What research agenda could be generated from the European General Practice Research Network concept of Multimorbidity in Family Practice?

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Multimorbidity is an intuitively appealing, yet challenging, concept for Family Medicine (FM). An EGPRN working group has published a comprehensive definition of the concept based on a systematic review of the literature which is closely linked to patient complexity and to the biopsychosocial model. This concept was identified by European Family Physicians (FPs) throughout Europe using 13 qualitative surveys. To further our understanding of the issues around multimorbidity, we needed to do innovative research to clarify this concept. The research question for this survey was: what research agenda could be generated for Family Medicine from the EGPRN concept of Multimorbidity? METHODS: Nominal group design with a purposive panel of experts in the field of multimorbidity. The nominal group worked through four phases: ideas generation phase, ideas recording phase, evaluation and analysis phase and a prioritization phase. RESULTS: Fifteen international experts participated. A research agenda was established, featuring 6 topics and 11 themes with their corresponding study designs. The highest priorities were given to the following topics: measuring multimorbidity and the impact of multimorbidity. In addition the experts stressed that the concept should be simplified. This would be best achieved by working in reverse: starting with the outcomes and working back to find the useful variables within the concept. CONCLUSION: The highest priority for future research on multimorbidity should be given to measuring multimorbidity and to simplifying the EGPRN model, using a pragmatic approach to determine the useful variables within the concept from its outcomes.The study had a Grant of 8000 Euros from the EGPRN

A Cryptic Frizzled Module in Cell Surface Collagen 18 Inhibits Wnt/β−Catenin Signaling

Collagens contain cryptic polypeptide modules that regulate major cell functions, such as cell proliferation or death. Collagen XVIII (C18) exists as three amino terminal end variants with specific amino terminal polypeptide modules. We investigated the function of the variant 3 of C18 (V3C18) containing a frizzled module (FZC18), which carries structural identity with the extracellular cysteine-rich domain of the frizzled receptors. We show that V3C18 is a cell surface heparan sulfate proteoglycan, its topology being mediated by the FZC18 module. V3C18 mRNA was expressed at low levels in 21 normal adult human tissues. Its expression was up-regulated in fibrogenesis and in small well-differentiated liver tumors, but decreased in advanced human liver cancers. Low FZC18 immunostaining in liver cancer nodules correlated with markers of high Wnt/β−catenin activity. V3C18 (Mr = 170 kD) was proteolytically processed into a cell surface FZC18-containing 50 kD glycoprotein precursor that bound Wnt3a in vitro through FZC18 and suppressed Wnt3a-induced stabilization of β−catenin. Ectopic expression of either FZC18 (35 kD) or its 50 kD precursor inhibited Wnt/β−catenin signaling in colorectal and liver cancer cell lines, thus downregulating major cell cycle checkpoint gatekeepers cyclin D1 and c-myc and reducing tumor cell growth. By contrast, full-length V3C18 was unable to inhibit Wnt signaling. In summary, we identified a cell-surface signaling pathway whereby FZC18 inhibits Wnt/β−catenin signaling. The signal, encrypted within cell-surface C18, is released by enzymatic processing as an active frizzled cysteine-rich domain (CRD) that reduces cancer cell growth. Thus, extracellular matrix controls Wnt signaling through a collagen-embedded CRD behaving as a cell-surface sensor of proteolysis, conveying feedback cues to control cancer cell fate

"I Can't Find Anything Wrong: It Must Be a Pulmonary Embolism": Diagnosing Suspected Pulmonary Embolism in Primary Care, a Qualitative Study

Background: Before using any prediction rule oriented towards pulmonary embolism (PE), family physicians (FPs) should have some suspicion of this diagnosis. The diagnostic reasoning process leading to the suspicion of PE is not well described in primary care. Objective: to explore the diagnostic reasoning of FPs when pulmonary embolism is suspected. Method: Semi-structured qualitative interviews with 28 FPs. The regional hospital supplied data of all their cases of pulmonary embolism from June to November 2011. The patient's FP was identified where he/she had been the physician who had sent the patient to the emergency unit. The first consecutive 14 FPs who agreed to participate made up the first group. A second group was chosen using a purposeful sampling method. The topic guide focused on the circumstances leading to the suspicion of PE. A thematic analysis was performed, by three researchers, using a grounded theory coding paradigm. Results: In the FPs' experience, the suspicion of pulmonary embolism arose out of four considerations: the absence of indicative clinical signs for diagnoses other than PE, a sudden change in the condition of the patient, a gut feeling that something was seriously wrong and an earlier failure to diagnose PE. The FPs interviewed did not use rules in their diagnostic process. Conclusion: This study illustrated the diagnostic role of gut feelings in the specific context of suspected pulmonary embolism in primary care. The FPs used the sense of alarm as a tool to prevent the diagnostic error of missing a PE. The diagnostic accuracy of gut feelings has yet to be evaluated

Note de synthèse

Barbier Jean-Marie, Caspar P., Chaix Marie-Laure, Ferrand J.-L., Lietard B., Thesmar C., Volery L. Note de synthèse. In: Revue française de pédagogie, volume 97, 1991. pp. 75-108

Diversity and antibiotic resistance of uropathogenic bacteria from Abidjan

Background: Urinary tract infections (UTI) are one of the major causes of prescribing and antibiotic consumption. In order to use the best antibiotic treatment for their patients, reliable and recent data about epidemiology and antibiotic resistance profile of uropathogenic bacteria must be available for clinicians. Therefore regular monitoring in each country is required. Objectives: The aims of this study were to investigate the bacterial pathogenic diversity and antimicrobial resistance rates of uropathogenic bacteria at the Treichville Teaching Hospital (Abidjan, Ivory Coast) over a 12-year period (2000–2011) and also to contribute to the monitoring and the geographical adaptation of antibiotic therapy. Materials and methods: A retrospective analysis of 12,175 urine samples over a 12-year period 2000–2011 at Treichville Teaching Hospital was carried out according to the routine protocol of urinalysis. The results were processed to obtain the profile prevalence of UTI, the rate of bacterial resistance to antibiotics, the trend of their evolution over time and the rate of multidrug resistance. Results: The presence of bacteria was detected in about 25% of samples in which 3071 bacterial germs belonging to 12 species were identified. Escherichia coli was the dominant species (28.7%) but much lower than observed in European countries (70–80%). Other main detected species were Staphylococcus aureus (17.4%), Klebsiella pneumoniae (14.9%) and Enterobacter aerogenes (10%). These genera were responsible of 71% of the UTI. Resistance tests to antibiotics indicated very high rates of resistance to amoxicillin (78.9%), tetracyclin (76.4%), and trimethoprim/sulfamethoxazole (77.9%). Only a few molecules maintain their effectiveness such as cefotaxime and netilmicin which respectively exhibit 13.9% and 3.1% of bacterial resistance. However bacterial resistance is increasing over a time for all antibiotics except chloramphenicol. Conclusions: The diversity of uropathogenic bacteria obtained appeared to be a characteristic of sub-Saharan African countries. Their resistances to different antibiotics were following a dramatic trend. Waiting to be confronted with therapeutic dead end with the advent of multi-resistant bacteria, identifying the region-specific causes is crucial to adapt antibiotic therapy