[Regional management tool and analysis of hospital prescriptions delivered in community pharmacies: A different approach to support French health institutions]. / Outil de pilotage territorial et d'analyse des prescriptions hospitalières exécutées en ville : une nouvelle approche de l'accompagnement des établissements de santé.

Health economic regulation and relevance of care are key points for every industrialised country. To get a better medicalised control of expenditure developments, French hospitals contracts with regulation authorities (Agence Régionale de Santé) and healthcare insurance within a "contract for the improvement of the quality and efficiency of care" (CAQES). One of the monitored element is the expenses related to hospital initial prescriptions delivered in community pharmacies (PHEV). The PHEV evolution is driven by prescribing practices (in terms of relevance) But others explanatory factor are structural and more complex to identify. Among these, the characteristics of the health care institution have a strong but unmeasured impact (environment, ambulatory medical demography, etc.). To evaluate the impact of these factors and help healthcare institutions, OMéDIT BFC (Regional Healthcare Products Observatory) and ARS, developed a tool for territorial management and analysis of PHEV named OPTA-PHEV. It makes it possible to individualize their expenditure data and to identify any prescription atypicalities integrating these extrinsic parameters. This will make it possible to compare and put into perspective the different regions in order to optimize PHEV-related expenses.

18F-FDG brain PET hypometabolism in patients with long COVID.

PURPOSE: In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent recovery from COVID-19. This clinical presentation has been referred as "long COVID." We here present a retrospective analysis of 18F-FDG brain PET of long COVID patients from the same center with a biologically confirmed diagnosis of SARS-CoV-2 infection and persistent functional complaints at least 3 weeks after the initial infection. METHODS: PET scans of 35 patients with long COVID were compared using whole-brain voxel-based analysis to a local database of 44 healthy subjects controlled for age and sex to characterize cerebral hypometabolism. The individual relevance of this metabolic profile was evaluated to classify patients and healthy subjects. Finally, the PET abnormalities were exploratory compared with the patients' characteristics and functional complaints. RESULTS: In comparison to healthy subjects, patients with long COVID exhibited bilateral hypometabolism in the bilateral rectal/orbital gyrus, including the olfactory gyrus; the right temporal lobe, including the amygdala and the hippocampus, extending to the right thalamus; the bilateral pons/medulla brainstem; the bilateral cerebellum (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected). These metabolic clusters were highly discriminant to distinguish patients and healthy subjects (100% correct classification). These clusters of hypometabolism were significantly associated with more numerous functional complaints (brainstem and cerebellar clusters), and all associated with the occurrence of certain symptoms (hyposmia/anosmia, memory/cognitive impairment, pain and insomnia) (p < 0.05). In a more preliminary analysis, the metabolism of the frontal cluster which included the olfactory gyrus was worse in the 7 patients treated by ACE drugs for high blood pressure (p = 0.032), and better in the 3 patients that had used nasal decongestant spray at the infectious stage (p < 0.001). CONCLUSION: This study demonstrates a profile of brain PET hypometabolism in long COVID patients with biologically confirmed SARS-CoV-2 and persistent functional complaints more than 3 weeks after the initial infection symptoms, involving the olfactory gyrus and connected limbic/paralimbic regions, extended to the brainstem and the cerebellum. These hypometabolisms are associated with patients' symptoms, with a biomarker value to identify and potentially follow these patients. The hypometabolism of the frontal cluster, which included the olfactory gyrus, seems to be linked to ACE drugs in patients with high blood pressure, with also a better metabolism of this olfactory region in patients using nasal decongestant spray, suggesting a possible role of ACE receptors as an olfactory gateway for this neurotropism.

18F-FDG brain PET hypometabolism in post-SARS-CoV-2 infection: substrate for persistent/delayed disorders?

