[Ten years of nurse consultation at the pediatric emergency department]. / Dix ans de consultation infirmière médico-déléguée aux urgences pédiatriques.

The Nurse consultation (CI) was implemented in 2013 at the emergency department of the Lausanne Children's Hospital. It offers medical delegated care for children aged three to 18. Ten years after its implementation, this article takes stock of its progress. Patients and families are satisfied with the care provided at a rate of 94.3 %. The CI seems to offer quality and safe healthcare. It allows the emergency team to have more time and resources for patients whose lives are at risk or need careful assessment due to their age or medical history. The CI is an innovative and relevant model of care in the context of uncomplicated childhood illnesses.

La consultation infirmière (CI) a été mise en place en 2013 aux urgences de l'Hôpital de l'enfance de Lausanne (HEL). Elle propose une prise en charge sous délégation médicale d'enfants âgés de trois à 18 ans. Dix ans après son implantation, cet article fait le point. Les patients et familles sont satisfaits de la prise en charge à 94,3 %. La CI semble offrir des soins de qualité et sécuritaires. Elle permet à l'équipe des urgences d'avoir plus de temps et de moyens pour les patients dont le pronostic vital est engagé ou qui sont à risque au vu de leur âge ou leurs antécédents. La CI est un modèle innovant et pertinent de prise en charge dans un contexte de pathologies simples de pédiatrie.

[Mobile applications for smoking cessation in primary care]. / Applications mobiles et désaccoutumance au tabac avec l'aide du praticien.

Primary care physicians are in an excellent position to address smoking during routine consultations. To this end, physicians have assessment tools and brief interventions appropriate for the duration of consultations. However, these tools are difficult to use consistently in practice. Mobile applications (apps) aimed at stopping smoking could help solve this problem, provided they meet certain quality criteria. This article provides criteria for evaluating these apps to facilitate their identification and use by clinicians. Five French-speaking apps are described. If integrated into routine Primary Care, these apps could facilitate smoking cessation.

Le médecin de premier recours a une place privilégiée pour aborder le problème du tabagisme en consultation de routine. Il dispose, à cet effet, d'outils d'évaluations et d'interventions brèves compatibles avec le temps de consultation. Ces outils sont difficiles à implémenter systématiquement. Les applications mobiles (apps) visant à l'arrêt du tabac pourraient contribuer à résoudre ce problème pour autant qu'elles satisfassent à certains critères de qualité. Le présent article propose des critères d'évaluation de ces apps pour faciliter leur identification et leur utilisation par le clinicien. Cinq apps francophones sont décrites. Intégrées à la consultation de médecine générale, de telles apps, pourraient faciliter la désaccoutumance au tabac.

Demonstration of the effectiveness of zinc in diarrhoea of children living in Switzerland.

UNLABELLED: We designed a double-blinded randomized clinical trial of zinc (10 or 20 mg of zinc sulphate for 2-5 month-old or 6-59 month-old children, respectively, during 10 days) vs. placebo in otherwise healthy children aged 2 months to 5 years who presented with acute diarrhoea (i.e. ≥3 stools/day for less than 72 h). Eighty-seven patients (median age 14 months; range 3.1-58.3) were analysed in an intention-to-treat approach. Forty-two patients took zinc and 45 placebo. There was no difference in the duration nor in the frequency of diarrhoea, but only 5% of the zinc group still had diarrhoea at 120 h of treatment compared to 20% in the placebo group (P = 0.05). Thirty-one patients (13 zinc and 18 placebo) were available for per-protocol analyses. The median (IQR) duration of diarrhoea in zinc-treated patients was 47.5 h (18.3-72) and differed significantly from the placebo group (median 76.3; IQR 52.8-137) (P = 0.03). The frequency of diarrhoea was also lower in the zinc group (P = 0.02). CONCLUSION: zinc treatment decreases the frequency and severity of diarrhoea in children aged 2 months to 5 years living in Switzerland. However, the intention-to-treat analysis reveals compliance issues that question the proper duration of treatment and the choice of optimal pharmaceutical formulation.

[The nurse consultation in a Swiss university paediatric emergency department]. / La consultation infirmière dans un centre d'urgence pédiatrique universitaire suisse.

