[The contribution of teleconsultation and isolation of symptomatic cases in control of the COVID-19 outbreak a military base]. / Apport de la téléconsultation et de l'isolement des cas symptomatiques dans la maîtrise de l'épidémie COVID-19 au sein d'une base militaire.

BACKGROUND: The first wave of COVID-19 swept over France during the first quarter of 2020, leading to saturation of the health care system. We wished to study, in a French military medical unit assisting one of the country's largest armed forces populations, the impact of teleconsultation and the systematic isolation of all possible, probable and confirmed cases of COVID-19. METHODS: This is a retrospective study carried out from March 9 to May 31, 2020 on the basis of our activity register. The variables collected included type of medical consultation procedure, occupational status, classification of cases and date of onset of first symptoms. We have paralleled our activity with that of SOS Médecins and the emergency departments of the Île-de-France region. RESULTS/DISCUSSION: During this period, 1719 episodes of care (teleconsultations or physical consultations) were recorded, of which 91% (n=1561) were linked to COVID-19. We identified 598 "suspected" (possible and probable) and confirmed cases. "Isolated" teleconsultations (not followed by a face-to-face medical consultation, sample taking or necessitating the dispatch of prompt assistance) represented 86% of episodes of care (n=1482). Comparison of our activity and the number of new cases with the databases of SOS Médecins and the Île-de-France emergency services suggests that our isolation strategy was timely and effective. CONCLUSION: The contribution of teleconsultation was substantial and reassuring. Teleconsultation makes it possible to absorb a large volume of patients, is easy to implement, and entails no nosocomial risk. Isolation of infected patients should be a priority during an outbreak. Once it has become a priority to rapidly bring an epidemic under control, this attitude must be extended to all symptomatic patients.

Hypophosphatasia: Canadian update on diagnosis and management.

Hypophosphatasia (HPP) is a rare inherited disorder of bone and mineral metabolism caused by loss of function mutations in the ALPL gene. The presentation in children and adults can be extremely variable and natural history is poorly understood particularly in adults. Careful patient evaluation is required with consideration of pharmacologic intervention in individuals meeting criteria for therapy. INTRODUCTION: The purposes of this review are to present current evidence regarding the diagnosis and management of hypophosphatasia in children and adults and provide evidence-based recommendations for management. METHOD: A MEDLINE, EMBASE, and Cochrane database search and literature review was completed. The following consensus recommendations were developed based on the highest level of evidence as well as expert opinion. RESULTS: Hypophosphatasia is a rare inherited disorder of bone and mineral metabolism due to loss of function mutations in the tissue non-specific alkaline phosphatase (ALPL) gene causing reductions in the activity of the tissue non-specific isoenzyme of alkaline phosphatase (TNSALP). Deficient levels of alkaline phosphatase result in elevation of inhibitors of mineralization of the skeleton and teeth, principally inorganic pyrophosphate. The impaired skeletal mineralization may result in elevations in serum calcium and phosphate. Clinical features include premature loss of teeth, metatarsal and subtrochanteric fractures as well as fragility fractures. Poor bone healing post fracture has been observed. Myalgias and muscle weakness may also be present. In infancy and childhood, respiratory and neurologic complications can occur. CONCLUSIONS: HPP is associated with significant morbidity and mortality. Pharmacologic intervention can result in significant clinical improvement. This Canadian position paper provides an overview of the musculoskeletal, renal, dental, respiratory, and neurologic manifestations of hypophosphatasia. The current state of the art in the diagnosis and management of hypophosphatasia is presented.

Correction to: Hypophosphatasia: Canadian update on diagnosis and management.

In the article mentioned above an author's name was misspelled.

Patient preference: a comparison of electronic patient-completed questionnaires with paper among cancer patients.

