Association of silodosin, tamsulosin, and naftopidil with delirium: analysis of the pharmacovigilance database in Japan.

BACKGROUND: An association between adrenergic alpha-1 receptor antagonists and delirium has been suggested, but the details are unclear. AIM: This study investigated the association between adrenergic alpha-1 receptor antagonists and delirium in patients with benign prostatic hyperplasia using the Japanese Adverse Drug Event Report database. METHOD: First, disproportionality analysis compared the frequency of delirium in the adrenergic alpha-1 receptor antagonists silodosin, tamsulosin, and naftopidil. Next, multivariate logistic analysis was performed to examine the association between delirium and adrenergic alpha-1 receptor antagonists where disproportionality was detected. RESULTS: A disproportionality in delirium was observed in patients receiving tamsulosin (reporting odds ratio [ROR] 1.85, 95% confidence interval [CI] 1.38-2.44, P < 0.01) compared with those who did not, and also in patients receiving naftopidil (ROR 2.23, 95% CI 1.45-3.28, P < 0.01) compared with those who did not. Multivariate logistic analysis revealed that in addition to previously reported risk factors for delirium, delirium in patients receiving tamsulosin was significantly increased with concomitant use of anticholinergics (odds ratio 2.73, 95% CI 1.41-5.29, P < 0.01) and delirium in patients receiving naftopidil was significantly increased with concomitant use of beta3-adrenergic receptor agonists (odds ratio 4.19, 95% CI 1.66-10.6, P < 0.01). CONCLUSION: Anticholinergics or beta3-adrenergic receptor agonists to treat overactive bladder in patients receiving tamsulosin and naftopidil was strongly associated with delirium. Confirming the medical history and concomitant medications of patients receiving tamsulosin or naftopidil may contribute to preventing delirium in patients with benign prostatic hyperplasia and to improving their outcomes.

Yokukansan (TJ-54) in patients undergoing surgery: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the efficacy and safety of Yokukansan (TJ-54) in patients undergoing surgery. METHODS: Efficacy was assessed by the onset of delirium, delirium rating scales, anxiety evaluated by Hospital Anxiety and Depression Scale-Anxiety (HADS-A) score, and safety was assessed by any reported adverse events. RESULTS: Six studies were included. There were no significant differences between the groups in the onset of delirium (risk ratio 1.15, 95% confidence interval [CI] 0.77-1.72), delirium rating scales (early postoperative period: standardized mean difference [SMD] -0.24, 95% CI -1.11 to 0.63; late postoperative period: SMD -0.06, 95% CI -1.56 to 1.45), HADS-A score (mean difference -0.47, 95% CI -1.90 to 0.96), and any adverse events (risk ratio 1.18, 95% CI 0.35-4.00). CONCLUSIONS: The use of TJ-54 in patients undergoing surgery is not an effective strategy for postoperative delirium and anxiety. Further research considering target patients and durations of administration should be conducted.

Identification of Risk Factors for Phlebitis in Patients Treated with Nafamostat Mesylate.

The proteolytic enzyme inhibitor nafamostat mesylate is widely used for the treatment of acute pancreatitis and disseminated intravascular coagulation. This drug may be a risk factor for phlebitis, but this risk has not been studied. Therefore, we aimed to investigate the frequency of phlebitis and its risk factors in patients treated with nafamostat mesylate in intensive care units (ICU) or high care units (HCU). During the study period, 83 patients met the inclusion criteria, and 22 of them (27%) experienced phlebitis. A multivariate logistic regression analysis was performed for severe acute pancreatitis, administration duration, and administration concentration of nafamostat mesylate in ICU or HCU. As a result, the administration of nafamostat mesylate for ≥3 d in the ICU or HCU was an independent predictor of phlebitis caused by nafamostat mesylate [odds ratio (OR), 10.3; 95% confidence interval (CI), 1.28-82.5; p=0.03]. This study suggests that the number of days of nafamostat mesylate administration is associated with phlebitis in patients treated with the drug, and it may be necessary to pay attention to its administration for ≥3 d in ICU or HCU.

Evaluation of Risk of Cardiac or Cerebrovascular Events in Romosozumab Users Focusing on Comorbidities: Analysis of the Japanese Adverse Drug Event Report Database.

