[Linking Interventional Cardiology clinical registry data with French hospital administrative data: Development and validation of deterministic record linkage]. / Appariement entre un registre régional de pratiques en cardiologie interventionnelle et la base médico-administrative d'hospitalisation française : développement et validation d'un algorithme d'appariement déterministe.

BACKGROUND: To recreate the in-hospital healthcare pathway for patients treated with coronary angiography or percutaneous coronary intervention, we linked the interventional cardiology registry (ACIRA) and the pseudonymized French hospital medical information system database (PMSI) in the Aquitaine region. The objective of this study was to develop and validate a deterministic merging algorithm between these exhaustive and complementary databases. METHODS: After a pre-treatment phase of the databases to standardize the 11 identified linking variables, a deterministic linking algorithm was developed on ACIRA hospital stays between December 2011 and December 2014 in nine interventional cardiology centers as well as the data from the consolidated PMSI databases of the Aquitaine region from 2011 to 2014. Merging was carried out through 12 successive steps, the first consisting in strict linking of the 11 variables. The performance of the algorithm was analyzed in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Strategies complementary to the initial algorithm (change in the order of variables and base preprocessing) were tested. Comparative analysis of merged/unmerged patients explored potential causes of mismatch. RESULTS: The algorithm found 97.2% of the 31,621 ACIRA stays to have sensitivity of 99.9% (95% CI [99.9; 99.9]), specificity of 97.9% (95% CI [97.7; 98.1]), PPV of 99.9% (95% CI [99.9; 99.9]) and NPV of 96.9% (95% CI [96.7; 97.1]). Complementary strategies did not yield better results. The unmerged patients were older, and hospitalized mostly in 2012 in two interventional cardiology centers. CONCLUSION: This study underscored the feasibility and validity of an indirect deterministic pairing to routinely link a registry of practices using hospital data to pseudonymized medico-administrative databases. This method, which can be extrapolated to other health events leading to hospitalization, renders it possible to effectively reconstruct patients' hospital healthcare pathway.

Dual-energy computed tomography in calcium pyrophosphate deposition: initial clinical experience.

OBJECTIVE: To determine the dual-energy computed tomography (DECT) attenuation properties of meniscal calcifications in calcium pyrophosphate deposition (CPPD) in vivo, and assess whether DECT was able to discriminate meniscal CPP deposits from calcium hydroxyapatite (HA) in subchondral and trabecular bone. METHOD: Patients with clinical suspicion of crystal-related arthropathy (gout and/or CPPD) and knee DECT scans were retrospectively assigned to CPPD (n = 19) or control (n = 21) groups depending on the presence/absence of chondrocalcinosis on DECT. Two observers drew standardized regions of interest (ROI) in meniscal calcifications, non-calcified menisci, as well as subchondral and trabecular bone. Five DECT parameters were obtained: CT numbers (HU) at 80 and 140 kV, dual-energy index (DEI), electron density (ρe), and effective atomic number (Zeff). The four different knee structures were compared within/between patients and controls using linear mixed models, adjusting for confounders. RESULTS: Meniscal calcifications (n = 89) in CPPD patients had mean ± SD CT numbers at 80 and 140 kV of 257 ± 64 and 201 ± 48 HU, respectively; with a DEI of 0.023 ± 0.007, and ρe and Zeff of 140 ± 35 and 8.8 ± 0.3, respectively. Meniscal CPP deposits were readily distinguished from calcium HA in subchondral and trabecular bone (p ≤ 0.001), except at 80 kV separately (p = 0.74). Zeff and ρe both significantly differed between CPP deposits and calcium HA in subchondral and trabecular bone (p < 0.0001). CONCLUSION: This proof-of-concept study shows that DECT has the potential to discriminate meniscal CPP deposits from calcium HA in subchondral and trabecular bone in vivo, paving the way for the non-invasive biochemical signature assessment of intra- and juxta-articular calcium crystal deposits.

Late presentation to HIV testing is overestimated when based on the consensus definition.