In this study, we compared cancer patients preference for computerised (tablet/web-based) surveys versus paper. We also assessed whether the understanding of a cancer-related topic, pharmacogenomics is affected by the survey format, and examined differences in demographic and medical characteristics which may affect patient preference and understanding. Three hundred and four cancer patients completed a tablet-administered survey and another 153 patients completed a paper-based survey. Patients who participated in the tablet survey were questioned regarding their preference for survey format administration (paper, tablet and web-based). Understanding was assessed with a 'direct' method, by asking patients to assess their understanding of genetic testing, and with a 'composite' score. Patients preferred administration with tablet (71%) compared with web-based (12%) and paper (17%). Patients <65 years old, non-Caucasians and white-collar professionals significantly preferred the computerised format following multivariate analysis. There was no significant difference in understanding between the paper and tablet survey with direct questioning or composite score. Age (<65 years) and white-collar professionals were associated with increased understanding (both P = 0.03). There was no significant difference in understanding between the tablet and print survey in a multivariate analysis. Patients overwhelmingly preferred computerised surveys and understanding of pharmacogenomics was not affected by survey format.

Decoupling of inorganic and organic carbon during slab mantle devolatilisation.

Serpentinites are an important sink for both inorganic and organic carbon, and their behavior during subduction is thought to play a fundamental role in the global cycling of carbon. Here we show that fluid-derived veins are preserved within the Zermatt-Saas ultra-high pressure serpentinites providing key evidence for carbonate mobility during serpentinite devolatilisation. We show through the O, C, and Sr isotope analyses of vein minerals and the host serpentinites that about 90% of the meta-serpentinite inorganic carbon is remobilized during slab devolatilisation. In contrast, graphite-like carbonaceous compounds remain trapped within the host rock as inclusions within metamorphic olivine while the bulk elemental and isotope composition of organic carbon remains relatively unchanged during the subduction process. This shows a decoupling behavior of carbon during serpentinite dehydration in subduction zones. This process will therefore facilitate the transfer of inorganic carbon to the mantle wedge and the preferential slab sequestration of organic carbon en route to the deep mantle.

[Expression of the elastic fibers components during the fœtal liver development]. / Expression des composants de la matrice élastique au cours du développement hépatique fœtal.

Elastic fibers are composed of microfibrils containing fibrillin-1 and an elastic component, elastin. Microfibrils may not be associated with elastin. In the adult liver, fibrillin-1 and elastin are coexpressed within the stroma and portal tracts vessel walls. Fibrillin-1 is expressed alone around the bile ducts and within the Disse space. There is little work that has studied the elastic fiber organization during the fœtal liver development. Here, we studied the expression of fibrillin-1 and elastin by immunohistochemistry on 20 cases of fœtal liver. During the development of the portal tract, the two components are coexpressed on interstitial elastic fibers and within vessel walls. Fibrillin-1 is expressed alone around the bile structures during their maturation. Unlike adult liver, fibrillin-1 is expressed on thin and very irregular microfibrils within the Disse space. Our study shows that the elastic matrix development in the portal tract follows the development of the different structures, notably biliary structures. In the Disse space, microfibrils are not continuous. Their maturation may be in relation with the change of the hepatic blood flow after birth.

Process-based analysis of waste management systems: a case study.

This paper presents an analysis, using process simulation, of the waste management system applied in a collection basin located in the south of Paris (France). The study was conducted in close cooperation with the "SYCTOM of Paris agglomeration", an operator in charge of managing 2.5 milliontons/yr of municipal solid waste in the Paris area. The analysis includes a description of the current situation of waste management in this collection basin, the construction and calibration of a simulator that reproduces this situation, the simulation of scenarios that account for possible future changes in waste flows and treatment options and finally a comparison of scenario results. Results illustrate the interest of a process-based approach to waste management systems. Such an approach is complementary to life cycle analyses, which usually rely on more generic descriptions of waste treatment units. The detailed analysis of a waste management system using local data on waste streams and treatment units provides technical indicators of system efficiency expressed in terms of recycling rates, energy recovery, emission fluxes and costs. Such information can help reach a consensus with respect to the actual situation of waste management and provides decision-makers with quantitative arguments that can be brought into the public debate.

Polychlorinated biphenyl congeners in the aquatic environment of the Mekong River, South of Vietnam.

Polychlorinated biphenyl compounds (PCBs) were analyzed in sediments and clams' soft tissues from sampling sites in the Mekong River delta from the border with Cambodia to the coast of South China Sea. Concentrations of 13 individual PCB congeners are reported. Median concentration of SigmaPCB congeners was 0.279 ng g(-1) dry weight (range 0.106-2.016 ng g(-1) dry weight) in sediments, and 5.20 ng g(-1) dry weight (range 1.89-19.37 ng g(-1)) in clams. Distribution and bioaccumulation of PCBs in the delta are discussed. It is concluded that in the Mekong River delta PCB concentrations were generally lower than in other regions of Vietnam and their likely sources have been waste discharges from repair workshops and other facilities in the delta cities.

