A data-driven pipeline to extract potential adverse drug reactions through prescription, procedures and medical diagnoses analysis: application to a cohort study of 2,010 patients taking hydroxychloroquine with an 11-year follow-up.

CONTEXT: Real-life data consist of exhaustive data which are not subject to selection bias. These data enable to study drug-safety profiles but are underused because of their temporality, necessitating complex models (i.e., safety depends on the dose, timing, and duration of treatment). We aimed to create a data-driven pipeline strategy that manages the complex temporality of real-life data to highlight the safety profile of a given drug. METHODS: We proposed to apply the weighted cumulative exposure (WCE) statistical model to all health events occurring after a drug introduction (in this paper HCQ) and performed bootstrap to select relevant diagnoses, drugs and interventions which could reflect an adverse drug reactions (ADRs). We applied this data-driven pipeline on a French national medico-administrative database to extract the safety profile of hydroxychloroquine (HCQ) from a cohort of 2,010 patients. RESULTS: The proposed method selected eight drugs (metopimazine, anethole trithione, tropicamide, alendronic acid & colecalciferol, hydrocortisone, chlormadinone, valsartan and tixocortol), twelve procedures (six ophthalmic procedures, two dental procedures, two skin lesions procedures and osteodensitometry procedure) and two medical diagnoses (systemic lupus erythematous, unspecified and discoid lupus erythematous) to be significantly associated with HCQ exposure. CONCLUSION: We provide a method extracting the broad spectrum of diagnoses, drugs and interventions associated to any given drug, potentially highlighting ADRs. Applied to hydroxychloroquine, this method extracted among others already known ADRs.

Choosing a career in oncology: results of a nationwide cross-sectional study.

BACKGROUND: Little information is currently available concerning young medical students desire to pursue a career in oncology, or their career expectations. METHODS: This project is a cross-sectional epidemiological study. A voluntary and anonymous questionnaire was distributed to all young oncologists studying in France between the 2nd of October 2013 and the 23rd of February 2014. RESULTS: The overall response rate was 75.6%. A total of 505 young oncologists completed the questionnaire. The main determining factors in the decision to practice oncology were the cross-sectional nature of the field (70.8%), the depth and variety of human relations (56.3%) and the multi-disciplinary field of work (50.2%). Most residents would like to complete a rotation outside of their assigned region (59.2%) or abroad (70.2%) in order to acquire additional expertise (67.7%). In addition, most interns would like to undertake a fellowship involving care, teaching and research in order to hone their skills (85.7%) and forge a career in public hospitals (46.4%). Career prospects mainly involve salaried positions in public hospitals. Many young oncologists are concerned about their professional future, due to the shortage of openings (40.8%), the workload (52.8%) and the lack of work-life balance (33.4%). CONCLUSIONS: This investigation provides a comprehensive profile of the reasons young oncologists chose to pursue a career in oncology, and their career prospects.

[Evaluation of the theoretical teaching of postgraduate medical students in France]. / Évaluation nationale de l'enseignement théorique du troisième cycle des études médicales en France.

OBJECTIVES: In France, medical students regularly complain about the shortcomings of their theoretical training and the necessity of its adaptation to better fit the needs of students. The goal was to evaluate the theoretical teaching practices in postgraduate medical studies by: 1) collecting data from medical students in different medical faculties in France; 2) comparing this data with expected practices when it is possible; 3) and proposing several lines of improvement. METHODS: A survey of theoretical practices in the 3rd cycle of medical studies was conducted by self-administered questionnaires which were free of charge, anonymous, and administered electronically from July 3 to October 31, 2013 to all medical students in France. RESULTS: National, inter-regional, regional and field internship educational content was absent in respectively 50.5%, 42.8%, 26.0% and 30.2% of cases. Medical students follow complementary training due to insufficient DES and/or DESC 2 training in 43.7% of cases or as part of a professional project in 54.9% of cases. The knowledge sought by medical students concerns the following crosscutting topics: career development (58.9%), practice management (50.7%), medical English (50.4%) and their specialty organization (49.9%). Fifty-four point one percent would like to be evaluated on their theoretical training on an annual basis. CONCLUSION: The results of this first national survey give insights into the theoretical teaching conditions in postgraduate medical education in France and the aspirations of medical students.

Regulation of the Ascaris suum pyruvate dehydrogenase complex by phosphorylation and dephosphorylation.

The pyruvate dehydrogenase complex isolated from 'anaerobic' mitochondria of Ascaris suum has a subunit composition similar to complexes isolated from most other eukaryotic organisms and is regulated by phosphorylation and dephosphorylation. Pyruvate dehydrogenase kinase activity is stimulated by NADH and a number of physiologically important acyl-CoA intermediates and is inhibited by CoA, propionate, tiglate and pyruvate. It is suggested that the elevated levels of pyruvate observed in the ascarid organelle may be important in maintaining the pyruvate dehydrogenase complex in an active state, even in the presence of a reduced pyridine nucleotide pool.

Outcomes of an antimicrobial control program in a teaching hospital.

