ANTIFON-CLIC®, a new clinical decision support system for the treatment of invasive aspergillosis: is it clinically relevant?

BACKGROUND: Invasive aspergillosis (IA) is increasing especially in new groups of patients. Despite advances in management, morbidity and mortality related to IA remain high. Thus, Clinical Decision Support System (CDSS) dedicated to IA are needed to promote the optimal antifungal for each group of patients. PATIENTS AND METHODS: This was a retrospective multicenter cohort study involving intensive care units and medical units. Adult patients who received caspofungin, isavuconazole, itraconazole, liposomal amphotericin B, posaconazole, or voriconazole, for the treatment of IA were eligible for enrollment. The primary objective was the concordance between the clinician's prescription and the prescription recommended by the CDSS. The secondary objective was the concordance according to different hospitals, departments, and indications. RESULTS: Eighty-eight patients (n=88) from three medical hospitals were included. The overall concordance was 97% (85/88) including 100% (41/41) for center A, 92% (23/25) for center B, and 95% (21/22) for center C. There was no significant difference in concordance among the hospitals (P=0.973), the departments (P=1.000), and the indications (P=0.799). The concordance was 70% (7/10) for isavuconazole due to its use as an empirical treatment and 100% (78/78) for the other antifungals. DISCUSSION: The concordance rate was high whatever the hospital, the department, and the indication. The only discrepancy was attributed to the use of isavuconazole as an empirical treatment which is a therapeutic option not included in the CDSS. CONCLUSIONS: This new CDSS dedicated to IA is meeting the clinical practice. Its implementation in routine will help to support antifungal stewardship.

[What is the impact of changes in the drug circuit on dispensing activity during pharmaceutical duty?] / Quel impact des évolutions du circuit du médicament sur l'activité de dispensation durant la permanence pharmaceutique ?

INTRODUCTION: Pharmaceutical permanence (PP), outside the working hours of an in-house pharmacy (PUI), allows to guarantee the continuity of care in health-care institutions. A retrospective review of urgent drug dispensing was carried out in the light of changes in the drug circuit. MATERIALS AND METHOD: The analysis of drug dispensations was performed over a period from 2011 to 2019. The average number of drugs dispensed per shift, annual dispensations, and their variation by day of the week were studied. The increase is statistically significant and is found on both weekdays and weekends. Each drug was identified according to its Anatomical Therapeutic Chemical (ATC) classification. Data on the activities of our institution (number of hospitalizations, average length of stay) were also collected. RESULTS: In 2011, an average of 36 medications were dispensed per on-call period, compared with 77 in 2019 (a doubling of activity). The increase is statistically significant and is found on both weekdays and weekends. Neurological drugs and anti-infectives represent on average 43 % of the drugs dispensed. At the same time, there was a decrease in average length of stay and an increase in hospitalizations (-10 % and +16 % respectively). DISCUSSION: The increase in the average number of medications dispensed per shift is notable. It reflects a strong and gradual increase in activity, which was increased when the full vacuum cabinets (FVCs) were introduced, which improved the quality and safety of the pharmaceutical circuit. The revision of the allocations and the information of prescribers on the drug circuit will optimize the activity and refocus it on the pharmaceutical analysis of urgent needs.

Integrating a pharmacist into an anaesthesiology and critical care department: Is this worthwhile?

Background Operating rooms and Intensive Care Units are places where an optimal management of drugs and medical devices is required. Objective To evaluate the impact of a dedicated pharmacist in an academic Anaesthesiology and Critical Care Department. Setting This study was conducted in the Anaesthesiology and Critical Care Department of Grenoble University Hospital. Method Between November 2013 and June 2017, the drug-related problems occurring in three Intensive Care Units and their corrections by a full-time clinical pharmacist were analyzed using a structured order review instrument. Pharmaceutical costs in the Anaesthesiology and Critical Care Department were analyzed over a 7 year period (2010-2016), during which automated dispensing systems and recurrent meetings to review indications of medications and medical devices were implemented in the department. Main outcome measure Analysis of two issues: correcting drug-related problems and containing pharmaceutical costs. Results A total of 324 drug-related problems were identified. The most frequent problem concerned anti-infective agents (45%), and this was mainly due to the over-dosage of drugs (30%). Dosage adjustments were the most frequent interventions performed by the pharmacist (43%). Over the 7 year period, pharmaceutical costs decreased by 9% (€365,469), while the care activity of the department increased by 55% (+ 12,022 surgical procedures and + 1424 admissions in the ICU). Conclusion Integrating a pharmacist into the Anaesthesiology and Critical Care Department was associated with interventions to correct drug-related problems and containing pharmaceutical costs. Pharmacists should play a central role in such medical environments, to optimize the use of drugs and medical devices.

