Safety of biologics: elaboration and validation of a questionnaire assessing patients' self-care safety skills: the BioSecure questionnaire. An initiative of the French Rheumatology Society Therapeutic Education section.

BACKGROUND: Biologics are known to entail specific risks (e.g. infections). Patients should possess self-care safety skills to develop appropriate behaviors in situations of risks (e.g. fever). To date, there is no adequate tool to assess these skills. OBJECTIVES: To elaborate a questionnaire to measure knowledge and skills regarding safety issues, for patients treated by biologics. METHODS: Three-step process. (1) A steering group of 10 rheumatologists, one pharmacist and two allied health professionals elaborated an exhaustive list of safety skills. Through a 3-round Delphi process involving the steering group, 14 patients on biologics and 14 other allied health professionals, the list of skills was reduced. (2) A corresponding series of questions and of clinical situations with multiple-choice answers were designed. (3) Preliminary validation was performed against the physician's opinion on skills, and reliability was assessed. RESULTS: The list includes 24 skills e.g. how to deal with fever, planned surgery, dental care, travel, minor traumas, and immunizations. A 55-question questionnaire was constructed. Preliminary validation (62 patients) showed the questionnaire was filled in 10 minutes (median) and correlated to the physician's opinion of skills (R=0.47, P<0.0001) but not to disease status or disease duration. The median score was 75% (range 20%-96%). The questionnaire was reliable: intraclass correlation coefficient, 0.83 (95% CI: 0.63-0.93). CONCLUSION: A simple (multiple-choice questionnaire) and valid tool investigating a core set of safety skills has been developed. This tool could be useful to detect further educational needs regarding biologics safety, and to assess the efficacy of oriented educational interventions.

Professional practice assessment in ambulatory private rheumatology: a pilot evaluation of the medical file content for rheumatoid arthritis.

OBJECTIVE: Professional Practice Assessment (PPA) has become an obligation for all physicians in France, however its modalities remain unclear. The objective of this work was to evaluate the feasibility and accuracy of a PPA for private practice rheumatologists performed in the context of a network. METHODS: A list of items considered mandatory to collect during an outpatient visit for rheumatoid arthritis, was prepared by the network. Non hospital-based rheumatologists, members of the network then evaluated some of their patient files selected by chronological order over a one-month period of time using this list. These files were then assessed by another private rheumatologist, member of the group, randomly allocated, using the same list of items. RESULTS: Eighty percent of the private-practice doctors accepted to participate. The mean time to evaluate 15 patient files was 2 hours. Agreement between auto-evaluation and external evaluation for each file was good (agreement statistic, 0.75-1.0). Items mandatory to collect were collected in a high proportion of cases (84.6%). CONCLUSION: PPA can be performed in the context of a network, auto-evaluation is a valid method and when the list of items is decided on by the network, the data are collected satisfactorily.

Practice patterns in outpatient rheumatology: a pilot evaluation of medical file content.

OBJECTIVES: High-quality medical records that contain detailed data on the patient and disease are essential to high-quality patient care. RHEVER is a network of hospital- and office-based rheumatologists created in 1999 to pursue a number of objectives, including the development of recommendations about items that should be recorded routinely at each patient visit. Subsequently, one of the RHEVER members investigated whether these recommendations were followed by RHEVER participants at a teaching hospital. METHODS: A cross-section of paper-based outpatient files at the rheumatology clinic of the Cochin Teaching Hospital, Paris, France, was studied. The sample comprised 50 files taken at random and 30 files of patients with rheumatoid arthritis. RESULTS: In the 50 unselected files, the reason for the visit was consistently provided, but the diagnosis was variably recorded and decisions about investigations and treatments were not always described. Of the 30 files in patients with rheumatoid arthritis, 75% contained the full set of recommended clinical items. CONCLUSION: This pilot study establishes the feasibility of practice pattern evaluation by rheumatologists. A similar study should be conducted among office-based RHEVER participants. Follow-up investigations are needed to evaluate the impact of medical record evaluations on quality of care.

Continuing medical education for rheumatologists in France. Results of a national survey.

