[Evaluation of the implantation of a de-prescribing process for proton pump inhibitor (PPI) using an algorithm within an internal medicine department]. / Évaluation de l'implantation d'un processus de dé-prescription des inhibiteurs de la pompe à protons (IPP) à l'aide d'un algorithme au sein d'un service de médecine interne.

INTRODUCTION: The prescription of proton pump inhibitors (PPIs) seems excessive. Taken over the long term, PPIs can cause serious side effects. It therefore turns out to be justified to suspend treatments whose expected benefit seems too low compared to the risks involved : it is deprescription. The objective of this study is to assess a process for the deprescription of PPIs in a hospital internal medicine department. METHOD: After collegial deliberation, an algorithm for assisting in the deprescription of PPIs was validated. If necessary, the PPI was phased out over 1 month. A telephone follow-up at 1, 2 and 3 months was carried out in order to assess the maintenance of deprescription and the occurrence of digestive symptoms. The evaluation criteria were the rate of deprescription and the rate of maintenance of deprescription at 3 months following reports from patients, their caregivers or a family member. RESULTS: 105 patients with a mean age of 72 years were included over a period of 21 weeks, and in 31 cases (29%), deprescription was performed. After 3 months of follow-up, there was 71% maintenance of deprescription. Three patients were lost to follow-up and 6 patients resumed PPI. CONCLUSION: The approach undertaken resulted in the suspension of PPI intake in almost 3 out of 10 cases. This result was maintained at least three months for a large majority of patients. It will be interesting to continue this process and extend the monitoring over longer periods, in order to ensure that PPI de-prescription is maintained in the long term.

[Characteristics of patients admitted from emergency units in 18 internal medicine departments and organisation of these departments: A cross sectional study from SNFMI (SiFMI study group) in 2015]. / Caractéristiques des patients admis en médecine interne dans 18 hôpitaux français en aval des urgences et organisation de ces services : enquête transversale de la SNFMI (groupe d'étude SiFMI) en 2015.

INTRODUCTION: Patients admitted from emergency units represent a large portion of the population in internal medicine departments. The aim of this study is to identify characteristics of patients and organization of these departments. METHODS: Between June 29th and July 26th 2015, voluntary internal medicine departments from the SiFMI group prospectively filled anonymized internet forms to collect data of each patients admitted in their ward from emergency units, during seven consecutive days. RESULTS: Three hundred and sixty-five patients from emergency departments were admitted in 18 internal medicine inpatients departments, totalling 1100 beds and 33,530 annual stays, 56% of them for emergency units inpatients. Mean age was 68 years, 54% were women, mean Charlson score was 2.6 and 44% of the patients took at least three drugs. Main causes of hospitalization were infectious (29%) and neurological (17%) diseases. Mean length of stay was 9.2 days. The medical team was composed by a median value of 4,5 [2,75-6,25] senior full-time equivalents, 86% were internists. Each department except one received residents, two third of them were from general medicine. CONCLUSION: This study highlights a high organizational variability among internal medicine departments and patients, and sets internal medicine as a specialty with a great capacity to achieve an integrative/comprehensive management of patients and to offer a comprehensive basis for physicians in training.

Optimization of Time- and Code-Division-Multiplexed Readout for Athena X-IFU.

Readout of a large, spacecraft-based array of superconducting transition-edge sensors (TESs) requires careful management of the layout area and power dissipation of the cryogenic-circuit components. We present three optimizations of our time- (TDM) and code-division-multiplexing (CDM) systems for the X-ray Integral Field Unit (X-IFU), a several-thousand-pixel-TES array for the planned Athena-satellite mission. The first optimization is a new readout scheme that is a hybrid of CDM and TDM. This C/TDM architecture balances CDM's noise advantage with TDM's layout compactness. The second is a redesign of a component: the shunt resistor that provides a dc-voltage bias to the TESs. A new layout and a thicker Pd-Au resistive layer combine to reduce this resistor's area by more than a factor of 5. Third, we have studied the power dissipated by the first-stage SQUIDs (superconducting quantum-interference devices) and the readout noise versus the critical current of the first-stage SqUIDs. As a result, the X-IFU TDM and C/TDM SQUIDs will have a specified junction critical current of 5 µA. Based on these design optimizations and TDM experiments described by Durkin, et al. (these proceedings), TDM meets all requirements to be X-IFU's backup-readout option. Hybrid C/TDM is another viable option that could save spacecraft resources.