PURPOSE: Several brain complications of SARS-CoV-2 infection have been reported. It has been moreover speculated that this neurotropism could potentially cause a delayed outbreak of neuropsychiatric and neurodegenerative diseases of neuroinflammatory origin. A propagation mechanism has been proposed across the cribriform plate of the ethmoid bone, from the nose to the olfactory epithelium, and possibly afterward to other limbic structures, and deeper parts of the brain including the brainstem. METHODS: Review of clinical examination, and whole-brain voxel-based analysis of 18F-FDG PET metabolism in comparison with healthy subjects (p voxel < 0.001, p-cluster < 0.05, uncorrected), of two patients with confirmed diagnosis of SARS-CoV-2 explored at the post-viral stage of the disease. RESULTS: Hypometabolism of the olfactory/rectus gyrus was found on the two patients, especially one with 4-week prolonged anosmia. Additional hypometabolisms were found within amygdala, hippocampus, parahippocampus, cingulate cortex, pre-/post-central gyrus, thalamus/hypothalamus, cerebellum, pons, and medulla in the other patient who complained of delayed onset of a painful syndrome. CONCLUSION: These preliminary findings reinforce the hypotheses of SARS-CoV-2 neurotropism through the olfactory bulb and the possible extension of this impairment to other brain structures. 18F-FDG PET hypometabolism could constitute a cerebral quantitative biomarker of this involvement. Post-viral cohort studies are required to specify the exact relationship between such hypometabolisms and the possible persistent disorders, especially involving cognitive or emotion disturbances, residual respiratory symptoms, or painful complaints.

Evaluating the serological status of COVID-19 patients using an indirect immunofluorescent assay, France.

An indirect in-house immunofluorescent assay was developed in order to assess the serological status of COVID-19 patients in Marseille, France. Performance of IFA was compared to a commercial ELISA IgG kit. We tested 888 RT-qPCR-confirmed COVID-19 patients (1302 serum samples) and 350 controls including 200 sera collected before the pandemic, 64 sera known to be associated with nonspecific serological interference, 36 sera from non-coronavirus pneumonia and 50 sera from patient with other common coronavirus to elicit false-positive serology. Incorporating an inactivated clinical SARS-CoV-2 isolate as the antigen, the specificity of the assay was measured as 100% for IgA titre ≥ 1:200, 98.6% for IgM titre ≥ 1:200 and 96.3% for IgG titre ≥ 1:100 after testing a series of negative controls. IFA presented substantial agreement (86%) with ELISA EUROIMMUN SARS-CoV-2 IgG kit (Cohen's Kappa = 0.61). The presence of antibodies was then measured at 3% before a 5-day evolution up to 47% after more than 15 days of evolution. We observed that the rates of seropositivity as well as the titre of specific antibodies were both significantly higher in patients with a poor clinical outcome than in patients with a favourable evolution. These data, which have to be integrated into the ongoing understanding of the immunological phase of the infection, suggest that detection anti-SARS-CoV-2 antibodies is useful as a marker associated with COVID-19 severity. The IFA assay reported here is useful for monitoring SARS-CoV-2 exposure at the individual and population levels.

The value of post-operative antibiotic therapy after laparoscopic appendectomy for complicated acute appendicitis: a prospective, randomized, double-blinded, placebo-controlled phase III study (ABAP study).

