A Survey of Near-Miss Dispensing Errors in Hospital Pharmacies in Japan: DEPP-J Study-Multi-Center Prospective Observational Study-

The aim of this study was to determine the proportion of near-miss dispensing errors in hospital pharmacies in Japan. A prospective multi-center observational study was conducted between December 2018 and March 2019. The primary objective was to determine the proportion of near-miss dispensing errors in hospital pharmacy departments. The secondary objective was to determine the predictive factors for near-miss dispensing errors using multiple logistic regression analysis. The study was approved by the ethical committee at The Institute of Medical Sciences, University of Tokyo, Japan. A multi-center prospective observational study was conducted in 20 hospitals comprising 8862 beds. Across the 20 hospitals, we assessed data from 553 pharmacists and 53039 prescriptions. A near-miss dispensing error proportion of 0.87% (n = 461) was observed in the study. We found predictive factors for dispensing errors in day-time shifts: a higher number of drugs in a prescription, higher number of quantified drugs, such as liquid or powder formula, in a prescription, and higher number of topical agents in a prescription; but we did not observe for career experience level for clinical pharmacists. For night-time and weekend shifts, we observed a negative correlation of near-miss dispensing errors with clinical pharmacist experience level. We found an overall incidence of near-miss dispensing errors of 0.87%. Predictive factors for errors in night-time and weekend shifts was inexperienced pharmacists. We recommended that pharmacy managers should consider education or improved work flow to avoid near-miss dispensing errors by younger pharmacists, especially those working night or weekend shifts.

Intracranial hemorrhage following allogeneic hematopoietic stem cell transplantation.

Charts and radiographs of 622 allogeneic hematopoietic stem cell transplant (HSCT) recipients, over a 20-year period, were retrospectively reviewed for intracranial hemorrhage (ICH) following transplant. A total of 21 cases of ICH were identified (3.4%) including 15 cases of intraparenchymal hemorrhage (IPH), two cases of subarachnoid hemorrhage (SAH), and four cases of subdural hematoma (SDH). The median time from transplantation to the onset of ICH was 63 days (range, 6-3,488 days). The clinical features of post-transplant ICH patients were similar and included hypertension, diabetes mellitus, chronic graft-versus-host disease (GVHD), systemic infection, and veno occlusive disease (VOD), recently referred to as sinusoidal obstruction syndrome, in addition to severe thrombocytopenia. Mortality rate was especially high (89%) after IPH with a median survival of 2 days (range, 0-148 days). In contrast, all patients with SAH or SDH following HSCT survived. The cause of post-transplant ICH appears to be multifactorial, including thrombocytopenia, hypertension, acute GVHD, VOD, and radiation therapy. Most patients in our series displayed severe thrombocytopenia at the onset of ICH, even though adequate prophylactic platelet transfusions were given. By univariate analysis, cord blood transplantation, acute GVHD, systemic infection, and VOD were related to the incidence of ICH, whereas prior CNS episodes and radiation therapy did not reach statistical significance. A multivariate analysis with logistic regression identified acute GVHD as the only factor that significantly influenced ICH occurrence.

Multiple myeloma with multiple and bulky extramedullary plasmacytomas as initial presentation.

We herein describe a rare case of multiple myeloma with an aggressive clinical course and the unusual manifestation of multiple organ involvement by plasma cells. A 58-year-old man noted difficulty in walking due to progressive swelling of his left lower limb. CT scan revealed a huge mass in the inguinal region in addition to masses located on the head, and in the aero-digestive tract and spinal canal. The pathological diagnosis of plasmacytoma was made on biopsied specimens of these masses, while plasma cells did not increase (5.8%) in aspirated bone marrow obtained at the same time. Serum IgG level was 6,387 mg/dl and immunoelectrophoresis demonstrated monoclonal IgG-kappa in the serum. Chemotherapy with vincristine, adriamycin, dexamethasone, subsequent high-dose cyclophosphamide, and irradiation involving both thoracic vertebral canal and inguinal regions resulted in improvement of initial symptoms. However, the patient relapsed soon after; new lesions developed in various parts of the body, including the left thigh and body trunk. Salvage therapy including bortezomib was no longer effective, and he eventually died 10 months after the initial diagnosis. Autopsy revealed the diffuse involvement of plasma cells of multiple organs, including the liver, spleen, abdominal lymph node, and bone marrow in addition to the left leg.

A high risk of life-threatening infectious complications in mycophenolate mofetil treatment for acute or chronic graft-versus-host disease.

We describe herein the clinical courses and outcomes of 26 patients who received oral mycophenolate mofetil (MMF) for the treatment of steroid-resistant refractory or steroid-dependent acute or chronic graft-versus-host disease (GVHD) in a single institution. In most cases, 1,500 mg/day of MMF is a median dose (range 500-3,000 mg/day) and administered for 116.5 days (range 9-584 days) along with calcineurin inhibitors and steroids. Although 20 patients (77%) showed rapid improvement of GVHD symptoms, of 15 patients, 13 (87%) showed acute GVHD; of 11 patients, 7 (64%) showed chronic GVHD; most patients (54%) experienced infection during MMF administration, including 5 cases with life-threatening infection. Positive cytomegalovirus (CMV) antigenemia was also observed in 19 patients (73%), but no patients developed CMV infection. Within the median follow-up of 12.5 months (range 0.5-67 months), 10 patients (39%) died. This small study demonstrates that MMF offers an alternative tool for rescuing steroid-refractory or steroid-dependent GVHD, but increases the risk of developing life-threatening infection.