Radiology residents' skill level in chest x-ray reading.

RATIONALE AND OBJECTIVES: To evaluate the mean skill level of radiology residents in chest X-ray (CXR) reading, with regard to cognitive mechanisms involved in this task and to investigate for potential factors influencing residents' skill. MATERIALS AND METHODS: Eighty-one residents were evaluated through a test set including CXR expected to mobilize detection skills (n=10), CXR expected to mobilize interpretation skills (n=10) and normal CXR (n=4). For each radiograph, residents were asked to answer three questions: Does this radiograph show normal or abnormal findings? Does it require complementary computed tomography study? What is your diagnosis? Residents' answers were evaluated against an experts' consensus and analyzed according to year of residency, attendance at CXR training course during residency and the average number of CXR read per week. RESULTS: Residents' mean success rate was 90.4%, 76.6% and 52.7% for the three questions, respectively. Year of residency was associated with better diagnostic performances in the detection CXR category (P=0.025), while attendance at CXR training course was associated with better performances in the interpretation CXR category (P=0.031). There was no influence of the number of CXR read per week. CONCLUSION: These results may suggest promoting systematic CXR theoretical training course in the curriculum of radiology residents.

Compliance with carbapenem guidelines in a university hospital.

OBJECTIVE: We aimed to evaluate carbapenem prescription compliance with guidelines for nosocomial and community-acquired infections. PATIENTS AND METHODS: We conducted a prospective study over a four-month period at our university hospital. We included all adult and pediatric hospitalized patients who had received at least one dose of carbapenem. Data was collected from patients' medical records (hard copy and computerized data; CristalLink software). Compliance with guidelines was assessed by two infectious disease specialists. Assessment criteria included indication, antibiotic choice, dosage, and treatment duration. RESULTS: We included 152 patients in the study (65.4% of men). Carbapenem prescription was appropriate for 76.3% of prescriptions. The use of carbapenems was considered appropriate for 73.9% of empirical prescriptions and for 77.8% of documented prescriptions. Non-compliance with guidelines was mainly due to prescriptions for community-acquired infections. Antibiotic de-escalation could not be initiated in 40.3% of patients and was only initiated in 51.7% of patients for whom it could be considered. Although the average treatment duration was 7.5 days, 23.7% of patients received carbapenems for more than 10 days. CONCLUSION: These results highlight the need for a strong carbapenem stewardship program in our hospital.

Vesicle permeabilization by purified soluble oligomers of prion protein: a comparative study of the interaction of oligomers and monomers with lipid membranes.

The conversion of normal cellular prion protein (PrP) into its pathological isoform, scrapie PrP, may occur at the cell surface or, more probably, in late endosomes. The early events leading to the structural conversion of PrP appear to be related to the presence of more or less stable soluble oligomers, which might mediate neurotoxicity. In the current study, we investigate the interaction of alpha-rich PrP monomers and beta-rich size-exclusion-chromatography-purified PrP oligomers with lipid membranes. We compare their structural properties when associated with lipid bilayers and study their propensities to permeabilize the membrane at physiological pH. We also study the influence of the N-terminal flexible region (residues 24-103) by comparing full-length PrP(24-234) and N-terminally truncated PrP(104-234) oligomers. We showed that both 12-subunit oligomers cause an immediate and large increase in the permeability of the membrane, whereas equivalent amounts of monomeric forms cause no detectable leakage. Although the two monomeric PrP constructs undergo an alpha-to-beta conformational change when bound to the negatively charged membrane, only the full-length form of monomeric PrP has a weak fusogenic effect. Finally, the oligomers affect the integrity of the membrane differently from the monomers, independently of the presence of the N-terminal flexible domain. As for other forms of amyloidogenesis, a reasonable mechanism for the toxicity arising from PrP fibrillization must be associated with low-molecular-weight oligomeric intermediates, rather than with mature fibrils. Knowledge of the mechanism of action of these soluble oligomers would have a high impact on the development of novel therapeutic targets.