BACKGROUND: Approximately 30% of appendectomies are for complicated acute appendicitis (CAA). With laparoscopy, the main post-operative complication is deep abscesses (12% of cases of CAA, versus 4% for open surgery). A recent cohort study compared short and long courses of postoperative antibiotic therapy in patients with CAA. There was no significant intergroup difference in the post-operative complication rate (12% of organ/space surgical site infection (SSI)). Moreover, antibiotic therapy is increasingly less indicated for other situations (non-complicated appendicitis, post-operative course of cholecystitis, perianal abscess), calling into question whether post-operative antibiotic therapy is required after laparoscopic appendectomy for CAA. METHODS/DESIGN: This study is a prospective, multicenter, parallel-group, randomized (1:1), double-blinded, placebo-controlled, phase III non-inferiority study with blind evaluation of the primary efficacy criterion. The primary objective is to evaluate the impact of the absence of post-operative antibiotic therapy on the organ/space surgical site infection (SSI) rate in patients presenting with CAA (other than in cases of generalized peritonitis). Patients in the experimental group will receive at least one dose of preoperative and perioperative antibiotic therapy (2 g ceftriaxone by intravenous injection every 24 h up to the operation) and metronidazole (500 mg by intravenous injection every 8 h up to the operation) and, in the post-operative period, a placebo for ceftriaxone (2 g/24 h in one intravenous injection) and a placebo for metronidazole (1500 mg/24 h in three intravenous injections, for 3 days). In the control group, patients will receive at least one dose of preoperative and perioperative antibiotic therapy (2 g ceftriaxone by intravenous injection every 24 h up to the operation) and metronidazole (500 mg by intravenous injection every 8 h up to the operation) and, in the post-operative period, antibiotic therapy (ceftriaxone 2 g/24 h and metronidazole 1500 mg/24 h for 3 days). In the event of allergy to ceftriaxone, it will be replaced by levofloxacin (500 mg/24 h in one intravenous injection, for 3 days). The expected organ space SSI rate is 12% in the population of patients with CAA operated on by laparoscopy. With a non-inferiority margin of 5%, a two-sided alpha risk of 5%, a beta risk of 20%, and a loss-to-follow-up rate of 10%, the calculated sample size is 1476 included patients, i.e., 738 per group. Due to three interim analyses at 10%, 25%, and 50% of the planned sample size, the total sample size increases to 1494 patients (747 per arm). TRIAL REGISTRATION: Ethical authorization by the Comité de Protection des Personnes and the Agence Nationale de Sécurité du Médicament: ID-RCB 2017-00334-59. Registered on ClinicalTrials.gov (NCT03688295) on 28 September 2018.

The association of lung ultrasound images with COVID-19 infection in an emergency room cohort.

Lung ultrasound could facilitate the triage of patients with suspected COVID-19 infection admitted to the emergency room. We developed a predictive model for COVID-19 diagnosis based on lung ultrasound and clinical features. We used ultrasound to image the lung bilaterally at two anterior sites, one and two hands below each clavicle, and a posterolateral site that was the posterior transverse continuation from the lower anterior site. We studied 100 patients, 31 of whom had a COVID-19 positive reverse transcriptase polymerase chain reaction. A positive test was independently associated with: quick sequential organ failure assessment score ≥1; ≥3 B-lines at the upper site; consolidation and thickened pleura at the lower site; and thickened pleura line at the posterolateral site. The model discrimination was an area (95%CI) under the receiver operating characteristic curve of 0.82 (0.75-0.90). The characteristics (95%CI) of the model's diagnostic threshold, applied to the population from which it was derived, were: sensitivity, 97% (83-100%); specificity, 62% (50-74%); positive predictive value, 54% (41-98%); and negative predictive value, 98% (88-99%). This model may facilitate triage of patients with suspected COVID-19 infection admitted to the emergency room.

Polymerization of cellulose nanocrystals-based Pickering HIPE towards green porous materials.

Porous materials were produced based on high internal phase emulsions (HIPE) formulation stabilized by modified cellulose nanocrystals (CNCs). CNCs were first modified with bromoisobutyryl bromide and used as Pickering emulsion stabilizers to formulate highly concentrated inverse emulsions. Solid foams with an open porosity were successively produced by free radical polymerization of styrene/divinylbenzene continuous phase. The final materials were characterized regarding their cell size distribution, porosity and mechanical properties and then compared with well-known styrene/DVB polyHIPE stabilized either with usual surfactants or solid particles.

Cluster of serogroup W invasive meningococcal disease in a university campus.

INTRODUCTION: In France, the expansion of an hypervirulent strain causing serogroup W invasive meningococcal disease (MenW) has been observed since 2015/16. We describe a cluster of three MenW cases, causing two deaths, at the end of 2016 in a university campus, and the vaccination campaign which was consequently organized. METHODS: Epidemiological and microbiological analyses led a multidisciplinary expertise group to recommend the organization of a mass vaccination campaign using ACWY vaccine targeting more than 30,000 students and staff in the university campus. Individual data on vaccination was collected using the lists of students and staff registered at the university to estimate vaccine coverage. RESULTS: Three MenW cases occurred within a 2-month period among students in different academic courses. All three isolates were identical and belonged to the "UK-2013 strain" phylogenetic branch. The attack rate was 10.8/100,000 students. The vaccination campaign was organized only 15 days after the third case occurred. In total, 13,198 persons were vaccinated. Vaccine coverage was estimated at 41% for students of the university and 35% for university staff. CONCLUSION: Timely notification of cases to health authorities was essential for the detection of the cluster and the rapid implementation of the vaccination campaign. No further cases occurred in the campus in the year following the vaccination campaign. This episode is the second cluster of MenW caused by the "UK-2013 strain" in a university since 2016.

