Attention! A good bedside test for delirium?

peer-reviewedBackground Routine delirium screening could improve delirium detection, but it remains unclear as to which screening tool is most suitable. We tested the diagnostic accuracy of the following screening methods (either individually or in combination) in the detection of delirium: MOTYB (months of the year backwards); SSF (Spatial Span Forwards); evidence of subjective or objective 'confusion'.Methods We performed a cross-sectional study of general hospital adult inpatients in a large tertiary referral hospital. Screening tests were performed by junior medical trainees. Subsequently, two independent formal delirium assessments were performed: first, the Confusion Assessment Method (CAM) followed by the Delirium Rating Scale-Revised 98 (DRS-R98). DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria were used to assign delirium diagnosis. Sensitivity and specificity ratios with 95% CIs were calculated for each screening method.Results 265 patients were included. The most precise screening method overall was achieved by simultaneously performing MOTYB and assessing for subjective/objective confusion (sensitivity 93.8%, 95% CI 82.8 to 98.6; specificity 84.7%, 95% CI 79.2 to 89.2). In older patients, MOTYB alone was most accurate, whereas in younger patients, a simultaneous combination of SSF (cutoff 4) with either MOTYB or assessment of subjective/objective confusion was best. In every case, addition of the CAM as a second-line screening step to improve specificity resulted in considerable loss in sensitivity.Conclusions Our results suggest that simple attention tests may be useful in delirium screening. MOTYB used alone was the most accurate screening test in older people.PUBLISHEDpeer-reviewe

Experiences of Pharmacy Trainees from an Interprofessional Immersion Training

Interprofessional education is essential in that it helps healthcare disciplines better utilize each other and provide team-based collaboration that improves patient care. Many pharmacy training programs struggle to implement interprofessional education. This purpose of the study was to examine the effect of a 30-h interprofessional training that included pharmacy students to determine if the training helped these students build valuable knowledge and skills while working alongside other health care professions. The interprofessional training included graduate-level trainees from pharmacy, behavioral health, nursing, and family medicine programs where the trainees worked within teams to build interprofessional education competencies based on the Interprofessional Education Collaborative core competencies. Sixteen pharmacy trainees participated in the training and completed pre- and post-test measures. Data were collected over a two-year period with participants completing the Team Skills Scale and the Interprofessional Attitudes Scale. Paired sample t-tests indicated that, after this training, pharmacy trainees showed significant increases in feeling better able to work in healthcare teams and valuing interprofessional practice

Attention! A good bedside test for delirium?

Background Routine delirium screening could improve delirium detection, but it remains unclear as to which screening tool is most suitable. We tested the diagnostic accuracy of the following screening methods (either individually or in combination) in the detection of delirium: MOTYB (months of the year backwards); SSF (Spatial Span Forwards); evidence of subjective or objective 'confusion'.Methods We performed a cross-sectional study of general hospital adult inpatients in a large tertiary referral hospital. Screening tests were performed by junior medical trainees. Subsequently, two independent formal delirium assessments were performed: first, the Confusion Assessment Method (CAM) followed by the Delirium Rating Scale-Revised 98 (DRS-R98). DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria were used to assign delirium diagnosis. Sensitivity and specificity ratios with 95% CIs were calculated for each screening method.Results 265 patients were included. The most precise screening method overall was achieved by simultaneously performing MOTYB and assessing for subjective/objective confusion (sensitivity 93.8%, 95% CI 82.8 to 98.6; specificity 84.7%, 95% CI 79.2 to 89.2). In older patients, MOTYB alone was most accurate, whereas in younger patients, a simultaneous combination of SSF (cutoff 4) with either MOTYB or assessment of subjective/objective confusion was best. In every case, addition of the CAM as a second-line screening step to improve specificity resulted in considerable loss in sensitivity.Conclusions Our results suggest that simple attention tests may be useful in delirium screening. MOTYB used alone was the most accurate screening test in older people

The PI3K/mTOR pathway Is targeted by rare germline variants in patients with both melanoma and renal cell carcinoma

