Mapas conceptuales para el diagnóstico de enfermedades raras en atención primaria

Rare diseases are a real public health problem for hospitals and also for primary care. We describe some metaphor-based diagnosis procedures, such as: “When you hear hoof beats don’t always think horses, sometimes they could be zebras”, or that one about the antiquarian who recognised a museum masterpiece while walking in the Rastro (Madrid). The “lightning diagnoses” by Skoda are an important historic record.T. Greenhalgh has tried to cover the gap between evidence based medicine and the intuitive diagnosis. We point out some clinical epidemiology rules in order to improve their early detection by family practitioners and paediatricians. In our opinion, the training in the diagnosis of rare diseases has to be different for primary care level and for hospital doctors. Concept maps are useful for diagnosis in primary care clinics.     

Burden of disease due to cancer in Spain

Background  

Burden of disease is a joint measure of mortality and morbidity which makes it easier to compare health problems in which these two components enjoy different degrees of relative importance. The objective of this study is ascertaining the burden of disease due to cancer in Spain via the calculation of disability-adjusted life years (DALYs).     

El torbellino de la violencia. Relatos biográficos de mujeres que sufren maltrato

ObjectivesTo analyse the experience from the point of view of women who have suffered domestic violence. To identify factors related to continuing or resolving the problem.DesignQualitative interpretative research from a phenomenological perspective.Population sampleWomen, detected in primary care, who have suffered domestic violence and have recognised the problem, and who accepted to participate in this research.Multicentre StudySix health centres in the city of Malaga.Methods and techniquesThe technique used is the biographical narration using individual open interviews between social workers and women. This narration was tape-recorded and verbatim transcribed to written text. Grounded theory. Qualitative analysis was made with ATLAS-TI 5.2.OutcomesA total of 35 narrations were analysed. The abuse situation was described as “whirl-wind” metaphor (blindness-isolation-helplessness-suffering-destiny-dependence-fantasies -about love, protection, happiness, change- and vicious circles). Enduring experience is reported to be related to several factors: inculcated gender values, family-ideal, uncertainty, annulment, personal failure sensation, love, support defects, self-image, children protection, multiple fears and material aspects. They identified two types of “exit”: passive and active with different mechanisms and repercussions. Exit experience is related to: limit situations, children intervention, family ideal attempts, and fear-loss. Leaving is a transitional process or “pathway”. Institutional support is not always guaranteed and emotional support is better evaluated than a legal one.ConclusionsEnduring and coming out are reported as two qualitatively different states, which involve many cultural and personal factors. There is a gap between these two states with a process that varies depending on the involvement of the women in decision-making.     

Fibrilación auricular en pacientes con COVID-19. Utilidad de la puntuación CHA2DS2-VASc: un análisis del registro internacional HOPE COVID-19

Introduction and objectivesCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Atrial fibrillation (AF) is common in acute situations, where it is associated with more complications and higher mortality.MethodsAnalysis of the international HOPE registry (NCT04334291). The objective was to assess the prognostic information of AF in COVID-19 patients. A multivariate analysis and propensity score matching were performed to assess the relationship between AF and mortality. We also evaluated the impact on mortality and embolic events of the CHA₂DS₂-VASc score in these patients.ResultsAmong 6217 patients enrolled in the HOPE registry, 250 had AF (4.5%). AF patients had a higher prevalence of cardiovascular risk factors and comorbidities. After propensity score matching, these differences were attenuated. Despite this, patients with AF had a higher incidence of in-hospital complications such as heart failure (19.3% vs 11.6%, P = .021) and respiratory insufficiency (75.9% vs 62.3%, P = .002), as well as a higher 60-day mortality rate (43.4% vs 30.9%, P = .005). On multivariate analysis, AF was independently associated with higher 60-day mortality (hazard ratio, 1.234; 95%CI, 1.003-1.519). CHA₂DS₂-VASc score acceptably predicts 60-day mortality in COVID-19 patients (area ROC, 0.748; 95%CI, 0.733-0.764), but not its embolic risk (area ROC, 0.411; 95%CI, 0.147-0.675).ConclusionsAF in COVID-19 patients is associated with a higher number of complications and 60-day mortality. The CHA₂DS₂-VASc score may be a good risk marker in COVID patients but does not predict their embolic risk.     

