It is currently unclear if next-generation sequencing (NGS) technologies can be implemented in the diagnosis setting at an affordable cost. The aim of this study was to measure the total cost of performing NGS in clinical practice in France, in both germline and somatic cancer genetics.The study was performed on 15 French representative cancer molecular genetics laboratories performing NGS panels' tests. The production cost was estimated using a micro-costing method with resources consumed collected in situ in each laboratory from a healthcare provider perspective. In addition, we used a top-down methodology for specific post-sequencing steps including bioinformatics, technical validation, and biological validation. Additional non-specific costs were also included. Costs were detailed per step of the process (from the pre-analytical phase to delivery of results), and per cost driver (consumables, staff, equipment, maintenance, overheads). Sensitivity analyses were performed.The mean total cost of NGS for targeted gene panels was estimated to 607€ (±207) in somatic genetics and 550€ (±140) in germline oncogenetic analysis. Consumables were the highest cost driver of the sequencing process. The sensitivity analysis showed that a 25% reduction of consumables resulted in a 15% decrease in total NGS cost in somatic genetics, and 13% in germline analysis. Additional costs accounted for 30-32% of the total NGS costs.Beyond cost assessment considerations, the diffusion of NGS technologies will raise questions about their efficiency when compared to more targeted approaches, and their added value in a context of routine diagnosis.

BackgroundMitochondrial DNA (mtDNA) diseases are rare disorders whose prevalence is estimated around 1 in 5000. Patients are usually tested only for deletions and for common mutations of mtDNA which account for 5–40% of cases, depending on the study. However, the prevalence of rare mtDNA mutations is not known.MethodsWe analysed the whole mtDNA in a cohort of 743 patients suspected of manifesting a mitochondrial disease, after excluding deletions and common mutations. Both heteroplasmic and homoplasmic variants were identified using two complementary strategies (Surveyor and MitoChip). Multiple correspondence analyses followed by hierarchical ascendant cluster process were used to explore relationships between clinical spectrum, age at onset and localisation of mutations.Results7.4% of deleterious mutations and 22.4% of novel putative mutations were identified. Pathogenic heteroplasmic mutations were more frequent than homoplasmic mutations (4.6% vs 2.8%). Patients carrying deleterious mutations showed symptoms before 16 years of age in 67% of cases. Early onset disease (<1 year) was significantly associated with mutations in protein coding genes (mainly in complex I) while late onset disorders (>16 years) were associated with mutations in tRNA genes. MTND5 and MTND6 genes were identified as ‘hotspots’ of mutations, with Leigh syndrome accounting for the large majority of associated phenotypes.ConclusionsRare mitochondrial DNA mutations probably account for more than 7.4% of patients with respiratory chain deficiency. This study shows that a comprehensive analysis of mtDNA is essential, and should include young children, for an accurate diagnosis that is now accessible with the development of next generation sequencing technology.

ContextThe prevalence of skin diseases among prisoners is higher than in the general population. Diagnosing and treating these lesions require a dermatologic advice. A tele-expertise network in dermatology for prisoners including 8 health facilities in prison and 2 hospital dermatological departments was developed to improve access to dermatologists’ expertise in correctional facilities. Our objective was to evaluate the effectiveness and costs of tele-expertise in dermatology for prisoners.MethodsWe carried out a retrospective cohort study on data collected by the information system of the tele-expertise network. We used the MAST (Model for ASsessment of Telemedicine) model to perform a multidimensional assessment including the proportion of patients with a completed treatment plan for the skin lesions, the proportion of technical problems, the quality of the pictures, the investment and operating costs and the satisfaction of the professionals.ResultsMean patient age was 34.2 years with 90% men. 511 requests for 450 patients were initiated. The delay from the connection to the tele-expertise software to the validation of the request was inferior to 7 min for 50% of the requests and inferior to 30 min for 85% of the requests. Overall, with tele-expertise, 82% of the patients had a completed treatment plan for the skin lesions, with 2.9% of all patients requiring a later face-to-face appointment or hospitalization, to be compared to a proportion of 35% of patients with a completed treatment plan when tele-expertise was not available. The most frequent lesions were acnea (22%) and atopic dermatitis (18%). The mean cost for one completed treatment plan was €184 by tele-expertise and €315 without tele-expertise. Tele-expertise was well accepted among physicians with all responders (n = 9) willing to continue using it.ConclusionTele-expertise is a dominant intervention in comparison to a face-to face consultation taking into account the cost of transportation and the proportion of canceled appointments and is acceptable for physicians.Trial registrationNCT02309905.

The funder had no role in the design and conduct of the study, collection, management, analysis,