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.

Effects of a multifaceted intervention to promote the use of intravenous iron sucrose complex instead of ferric carboxymaltose in patients admitted for more than 24 h.

PURPOSE: Although more practical for use, the impact of ferric carboxymaltose (FCM) on the hospital budget is considerable, and intravenous iron sucrose complex (ISC) represents a cost-saving alternative for the management of iron deficiency anemia in patients during hospitalization. The Drug Committee decided to reserve FCM for day hospitalizations and contraindications to ISC, especially allergy. ISC was available for prescription for all other situations. METHODS: The impact of a multifaceted intervention promoting a switch from FCM to ISC was evaluated using an interrupted time series model with segmented regression analysis. The standardized rate of the dispensing of FCM, ISC, and oral iron by the hospital pharmacy, as well as the rate of the dispensing of packed red blood cells and the number of biological iron status measurements, was analyzed before and after the intervention. RESULTS: There was an immediate decrease in FCM consumption following the intervention, with a reduction of 88% (RR: 0.12 [CI95% 0.10 to 0.15]). Conversely, there was a large increase in ISC use (RR: 5.1 [CI95% 4.4 to 5.9]). We did not observe a prescription shift to packed red blood cells or oral iron after the intervention. The time series analysis showed the frequency of iron status testing to remain stable before and after. The direct savings for intravenous iron for 8 months were 187,417.54 €. CONCLUSION: Our intervention to lower the impact of intravenous iron therapy on the hospital budget was effective.

[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.

Consequences of the new zolpidem prescription regulations: a cohort study from the French national healthcare database.

PURPOSE: To determine changes in the prevalence of zolpidem consumption since the change in the regulations of prescription. Formulations containing zolpidem were subject to the regulations of narcotics by the French decree of April 7, 2017. METHODS: Longitudinal cohort study using data from the representative French healthcare database. The main outcome was the prevalence of oral hypnotic drug reimbursement before and after April 2017. The secondary outcome was the change in prescription habits for zolpidem since the decree in long-term users and excessive users. RESULTS: A total of 81,174 individuals had at least one hypnotic drug reimbursement; among, whom 2143 had at least one reimbursement of zolpidem. Before the decree, 26% had at least one reimbursement of zolpidem, whereas it dropped to 18.4% after the decree. Among the 545 long-term users, the reimbursement of zolpidem was discontinued after the decree for 60.4% and 24.2% retained zolpidem as a treatment. The main replacement drug was zopiclone for 6.4% of them. Among the 1598 excessive users, the reimbursement of zolpidem was stopped after the decree for 16.5% and 56.3% retained zolpidem as a treatment. The main replacement drug was zopiclone for 12.1% of them. CONCLUSIONS: The French decree had a major impact on the reimbursement of oral zolpidem. Indeed, prescription of the hypnotic was discontinued for half of the long-term users of zolpidem, and just over one-sixth of the excessive users discontinued the prescription of zolpidem after the decree.

Iatrogenic risk factors associated with hospital readmission of elderly patients: A matched case-control study using a clinical data warehouse.

WHAT IS KNOWN: Hospital readmission within 30 days of patient discharge has become a standard to judge the quality of hospitalizations. It is estimated that 14% of the elderly, people over 75 years old or those over 65 with comorbidities, are at risk of readmission, of which 23% are avoidable. It may be possible to identify elderly patients at risk of readmission and implement steps to reduce avoidable readmissions. OBJECTIVE: The aim of this study was to identify iatrogenic risk factors for readmission. The secondary objective was to evaluate the rate of drug-related readmissions (DRRs) among all readmissions and compare it to the rate of readmissions for other reasons. METHODS: We conducted a retrospective, matched, case-control study to identify non-demographic risk factors for avoidable readmission, specifically DRRs. The study included patients hospitalized between 1 September 2014 and 31 October 2015 in an 800-bed university hospital. We included patients aged 75 and over. Cases consisted of patients readmitted to the emergency department within 30 days of initial discharge. Controls did not return to the emergency department within 30 days. Cases and controls were matched on sex and age because they are known as readmissions risk factors. After comparison of the mean or percentage between cases and controls for each variable, we conducted a conditional logistic regression. RESULTS: The risk factors identified were an emergency admission at the index hospitalization, returning home after discharge, a history of unplanned readmissions and prescription of nervous system drugs. Otherwise, 11.4% of the readmissions were DRRs, of which 30% were caused by an overdose of antihypertensive. The number of drugs at readmission was higher, and potentially inappropriate medications were more widely prescribed for DRRs than for readmissions for other reasons. WHAT IS NEW AND CONCLUSION: In this matched case-control retrospective study, after controlling for gender and age, we identified the typical profile of elderly patients at risk of readmission. These patients had an unplanned admission at the index hospitalization and prescribed nervous system drugs at discharge from the index admission; they have a history of unplanned readmission within 30 days and return home after discharge.

