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Randomized Phase II Trial Evaluating Treatment with EGFR-TKI Associated with Antiestrogen in Women with Nonsquamous Advanced-Stage NSCLC: IFCT-1003 LADIE Trial
No full textInternational audiencePurpose: The incidence of lung cancer has dramatically increased in women. Preclinical data have suggested that combining EGFR-tyrosine kinase inhibitor (TKI) with an antiestrogen may overcome resistance to EGFR-TKI.Patients and Methods: The IFCT-1003 LADIE trial was a 2 Â 2 arms parallel open-label randomized phase II trial. EGFR-TKI-na€ ve postmenopausal women with advanced lung cancer were treated with gefitinib (G) versus gefitinib þ fulvestrant (GþF) in the EGFR-mutated group (EGFR þ ) or with erlotinib (E) versus erlotinib þ fulvestrant (EþF) in the EGFR wild-type group (EGFR-WT). The primary objective was progression-free survival (PFS) at 3 and 9 months for EGFR-WT and EGFR þ patients.Results: Overall, 204 patients (gefitinib 104 and GþF 100) and 175 patients (erlotinib 87 and EþF 88) were enrolled in the EGFR þ and EGFR-WT cohorts. In the EGFR þ cohort, the primary endpoint was reached, with 58% of the GþF group patients being nonprogressive at 9 months. Adding fulvestrant to gefitinib was not associated with improved PFS (9.9 vs 9.4 months) or overall survival (OS; 22.1 vs 28.6 months). In the EGFR-WT cohort, the primary endpoint was also achieved (33.7% of the patients were nonprogressive at 3 months). Adding fulvestrant to erlotinib was not associated with improved outcome (PFS 1.8 vs 2.0 and OS 10.3 vs 7.3 months). No PFS difference was observed regarding estrogen receptor alpha expression. The tolerance was as expected with no treatmentrelated death.Conclusions: Adding fulvestrant to EGFR-TKI is feasible, but not associated with prolonged PFS regardless of EGFR status. The lack of benefits while combining fulvestrant to EGFR-TKI does not support its future development in an unselected population.</div
Évaluation de la formation en transfert de connaissances à l’Institut Pasteur de Madagascar
No full textInternational audienceCette étude évaluative porte sur la mise en œuvre et les effets perçus d’une formation en présence sur le transfert de connaissances, qui s’appuie sur deux cours en ligne ouverts et massifs (massive open online course – MOOC). La formation ciblait des membres du personnel ainsi que des partenaires de l’Institut Pasteur de Madagascar. L’étude a suivi le modèle de Kirkpatrick pour évaluer les effets perçus de la formation et le cadre TIPEC (Technology, Individual, Pedagogy and Enabling Conditions) pour identifier les facilitateurs et les obstacles de sa mise en œuvre. La collecte des données a suivi un devis mixte convergent. Trente-deux personnes (32) ont répondu au questionnaire de préformation, dont 18 personnes au questionnaire postformation et 24 à des entretiens semi-dirigés cinq mois après la fin de la formation. La plupart des personnes ont indiqué que la formation à l’aide des MOOC et d’un accompagnement en présence a répondu à leurs besoins, bien que son intensité et son niveau élevé de difficulté aient été soulignés par certains. Le volet pratique de la formation ainsi que la présence d’une formatrice ou d’un formateur ont été jugés essentiels à l’apprentissage. Les résultats suggèrent que le format pédagogique adopté pourrait constituer un outil pertinent et accessible pour la formation continue des professionnels. Mots clés : Transfert des connaissances, renforcement des capacités, MOOC, évaluation, Madagascar Evaluation of Knowledge Translation Training at the Institut Pasteur de Madagascar Abstract: This evaluative study focuses on the implementation and perceived effects of an in-person training program on knowledge translation, which is based on two massive open online courses (MOOCs). The training targeted staff members as well as partners of the Institut Pasteur de Madagascar. The study followed the Kirkpatrick model to evaluate the perceived effects of the training and the TIPEC framework (Technology, Individual, Pedagogy, and Enabling Conditions) to identify facilitators and barriers to its implementation. Data collection was guided by a convergent mixed-methods design. Thirty-two people completed the pre-training questionnaire, of these, 18 responded to the post-training questionnaire and 24 took part in semi-structured interviews five months after the training ended. Most participants indicated that the training, combining MOOCs with in-person support, met their needs, although some highlighted its intensity and high level of difficulty. The practical component of the training and the presence of a trainer were deemed essential to learning. The results suggest that the adopted pedagogical format may represent a relevant and accessible tool for the continuing education of professionals. Keywords: knowledge translation, capacity building, MOOC, evaluation, Madagasca
Couverture des besoins en micronutriments : est-ce possible sans recours aux compléments alimentaires ?
