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.

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.

Reducing the use of psychotropics in a convalescent rehabilitation ward.

AIMS: Many patients who are transferred to the convalescent rehabilitation ward of Kawasaki Kokoro Hospital (hereinafter, our hospital) are on psychotropics prescribed for delirium by their physicians at acute care hospitals. In this study, psychiatrists and pharmacists collaborated with rehabilitation physicians to reduce the use of psychotropics. METHODS: The basic information and psychotropics prescription statuses of 88 patients discharged from the convalescent rehabilitation ward of our hospital between April 1, 2021 and March 31, 2022 were derived from their medical records. RESULTS: At admission, psychotropics were prescribed to 55 patients and the number of prescribed drugs was 2 (median). At discharge, psychotropics were prescribed to 41 patients and the number of prescribed drugs was 1 (median), showing a significant decrease (p < 0.05). Compared with those at admission, prescribed psychotropic doses at discharge were significantly higher for lemborexant but significantly lower for antipsychotics, benzodiazepine/nonbenzodiazepine hypnotics, antidepressants, suvorexant, ramelteon, and sodium valproate (p < 0.05). CONCLUSIONS: These results suggest that it may be possible to reduce the types and doses of psychotropics prescribed at acute care hospitals in convalescent rehabilitation wards. However, further investigation is needed because the number of patients in this study was limited, and selection bias due to different patient characteristics cannot be ruled out.

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.

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.

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.

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.

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.

Two-way crossover comparison of insulin glargine and insulin detemir in basal-bolus therapy using continuous glucose monitoring.

OBJECTIVE: This study aimed to compare the glucose-lowering effect and glycemic variability of insulin glargine with those of insulin detemir. MATERIAL AND METHODS: This was an open-label, single-center, randomized, two-way crossover study in patients with diabetes on basal-bolus insulin therapy, with neutral protamine Hagedorn (NPH) insulin as basal insulin. Patients switched from NPH insulin to a course either of insulin glargine followed by insulin detemir, or insulin detemir followed by insulin glargine, continuing the same dose of the prior bolus of insulin. To evaluate the glucose-lowering effect, daily glycemic profiles were recorded for 72 hours by continuous glucose monitoring (CGM) in an outpatient setting. The mean amplitude of glycemic excursions, standard deviation (SD), and the mean of daily difference (MODD) were used to assess intraday and day-to-day glycemic variability. RESULTS: Eleven patients were enrolled and nine completed the study. Mean blood glucose calculated from CGM values was significantly lower with insulin glargine compared with insulin detemir (9.6 ± 2.4 mmol/L versus 10.4 ± 2.8 mmol/L, P = 0.038). The SD was significantly lower with insulin glargine versus insulin detemir (2.5 ± 0.9 mmol/L vs 3.5 ± 1.6 mmol/L, P = 0.011). The MODD value was significantly lower with insulin glargine than with insulin detemir (2.2 ± 1.1 mmol/L vs 3.6 ± 1.7 mmol/L, P = 0.011). There was no significant difference between the two insulin analogs in terms of hypoglycemia. CONCLUSION: This study suggests that insulin glargine leads to more effective and more stable glycemic control than the same dose of insulin detemir.

Comparison of oxidative stress markers in type 2 diabetes: basal bolus therapy versus twice daily premixed insulin analogs.

AIMS: Several studies have shown that twice-daily injection of premixed insulin analog (MIX) therapy achieves glycemic control equivalent to that with basal-bolus (BB) therapy. However, glycemic fluctuations that lead to oxidative stress may be associated with the risk of diabetic complications. Therefore, in this study, we compared oxidative stress markers between MIX therapy and BB therapy. METHODS: In this cross-sectional study, we recruited a total of 37 patients (17 patients in the BB group and 20 patients in the MIX group) and compared urinary 8-isoprostane and urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. RESULTS: There were no significant differences in urinary 8-isoprostane (BB vs MIX: 199+/-92 pg/mg Cr vs 266+/-107 pg/mg Cr) or urinary 8-OHdG (4.7+/-1.6 ng/mg Cr vs 5.4+/-1.9 ng/mg Cr, respectively). Conclusion These results suggest that MIX is equivalent to BB in terms of glycemic fluctuations and oxidative stress.

Clinical application of the leukocyte migration test and new diagnostic criteria for identifying causative agents in patients with drug-induced liver injury.

BACKGROUND/AIMS: We examined the usefulness of the leukocyte migration test (LMT) in the identification of agents causing drug-induced liver injury (DILI). METHODOLOGY: In 14 patients who were tentatively diagnosed as having DILI in Kitasato Institute Hospital, pharmacists collected and evaluated drug information and patients' medication histories to identify causative agents. Simultaneously, LMT and drug lymphocyte stimulation test (DLST) were performed. Furthermore, scoring was performed according to the diagnostic criteria established by the International Consensus Meeting (ICM) and the Digestive Disease Week-Japan 2004 (DDW-J). RESULTS: LMT-positive agents showed a higher ICM score compared to DLST-positive agents. The rate of LMT-positive agents was examined with respect to ICM assessment, and 0%, 25%, 33%, and 100% of agents regarded as unrelated/unlikely, possible, probable, and highly probable showed positive reactions on LMT, respectively; the rate of LMT-positive agents increased with the degree of the agent's involvement. When the results of LMT were applied to the DDW-J criteria, there was a correlation with the ICM criteria in comparison to scoring based on the results of DLST. CONCLUSIONS: LMT may be useful for identifying agents causing DILI. Furthermore, the collection and evaluation of drug and patient information and in vitro testing in the identification of causative agents may support more reliable diagnosis.