[Which factors are associated to hemorrhagic adverse drug events related to antivitamin K?]. / Quels facteurs associés à la survenue d'un événement iatrogène hémorragique chez les patients sous antivitamines K ?

INTRODUCTION: Hemorrhagic events constitute a major risk for patients on oral anticoagulant therapy. PATIENTS AND METHODS: We conducted a prospective survey of all patients taking oral anticoagulants and admitted to the emergency room of Grenoble University Hospital over a period of 10 months. The objective was to identify the causes of drug-induced adverse hemorrhagic events, and whether they were related to health care practices or patient behavior concerning their treatment. RESULTS: Two hundred and sixteen patients treated with oral anticoagulants were identified and 68 of them had a hemorrhagic adverse drug event. Not taking into account prior medial history before prescribing an anticoagulant was noted for 21 of the patients who experienced a hemorrhagic event (p = 0.0003). In addition, compared with patients who had not had a hemorrhagic event, inadequate prescribing with regard to doses and administration frequency there were also more common in the hemorrhagic event group (p < 0.0001). Pharmacists delivering the drugs had not intervened to correct drug interactions, contraindications and inadequate doses in 72% of patients with hemorrhage (p < 0.0001). Other factors associated with increased the risk of hemorrhage were self-medication, not taking the prescribed drug at a predefined time of the day, insufficient INR monitoring and poor compliance (p < 0.0001). DISCUSSION AND CONCLUSION: To achieve the beneficial effects expected with anticoagulants, physicians must carefully comply with prescription recommendations, especially for elderly patients. Pharmacists delivering the drugs should also intervene more readily when required.

[Hemorrhagic complications of anti-vitamin K]. / Complications hémorragiques des anti vitamine K: enquête de prévalence aux urgences du CHU de Grenoble.

Adverse events related to oral anticoagulants represent a major public health problem. Hemorrhagic episodes are the most frequent complications and can be life-threatening. A 10 month prospective survey on all cases treated with anti-vitamin K (AVK), and admitted to emergency room of CHU Grenoble, was conducted to identify the hemorrhagic adverse drug events (HADE). The evaluation support was a directive questionnaire and consisted of 3 parts: patient characteristics, patient's medicated treatment and the hemorrhagic event. 216 patients treated with AVK were identified and 68 of them presented a hemorrhagic adverse drug event. 60 patients older than 65 years out of 158, presented HADE (38%); versus 8 patients < or = 65 years out of 58 (RR = 2.75; p = 0.0007). Among the patients who have their INR > or = 5, 79% developed HADE versus 16% in the group who had their INR < 5 (< 0.0001). In the group of patients who had a change in drug therapy within the 7 days preceding their admission, 47% developed HADE versus 25% of patients whose treatment was not modified: Anti-microbial agents were the drug most frequently involved. The patient's knowledge of INR value and signs of excess AVK were significant. Concerning missed dose, 48 patients declared taking the missed dose with the next dose or when they remembered: 35% of them developed HADE (p = 0.49).

Drug-related problems in medical wards with a computerized physician order entry system.

OBJECTIVE: Identification and estimation, by clinical pharmacists participating in routine medical rounds, of drug-related problems (DRPs), arising despite the use of a computerized physician order entry (CPOE) system. METHODS: An 18-month prospective study of DRPs through a CPOE was conducted by seven clinical pharmacists participating in ward activity. DRPs were identified by two independent pharmacists using a structured order review (French Society of Clinical Pharmacy instrument). RESULTS: A total of 29 016 medication orders relating to 8152 patients were analysed, and 2669 DRPs, involving 1564 patients (56% female; mean age 72.6 years), were identified representing 33 DRPs per 100 admissions. The most commonly identified DRPs were non-conformity to guidelines or contra-indication (29.5%), improper administration (19.6%), drug interaction (16.7%) and overdosage (12.8%). There were 429 different drugs associated with these DRPs. Cardiovascular drugs were the most frequently implicated (22.2%), followed by antibiotics/anti-infectives (13.3%) and analgesics/antiinflammatory drugs (11.3%). Different types of DRPs were closely associated with specific classes of drugs. CONCLUSIONS: Drug-related problems are common even after implementation of CPOE. In this context, routine participation of clinical pharmacists in clinical medical rounds may facilitate identification of DRPs. Pharmacists should be able to enhance patient safety through such involvement.