Demonstration of Athena X-IFU Compatible 40-Row Time-Division-Multiplexed Readout.

Time-division multiplexing (TDM) is the backup readout technology for the X-ray Integral Field Unit (X-IFU), a 3,168-pixel X-ray transition-edge sensor (TES) array that will provide imaging spectroscopy for ESA's Athena satellite mission. X-0IFU design studies are considering readout with a multiplexing factor of up to 40. We present data showing 40-row TDM readout (32 TES rows + 8 repeats of the last row) of TESs that are of the same type as those being planned for X-IFU, using measurement and analysis parameters within the ranges specified for X-IFU. Singlecolumn TDM measurements have best-fit energy resolution of (1.91 ± 0.01) eV for the Al Kα complex (1.5 keV), (2.10 ± 0.02) eV for Ti Kα (4.5 keV), (2.23 ± 0.02) eV for Mn Kα (5.9 keV), (2.40 ± 0.02) eV for Co Kα (6.9 keV), and (3.44 ± 0.04) eV for Br Kα (11.9 keV). Three-column measurements have best-fit resolution of (2.03 ± 0.01) eV for Ti Kα and (2.40 ± 0.01) eV for Co Kα. The degradation due to the multiplexed readout ranges from 0.1 eV at the lower end of the energy range to 0.5 eV at the higher end. The demonstrated performance meets X-IFU's energy-resolution and energy-range requirements. True 40-row TDM readout, without repeated rows, of kilopixel scale arrays of X-IFU-like TESs is now under development.

[Reversible posterior encephalopathy syndrome and cardiomyopathy after bevacizumab therapy]. / Syndrome d'encéphalopathie postérieure et atteinte cardiaque réversibles sous bévacizumab.

INTRODUCTION: Bevacizumab is an antibody directed against VEGF-A. It is approved for the treatment of many cancer diseases. Its side effects are currently not well known by physicians. CASE REPORT: A 70-year-old female with metastatic colonic adenocarcinoma was admitted in the intensive care unit because of a coma, four days after having received a combined monthly chemotherapy containing bevacizumab, oxaliplatine, 5 fluorouracil, and folinic acid for the fourth time. On clinical examination, she presented with lower limbs spasticity and hypertension. Etiologic investigations, including cerebral tomodensitometry, cerebrospinal fluid examination, psychotropic drugs urinary testing, and electroencephalogram, were negative. Consciousness improved without any other treatment than nicardipine and urapidil, but the patient was initially confused. Cerebral magnetic resonance imaging showed changes suggestive of posterior reversible encephalopathy syndrome, but also involving frontal lobes. There were additional biological and echocardiographic changes suggestive of cardiac involvement. The patient recovered completely of both cardiac and neurologic manifestations 10 days later. CONCLUSION: Physicians should be aware of cardiovascular adverse effects of bevacizumab. High blood pressure must be treated to avoid more severe complications. When a posterior reversible encephalopathy syndrome occurs, cardiac involvement should be investigated.

[Practical judgment and burn-out syndrome among physicians]. / Jugement pratique et burn-out des médecins.

The growing incidence of burn-out syndrome among physicians has become a major concern for public policy. The root causes are not fully understood. We make the assumption that the most powerful cause of their suffering at work is the challenging of physician's practical judgment. Practical judgment is the faculty, which connects knowledge and reason, science and experience, general and individual issues. It lies at the core of medical action and its exercise is closely associated with a pleasure at work. The evolution of medicine, particularly the proliferation of procedures, has a harmful influence on its training and its exercise.

Adaptive and robust statistical methods for processing near-field scanning microwave microscopy images.