Aporte de hierro en mujeres sin anemia pero con posible carencia para la fatiga de origen desconocido / Iron intake without anemia in women, with a possible deficit in fatigue of unknown origin

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[Acute pulmonary edema during nicardipine and salbutamol therapy for preterm labor in twin pregnancy]. / Oedème aigu du poumon au décours d'une tocolyse par nicardipine et salbutamol lors d'une menace d'accouchement prématuré sur grossesse gémellaire.

We report the case of a 38-year-old parturient at 30 weeks 2 days term of a multiple pregnancy who experienced acute pulmonary edema more than 48 hours after tocolytic treatment with nicardipine and salbutamol. The patient was transferred from a level 1 perinatal center to a level 3 perinatal center by the Grenoble mobile intensive care unit in application of the in utero transfer protocol for preterm labor before 33 weeks with twin pregnancy. This case illustrates the risk of tocolytic treatment and potential adverse effects in the event of preterm labor on twin pregnancy. The question of associating a second tocolytic after failure of the first is also raised.

[Changing medical practices and nosocomial infection rates in French maternity units from 1997 to 2000]. / Surveillance des infections nosocomiales dans les maternités du sud-est de la France entre 1997 et 2000.

OBJECTIVES: In this study we describe the changes in medical practices and nosocomial infection rates in obstetrics observed through a surveillance network in the South East of France. MATERIAL AND METHOD: The maternity units which belong to this network participated in voluntary surveillance using the network's methodology. The criteria for the diagnosis of nosocomial infections were in accordance with the methods described by the Centers for Disease Control and Prevention. RESULTS: 101240 pregnancies including 18503 caesareans (18.3%) were included in the network from 1997 to 2000. During the study period, nosocomial infection rates following caesarean section and vaginal delivery decreased respectively from 7.8% to 4.3% (p < 0.001) and from 2.2% to 0.9% (p < 0.001). This evolution was compared with the evolution of collected risk factors. CONCLUSION: In spite of the methodology limits, general value of surveillance and infection control programs in maternity units has been confirmed by the results of this surveillance network. During the study period, both obstetrics-related risk factors for nosocomial infection and observed hospital-acquired infection rates were dramatically reduced, what prove an improvement of quality of care in maternity units.

[Management of infectious risk associated with therapeutic pools]. / Gestion des risques infectieux liés aux piscines et bains collectifs à usage médical.

UNLABELLED: There is no specific legislation concerning pools and others medical hydrotherapy equipments relating hygiene and security rules. For this reason, the hydrotherapy pools use the public swimming pools legislation. METHOD: This article is based on literature review (database Medline and Embase--manual research). RESULTS: This article offers a review of pool associated infections along with the description of the measures designed to minimise the possible transmission of infection during hydrotherapy activities such as: Technical measures: pool and premises conception, water treatments, feed tanks, air quality. Hygiene rules for patients and hospital staff and pathologies which are contra-indications to hydrotherapy activities. Microbiological and physico-chemical monitoring. DISCUSSION: The infectious risk remains low with therapeutic pools. However, the development of specific legislation and surveillance should be enhanced. CONCLUSION: All these measures are part of the quality assurance program that must be implemented to control the safety of these installations.

Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial.

OBJECTIVE: To determine the subjective response to iron therapy in non-anaemic women with unexplained fatigue. DESIGN: Double blind randomised placebo controlled trial. SETTING: Academic primary care centre and eight general practices in western Switzerland. PARTICIPANTS: 144 women aged 18 to 55, assigned to either oral ferrous sulphate (80 mg/day of elemental iron daily; n=75) or placebo (n=69) for four weeks. MAIN OUTCOME MEASURES: Level of fatigue, measured by a 10 point visual analogue scale. RESULTS: 136 (94%) women completed the study. Most had a low serum ferritin concentration;

Asymmetric induction in the [4+2]cycloaddition of cyclopentadiene and furan to chiral derivatives of fumaric acid.