[Alcohol consumption : from epidemiology to prevention]. / La consommation d'alcool : de l'épidémiologie à la prévention.

The epidemiological data about alcohol consumption show that the current preventive measures have their limits. Worryingly, the morbidity and mortality associated remain significant in the world. Two main types of preventive approaches, based on individual affect exist: the negative approach based on fear and threat and the so-called Social Norm Approach (SNA). The last original and more positive approach has been used across the Atlantic for thirty years and shows to be efficient. It aims to reduce an individual's consumption of addictive substance by confronting his own social norm (what he thinks people drink, quantities generally overestimated) to the real norm of consumption by a reference social group. A cross-border project is currently evaluating the feasibility of this approach in the Euregio Meuse-Rhin.

Les données épidémiologiques de la consommation d'alcool les plus récentes montrent que les mesures préventives actuelles connaissent leurs limites. De façon inquiétante, la morbidité et la mortalité qui lui sont associées restent importantes dans le monde. Deux grands types d'approches préventives ciblant directement les affects des individus existent : l'approche négative basée sur la peur et la menace et l'approche dite par la norme sociale (SNA pour Social Norm Approach). Cette dernière approche originale et plus positive de la santé est utilisée depuis une trentaine d'années outre-Atlantique et montre une certaine efficacité. Elle vise à réduire la consommation d'une substance addictive par un individu en confrontant sa norme sociale (ce qu'il pense que les gens boivent, quantités généralement surestimées) à la norme réelle de consommation du groupe social de référence. Un projet transfrontalier évalue actuellement la faisabilité de ce genre d'approche dans l'Eurégio Meuse-Rhin.

Fecal calprotectin and fecal indole predict outcome of fecal microbiota transplantation in subjects with recurrent Clostridium difficile infection.

Fecal calprotectin and indole were studied in 134 subjects with recurrent CDI before and after FMT. Reduced fecal calprotectin (p = 0.0353, 95% CI 0.1305-0.1439) and rising levels of indole (p < 0.0001, 95% CI < 0.0001-0.0003) predicted successful treatment. A ratio of recal calprotectin/indole may provide prognostic value for FMT (p = 0.0004, 95% CI 0.22-0.87).

Antibioprophylaxis in surgery and interventional medicine (adult patients). Update 2017.

Infection is a risk for any intervention. In surgery, for example, pathogenic bacteria are found in more than 90% of operative wounds during closure. This exists whatever the surgical technique and whatever the environment (the laminar flow does not entirely eliminate this risk). These bacteria are few in number but can proliferate. They find in the operative wound a favourable environment (haematoma, ischaemia, modification of oxido-reduction potential...) and the intervention induces anomalies of the immune defences. In the case of the installation of foreign material, the risk is increased. The objective of antibiotic prophylaxis (ABP) is to prevent bacterial growth in order to reduce the risk of infection at the site of the intervention. The preoperative consultation represents a privileged moment to decide on the prescription of a ABP. It is possible to define the type of intervention planned, the associated risk of infection (and therefore the necessity or not of ABP), the time of prescription before surgery and any allergic antecedents which may modify the choice of the selected antibiotic molecule.

Influence of bacterial resistance on mortality in intensive care units: a registry study from 2000 to 2013 (IICU Study).

