Increasing the number of pharmacist-led medication order reviews using the available workforce: a retrospective study.

BACKGROUND: Due to staffing constraints, several hospitals have defined targeting strategies for pharmacist-led medication order review, leaving non-targeted patients exposed to potential harmful drug-related problems (DRPs). Using targeting criteria to stratify medication order review level (level 1 (L1): orders, basic patient characteristics; level 2 (L2) or comprehensive medication order review: orders, patient characteristics, medical records, laboratory results) could make it possible to save time and increase the overall number of medication order reviews. This study aims to define targeting criteria to stratify medication order review level and estimate the time saved for the performance of additional medication order reviews. METHOD: This retrospective single-centre study included all medication order reviews performed in 2020; DRPs were collected to assess the medication order review level required to detect them. Logistic regressions were performed to define patient characteristics associated with L2. These targeting criteria were applied to the cohort to estimate the time saved and the number of additional medication order reviews which could have been performed using this approach. RESULTS: 2478 DRPs were reported; 54.2% (1343/2748) could have been detected using an L1 medication order review (representing 48.2% of the patients (829/1721)). L2 medication order reviews were significantly associated with age ≥65 years, male, and renal clearance <60 mL/min (OR≥75yo=1.79; OR65-74yo=1.74; ORfemale=0.74; OR30-59mL/min=1.67; OR<30mL/min=2.62; p<0.05). Sex being a confounding factor, only age and renal clearance were used as targeting criteria. The time saved was estimated at 274 hours per year, leading to an additional 1720 medication order reviews (54 hospital beds). CONCLUSION: The proposed approach would maintain a satisfying level of safety and quality for patients, by performing an L2 medication order review for targeted patients based on age and renal clearance, while improving medication order review coverage with an L1 medication order review for non-targeted patients, using the available workforce.

Predictive stability, novel HPLC-MS analysis and semi-automatic compounding process for the emergency implementation of a production line of pancuronium in injectable solution.

During the early months of the COVID-19 pandemic, the international medical product supply chain was tight, causing breaks in the availability of neuromuscular blocking agents essential for the treatment of patients in intensive care units. The present study describes the pharmaceutical development of an injectable 2 mg/mL solution of pancuronium bromide (PC) in a very short lapse of time. The sterile solution was compounded into a good manufacturing practice grade A clean room, filtered (0.2 µm) and filled into 10 mL type I glass, manually sealed with bromobutyl rubber stoppers. A novel HPLC-MS stability indicating method for pancuronium quantification and its degradation product was developed and validated. This fast, sensitive and straightforward method was used to study the stability of the formulation using a semi-predictive method, enabling a very fast attribution of a temporary shelf-life, which was confirmed by a classic prospective stability study. The production line and the analytical tools set-up were performed in six weeks and the semi-predictive stability study was conducted in 90 days, allowing us to predict a shelf life, which was successfully confirmed by prospective study. In conclusion, using innovative methods, we were able to rapidly overcome the shortage of a critical drug.

Impact of COVID-19 pandemic on antifungal consumption: a multicenter retrospective analysis.

BACKGROUND: In the context of COVID-19 pandemic, antifungal overuse may have occurred in our hospitals as it has been previously reported for antibacterials. METHODS: To investigate the impact of COVID-19 on antifungal consumption, a multicenter retrospective study including four medical sites and 14 intensive care units (ICU) was performed. Antifungal consumption and incidences of invasive fungal diseases before and during COVID-19 pandemic, for non-COVID-19 patients and COVID-19 patients, were described. RESULTS: An increase in voriconazole consumption was observed in 2020 compared with 2019 for both the whole hospital and the ICU (+ 40.3% and + 63.7%, respectively), whereas the incidence of invasive aspergillosis significantly increased in slightly lower proportions in the ICU (+ 46%). Caspofungin consumption also increased in 2020 compared to 2019 for both the whole hospital and the ICU (+ 34.9% and + 17.0%, respectively) with an increased incidence of invasive candidiasis in the whole hospital and the ICU but in lower proportions (+ 20.0% and + 10.9%, respectively). CONCLUSIONS: We observed an increased consumption of antifungals including voriconazole and caspofungin in our hospital during the COVID-19 pandemic and explained in part by an increased incidence of invasive fungal diseases in COVID-19 patients. These results are of utmost importance as it raises concern about the urgent need for appropriate antifungal stewardship activities to control antifungal consumption.

[Long-term benzodiazepine use among dialysis patient: A descriptive study]. / Prise de benzodiazépines au long cours chez les patients dialysés : une étude descriptive.

