Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study.

BACKGROUND: Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes. METHODS: We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort). FINDINGS: We included 14 726 participants: 6357 (43·2%) in the derivation cohort, 4370 (29·7%) in the first external validation cohort, and 3999 (27·2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC; 0·83 [95% CI [0·78-0·89]) versus the fibrosis-4 index (FIB-4; 0·68 [0·61-0·75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI 347-641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liver-related mortality was 0·90 (0·88-0·91) versus 0.84 (0·82-0·86) for FIB-4. INTERPRETATION: The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care. FUNDING: European Commission under the H20/20 programme; Fondo de Investigación Sanitaria de Salud; Instituto de Salud Carlos III; Spanish Ministry of Economy, Industry, and Competitiveness; the European Regional Development Fund; and the German Ministry of Education and Research (BMBF).

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries.

BACKGROUND: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. METHODS: This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. DISCUSSION: This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. TRIAL REGISTRATION: This study is registered on Clinicaltrials.gov ( NCT03789825 ).

[Evolution of the prevalence of peripheral artery disease in clinical practice: A descriptive population study with real databases (SIDIAP-CMBD)]. / Evolución de la prevalencia de arteriopatía periférica en la práctica clínica: Estudio descriptivo poblacional con bases de datos reales (SIDIAP-CMBD).

OBJECTIVE: To evaluate, with real world data (SIDIAP and CMBD), the evolution of the prevalence of peripheral arterial disease (PAD) in the Catalan population and the cardiovascular risk factors present in people with this pathology. DESIGN: Longitudinal descriptive population study. SITE: Primary health care. PARTICIPANTS: Patients listed in SIDIAP and CMBD with a diagnosis of peripheral artery disease between 2008 and 2018 ≥ 35 years, as well as those without a diagnosis, but with an ABI < 0.9 in SIDIAP. INTERVENTIONS AND MAIN MEASUREMENTS: Main variable AP (ICD-9, ICD-10). Sociodemographic data, risk factors and cardiovascular disease, drug use and prevalent cardiovascular events at the time of diagnosis. RESULTS: 141,520 patients were studied. 75% had hypertension, 58% were smokers or former smokers, and 23% had a myocardial infarction. The global prevalence increased from 1.15% in 2008 to 3.10% in 2018. The prevalence of PAD increased with age, with a moderate increase at younger ages, and more pronounced in > 55 years, exceeding 10% in > 85 years. CONCLUSION: This is a population study where it is observed that the evolution of the prevalence of peripheral artery disease has presented a constant increase during the years 2008-2018, being higher in men, especially from 55 years of age. Studies with large databases can facilitate the design and implementation of new policies in national health systems.

[Interarm blood pressure difference: Concordance between two methods of automatic simultaneous measurement and between visits reproducibility]. / Diferencia de presión arterial entre brazos: concordancia entre 2 métodos automáticos de medición simultánea y reproducibilidad entre visitas.

OBJECTIVE: An increased interarm blood pressure difference (IAD) (≥10mmHg) has been associated with increased cardiovascular morbidity and mortality. There are few studies determining how IAD has to be measured and its reliability between visits. The objectives of our study were twofold. First, to evaluate the concordance between two automatic oscillometric devices for IAD measurement (two OMRON devices and one Microlife WatchBP™ device (WBP™)) and to analyse the reproducibility of IAD between visits in the general population attending a primary care centre. DESIGN: Descriptive cross-sectional study of concordance between the two methods and reproducibility of IAD between two visits separated by one week. SITE: Parets del Vallès primary care centre (Barcelona). PARTICIPANTS: General population aged 35-74 years. INTERVENTIONS AND MAIN MEASUREMENTS: One hundred and forty-nine patients completed the two visits. At each visit, IAD was measured three times with both methods and the mean of the three determinations was considered. Other variables such as sociodemographic and anthropometric variables, pathological antecedents and pharmacological treatment were collected through a review of the medical history and an interview with the patient. Concordance between the two devices and between visits reproducibility were calculated using the Lin concordance coefficient (CCL) for IAD expressed continuously and kappa(k) indices for IAD categorised as normal or pathological. RESULTS: Concordance for IAD expressed continuously was low: CCL=0.13 (0.02-0.24). Concordance was also low for IAD categorised as normal or pathological (k=-0.03 (-0.05-0.00)). Reproducibility between visits was low for both methods and for both continuous and categorised IAD: with OMRON™ CCL=0.19 (0.03-0.34) and k=-0.02 (-0.16-0.12) and for WBP™ CCL=0.14 (-0.01-0.29) and k=0.49 (0.33-0.64). CONCLUSIONS: Concordance between two automatic oscillometers in the simultaneous IAD measurement was low. Reproducibility between visits was also low for both methods.

