Analysis of referrals after a synergic work between Primary Care and Urology. Impact of joint protocol implementation and a continuing education program in our healthcare area. / Evolución de las derivaciones desde Atención Primaria a Urología tras la creación de un grupo de trabajo y la instauración de protocolos y cursos de formación continuada.

OBJECTIVE: To analyse the evolution and adequacy of referrals from Primary Care to Urology, after the implementation of referral protocols on the most frequent urological diseases and the establishment of a continuing education program. MATERIAL AND METHODS: A Primary Care-Urology work group was created in 2011. Initially, performance and clinical practice protocols in prostatic pathology (BPH and PSA) were established. These were supported by training sessions for primary care physicians. After analysing the effect of the mentioned joint work, 3more (scrotal pathology, urinary tract infections and urinary incontinence) were included. We analysed and compared the referrals and their adequacy before and after the establishment of the protocols. RESULTS: The most common referral causes were symptoms of the lower urinary tract due to BPH, which initially represented 22.8% of the total, and decreased to 16.9%. After the introduction of the new algorithms, we observed a decrease in referrals for scrotal pathology (13-14% to 7.8%), an increase in urinary incontinence referrals (3% al 10.3%) and those related to urinary tract infections remained stable. The adequacy to the protocols improved progressively: LUTS from 46% to 65.3%; PSA from 55% to 84.4% and urinary incontinence from 66.2% to 73.1%. Adequacy in scrotal pathology decreased (de 67.1% a 63.3%), while in UTI it stayed much the same (around 76%). CONCLUSIONS: The joint work between Urology and Primary Care achieves an improvement in referrals adequacy regarding the most frequent urological pathologies.

Circulating tumour DNA in EGFR-mutant non-small-cell lung cancer.

The advent of targeted therapy in non-small-cell lung cancer (nsclc) has made the routine molecular diagnosis of EGFR mutations crucial for optimal patient management. Obtaining tumour tissue for biomarker testing, especially in the setting of re-biopsy, can present many challenges. A potential alternative source of tumour dna is circulating cell-free tumour-derived dna (ctdna). Although ctdna is present in low quantities in plasma, the convenience of sample acquisition and the increasing reliability of detection methods make this approach a promising one. The various performance characteristics of both digital and nondigital platforms are still variable, and a standardized approach is needed that will make those platforms reliable clinical tools for the detection of EGFR sensitizing mutations and resistance mutations, including the T790M resistance mutation. Information derived from ctdna can be used to assess tumour burden, to identify genomic-based resistance mechanisms, and to track dynamic changes during therapy.

Management of EGFR-mutated non-small-cell lung cancer: practical implications from a clinical and pathology perspective.

Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have evolved from being histologically described to molecularly defined. Management of lung adenocarcinomas now generally requires multiple molecular tests at baseline to define the optimal treatment strategy. More recently, second biopsies performed at progression in patients treated with tyrosine kinase inhibitors (tkis) have further defined the continued use of molecularly targeted therapy. In the present article, we focus on one molecular subtype: EGFR-mutated nsclc. For that patient population, multiple lines of tki therapy are now available either clinically or in clinical trials. Each line of treatment is guided by the specific mutations (for example, L858R, T790M, C797S) identified in EGFR. We first describe the various mechanisms of acquired resistance to EGFR tki treatment. We then focus on strategies that clinicians and pathologists can both use during tissue acquisition and handling to optimize patient results. We also discuss future directions for the molecular characterization of lung cancers with driver mutations, including liquid biopsies. Finally, we provide an algorithm to guide treating physicians managing patients with EGFR-mutated nsclc. The same framework can also be applied to other molecularly defined nsclc subgroups as resistance patterns are elucidated and additional lines of treatment are developed.

A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder.

The genetic basis of bipolar disorder has long been thought to be complex, with the potential involvement of multiple genes, but methods to analyze populations with respect to this complexity have only recently become available. We have carried out a genome-wide association study of bipolar disorder by genotyping over 550,000 single-nucleotide polymorphisms (SNPs) in two independent case-control samples of European origin. The initial association screen was performed using pooled DNA, and selected SNPs were confirmed by individual genotyping. While DNA pooling reduces power to detect genetic associations, there is a substantial cost saving and gain in efficiency. A total of 88 SNPs, representing 80 different genes, met the prior criteria for replication in both samples. Effect sizes were modest: no single SNP of large effect was detected. Of 37 SNPs selected for individual genotyping, the strongest association signal was detected at a marker within the first intron of diacylglycerol kinase eta (DGKH; P=1.5 x 10(-8), experiment-wide P<0.01, OR=1.59). This gene encodes DGKH, a key protein in the lithium-sensitive phosphatidyl inositol pathway. This first genome-wide association study of bipolar disorder shows that several genes, each of modest effect, reproducibly influence disease risk. Bipolar disorder may be a polygenic disease.

[Guidelines of the Spanish Society of Cardiology for clinical practice in exercise testing]. / Guías de práctica clínica de la Sociedad Española de Cardiología en pruebas de esfuerzo.

Most exercise testing is performed in adults with known or suspected ischemic heart disease. In the last few years cardiac imaging techniques have been applied in this field, improving the information obtained with the procedure. However, the exceptions to this rule are emerging rapidly not only in healthy people (asymptomatic individuals, athletes, handicapped people) but also in cardiac patients (advanced congestive heart failure, hypertension, rhythm disorders, congenital heart disease, etc.). All the-se issues justify the need for a multidisciplinary consensus document in Spain. This paper reviews and updates the methodological aspects of the stress test, including those related to oxygen consumption measurements. The main aim of this review was to determine the role of exercise testing in the evaluation of ischemic heart disease as well as the applications of imaging stress testing. The usefulness of this test in other non-ischemic cardiac disorders and in selected subsets of healthy people is also reviewed.