No full textInternational audiencehe criteria for a nutritionally correct diet include meeting recommended micronutrient intakes. In theory, a balanced diet covers these requirements. Given that a number of people use food supplements containing micronutrients (vitamins, minerals and trace elements), we sought to assess whether this practice was justified, and if so, for which population groups, and for which micronutrients
Virus‐Induced Cellular Senescence Causes Pulmonary Sequelae Post‐Influenza Infection
No full textInternational audienceInfluenza A virus (IAV) infection causes acute and long‐term lung damage. Here, we used immunostaining, genetic, and pharmacological approaches to determine whether IAV‐induced cellular senescence causes prolonged alterations in lungs. Mice infected with a sublethal dose of H1N1p2009 exhibited cellular senescence, as evidenced by increased pulmonary expression of p16, p21, β‐galactosidase and the DNA damage marker gamma‐H2A.X. Cellular senescence began 4 days post‐infection (dpi) in the bronchial epithelium, then spread to the lung parenchyma by 7 and 28 dpi (long after viral clearance), and then declined by 90 dpi. At 28 dpi, the lungs showed severe remodeling with structural bronchial and alveolar lesions, abrasion of the airway epithelium, and pulmonary emphysema and fibrotic lesions that persisted up to 90 dpi. In mice and nonhuman primates, persistence of senescent cells in the bronchial wall on 28 dpi was associated with abrasion of the airway epithelium. In p16‐ATTAC mice, depletion of p16‐expressing cells with AP20187 reduced pulmonary emphysema and fibrosis and led to complete recovery of the airway epithelium at 28 dpi, indicating a marked acceleration of the epithelial repair process. Treatment with the senolytic drug ABT‐263 also accelerated epithelial repair without affecting pulmonary fibrosis or emphysema. These positive effects occurred independently of viral clearance and lung inflammation at 7 dpi. Finally, AP20187 treatment of p16‐ATTAC mice at 15 dpi led to complete recovery of the airway epithelium at 28 dpi. Thus, virus‐induced senescent cells contribute to the pulmonary sequelae of influenza; targeting senescent cells may represent a new preventive therapeutic option
Advertising ultra-processed foods around urban and rural schools in Kenya
No full textInternational audienceMarketing of ultra-processed foods (UPFs) can influence children's food preferences and consumption patterns. However, limited data exist on the extent and nature of UPF marketing around schools in low-and middle-income countries, including Kenya. This study assessed the extent, type, and content of food and beverage advertising near schools in urban and rural settings in Kenya. We conducted a cross-sectional study in June-July 2021 across three Kenyan counties-Nairobi (urban), Mombasa (coastal urban), and Baringo (rural). Each county was stratified by socioeconomic status (SES), and schools were randomly selected. Food and beverage advertisements within a 250-meter radius of schools were documented.Data collected included the type of product, location, and promotional techniques used. Advertised products were categorized using the NOVA classification and the INFORMAS framework. Descriptive statistics were used to summarize advertisement patterns, and Poisson regression was applied to identify factors associated with UPF advertising. A total of 2,300 food and beverage advertisements were documented around 500 schools. Urban areas had a higher median number of advertisements (median = 25, IQR: 25-160) compared to rural areas (median = 10, IQR: 4-13). Nearly 48% of all advertisements featured UPFs. The most frequent promotional strategy involved cartoon and company-owned characters, while price discounts were the most common premium offers. In multivariate analysis, Baringo County showed a higher rate of UPF advertisements compared to Nairobi (PRR: 1.17, 95% CI: 1.01-1.36), as did lower versus higher SES areas (PRR: 1.10, 95% CI: 1.01-1.20). UPFs</div
Genomic analysis of Plasmodium vivax field isolates circulating in sub-Saharan Africa