Interaction between metabolic syndrome and alcohol consumption, risk factors of liver fibrosis: A population-based study.

BACKGROUND AND AIMS: Alcohol and metabolic syndrome (MS) coexist frequently as cofactors of liver disease. Previous studies suggest a deleterious effect of MS in advanced alcohol-related liver disease (ArLD). However, it is unknow whether MS can increase the risk of liver fibrosis in early stages of ArLD. The aim of this study was to investigate the effect of MS on liver fibrosis in subjects with alcohol consumption from a population-based cohort. METHODS: The number of subjects include 1760(58%) of 3014 who were randomly selected from the community consumed alcohol and were classified as current drinkers, divided in moderate (n = 1222) or high-risk drinkers (n = 275) (>21 units/week men, >14 units/week women for high-risk drinkers), or former drinkers (n = 263). Liver fibrosis was estimated by measuring liver stiffness(LS) with transient elastography (TE). RESULTS: Prevalence of significant LS using cutoff values of TE of 8 and 9.1kPa was increased in high-risk compared with moderate or former drinkers and lifetime abstainers. In subjects with alcohol consumption, LS was associated with male gender, AST, ALT, years of consumption, and MS. In high-risk drinkers, MS and intensity of consumption were the only factors associated with significant LS (OR 3.7 and 4.6 for LS ≥ 8 kPa and 3.9 and 9.2 kPa for LS ≥ 9.1 kPa, respectively). Presence of significant liver fibrosis in the liver biopsy was higher among high-risk as compared with moderate or former drinkers. CONCLUSION: MS increases the risk of liver fibrosis in subjects with alcohol consumption. Among high-risk drinkers, only MS and consumption of high amount of alcohol are associated with risk of liver fibrosis.

Lung Ultrasound for Heart Failure Diagnosis in Primary Care.

BACKGROUND: Lung ultrasound (LUS) is useful for diagnosing pulmonary congestion, but its value in primary care remains unclear. We investigated whether LUS improved diagnostic accuracy in outpatients with heart failure (HF) suspicion. METHODS AND RESULTS: LUS was performed on 2 anterior (A), 2 lateral (L), and 2 posterior (P) areas per hemithorax. An area was positive when ≥3 B-lines were observed. Two diagnostic criteria were used: for LUS-C1, 2 positive areas of 4 (A-L) on each hemithorax; and for LUS-C2, 2 positive areas of 6 (A-L-P) on each hemithorax. A cardiologist blinded to LUS validated HF diagnosis. 162 patients were included (age 75.6 ± 9.4 years, 70.4% women). Both LUS criteria, alone and combined with other HF diagnostic criteria, were accurate for identifying HF. LUS-C2 outperformed LUS-C1, showing remarkable specificity (0.99) and positive predictive value (0.92). LUS-C2, together with Framingham criteria, N-terminal pro-B-type natriuretic peptide, and electrocardiogram, added diagnostic value (area under the receiver operating characteristic curves 0.90 with LUS-C2 vs 0.84 without; P = .006). In the absence of N-terminal pro-B-type natriuretic peptide, LUS-C2 significantly reclassified one-third of patients above Framingham criteria and electrocardiogram (net reclassification improvement 0.65, 95% confidence interval 0.04-1.1). CONCLUSIONS: LUS was accurate enough to rule-in HF in a primary care setting. The accuracy of diagnostic workup for HF in primary care is enhanced by incorporating LUS, irrespective NT-proBNP availability.

