Departament de Salut

During the last 3 years, a number of approaches for the normalization of RNA sequencing data have emerged in the literature, differing both in the type of bias adjustment and in the statistical strategy adopted. However, as data continue to accumulate, there has been no clear consensus on the appropriate normalization method to be used or the impact of a chosen method on the downstream analysis. In this work, we focus on a comprehensive comparison of seven recently proposed normalization methods for the differential analysis of RNA-seq data, with an emphasis on the use of varied real and simulated datasets involving different species and experimental designs to represent data characteristics commonly observed in practice. Based on this comparison study, we propose practical recommendations on the appropriate normalization method to be used and its impact on the differential analysis of RNA-seq data.

In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.

Fungal infections, especially those caused by opportunistic species, have become substantially more common in recent decades. Numerous species cause human infections, and several new human pathogens are discovered yearly. This situation has created an increasing interest in fungal taxonomy and has led to the development of new methods and approaches to fungal biosystematics which have promoted important practical advances in identification procedures. However, the significance of some data provided by the new approaches is still unclear, and results drawn from such studies may even increase nomenclatural confusion. Analyses of rRNA and rDNA sequences constitute an important complement of the morphological criteria needed to allow clinical fungi to be more easily identified and placed on a single phylogenetic tree. Most of the pathogenic fungi so far described belong to the kingdom Fungi; two belong to the kingdom Chromista. Within the Fungi, they are distributed in three phyla and in 15 orders (Pneumocystidales, Saccharomycetales, Dothideales, Sordariales, Onygenales, Eurotiales, Hypocreales, Ophiostomatales, Microascales, Tremellales, Poriales, Stereales, Agaricales, Schizophyllales, and Ustilaginales).

BACKGROUND: Autologous platelet-rich plasma (PRP) is a treatment that contains fibrin and high concentrations of growth factors with the potential to improve the healing of chronic wounds. This is the first update of a review first published in 2012. OBJECTIVES: To determine whether autologous PRP promotes the healing of chronic wounds. SEARCH METHODS: In June 2015, for this first update, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library): Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also searched for ongoing and unpublished clinical trials in the WHO International Clinical Trials Registry Platform (ICTRP) (searched January 2015). We did not impose any restrictions with respect to language, date of publication, or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared autologous PRP with placebo or alternative treatments for any type of chronic wound in adults. We did not apply any date or language restrictions. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology, including two reviewers independently selecting studies for inclusion, extracting data, and assessing risk of bias. MAIN RESULTS: The search identified one new RCT, making a total of 10 included RCTs (442 participants, 42% women). The median number of participants per RCT was 29 (range 10 to 117). Four RCTs recruited people with a range of chronic wounds; three RCTs recruited people with venous leg ulcers, and three RCTs considered foot ulcers in people with diabetes. The median length of treatment was 12 weeks (range 8 to 40 weeks).It is unclear whether autologous PRP improves the healing of chronic wounds generally compared with standard treatment (with or without placebo) (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.95 to 1.50; I(2) = 27%, low quality evidence, 8 RCTs, 391 participants). Autologous PRP may increase the healing of foot ulcers in people with diabetes compared with standard care (with or without placebo) (RR 1.22, 95% CI 1.01 to 1.49; I(2) = 0%, low quality evidence, 2 RCTs, 189 participants). It is unclear if autologous PRP affects the healing of venous leg ulcers (RR 1.02, 95% CI 0.81 to 1.27; I(2) = 0% ). It is unclear if there is a difference in the risk of adverse events in people treated with PRP or standard care (RR 1.05, 95% CI 0.29 to 3.88; I(2) = 0%, low quality evidence from 3 trials, 102 participants). AUTHORS' CONCLUSIONS: PRP may improve the healing of foot ulcers associated with diabetes, but this conclusion is based on low quality evidence from two small RCTs. It is unclear whether PRP influences the healing of other chronic wounds. The overall quality of evidence of autologous PRP for treating chronic wounds is low. There are very few RCTs evaluating PRP, they are underpowered to detect treatment effects, if they exist, and are generally at high or unclear risk of bias. Well designed and adequately powered clinical trials are needed.