BACKGROUND: Dialysis patients frequently have anxiety and sleeping disorders and that explains a benzodiazepine treatment. A significant proportion of dialysis patients are long-term users even though it is not recommended to take benzodiazepine for more than 3 months. Risks of such a use are well identified. Nephrologists frequently have to prescribe benzodiazepines. This prescription is complex and there are few studies regarding the factors of benzodiazepine use among this population. OBJECTIVES: To determine the prevalence and the factors related to a long-term benzodiazepine use by dialysis patients. To determine the prevalence and the motivation of patients to stop taking medication among the long-term users who got information about the risk of such a use. METHOD: The study includes 91 dialysis chronic patients. Their characteristics were collected from medical records and interviews with the patients. RESULTS: The average age of patients is 65,8 years. In all, 50.5% take benzodiazepines. Among benzodiazepine users, the prevalence of long-term use is 78.3%. Long-term benzodiazepine users (a) are older, (b) less active, (c) frequently diabetic, (d) depressive, (e) unable to walk, (f) less often registered on the kidney transplant waiting list, and (g) had less kidney transplant previously. Benzodiazepine doses of long-term users were higher than the doses of short-term users. Moreover, 60% of patients who are chronic users want to take action and stop the treatment. Observation of side effects, impression of ineffectiveness and fear of addiction are the most identified motivation to stop treatment. CONCLUSION: The prevalence of benzodiazepine chronic use by dialysis patients is high. Giving information to the patient about the use of these molecules seems to have a positive impact on the decision to stop.

[Capsaicin Cutaneous Patch: a Cost-consequences Study in a French University Hospital]. / Étude coût-conséquences sur la capsaïcine en patch cutané dans un CHU français.

INTRODUCTION: The capsaïcine 8% cutaneous patch (Qutenza®) was recently approved for the management of patients with peripheral neuropathic pain (PNP). Considering its limited clinical efficacy data, its improvement of medical benefit was determined to be 5 which was insufficient to support its reimbursement in addition to diagnosis related groups'tarifs. Nevertheless its commercialization was associated with a marked interest considering the unmet therapeutic needs for patients with PNP. OBJECTIVES: Our objectives were to assess the effectiveness, the safety, and the economic impact of Qutenza® in real-life conditions. METHODS: An observational cost-consequences study was launched under the aegis of the Drug Committee of our hospital. Medical charts and prescriptions of all patients who received at least one patch application were analyzed. Effectiveness and safety were assessed after 12-week and 24-week of follow-up. The economic impact was measured within the Hospital and Health Insurance perspective and with limitation to direct costs. RESULTS: From March 2012 to October 2013, 91 patients (54.3 ± 14.1 years; 52.7% of male) received at least one application. The average follow- up duration was 188.3 ± 86.4 days. The PNP etiologies were mainly post-surgery (42.9%) and post-traumatology (20.8%). A therapeutic response (decrease of ENS score of least 30%) after 12 weeks and 24 weeks was observed in 27.9% and 37.1% of patients respectively. The SF-36 mental score was significantly improved. The safety profile was good. The application of the patch resulted in incremental costs of 154 euros per hospital stay without impact on outpatient-prescription drug expenditures. CONCLUSION: This study confirms the interest of Qutenza® for heavily pretreated, refractory patients with PNP. The clinical profile of responders has to be further investigated in large observational studies.

Prospective study of erythropoietin use on quality of life and cost effectiveness in acute myeloid leukemia and allogeneic hematopoietic stem cell transplantation patients.

BACKGROUND: Despite frequent anemia and multiple transfusions in patients undergoing chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia , recommendations for use of erythropoiesis-stimulating agents (ESAs) in these populations are still missing. The primary objective was the effect of ESA administration on patient's quality of life (QoL). Secondary objectives were hemoglobin (Hb) recovery, red blood cell (RBC) transfusions, overall survival, and event-free survival. METHODS: Adult patients with Hb ≤ 11 g/dL after consolidation chemotherapy for acute myeloid leukemia (group 1), or after allo-HSCT for any hematological diseases (group 2), were prospectively included. ESA was administered subcutaneously once per week during a maximum period of 6 months and was stopped when Hb level reached 12 g/dL. A paired-matched analysis using a historical control group was performed for secondary endpoints. Fifty-two patients were included in group 1, and 55 patients were in group 2. RESULTS: For the global population, a significant improvement of QoL was noticed with ESA use; 83% (group 1) and 71% (group 2) of patients achieved an Hb level ≥ 12 g/dL without transfusion requirement. The pair-matched analysis showed a reduction of 4 RBC units per patient in group 1 (P = .0002) and 3 RBC units per patient in group 2 (P = .04). No significant difference in terms of thromboembolic events, overall survival, and event-free survival was observed between ESA and control groups. A RBC transfusion median savings of €1712 per patient was estimated in each group. CONCLUSIONS: ESAs have a clinical and economic benefit on Hb recovery, could improve a patient's QoL, and lead to a significant reduction in number of RBC transfusions with no effect on survival.

Evaluation of miglustat treatment in patients with type III mucopolysaccharidosis: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of oral miglustat treatment in patients with mucopolysaccharidosis type III. The primary outcome was efficacy with improvement or stabilization in at least two domains of Vineland Adaptative Behavior Scales at 6 months. The secondary outcome measured the evolution of other cognitive tests at 12 months. The safety and tolerability were assessed throughout the study. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled, monocenter, institutional, phase IIb to III study. In case of efficacy at 6 months, the study would go on for another 6 months on an open design with all patients receiving miglustat. In the absence of efficacy at 6 months, the trial had to be continued for 6 more months with the initial design. RESULTS: After 6 months, efficacy was not superior in patients with miglustat. The independent review board confirmed continuing the study until 12 months. CONCLUSION: Miglustat treatment was not associated with any improvement/stabilization in behavior problems in patients with mucopolysaccharidosis type III. Miglustat has an acceptable safety profile. However, the study has confirmed that miglustat is able to pass through the blood-brain barrier without significantly decreasing ganglioside levels.