Biological toxicities as surrogate markers of efficacy in patients treated with mTOR inhibitors for metastatic renal cell carcinoma.

BACKGROUND: Metabolic toxicities of mTOR inhibitors (mTORi) are well characterized. The purpose of the study was to investigate the relationship between these metabolic toxicities and mTORi efficacy. METHODS: From 2007 to 2011, metabolic toxicities were retrospectively collected in patients treated with an mTORi (everolimus, temsirolimus) for a metastatic renal cell carcinoma (mRCC) in a single institution. Patients were eligible if they have received an mTORi for at least 28 days. Changes in the following parameters were analyzed: lymphocytes, serum creatinine, glycemia, serum phosphate, liver transaminases, cholesterol, and triglycerides. The efficacy was assessed by progression-free survival (PFS) and tumor response. RESULTS: Data were collected from seventy-five patients (everolimus = 44 patients; temsirolimus = 31 patients). Six patients exhibited a partial response, 42 a stable disease and 15 had a progressive disease (12 missing). After a median follow-up of 12.8 months, the median PFS was 6.7 months (95% confidence interval: 4.0-9.1 months). Patients with CB had a statistically more severe absolute increase of glycemia and absolute decrease in phosphatemia (p = 0.002 and p = 0.02 respectively). The Progression Free Survival was significantly higher with the onset rate of hypophosphatemia (p = 0.03) and hyperglycemia (p = 0.001) and lower with the onset rate of lymphopenia (p = 0.004). CONCLUSIONS: Hyperglycemia, hypophosphatemia and lymphopenia, were significantly associated with tumor response and/or PFS. Those events, as well as their onset rate, should be prospectively monitored as predictors of response to mTORi.

Medicinal leech therapy and Aeromonas spp. infection.

While the use of medicinal leech therapy (MLT) in reconstructive and orthopaedic surgery is widely described, post-operative complications related to leeches remain a major concern. Aeromonas spp. strains are involved in the majority of reported cases. As surgical success rate is directly impacted, an adapted antibiotic prophylaxis should be instituted in order to minimize these complications. We assessed pharmaceutical process, microbiological control and related infections in order to provide data and choose the appropriate antibiotherapy for patients requiring MLT. We report a clinical and microbiological study over a 24-month period. Clinical data were collected from patients' database, and microbiological analysis both on leeches' tank water and crushed leeches were performed to characterize isolated strains and their susceptibility to antibiotics. A total of 595 leeches were used to treat 28 patients (12 in plastic surgery and 16 in orthopaedic surgery), and three documented cases of post-operative infections were reported. Aeromonas spp. isolates yielded from 62 % of analyzed batches (75 % of Aeromonas veronii). Eighteen Aeromonas spp. isolates yielded from 23 water samples and three crushed leeches. Isolates were similar in tank and crushed leeches. Strains were susceptible to fluoroquinolones, sulfamethoxazole/trimethoprim, aminosides, and third-generation cephalosporins but resistant to amoxicillin/clavulanic acid and second-generation cephalosporins. According to collected data, routine tank water microbiological analyses are mandatory in order to identify leeches' batches containing resistant strains and to discard them. In this context, the surgeon is able to select an appropriated antibiotic prophylaxis in order to avoid MLT associated serious post-operative complications.

Fighting the spread of AmpC-hyperproducing Enterobacteriaceae: beneficial effect of replacing ceftriaxone with cefotaxime.