OBJECTIVES: In 2011, a consensus was reached defining "late presenters" (LPs) as individuals presenting for care with a CD4 count < 350 cells/µL or with an AIDS-defining event, regardless of CD4 count. However, a transient low CD4 count is not uncommon in recent infections. The objective of this study was to investigate how measurements of late presentation change if the clinical stage at the time of diagnosis is taken into account. METHODS: Case surveillance data for newly diagnosed patients in Belgium in 1998-2012 were analysed, including CD4 count at diagnosis, the presence of AIDS-defining events, and recent infections (< 6 months) as reported by clinicians in the case of acute illness or a recent negative test. First, proportions of LPs were calculated according to the consensus definition. Secondly, LPs were reclassified as "nonlate" if infections were reported as recent. RESULTS: A total of 7949 HIV diagnoses were included in the study. Recent infections were increasingly reported over time, accounting for 8.2% of new infections in 1998 and 37.5% in 2012. The consideration of clinical stage significantly modified the proportion of LPs: 18.2% of men who have sex with men (MSM) diagnosed in 2012 would be classified as LPs instead of 30.9% using the consensus definition (P < 0.001). The proportion of patients misclassified as LPs increased significantly over time: 5% in MSM in 1998 vs. 41% in 2012. CONCLUSIONS: This study suggests that low CD4 counts in recent infections may lead to overestimation of late presentation when applying the consensus definition. The impact of transient CD4 count on late presentation estimates should be assessed and, if relevant, the introduction of clinical stage in the definition of late presentation should be considered.

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium.

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp).

A randomized controlled trial of single-class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy: final 96-week results from the FREE study.

OBJECTIVES: The aim of the study was to test the antiviral efficacy of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen, with potential beneficial metabolic effects, as maintenance therapy after induction with dual NRTIs and a boosted protease inhibitor (PI). METHODS: An open-label, noninferiority study was carried out. Antiretroviral therapy (ART)-naïve patients with CD4 count ≤ 350 cells/µL and HIV-1 RNA >30000 copies/mL (n=207) were treated with zidovudine/lamivudine and lopinavir/ritonavir. After achieving HIV-1 RNA <50 copies/mL on two consecutive occasions between weeks 12 and 24 after baseline, 120 patients (baseline: median HIV-1 RNA 5.19 log10 copies/mL; median CD4 count 180 cells/µL) were randomized to receive abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) (n=61) or to continue the PI-based ART (n=59). RESULTS: For the proportions of patients (intention-to-treat; missing=failure) with HIV-1 RNA <400 copies/mL (PI group, 66%; ABC/3TC/ZDV group, 71%) and <50 copies/mL (PI group, 63%; ABC/3TC/ZDV group, 62%) at 96 weeks, switching to ABC/3TC/ZDV was noninferior compared with continuing the PI regimen; the difference in failure rate (ABC/3TC/ZDV minus PI) was -4.4 percentage points [95% confidence interval (CI) -21.0 to +12.3 percentage points] and +0.4 percentage points (95% CI -16.9 to +17.7 percentage points), respectively. In the per protocol analysis, the difference in virological failure for HIV-1 RNA >400 copies/mL (0 of 39 patients in the PI group and two of 45 patients in the NRTI group) and for HIV-1 RNA >50 copies/mL (two of 39 and three of 45 patients, respectively) was +4.4 percentage points (95% CI -2.1 to +11.0 percentage points) and +1.5 percentage points (95% CI -8.6 to +11.7 percentage points), respectively, also showing noninferiority. Serum lipids significantly improved in the NRTI group, but not in the PI arm. CONCLUSIONS: A single-class NRTI regimen after successful induction with standard ART had similar antiviral efficacy compared to continuation of a PI-based regimen at 96 weeks after baseline, with improved serum lipids.

Kinetic modeling of light limitation and sulfur deprivation effects in the induction of hydrogen production with Chlamydomonas reinhardtii. Part II: Definition of model-based protocols and experimental validation.

Photosynthetic hydrogen production under light by the green microalga Chlamydomonas reinhardtii was investigated in a torus-shaped PBR in sulfur-deprived conditions. Culture conditions, represented by the dry biomass concentration of the inoculum, sulfate concentration, and incident photon flux density (PFD), were optimized based on a previously published model (Fouchard et al., 2009. Biotechnol Bioeng 102:232-245). This allowed a strictly autotrophic production, whereas the sulfur-deprived protocol is usually applied in photoheterotrophic conditions. Experimental results combined with additional information from kinetic simulations emphasize effects of sulfur deprivation and light attenuation in the PBR in inducing anoxia and hydrogen production. A broad range of PFD was tested (up to 500 µmol photons m(-2) s(-1) ). Maximum hydrogen productivities were 1.0 ± 0.2 mL H2 /h/L (or 25 ± 5 mL H2 /m(2) h) and 3.1 mL ± 0.4 H2 /h L (or 77.5 ± 10 mL H2 /m(2) h), at 110 and 500 µmol photons m(-2) s(-1) , respectively. These values approached a maximum specific productivity of approximately 1.9 mL ± 0.4 H2 /h/g of biomass dry weight, clearly indicative of a limitation in cell capacity to produce hydrogen. The efficiency of the process and further optimizations are discussed.