[Drug supply chain safety in hospitals: current data and experience of the Grenoble university hospital]. / La sécurisation du circuit du médicament dans les établissements de santé : données actuelles et expérience du centre hospitalier universitaire de Grenoble.

Drug supply chain safety has become a priority for public health which implies a collective process. This process associates all health professionals including the pharmacist who plays a major role. The objective of this present paper is to describe the several approaches proven effective in the reduction of drug-related problem in hospital, illustrated by the Grenoble University Hospital experience. The pharmacist gets involved first in the general strategy of hospital drug supply chain, second by his direct implication in clinical activities. The general strategy of drug supply chain combines risk management, coordination of the Pharmacy and Therapeutics Committee, selection and purchase of drugs and organisation of drug supply chain. Computer management of drug supply chain is a major evolution. Nominative drug delivering has to be a prior objective and its implementation modalities have to be defined: centralized or decentralized in wards, manual or automated. Also, new technologies allow the automation of overall drug distribution from central pharmacy and the implementation of automated drug dispensing systems into wards. The development of centralised drug preparation allows a safe compounding of high risk drugs, like cytotoxic drugs. The pharmacist should develop his clinical activities with patients and other health care professionals in order to optimise clinical decisions (medication review, drug order analysis) and patients follow-up (therapeutic monitoring, patient education, discharge consultation).

[Economic impact of an automated dispensing system in an intensive care unit]. / Impact économique de la mise en place d'un automate de distribution des médicaments dans un service de réanimation.

OBJECTIVE: Automated dispensing systems (ADS) allow a reduction of medication errors and an improvement of drug distribution in clinical ward. The objective of this study was to evaluate the economic impact of ADS in an intensive care unit. STUDY DESIGN: A cost-benefit model was constructed based on the hospital perspective. METHODS: The system was evaluated before-after implementation of an ADS in a 12-bed cardiovascular intensive care unit of a French teaching hospital: (a) by a measuring nurse and pharmacy technician working time required for various tasks; (b) by measuring the cost of drug storage and the cost of expired drug; (c) by measuring the nurses' acceptability. RESULTS: After ADS was installed, nursing personnel spent less time on medication-related activities (mean of 1.9 hour/day of nursing time). Pharmacy technicians spent more time on floor-stock activities (mean of 0.7 hour/day of technician time). Implementation reduced the cost of drug storage by 56% (14,742 euros) and cost of expired drug by 9,086 euros per year. Finally, cost-benefit analysis including potential savings in terms of working time showed a net benefit of 71,586 euros (14,317 euros/year). The ADS was given high marks by the nurses; 77% wanted to keep it on their unit. CONCLUSIONS: Implementation of ADS is expected to generate direct savings for the hospital and working time reallocation, for nurses to interact with patients and for pharmacy technicians to get involved on the ward.

[Oral anticoagulants: a literature review of herb-drug interactions or food-drug interactions]. / Interactions des anticoagulants oraux avec les plantes médicinales ou aliments: une revue de littérature.

OBJECTIVE: To identify herbal medicines and food products which can interact with anticoagulant therapy. MATERIAL AND METHOD: Literature review using key words: "anticoagulants", "herb-drug interaction", "food-drug interaction", "drug chinese herbal", "medicine herbal", "plant preparation", "dietary supplements". DATA SOURCES: Medline (january 1966 to june 2006) and Pascal (1987 to 2006). Case reports, systematic reviews, in vitro studies, clinical studies published in french or in english (or with an english extract) have been undertaken. RESULTS: Eighty articles were selected (two both including a case report and a study): 14 systemic review, 43 case reports, 25 studies (17 studies in humans: nine randomized and controlled, three controlled), six controlled studies in animals and two in vitro studies. DISCUSSION: A wide range of herbal medicines and food products can interact with anticoagulants. Clinical relevance of these effects is difficult to characterise (nature of existing reports, contradiction between studies, difficult extrapolation to human). CONCLUSION: It is difficult to predict the incidence or severity of such interactions. However, awareness of these potential interactions is necessary to achieve optimal anticoagulation therapy: pharmacist can play a crucial role identifying such interactions in case of disturbed INR; clinicians should be informed to monitor closely the therapy, particularly when such products are started or discontinued.