In Switzerland, overcrowding in tertiary emergency departments is a frequent problem, resulting in lengthy waiting times, lower satisfaction on the part of families and a risk for patient's safety. The setting up of a nurse consultation in a university paediatric emergency centre has helped to improve the quality of care in this context.

[Zinc and diarrhea in children under 5 years: WHO recommendations implemented in Switzerland]. / Zinc et diarrhées chez les enfants de moins de cinq ans: les recommandations de l'OMS applicables en Suisse?

In Europe, acute diarrhea, particularly caused by rotavirus are frequently the cause of epidemics in nurseries, schools, and even hospitals. Studies in many developing countries show that taking 10 to 20 mg per day of zinc for 10 to 14 days, during and after diarrhea, decreases the severity and reduces the number of episodes of diarrhea occurring within 2 to 3 months following the intake of zinc. However, the few studies conducted in developed countries do not confirm or deny its effectiveness in these countries, thereby limiting the global implementation of WHO recommendations for acute diarrhea. The ongoing study at the HEL (Children hospital - Lausanne) aims to promote this additional therapy in children under 5 years of age, perhaps allowing the helvetic application of the new WHO recommendations.

A whole-grain cereal-rich diet increases plasma betaine, and tends to decrease total and LDL-cholesterol compared with a refined-grain diet in healthy subjects.

Epidemiological studies have repeatedly found that whole-grain (WG) cereal foods reduce the risk of several lifestyle-related diseases, though consistent clinical outcomes and mechanisms are elusive. To compare the effects of a WG-rich diet with a matched refined-grain (RG) diet on plasma biomarkers and bowel health parameters, seventeen healthy subjects (eleven females and six males) completed an exploratory cross-over study with a 2-week intervention diet based on either WG- or RG-based foods, separated by a washout of at least 5 weeks. Both diets were the same except for the use of WG (150 g/d) or RG foods. Subjects undertook a 4 h postprandial challenge on day 8 of each intervention diet. After 2 weeks, the WG diet tended to decrease plasma total and LDL-cholesterol (both P = 0·09), but did not change plasma HDL-cholesterol, fasting glucose, C-reactive protein or homocysteine compared with the RG diet. Plasma betaine and alkylresorcinol concentrations were elevated after 1 week of the WG diet (P = 0·01 and P < 0·0001, respectively). Clostridium leptum populations in faeces were increased after the WG diet, along with a trend for decreased faecal water pH (P = 0·096) and increased stool frequency (P < 0·0001) compared with the RG diet. A short controlled intervention trial with a variety of commercially available WG-based products tended to improve biomarkers of CVD compared with a RG diet. Changes in faecal microbiota related to increased fibre fermentation and increased plasma betaine concentrations point to both fibre and phytochemical components of WG being important in mediating any potential health effects.

The role of prophage for genome diversification within a clonal lineage of Lactobacillus johnsonii: characterization of the defective prophage LJ771.

Two independent isolates of the gut commensal Lactobacillus johnsonii were sequenced. These isolates belonged to the same clonal lineage and differed mainly by a 40.8-kb prophage, LJ771, belonging to the Sfi11 phage lineage. LJ771 shares close DNA sequence identity with Lactobacillus gasseri prophages. LJ771 coexists as an integrated prophage and excised circular phage DNA, but phage DNA packaged into extracellular phage particles was not detected. Between the phage lysin gene and attR a likely mazE ("antitoxin")/pemK ("toxin") gene cassette was detected in LJ771 but not in the L. gasseri prophages. Expressed pemK could be cloned in Escherichia coli only together with the mazE gene. LJ771 was shown to be highly stable and could be cured only by coexpression of mazE from a plasmid. The prophage was integrated into the methionine sulfoxide reductase gene (msrA) and complemented the 5' end of this gene, creating a protein with a slightly altered N-terminal sequence. The two L. johnsonii strains had identical in vitro growth and in vivo gut persistence phenotypes. Also, in an isogenic background, the presence of the prophage resulted in no growth disadvantage.

Plasmodium vivax resistance to chloroquine in Dawei, southern Myanmar.