Control of structure and growth of polymorphic crystalline thin films of amphiphilic molecules on liquid surfaces.

The spontaneous formation and coexistence of crystalline polymorphic trilayer domains in amphiphilic films at air-liquid interfaces is demonstrated by grazing incidence synchrotron x-ray diffraction. These polymorphic crystallites may serve as models for the early stages of crystal nucleation and growth, helping to elucidate the manner in which additives influence the progress of crystal nucleation, growth, and polymorphism and suggesting ways of selectively generating and controlling multilayers on liquid surfaces. Auxiliary molecules have been designed to selectively inhibit development of the polymorphs, leading primarily to a single phase monolayer.

Bacterial colonization after tunneling in 402 perineural catheters: a prospective study.

BACKGROUND: Bacterial colonization of peripheral nerve catheters is frequent, although infection is relatively rare. With central venous catheters, the tunneling of the catheter into the subcutaneous tissue significantly decreases catheter colonization and catheter-related sepsis. We evaluated the incidence of bacterial colonization in adult patients with tunnelized perineural nerve catheters. METHODS: Peripheral nerve catheters placed under sterile conditions for postoperative analgesia were evaluated prospectively. After removal, they were analyzed for colonization. Quantitative culture was used as described by Brun-Buisson for intravascular catheters. The site of insertion was monitored daily for any signs of infection. RESULTS: Four-hundred-two patients were included in the study during a 2-yr period. The mean duration of peripheral nerve catheters was 48 h (47-50.4). Positive culture occurred in 25 catheters, indicating that the incidence of colonization was 6.22% (3.8-8.5). The microbiological analysis of the catheter tip cultures revealed coagulase-negative staphylococci in 72%. Twenty-two catheters of 25 catheters each had one microorganism, and for three catheters, two microorganisms were identified. No infection was found in any patient. CONCLUSION: The incidence of perineural catheter colonization is low with subcutaneous tunneling. Controlled randomized studies are warranted to determine whether this procedure decreases the risk for infection.

Onset of the alpha-relaxation in the glass-forming solution LiCl-6H2O revealed by Brillouin scattering techniques.

We measured the dynamic structure factor of the liquid and glassy phases of the LiCl-6H(2)O solution by means of inelastic scattering of radiation in the visible, UV, and x-ray range, between 1 GHz and 10 THz, and by means of photon-correlation spectroscopy, between 0.01 Hz and 20 kHz. The measurements were performed in the temperature range between 353 and 80 K. Our data show that a single-relaxation process exists at high temperature, which has features similar to those of the single relaxation of pure water. Upon cooling the system below approximately 220 K, this single mode starts to differentiate two processes, a structural (alpha-) and a secondary (beta-) relaxation. As the temperature is decreased, the beta-relaxation is the vanishing continuation of the single, high-temperature process, while the onset of the alpha-relaxation occurs at the expense of the beta-process.

Optimal selection of organic solvents for biocompatible extraction of beta-carotene from Dunaliella salina.

In the aim of beta-carotene biocompatible extraction, toxicity of various pure solvents belonging to different homologous series has been investigated for Dunaliella salina. The results showed that solvents having logP(oct) > 5 or having a molecular weight over 150 g/mol can be considered biocompatible for this microalga. The membrane critical solvent concentration for each series of solvents has been calculated applying Osborne's model, showing that the aliphatic chlorinated hydrocarbon is the most toxic family studied. Mixtures of a biocompatible solvent (decane) with a toxic solvent (CH(2)Cl(2), MEK, MTBE) have been studied. The beta-carotene extraction ability of CH(2)Cl(2)-decane mixture was found six times more efficient than with pure decane. It has been demonstrated that the extraction ability of solvent depends on its affinity with the product extracted and on its concentration incorporated in the cellular membrane.

[Klebsiella pneumoniae septicaemia and meningitis in a diabetic patient with an hepatic abscess]. / Septicémie et méningite à Klebsiella pneumoniae au depart d'un abcès hépatique chez un patient diabétique.

Klebsiella pneumoniae infections show particular features depending on the geographical localization as well as comorbidity factors. We are presenting the case of a european patient with diabetes mellitus who presented a septicaemia, a meningitis as well as an hepatic abscess due to a K. pneumoniae and whose evolution was excellent under antibiotics. Usually described among Asian patients, the primary hepatic K. pneumoniae abscess, which is a clinical entity recently described, can give rise to potentially serious and multiple septic metastasis. We also discuss the diagnostic and therapeutic attitudes related to this infection.