The clinical outcomes and cost-effectiveness of an antimicrobial control program (ACP) were studied. The impact of an ACP in a teaching hospital was analyzed by comparing clinical outcomes and intravenous antimicrobial costs over two two-year periods, the two years before the program and the first two years after the program's inception. Admission baseline data, length of stay, mortality, and readmission rates were gathered for each patient. Patients were identified by using the International Classification of Diseases. Multivariate logistic regression models were constructed for mortality and for lengths of stay of 12 or more days. The acquisition costs of intravenous antimicrobial agents for the second baseline year and the entire program period were tabulated and compared. The average daily inpatient census was determined. The ACP was associated with a 2.4-day decrease in length of stay and a reduction in mortality from 8.28% to 6.61%. Rates of readmission for infection within 30 days of discharge remained about the same. Inpatient pharmacy costs other than intravenous antimicrobials decreased an average of only 5.7% over the two program years, but the acquisition cost of intravenous antimicrobials for both program years yielded a total cost saving of $291,885, a reduction of 30.8%. The institution's average daily census fell 19% between the second baseline year and the second program year. An ACP directed by a clinical pharmacist trained in infectious diseases was associated with improvements in inpatient length of stay and mortality. The ACP decreased intravenous antimicrobial costs and facilitated the approval process for restricted and nonformulary antimicrobial agents.

Immunomodulatory effects of arabinogalactan-proteins from Baptisia and Echinacea.

The influences of different arabinogalactan-proteins (AGPs) on proliferation and IgM-production of mouse lymphocytes as well as nitrite- and IL6-production of mouse macrophages were investigated in vitro. AGPs have been isolated and purified from roots of Baptisia tinctoria and Echinacea pallida and suspension culture of Echinacea purpurea. Comparing the AGPs, there are differences with regard to fine structure as well as to activities. AGPs from roots of B. tinctoria and E. pallida show high activity in all test systems. AGP from cell culture of E. purpurea shows no influence on proliferation of mouse lymphocytes, only weak influence on the IgM-production of mouse lymphocytes and weak stimulation of nitrite- and IL6-production in alveolar mouse macrophage culture.

Electroretinographic findings in human oculocutaneous albinism.

Electroretinograms (ERGs) were obtained under dark- and light-adapted conditions from 15 human oculocutaneous albinos and compared with the results from a group of 30 normally pigmented subjects. Amplitude and implicit time measures of the ERG recordings obtained from six autosomal recessive and three autosomal dominant tyrosinase-positive albinos fell within the normal range. The six tyrosinase-negative albinos examined also had normal ERGs at low-to-moderate flash luminances. However, at the highest flash luminances, the dark-adapted ERGs of five such subjects were at or just above the normal range in amplitude, and were shorter than normal in implicit time. The dark-adapted luminance-response functions of these subjects were positioned normally on the luminance axis; light-adapted functions were shifted slightly to the left of normal. The possibility that anterior parts of the retina responding to light passing through the anterior eyewall may contribute to the ERGs obtained from tyrosinase-negative albinos was examined by recording dark-adapted ERGs with the sclera occluded. Amplitudes were reduced compared with those obtained with the sclera unoccluded, suggesting that responses to transscleral illumination contributed to the ERG in this type of albinism.

Augmented production of extracellular superoxide by blood isolates of Enterococcus faecalis.

To assess the frequency of extracellular superoxide (O-2) production by enterococci, multiple species were surveyed in a whole organism assay for their ability to reduce ferricytochrome c in a superoxide dismutase-inhibitable fashion. For stool and clinical enterococcal isolates and 12 type strains, only Enterococcus faecalis (87/91 isolates and ATCC 19433), Enterococcus faecium (5/13 isolates), Enterococcus casseliflavus (ATCC 25778), and Enterococcus gallinarum (ATCC 35038) produced extracellular O-2. Among 106 strains comprising 13 species of enteric gram-negative bacilli and gram-positive cocci, only Lactococcus lactis subspecies lactis produced extracellular O-2. Mean (+/-SE) rates of extracellular O-2 production in vitro by E . faecalis for isolates associated with bacteremia and endocarditis and for isolates from stool were 2.4+/-0.2, 1.9+/-0.2, 1.5+/-0.3 nmol of O-2 min(-1) 10(9) cfu(-1), respectively (P=.025, analysis of variance), suggesting an association between invasiveness and extracellular O-2 production.

Amino acid metabolism in the rat tapeworm, Hymenolepis diminuta.

1. The amino acid metabolism of the rat tapeworm, Hymenolepis diminuta was investigated. 2. In addition to the characteristic end products of helminth metabolism, H. diminuta also forms substantial amounts of 14C-alanine during incubations in 14C-glucose. 3. Of 10 amino acids tested, only 14C-labelled asparate and, to a lesser extent alanine, generated substantial amounts of 14CO2 when incubated with H. diminuta. 4. 14C-aspartate was incorporated into both succinate and acetate, major products of the worms mitochondrial metabolism, but the rates were low when compared to the metabolism of exogenous glycogen. 5. These results suggest that amino acid metabolism in H. diminuta is very limited.

Quantitation of protein-bound 3-nitrotyrosine and 3,4-dihydroxyphenylalanine by high-performance liquid chromatography with electrochemical array detection.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been implicated in myriad disease etiologies and may represent an obligate pathologic sequelus of inflammation. Unfortunately, few sensitive and specific analytical techniques exist for the routine assay of biomarkers indicative of ROS and RNS elaboration. In this study, high-performance liquid chromatography is used in conjunction with coulometric electrochemical array (HPLC-EC) detection to allow ultrasensitive determination of protein-bound 3-nitrotyrosine and 3, 4-dihydroxyphenylalanine (3-hydroxytyrosine) as specific in situ biomarkers of protein exposure to reactive nitrating and oxidizing species. Tyrosine and derivatives can be analyzed simultaneously with practical detection limits for tyrosine, 3-NT, and 3,4-Dopa being 10, 50, and 2 pmol, respectively, in as little as 20 microL of sample. HPLC-EC array detection allows two-dimensional resolution of chromatograms, greatly facilitating peak detection and confidence assignment. A method of sample preparation wherein tyrosine analogs are enzymatically hydrolyzed from protein without the need for sample extraction, concentration, or derivatization is reported.