Variation in blood levels of inflammatory markers related and unrelated to smoking cessation in women

This study assessed the influence of short-term changes in smoking habit on blood levels of inflammatory markers, which have been associated with increased cardiovascular risk. Five inflammatory markers were measured before and 6 weeks after attempting smoking cessation in 138 healthy women. In the 48 participants who stopped smoking, white blood cell count (-0.7+/-1.2 x 10(9)/L; P<.001) and fibrinogen (-0.6+/-1.5 micromol/L; P<.01) decreased, but there was no significant (P>.1) change in the plasma level of C-reactive protein (median change +0.1; interquartile range -0.2, 0.9 mg/L), intercellular adhesion molecule 1 (+17+/-75 ng/mL), or CD40 ligand (+0.4+/-2.1 ng/mL). Most of the individual variation in inflammatory marker levels was unrelated to changes in smoking habit.     

Distribution of somatostatin-like immunoreactivity in the brain of the caecilian Dermophis mexicanus (Amphibia: Gymnophiona): comparative aspects in amphibians

The organization of the somatostatin-like-immunoreactive (SOM-ir) structures in the brain of anuran and urodele amphibians has been well documented, and significant differences were noted between the two amphibian orders. However, comparable data are not available for the third order of amphibians, the gymnophionans (caecilians). In the present study, we analyzed the anatomical distribution of SOM-ir cells and fibers in the brain of the gymnophionan Dermophis mexicanus. In addition, because of its known relationship with catecholamines in other vertebrates, double immunostaining for SOM and tyrosine hydroxylase was used to investigate this situation in the gymnophionan. Abundant SOM-ir cell bodies and fibers were widely distributed throughout the brain. In the telencephalon, pallial and subpallial cells were labeled, being most numerous in the medial pallium and amygdaloid region. Most of the SOM-ir neurons were found in the preoptic area and hypothalamus and showed a clear projection to the median eminence. Less conspicuously, SOM-ir structures were found in the thalamus, tectum, tegmentum, and reticular formation. Both SOM-ir cells and fibers were demonstrated in the spinal cord. The double-immunohistofluorescence technique revealed that catecholaminergic neurons and SOM-ir cells are largely intermingled in many brain regions but form totally separated populations. Many differences were found between the distribution of SOM-ir structures in Dermophis and that in anurans or urodeles. Some features were shared only with anurans, such as the abundant pallial SOM-ir cells, whereas others were common only to urodeles, such as the organization of the hypothalamohypophysial SOM-ir system. In addition, some characteristics were found only in Dermophis, such as the localization of the SOM-ir spinal cells and the lack of colocalization of catecholamines and SOM throughout the brain. Therefore, any conclusions concerning the SOM system in amphibians are incomplete without considering evidence for gymnophionans.     

Tonsillar hypertrophy and mesenteric adenopathies as the main manifestations in a patient with Whipple's disease

Whipple's disease is an infrequent chronic infection caused by Tropheryma whipplei, identified in 1992. Intestinal, articular, central nervous system and cardiac involvement is common. The presence of abdominal adenopathies, especially mesenteric adenopathies, without peripheral adenopathies or gastrointestinal, articular, neurological or cardiac symptoms is rare. We present the case of a male patient with tonsillar hypertrophy, mesenteric adenopathies, fever and constitutional syndrome, leading to suspicion of lymphoma. Biopsy findings of the lingual tonsil and mesenteric adenopathies were compatible with Whipple's disease. The diagnosis was confirmed by blood polymerase chain reaction.     

Evaluation of an Array-Based Method for Human Papillomavirus Detection and Genotyping in Comparison with Conventional Methods Used in Cervical Cancer Screening