Pegylated IFN-α2a combined to imatinib mesylate 600mg daily can induce complete cytogenetic and molecular responses in a subset of chronic phase CML patients refractory to IFN alone or to imatinib 600mg daily alone.

This phase I/II study was designed to demonstrate the tolerance and the efficacy of a combination of pegylated interferon-α 2a to Imatinib mesylate (IM) 600mg daily in cytogenetically IM-resistant but in CHR chronic phase CML patients. The combination was generally well tolerated in the 15 evaluable patients. A significant reduction of the Ph1(+) BM metaphases was observed in these poor prognosis patients, with 2 long-term CCyR including 2 MMR. After a median follow-up of 43 months, 93% of patients are alive. The addition of PegIFNα2a to IM600 is feasible, and able to overcome resistance within this context.

Gemcitabine and oxaliplatin combination chemotherapy for metastatic well-differentiated neuroendocrine carcinomas: a single-center experience.

BACKGROUND: Beyond the usual regimens based on streptozocin and doxorubicin or 5-fluorouracil, no second-line therapy of metastatic neuroendocrine tumor has gained wide acceptance. Gemcitabine and oxaliplatin are generally well tolerated and have shown activity against a wide range of malignancies. The authors assessed the efficacy of gemcitabine-oxaliplatin combination (GEMOX) in the treatment of patients with metastatic neuroendocrine tumors. METHODS: Twenty consecutive patients with progressive disease were treated with GEMOX, in most cases after failure of other chemotherapy regimens (median=2). Patients were followed for evidence of toxicity, response, and survival. Two patients were chemotherapy-naive at treatment initiation and were excluded from the efficacy analysis. RESULTS: Toxicity was manageable overall; however, 6 (30%) patients had to discontinue treatment because of oxaliplatin-induced neurotoxicity (grade 2). Three (17%) of 18 patients had a partial response, median progression-free survival was 7.0 months, and median overall survival was 23.4 months. CONCLUSIONS: Gemcitabine-oxaliplatin combination shows interesting activity and is well tolerated in pretreated patients with neuroendocrine tumors.

Irinotecan drug eluting beads used as a treatment of advanced intra hepatic cholangiocarcinoma.

This report describes a 74-year-old male with unresectable intrahepatic cholangiocarcinoma (ICC). However surgical procedure is the only curative treatment, it often seems to be ineffective because of the aggressive behaviour of the disease. The role of systemic chemotherapy in the ICC is undefined with a median survival between 6.43 to 12.17 months obtained by using the combination chemotherapy of gemcitabine with cisplatin. In the present case, we performed a targeted treatment using drug eluting beads (DEB) with irinotecan (IRI) administered as transarterial-chemoembolization (TACE). After one session, the tumour vascularity decreased significantly at the one month evaluation on computed tomography (CT) scan of the liver. This case report suggested that minimally invasive transcatheter DEB embolization could be a promising, safe and effective treatment for selective patients with unresectable ICC.

[Liver transplantation for chronic liver disease: hospital costs]. / Transplantation hépatique pour maladie chronique du foie: coût hospitalier.

OBJECTIVES: Alcoholic cirrhosis and viral (especially hepatitis C) cirrhosis account for 50% of liver transplantation indications. The aim of our study was to evaluate the cost of liver transplantation from the hospital's perspective, according to indication. METHODS: This retrospective study at a university hospital included 60 patients (cause of liver disease: alcoholic or hepatitis C-induced cirrhosis) who underwent liver transplantation between 1996 and 1999. All patients received the liver of brain-dead donors. The outcome measure was the cost of hospitalization from admission for transplantation through two years afterwards. The study does not include the costs of pre-transplantation evaluation or organ procurement. To calculate medical costs, we collected data about pharmaceutical use and laboratory tests for each patient. Logistic costs were calculated from French data for diagnosis-related groups, according to length of stay. Consultations and admissions in the two years after transplantation were collected, and their costs calculated. RESULTS: Length of stay for transplantation (mean: 24 days, range 11-66) and costs (average 40 keuro per patient, range: 27.8-75.7, i.e., 52 keuro after escalation to 2006 levels) were similar. The cost of transplantation was higher (p=0.002) for Child C patients (mean: 46 keuro per patient, range: 31,1-72,8). Costs of follow-up after transplant (mean 5.4 keuro per patient, range: 0.87-19.7) varied, with consultation costs higher (p=0.002) in the alcoholic cirrhosis group (0.38 keuro versus 0.3 keuro) and hospitalization more expensive (p=0.0496) for the viral cirrhosis group (6 keuro versus 4,6 keuro). CONCLUSION: We found that length of stay was the most important determinant of hospital costs for liver transplantation and that the indication for transplantation has a slight influence on resource utilization during the first two years after surgery.