Near-field scanning microwave microscopy offers great potential to facilitate characterization, development and modeling of materials. By acquiring microwave images at multiple frequencies and amplitudes (along with the other modalities) one can study material and device physics at different lateral and depth scales. Images are typically noisy and contaminated by artifacts that can vary from scan line to scan line and planar-like trends due to sample tilt errors. Here, we level images based on an estimate of a smooth 2-d trend determined with a robust implementation of a local regression method. In this robust approach, features and outliers which are not due to the trend are automatically downweighted. We denoise images with the Adaptive Weights Smoothing method. This method smooths out additive noise while preserving edge-like features in images. We demonstrate the feasibility of our methods on topography images and microwave |S11| images. For one challenging test case, we demonstrate that our method outperforms alternative methods from the scanning probe microscopy data analysis software package Gwyddion. Our methods should be useful for massive image data sets where manual selection of landmarks or image subsets by a user is impractical.

Prediction of fraction metabolized via CYP3A in humans utilizing cryopreserved human hepatocytes from a set of 12 single donors.

1. It has previously been demonstrated that metabolism of drugs via a single enzymatic pathway, particularly CYP3A4, is associated with increased risk for drug-drug interactions (DDI). Quantitative experimental systems as well as integrated prediction models to assess such risk during the preclinical phase are highly warranted. 2. The present study was designed to systematically investigate the performance of human cryopreserved hepatocytes in suspension to predict fraction metabolized via CYP3A (fmCYP3A) by assessing the ketoconazole sensitive intrinsic clearance (CLint) for five prototypical CYP3A substrates with varying degree of CYP3A dependent CLint in twelve individual hepatocyte batches. 3. We demonstrate that in contrast to well predicted mean hepatic metabolic clearance (CLH) and mean fmCYP3A data, the variability in CYP3A contribution for compounds having multiple metabolic pathways cannot be predicted from inhibition experiments using ketoconazole as inhibitor. Instead, data in the present paper indicate that the variability is larger after inhibition of CYP3A for compounds having multiple metabolic pathways. 4. It is therefore recommended to estimate the average CLint and fmCYP3A for a given test compound in a series (n = 10) of individual human hepatocyte batches.

A near-field scanning microwave microscope for characterization of inhomogeneous photovoltaics.

We present a near-field scanning microwave microscope (NSMM) that has been configured for imaging photovoltaic samples. Our system incorporates a Pt-Ir tip inserted into an open-ended coaxial cable to form a weakly coupled resonator, allowing the microwave reflection S(11) signal to be measured across a sample over a frequency range of 1 GHz - 5 GHz. A phase-tuning circuit increased impedance-measurement sensitivity by allowing for tuning of the S(11) minimum down to -78 dBm. A bias-T and preamplifier enabled simultaneous, non-contact measurement of the DC tip-sample current, and a tuning fork feedback system provided simultaneous topographic data. Light-free tuning fork feedback provided characterization of photovoltaic samples both in the dark and under illumination at 405 nm. NSMM measurements were obtained on an inhomogeneous, third-generation Cu(In,Ga)Se(2) (CIGS) sample. The S(11) and DC current features were found to spatially broaden around grain boundaries with the sample under illumination. The broadening is attributed to optically generated charge that becomes trapped and changes the local depletion of the grain boundaries, thereby modifying the local capacitance. Imaging provided by the NSMM offers a new RF methodology to resolve and characterize nanoscale electrical features in photovoltaic materials and devices.

[Pulmonary hypertension due to tumor embolism]. / Hypertension artérielle pulmonaire par embolisation de cellules tumorales.

We report a 46-year-old woman with a metastatic breast cancer who developed a subacute pulmonary hypertension. The final diagnosis was microscopic pulmonary neoplastic emboli. She presented with the typical clinical picture of a pulmonary hypertension with a normal pulmonary angiographic computer tomography and multiple sub-segmental perfusion defects on radionuclide imaging. This serious condition must be known by physicians, because of an opportunity to obtain the diagnosis by the cytologic analysis of sampled microvascular blood obtained with a pulmonary artery catheterization. The prognosis is poor and there is no efficient therapy.

Value of (18)F-FDG-PET/CT in patients with fever of unknown origin and unexplained prolonged inflammatory syndrome: a single centre analysis experience.

