Cost of exome analysis in patients with intellectual disability: a micro-costing study in a French setting.

BACKGROUND: With the development of next generation sequencing technologies in France, exome sequencing (ES) has recently emerged as an opportunity to improve the diagnosis rate of patients presenting an intellectual disability (ID). To help French policy makers determine an adequate tariff for ES, we aimed to assess the unit cost per ES diagnostic test for ID from the preparation of the pre-analytical step until the report writing step and to identify its main cost drivers. METHODS: A micro-costing bottom-up approach was conducted for the year 2018 in a French setting as part of the DISSEQ study, a cost-effectiveness study funded by the Ministry of Health and performed in collaboration with the GAD (Génétique des Anomalies du Développement), a genetic team from the Dijon University Hospital, and a public sequencing platform, the Centre National de Recherche en Génomique Humaine (CNRGH). The analysis was conducted from the point of view of these two ES stakeholders. All of the resources (labor, equipment, disposables and reagents, reusable material) required to analyze blood samples were identified, collected and valued. Several sensitivity analyses were performed. RESULTS: The unit nominal cost per ES diagnostic test for ID was estimated to be €2,019.39. Labor represented 50.7% of the total cost. The analytical step (from the preparation of libraries to the analysis of sequences) represented 88% of the total cost. Sensitivity analyses suggested that a simultaneous price decrease of 20% for the capture kit and 50% for the sequencing support kit led to an estimation of €1,769 per ES diagnostic test for ID. CONCLUSION: This is the first estimation of ES cost to be done in the French setting of ID diagnosis. The estimation is especially influenced by the price of equipment kits, but more generally by the organization of the centers involved in the different steps of the analysis and the time period in which the study was conducted. This information can now be used to define an adequate tariff and assess the efficiency of ES. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03287206 on September 19, 2017.

Autosomal recessive variations of TBX6, from congenital scoliosis to spondylocostal dysostosis.

Proximal 16p11.2 microdeletions are recurrent microdeletions with an overall prevalence of 0.03%. In patients with segmentation defects of the vertebra (SDV), a burden of this microdeletion was observed with TBX6 as a candidate gene for SDV. In a published cohort of patients with congenital scoliosis (CS), TBX6 haploinsufficiency was compound heterozygous with a common haplotype. Besides, a single three-generation family with spondylocostal dysostosis (SCD) was reported with a heterozygous stop-loss of TBX6. These observations questioned both on the inheritance mode and on the variable expressivity associated with TBX6-associated SDV. Based on a national recruitment of 56 patients with SDV, we describe four patients with variable SDV ranging from CS to SCD associated with biallelic variations of TBX6. Two patients with CS were carrying a proximal 16p11.2 microdeletion associated with the previously reported haplotype. One patient with extensive SDV was carrying a proximal 16p11.2 microdeletion associated with a TBX6 rare missense change. One patient with a clinical diagnosis of SCD was compound heterozygous for two TBX6 rare missense changes. The three rare variants were affecting the chromatin-binding domain. Our data illustrate the variable expressivity of recessive TBX6 ranging from CS to SCD.

Studies on Synthetic and Natural Melanin and Its Affinity for Fe(III) Ion.

In this work, we measured the metal-binding sites of natural and synthetic dihydroxyindole (DHI) melanins and their respective interactions with Fe(III) ions. Besides the two acid groups detected for the DHI system: catechol (Cat) and quinone-imine (QI), acetate groups were detected in the natural oligomer by potentiometric titrations. At acidic pH values, Fe(III) complexation with synthetic melanin was detected in an Fe(OH)(CatH(2)Cat) interaction. With an increase of pH, three new interactions occurred: dihydroxide diprotonated catechol, Fe(OH)(2)(CatH(2)Cat)(-), dihydroxide monoprotonated catechol, [Fe(OH)(2)(CatHCat)](2-), and an interaction resulting from the association of one quinone-imine and a catechol group, [Fe(OH)(2)(Qi(-))(CatHCat)](3-). In the natural melanin system, we detected the same interactions involving catechol and quinone-imine groups but also the metal interacts with acetate group at pH values lower than 4.0. Furthermore, interactions in the synthetic system were also characterized by infrared spectroscopy by using the characteristic vibrations of catechol and quinone-imine groups. Finally, scanning electronic microscopy (SEM) and energy-dispersive X-ray (EDS) analysis were used to examine the differences in morphology of these two systems in the absence and presence of Fe(III) ions. The mole ratio of metal and donor atoms was obtained by the EDS analysis.

Syndrome of inappropriate antidiuretic hormone: assessment and nursing implications.

Syndrome of inappropriate antidiuretic hormone (SIADH) is a condition characterized by serum hypoosmolality and hyponatremia, resulting from the aberrant or sustained secretion of antidiuretic hormone (ADH). Its most frequent cause is malignancy, of which small cell or oat cell bronchogenic carcinoma is most common. Because it mimics the clinical manifestations of various disorders, SIADH often is difficult to diagnose. However, with early detection and prompt management, it can be reversed. The oncology nurse frequently is in a position to assist in the early recognition of this condition. The ability to maintain a high index of suspicion for patients at risk is critical to prompt recognition. Familiarity with the conditions that lead to this crisis and its early signs are essential to establishing a diagnosis and administering prompt treatment.

Laser welding of pedicled flap skin tubes.

The efficacy of the carbon dioxide laser used at high power levels for tissue destruction is well established. This laser at lower power levels has been used to incise and anastomose blood vessels, tendons, nerves, dura, bowel, fallopian tube, vasa deferentia, ureters and skin. Laser welding is faster, reduces surgical manipulation and introduces less foreign material into the wound than conventional suturing techniques. We tested the feasibility of laser welding of pedicled flap skin tubes to determine if there is a potential application in reconstruction, particularly for hypospadias repair.