Impact of medical and pharmaceutical interventions on anti-infective prescriptions: an observational study.

Appropriate prescribing of anti-infectives is a public health challenge. In our hospital, clinical microbiologists (clinical microbiology mobile unit, UMMc) and clinical pharmacists (clinical pharmacy, PHAc) carry out interventions on anti-infective prescriptions to improve practices. Our main objective was to evaluate the acceptance of UMMc and PHAc interventions on anti-infective prescriptions by quantifying the rate of prescription change 24 h after intervention. The secondary objective was to characterize the type of intervention and associate the rate of change for each. All prescriptions are computerized, and interventions traced via DxCare® software, which feeds a local data warehouse (HEGP-CDW). This descriptive, retrospective, single-center, uncontrolled study was conducted from January 2015 to December 2018. The data were extracted over this period from the data warehouse and analyzed using R software. UMMc interventions were accepted 72.2% of the time and PHA interventions 87.3%. The types of interventions found were mostly dose adjustments (61.1% for the UMMc and 54.2% for the PHAc) and proposals to change or stop a drug. Interventions have an impact on anti-infective prescriptions and are generally followed by clinicians. For the category "discontinuation of a molecule", almost half of the advice from the UMMc was refused. The collaboration between the UMMc and PHAc should be reinforced to improve acceptance.

[Improvement of antibiotic therapy adequacy with local guidelines and their reassessment through a multidisciplinary action: Prospective study in an Internal Medicine department]. / Amélioration de l'adéquation des antibiothérapies aux recommandations et de leur réévaluation par une action pluridisciplinaire : étude prospective dans un service de médecine interne.

INTRODUCTION: The implementation of antimicrobial stewardship actions is important in the fight against antimicrobial resistance. The objective of our study was to evaluate the impact of a multidisciplinary program on the adequacy of antibiotic prescriptions with local guidelines in terms of indication, molecule, dosage and treatment duration during the 48-72h reassessment in an internal medicine department. METHOD: This was a before/after monocentric, prospective study. All patients hospitalized in the internal medicine department who were treated with antibiotics for at least 48h were included. The intervention had two components: training of residents about antibiotic treatment and development of a multidisciplinary 48-72h reassessment team. Our primary endpoint was the adequacy of prescriptions with local guidelines, assessed by an independent blinded committee. We also measured antibiotic consumptions. RESULTS: One hundred and twelve patients were included. Adequacy with local recommendations increased from 57.1% to 97.8% (P<0.01), including for the duration of treatment. Traceability of reassessment in medical records increased from 65.3 % to 97.8 % (P<0.01). Finally, the part of consumption of antibiotics with high risk of resistance selection decreased during the period "after" (-10.2 %, P<0.01). CONCLUSION: The set-up of a multimodal (association of pedagogic and incentive actions) and multidisciplinary (internist, clinical pharmacist and antimicrobial stewards) action improved the adequacy of antibiotic prescriptions with local guidelines.

Validity of a clinical decision rule-based alert system for drug dose adjustment in patients with renal failure intended to improve pharmacists' analysis of medication orders in hospitals.

OBJECTIVE: The main objective of this study was to assess the diagnostic performances of an alert system integrated into the CPOE/EMR system for renally cleared drug dosing control. The generated alerts were compared with the daily routine practice of pharmacists as part of the analysis of medication orders. MATERIALS AND METHODS: The pharmacists performed their analysis of medication orders as usual and were not aware of the alert system interventions that were not displayed for the purpose of the study neither to the physician nor to the pharmacist but kept with associate recommendations in a log file. A senior pharmacist analyzed the results of medication order analysis with and without the alert system. The unit of analysis was the drug prescription line. The primary study endpoints were the detection of drug dose prescription errors and inter-rater reliability (Kappa coefficient) between the alert system and the pharmacists in the detection of drug dose error. RESULTS: The alert system fired alerts in 8.41% (421/5006) of cases: 5.65% (283/5006) "exceeds max daily dose" alerts and 2.76% (138/5006) "under-dose" alerts. The alert system and the pharmacists showed a relatively poor concordance: 0.106 (CI 95% [0.068-0.144]). According to the senior pharmacist review, the alert system fired more appropriate alerts than pharmacists, and made fewer errors than pharmacists in analyzing drug dose prescriptions: 143 for the alert system and 261 for the pharmacists. Unlike the alert system, most diagnostic errors made by the pharmacists were 'false negatives'. The pharmacists were not able to analyze a significant number (2097; 25.42%) of drug prescription lines because understaffing. CONCLUSION: This study strongly suggests that an alert system would be complementary to the pharmacists' activity and contribute to drug prescription safety.