En España, la nueva Clasificación Nacional de Ocupaciones (CNO-2011), que ha variado sustancialmente respecto a la del año 1994, requiere la adaptación de la clase social ocupacional para ser utilizada en estudios de desigualdades en salud. En este artículo se presentan dos propuestas para medir la clase social: la nueva clasificación de clase social ocupacional (CSO-SEE12), basada en la CNO-2011, desde un enfoque neoweberiano, y una propuesta de clase social desde un enfoque neomarxista. La CSO-SEE12 se construye a partir de una revisión detallada de los códigos de la CNO-2011. Por su parte, la clase social neomarxista se establece a partir de variables sobre los bienes de capital, de organización y de cualificación. La CSO-SEE12 que se propone consta de siete clases sociales que pueden ser agrupadas en un número menor de categorías, según las necesidades del estudio. La clasificación neomarxista consta de 12 categorías, en las cuales las y los propietarios se dividen en tres categorías en función de los bienes de capital y las personas asalariadas en nueve categorías formadas a partir de los bienes de organización y cualificación. Estas propuestas se complementan con la proposición de una clasificación del nivel educativo que integra los diferentes planes de estudio en España, y ofrece las correspondencias con la Clasificación Internacional Normalizada de la Educación. In Spain, the new National Classification of Occupations (Clasificación Nacional de Ocupaciones [CNO-2011]) is substantially different to the 1994 edition, and requires adaptation of occupational social classes for use in studies of health inequalities. This article presents two proposals to measure social class: the new classification of occupational social class (CSO-SEE12), based on the CNO-2011 and a neo-Weberian perspective, and a social class classification based on a neo-Marxist approach. The CSO-SEE12 is the result of a detailed review of the CNO-2011 codes. In contrast, the neo-Marxist classification is derived from variables related to capital and organizational and skill assets. The proposed CSO-SEE12 consists of seven classes that can be grouped into a smaller number of categories according to study needs. The neo-Marxist classification consists of 12 categories in which home owners are divided into three categories based on capital goods and employed persons are grouped into nine categories composed of organizational and skill assets. These proposals are complemented by a proposed classification of educational level that integrates the various curricula in Spain and provides correspondences with the International Standard Classification of Education.

BACKGROUND: No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. METHODS: Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. RESULTS: A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (-1.41 vs -1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (-3.37 vs -3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. CONCLUSIONS: In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care.

Background and aims The role of GATA factors in cancer has gained increasing attention recently, but the function of GATA6 in pancreatic ductal adenocarcinoma (PDAC) is controversial. GATA6 is amplified in a subset of tumours and was proposed to be oncogenic, but high GATA6 levels are found in well-differentiated tumours and are associated with better patient outcome. By contrast, a tumour-suppressive function of GATA6 was demonstrated using genetic mouse models. We aimed at clarifying GATA6 function in PDAC. Design We combined GATA6 silencing and overexpression in PDAC cell lines with GATA6 ChIP-Seq and RNA-Seq data, in order to understand the mechanism of GATA6 functions. We then confirmed some of our observations in primary patient samples, some of which were included in the ESPAC-3 randomised clinical trial for adjuvant therapy. Results GATA6 inhibits the epithelial–mesenchymal transition (EMT) in vitro and cell dissemination in vivo. GATA6 has a unique proepithelial and antimesenchymal function, and its transcriptional regulation is direct and implies, indirectly, the regulation of other transcription factors involved in EMT. GATA6 is lost in tumours, in association with altered differentiation and the acquisition of a basal-like molecular phenotype, consistent with an epithelial-to-epithelial (ET 2 ) transition. Patients with basal-like GATA6 low tumours have a shorter survival and have a distinctly poor response to adjuvant 5-fluorouracil (5-FU)/leucovorin. However, modulation of GATA6 expression in cultured cells does not directly regulate response to 5-FU. Conclusions We provide mechanistic insight into GATA6 tumour-suppressive function, its role as a regulator of canonical epithelial differentiation, and propose that loss of GATA6 expression is both prognostic and predictive of response to adjuvant therapy.