OBJECTIVE: To assess the efficacy of chloroquine in the treatment of Plasmodium vivax malaria in in Dawei District, southern Myanmar. METHODS: Enrolled patients at Sonsinphya clinic >6 months of age were assessed clinically and parasitologically every week for 28 days. To differentiate new infections from recrudescence, we genotyped pre- and post-treatment parasitaemia. Blood chloroquine was measured to confirm resistant strains. RESULTS: Between December 2002 and April 2003, 2661 patients were screened, of whom 252 were included and 235 analysed. Thirty-four per cent (95% CI: 28.1-40.6) of patients had recurrent parasitaemia and were considered treatment failures. 59.4% of these recurrences were with a different parasite strain. Two (0.8%) patients with recurrences on day 14 had chloroquine concentrations above the threshold of 100 ng/ml and were considered infected with chloroquine resistant parasites. 21% of failures occurred during the first 3 weeks of follow-up: early recurrence and median levels of blood chloroquine comparable to those of controls suggested P. vivax resistance. CONCLUSIONS: Plasmodium vivax resistance to chloroquine seems to be emerging in Dawei, near the Thai-Burmese border. While chloroquine remains the first-line drug for P. vivax infections in this area of Myanmar, regular monitoring is needed to detect further development of parasite resistance.

Hydrogen peroxide production by Lactobacillus johnsonii NCC 533 and its role in anti-Salmonella activity.

The human intestinal isolate Lactobacillus johnsonii NCC 533 (La1) is a probiotic strain with well-documented antimicrobial properties. Previous research has identified the production of lactic acid and bacteriocins as important factors, but that other unidentified factors are also involved. We used the recently published genome sequence of L. johnsonii NCC 533 to search for novel antipathogen factors and identified three potential gene products that may catalyze the synthesis of the known antimicrobial factor hydrogen peroxide, H(2)O(2). In this work, we confirmed the ability of NCC 533 as well as eight different L. johnsonii strains and Lactobacillus gasseri to produce H(2)O(2) when resting cells were incubated in the presence of oxygen, and that culture supernatant containing NCC 533-produced H(2)O(2) was effective in killing the model pathogen Salmonella enterica serovar Typhimurium SL1344 in vitro.

Fusion of the BCL9 HD2 domain to E1A increases the cytopathic effect of an oncolytic adenovirus that targets colon cancer cells.

BACKGROUND: The Wnt signaling pathway is activated by mutations in the APC and beta-catenin genes in many types of human cancer. beta-catenin is stabilized by these mutations and activates transcription in part by acting as a bridge between Tcf/LEF proteins and the HD2 domain of the BCL9 coactivator. We have previously described oncolytic adenoviruses with binding sites for Tcf/LEF transcription factors inserted into the early viral promoters. These viruses replicate selectively in cells with activation of the Wnt pathway. To increase the activity of these viruses we have fused the viral transactivator E1A to the BCL9 HD2 domain. METHODS: Luciferase assays, co-immunoprecipitation and Western blotting, immunofluorescent cell staining and cytopathic effect assays were used to characterize the E1A-HD2 fusion protein and virus in vitro. Growth curves of subcutaneous SW620 colon cancer xenografts were used to characterize the virus in vivo. RESULTS: The E1A-HD2 fusion protein binds to beta-catenin in vivo and activates a Tcf-regulated luciferase reporter better than wild-type E1A in cells with activated Wnt signaling. Expression of the E1A-HD2 protein promotes nuclear import of beta-catenin, mediated by the strong nuclear localization signal in E1A. Tcf-regulated viruses expressing the fusion protein show increased expression of viral proteins and a five-fold increase in cytopathic effect (CPE) in colorectal cancer cell lines. There was no change in viral protein expression or CPE in HeLa cells, indicating that E1A-HD2 viruses retain selectivity for cells with activation of the Wnt signaling pathway. Despite increasing the cytopathic effect of the virus in vitro, fusion of the HD2 domain to E1A did not increase the burst size of the virus in vitro or the anti-tumor effect of the virus in an SW620 xenograft model in vivo. CONCLUSION: Despite an increase in the nuclear pool of beta-catenin, the effects on viral activity in colon cancer cells were small, suggesting that factors acting downstream of beta-catenin are limiting for viral replication and toxicity in these cells. The approach of fusing E1A to a protein domain implicated in oncogenic signaling could be used to selectively increase the activity of oncolytic viruses targeting several other pathways defective in cancer.