[Reliability of retinography for the detection of hypertensive retinopathy in Primary Care]. / Fiabilidad de la retinografía para la detección de retinopatía hipertensiva en Atención Primaria.

OBJECTIVE: High blood pressure is one of the most prevalent diseases in general adult population. Its importance lies in the complications it causes in target organs such as kidney, heart, brain and eye. The aim of this work is to evaluate the agreement in the evaluation and interpretation of retinographies of hypertensive patients by family doctors and ophthalmologists. MATERIAL AND METHODS: This is a multicentric cross-sectional study in which 976 hypertensive patients from 50 to 70 years old were involved. They were participants of the «Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study¼ (ISSYS project) carried out in primary care centers of Barcelona and who agreed to undergo retinography. Six family physicians and 2 ophthalmologists evaluated the presence of retinal lesions through the Keith-Wagener-Barker criteria. RESULTS: The inter/intra-observer Kappa concordance of the evaluations was analyzed. The evaluation of the retinographies under the usual conditions of clinical practice obtained a high subjective component with slight and fair intra-observer concordance values in the Keith-Wagener-Barker criteria. Only the assessment of the microaneurysms showed a moderate concordance and the ratio artery/vein was the worst concordant. CONCLUSIONS: The evaluation of the retinographies in habitual conditions of clinical practice has a high subjective component that is reflected in slight and fair inter-intraobserver concordance values. The use of objective reading systems in the assessment of retinography in hypertensive patients would be useful.

Transient elastography for screening of liver fibrosis: Cost-effectiveness analysis from six prospective cohorts in Europe and Asia.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease and alcohol-related liver disease pose an important challenge to current clinical healthcare pathways because of the large number of at-risk patients. Therefore, we aimed to explore the cost-effectiveness of transient elastography (TE) as a screening method to detect liver fibrosis in a primary care pathway. METHODS: Cost-effectiveness analysis was performed using real-life individual patient data from 6 independent prospective cohorts (5 from Europe and 1 from Asia). A diagnostic algorithm with conditional inference trees was developed to explore the relationships between liver stiffness, socio-demographics, comorbidities, and hepatic fibrosis, the latter assessed by fibrosis scores (FIB-4, NFS) and liver biopsies in a subset of 352 patients. We compared the incremental cost-effectiveness of a screening strategy against standard of care alongside the numbers needed to screen to diagnose a patient with fibrosis stage ≥F2. RESULTS: The data set encompassed 6,295 participants (mean age 55 ±â€¯12 years, BMI 27 ±â€¯5 kg/m2, liver stiffness 5.6 ±â€¯5.0 kPa). A 9.1 kPa TE cut-off provided the best accuracy for the diagnosis of significant fibrosis (≥F2) in general population settings, whereas a threshold of 9.5 kPa was optimal for populations at-risk of alcohol-related liver disease. TE with the proposed cut-offs outperformed fibrosis scores in terms of accuracy. Screening with TE was cost-effective with mean incremental cost-effectiveness ratios ranging from 2,570 €/QALY (95% CI 2,456-2,683) for a population at-risk of alcohol-related liver disease (age ≥45 years) to 6,217 €/QALY (95% CI 5,832-6,601) in the general population. Overall, there was a 12% chance of TE screening being cost saving across countries and populations. CONCLUSIONS: Screening for liver fibrosis with TE in primary care is a cost-effective intervention for European and Asian populations and may even be cost saving. LAY SUMMARY: The lack of optimized public health screening strategies for the detection of liver fibrosis in adults without known liver disease presents a major healthcare challenge. Analyses from 6 independent international cohorts, with transient elastography measurements, show that a community-based risk-stratification strategy for alcohol-related and non-alcoholic fatty liver diseases is cost-effective and potentially cost saving for our healthcare systems, as it leads to earlier identification of patients.

High Prevalence of Liver Fibrosis Among European Adults With Unknown Liver Disease: A Population-Based Study.