[4+2]Cycloaddition reactions of cyclopentadiene (1a) and furan (1b) to N,N'-fumaroyldi[(2R)-bornane-10,2-sultam] (2) and to N,N'-fumaroyldi[(2R)-bornane-10,2-(2'-phenyl-pyrazol-3'-one)] (3) are presented. A correlation between the solvent polarity and the logarithm of the diastereoisomer ratio (dr) was found for the uncatalyzed [4+2]cycloaddition of 1a to 3.

The Distance to the Soft Gamma Repeater SGR 1627-41.

We report millimeter observations of the line of sight to the recently discovered soft gamma repeater SGR 1627-41, which has been tentatively associated with the supernova remnant (SNR) G337.0-0.1. Among the eight molecular clouds along the line of sight to SGR 1627-41, we show that SNR G337.0-0.1 is probably interacting with one of the most massive giant molecular clouds (GMCs) in the Galaxy, at a distance of 11 kpc from the Sun. Based on the high extinction to the persistent X-ray counterpart of SGR 1627-41, we present evidence for an association of this new soft gamma repeater (SGR) with the SNR G337.0-0.1; they both appear to be located on the near side of the GMC. This is the second SGR located near an extraordinarily massive GMC. We suggest that SGR 1627-41 is a neutron star with a high transverse velocity ( approximately 1000 km s-1) escaping the young ( approximately 5000 yr) SNR G337.0-0.1.

An economic approach to the MIC.

The determination of the Inhibitory Concentration in Diffusion (ICD) is proposed as an alternative to the agar dilution Minimal Inhibitory Concentration (MIC) that is time-consuming and cumbersome for routine use. Based on the technique of the disk diffusion test, it consists in calculating a continuous variable, the ICD, corresponding to the antibiotic concentration in the agar at the edge of the inhibition zone. Six antibiotics were tested (ampicillin, cefotaxime, erythromycin, gentamicin, nalidixic acid and rifampicin) each against 17 to 51 strains of enterobacteria, Staphylococcus aureus and Enterococcus spp. and six other antibiotics (cefsulodin, ceftazidime, imipenem, piperacillin, ticarcillin and tobramycin), against 13 to 25 strains of Pseudomonas aeruginosa. A total of 284 antibiotic-strain combinations were tested. Three different antibiotic charges were obtained for each antibiotic by cutting commercial disks in two and four equal pieces. The ICD was calculated for each strain from the size of inhibition zones around a full disk, a half and a quarter of a disk. Concurrently, the MIC was performed, using a conventional agar dilution method. There was a good correlation between the two methods and reproducibility for the ICD proved to be correct. This reliable technique is very efficient both in terms of laboratory time and cost of materials and could be proposed for widespread use in clinical laboratories.

Mathematical model of the interactions between Micrococcus spp. and Pseudomonas aeruginosa on agar surface.

The interactions between six different Micrococcus species and two strains of Pseudomonas aeruginosa were studied on an agar surface. This type of interaction on solid surface could act as a model of situations occurring either in the environment, in food or in man. The hypothesis of an amensalistic relationship between a Micrococcus spp. and Pseudomonas aeruginosa, due essentially to Ps. aeruginosa bacteriolytic enzymes, is retained as the basis for a mathematical model of the variations of the colony surface of Micrococcus spp. (S) with respect to the distance (d) from Ps. aeruginosa cells. The diffusion of the bacteriolytic substance in agar explains the limitation of the growth of the Micrococcus spp. This model S = Smax (1-e-md2) is shown to be adapted to all the interactions studied.

[Post-antibiotic effect of three aminoglycosides against Klebsiella pneumoniae]. / Effet post-antibiotique de trois aminosides sur Klebsiella pneumoniae.

This paper introduces a new method to quantify post antibiotic effect. This method was applied to the study of the effect of three aminoglycosides antibiotics on seven strains of Klebsiella pneumoniae. The antimicrobial was removed by filtration, washing with peptone broth and neutralization by heparin. Growth curves were monitored by automated measurement of optical density with Urimat-ATB (bioMérieux). The inoculum fluctuation bias was eliminated with the help of a mathematical analysis of results. Absence of carry-over was controlled for each bacteria-antibiotic combination. A significant post antibiotic effect was observed with the three antibiotics after 2 hours exposure to a concentration equivalent to 2 x MIC. There was no significant difference between the 3 aminoglycosides tested.