Cost analysis of bivalirudin versus reference anticoagulants without GP IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention for acute coronary syndrome in routine clinical practice. Pompidou registry.

Randomized controlled trials have shown improved short-term bleeding outcomes for bivalirudin compared to other anticoagulant in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). This study analyzed the cost/efficacy profile of bivalirudin-based anticoagulation strategy versus non bivalirudin-based anticoagulant strategy without use of GP IIb/IIIa inhibitors in routine clinical practice. From January 2009 to December 2010, 216 patients who underwent PCI for ACS at hospital Georges-Pompidou without GP IIb/IIIa inhibitors were studied. Of these patients, 24 (11%) received bivalirudin and 192 (88%) received others anticoagulants (mainly unfractionated heparin or low molecular weight heparin). Ischemic events and bleeding or transfusion were slightly lower in bivalirudin group (0 vs. 4.2%, P=0.60 and 4.2 vs. 8.9%, P=0.70, respectively). In spite of a higher cost of the medication, the overall cost of the bivalirudin strategy was slightly lower (9167±3688 € vs. 14,016±14,749 €, P=0.23), in relation with a shorter average duration of the hospital stay. In conclusion, in this limited, single-center, population of patients with ACS, the clinical efficacy and safety of bivalirudin appeared at least as good as that of reference anticoagulants in real world clinical practice, with no increase in overall costs.

A business rules design framework for a pharmaceutical validation and alert system.

OBJECTIVES: Several alert systems have been developed to improve the patient safety aspects of clinical information systems (CIS). Most studies have focused on the evaluation of these systems, with little information provided about the methodology leading to system implementation. We propose here an 'agile' business rule design framework (BRDF) supporting both the design of alerts for the validation of drug prescriptions and the incorporation of the end user into the design process. METHODS: We analyzed the unified process (UP) design life cycle and defined the activities, subactivities, actors and UML artifacts that could be used to enhance the agility of the proposed framework. We then applied the proposed framework to two different sets of data in the context of the Georges Pompidou University Hospital (HEGP) CIS. RESULTS: We introduced two new subactivities into UP: business rule specification and business rule instantiation activity. The pharmacist made an effective contribution to five of the eight BRDF design activities. Validation of the two new subactivities was effected in the context of drug dosage adaption to the patients' clinical and biological contexts. Pilot experiment shows that business rules modeled with BRDF and implemented as an alert system triggered an alert for 5824 of the 71,413 prescriptions considered (8.16%). CONCLUSION: A business rule design framework approach meets one of the strategic objectives for decision support design by taking into account three important criteria posing a particular challenge to system designers: 1) business processes, 2) knowledge modeling of the context of application, and 3) the agility of the various design steps.

[Prospective evaluation of the relevance of prescribing antibiotic combinations in an internal medicine department]. / Evaluation prospective de la pertinence des associations d'antibiotiques en médecine interne.