The EUROGIN 2011 roadmap reviews the current burden of human papillomavirus (HPV)-related morbidity, as well as the evidence and potential practice recommendations regarding primary and secondary prevention and treatment of cancers and other disease associated with HPV infection. HPV infection causes ~600,000 cases of cancer of the cervix, vulva, vagina, anus and oropharynx annually, as well as benign diseases such as genital warts and recurrent respiratory papillomatosis. Whereas the incidence of cervical cancer has been decreasing over recent decades, the incidence of anal and oropharyngeal carcinoma, for which there are no effective screening programs, has been rising over the last couple of decades. Randomized trials have demonstrated improved efficacy of HPV-based compared to cytology-based cervical cancer screening. Defining the best algorithms to triage HPV-positive women, age ranges and screening intervals are priorities for pooled analyses and further research, whereas feasibility questions can be addressed through screening programs. HPV vaccination will reduce the burden of cervical precancer and probably also of invasive cervical and other HPV-related disease in women. Recent trials demonstrated that prophylactic vaccination also protects against anogenital HPV infection, anogenital intraepithelial lesions and warts associated with vaccine types, in males; and anal HPV infection and anal intraepithelial neoplasia in MSM. HPV-related oropharyngeal cancer could be treated less aggressively because of better survival compared to cancers of the oropharynx unrelated to HPV. Key findings in the field of cervical cancer prevention should now be translated in cost-effective strategies, following an organized approach integrating primary and secondary prevention, according to scientific evidence but adapted to the local situation with particular attention to regions with the highest burden of disease.

Covering: 1958 to June 2018 Phenyl-γ-valerolactones (PVLs) and their related phenylvaleric acids (PVAs) are the main metabolites of flavan-3-ols, the major class of flavonoids in the human diet. Despite their presumed importance, these gut microbiota-derived compounds have, to date, in terms of biological activity, been considered subordinate to their parent dietary compounds, the flavan-3-ol monomers and proanthocyanidins. In this review, the role and prospects of PVLs and PVAs as key metabolites in the understanding of the health features of flavan-3-ols have been critically assessed. Among the topics covered, are proposals for a standardised nomenclature for PVLs and PVAs. The formation, bioavailability and pharmacokinetics of PVLs and PVAs from different types of flavan-3-ols are discussed, taking into account in vitro and animal studies, as well as inter-individual differences and the existence of putative flavan-3-ol metabotypes. Synthetic strategies used for the preparation of PVLs are considered and the methodologies for their identification and quantification assessed. Metabolomic approaches unravelling the role of PVLs and PVAs as biomarkers of intake are also described. Finally, the biological activity of these microbial catabolites in different experimental models is summarised. Knowledge gaps and future research are considered in this key area of dietary (poly)phenol research.

Hypertension is an independent and preventable risk factor for the development of cardiovascular diseases, however, little is known about the impact of gut microbiota composition in its development. We carried out comprehensive gut microbiota analysis and targeted metabolomics in a cross-sectional study of 29 non-treated hypertensive (HT) and 32 normotensive (NT) subjects. We determined fecal microbiota composition by 16S rRNA gene sequencing and bacterial functions by metagenomic analysis. The microbial metabolites analysed were short chain fatty acids (SCFA) both in plasma and feces, and trimethylamine N-oxide (TMAO) in plasma. The overall bacterial composition and diversity of bacterial community in the two groups were not significantly different. However, Ruminococcaceae NK4A214, Ruminococcaceae_UCG-010, Christensenellaceae_R-7, Faecalibacterium prausnitzii and Roseburia hominis were found to be significantly enriched in NT group, whereas, Bacteroides coprocola, Bacteroides plebeius and genera of Lachnospiraceae were increased in HT patients. We found a positive correlation between the HT-associated species and systolic and diastolic blood pressure after adjusted for measured confounders. SCFA showed antagonistic results in plasma and feces, detecting in HT subjects significant higher levels in feces and lower levels in plasma, which could indicate a less efficient SCFA absorption. Overall, our results present a disease classifier based on microbiota and bacterial metabolites to discriminate HT individuals from NT controls in a first disease grade prior to drug treatment.

The intraclass correlation coefficient (ICC) and the concordance correlation coefficient (CCC) are two of the most popular measures of agreement for variables measured on a continuous scale. Here, we demonstrate that ICC and CCC are the same measure of agreement estimated in two ways: by the variance components procedure and by the moment method. We propose estimating the CCC using variance components of a mixed effects model, instead of the common method of moments. With the variance components approach, the CCC can easily be extended to more than two observers, and adjusted using confounding covariates, by incorporating them in the mixed model. A simulation study is carried out to compare the variance components approach with the moment method. The importance of adjusting by confounding covariates is illustrated with a case example.