Background: Romosozumab is associated with an increased risk of cardiac or cerebrovascular events. Identifying the risk factors for these events could contribute to the safe use of romosozumab. Objective: This study aimed to investigate risk factors for cardiac or cerebrovascular events in romosozumab users. Methods: First, disproportionality analysis was performed to compare the frequency of cardiac or cerebrovascular events, using data from the Japanese Adverse Drug Event Report database. Next, multivariate logistic analysis was performed to investigate risk factors for cardiac or cerebrovascular events in romosozumab users. Results: In total, 859 romosozumab users were identified. A disproportionality of both cardiac and cerebrovascular events was observed in only romosozumab users. Multivariate logistic analysis revealed that the risk of cardiac events in romosozumab users was significantly increased in patients with cardiac disease (odds ratio [OR]: 5.9, 95% confidence interval [CI] 3.5-9.9; P < 0.01) and hypertension (OR: 1.6, 95% CI 1.0-2.7; P = 0.047). In addition, the risk of cerebrovascular events in romosozumab users was significantly increased in the presence of cerebrovascular disease (OR: 2.7, 95% CI 1.2-6.2; P = 0.02) and hypertension (OR: 2.6, 95% CI 1.7-3.9; P < 0.01). Conclusion: Our findings suggest that hypertension may increase the risk of cardiac or cerebrovascular events in romosozumab users. Although additional studies are needed to assess other associated factors, these findings may contribute to the appropriate use of romosozumab and limit adverse events.

Successful Resuscitation of Cardiac Arrest After Refeeding Syndrome Associated with Hiatal Hernia: A Case Report.

BACKGROUND Refeeding syndrome (RFS) is a life-threatening syndrome, which can cause sudden death. RFS has been reported frequently in young patients with anorexia without organic disease; however, there are few reports in elderly patients with organic disease. Herein, we report a case of cardiac arrest after refeeding syndrome associated with hiatal hernia. CASE REPORT We report the case of a 59-year-old woman who had a diagnosis of RFS during treatment for anorexia secondary to hiatal hernia. She was hospitalized with hypothermia, anemia, and hypovolemic shock and treated with electrolytes, hydration, and transfusion at the Emergency Department. Upper gastrointestinal endoscopy revealed hiatal hernia with severe reflux esophagitis. We initiated parenteral nutrition (8.7 kcal/kg/day). However, QTc prolongation caused pulseless ventricular tachycardia. Temporary cardiac pacing was performed to prevent recurrence. Her nutritional status steadily improved, and she was transferred to another hospital without complications. CONCLUSIONS Patients with gastrointestinal comorbidities are more likely to have inadequate food intake and to be undernourished on admission and therefore should be carefully started on nutritional therapy, considering their risk of RFS.

Factors Determining the Efficacy of Recombinant Human Thrombomodulin in the Treatment of Sepsis-Induced Disseminated Intravascular Coagulation.

Recombinant human thrombomodulin (rhTM) is an anti-coagulant used to treat disseminated intravascular coagulation (DIC). The efficacy of rhTM in patients with sepsis-induced DIC has been proved in some clinical trials, but the determining factors are not known. The aim of this study was to identify patients for whom rhTM will be effective and the factors that determine rhTM efficacy in alleviating DIC. A single-center, retrospective, observational study was conducted in patients with sepsis-induced DIC who were treated with rhTM in Okayama Saiseikai General Hospital (Okayama, Japan) between January 2010 and December 2019. Among 67 patients who were treated with rhTM, DIC was resolved in 24 patients. The multivariate logistic regression analysis revealed that age (odds ratio (OR) 1.05; 95% confidence interval (CI) 1.00-1.10; p < 0.05) and acute physiology and chronic health evaluation II scores (OR 0.88; 95% CI 0.78-0.98; p < 0.05) were factors that determined rhTM efficacy in alleviating DIC. Overall, our study provides valuable information on factors that should be considered before rhTM administration to patients with sepsis-induced DIC for a better management of healthcare costs.

Cholinergic Crisis Owing to Distigmine Bromide Complicated by Hyperosmolar Hyperglycemic State.

Distigmine bromide is widely used to treat neurogenic bladder and causes cholinergic crisis, a serious side effect. We herein report about a patient with distigmine bromide-induced cholinergic crisis complicated by a hyperosmolar hyperglycemic state (HHS). On admission, the patient was diagnosed with HHS based on the medical history and laboratory test results. However, she also had bradycardia, miosis, and low plasma cholinesterase activity. We later found that she had received distigmine bromide, which led to a diagnosis of cholinergic crisis. We suggest that the exacerbation of pathology, including HHS, can cause cholinergic crisis in patients receiving distigmine bromide.

Clarification of vaccines: An overview of filter based technology trends and best practices.