Assessing a pharmacist-run anaemia educational programme for patients with chronic renal insufficiency.

OBJECTIVE: Assessment of a pharmacist-run anaemia educational programme for patients with chronic renal insufficiency. SETTING: Nephrology Department, Grenoble Hospital, France. METHOD: A 12-week prospective study, using a before-after intervention design. Included in the study were predialysis outpatients with a haemoglobin level < 10 g/dl, de novo EPO prescription; judged qualified by the nephrologist for self-injections; accepting self-injections. The intervention was a single one-hour individual session between the pharmacist and the patient to target (1) medical and therapeutic information; (2) information on the device, a pen used with a cartridge of beta epoietin; (3) training with the pen; and (4) self-injection of the first dose by the patient, in front of the pharmacist. Main outcome measures were knowledge (7-item questionnaire); handling skills (observation) and Quality of Life (1 Likert scale on apprehension towards self-injections and 3 Linear Analog Scales on energy, daily activities, and general well-being); compliance (self-report on self-administered injections) and haemoglobin level. RESULTS: Ten patients were followed for 3 months after intervention. The evolution of the knowledge was positive but not statistically significant after the programme (80% of good answers before; 93% 3 months later). Concerning the patients' skills, difficulties with the pen were important at inclusion, (1) to reset the pen into zero position (2.8 tries/patient +/- 1.8); (2) to insert a new cartridge (1.9 +/- 1.1); and (3) to take air out of the cartridge (2.3 +/- 1.2). After the session, results were satisfactory, since 3 months later, all patients were still on self-injections. QoL improved significantly over the study period respectively on energy, daily activities, and general well-being. The mean level of compliance remained above 90% at 3 months for 8 out of 10 patients. Patients reached the haemoglobin target value of 11 g/dl during the second month of treatment. CONCLUSION: A tailored educational programme conducted by a pharmacist is beneficial for anaemia patients with chronic renal insufficiency. The programme seems to result in a high level of compliance, leading to an optimal haemoglobin level within two months.

[Physicians' expectations towards pharmacy services on ward]. / Service pharmaceutique en service de soins: quelle adéquation avec les attentes des prescripteurs?

Clinical pharmacy practice reveals an effective strategy to reduce medication errors and related costs. The present study aimed at confronting hospital perscribers' expectations towards pharmacy services and their jugement on the usefulness of routine pharmacist interventions. A questionnaire was sent to 562 prescribers of the Grenoble Teaching Hospital. They were asked to rank 1. key-points of prescribing process and specify those that could be shared with the pharmacist, 2. usefulness of a series of pharmacist interventions extracted from daily routine, 3. opportunity to perpetuate pharmacy service on ward. Questionnaire response rate was 18%. Concerning the key-points of the prescription process, (compliance to indications and guidelines, drug choice, dosage), responses express the physician's monopoly. Pharmacist's input in terms of drug choice or monitoring seems reduced. Experience in working with a clinical pharmacist or "junior prescriber" status have a positive effect on precribers' perception towards clinical pharmacy. 25% of the respondents cite the pharmacist as an active player in managing different key-points of the prescription. After being confronted with clinical examples, 73% of the prescribers consider pharmacists' interventions as useful.

[Osteofluorosis caused by excess use of toothpaste]. / Ostéose fluorée due à une consommation excessive de dentifrice fluoré.