International audienceBackground: Malignant melanoma and RCC have different embryonic origins, no common lifestyle risk factors but intriguingly share biological properties such as immune regulation and radioresistance. An excess risk of malignant melanoma is observed in RCC patients and vice versa. This bidirectional association is poorly understood, and hypothetic genetic co-susceptibility remains largely unexplored. Results: We hereby provide a clinical and genetic description of a series of 125 cases affected by both malignant melanoma and RCC. Clinical germline mutation testing identified a pathogenic variant in a melanoma and/or RCC predisposing gene in 17/125 cases (13.6%). This included mutually exclusive variants in MITF (p.E318K locus, N = 9 cases), BAP1 (N = 3), CDKN2A (N = 2), FLCN (N = 2), and PTEN (N = 1). A subset of 46 early-onset cases, without underlying germline variation, was whole-exome sequenced. In this series, thirteen genes were significantly enriched in mostly exclusive rare variants predicted to be deleterious, compared to 19,751 controls of similar ancestry. The observed variation mainly consisted of novel or low-frequency variants (<0.01%) within genes displaying strong evolutionary mutational constraints along the PI3K/mTOR pathway, including PIK3CD, NFRKB, EP300, MTOR, and related epigenetic modifier SETD2. The screening of independently processed germline exomes from The Cancer Genome Atlas confirmed an association with melanoma and RCC but not with cancers of established differing etiology such as lung cancers. Conclusions: Our study highlights that an exome-wide case-control enrichment approach may better characterize the rare variant-based missing heritability of multiple primary cancers. In our series, the co-occurrence of malignant melanoma and RCC was associated with germline variation in the PI3K/mTOR signaling cascade, with potential relevance for early diagnostic and clinical management

The PI3K/mTOR Pathway Is Targeted by Rare Germline Variants in Patients with Both Melanoma and Renal Cell Carcinoma

Background: Malignant melanoma and RCC have different embryonic origins, no common lifestyle risk factors but intriguingly share biological properties such as immune regulation and radioresistance. An excess risk of malignant melanoma is observed in RCC patients and vice versa. This bidirectional association is poorly understood, and hypothetic genetic co-susceptibility remains largely unexplored. Results: We hereby provide a clinical and genetic description of a series of 125 cases affected by both malignant melanoma and RCC. Clinical germline mutation testing identified a pathogenic variant in a melanoma and/or RCC predisposing gene in 17/125 cases (13.6%). This included mutually exclusive variants in MITF (p.E318K locus, N = 9 cases), BAP1 (N = 3), CDKN2A (N = 2), FLCN (N = 2), and PTEN (N = 1). A subset of 46 early-onset cases, without underlying germline variation, was whole-exome sequenced. In this series, thirteen genes were significantly enriched in mostly exclusive rare variants predicted to be deleterious, compared to 19,751 controls of similar ancestry. The observed variation mainly consisted of novel or low-frequency variants (&lt;0.01%) within genes displaying strong evolutionary mutational constraints along the PI3K/mTOR pathway, including PIK3CD, NFRKB, EP300, MTOR, and related epigenetic modifier SETD2. The screening of independently processed germline exomes from The Cancer Genome Atlas confirmed an association with melanoma and RCC but not with cancers of established differing etiology such as lung cancers. Conclusions: Our study highlights that an exome-wide case-control enrichment approach may better characterize the rare variant-based missing heritability of multiple primary cancers. In our series, the co-occurrence of malignant melanoma and RCC was associated with germline variation in the PI3K/mTOR signaling cascade, with potential relevance for early diagnostic and clinical management

Effect of 17q21 variants and smoking exposure in early-onset asthma.

International audienceBACKGROUND: A genomewide association study has shown an association between variants at chromosome 17q21 and an increased risk of asthma. To elucidate the relationship between this locus and disease, we examined a large, family-based data set that included extensive phenotypic and environmental data from the Epidemiological Study on the Genetics and Environment of Asthma. METHODS: We tested 36 single-nucleotide polymorphisms (SNPs) in the 17q21 region in 1511 subjects from 372 families for an association with asthma. We also tested for genetic heterogeneity according to the age at the onset of asthma and exposure to environmental tobacco smoke in early life. RESULTS: Eleven SNPs were significantly associated with asthma (P<0.01), of which three (rs8069176, rs2305480, and rs4795400) were strongly associated (P<0.001). Ordered-subset regression analysis led us to select an onset at 4 years of age or younger to classify patients as having early-onset asthma. Association with early-onset asthma was highly significant (P<10(-5) for four SNPs), whereas no association was found with late-onset asthma. With respect to exposure to environmental tobacco smoke in early life, we observed a significant association with early-onset asthma only in exposed subjects (P<5x10(-5) for six SNPs). Under the best-fitting recessive model, homozygous status (GG) at the most strongly associated SNP (rs8069176) conferred an increase in risk by a factor of 2.9, as compared with other genotypes (AG and AA) in the group exposed to environmental tobacco smoke (P=2.8x10(-6); P=0.006 for the test for heterogeneity of the SNP effect on early-onset asthma between groups with tobacco exposure and those without such exposure). CONCLUSIONS: This study shows that the increased risk of asthma conferred by 17q21 genetic variants is restricted to early-onset asthma and that the risk is further increased by early-life exposure to environmental tobacco smoke. These findings provide a greater understanding of the functional role of the 17q21 variants in the pathophysiology of asthma