Building legitimacy by criticising the pharmaceutical industry: a qualitative study among prescribers and local opinion leaders.

PRINCIPLES: The literature has described opinion leaders not only as marketing tools of the pharmaceutical industry, but also as educators promoting good clinical practice. This qualitative study addresses the distinction between the opinion-leader-as-marketing-tool and the opinion-leader-as-educator, as it is revealed in the discourses of physicians and experts, focusing on the prescription of antidepressants. We explore the relational dynamic between physicians, opinion leaders and the pharmaceutical industry in an area of French-speaking Switzerland. METHODS: Qualitative content analysis of 24 semistructured interviews with physicians and local experts in psychopharmacology, complemented by direct observation of educational events led by the experts, which were all sponsored by various pharmaceutical companies. RESULTS: Both physicians and experts were critical of the pharmaceutical industry and its use of opinion leaders. Local experts, in contrast, were perceived by the physicians as critical of the industry and, therefore, as a legitimate source of information. Local experts did not consider themselves opinion leaders and argued that they remained intellectually independent from the industry. Field observations confirmed that local experts criticised the industry at continuing medical education events. CONCLUSIONS: Local experts were vocal critics of the industry, which nevertheless sponsor their continuing education. This critical attitude enhanced their credibility in the eyes of the prescribing physicians. We discuss how the experts, despite their critical attitude, might still be beneficial to the industry's interests.

Card agglutination test for trypanosomiasis (CATT) end-dilution titer and cerebrospinal fluid cell count as predictors of human African Trypanosomiasis (Trypanosoma brucei gambiense) among serologically suspected individuals in southern Sudan.

The diagnosis of human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense relies on an initial serologic screening with the card agglutination test for trypanosomiasis (CATT) for T. b. gambiense, followed by parasitologic confirmation in most endemic areas. Unfortunately, field parasitologic methods lack sensitivity and the management of serologically suspected individuals (i.e., individuals with a positive CATT result but negative parasitology) remains controversial. In Kajo-Keji County in southern Sudan, we prospectively collected sociodemographic and laboratory data of a cohort of 2,274 serologically suspected individuals. Thirty-three percent (n = 749) attended at least one follow-up visit and HAT was confirmed in 64 (9%) cases. Individuals with lower initial CATT-plasma (CATT-P) end-dilution titers had lowest risks (10.4 and 13.8/100 person-years for 1:4 and 1:8 titers, respectively) that significantly increased for higher dilutions: relative risks = 5.1 (95% confidence interval [CI] = 2.6-9.5) and 4.6 (95% CI = 2.8-9.8) for 1:16 and 1:32 titers, respectively. The cumulative yearly risk was also high (76%) in individuals found with 11-20 cells in the cerebrospinal fluid, but this involved only eight patients. Adjustment for potential confounders did not affect the results. In conclusion, treatment with pentamidine should be considered for all serologically suspected individuals with a CATT-P end-dilution titer >/= 1:16 in areas of a moderate to high prevalence of HAT.

Coverage of diarrhoea-associated Escherichia coli isolates from different origins with two types of phage cocktails.

Eighty-nine T4-like phages from our phage collection were tested against four collections of childhood diarrhoea-associated Escherichia coli isolates representing different geographical origins (Mexico versus Bangladesh), serotypes (69 O, 27 H serotypes), pathotypes (ETEC, EPEC, EIEC, EAEC, VTEC, Shigella), epidemiological settings (community and hospitalized diarrhoea) and years of isolation. With a cocktail consisting of 3 to 14 T4-like phages, we achieved 54% to 69% coverage against predominantly EPEC isolates from Mexico, 30% to 53% against mostly ETEC isolates from a prospective survey in Bangladesh, 24% to 61% against a mixture of pathotypes isolated from hospitalized children in Bangladesh, and 60% coverage against Shigella isolates. In comparison a commercial Russian phage cocktail containing a complex mixture of many different genera of coliphages showed 19%, 33%, 50% and 90% coverage, respectively, against the four above-mentioned collections. Few O serotype-specific phages and no broad-host range phages were detected in our T4-like phage collection. Interference phenomena between the phage isolates were observed when constituting larger phage cocktails. Since the coverage of a given T4-like phage cocktail differed with geographical area and epidemiological setting, a phage composition adapted to a local situation is needed for phage therapy approaches against E. coli pathogens.

