NGS and phenotypic ontology-based approaches increase the diagnostic yield in syndromic retinal diseases.

Syndromic retinal diseases (SRDs) are a group of complex inherited systemic disorders, with challenging molecular underpinnings and clinical management. Our main goal is to improve clinical and molecular SRDs diagnosis, by applying a structured phenotypic ontology and next-generation sequencing (NGS)-based pipelines. A prospective and retrospective cohort study was performed on 100 probands with an a priori diagnosis of non-Usher SRDs, using available clinical data, including Human Phenotype Ontology annotation, and further classification into seven clinical categories (ciliopathies, specific syndromes and five others). Retrospective molecular diagnosis was assessed using different molecular and bioinformatic methods depending on availability. Subsequently, uncharacterized probands were prospectively screened using other NGS approaches to extend the number of analyzed genes. After phenotypic classification, ciliopathies were the most common SRD (35%). A global characterization rate of 52% was obtained, with six cases incompletely characterized for a gene that partially explained the phenotype. An improved characterization rate was achieved addressing prospective cases (83%) and well-recognizable syndrome (62%) subgroups. The 27% of the fully characterized cases were reclassified into a different clinical category after identification of the disease-causing gene. Clinical-exome sequencing is the most appropriate first-tier approach for prospective cases, whereas whole-exome sequencing and bioinformatic reanalysis increases the diagnosis of uncharacterized retrospective cases to 45%, mostly those with unspecific symptoms. Our study describes a comprehensive approach to SRDs in daily clinical practice and the importance of thorough clinical assessment and selection of the most appropriate molecular test to be used to solve these complex cases and elucidate novel associations.

The present and future of gene profiling in breast cancer.

Gene signatures can provide prognostic and predictive information to help in the treatment of early-stage breast cancer. Although many of these signatures have been described, only a few have been properly validated. MammaPrint and OncoType offer prognostic information and identify low-risk patients who do not benefit from adjuvant chemotherapy. With regard to prediction of response, molecular subtypes of breast cancer differ in their sensitivity to chemotherapy, although further studies are needed in this field. Cost, small sample size, and the need to use central laboratories are common limitations to the widespread use of these tools.

The efficacy of a medication review programme conducted in an emergency department.

Background Older age and inappropriate prescribing is related to a greater rate of emergency department visits and hospitalisations. Objective To assess the efficacy of an interprofessional collaboration programme in which a review of the medication of older patients seen in the emergency observation unit was carried out. Setting Emergency departments at four Spanish hospitals. Method Randomised, controlled study. Patients over 65 years of age presenting to the emergency department were randomised to a control or an intervention group. In the intervention group, a pharmacist reviewed the patients' chronic medication and identified any potentially inappropriate prescriptions based on the STOPP/START criteria. Each case was discussed with the emergency specialist and a recommendation to modify the treatment was sent to the general practitioner. Main outcome measure Rate of emergency visits and hospital admissions. Results The adjusted rate ratio of emergency visits and hospital admissions was 0.808 (95% CI 0.617 to 1.059) at 3 months, 0.888 (95% CI 0.696 to 1.134) at 6 months and 0.954 (95% CI 0.772 to 1.179) at 12 months. There was a statistically significant reduction at 3 months in two of the hospitals that participated in the study [adjusted rate ratio at 3 months was 0.452 (95% CI 0.222 to 0.923) in hospital 3 and 0.567 (95% CI 0.328 to 0.983) in hospital 4]. Conclusion Overall, the intervention did not reduce the number of emergency visits and hospital admissions. However, a significant effect was observed in centres were a high acceptance rate of treatment recommendations was achieved.