A public health enhanced surveillance system for a mass gathering event.

BACKGROUND: From June 7 to June 9, 2018, a G7 Summit was held in the Canadian province of Quebec. This international political mass gathering event posed a number of potential risks to public health. OBJECTIVE: To assess three additional monitoring strategies to detect public health threats during a mass gathering event. INTERVENTION: In addition to routine public health monitoring, a partnership was created and three monitoring strategies were put in place three days before, during and six days after the G7 event: the analysis of data on the presenting complaint and discharge diagnosis from 11 emergency departments in the area using the logical Early Aberration Reporting System; the daily polling of key health partners with an online questionnaire; and the analysis of calls to Info-Santé, a government-run telephone consultation service for the public regarding health and social issues. RESULTS: Emergency room data produced 78 alerts from the presenting complaints and 39 alerts from the discharge diagnoses. Of these 117 alerts, two were investigated (one in the respiratory and one in the neurological-muscular categories) and no other interventions were required. With a few exceptions, all of the health partners completed the online survey each day and no signal of concern was generated. Compared with historical data, no increase or differences in calls to Info-Santé were detected during the monitoring period. CONCLUSION: The three additional monitoring strategies developed to detect events of public health importance during the 2018 G7 Summit in Quebec were successful in gathering timely data for analysis. Close collaboration and good participation from the different partners were essential to this project. However, because no public health event occurred, it was not possible to determine whether the enhanced surveillance system had sufficient speed and sensitivity for timely detection and response.

Agrochemical and polychlorobyphenyl (PCB) residues in the Mekong River delta, Vietnam.

An environmental survey on pesticide residues and polychlorobyphenyl compounds (PCBs), encompassing more than 70 polar and non-polar compounds quantifiable by the techniques used, was performed in the Mekong River delta based on analyses of water, sediment and bivalve mollusc samples. Few polar compounds, such as diazinon and fenotrothion, were detected in water but a high number of non-polar chlorinated compounds, such as DDT, HCH, endosulfan and PCBs, were detected in sediments and biota. The highest concentrations measured were of DDT with an average 6.3 ng g(-1) dry weight (range 0.32-67 ng g(-1)) in sediments and 38.6 ng g(-1) (range 5.5-123 ng g(-1)) in molluscs' soft tissues. Amongst chlorinated compounds, DDT concentrations were followed in decreasing order by those of PCB, endosulfan, hexachlorocyclohexane and chlordane. Residues of organochlorine compounds originate from local usage of agrochemicals although with a likely contribution also of atmospheric deposition of residues (not measured) originated elsewhere. Concentrations of PCB and pesticide residues in the aquatic environment of the Mekong River delta are lower than values reported for other regions of Vietnam and Asia. Nevertheless, current concerns about the effects of chlorinated compounds on public health advise improved control of chemical residue discharges in order to abate environmental contamination.

Real-world benefit of nivolumab in a Canadian non-small-cell lung cancer cohort.

Background: Nivolumab was the first immuno-oncology agent available for the treatment of lung cancer in Canada. In the present study, we evaluated the real-world benefit of nivolumab in Canadian patients with lung cancer. Methods: Patients included in the cohort were identified from a registry of patients treated through expanded access to nivolumab before and after Health Canada approval. Demographics were collected from the application forms. Outcome data for the duration of treatment and survival were collected retrospectively. Results: In contrast to the randomized clinical trial populations, our study cohort included patients who were older (median age: 66 years; range: 36-92 years) and who had an Eastern Cooperative Oncology Group performance status of 2 (8.9%). Despite the poorer-prognosis cohort, median overall survival was 12.0 months, which is comparable to the survival demonstrated in the randomized phase iii trials of nivolumab in lung cancer. Median time to treatment discontinuation was 3.45 months and was similar for all patient subgroups, including poorer-prognosis groups such as those with a performance status of 2, those 75 years of age and older, and those with brain metastases. Conclusions: Nivolumab given in a real-world clinical setting was associated with results similar to those reported in the phase iii clinical trial setting.