BACKGROUND: Osteofluorosis is caused by chronic fluoride intoxication. Fluoride is used in toothpaste for the prevention of dental caries, and dental fluorosis has often been reported among children and attributed to ingestion of fluoride toothpaste. We report a case of chronic fluoride intoxication caused by excess use of toothpaste in an adult. CASE: A 45-year-old woman consulted a rheumatologist for painful swelling of the fingers, phalangeal rather than articular. She also had brown staining on her teeth. Radiography of the hands showed periosteal apposition on the phalanges. Further work-up ruled out tumoral or thyroid causes. Laboratory tests showed elevated fluoride levels in the blood (50.9 micromol/L, normal<1.5 micromol/L) and in the urine (721 micromol/L, normal<46 micromol/L). On questioning, we found only one cause for chronic fluoride intoxication: excess and unusual use of toothpaste. The patient brushed her teeth 18 times a day and swallowed the toothpaste, because she liked the taste. She consumed a tube of toothpaste every 2 days, thereby swallowing 68.5 mg of fluoride every day. Suspecting fluorosis from toothpaste, we asked the patient to use a toothpaste without fluoride. Sixteen weeks later, the pain had ceased, and laboratory tests showed massively reduced but still elevated fluoride levels in the blood (6.9 micromol/L) and urine (92.7 micromol/L). CONCLUSION: In this rare case of fluoride intoxication, misuse of a normally innocuous product caused osteofluorosis.

[Therapeutic education of patients receiving anticoagulants for thromboembolic venous disease: description of the Educ'AVK program]. / Education thérapeutique des patients sous anticoagulants oraux pour maladie thromboembolique veineuse: description du programme Educ'AVK.

Educ'AVK is an education program designed for patients starting an oral anticoagulant treatment following a thromboembolic event (deep venous thrombosis or pulmonary embolism). Patients enrolled are judged capable of self-management of their drug treatment. The intervention, adapted to a short-term treatment, consists in an 3-step one-on-one teaching session conducted by a trained pharmacist. 1) Identification of the patient's needs--or educational diagnosis. 2) Definition of educational objectives adapted, first, to the patient's cognition: to be able to describe indications for therapy and potential risks factors for anticoagulant bleeding, to interpret INR lab tests and to solve a problematic treatment situation related second, to the patient's behaviour: to be able to anticipate the risk (how to enhance compliance, how to deal with a missed dose.), to take relevant decisions when dealing a therapeutic incident (bleeding, INR outside of the targeted range). 3) Choice of appropriate teaching contents and methods to reach the objectives. We used the "individual guidance" technique associated with original tools: a picture book to describe the pathology and the treatment; a booklet synthesizing all the information given by the educator during the consultation. This booklet presents 3 key-points: the information is specifically targeted to thromboembolic venous disease; the information integrates the risk-level of the patient (3 different booklets according to the patient's level of risk, of bleeding, of thromboemboly, no specific risk); there is a section where the patient writes down his/her INR results in a table specifically adapted to his/her risk level--bleeding, thromboemboly, no specific risk--and giving recommendations for the management of INR out of the targeted range.

[Impact of an education program on patient behaviour favoring prevention of drug-related adverse events: a pilot study in patients receiving oral anticoagulants for thromboembolic venous disease]. / Impact d'un programme d'éducation thérapeutique sur les attitudes de prévention vis-à-vis du risque iatrogène: étude pilote contrôlée visant les patients sous anticoagulants oraux pour maladie thromboembolique veineuse.

OBJECTIVE: Adverse events related to oral anticoagulants represent a major public health problem. Including patient education as part of the prevention strategy could contribute to improved effectiveness and safer use of drugs. The present study aimed at evaluating the outcomes of a patient education program inspired by recommendations from French Health Authorities (AFSSAPS) and based on an "individual guidance" approach. METHOD: The study was conducted in two groups of hospitalized patients treated with oral anticoagulants for thromboembolic disease. Each patient in the first (intervention) group attended an individual teaching session conducted at discharge by a trained pharmacist. Patients in the second (control) group were given usual care. These two groups were compared at inclusion (before intervention) and three months later. The outcomes considered were the acquisition of: 1) knowledge, 2) risk anticipation and compliance behaviours characterized by the stability of INR and the incidence of hemorrhagic episodes during the period of observation. RESULTS: Fifty-nine patients (average age 65 years) were included (29 in the intervention group and 30 in the control group). Three months after the intervention, the intervention group exhibited 1) better knowledge (higher rate of restitution of treatment-related information--name of the drug, administration plan, targeted range for INR (...), interpretation of INR results (p<0.05), management of a specific scenario where INR declines concomitant to elevation of anticoagulant dose (p<0.05)); 2) higher rates of relevant behaviours (p<0.05)--in the event of a missed dose, anticipating an event with a high risk of bleeding, dealing with signs of overdose--and higher compliance profile (ns) (stability of INR, and number of hemorragic episodes). A multivariate model integrating the potential explanatory variables for frequency of hemorrhagic episodes at 3 months (demographic data, history of thrombotic disease, INR stability, reference group (intervention/control)), showed that the only variable significantly associated with frequency of bleeding events was the reference group of the patient (p=0.05; odds-ratio=4.5, interval of confidence: [1-21]). CONCLUSION: Multivariate analysis demonstrated that the probability of developing a hemorrhagic event when taking an oral anticoagulant is on average 4-fold greater in patients given usual care than in patients given individual guidance a pharmacist. A larger randomized trial is currently under way in the Rhône-Alpes region, France, to validate these exploratory results.