BACKGROUND & AIMS: Liver fibrosis is the main determinant of long-term outcome in chronic liver diseases. Little is known about the prevalence of liver fibrosis in the general population. The aim of the study was to investigate the prevalence of liver fibrosis in the general adult population with unknown liver disease. METHODS: This was a population-based, cross-sectional study performed in the Barcelona metropolitan area. Subjects aged 18 to 75 years old were identified randomly from citizens included in the primary health care registry. Of 4866 subjects invited, 3076 participated (63.2%). Liver fibrosis was estimated by measuring liver stiffness (LS) with transient elastography (TE). Liver histology was assessed in 92 subjects with increased LS. RESULTS: Prevalence estimates of increased LS (≥6.8, ≥8.0, and ≥9.0 kPa) were 9.0%, 5.8%, and 3.6%, respectively. The etiology of liver disease was mainly nonalcoholic fatty liver disease (NAFLD), followed by alcohol risk consumption (consumption of ≥21 standard drinking units/wk in men and ≥14 standard drinking units/wk in women). Factors independently associated with increased LS were male sex, abdominal obesity, type 2 diabetes, serum glucose, high-density lipoprotein, and triglyceride levels. Subjects without risk factors for NAFLD or without alcohol risk consumption had a very low prevalence of increased LS. The best cut-off value of LS for significant liver fibrosis (F2-F4) was 9.2 kPa, with high sensitivity and specificity. TE was more accurate than alanine aminotransferase, NAFLD fibrosis score, or Fibrosis 4. An algorithm for screening for liver fibrosis using TE in the community setting is proposed. CONCLUSIONS: These findings show a high prevalence of silent liver disease with advanced fibrosis mainly related to NAFLD in adult European subjects without known liver disease. An LS value less than 9.2 kPa predicts the absence of significant liver fibrosis with high accuracy and could be used for screening purposes.

Impact of comorbid conditions on participation in an organised colorectal cancer screening programme: a cross-sectional study.

BACKGROUND: There is controversy regarding how comorbidity impacts on colorectal cancer screening, especially in the context of organised programmes. The aim of this study is to assess the effect of comorbidities on participation in the Barcelona population-based colorectal cancer screening programme (BCCSP). METHODS: Cross-sectional study carried out in ten primary care centres involved in the BCCSP. Individuals aged 50 to 69, at average risk of colorectal cancer, who were invited to participate in the first round of the faecal immunochemical test-based BCCSP were included (2011-2012). The main variable was participation in the BCCSP. Comorbidity was assessed by clinical risk group status. Other adjusting variables were age, sex, socioeconomic deprivation, visits to primary care, smoking, alcohol consumption and body mass index. Logistic regression models were used to test the association between participation in the programme and potential explanatory variables. The results were given as incidence rate ratios (IRR) and their 95% confidence intervals (CI). RESULTS: Of the 36,208 individuals included, 17,404 (48%) participated in the BCCSP. Participation was statistically significantly higher in women, individuals aged 60 to 64, patients with intermediate socioeconomic deprivation, and patients with more medical visits. There was a higher rate of current smoking, high-risk alcohol intake, obesity and individuals in the highest comorbidity categories in the non-participation group. In the adjusted analysis, only individuals with multiple minor chronic diseases were more likely to participate in the BCCSP (IRR 1.14; 95% CI [1.06 to 1.22]; p < 0.001). In contrast, having three or more dominant chronic diseases was associated with lower participation in the screening programme (IRR 0.76; 95% CI [0.65 to 0.89]; p = 0.001). CONCLUSIONS: Having three or more dominant chronic diseases, was associated with lower participation in a faecal immunochemical test-based colorectal cancer screening programme, whereas individuals with multiple minor chronic diseases were more likely to participate. Further research is needed to explore comorbidity as a cause of non-participation in colorectal cancer screening programmes and which individuals could benefit most from colorectal cancer screening.

Iodine nutritional status of women in their first trimester of pregnancy in Catalonia.