Assessment of liver microcirculation in human cirrhosis.

Alterations in the liver microcirculation were characterized by use of the multiple-indicator dilution technique in 25 cirrhotic patients undergoing hemodynamic evaluation of portal hypertension. Hepatic vein outflow dilution curves were obtained after portal vein or hepatic artery injections of a vascular reference substance (labeled erythrocytes) and of diffusible substances (labeled albumin and sucrose). In 23 of these patients (19 with alcoholic cirrhosis and 4 with postnecrotic cirrhosis), unimodal erythrocytes and albumin curves were obtained; the immediately accessible albumin space ranged from normal values (that were substantially larger than the erythrocyte space) to low values (that were little larger than the erythrocyte space). In parallel with this, the hepatic extraction of indocyanine green decreased and was correlated with the albumin space (r = 0.821, P less than 0.001). The form of labeled sucrose curves showed progressive changes indicating limited diffusion into the interstitial space. In contrast, bimodal curves were found in two patients (with macronodular cirrhosis); a large proportion of all labels appeared simultaneously in the early part of the outflow curves. Model analysis of the unimodal data indicated that the spectrum of findings could best be explained by progressive development of a barrier to exchange by progressive capillarization of the microvascular bed, and the form of the bimodal data suggested that large vessel shunting was occurring. Both changes, in turn, will contribute to the reduced extraction of protein-bound materials in cirrhosis.

Multimodality imaging for focus localization in pediatric pharmacoresistant epilepsy.

UNLABELLED: Multiple structural and functional imaging modalities are available to localize the epileptogenic focus. In pre-surgical evaluation of children with pharmacoresistant epilepsy, investigations with the maximum yield should be considered in order to reduce the complexity of the workup. OBJECTIVE: To determine the extent to which PET, ictal/interictal SPECT and its co-registration with the patient's MRI contributes to correct localization of the epileptogenic focus, surgical intervention and to the post surgical outcome in paediatric patients. METHODS: The study population included children and adolescents with pharmacoresistant epilepsy (n = 50) who underwent preoperative evaluation, surgery and had postoperative follow-up for at least 12 months. Outcome was measured by postoperative seizure frequency using Engel's classification. RESULTS: Thirty-nine patients (78%) became completely seizure free after surgical intervention. The likelihood to benefit from surgical treatment was significantly higher if localization with more imaging modalities (MRI, PET, SPECT) were concordant with respect to the resected brain area (p < 0.01). Preoperative PET examination provided better localizing information in patients with extratemporal epilepsy and/or dysplastic lesions, whereas SPECT was found to be superior to PET in patients with temporal lobe epilepsy and/or tumors (p < 0.05). No significant difference was noted in the surgical outcome in younger or older age group, in children with or without special education needs. CONCLUSION: In paediatric epilepsy pre-surgical evaluation, the combined use of multiple functional imaging modalities for a precise localisation of the epileptogenic focus is worthwhile for both extratemporal and temporal lobe epilepsy, also when EEG and MRI alone are non-contributive, given the potential benefit of complete postoperative seizure control.

Trends in the use of laboratory tests for the diagnosis of Clostridium difficile infection and association with incidence rates in Quebec, Canada, 2010-2014.

BACKGROUND: Several Clostridium difficile infection (CDI) surveillance programs do not specify laboratory strategies to use. We investigated the evolution in testing strategies used across Quebec, Canada, and its association with incidence rates. METHODS: Cross-sectional study of 95 hospitals by surveys conducted in 2010 and in 2013-2014. The association between testing strategies and institutional CDI incidence rates was analyzed via multivariate Poisson regressions. RESULTS: The most common assays in 2014 were toxin A/B enzyme immunoassays (EIAs) (61 institutions, 64%), glutamate dehydrogenase (GDH) EIAs (51 institutions, 53.7%), and nucleic acid amplification tests (NAATs) (34 institutions, 35.8%). The most frequent algorithm was a single-step NAAT (20 institutions, 21%). Between 2010 and 2014, 35 institutions (37%) modified their algorithm. Institutions detecting toxigenic C difficile instead of C difficile toxin increased from 14 to 37 (P < .001). Institutions detecting toxigenic C difficile had higher CDI rates (7.9 vs 6.6 per 10,000 patient days; P = .01). Institutions using single-step NAATs, GDH plus toxigenic cultures, and GDH plus cytotoxicity assays had higher CDI rates than those using an EIA-based algorithm (P < .05). CONCLUSIONS: Laboratory detection of CDI has changed since 2010. There is an association between diagnostic algorithms and CDI incidence. Mitigation strategies are warranted.