No full textInternational audiencePlasmodium vivax malaria is a major public health problem outside sub-Saharan Africa. However, an increasing number of P. vivax infections in Duffy-negative individuals has been reported across Africa in recent years, raising concerns that the parasites may have evolved alternative pathways to invade reticulocyte and overcome Duffy-negativity. Here, we investigated the global genetic structure and diversity of sub-Saharan African P. vivax populations, exploring possible molecular signatures of adaptation to Duffy-negative hosts. We analyzed 204 previously published P. vivax genome sequences from Africa, Southeast Asia, the Pacific Coral Triangle, and South America and generated whole-genome sequences of 133 P. vivax field isolates collected from 10 sub-Saharan African countries. Our analysis revealed four distinct geographic clusters, with clear contrasts between East/West Africa and the Indian Ocean populations. Despite the limited number of interpretable sequences from Duffy-negative individuals - attributable to low parasitemia - and the lack of clear evidence of selective pressure acting on invasion-related genes of the P. vivax parasite populations circulating in sub-Saharan Africa, our study offers valuable insights into the genetic diversity of P. vivax and lays the groundwork for future research exploring parasite adaptation to Duffy-negative hosts
Intermediate-Dose Cytarabine as Postinduction AML Therapy
No full textInternational audienceBackground: We conducted a randomized controlled trial to compare intermediate doses (IDAC) with high doses of cytarabine (HDAC) as postinduction therapy in patients 18 to 60 years of age with newly diagnosed acute myeloid leukemia (AML). The main objectives were to evaluate noninferiority in overall survival (OS) after IDAC and safety.Methods: Patients 18 to 60 years of age with newly diagnosed AML, except those with core-binding factor, acute promyelocytic, Philadelphia chromosome-positive, or post-myeloproliferative neoplasm AML, were eligible. After the induction course, we randomly assigned patients to either IDAC (1500 mg/m2/12 hours) or HDAC (3000 mg/m2/12 hours). Patients with intermediate- and adverse-risk AML were eligible for allogeneic hematopoietic stem cell transplantation (HSCT) in first remission. The primary end point was OS in a predefined per-protocol analysis population. The primary analyses were performed in 1132 randomly assigned patients, with a noninferiority outcome adjusted on the European Leukemia Net (ELN) 2022 risk group, the use of induction anthracycline, the response to induction, and HSCT as a function of time following treatment.Results: At 5 years, OS was estimated at 59.3% (95% confidence interval [CI], 55.0 to 63.3) in the IDAC group versus 57.5% (95% CI, 53.3 to 61.5) in the HDAC group (adjusted hazard ratio, 0.96; 95% CI, 0.80 to 1.15; noninferiority test, P=0.0042). A preplanned analysis was unable to detect any interaction between IDAC or HDAC treatment effect and patient subgroups, including those defined by the ELN 2022 risk group or response to induction prior to random assignment. In addition, the severity of chemotherapy-induced myelosuppression and the incidence of related adverse events were lower after IDAC.Conclusions: Our trial shows noninferior outcomes in patients 18 to 60 years of age with newly diagnosed AML treated with low- versus high-dose cytarabine; this occurred with similar or lower toxicities.(Funded by the Regional Clinical Research Office, Angers and others; EudraCT number, 2014-000699-24; ClinicalTrials.gov number, NCT02416388)
Screening for the ciliate Buxtonella sulcata in free-ranging dairy cattle on Terceira Island, Azores archipelago
No full textInternational audienceBuxtonella sulcata is an alveolate ciliate protist, historically considered a commensal of the gastrointestinal tract of cattle. Despite the fact that its cysts are morphologically identical to those of Balantioides coli, molecular identification techniques have shed new light on its role as a pathogen. This work aimed to assess the presence of this ciliate in the population of dairy cattle on the Azorean island of Terceira by means of molecular analyses (ITS1–5.8S–ITS2 rRNA) of stool samples. A total of 116 samples were collected from adult Holstein-Friesian dairy cows, with no signs of gastrointestinal disease. A proportion of 49.1% of the samples were PCR-positive for Bu. sulcata, and 12 different genetic sequences were identified. These findings highlight the need for future research concerning the factors that influence the presence of Bu. sulcata in the gastrointestinal tract of dairy cows, the role of bovines as possible sources of infection, and the impact this ciliate may have on the health, welfare, and productivity of these animals