Against all odds: molecular confirmation of an implausible case of bone tuberculosis.

We report the use of typing based on a variable number of tandem repeats of genetic elements called "mycobacterial interspersed repetitive units" to clarify a puzzling situation involving a patient with an exceptional case of spondylodiskitis that initially led to the suspicion of a possible event of laboratory cross-contamination with Mycobacterium tuberculosis.

Photocatalytic oxidation of methyl ethyl ketone over sol-gel and commercial TiO2 for the improvement of indoor air.

This work focuses on the photocatalytic oxidation of gaseous methyl ethyl ketone chosen as a typical indoor air pollutant. Two types of TiO coatings were prepared and deposited on glass plates: one using the commercial Degussa P25 TiO2 and the other one by sol-gel method. The first objective of this study was to compare different ways of preparing thin films of sol-gel TiO2 coated on glass plates, taking into account their general aspect and their photocatalytic efficiency. Several parameters were tested, such as the stabilising agent, the glass type of the support, the number of coatings and the calcination temperature. One of the synthesised materials was then kept to carry out the following study. The study aimed to assess the influence of TiO2 coating types on the effect of water vapour. This was achieved by performing MEK photocatalytic degradation kinetics under two levels of humidity at a fixed temperature. Experimental results were then modelled by the Langmuir-Hinshelwood equation. The obtained parameters gave specific trends in function of the considered catalyst. The second part of this work was to identify MEK degradation byproducts during its photocatalytic oxidation. The main detected intermediate was acetaldehyde, followed by methyl formate. A MEK degradation pathway was then proposed.

Antimicrobial therapy for intra-abdominal infections: guidelines from the Infectious Disease Advisory Board (IDAB).

Intra-abdominal infection is a common cause of severe sepsis in a hospital setting and remains associated with a significant morbidity, mortality and resource use. Early adequate surgery or drainage remain the cornerstones of intra-abdominal infection management and impact on patients outcome. Concomitant early and adequate empiric antimicrobial therapy further influences patients morbidity and mortality. Multiple empirical regimens have been proposed in this setting, but rarely supported by well designed, randomized-controlled studies. The current manuscript summarizes the recommendations of the Infection Disease Advisory Board on the management of intra-abdominal infections. Empiric antimicrobial therapy for the most common causes of abdominal infections is proposed. In addition, particular attention has been paid on antibiotic treatment duration.

Hydrothermal liquefaction of Nannochloropsis oceanica in different solvents.

Although the hydrothermal liquefaction is considered a promising technology for converting microalgae into liquid biofuels, there are still some disadvantages. This paper demonstrated that the bio-oil yield can be significantly improved by adding alcohols as co-solvents and carrying out the conversion at mild conditions (<250°C), but at the expense of a reduced bio-oil quality. By adding ethanol, the bio-oil yields obtained (up to ∼60%) were comparable to the yield obtained at severe operating conditions using only water as solvent (54±2% on average), but the quality of the bio-oil was lower. However, the main advantages of the process here described lie in the utilisation of wet microalgae (∼75% moisture) and alcohol concentrations which avoid both drying the microalgae and decreasing the amount of microalgae loaded in the reactor.

A novel pre-treatment for the methane production from microalgae by using N-methylmorpholine-N-oxide (NMMO).

The aim of this work was to study the effect of the solvent N-methylmorpholine-N-oxide (NMMO) to pre-treat Nannochloropsis oculata before the anaerobic digestion process. The results indicated that the pre-treatment affects the characteristics of the cell wall, which consequently becomes more susceptible to the microorganisms attack during anaerobic digestion. The methane production was increased by 43% after the pre-treatment, from 238±6mLCH4/gVS until 339±4mLCH4/gVS. On the contrary, the methane production from Chlorella vulgaris decreased after the pre-treatment from 251±4mLCH4/gVS to 231±3mLCH4/gVS. The failure on the pre-treatment was attributed to the particular characteristics of the substrate in consequence of a previous drying step.

Screening of freshwater and seawater microalgae strains in fully controlled photobioreactors for biodiesel production.

Strain selection is one of the primary hurdles facing cost-effective microalgal biodiesel production. Indeed, the strain used affects both upstream and downstream biodiesel production processes. This study presents a screening procedure that considers the most significant criteria in microalgal biodiesel production including TAG production and wet extraction and recovery of TAGs. Fourteen freshwater and seawater strains were investigated. Large variation was observed between the strains in all the screening criteria. The overall screening procedure ultimately led to the identification of Parachlorella kessleri UTEX2229 and Nannochloropsis gaditana CCMP527 as the best freshwater and seawater strains, respectively. They featured the largest areal TAG productivity equal to 2.7×10(-3) and 2.3×10(-3)kgm(-2)d(-1), respectively. These two strains also displayed encouraging cell fragility in a high pressure bead milling process with 69% and 98% cell disruption at 1750bar making them remarkable strains for TAG extraction in wet environment.