[Epileptic seizures and hematemesis in a young patient with sickle cell disease]. / Épilepsie puis hématémèse chez une jeune patiente drépanocytaire.

INTRODUCTION: Sickle cell disease is a multi-faceted disease, which can affect all organs. Here, we report the case of a young woman whose clinical presentation was confusing. CASE REPORT: An 18-year-old patient from Martinique in Caribbean area presented to the emergency room with widespread pain, as part of a vaso-occlusive crisis. She reported being followed for SS sickle cell anemia, with a history of vaso-occlusive crises and exchange transfusions in the past. Her hemoglobin rate was 83g/L. She was treated with opioid analgesics. Then, she presented several generalized tonic-clonic seizures and major episodes of hematemesis, which proved to be simulated by the patient, whose hemoglobin electrophoresis result was finally AS. CONCLUSION: This patient had therefore the Münchausen syndrome, mimicking sickle cell anemia, like eight other cases reported in the literature.

Triamterene kinetics and dynamics in cirrhosis.

Triamterene is extensively metabolized by the liver and undergoes important presystemic elimination in normal subjects after oral doses. We examined triamterene disposition in eight healthy controls and seven patients with cirrhosis and ascites. A specific and sensitive HPLC assay was used to measure concentrations of triamterene and of its major metabolite p-hydroxy-triamterene sulfate (OH-T-S). Apparent oral clearance of triamterene in controls averaged 1617 +/- 219 ml/min. Plasma concentration of OH-T-S was 7.2 +/- 1.1 times that of the parent compound (estimated by the ratio AUCOH -T-S/ AUCtriamterene ). Urinary recovery of OH-T-S accounted for 45% of the triamterene dose. There was 92% reduction in apparent oral clearance of triamterene (134 +/- 42 ml/min) in patients with cirrhosis. The ratio AUCOH -T-S/ AUCtriamterene fell to 0.55 +/- 0.2, and urinary recovery of OH-T-S accounted for only 15% of the dose. These changes in triamterene kinetics in patients with cirrhosis resulted in prolongation of its natriuretic effect, which lasted for up to 48 hr, whereas it was only 8 hr in the controls. These observations reinforce the concept that cirrhosis is associated with a markedly impaired disposition of drugs that have a large first-pass effect.

Prediction of cyclosporine clearance in liver transplant recipients by the use of midazolam as a cytochrome P450 3A probe.

BACKGROUND: Interindividual differences in the kinetics of cyclosporine (INN, ciclosporin) result in part from variations in the activity of cytochrome P450 3A (CYP3A). The biotransformation of midazolam to 1'-hydroxymidazolam is also catalyzed by CYP3A. The objective of this study was to examine the usefulness of midazolam as a CYP3A probe to predict cyclosporine clearance. METHODS: Twenty-six stable liver transplant recipients receiving immunosuppressive therapy with oral cyclosporine (Neoral) were studied. Midazolam (0.015 mg/kg) was administered intravenously and a blood sample was obtained 1 hour later. The plasma concentration of midazolam and 1'-hydroxymidazolam was measured by gas chromatography-mass spectrometry. Blood concentration of cyclosporine was measured by a fluorescence polarization assay. Cyclosporine clearance was calculated as daily dose divided by trough level. RESULTS: There were large interindividual variations in cyclosporine clearance and in midazolam metabolism. Cyclosporine blood levels correlated poorly with dose (r = -0.016). However, there was a significant correlation between cyclosporine clearance and the plasma concentration of 1'-hydroxymidazolam (r = 0.559; P < .001) or the midazolam/1'-hydroxymidazolam plasma concentration ratio (r = 0.668; P < .001). CONCLUSION: Heterogeneity in CYP3A activity contributes to interpatient differences in cyclosporine dosage requirements after liver transplantation. Midazolam metabolism correlated with cyclosporine clearance, but it accounted for only about 40% of the variability in the apparent oral clearance of cyclosporine and this relationship is not tight enough to be useful in the prediction of cyclosporine dosage requirements in the clinical setting.