BACKGROUND: Sufficient iodine intake is needed during pregnancy to ensure proper fetal development. The iodine levels of women in their first trimester of pregnancy in Catalonia are currently unknown. This data would help to determine whether our public health services should establish recommendations or interventions in this line. The aim of this study was to investigate the iodine nutritional status, prevalence of urinary iodine <150 µg/L, and tobacco use in the first trimester of pregnancy in our setting. METHODS: Cross-sectional study. Data were collected during 2008-2009 from women in their first trimester at the primary care centers of the province of Barcelona (Spain). Pregnant women included in the study completed a questionnaire on eating habits and underwent urinary iodine concentration (UIC) assessment. RESULTS: Nine hundred forty five women completed the dietary questionnaire and urinary iodine testing. Median UIC was 172 µg/L, with 407 participants (43.1%) showing levels <150 µg/L. On multivariate logistic regression analysis, intake of 1-2 glasses of milk per day, OR = 0.636 95% CI (0.45-0.90) or >2 glasses, OR = 0.593 95% CI (0.37-0.95); iodized salt consumption, OR = 0.678 95% CI (0.51-0. 90); and use of iodine supplementation, OR = 0.410 95% CI (0.31-0.54), protected against the risk of UIC <150 µg/L. Simultaneous consumption of iodized salt and milk (≥1 glass/day) showed a larger protective effect: OR = 0.427, 95% CI (0.31-0.54). CONCLUSION: The median UIC of the pregnant women surveyed indicated an acceptable iodine nutritional status according to the criteria established by the WHO and ICCIDD. The risk of urinary iodine <150 µg/L decreased with simultaneous consumption of milk and iodized salt, similar to the decrease seen with iodine supplementation.

Incidence of peripheral arterial disease in the ARTPER population cohort after 5 years of follow-up.

BACKGROUND: To know the epidemiology (prevalence, incidence, progression and morbidity and mortality associated) of peripheral artery disease in general population and the factors associated with this progression is essential to know the evolution of atherosclerosis and develop preventive strategies. The aim of the study was to determine the incidence of PAD after 5 years of follow-up population-based cohort ARTPER, and the evolution of Ankle brachial Index (ABI) in this period. METHODS: Peripheral artery disease incidence analysis after 5 years of follow-up of 3786 subjects > 50 years old. Peripheral artery disease incident when the second cross section Ankle brachial Index was <0.9 in any of the lower limbs, with normal baseline (0.9 to 1.4). RESULTS: Between 2012 and 2013 2762 individuals (77% participation) were re-examined . Finally analyzed 2256 subjects (after excluding pathological Ankle brachial Index) followed for 4.9 years (range 3.8 to 5.8 years), totalling 11,106 person-years. Peripheral artery disease 95 new cases were detected, representing an incidence of 4.3% at 5 years and 8.6 per 1000 person-years (95% CI 6.9 to 10.5) being higher in men (10.2, 95% CI 7.4 to 13.5) than in women (7.5, 95% CI 5.5 to 9.9). Linear correlation between the baseline Ankle brachial Index and the second cross section was low (r = 0.23). CONCLUSIONS: The incidence of peripheral artery disease in ARTPER cohort was 8.6 cases per 1000 person-years, being higher in men, especially <65 years. The correlation between two measures Ankle brachial Index after 5 years of follow-up was low. One might consider whether Ankle brachial Index repeated measures could improve the correlation.

[Acceptability and quality of abdominal ultrasound studies requested by medical professionals]. / Adecuación y calidad de las ecografías abdominales solicitadas por los profesionales de medicina.