OBJECTIVE: The aim of our study was to evaluate the diagnostic contribution of (18)F-fluoro-deoxyglucose ((18)F-FDG)-positron emission tomography (PET)/computed tomography (CT) in patients with fever of unknown origin (FUO) or unexplained prolonged inflammatory syndrome (UPIS) in real life. PATIENTS AND METHODS: We performed a retrospective study including 14 patients with FUO or UPIS hospitalised in our institution (Strasbourg University Hospital, France) between January 2005 and July 2006. (18)F-FDG-PET/CT was considered helpful when abnormal results allowed an accurate diagnosis. RESULTS: (18)F-FDG-PET/CT was helpful in half the patients (7/14) for final diagnosis. A diagnosis was reached in 87.5% of the patients (7/8) with an abnormal (18)F-FDG-PET/CT but only in 50% of the patients (3/6) with a normal (18)F-FDG-PET/CT. Conventional chest and abdominal CT was performed in 13 patients before ordering (18)F-FDG-PET/CT. We considered that (18)F-FDG-PET/CT was essential to establish the final diagnosis in only 23% of the patients (3/13) since neither chest nor abdominal CT identified abnormalities consistent with the final diagnosis. However, among the three patients, two were diagnosed with large vessel vasculitis and one patient with local prosthetic infection. CONCLUSIONS: Our study supports the potential interest of (18)F-FDG-PET/CT in the diagnostic workup of FUO and UPIS as it helped establish a fine diagnosis in half of the cases. However, (18)F-FDG-PET/CT appeared to be essential to the final diagnosis in only 23% of the cases. In our opinion, this protocol should be performed as a second level test, especially when conventional CT is normal or is unable to discriminate between active and silent lesions.

Does the (13)C of foliage-respired CO(2) and biochemical pools reflect the (13)C of recently assimilated carbon?

Isotopic labelling experiments were conducted to assess relationships among (13)C of recently assimilated carbon (deltaC(A)), foliage respiration (deltaC(F)), soluble carbohydrate (deltaC(SC)), leaf waxes (deltaC(LW)) and bulk organic matter (deltaC(OM)). Slash pine, sweetgum and maize were grown under (13)C depleted CO(2) to label biomass and then placed under ambient conditions to monitor the loss of label. In pine and sweetgum, deltaC(F) of labelled plants (approximately -44 and -35 per thousand, respectively) rapidly approached control values but remained depleted by approximately 4-6 per thousand after 3-4 months. For these tree species, no or minimal label was lost from deltaC(SC), deltaC(LW) and deltaC(OM) during the observation periods. deltaC(F) and deltaC(SC) of labelled maize plants rapidly changed and were indistinguishable from controls after 1 month, while deltaC(LW) and deltaC(OM) more slowly approached control values and remained depleted by 2-6 per thousand. Changes in deltaC(F) in slash pine and sweetgum fit a two-pool exponential model, with the fast turnover metabolic pool (approximately 3-4 d half-life) constituting only 1-2% of the total. In maize, change in deltaC(F) fits a single pool model with a half-life of 6.4 d. The (13)C of foliage respiration and biochemical pools reflect temporally integrated values of deltaC(A), with change in isotopic composition dampened by the size of metabolic carbon reserves and turnover rates.

Mycorrhizal fungi supply nitrogen to host plants in Arctic tundra and boreal forests: 15N is the key signal.