OBJECTIVES: Considering the hypothesis that the high biliary elimination of ceftriaxone could be responsible for the selection of Enterobacteriaceae harbouring high-level AmpC ß-lactamase (HL-CASE), the use of ceftriaxone was discontinued in our hospital in 2006 and replaced with cefotaxime. METHODS: Antibiotic consumption, expressed as defined daily dose (DDD)/1000 patient-days (PD), and HL-CASE incidence, expressed as the number of patients carrying HL-CASE/1000 PD, were compared between the pre-intervention period (Period 1, 2001-05) and the post-intervention period (Period 2, 2006-12) using an interrupted time series analysis. RESULTS: The incidence of HL-CASE increased significantly from 0.32 to 0.69/1000 PD during Period 1 (coefficient = 0.082, P < 0.01). A significant inflection of the slope in the incidence curve occurred in Period 2 (coefficient = -0.061, P = 0.05), mainly owing to the stabilization of the HL-CASE incidence of Enterobacteriaceae harbouring chromosomally inducible cephalosporinase (Period 1, 0.27 to 0.64/1000 PD; Period 2, 0.58 to 0.61/1000 PD) and especially for Enterobacter cloacae (Period 1, 0.09 to 0.30/1000 PD; Period 2, 0.26 to 0.27/1000 PD). This deceleration was observed despite a significant increase in the slope of cefotaxime consumption over Period 2 (coefficient = 2.97, P < 0.01). CONCLUSION: Despite the disadvantages of using cefotaxime compared with ceftriaxone (administration three times daily versus once a day), the ecological benefits of this substitution seem sufficiently convincing to preferentially use cefotaxime. Control of HL-CASE incidence is crucial to limiting carbapenem use and preventing the selection of carbapenemase-producing Enterobacteriaceae.

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.

Non-adherence with drug treatment after heart or lung transplantation in adults: a systematic review.

OBJECTIVE: Heart or lung transplantation is a complex intervention requiring medication adherence. The objective of this systematic review is to estimate the prevalence of non-adherence (NA) with post-transplantation medication in heart or lung recipients and to assess its clinical impact. We examined in the selected studies if the authors considered the patient's perspective in their evaluations. METHODS: The electronic database MEDLINE, EMBASE and The Cochrane Central Register were searched. Only studies that reported the number of non-adhere subjects were eligible. The different methods of measurement, the ways in which authors defined NA and if authors had integrated patient's perspective in their secondary objectives were also assessed. RESULTS: The range frequency of NA was 1-42.9% for all drugs. Non-adherent patients tend to experience worse outcomes compared to adherent patients. The patient's perception of drug side-effects is the most reported patient-related factor for impairing adherence. CONCLUSION: NA after heart or lung transplantation is an important issue and concerns not only immunosuppressant treatments. The main striking point of the selected studies is the lack of patient perspective and the omission of patients-healthcare providers' relationship. PRACTICE IMPLICATIONS: Future research must focus on patients' motivation for the medication-taking behaviour.

[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.

Long-term effects of a multifaceted intervention to encourage the choice of the oral route for proton pump inhibitors: an interrupted time-series analysis.

PROBLEM: Drugs are often given intravenously even when the patient is able to swallow and when an oral form would be more cost-effective. DESIGN: Evaluation of the impact of a multifaceted intervention on the early switch from intravenous to oral administration of proton pump inhibitors (PPI) in a hospital setting. The interrupted time series of intravenous PPI consumption was analysed. BACKGROUND AND SETTING: At a French University Hospital, the Drug Committee, composed of multidisciplinary pharmacy and medical staff, addressed the issue of increasing consumption of intravenous PPI drugs (May 2003). STRATEGY FOR CHANGE: Letters to department heads, academic analyses from members of the Drug Committee, paper reminders at the point of care and audit-feedbacks by pharmacists. Monitoring of consumption and repeated reminder letters were planned. EFFECT OF CHANGE: The consumption of PPI was stable before the first intervention (mean level: 954 units/month). An immediate decrease occurred after the first Drug Committee letter (30% relative reduction, 95% CI -16% to -46%; p<0.001) with a significant trend change during the first multifaceted intervention (-24 units/month, 95% CI -42 to -7; p = 0.007). After the end of the outreach visits (July 2004), the consumptions increased (+32 units/month, 95% CI: 14 to 50, p<0.001). The second intervention had no significant impact. LESSONS LEARNT: A complex intervention (audit, feedbacks, outreach visits) had an effect on practice. It was not sustained even after a less resource-intensive intervention. Other types of interventions are needed that could be continuously implemented to improve ordering practices long term.

Medication errors in intravenous drug preparation and administration: a multicentre audit in the UK, Germany and France.