OBJECTIVE: To determine how continuing medical education is rated and used by French rheumatologists. MATERIAL AND METHODS: All French rheumatologists (n = 2579) were sent a questionnaire in September 1998. Results were evaluated using the test for differences between two proportions, with the significance level set at 0.05. RESULTS: 46% of the questionnaires (n = 1197) were returned completed. Mean age of respondents was 45 +/- 8 years; 41.2% of respondents were in full-time office practice, 14.8% were in full-time hospital practice, and 32.7% divided their time between the office and hospital. Nineteen percent worked in the Paris area. Nearly all the respondents (99.6 to 100%) attended continuing education meetings. Respondents working in Paris were significantly (P < 0.05) more likely than those working elsewhere to attend national conventions (99.6% vs 88.4%), whereas a difference in the other direction was found for regional and local conventions. The mean score assigned by respondents to national, regional and local conventions was 60/100. Respondents in full-time hospital practice were more likely than other respondents to attend international conventions; they were the only subgroup that assigned a score greater than 50/100 to this resource. University classes were attended by 44.4% of respondents and obtained a mean score of 65/100. Rheumatology journals were used by 99.2% of respondents and obtained scores greater than 65/100 in all subgroups. Respondents in full-time hospital practice were more likely to read international rheumatology journals than the other subgroups; they were the only subgroup that assigned a score greater than 50/100 to this resource. CD ROMs, videocassettes, and the Internet were used by less than one-fourth of respondents and were assigned low scores. The proportion of respondents who participated in the provision of education ranged from 23.6% to 53.3%. Opinions on the usefulness of the various educational resources varied across type-of-practice subgroups. CONCLUSIONS: Most respondents attended meetings and used resources for independent learning. The findings from our study could be used to plan further investigations into the use of continuing medical education by French rheumatologists, particularly those who did not send back our questionnaire.

Requirement of prestimulated THP-1 monocytic cells for endothelial cell activation. Involvement of TNF alpha.

Blood monocytes spontaneously activate endothelial cells in culture, leading to adhesion of monocytic cells onto the endothelial surface and overproduction of endothelial proteins such as von Willebrand factor (vWf) and plasminogen activator inhibitor type 1 (PAI-1). To overcome the difficulty in obtaining quiescent monocytes, we studied the ability of promonocytic THP-1 cells to activate endothelial cells. Lipopolysaccharide (LPS)-prestimulated and untreated THP-1 cells were cocultured with resting human umbilical vein endothelial cells (HUVEC) for 3 and 24 h in the presence of colimycin to neutralize LPS traces. Addition of untreated THP-1 cells had little effect on HUVEC adhesiveness. Addition of prestimulated THP-1 cells was followed by a noticeable adhesion after 3 h which reversed to basal values within 24 h. Under these conditions HUVEC adhesion molecules, E-selectin, VCAM-1 and ICAM-1, were increased at 3 h with only ICAM-1 remaining overexpressed at 24 h. Diffusible endothelial proteins such as soluble E-selectin, PAI-1 and vWf to a minimal extent, increased in supernatants from HUVEC cocultured for 24 h with prestimulated THP-1 cells. In those cocultures, TNF alpha concentrations peaked at 3 h whereas IL-1 beta levels progressively rose until 24 h. Addition of an anti-TNF alpha antibody decreased by 40% E-selectin and ICAM-1 induction and suppressed PAI-1 overproduction with a weak effect on vWf. An anti-IL-1 beta antibody had negligible effects on HUVEC adhesion molecules, PAI-1 or vWf production. These results provide evidence that promonocytic THP-1 cells require prestimulation in order to activate HUVEC and that TNF alpha contributes to this phenomenon.

Cyclic adenosine monophosphate-dependent mechanisms induce von Willebrand factor expression in the Dami megakaryoblastic cell line.

It has been proposed that cyclic adenosine monophosphate (cAMP) is involved in the differentiation of several cell types and this study analysed whether von Willebrand factor (vWf) synthesis, which is a marker of the megakaryocyte maturation of these cells, would be enhanced by agents acting on cAMP formation. Different compounds known to stimulate cAMP accumulation in cells were used: dibutyryl cAMP (db-cAMP), isobutyl-methylxanthine (IBMX) or pentoxifylline (PTX) and forskolin. Treatments with db-cAMP or IBMX (10-1,000 microM) induced a dose-dependent increase in vWf synthesis. Associations of IBMX with forskolin produced a synergistic enhancement in vWf synthesis. PTX alone did not enhance vWf synthesis but a latent effect was revealed in the presence of forskolin or db-cAMP. The increase in vWf mRNA shown by Northern blot analysis demonstrates that the protein synthesis correlates with the transcript expression after db-cAMP or IBMX treatments. vWf synthesis paralleled the accumulation of cAMP in the cells. Moreover vWf expression induced by combination of IBMX with forskolin was associated with a moderate increase in the percentage of GPIIb/IIIa positive cells and in the ploidy level related to an important inhibition of cell growth. These data provide evidence that agents acting on cAMP metabolism induce vWf synthesis in the Dami megakaryoblastic cells.