Cervical cancer is the second-most prevalent cancer in young women around the world. Infection with human papillomavirus (HPV), especially high-risk HPV types (HR-HPV), is necessary for the development of this cancer. HPV-DNA detection is increasingly being used in cervical cancer screening programs, together with the Papanicolau smear test. We evaluated the usefulness of introducing this new array-based HPV genotyping method (i.e., Clinical Arrays Papillomavirus Humano) in the cervical cancer screening algorithm in our center. The results obtained using this method were compared to those obtained by the hybrid capture II high-risk HPV DNA test (HC-II) and Papanicolau in a selected group of 408 women. The array-based assay was performed in women that were HC-II positive or presented cytological alterations. Among 246 array-positive patients, 123 (50%) presented infection with ≥2 types, and HR-HPV types were detected in 206 (83.7%), mainly HPV-16 (24.0%). Up to 132 (33.2%) specimens were classified as ASCUS (for atypical squamous cells of undetermined significance), and only 48 (36.4%) of them were HPV-DNA positive by either assay; however, 78.7% of these cases were caused by HR-HPV types. The agreement between both HPV-DNA detection techniques was fairly good (n = 367). Screening with Papanicolau smear and HC-II tests, followed by HPV detection and genotyping, provided an optimal identification of women at risk for the development of cervical cancer. Furthermore, with the identification of specific genotypes, either in single or multiple infections, a better prediction of disease progression was achieved. The array method also made allowed us to determine the possible contribution of the available vaccines in our setting.Cervical cancer is the second most prevalent type of cancer in women worldwide. A total of 500,000 new cases are diagnosed each year and cause more than 270,000 deaths (15). Since the 1940s, screening programs for cervical cancer prevention, mainly based on the Papanicolau smear test, have been implemented in resource-rich countries, resulting in a remarkable decrease in its incidence and related mortality (16). However, this test has a limited sensitivity, especially for detecting precancerous lesions (1, 6).Genital human papillomavirus (HPV) is a highly common sexually transmitted infection. Although most HPV infections are transient and asymptomatic, epidemiological studies worldwide have demonstrated that persistent infection with certain genotypes is the necessary cause for the development of cervical cancer and its precursor lesions (3, 19, 24). More than 100 HPV types have been described and classified into high-risk types (HR-HPV) and low-risk types (LR-HPV) according to the probability of developing cervical cancer (14). Therefore, in addition to the Papanicolau smear test, HPV detection assays have been implemented in many countries to improve cervical cancer screening. These assays have a higher sensitivity than the Papanicolau smear test for the detection of women at risk of developing precancerous lesions (12).Since HPV cannot be grown in conventional cell cultures and serological assays are unreliable, molecular techniques constitute the best choice to diagnose HPV infection. Currently, the only assay that has been approved by the U.S. Food and Drug Administration for the detection of HPV-DNA is the Hybrid Capture II system (HC-II; Digene Corp., Gaithersburg, MD). This signal amplification assay was designed to detect LR-HPV and HR-HPV genotypes in two different kits but does not provide genotype information.The interest of HPV genotyping has increased in light of the recently licensed HPV bivalent and tetravalent vaccines (9, 23). Genotyping also allows clinicians to monitor patients according to the oncogenic risk of the HPV types identified. Several genotyping assays have been developed over the last years with a variety of amplification and detection strategies (reviewed in references 4 and 13). Methods based on consensus PCR and reverse hybridization of PCR products provide high sensitivity and extensive typing information, including identification of multiple infections. Recently, an assay based on amplification and array hybridization has been commercialized for the detection and genotyping of HPV in routine clinical specimens (Clinical Arrays Papillomavirus Humano [CAPH]; Genomica S.A.U., Madrid, Spain). This assay provides the possibility to detect simple or mixed-type infections with 35 HPV types (20 HR-HPV and 15 LR-HPV).The aim of the present study was to assess the usefulness of introducing this new array-based HPV detection and genotyping method in the cervical cancer screening algorithm in our center, a reference hospital with 600,000-habitant coverage. With this goal, we compared the results obtained using this method with those obtained by HC-II and the cytology findings.     

Genetic variability of the fatty acid synthase pathway is not associated with prostate cancer risk in the European Prospective Investigation on Cancer (EPIC)

A western lifestyle, characterised by low rates of energy expenditure and a high-energy diet rich in animal protein, saturated fats and refined carbohydrates, is associated with high incidence of prostate cancer in men. A high-energy nutritional status results in insulin/IGF signalling in cells, which in turn stimulates synthesis of fatty acids. We investigated whether the genetic variability of the genes belonging to the fatty acid synthesis pathway is related to prostate cancer risk in 815 prostate cancer cases and 1266 controls from the European Prospective Investigation on Cancer (EPIC). Using a tagging approach and selecting 252 SNPs in 22 genes, we covered all the common genetic variation of this pathway. None of the SNPs reached statistical significance after adjusting for multiple comparisons. Common SNPs in the fatty acid synthase pathway are not major contributors to prostate cancer risk.