[Why psychotic patients are not drug compliant?]. / Pourquoi les patients souffrant de troubles psychotiques ne sont-ils pas observants à leurs médicaments?

Improving patient's compliance with antipsychotics is a major issue in psychosis management. As the point is to convince patients to take their drugs, we have to better understand why they should want or not want to do that. Compliance is actually a complex behavior, involving many psychosocial factors. Thus, we conducted a survey to assess compliance rate and to investigate determinant compliance factors of psychotic outpatients (according to CIM-10 diagnosis). Method - Investigated factors were selected according both to biomedical researches and to psychosocial theories (Health Belief Model). Around 20 influential factors, described in publication, were investigated. The questionnaire design conformed to sociological survey's rules. More, in order to promote patients frankness, the investigator was independent of the medical team. We processed the answers of 63 patients (61% men, average age 40 years), having presented with psychotic disorders for an average of 10 years, without addictive comorbidity (CIM-10). Results - The compliance rate was only 47%. Biomedical factors related to patients (sex, age, social way of life, professional state, and study level), as well as those related to treatment (complexity, duration, side effects occurring), don't affect compliance behavior. The psychosocial factors investigation reveals more interesting results. If the patient trusts his medicines, and do not subscribe to drug's negative beliefs , compliance rate is significantly improved (p=0,0062). It appears to be the survey's best factor for a good compliance, but it concerns only 29% of the investigated patients. When patients aknowledge the whole positive effects of their medicines, compliance is also inclined to improved (p=0,075). But compliance significantly decreases when patients felt that adverse effects are difficult to undergo or unbearable (p=0,04). It also inclined to decrease when family or friends have a negative opinion or are hostile to the pharmacological treatment. None of the other factors influence patient's compliance. Conclusion - These results demonstrate that convincing psychotic patients to be compliant is mandatory. As determinant compliance factors appear to be complex psychosocial ones, it also demonstrates that information procedure needs to be extensively structured.

[Evaluation of the impact of individual antibiotic order forms on consumption of antibiotics]. / Evaluation de l'impact d'une prescription nominative sur les consommations d'antibiotiques.

The aim of the study was to assess the impact of an individual patient order form which concerned the 21 most costly antibiotics in a university hospital. Antibiotics expenditures were monitored from 1995 to 1999 and were expressed in 1999 French Francs per 100 patient days (p.d.). The time series were analyzed by auto-regressive models. The trend of antibiotics expenditures which were concerned by the individual patient order form was a yearly increase of 50 FF/100 p.d. (p < 0.01). The individual patient order form had no significant impact on global antibiotics expenditures but there were some differences across departments: antibiotics costs decreased 1.293 FF/100 p.d. (p = 0.02) in intensive care departments. Monitoring antibiotics consumption should be continued in order to increase power of analysis and to assess the impact of the implementation of guidelines.

Evaluation of a program to improve the prescription-writing quality in hospital.

This paper aims to evaluate the effectiveness of a program designed to improve the quality of drug prescription-writing at a university hospital in France. Improvement actions included feed-back from yearly audits and the dissemination of recommendations on how best to write the prescriptions. A random sample of 30 stays was selected from among the hospitalizations for the year 1996. From each patient, medical records were searched for the first prescription order of the stay and its quality was assessed according to standards. A total of 872 records were relevant and included 3,289 medications. The results were compared to those obtained for the two previous years. Actions to sensitize prescribers resulted in an insufficient improvement of most indicators of prescription-writing quality with results remaining well below ideal standards. The hospital staff concerned had a positive opinion of the program which led to an awareness of prescription problems. This assessment showed that the program had a moderate impact on prescribers' practice and efforts must be continued.