Complete sequence and transcriptional analysis of the spo0F region of the Bacillus subtilis chromosome.

The total sequence of a 6,314-base-pair BglII fragment of the Bacillus subtilis chromosome containing the spo0F locus has been accomplished. Several genes of interest have been identified on this DNA fragment. The ctrA locus was recognized as coding for CTP synthetase by comparison of its deduced sequence with that of Escherichia coli CTP synthetase. A total of 53% of the residues are identical between the enzymes from these organisms. The spo0F locus was followed immediately by a locus, tsr, required for RNA synthesis in this organism. Temperature-sensitive mutations within the tsr locus have been identified, but strains with deletions of the locus are nonviable. It was concluded that tsr codes for an unknown essential component of the RNA synthesis machinery. The tsr gene was followed by another open reading frame which could code for a protein of 19,975 Mr. This gene was translated in vivo, but deletion-insertion mutations within the gene had no phenotype. The gene was cotranscribed with the tsr gene, although about 50% of the transcripts terminated between the two genes. The rev-4 mutation which reverts the sporulation-defective phenotype of erythromycin-resistant mutants was located to a partial open reading frame at the end of the fragment. Disruption of this open reading frame by deletion-insertion mutation did not result in a discernible phenotype. S1 protection experiments located the start sites of transcription for several of the genes on this fragment. The spo0F gene was found to be monocistronic. Regulation of the identified genes was investigated by using beta-galactosidase gene fusions.

Characterization of the spo0A locus and its deduced product.

The highly pleiotropic stage 0 sporulation locus of Bacillus subtilis, spo0A, has been cloned in bacteriophage lambda, subcloned in plasmids, and sequenced. The locus was found to code for a protein of 29,691 Da. Analysis of the in vivo transcripts from this region by nuclease S1 protection experiments located the start and stop of transcription of the locus. The transcription start site was preceded by a promoter resembling sigma 37-dependent promoters. Two mutations originally assigned to a second locus, spo0C, in this region because of their weakly pleiotropic phenotypes were cloned and sequenced. The mutations were found to be different missense alterations in the same base of the 10th codon preceding the carboxyl end of the Spo0A protein. These results, along with the finding that mutations in the spo0A gene product [Hoch, J. A., Trach, K., Kawamura, F. & Saito, H. (1985) J. Bacteriol. 161, 552-555] suppress the requirement for spo0B, spo0E, and spo0F gene products in transcription from sigma 28-dependent promoters, suggest that the Spo0A protein interacts directly with the transcription machinery to effect the initiation of sporulation. The deduced amino acid sequence of the Spo0A protein was highly related to that of the OmpR regulatory protein of Escherichia coli.

Comparative electron-microscopic study of the erythrocytic line in refractory anemia (preleukemia) and myelomonocytic leukemia.

The bone marrow erythrocytic precursors of 12 patients with refractory anemia (preleukemia) or myelomonocytic leukemia were studied by transmission electron microscopy. The results were tabulated in a semiquantitative manner and a comparison was established between the two main diagnostic groups. The following results are reported. 1. Similar nuclear and cytoplasmic abnormalities of the normoblasts were observed in preleukemia and leukemia. 2. A nuclear lesion consisting of nuclear clefts and blebs was demonstrated in at least some of the normoblasts in all of the patients. Although not specific, this finding appears to be a new contribution in the field of preleukemia and myelomonocytic leukemia. 3. Iron overload, including the presence of pathologic sideroblasts, is common to both preleukemia and leukemia.

The kinetic behavior of an artificial bienzyme membrane.

Artificial membranes bearing immobilized enzymes can be used to study some effects of membrane structure on enzyme kinetic behavior. The bienzyme system described is a mixture of beta-glucosidase and glucose oxidase. Gluconolactone, the product of thesecond enzyme, is an inhibitor of the first one. The resulting feedback effect has been compared using a mixed two-enzyme membrane, two separated one-enzyme membranes, and astirred bienzyme solution. The feedback effect is quicker and more efficient in the two-enzyme membrane than in solution; it is slower and less efficient in the case of the separated one-enzyme membranes. Effects of enzyme proximity in the structure are discussed. Conclusions are drawn concerning the efficiency of feedback mechanisms when enzymes are embedded within a single structure.