The goal of the study was to ascertain the factor structure and prevalence of psychiatric disability in children and adolescents in relation to demographic variables and diagnosis. A representative sample of 1,420 children (9-13 years) from 11 countries in North Carolina was followed for up to 6 years. Children and caretakers were interviewed with the Child and Adolescent Psychiatric Assessment, which generates DSM-IV diagnoses and includes a measure of disability secondary to psychological symptoms. Three broad areas of disability were identified (relating to family, school, and peers). School disabilities were more common in boys than girls. while the reverse was true of family disability. Effects of age were complex, and partially gender-differentiated. Children from minority ethnic groups had a higher overall prevalence of school disabilities, and were more prone than Whites to the disabling effects of disruptive behavior disorders. Anxiety disorders were as likely to result in disability as depressive disorders, and oppositional defiant disorders were more strongly associated with disability in some areas than was conduct disorder. The areas where disability is manifested are different depending on race, gender, age, and the type of disorder suffered. The implications of these findings for nosology and prevention are discussed.

Malnutrition in the elderly could be tackled by addressing socioeconomic factors. This study aimed to determine the magnitude of the relationship between socioeconomic factors and the malnutrition or malnutrition risk (MR) in the elderly. The PubMed and SCOPUS databases were searched for observational studies that included assessment of malnutrition or/and MR and socioeconomic variables (educational level, living alone, marital status, income and occupational level, feeling of loneliness, place of residence, and food expenditure) in ≥60-year-old subjects, published in English among 2000–2018 (PROSPERO: CRD42019137097). The systematic review included 40 observational studies (34 cross-sectional and 4 cohort studies) and 16 cross-sectional studies in the meta-analysis (34,703 individuals) of malnutrition and MR in relation to low educational level (Odds Ratio (OR): 1.48; 95% Confidence Interval (CI): 1.33–1.64; p &lt; 0.001), living alone (OR: 1.92; 95% CI: 1.73–2.14; p &lt; 0.001), being single, widowed, or divorced (OR: 1.73; 95% CI: 1.57–1.90; p &lt; 0.001), and low income level (OR: 2.69; 95% CI: 2.35–3.08; p &lt; 0.001), and considering these four socioeconomic factors, malnutrition and MR is associated with them (OR: 1.83; 95% CI: 1.73–1.93; p &lt; 0.001). Malnutrition and MR could be reduced by increasing economic level, supporting people living alone or being single, widowed, and divorced, and improving lifelong learning.

BACKGROUND: Inhalation is one of the main means of human exposure to polycyclic aromatic hydrocarbons (PAHs) because of their ubiquitous presence in the atmosphere. However, most studies have considered only PAHs found in the particle phase and have omitted the contribution of the gas-phase PAHs to the risk. OBJECTIVE: We estimated the lifetime lung cancer risk from PAH exposure by inhalation in people living next to the largest chemical site in Southern Europe and the Mediterranean area. METHODS: We determined 18 PAHs in the atmospheric gas and particle phase. We monitored the PAHs for 1 year in three locations near the chemical site in different seasons. We used toxic equivalence factors to calculate benzo[a]pyrene (BaP) equivalents (BaP-eq) for individual PAHs and applied the World Health Organization unit risk (UR) for BaP (UR = 8.7 × 10-5) to estimate lifetime cancer risks due to PAH exposures. RESULTS: We observed some spatial and seasonal variability in PAH concentrations. The contribution of gas-phase PAHs to the total BaP-eq value was between 34% and 86%. The total estimated average lifetime lung cancer risk due to PAH exposure in the study area was 1.2 × 10-4. CONCLUSIONS: The estimated risk was higher than values recommended by the World Health Organization and U.S. Environmental Protection Agency but lower than the threshold value of 10-3 that is considered an indication of definite risk according to similar risk studies. The results also showed that risk may be underestimated if the contributions of gas-phase PAHs are not considered.

