10 years of age did not increase although the proportion of oseltamivir prescriptions increased after the revision of the oseltamivir package insert.

A case with a trend of QT interval prolongation due to the introduction of methadone to a pancreatic cancer patient on levofloxacin.

BACKGROUND: As methadone can prevent the development of opioid resistance, it has application in alleviating cancer-related pain that proves challenging to manage with other opioids. QT interval prolongation is a serious side effect of methadone treatment, with some reported deaths. In particular, owing to the increased risk of QT interval prolongation, caution should be exercised when using it in combination with drugs that also prolong the QT interval. CASE PRESENTATION: This study presents a case in which methadone was introduced to a patient (a man in his 60s) already using levofloxacin, which could prolong the QT interval-a serious side effect of methadone treatment-and whose QTc value tended to increase. Given that levofloxacin can increase the risk of QT interval prolongation, we considered switching to other antibacterial agents before introducing methadone. However, because the neurosurgeon judged that controlling a brain abscess was a priority, low-dose methadone was introduced with continuing levofloxacin. Owing to the risks, we performed frequent electrocardiograms. Consequently, we responded before the QTc increased enough to meet the diagnostic criteria for QT interval prolongation. Consequently, we prevented the occurrence of drug-induced long QT syndrome. CONCLUSIONS: When considering the use of methadone for intractable cancer pain, it is important to eliminate possible risk factors for QT interval prolongation. However, as it may be difficult to discontinue concomitant drugs owing to comorbidities, there could be cases in which the risk of QT interval prolongation could increase, even with the introduction of low-dose methadone. In such cases, frequent monitoring, even with simple measurements such as those used in this case, is likely to prevent progression to more serious conditions.

Temporal trends in antipsychotic prescriptions for pediatric patients using an administrative hospital database in Japan: a retrospective study.

BACKGROUND: Schizophrenia is a psychiatric disorder characterized by hallucinations, delusions, and other symptoms. Although treatment guidelines for schizophrenia have been established in Japan, drugs are not recommended for pediatric schizophrenia. Additionally, the temporal trends in prescribing antipsychotics for pediatric patients with schizophrenia are unclear. Therefore, we aimed to clarify the trends in antipsychotic prescriptions for Japanese pediatric outpatients from 2015 to 2022. METHODS: Administrative data (as of November 2023) of Japanese pediatric outpatients with schizophrenia aged 0-18 years who visited acute-care diagnosis procedure combination hospitals between January 1, 2015, and December 31, 2022, were included in this study. The target drugs for schizophrenia were all indicated for treating schizophrenia and marketed in Japan as of December 2022. Annual prescription trends for antipsychotics during this period were calculated based on their proportions. The Cochran-Armitage trend test was used to evaluate the proportion of prescriptions for each antipsychotic. RESULTS: The main drugs prescribed for these patients were aripiprazole and risperidone. Among male patients, the proportion of prescriptions for aripiprazole increased significantly from 21.2% in 2015 to 35.9% in 2022, whereas that for risperidone decreased significantly from 47.9% in 2015 to 36.7% in 2022 (both P < 0.001). Among female patients, the proportion of prescriptions for aripiprazole increased significantly from 21.6% in 2015 to 35.6% in 2022, whereas that for risperidone decreased significantly from 38.6% in 2015 to 24.8% in 2022 (both P < 0.001). CONCLUSIONS: Aripiprazole and risperidone were primarily prescribed for pediatric schizophrenia in Japan during the study period. Additionally, the proportion of aripiprazole prescriptions increased over time.

Prescription of renin-angiotensin system inhibitors in Japan during the COVID-19 pandemic: interrupted time series study.