QuantumClone: Clonal assessment of functional mutations in cancer based on a genotype-aware method for clonal reconstruction

International audienceMotivation In cancer, clonal evolution is assessed based on information coming from single nucleotide variants and copy number alterations. Nonetheless, existing methods often fail to accurately combine information from both sources to truthfully reconstruct clonal populations in a given tumor sample or in a set of tumor samples coming from the same patient. Moreover, previously published methods detect clones from a single set of variants. As a result, compromises have to be done between stringent variant filtering [reducing dispersion in variant allele frequency estimates (VAFs)] and using all biologically relevant variants. Results We present a framework for defining cancer clones using most reliable variants of high depth of coverage and assigning functional mutations to the detected clones. The key element of our framework is QuantumClone, a method for variant clustering into clones based on VAFs, genotypes of corresponding regions and information about tumor purity. We validated QuantumClone and our framework on simulated data. We then applied our framework to whole genome sequencing data for 19 neuroblastoma trios each including constitutional, diagnosis and relapse samples. We confirmed an enrichment of damaging variants within such pathways as MAPK (mitogen-activated protein kinases), neuritogenesis, epithelial-mesenchymal transition, cell survival and DNA repair. Most pathways had more damaging variants in the expanding clones compared to shrinking ones, which can be explained by the increased total number of variants between these two populations. Functional mutational rate varied for ancestral clones and clones shrinking or expanding upon treatment, suggesting changes in clone selection mechanisms at different time points of tumor evolution

Multimodal interactions

RevueInternational audienceIntroduction A central sensory characteristic of food is its flavor, which, most of the time, confers to a given food product its identity and typicality, and thus contribute to its liking (Prescott, 2015). Flavor has been defined as a sensory percept induced by food or beverage tasting. This holistic perception is constructed through the functional integration of information transmitted by the chemical senses: olfaction, gustation, and oral and nasal somatosensory inputs (Thomas-Danguin, 2009). Flavor may be influenced by other nonchemical sensory inputs such as texture, sound, or color (Spence, 2013). The functional integration of information transmitted by anatomically distinct senses relies on a multimodal processing, which is fundamental for our interaction with and behavioral adaptation to our environment. In the case of food flavor, the multimodal integration of chemosensory cues induces crossmodal perceptual interactions in which the perception of a tastant may affect the perceived intensity of an odorant, and vice versa (Delwiche, 2004). Nevertheless, although crossmodal interactions can result from perceptual processes, other factors may also contribute to the overall construction of the food flavor percept. In this chapter, we propose a review of multimodal interactions in the context of food flavor construction and modulation. In the first part, we focus on interactions within the chemical senses. We report evidences for the integration of olfactory and gustatory information at sub- and suprathreshold levels, and then review the mechanisms underpinning aroma–taste interactions, as well as the neurophysiological bases of perceptual flavor integration. Afterward, we provide more details on the impact of olfactory, gustatory and trigeminal interactions on food flavor perception. In the second part, we present interactions between aroma, taste, and texture while summarizing the possible mechanisms, and we consider the influence of texture on aroma and taste and the reverse. Along this chapter, several terms are used with a specific meaning that is not necessarily consensual, depending on the scientific area. The terms taste, odor, and aroma refer to the perceptions induced by chemicals which are respectively tastants or odorants, perceived through the ortho- or retronasal route, respectively. We also use the term of flavoring agent for a mixture of odorants formulated to produce a specific aroma. Finally, we use the term texture to define the perception of textural properties (eg, hardness, thickness, etc.), while the term structure refers to the physical organization of the food matrix

Retention and release of taste and aroma compounds from the food matrix during mastication and ingestion

RevueIntroductionDuring eating, food is submitted to mastication and salivation to form a bolus which is then swallowed for further digestion. Aroma and taste compounds are released from food bolus during the masticatory and post swallowing steps. Taste compounds are delivered to the receptors located on the tongue in order to be perceived. Aroma compounds are transferred from food to saliva then to the air phase in the oral cavity and transported to the nasal cavity via the respiratory flow in order to reach the olfactory receptors and be perceived. This chapter will present an overview of the different aroma and taste compounds, their interactions with the food matrix, and their transport to the taste and olfactory receptors