PURPOSE: To assess the relevance of antibiotic combinations according to available recommendations. METHODS: Prospective monocentric study of 12-month duration in the department of internal medicine of a teaching hospital. All antibiotic combinations were assessed taking into account the infection type, the involved bacteria, the antibiotic nature, dosage and duration of treatment. A scientific committee classified each combination antibiotic therapy as: (1) in agreement with existing recommendations; (2) adapted to the antibiogram in the absence of available recommendations; (3) irrelevant but with no adverse clinical outcome for the patient; (4) irrelevant with potential adverse clinical outcome for the patient. RESULTS: Among 87 antibiotic combinations prescribed, 67 (77%) agreed with available recommendations. The percentages of irrelevant combinations with and without potential adverse clinical outcome for the patient were 7% (six cases) and 16% (14 cases), respectively. Reasons for non-conformity included: (1) prescription of combination therapy while monotherapy could have been sufficient or antibiotic therapy was unjustified (14 cases); (2) prescribed antibiotics not adapted to antibiogram (three cases); (3) prescribed antibiotics not effective on the most likely bacteria when treatment of infection was empirical (three cases). The rate of prescription appropriateness was 97% when the mobile microbiology team had interfered with the decision, versus 53% (p<0.001) when it had not. CONCLUSION: Seventy-seven percent of antibiotic combinations were appropriate and agreed with available recommendations. The advice of a microbiology team markedly improves this rate.

Clinical outcomes of lung-transplant recipients treated by voriconazole and caspofungin combination in aspergillosis.

BACKGROUND AND OBJECTIVE: Invasive pulmonary aspergillosis (IPA) is a serious cause of death among immune-compromised patients such as organ-transplant recipients. Recently, voriconazole has been approved for first-line therapy in IPA. Theoretically, optimal voriconazole blood level (superior to 1 mg/L according to recent studies) should be reached within 24 h. In practice, a significantly longer time seems to be needed in lung-transplant recipients. Therefore, caspofungin is now used in combination with voriconazole to provide cover against Aspergillus spp. infection during this gap. The first aim of this study was to investigate Aspergillus spp. infection treated with this combination and the atter's tolerability. The median time for attainment of apparently active blood levels in lung transplant recipients were compared between those with cystic fibrosis and those without. METHODS: Lung-transplant recipients who received a combination of voriconazole and caspofungin between 2002 and 2008 as primary therapy were identified retrospectively. The median number of days to reach active voriconazole blood levels was compared between cystic fibrosis and other patients by Student's t-test. Statistical significance was defined by P-value <0.05. RESULTS: Four patients were treated for Aspergillus colonization before transplantation and their culture were negative at 90 days. Eleven patients were treated for proven or probable invasive aspergillosis and 14 of them had a complete response. Hallucinations (n = 2) and significant hepatic toxicity (n = 2) were reported. Among the 15 studied transplant recipients, a median of 12.3 days was observed for active voriconazole blood levels to be reached. With cystic fibrosis patients, time tended to be longer than with other recipients (14.9 days vs. 8.3 days). Tacrolimus blood levels (between 5 and 15 ng/mL) may have been increased by voriconazole. CONCLUSION: This retrospective study describes practical experience in the management of this rare and severe disease in a referral centre for cystic fibrosis lung transplantation. Voriconazole and caspofungin combination was acceptably safe and was associated with good clinical outcomes in almost all patients. We showed that in 15 lung-transplant recipients a median of 12.3 days was required for voriconazole to reach high enough blood levels. Caspofungin in combination with voriconazole provides cover against Aspergillus infection during the period when voriconazole may be at subtherapeutic levels with good tolerability.

[Clinical and economical evaluation of bivalirudin during percutaneous coronary interventions]. / Evaluations clinique et économique de la bivalirudine au cours des procédures d'angioplasties coronaires.