Furosemide disposition in cirrhosis.

Furosemide disposition after rapid intravenous injection (80 mg) was studied in 10 normal healthy subjects and eight patients with cirrhosis and ascites. In the cirrhotic patients the elimination half-life was modestly longer (81.0 +/- 8.0 min and 60.2 +/- 5.8 min). This prolongation was not associated with a difference in systemic clearance (156 +/- 7 ml/min in normal and 142 +/- 16 ml/min in cirrhotic subjects), rather it was a reflection of alterations in furosemide distribution. The steady-state volume of distribution was increased from 8.5 +/- 0.4 l in the healthy subjects to 12.1 +/- 1.3 l in the cirrhotic subjects; estimation in terms of unbound drug indicated an approximately 50% smaller value in cirrhosis. These observations were quantitatively consistent with the increased percentage of furosemide in plasma in the unbound form in the patients (10.2 +/- 1.0%) compared to in the normal subjects (4.0 +/- 0.1%). The 24-hr percentage urinary recovery of unchanged drug (58.8 +/- 2.8% and 53.1 6.5%) and the glucuronide metabolite (17.8 +/- 1.5 and 21.3 +/- 3.4) were on the same order in the normal and cirrhotic groups. The lack of major effects of cirrhosis on furosemide disposition suggests that changes in furosemide diuretic efficacy in such patients is a result of altered dynamic factors rather than altered disposition.

Furosemide kinetics and dynamics in patients with cirrhosis.

Factors that influence intersubject variability in response to furosemide have been investigated in normal subjects and patients with cirrhosis. Furosemide pharmacokinetics and pharmacodynamics were measured in eight normal subjects and 14 patients with cirrhosis, eight of whom were resistant to diuretic therapy. Furosemide renal clearance decreased in proportion to creatinine clearance, whereas nonrenal clearance and volume of distribution were unchanged. These pharmacokinetic changes were, however, minimal and resulted in an only marginal alteration in the plasma concentration-time curve. The maximal rate of urinary sodium excretion decreased with reductions in creatinine clearance (r = 0.77). However, the extent of reduction in urinary excretion of sodium was proportionally greater than the reduction in creatinine clearance, whereas the rate of urinary furosemide excretion required to achieve 50% of maximal response did not change. Furosemide's pharmacokinetics were not, therefore, appreciably altered by cirrhosis. However, cirrhosis was associated with a reduction in pharmacodynamic response to this diuretic.

Cytochrome P450 and liver diseases.

Cytochrome P-450 (CYPs) are involved in the metabolism of drugs, chemicals and endogenous substrates. The hepatic CYPs are also involved in the pathogenesis of several liver diseases. CYP-mediated activation of drugs to toxic metabolites induces hepatotoxicity. Well-known examples include acetaminophen and halothane. In some instances, covalent binding of the toxic metabolite to CYP leads to the formation of anti-CYP antibodies and immune-mediated hepatotoxicity (hydralazine, tienilic acid). Anti-CYP2D6 antibodies are also present in the serum of patients with type II autoimmune hepatitis, but the mechanism leading to their presence and their pathogenic significance remains unclear. Several studies support a role for CYP2E1 in the pathogenesis of alcoholic liver disease and non-alcoholic steatohepatitis. In these conditions, enhanced CYP2E1 activity is associated with lipid peroxidation and the production of reactive oxygen species with secondary damage to cellular membranes and mitochondria. Because of its ability to activate carcinogens, a role for CYP2E1 as a cofactor for hepatocellular carcinoma has also been postulated. On the other hand, drug metabolism is impaired in patients with liver disease, particularly that mediated by CYPs. The content and activity of CYP1A, 2C19 and 3A appear to be particularly vulnerable to the effect of liver disease while CYP2D6, 2C9 and 2E1 are less affected. The pattern of CYPs isoenzymes alterations also differs according to the etiology of liver disease. A strong relationship between the activity of CYPs and the severity of cirrhosis has been demonstrated, but the usefulness of measuring CYP activity to assess hepatic functional reserve remains uncertain.