OBJECTIVE: To evaluate the acceptability/quality of abdominal ultrasound studies requested by primary care physicians in Barcelona; to develop ultrasound guidelines and assess their impact on acceptability. DESIGN: 2-phase study, one retrospective, descriptive phase evaluating the acceptability/quality of requests (pre-intervention phase) and another to assess the impact of guidelines on acceptability/quality (post-intervention phase). SUBJECTS: Requests for ultrasound studies from January-June 2010 from 10 primary care centers and the same number of requests from the same centers after the intervention. VARIABLES: Pre-intervention phase: reason for consultation and request; presence of diagnostic orientation; results of ultrasound; acceptability/quality of the request. INTERVENTION: design guidelines using the nominal group technique, dissemination of guidelines in the same centers. Post-intervention phase: three months after dissemination analyze the same number of requests assessing the same variables included in the pre-intervention phase. RESULTS: Pre-intervention phase: 1,063 requests, 52.4% women, mean age 52±16years (range 11-94). Post-intervention phase: 1,060 requests, 57.6% women, mean age 54±17years (range 6-91). Main reasons for requests: abdominal pain/discomfort 38.3% (pre-intervention) and 43.1% (post-intervention). Diagnostic orientation in 14.5% (pre-intervention) and 40.8% (post-intervention). Normal ultrasound results in 46.0% (pre-intervention) and 42.3% (post-intervention). Good quality of requests in 42.7% (pre-intervention) and 46.5% (post-intervention). Acceptability of ultrasound: 70.5% (pre-intervention) and 94.1% (post-intervention). The better the quality of the request, the better the acceptability of the studies and the greater the number of pathological conditions identified. CONCLUSIONS: Guidelines for ultrasound improve the quality of requests, diagnostic orientation and acceptability of the studies.

Diffusion tensor imaging, intracranial vascular resistance and cognition in middle-aged asymptomatic subjects.

BACKGROUND: The contribution of traditional vascular risk factors to cognitive impairment and dementia is well known. However, in order to obtain possible targets for prevention of vascular cognitive impairment (VCI), it may be important to identify other early and noninvasive markers in asymptomatic middle-aged adults. The calculation of middle cerebral artery-pulsatility index (MCA-PI) is an ultrasonologic, noninvasive, validated and easily reproducible technique to assess increased distal resistance to blood flow. This study aims to assess the relationship between MCA-PI, microstructural white matter (WM) integrity and cognition in a middle-aged asymptomatic population. METHODS: Ninety-five participants from the Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) neuropsychology study were included. Subjects were 50-65 years old, free from dementia and without history of vascular disease. Transcranial color-coded duplex ultrasound examination was performed to assess MCA-PI as a measure of vascular resistance. WM integrity was evaluated by fractional anisotropy (FA) measurements of diffusion tensor images (DTI) acquired on a 3T-MRI. The neuropsychological battery was specifically selected to be sensitive to VCI, and included tests that were grouped into six cognitive domains: executive functioning, attention, verbal fluency, memory, visuospatial skills and psychomotor speed. A multivariate linear regression model adjusted for age, gender, years of education, diabetes and hypertension was performed. RESULTS: MCA-PI was significantly associated with WM disintegration in different tracts (fornix, corticospinal and anterior thalamic), all p < 0.05 uncorrected. Both mean MCA-PI and mean FA of those significant tracts were independently associated with poor performance in attention, psychomotor speed, and visuospatial skills after adjustment for age, gender, years of education, and vascular risk factors (all p < 0.05). MCA-PI was independently associated with lower scores in all cognitive domains, except for visuospatial skills. CONCLUSIONS: Our data suggest that MCA-PI may be related to WM disintegration and early vascular cognitive impairment in middle-aged subjects. Although further prospective studies are needed to provide evidence for its validity in longitudinal studies, our results support the proposal of including MCA-PI as part of clinical assessment in order to identify targets for VCI prevention.

Analysis of three strategies to increase screening coverage for cervical cancer in the general population of women aged 60 to 70 years: the CRICERVA study.