We surveyed changes in angiotensin-converting enzyme inhibitor (ACEIs) and angiotensin II receptor blocker (ARBs) prescription trends during the coronavirus disease 2019 (COVID-19) pandemic in Japan. Data of 1,605,708 outpatients with hypertension were extracted from the Medical Data Vision database. Trends for prescription of ACEIs and ARBs were assessed by analyzing the proportion of these prescriptions in each month, between April 2018 and November 2020. The proportion of ARBs prescriptions changed significantly in trend between the peri-pandemic and pre-pandemic periods (-0.05%/month, P = 0.012). In contrast, the proportion of ACEIs prescriptions did not change significantly in trend in the peri-pandemic period (0.01%/month, P = 0.189). There was no suggestion that the prescribing of ACEIs and ARBs was affected by the COVID-19 pandemic.

Pazopanib-Induced Liver Injury in Patients With Metastatic Renal Cell Carcinoma: A Report of Two Cases.

We report two cases of pazopanib (PAZ)-induced liver injury in patients with metastatic renal cell carcinoma. The first patient was a 70-year-old female who was diagnosed with right renal cell carcinoma and showed tumor embolism in the inferior vena cava. PAZ was started but discontinued after about one month due to a grade four liver injury. The second patient was a 60-year-old male who was diagnosed with left renal cell carcinoma and suspected multiple lung metastases. PAZ was started following a laparoscopic left radical nephrectomy but was stopped after about a month due to a grade three liver injury. We analyzed the plasma PAZ concentrations for treatment evaluation. High plasma PAZ concentrations were observed in both patients after PAZ treatment began. Severe liver injury after PAZ administration may be associated with high plasma PAZ concentrations; hence, we should reduce PAZ dosage early. We also recommend monitoring plasma PAZ concentrations, if possible, so that physicians can either reduce the dosage or discontinue treatment to avoid further liver damage.

Assessment of Information Sharing on Adverse Drug Reactions by Community Pharmacies with Other Medical Institutions.

Widespread coordination and sharing of information regarding adverse drug reactions (ADRs) are important for drug safety assessment. However, the actual status of coordination and sharing of information on ADRs in community pharmacies remains unclear. Therefore, a survey was conducted at community pharmacies to analyze the status. In this cross-sectional study conducted from 31 March 2021 to 9 April 2021, a request letter with the uniform resource locator of the questionnaire form was sent to 302 community pharmacies affiliated with Tsuruha Holdings Inc., and the responses were obtained online. The response rate for the questionnaires was 80.8% (n = 244). In total, 20.9% of the community pharmacies provided information on patients' ADRs to hospitals or clinics prescribing drugs. None of the community pharmacies provided patient ADR information to other community pharmacies. Of the community pharmacies, 98.8% felt that insufficient information was available to monitor ADRs from hospitals or clinics prescribing drugs. For example, the name of the disease (67.6%), considered to be the most common information, was insufficiently provided. Overall, the existing system for providing information on ADRs between community pharmacies and other medical institutions is insufficient and needs to be developed further.

Trends in the prescription of anti-seizure medicines for pregnant women outpatients with epilepsy during 2016-2020 in Japan.

PURPOSE: The temporal trends in prescribing anti-seizure medicines (ASMs) for pregnant women with epilepsy are unclear. In this study, we investigated the trends in ASM prescriptions in pregnant Japanese women with epilepsy. METHODS: Administrative data (as of December 2021), pertaining to Japanese pregnant outpatient women with epilepsy, aged 16-49 years, who visited hospitals between January 1, 2016 and December 31, 2020 were included in the study. Annual prescription trends in ASMs during this period were calculated based on the proportions. The Cochran-Armitage trend test was used to evaluate the proportion of prescriptions for each ASM. RESULTS: The numbers of pregnant women with epilepsy were 404, 421, 368, 378, 386 for the years 2016, 2017, 2018, 2019, and 2020, respectively. As of 2020, levetiracetam had the highest proportion of prescriptions, followed by lamotrigine and valproic acid. From 2016 to 2020, the proportions of levetiracetam and lamotrigine prescribed for pregnant women with epilepsy have increased significantly from 19.1% to 30.8% and from 12.1% to 18.4%, respectively. In contrast, there was no temporal change in the proportion of valproic acid prescribed, which was 12.4% in 2016 and 10.1% in 2020. CONCLUSION: Our findings suggest that the trends in the prescription of ASMs in Japanese pregnant women outpatients with epilepsy have shifted toward ASMs with a lower teratogenic risk.