Symbiotic fungi's role in providing nitrogen to host plants is well-studied in tundra at Toolik Lake, Alaska, but little-studied in the adjoining boreal forest ecosystem. Along a 570 km north-south transect from the Yukon River to the North Slope of Alaska, the 15N content was strongly reduced in ectomycorrhizal and ericoid mycorrhizal plants including Betula, Salix, Picea mariana (P. Mill.) B.S.P., Picea glauca Moench (Voss), and ericaceous plants. Compared with the 15N content of soil, the foliage of nonmycorrhizal plants (Carex and Eriophorum) was unchanged, whereas content of the ectomycorrhizal fungi was very much higher (e.g., Boletaceae, Leccinum and Cortinarius). It is hypothesized that similar processes operate in tundra and boreal forest, both nitrogen-limited ecosystems: (i) mycorrhizal fungi break down soil polymers and take up amino acids or other nitrogen compounds; (ii) mycorrhizal fungi fractionate against 15N during production of transfer compounds; (iii) host plants are accordingly depleted in 15N; and (iv) mycorrhizal fungi are enriched in 15N. Increased N availability for plant roots or decreased light availability to understory plants may have decreased N allocation to mycorrhizal partners and increased delta15N by 3-4 parts per million for southern populations of Vaccinium vitis-idaea L. and Salix. Fungal biomass, measured as ergosterol, correlated strongly with soil organic matter and attained amounts similar to those in temperate forest soils.

Use of mRNA expression to detect the induction of drug metabolising enzymes in rat and human hepatocytes.

It is important to investigate the induction of cytochrome P450 (CYP) enzymes by drugs. The most relevant end point is enzyme activity; however, this requires many cells and is low throughput. We have compared the CYP1A, CYP2B and CYP3A induction response to eight inducers in rat and human hepatocytes using enzyme activities (CYP1A2 (ethoxyresorufin), 2B (benzoxyresorufin for rat and bupropion for human) and CYP3A (testosterone)) and Taqman Low Density Array (TLDA) analysis. There was a good correlation between the induction of CYP1A2, CYP2B6 and CYP3A4 enzyme activities and mRNA expression in human hepatocytes. In contrast, BROD activities and mRNA expression in rat hepatocytes correlated poorly. However, bupropion hydroxylation correlated well with Cyp2b1 expression in rat hepatocytes. TLDA analysis of a panel of mRNAs encoding for CYPs, phase 2 enzymes, nuclear receptors and transporters revealed that the main genes induced by the 8 compounds tested were the CYPs. AhR ligands also induced UDP-glucuronosyltransferases and glutathione S-transferases in rat and human hepatocytes. The transporters, MDR1, MDR3 and OATPA were the only transporter genes significantly up-regulated in human hepatocytes. In rat hepatocytes Bsep, Mdr2, Mrp2, Mrp3 and Oatp2 were up-regulated. We could then show a good in vivo:in vitro correlation in the induction response of isolated rat hepatocytes and ex-vivo hepatic microsomes for the drug development candidate, EMD392949. In conclusion, application of TLDA methodology to investigate the potential of compounds to induce enzymes in rat and human hepatocytes increases the throughput and information gained from one assay, without reducing the predictive capacity.

[Breastfeeding and drug management in connective tissue and rheumatic diseases]. / Traitements de fond des affections inflammatoires systémiques au cours de l'allaitement.

Breastfeeding is often contraindicated when drugs are prescribed for a chronic maternal disease. Many of the restrictions are based on theoretical concerns only and may be excessively cautious. An updated review is mandatory. Many antirheumatic drugs can be safely used during lactation: nonsteroidal anti-inflammatory drugs, corticosteroids, sulfasalazine, antimalarial agents. Doubt remains about safety of cochicine or dapsone. Expert opinions still diverge but move on in favor the use of azathioprine, ciclosporin, and even methotrexate. Leflunomide, mycophenolate mofetil and cyclophosphamide are contraindicated. No conclusion can be reached regarding anti-TNF-alpha and rituximab. Current knowledge about drug transfer in breast-milk and cumulative empirical data have expanded the possibilities to allow breastfeeding when the mother is treated with antirheumatic medications. The data provided by pharmaceutical industry should not be the only source of the physician's information in the risk assessment.

[Digital arteritis preceding the diagnosis of a malignant B cell lymphoma]. / Artérite digitale précédant la découverte d'un lymphome malin B.

We report the case of a young smoker woman who developed a severe acrosyndrome of rapid onset, involving both hands except the thumbs. The angiography showed digital arteritis. Antinuclear antibodies were present at high level. Three months later, a large B cell lymphoma was diagnosed. Complete remission was achieved, but the acrosyndrome persisted with only partial improvement. The antinuclear antibodies disappeared. The paraneoplastic nature of the acrosyndrome is discussed.