BACKGROUND: Bacterial resistance to antibiotics is a daily concern in intensive care units. However, few data are available concerning the clinical consequences of in-vitro-defined resistance. AIM: To compare the mortality of patients with nosocomial infections according to bacterial resistance profiles. METHODS: The prospective surveillance registry in 29 French intensive care units (ICUs) participating during the years 2000-2013 was retrospectively analysed. All patients presenting with a nosocomial infection in ICU were included. FINDINGS: The registry contained 88,000 eligible patients, including 10,001 patients with a nosocomial infection. Among them, 3092 (36.7%) were related to resistant micro-organisms. Gram-negative bacilli exhibited the highest rate of resistance compared to Gram-positive cocci (52.8% vs 48.1%; P < 0.001). In-hospital mortality was higher in cases of patients with antibiotic-resistant infectious agents (51.9% vs 45.5%; P < 0.001), and critical care length of stay was longer (33 ± 26 vs 29 ± 22 days; P < 0.001). These results remained significant after SAPS II matching (P < 0.001) and in the Gram-negative bacilli and Gram-positive cocci subgroups. No difference in mortality was found with respect to origin prior to admission. CONCLUSION: Patients with bacterial resistance had higher ICU mortality and increased length of stay, regardless of the bacterial species or origin of the patient.

Epidemiology of respiratory pathogen carriage in the homeless population within two shelters in Marseille, France, 2015-2017: cross sectional 1-day surveys.

OBJECTIVES: To assess risk factors for respiratory tract infection symptoms and signs in sheltered homeless people in Marseille during the winter season, including pathogen carriage. METHODS: Data on 479 male participants within two shelters who completed questionnaires and a total of 950 nasal and pharyngeal samples were collected during the winters of 2015-2017. Respiratory pathogen carriage including seven viruses and four bacteria was assessed by quantitative PCR. RESULTS: The homeless population was characterized by a majority of individuals of North African origin (300/479, 62.6%) with a relatively high prevalence of chronic homelessness (175/465, 37.6%). We found a high prevalence of respiratory symptoms and signs (168/476, 35.3%), a very high prevalence of bacterial carriage (313/477, 65.6%), especially Haemophilus influenzae (280/477, 58.7%), and a lower prevalence of virus carriage (51/473, 10.8%) with human rhinovirus being the most frequent (25/473, 5.3%). Differences were observed between the microbial communities of the nose and throat. Duration of homelessness (odds ratio (OR) 1.77, p 0.017), chronic respiratory diseases (OR 5.27, p <0.0001) and visiting countries of origin for migrants (OR 1.68, p 0.035) were identified as independent risk factors for respiratory symptoms and signs. A strong association between virus (OR 2.40, p 0.012) or Streptococcus pneumoniae (OR 2.32, p 0.014) carriage and respiratory symptoms and signs was also found. CONCLUSIONS: These findings allowed identification of the individuals at higher risk for contracting respiratory tract infections to better target preventive measures aimed at limiting the transmission of these diseases in this setting.

Dynamic arterial elastance measured by uncalibrated pulse contour analysis predicts arterial-pressure response to a decrease in norepinephrine.

BACKGROUND: Dynamic arterial elastance (Eadyn) has been proposed as an indicator of vascular tone that predicts the decrease in arterial pressure in response to changes in norepinephrine (NE). The purpose of this study was to determine whether Eadyn measured by uncalibrated pulse contour analysis (UPCA) can predict a decrease in arterial pressure when the NE dosage is decreased. METHODS: We conducted a prospective study in a university hospital intensive care unit. Patients with vasoplegic syndrome for whom the intensive care physician planned to decrease the NE dosage were included. Haemodynamic and UPCA (VolumeView and FloTrac; Edwards Lifesciences, Irvine, CA, USA) values were obtained before and after decreasing the NE dosage. Responders were defined by a >10% decrease in mean arterial pressure (MAP). RESULTS: Of 35 patients included, 11 (31%) were pressure responders with a median decrease of 13%. Eadyn was correlated to systolic arterial pressure (SAP) (r=0.255; P=0.033), diastolic arterial pressure (r=0.271; P=0.024), MAP (r=0.310; P=0.009), heart rate (r=0.543; P=0.0001), and transthoracic echography cardiac output (r=0.264; P=0.024). Baseline Eadyn was correlated with MAP changes (r=0.394; P=0.019) and SAP changes (r=0.431; P=0.009). Eadyn predicted the decrease in arterial pressure with an area under the receiver-operating-characteristic curve of 0.84 (95% confidence interval: 0.70-0.97). The best cut-off was 0.90. CONCLUSIONS: The present study confirms the ability of Eadyn measured by UPCA to predict an arterial pressure response to a decrease in NE. Eadyn may constitute an easy-to-use functional approach to arterial tone assessment regardless of the monitor used to measure its determinant. CLINICAL TRIAL REGISTRATION: DRCIT95.