Syndromic algorithms for detection of gambiense human African trypanosomiasis in South Sudan.

BACKGROUND: Active screening by mobile teams is considered the best method for detecting human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense but the current funding context in many post-conflict countries limits this approach. As an alternative, non-specialist health care workers (HCWs) in peripheral health facilities could be trained to identify potential cases who need testing based on their symptoms. We explored the predictive value of syndromic referral algorithms to identify symptomatic cases of HAT among a treatment-seeking population in Nimule, South Sudan. METHODOLOGY/PRINCIPAL FINDINGS: Symptom data from 462 patients (27 cases) presenting for a HAT test via passive screening over a 7 month period were collected to construct and evaluate over 14,000 four item syndromic algorithms considered simple enough to be used by peripheral HCWs. For comparison, algorithms developed in other settings were also tested on our data, and a panel of expert HAT clinicians were asked to make referral decisions based on the symptom dataset. The best performing algorithms consisted of three core symptoms (sleep problems, neurological problems and weight loss), with or without a history of oedema, cervical adenopathy or proximity to livestock. They had a sensitivity of 88.9-92.6%, a negative predictive value of up to 98.8% and a positive predictive value in this context of 8.4-8.7%. In terms of sensitivity, these out-performed more complex algorithms identified in other studies, as well as the expert panel. The best-performing algorithm is predicted to identify about 9/10 treatment-seeking HAT cases, though only 1/10 patients referred would test positive. CONCLUSIONS/SIGNIFICANCE: In the absence of regular active screening, improving referrals of HAT patients through other means is essential. Systematic use of syndromic algorithms by peripheral HCWs has the potential to increase case detection and would increase their participation in HAT programmes. The algorithms proposed here, though promising, should be validated elsewhere.

Oral T4-like phage cocktail application to healthy adult volunteers from Bangladesh.

The genomic diversity of 99 T4-like coliphages was investigated by sequencing an equimolar mixture with Illumina technology and screening them against different databases for horizontal gene transfer and undesired genes. A 9-phage cocktail was given to 15 healthy adults from Bangladesh at a dose of 3×10(9) and 3×10(7) plaque-forming units and placebo respectively. Phages were detected in 64% of the stool samples when subjects were treated with higher titer phage, compared to 30% and 28% with lower-titer phage and placebo, respectively. No Escherichia coli was present in initial stool samples, and no amplification of phage was observed. One percent of the administered oral phage was recovered from the feces. No adverse events were observed by self-report, clinical examination, or from laboratory tests for liver, kidney, and hematology function. No impact of oral phage was seen on the fecal microbiota composition with respect to bacterial 16S rRNA from stool.

The genome sequence of the probiotic intestinal bacterium Lactobacillus johnsonii NCC 533.

Lactobacillus johnsonii NCC 533 is a member of the acidophilus group of intestinal lactobacilli that has been extensively studied for their "probiotic" activities that include, pathogen inhibition, epithelial cell attachment, and immunomodulation. To gain insight into its physiology and identify genes potentially involved in interactions with the host, we sequenced and analyzed the 1.99-Mb genome of L. johnsonii NCC 533. Strikingly, the organism completely lacked genes encoding biosynthetic pathways for amino acids, purine nucleotides, and most cofactors. In apparent compensation, a remarkable number of uncommon and often duplicated amino acid permeases, peptidases, and phosphotransferase-type transporters were discovered, suggesting a strong dependency of NCC 533 on the host or other intestinal microbes to provide simple monomeric nutrients. Genome analysis also predicted an abundance (>12) of large and unusual cell-surface proteins, including fimbrial subunits, which may be involved in adhesion to glycoproteins or other components of mucin, a characteristic expected to affect persistence in the gastrointestinal tract (GIT). Three bile salt hydrolases and two bile acid transporters, proteins apparently critical for GIT survival, were also detected. In silico genome comparisons with the >95% complete genome sequence of the closely related Lactobacillus gasseri revealed extensive synteny punctuated by clear-cut insertions or deletions of single genes or operons. Many of these regions of difference appear to encode metabolic or structural components that could affect the organisms competitiveness or interactions with the GIT ecosystem.