Vaccines are derived from a variety of sources including tissue extracts, bacterial cells, virus particles, recombinant mammalian, yeast and insect cell produced proteins and nucleic acids. The most common method of vaccine production is based on an initial fermentation process followed by purification. Production of vaccines is a complex process involving many different steps and processes. Selection of the appropriate purification method is critical to achieving desired purity of the final product. Clarification of vaccines is a critical step that strongly impacts product recovery and subsequent downstream purification. There are several technologies that can be applied for vaccine clarification. Selection of a harvesting method and equipment depends on the type of cells, product being harvested, and properties of the process fluids. These techniques include membrane filtration (microfiltration, tangential-flow filtration), centrifugation, and depth filtration (normal flow filtration). Historically vaccine harvest clarification was usually achieved by centrifugation followed by depth filtration. Recently membrane based technologies have gained prominence in vaccine clarification. The increasing use of single-use technologies in upstream processes necessitated a shift in harvest strategies. This review offers a comprehensive view on different membrane based technologies and their application in vaccine clarification, outlines the challenges involved and presents the current state of best practices in the clarification of vaccines.

[Investigation of Intravenous Azithromycin Treatment Safety When Reducing Solvent for Intensive Care Unit Patients].

Intravenous azithromycin (AZM) was approved for use in December 2011 in Japan. In general, intravenous AZM injections are diluted to 1 mg/mL, with a total infusion volume of 500 mL to avoid phlebitis. Patients in intensive care units (ICUs) require small infusion volumes. We retrospectively evaluated the total AZM infusion volume in 65 ICU patients receiving AZM treatment from December 2011 to August 2014. Thirteen patients (20.0%) received a reduced volume [100 mL (5 mg/mL) or 250 mL (2 mg/mL)] using an infusion pump over 2 h. No peripheral phlebitis was observed in any patient. Based on this result, it is assumed that AZM can be safely administered to ICU patients even though the volume of solvent is reduced. AZM is widely recommended for the treatment of community-acquired respiratory infections and is used in patients with severe infections. Further investigation is required in additional patients to understand the effects of AZM volume reduction in greater detail.

Late development of malignant fibrous histiocytoma at the site of a giant cell tumour 38 years after initial surgery.

The authors report on a patient who developed a malignant fibrous histiocytoma at the site of a benign giant cell tumour, which had been treated by curettage 38 years previously. This latency period is, to their knowledge, the longest yet reported. This female patient was initially treated for a benign giant cell tumour of the proximal tibia when she was 33 years old; she underwent curettage and Kiel bone grafting. She had not received radiation therapy. Twenty eight years later, she underwent a second operation due to recurrence of a tumour. No specific histological diagnosis was possible: histology suggested a benign tumour, however compatible with a low-grade malignant potential but not associated with giant cell tumour. The patient underwent a third operation, with extensive curettage and total knee arthroplasty 38 years after the initial surgery, because of progressive knee pain. Postoperative histopathology study showed high-grade malignant fibrous histiocytoma. Finally, she underwent above-knee amputation because of uncontrollable progression of the tumour. The use of xenogenic bone graft, bone cement and associated bone necrosis potentially contributed to the development of a malignant tumour adjacent to the primary giant cell tumour.

Malignant transformation of multiple enchondromas in the hand: case report.

Enchondromatosis can transform into chondrosarcoma, but this event is rare in the hand. We present the case of a patient with chondrosarcomas of the ring and little fingers. The chondrosarcomas had a long progression of 60 years and the patient presented with large tumors and a severely deformed appearance.

Effects of monoamine reuptake inhibitors on wet-dog shakes mediated by 5-HT2A receptors in ACTH-treated rats.

We examined the influence of imipramine, a serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor, desipramine, a NA reuptake inhibitor, bupropion, a dopamine reuptake inhibitor, fluvoxamine, a selective 5-HT reuptake inhibitor, and mazindol, a catecholamine reuptake inhibitor, on a 5-HT2A receptor-mediated behavior, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced wet-dog shakes, in naive and adrenocorticotropic hormone (ACTH)-treated rats. Chronic administration of imipramine, desipramine and mazindol suppressed the number of wet-dog shakes in naive rats. Chronic ACTH (100 microg/rat, s.c.) treatment increased the number. Chronic administration of imipramine did not decrease the number of wet-dog shakes in ACTH-treated rats. On the other hand, desipramine and mazindol inhibited the increase in wet-dog shakes in ACTH-treated rats. Fluvoxamine and bupropion did not have any effect on the (+/-)-DOI-induced response in naive and ACTH-treated rats. NA reuptake inhibitors may improve the hyperfunction of 5-HT2A receptors induced by chronic ACTH treatment.