Multicenter performance evaluation of the Unyvero IAI cartridge for detection of intra-abdominal infections.

Intra-abdominal infections (IAIs) are one of the most common type of infections in patients with sepsis and an important cause of death in intensive care units. Early detection and treatment are necessary to reduce patient complications and improve outcomes. The Unyvero IAI Application (Curetis GmbH) is the first automated assay to rapidly and simultaneously identify a large panel of bacteria, fungi, toxins, and antibiotic resistance markers directly from IAI-related samples. The assay was evaluated in four European clinical laboratories in comparison to routine microbiological practices. A total of 300 clinical samples were tested with an overall sensitivity of 89.3% and specificity of 99.5%, while time to results was reduced by an average of about 17 h compared to identification (ID) results and 41 h compared to full antibiotic susceptibility testing (AST) results. The Unyvero IAI was able to detect additional microorganisms compared with culture, in particular anaerobes, with most detections confirmed by sequencing. The most frequent resistance markers detected were mecA/mecC (n = 25), aacA4 (n = 20), and blaCTX-M (n = 17) and carbapenemase genes were identified in nine specimens. Further studies are now required to determine the clinical impact of this new rapid test which could play a role in the successful treatment of IAI.

Distinguishing fecal appendicular peritonitis from purulent appendicular peritonitis.

INTRODUCTION: Fecal appendicular peritonitis (FAP) is a poorly studied, rare form of acute appendicitis, corresponding to peritoneal inflammation with the presence of feces secondary to ruptured appendix. The purpose of this study was to describe FAP and to compare FAP with purulent appendicular peritonitis (PAP). PATIENTS AND METHODS: This single-center, retrospective study was conducted in consecutive patients to compare the FAP group and the PAP group. The primary endpoint was the 30-day postoperative morbidity and mortality according to the Clavien-Dindo classification. The secondary endpoints were description and comparison of intraoperative data (laparoscopy rate, conversion rate, type of procedure and the mean operating time), and short-term outcomes (types of complications, length of stay, readmission rate, and reoperation rate), comparison of intraoperative bacteriological samples of FAP and PAP as well as the rate of resistance to amoxicillin and clavulanic acid, used as routine postoperative antibiotic therapy. RESULTS: Between January 2006 and January 2016, 2.2% of appendectomies were performed for FAP. Patients of the FAP group reported a longer history of pain than patients of the PAP group (mean: 58 h [range: 24-120] vs 24 h [range: 6-504], p = 0.0001) and hyperthermia was more frequent in the FAP group than in the PAP group (72% vs 26%, p = 0.0001). Mean preoperative CRP was also higher in the FAP group than in the PAP group (110 mg/L [range: 67-468] vs 37.5 mg/L [range: 3.1-560], p = 0.007). Significantly less patients were operated by laparoscopy in the FAP group (89.7% vs 96.6%, p < 0.0001). Mean length of stay was significantly longer in the FAP group than in the PAP group (10 days [range: 3-24] vs 5 days [range: 1-32], p = 0.001). The overall 30-day complication rate was significantly higher in the FAP group than in the PAP group (62.1% vs 24.7%, p = 0.0005). The readmission rate was not significantly different between the two groups (14% vs 11.2%, p = 0.2), but the reoperation rate was higher in the FAP group than in the PAP group (31% vs 11%, p = 0.01). No significant difference was observed between the FAP and PAP groups in terms of the positive culture rate (75.9% vs 65.6%, p = 0.3). No significant difference was observed between the two groups in terms of resistance to amoxicillin and clavulanic acid (18.2% vs 20.5%, p = 0.8). CONCLUSION: FAP is associated with significantly more severe morbidity compared to PAP. Clinicians must be familiar with this form of appendicitis in order to adequately inform their patients.