Antihypertensive drug prescription trends for pregnant women with hypertension in acute hospitals in Japan.

Hypertensive disorders of pregnancy cause maternal organ damage. Therefore, appropriate management with antihypertensive medication is required from the first trimester. We aimed to clarify the antihypertensive drug prescription trends in pregnant women with hypertension in Japan. The administrative data of pregnant outpatients aged 16-49 years who visited acute hospitals between 2013 and 2020 were included. The annual antihypertensive drug prescription trends were evaluated based on their prescription proportions. The most prescribed drug in 2020 was nifedipine, followed by methyldopa and amlodipine. The proportion of nifedipine prescriptions significantly increased from 33.5 to 40.8% during the study period, whereas that of methyldopa significantly decreased from 16.6 to 11.6%. There was no change in the prescription trend of amlodipine. Dihydropyridine calcium channel blockers were the most commonly prescribed drug for pregnant women with hypertension.

Analysis of Risk Factors Associated with Reduced Trough Concentrations of Vancomycin in Relation to Renal Function in a Tertiary Hospital in Japan.

BACKGROUND: Low trough concentrations of vancomycin (VCM) are common in patients receiving the drug, because patients are often administered relatively low doses of VCM due to its high potential for renal toxicity. However, the clinical risk factors associated with low VCM trough concentration in relation to renal function are unclear. METHODS: Patients at our hospital who received VCM intravenously from January 2018 to December 2020 were analyzed. The patients were divided into two groups based on their renal function: normal and lower renal function, such as estimated glomerular filtration rate (eGFR) ≧60 and <60 mL/min/1.73 m2, respectively. In each renal function group, patients' background characteristics, laboratory data and treatments were compared between lower VCM concentration (<10 mg/L) and appropriate VCM concentration (10-20 mg/L) subgroups. RESULTS: Among 101 patients with normal renal function, 47 and 54 patients, respectively, showed lower and appropriate VCM trough concentrations. Elderly age, short stature, and higher C-reactive protein (CRP) level were significantly more common in the lower VCM concentration group compared with appropriate VCM concentration group. Among the 45 patients with renal dysfunction, 20 and 25 patients, respectively, showed lower and appropriate VCM trough concentrations. CRP levels were significantly higher in lower VCM concentration than appropriate VCM concentration subgroups. Multivariate analysis showed that insufficient total VCM doses and higher CRP might have affected the lower VCM trough concentration in patients with normal renal function. CONCLUSION: The results of this study suggest that higher CRP might be one of the risk factors associated with lower VCM concentration in both normal and low renal function patients. Severely ill and emergency patients might receive a lower VCM dose due to underestimation of the acceptable VCM dose.

Amantadine intoxication despite moderate renal dysfunction: A case of combined use with donepezil.

Amantadine intoxication occurred despite moderate renal dysfunction. This may have been affected by the use of donepezil, and we require careful attention to these combinations.

[Questionnaire survey of efficacy of patient support in outpatient chemotherapy by pharmacist].

The aim of this study is evaluation of the efficacy of the pharmacist in providing support at the ambulatory therapy center (ATC), especially in connection with chemotherapy side effects in patients. The unsigned questionnaire survey was conducted for patients receiving chemotherapy in ATC. 108 patients were enrolled, and 78 patients answered questions. Patients were asked which kind of specialists provide the most ideal support in the ATC, and what do patients suffer in the ATC. Interestingly, more patients chose pharmacists than nurses and doctors. Many of patients suffer hair loss, nausea and peripheral neuropathy, and many people feel time spent in the ATC is not so meaningful.