BACKGROUND: Previous studies have identified medication errors in preparing and administering intravenous medicines of 13-84% in hospitals in individual countries. OBJECTIVE: To compare the effect of the design and implementation of systems for the preparation and administration of intravenous therapy in hospitals in three European countries on the number of observed medication errors. To gain a better understanding of these risks and the methods used in each country to manage them. DESIGN: Prospective audit. SETTING: Six hospital departments in the UK, Germany and France willing to participate in the audit as part of a quality improvement programme. METHODS: Direct observation of the preparation and the administration of intravenous drugs made by a single observer in each country. MAIN OUTCOME MEASURES: Medication process errors. RESULTS: 824 doses were prepared and 798 doses administered. The product was either not labelled or incorrectly labelled in 43%, 99%, and 20% of doses administered in the UK, German and French hospitals, respectively. The wrong diluent was used in 1%, 49% and 18% of cases, respectively, and the wrong rate of administration was selected for 49%, 21% and 5% of doses observed, respectively. At least one deviation from aseptic technique was observed among 100%, 58%, and 19% of cases in the three countries. CONCLUSION: Uncontrolled risks in the intravenous systems studied were observed in all three countries. Intravenous therapy must be regarded as a high risk activity where the use of risk management procedures to minimise risk to patients is seen as a high priority by all those involved with these duties. There is a requirement to develop better national (possibly international) procedures for safe intravenous practice.

Double-blind placebo-controlled trial of oral dehydroepiandrosterone in patients with advanced HIV disease.

OBJECTIVE: Plasma levels of dehydroepiandrosterone sulphate (DHEA-S) decrease with the progression of HIV disease. Here, we report on the efficacy and safety of the oral administration of DHEA as replacement therapy, in patients with advanced HIV disease, in a trial that was primarily aimed at assessing quality of life. DESIGN: The trial was randomized and double-blind. Thirty-two patients were allocated to either DHEA 50 mg per day for 4 months (n = 14) or a matching placebo (n = 18). Clinical data, virological and immunological surrogate markers of HIV infection, plasma levels of DHEA-S and the Medical Outcomes Study HIV Health Survey (MOS-HIV) quality of life scale were recorded every month. RESULTS: The mean age of the patients was 40 +/- 11 years. The mean CD4 cell count at baseline was 32.5 +/- 32.4 x 10(6)/l. The mean DHEA-S plasma level at baseline was 5.23 +/- 0.76 micromol/l. No side-effects related to DHEA occurred during the study. A statistically significant increase in the levels of DHEA-S was observed in the treated group throughout the study (P < 0.01). A significant improvement in the Mental Health and Health Distress dimension of MOS-HIV was observed in the DHEA treated group; P = 0.001 and 0.004, respectively. No change in CD4 cell counts was seen during follow-up. CONCLUSIONS: The administration of DHEA in patients with advanced HIV infection results in improved mental function scores as assessed by the MOS-HIV quality of life scale.

Improvement of postischemic kidney function by reperfusion with a specifically developed solution (BT01).

Reperfusion is a critical phase of organ preservation. The purpose of this study was to develop a solution specifically for postischemic kidney reperfusion. Unilateral left normothermic kidney ischemia was induced for 60 minutes in two groups of micropigs. In group 1 (control pigs, n = 6) the kidney was reperfused immediately with pure blood at systemic pressure by unclamping the renal artery. In group 2 (test animals, n = 6) the kidney was initially reperfused with an intracellular flush solution enriched with solution BT01 composed of cytoprotectors (natriuretic factor, PGI2), free radical chelating agents (allopurinol, mannitol), and substrates for the mitochondrial respiratory chain (aspartate, glutamate). This solution was mixed immediately before use with blood in a ration of 1:4 parts and injected into the left renal artery with a perfuser at a constant pressure of 60 mm Hg. After 20 minutes, the kidney was reperfused with systemic blood for 100 minutes. Glomerular filtration rate (GFR) was determined by measuring inulin clearance. Kidney blood flow was measured throughout the experiment. After 120 minutes of reperfusion, the kidneys were removed for histologic examination. In the control pigs (group 1) 50% of the animals were anuric. The ratio between GFR measured in the left kidney at the end of perfusion and at equilibrium in the remaining animals was 0.16 +/- 0.01. In test animals (group 2) all animals recovered diuresis. The ratio between GFR measured in the left kidney at the end of perfusion and equilibrium was 0.51 +/- 0.12 (p < 0.001, group 2 vs. group 1). In group 2 postperfusion kidney blood flow was higher than in group 1 (63.0 ml/min vs. 27.4 ml/min; p < 0.05) because of a decrease in renal vascular resistance. Light microscopic examination of kidneys form animals in group 1 revealed tubular necrosis that extended to the parenchyma, with exposure of tubular interstitium. In group 2 only degenerative lesions with edema of tubular cells and disappearance of brush borders were observed. Our findings indicate that flushing the kidneys with BT01 solution mixed with blood improves postischemic kidney function by reducing reperfusion damage.