The role of socioeconomic position (SEP) in the development of asthma and allergies is unclear, with some pointing to the risks of low SEP and other research pointing in the direction of higher SEP being associated with higher prevalence rates. The aim of this systematic review is to clarify associations between SEP and the prevalence of asthma and allergies. Out of 4407 records identified, 183 were included in the analysis. Low SEP was associated with a higher prevalence of asthma in 63% of the studies. Research on allergies, however, showed a positive association between higher SEP and illness in 66% of studies. Pooled estimates for the odds ratio of disease for the highest compared with the lowest SEP confirmed these results for asthma (unadjusted OR 1.38, 95% CI 1.37-1.39), allergies in general (OR 0.67, 95% CI 0.62-0.72), atopic dermatitis (unadjusted OR 0.72, 95% CI 0.61-0.83) and allergic rhinoconjunctivitis (unadjusted OR 0.52, 95% CI 0.46-0.59). Sensitivity analyses with a subsample of high-quality studies led to the same conclusion. Evidence from this systematic review suggests that asthma is associated with lower SEP, whereas the prevalence of allergies is associated with higher SEP.

We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to determine its association with clinical variables and dietary intake. A cross-sectional study was performed with 96 overweight/obese subjects and 32 lean subjects. Anthropometric parameters were positively associated with Collinsella aerofaciens, Dorea formicigenerans and Dorea longicatena, which had higher abundance the overweight/obese subjects. Moreover, different genera of Lachnospiraceae were negatively associated with body fat, LDL and total cholesterol. Saturated fatty acids (SFAs) were negatively associated with the genus Intestinimonas, a biomarker of the overweight/obese group, whereas SFAs were positively associated with Roseburia, a biomarker for the lean group. In conclusion, Dorea formicigenerans, Dorea longicatena and Collinsella aerofaciens could be considered obesity biomarkers, Lachnospiraceae is associated with lipid cardiovascular risk factors. SFAs exhibited opposite association profiles with butyrate-producing bacteria depending on the BMI. Thus, the relationship between diet and microbiota opens new tools for the management of obesity.

BACKGROUND: Karyotype analysis has been the standard method for prenatal cytogenetic diagnosis since the 1970s. Although highly reliable, the major limitation remains the requirement for cell culture, resulting in a delay of as much as 14 days to obtaining test results. Fluorescent in situ hybridisation (FISH) and quantitative fluorescent PCR (QF-PCR) rapidly detect common chromosomal abnormalities but do not provide a genome wide screen for unexpected imbalances. Array comparative genomic hybridisation (CGH) has the potential to combine the speed of DNA analysis with a large capacity to scan for genomic abnormalities. We have developed a genomic microarray of approximately 600 large insert clones designed to detect aneuploidy, known microdeletion syndromes, and large unbalanced chromosomal rearrangements. METHODS: This array was tested alongside an array with an approximate resolution of 1 Mb in a blind study of 30 cultured prenatal and postnatal samples with microscopically confirmed unbalanced rearrangements. RESULTS: At 1 Mb resolution, 22/30 rearrangements were identified, whereas 29/30 aberrations were detected using the custom designed array, owing to the inclusion of specifically chosen clones to give increased resolution at genomic loci clinically implicated in known microdeletion syndromes. Both arrays failed to identify a triploid karyotype. Thirty normal control samples produced no false positive results. CONCLUSIONS: Analysis of 30 uncultured prenatal samples showed that array CGH is capable of detecting aneuploidy in DNA isolated from as little as 1 ml of uncultured amniotic fluid; 29/30 samples were correctly diagnosed, the exception being another case of triploidy. These studies demonstrate the potential for array CGH to replace conventional cytogenetics in the great majority of prenatal diagnosis cases.

BACKGROUND: The effects of probiotic Bifidobacterium animalis subsp. lactis CECT 8145 (Ba8145) and those of its heat-killed form (h-k Ba8145) on human anthropometric adiposity biomarkers are unknown. OBJECTIVE: To assess the effect of Ba8145 and h-k Ba8145 ingestion on anthropometric adiposity biomarkers. DESIGN: CFU of h-k Ba8145, or placebo (maltodextrin) for 3 months. RESULTS: Ba8145 ingestion decreased waist circumference, waist circumference/height ratio, and Conicity index (P < 0.05) versus its baseline. Changes versus the placebo group reached significance (P < 0.05) after the h-k Ba8145 treatment. Ba8145 decreased the body mass index compared with baseline and placebo group (P < 0.05). The decrease in visceral fat area after Ba8145 treatments reached significance (P < 0.05) only after h-k Ba8145. When analyses by gender were performed, significance remained only for women. Diastolic blood pressure and HOMA index decreased (P < 0.05) after h-k Ba8145. Gut microbiome analyses showed an increase in Akkermansia spp. after Ba8145 treatment, particularly in the live form, which was inversely related to weight (P = 0.003). CONCLUSIONS: In abdominally obese individuals, consumption of Ba8145, both as viable and mainly as heat-killed cells, improves anthropometric adiposity biomarkers, particularly in women. An increase in the gut Akkermansia genus appears as a possible mechanism involved. Our results support Ba8145 probiotic as a complementary strategy in obesity management.