[Medication reconciliation at hospital admission: Results and identification of target patients]. / Conciliación de la medicación al ingreso: resultados e identificación de pacientes diana.

OBJECTIVE: To quantify and to classify the discrepancies between the admission treatment and the usual patient treatment. To determine the variables that predict those patients that will have more benefit from medication reconciliation. MATERIAL AND METHODS: A prospective medication reconciliation study was conducted in the Vascular Surgery Unit from March 2014 to December 2014. When the patients were admitted to the Vascular Surgery Unit, they were informed about the study and asked to prepare information about their chronic treatment. The pharmacist then checked their clinical records, outpatient prescriptions, and also interviewed the patient, obtaining the best pharmacotherapeutic history available. The discrepancies with the admission treatment were written into the patient electronic clinical records. Finally, the physician classified the discrepancies, and changed the treatment, if needed. The statistical analysis included a comparison between patients with and without a non-justified discrepancy (NJD). The statistically different characteristics were used to plot Receiver Operating Characteristic curves, in order to determine the sensitivity and the specificity of these variables to select patients with discrepancies. RESULTS: A total of 380 patients were included. There were 845 non-justified, 600 justified non-documented, and 439 justified documented discrepancies. At least one NJD was identified in 293 patients (77%), with 65 patients (17%) having only justified discrepancies, and 22 patients (6%) having no discrepancies. NJD were: different dose, route or schedule (51%), omission (39%), wrong drug (8%) and commission (2%). The variables associated with discrepancies were number of chronic medications drugs and provider of information. CONCLUSIONS: In most studies, omission is the most frequent error. In contrast, in our study the most frequent error is different dose, route, or schedule. The variable that allows selecting patients at higher risk of discrepancies is the number of chronic drugs. This risk is also increased if the patients are not the manager of their own medication.

The final step of aldosterone biosynthesis requires reducing power. It is not a dehydrogenation.

A mitochondrial preparation from adult duck adrenal gland was used to study the mechanism (dehydrogenation or other) of the last step of aldosterone biosynthesis (18-oxidation) by incubation of tritiated 18-hydroxycorticosterone. Results show that the role of citric acid cycle metabolites is to provide reducing power. When reducing power is provided by malate, which yields NADH or NADPH directly, the reoxidation of reduced coenzymes in the oxidative phosphorylation chain is not necessary. In the presence of succinate, the oxidative phosphorylation chain is required, but only to provide ATP. Stimulation of the reaction by low concentrations of KCN in the presence of malate shows that the reducing power is not used in the oxidative phosphorylation chain. These data suggest that the reaction is not a dehydrogenation and that the reducing power is used in a pathway competing with the respiratory chain, most probably a hydroxylating pathway, in mitochondria.

Impact on energy metabolism of quantitative and functional cyclosporine-induced damage of kidney mitochondria.

In this study we have measured, under experimental conditions which maintained efficient coupling, respiratory intensity, respiratory control, oxidative phosphorylation capacity and protonmotive force. Succinate cytochrome-c reductase and cytochrome-c oxidase activities were also studied. These investigations were carried out using kidney mitochondria from cyclosporine-treated rats (in vivo studies) and from untreated rats in the presence of cyclosporine (in vitro studies). Inhibition of respiratory intensity by cyclosporine did not exceed 21.1% in vitro and 15.9% in vivo. Since there was no in vitro inhibition of succinate cytochrome-c reductase and cytochrome-c oxidase activities, the slowing of electron flow observed can be interpreted as a consequence of an effect produced by cyclosporine between cytochromes b and c1. Cyclosporine had no effect on respiratory control either in vitro or in vivo. Statistically significant inhibition of the oxidative phosphorylation was observed both in vitro (6.6%) and in vivo (12.1%). Moreover, cyclosporine did not induce any change of membrane potential either in vivo or in vitro. Our findings show that cyclosporine is neither a protonophore, nor a potassium ionophore. In cyclosporine-treated rats we notices a decrease of protein in subcellular fraction, including the mitochondrial fraction. The role of the inhibition respiratory characteristics by cyclosporine in nephrotoxicity in vivo must take account of these two parameters: inhibition of the respiratory characteristics measured in vitro and diminution of mitochondrial protein in cyclosporine-treated rats.