The proteotranscriptomic characterization of venom in the white seafan Eunicella singularis elucidates the evolution of Octocorallia arsenal
No full textInternational audienceAll the members of the phylum Cnidaria are characterized by the production of venom in specialized structures, the nematocysts. Venom of jellyfish (Medusozoa) and sea anemones (Anthozoa) has been investigated since the 1970s, revealing a remarkable molecular diversity. Specifically, sea anemones harbour a rich repertoire of neurotoxic peptides, some of which have been developed in drug leads. However, venoms of the vast majority of Anthozoa species remain uncharacterized, particularly in the class Octocorallia. To fill this gap, we applied a proteo-transcriptomic approach to investigate venom composition in Eunicella singularis, a gorgonian species common in Mediterranean hard-bottom benthic communities. Our results highlighted the peculiarities of the venom of E. singularis with respect to sea anemones, which is reflected in the presence of several toxins with novel folds, worthy of functional characterization. A comparative genomic survey across the octocoral radiation allowed us to generalize these findings and provided insights into the evolutionary history, molecular diversification patterns and putative adaptive roles of venom toxins. A comparison of whole-body and nematocyst proteomes revealed the presence of different cytolytic toxins inside and outside the nematocysts. Two instances of differential maturation patterns of toxin precursors were also identified, highlighting the intricate regulatory pathways underlying toxin expression
A multicountry evaluation of the Xpert MTB/RIF assay for the diagnosis of intrathoracic tuberculosis in children using alternative specimens (nasopharyngeal aspirate and stool): A prospective cohort study conducted in Madagascar, Ivory Coast and Cameroon (TB KIDS project)
No full textInternational audienceBackgroundAmidst a global resurgence of diphtheria cases with numerous outbreaks recorded worldwide since 2000, a better understanding of this vaccine-preventable disease's circulation is needed. Methods We retrospectively analyzed sera from 2 sero-epidemiological cross-sectional studies in Madagascar and Cambodia on fully primo-vaccinated 3- to 15-year-olds. Using enzyme-linked immunosorbent assay (ELISA) and seroneutralization (Vero Cell TNT) for the 3- to 8-year-olds with low ELISA titration values (<0.01 IU/mL), we assessed (i) the duration of protection by primary vaccination for 3- to 8-year-olds and (ii) the level of diphtheria in children and adolescents. Seropositivity was defined as a titration value (by ELISA or TNT) of at least 0.1 IU/mL and was used as a proxy for diphtheria infection among individuals >6 years postvaccination. Results Seven hundred forty-five children in Cambodia and 949 children in Madagascar were included. Our results show significantly more unprotected children among the 5- to 6-year-olds than among the 3- to 4-year-olds, with 41.1% (39/95) vs 26.7% (27/101; P = .03) in Cambodia and 21.4% (27/126) vs 8.0% (9/113; P < .01) in Madagascar. In Cambodia and Madagascar, respectively, 27.8% and 20.7% of the participants whose primary vaccination was performed >6 years earlier were seropositive, suggesting diphtheria infection. In both countries, we observed a higher rate of infected children when the last vaccine injection had been received 7–8 years or 11–12 years earlier vs 5–6 years earlier. Conclusions Our data show that the disease is present at high levels in Cambodia and Madagascar and that the national recommendation—primary vaccination—is not sufficient: Booster doses appear necessary at around 6 years of age and for adolescents, as recommended by the World Health Organization