Abstract High-risk neuroblastomas show a paucity of recurrent somatic mutations at diagnosis. As a result, the molecular basis for this aggressive phenotype remains elusive. Recent progress in regulatory network analysis helped us elucidate disease-driving mechanisms downstream of genomic alterations, including recurrent chromosomal alterations. Our analysis identified three molecular subtypes of high-risk neuroblastomas, consistent with chromosomal alterations, and identified subtype-specific master regulator proteins that were conserved across independent cohorts. A 10-protein transcriptional module—centered around a TEAD4–MYCN positive feedback loop—emerged as the regulatory driver of the high-risk subtype associated with MYCN amplification. Silencing of either gene collapsed MYCN-amplified (MYCNAmp) neuroblastoma transcriptional hallmarks and abrogated viability in vitro and in vivo. Consistently, TEAD4 emerged as a robust prognostic marker of poor survival, with activity independent of the canonical Hippo pathway transcriptional coactivators YAP and TAZ. These results suggest novel therapeutic strategies for the large subset of MYCN-deregulated neuroblastomas. Significance: Despite progress in understanding of neuroblastoma genetics, little progress has been made toward personalized treatment. Here, we present a framework to determine the downstream effectors of the genetic alterations sustaining neuroblastoma subtypes, which can be easily extended to other tumor types. We show the critical effect of disrupting a 10-protein module centered around a YAP/TAZ-independent TEAD4–MYCN positive feedback loop in MYCNAmp neuroblastomas, nominating TEAD4 as a novel candidate for therapeutic intervention. Cancer Discov; 8(5); 582–99. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 517

BACKGROUND: Health surveys (HS) are a well-established methodology for measuring the health status of a population. The relative merit of using information based on HS versus electronic health records (EHR) to measure multimorbidity has not been established. Our study had two objectives: 1) to measure and compare the prevalence and distribution of multimorbidity in HS and EHR data, and 2) to test specific hypotheses about potential differences between HS and EHR reporting of diseases with a symptoms-based diagnosis and those requiring diagnostic testing. METHODS: Cross-sectional study using data from a periodic HS conducted by the Catalan government and from EHR covering 80% of the Catalan population aged 15 years and older. We determined the prevalence of 27 selected health conditions in both data sources, calculated the prevalence and distribution of multimorbidity (defined as the presence of ≥2 of the selected conditions), and determined multimorbidity patterns. We tested two hypotheses: a) health conditions requiring diagnostic tests for their diagnosis and management would be more prevalent in the EHR; and b) symptoms-based health problems would be more prevalent in the HS data. RESULTS: We analysed 15,926 HS interviews and 1,597,258 EHRs. The profile of the EHR sample was 52% women, average age 47 years (standard deviation: 18.8), and 68% having at least one of the selected health conditions, the 3 most prevalent being hypertension (20%), depression or anxiety (16%) and mental disorders (15%). Multimorbidity was higher in HS than in EHR data (60% vs. 43%, respectively, for ages 15-75+, P <0.001, and 91% vs. 83% in participants aged ≥65 years, P <0.001). The most prevalent multimorbidity cluster was cardiovascular. Circulation disorders (other than varicose veins), chronic allergies, neck pain, haemorrhoids, migraine or frequent headaches and chronic constipation were more prevalent in the HS. Most symptomatic conditions (71%) had a higher prevalence in the HS, while less than a third of conditions requiring diagnostic tests were more prevalent in EHR. CONCLUSIONS: Prevalence of multimorbidity varies depending on age and the source of information. The prevalence of self-reported multimorbidity was significantly higher in HS data among younger patients; prevalence was similar in both data sources for elderly patients. Self-report appears to be more sensitive to identifying symptoms-based conditions. A comprehensive approach to the study of multimorbidity should take into account the patient perspective.