[Acceptability of computerized prescription writing in the hospital. Survey of 44 drug-prescribing physicians]. / Acceptabilité de la prescription informatisée à l'hôpital. Enquête auprès de 44 médecins prescripteurs.

OBJECTIVES: The purpose of this work was to assess the acceptability of computerized prescriptions delivered by hospital prescribers. METHODS: The study was conducted in four clinical units of the Grenoble University Hospital that have a computerized prescription system. Forty-four physicians using the system responded to a questionnaire concerning the act of prescribing and the benefits or drawbacks of the system. RESULTS: Generally, the computerized prescription system was well accepted. The first drawback mentioned was the time spent manipulating the software. Safe prescription was noted as one of the advantages. Overall, organizational rather than technical factors appeared to condition the development of computerized prescription writing. CONCLUSION: Optimization of computerized prescription writing requires a reorganization of the care unit. Consultation schedules and working relations between the prescriber and other healthcares and hospital pharmacies will have to be adapted.

Evaluation of the microbicidal efficacy of Steris System I for digestive endoscopes using GERMANDE and ASTM validation protocols.

In the light of more and more invasive procedures being carried out in digestive endoscopy using sterile devices, it appears necessary to put in place a process of endoscope reprocessing capable of ensuring the complete elimination of micro-organisms contaminating the device. We undertook a study of the microbial efficacy of STERIS SYSTEM 1 (SS1) which purports to achieve this objective. The channels of a gastroscope and a colonoscope were contaminated with suspensions of Pseudomonas aeruginosa, Aspergillus niger and Bacillus subtilis spores. Two procedures were then followed: (1) manual washing only, and (2) treatment in SS1 without prewashing. Recoveries of organisms were made from each channel according to a standard methodology to discover any survivors. Contamination controls we re assessed to measure the logarithmic reduction between the initial contamination and that recovered from the channels. Six cycles per micro-organisms, per type of endoscope, and per type of procedure were carried out. From an initial contamination leve l of 10(6) micro-organisms per endoscope, no micro-organisms were recovered in 35 of the 36 cycles with the SS1. In one cycle with the colonoscope, three B. subtilis organisms were recovered from the channels. Washing only gave microbial reductions which varied according to the micro-organism tested. The maximum reduction with washing alone was by a factor of 10(3 +/- 0.1)for B. subtilis and the minimum reduction factor was 10(3 +/- 0.3)for P. aeruginosa. Considering the results obtained with SS1 without prewashing and the efficacy obtained from washing only, the washing step offers an additional antimicrobial assurance reduction factor of between 10 and 103.1. This study shows that SS1, integrated into an overall reprocessing procedure for digestive endoscopes, is capable of delivering the complete elimination of contaminating micro-organisms in a reduced time and eliminates the toxic risk of reprocessing associated with aldehyde based disinfectants.

[Evaluation of 7 endoscope washer-disinfectors: bactericidal activity of the disinfectants, antibacterial efficacity of paired washer-disinfector products]. / Evaluation de sept laveurs-désinfecteurs d'endoscopes: activité bactéricide des désinfectants, efficacité antibactérienne des couples laveur-désinfecteur/produits.

The authors studied seven automatic washer disinfectors for flexible endoscopes with two methods. The first method, a microdilution method, studied the bactericidal activity of the seven disinfectants against 21 strains: four reference strains, 14 hospital strains reported in the literature as nosocomial strains responsible for infections transmitted by flexible endoscopes and three vancomycin-resistant Enterococci. The ability of the seven automatic washer disinfectors to decontaminate flexible endoscopes following inoculation with four reference strains was studied with the second method. There were three kinds of results: the results of three automatic washer disinfectors in conformity with both methods; the results of three automatic washer disinfectors conformity with 1 method only; the results of one automatic washer disinfector without conformity with any methods. Both methods should be used for evaluation of automatic washer disinfector. Then, these results emphasize the necessity to modify the use of disinfectants and/or the systems of some automatic washer disinfectors.