Bivalirudin, with provisional GP IIb/IIIa inhibitor use allows the same protection against ischemic complications while reducing the hemorrhagic complications compared with the systematic association of a GP IIb/IIIa inhibitor plus heparin (The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events-2 [Replace-2]). In clinical practice, the use of heparin is not systematically associated with a GP IIb/IIIa inhibitor. That's why we studied the clinical and economic interest of bivalirudin only versus heparin (UFH) only. Opened pragmatic monocentric study carried out in 2007. We made a chronological matching: for each patient treated with bivalirudin, we included the next patient with the same clinical presentation treated with unfractionated heparin. Ninety-two patients were included (46 in each group). The need for a GP IIb/IIIa inhibitor during the PCI was not significantly different between the two groups (p=0.11). No major hemorrhagic complications were observed in the two groups. Prevalence of ecchymosis was not significantly different: 22 % in the UFH group versus 13 % in the bivalirudin group (p=0.27). The average troponin level the next day was significantly higher in the bivalirudin group (p=0,049), although the change in troponin levels before and after the procedure was similar in the two groups. The average cost by patient of anticoagulation by bivalirudin and HNF is very different, respectively 473+/-150 and 51+/-146 euro (p=0.0001). Bivalirudin can be an interesting alternative for patients with a high risk of having complications. But considering its cost this therapy must be used only for selected patients.

[Evaluation of flow rate regulators for intravenous infusion]. / Evaluation des régulateurs de débit passifs utilisés pour la perfusion intraveineuse.

OBJECTIVE: The aim of our study is to evaluate seven flow rate regulators (FRR) to assess the reliability of these devices compared to standard perfuser with roller clamp. STUDY DESIGN: Each FRR was tested with 5% dextrose and 0.9% sodium chloride combined with three different theoretical flow rates (30, 80 and 250 ml/h). Accuracy was compared with the theoretical value. Repeatability of flow rate was assessed thanks to variance break-up. RESULTS: Each FFR exhibits at least one combination "flow rate-solution" significantly different of the theoretical flow rate. Exadrop was the least successful of the FFR according to the accuracy. This FFR had for each combination a flow rate different of the theoretical (mean error: -24.0 ml/h). Tutodrop was the most successful of the FFR according to the accuracy with five combinations comparable to the theoretical value (mean error: -1.2 ml/h). The standard perfuser with roller clamp, used without FRR, reported two combinations comparable to the theoretical value and showed lowest rates for repeatability. CONCLUSION: Our study exhibits the poor performances of the FRR studied: according to expected flow regulation, the reported results demonstrate the lack of accuracy. Their only one value added compare to the roller clamp is to improve the repeatability of the flow rate.

[Efficacy and efficiency of preoperative mydriasis: drops versus ocular insert]. / Mydriase préopératoire obtenue par insert ophtalmique versus collyres.

OBJECTIVE: The primary objective of this study was to compare eye drops and inserts in terms of the quality of preoperative mydriasis. The secondary objective was to evaluate the safety and ease of use of each modality. PATIENTS AND METHODS: Prospective randomized and simple blinded study. Patients were randomized into two groups: the insert protocol (atropine 1%, diclofenac 0.1% collyrium and Mydriasert) or the eye drop protocol (atropine 1%, diclofenac 0.1%, tropicamide 0.5%, and phenylephrine 10% collyrium). Fifty-one patients were included: 25 in the insert protocol and 26 in the drop protocol. Mydriasis quality was evaluated by nurses and surgeons. The ease of use was estimated by the number of gestures required to obtain mydriasis and the difficulties encountered. Safety was evaluated at the patient's bedside. RESULTS: Mydriasis of at least 6 mm was obtained in 92% of the patients in the insert protocol (23/25) and 85% of the patients in the drop protocol (22/26) (NS). Four patients lost their insert during the study. Of the patients in the insert group, 16% (4/25) experienced stinging in their eyes, as did 23% (6/26) of patients in the group using drops (NS). To reach effective mydriasis, the insert protocol required fewer nurse gestures per patient than the drop protocol (3.0 versus 8.3; p<0.001). CONCLUSION: With the protocol using an insert, preoperative mydriasis is not inferior to that obtained with drops only and is more efficient in terms of nurse time and number of gestures. Nurses should be trained in appropriate handling of the insert and avoiding the loss of the device.