BACKGROUND: Cervical cancer is a frequently diagnosed cancer in women worldwide. Despite having easy preventive and therapeutic approaches, it is an important cause of mortality among women. METHODS: The CRICERVA study is a cluster clinical trial which assigned one of three interventions to the target population registered in Cerdanyola, Barcelona. Among the 5,707 resident women aged 60 to 70 years in the study area, women with no record of cervical cytology over the last three years were selected. The study included four arms: three interventions all including a pre-assigned date for screening visit and i) personalized invitation letter; ii) adding to i) an informative leaflet; and, iii) in addition to ii) a personalized appointment reminder phone call, and iv) no specific action taken (control group). Participants were offered a personal interview about social-demographic characteristics and about screening attitudes. Cervical cytology and HPV DNA test (HC2) were offered as screening tests. In the case of screening positive in any of these tests, the women were followed up until a full diagnosis could be obtained. The effect size of each study arm was estimated as the absolute gain in coverage between the original coverage and the final coverage. RESULTS: From the intervention groups (4,775 women), we identified 3,616 who were not appropriately screened, of which 2,560 women answered the trial call and 1,376 were amenable to screening. HPV was tested in 920 women and cervical cytology in all 1,376. Overall, there was an absolute gain in coverage of 28.8% in the intervention groups compared to 6% in the control group. Coverage increased from 51.2% to 76.0% in strategy i); from 47.4% to 79.0% in strategy ii) and from 44.5% to 74.6% in strategy iii). Lack of information about the relevance of screening was the most important factor for not attending the screening program. CONCLUSIONS: The study confirms that actively contacting women and including a date for a screening visit, notably increased participation in the screening program. Efforts to improve health education in preventative activities are warranted. TRIAL REGISTRATION: Clinical Trials.gov Identifier NCT01373723. Registered 14 June 2011.

[Non-invasive markers of fibrosis in the diagnosis of non-alcoholic fatty liver disease]. / Marcadores no invasivos de fibrosis en el diagnóstico del hígado graso no alcohólico.

OBJECTIVE: To analyze the utility of three indices to predict hepatic fibrosis in the detection of non-alcoholic fatty liver disease (NAFLD) as a non-invasive method in primary care. DESIGN: We performed a descriptive, cross-sectional, multicenter study with a populational base from 25 primary care centers in the province of Barcelona. PARTICIPANTS: Healthy individuals aged 17 to 83 years randomly selected from the Primary Care Computer System. METHODS: Medical history, physical examination, and blood analyses were used to determine the following predictive indices of fibrosis; HAIR (hypertension, alanine-aminotransferase, insulin resistance); Fatty Liver Index (FLI) (body mass index, gammaglutamyl-transpeptidase, triglycerides, abdominal perimeter) and Lipid Accumulation Product (LAP) (triglycerides, abdominal perimeter), and abdominal echography. RESULTS: We included 702 individuals; 58% were women and the mean age was 53±14 years. The FLI was positive in 30.8%, HAIR was positive in 6.7%, and LAP was positive in 15.5%. Agreement among the three indices ranged from 63.1% to 84.9%, with kappa indices between 0.18 and 0.50. A total of 184 individuals met the echographic criteria of NAFLD, representing a prevalence of 26.29%. The prevalence of NAFLD in patients with positive FLI, HAIR and LAP indices was 46.8%, 68.1% and 56%, respectively. The index with the greatest sensitivity for NAFLD was tFLI≥60 with 84%. Specificity was highest for HAIR and LAP with 97% and 91%, respectively. CONCLUSIONS: FLI, HAIR and LAP are highly prevalent and have been shown to be independent markers for the diagnosis of NAFLD. Because of the lack of concordance between the indices, different prevalences are obtained, thus requiring criteria to be unified in order to obtain a more useful index for the diagnosis of NAFLD.

Cognitive patterns in relation to biomarkers of cerebrovascular disease and vascular risk factors.

BACKGROUND: Risk factors for vascular cognitive impairment (VCI) are the same as traditional risk factors for cerebrovascular disease (CVD). Early identification of subjects at higher risk of VCI is important for the development of effective preventive strategies. In addition to traditional vascular risk factors (VRF), circulating biomarkers have emerged as potential tools for early diagnoses, as they could provide in vivo measures of the underlying pathophysiology. While VRF have been consistently linked to a VCI profile (i.e., deficits in executive functions and processing speed), the cognitive correlates of CVD biomarkers remain unclear. In this population-based study, the aim was to study and compare cognitive patterns in relation to VRF and circulating biomarkers of CVD. METHODS: The Barcelona-AsIA Neuropsychology Study included 747 subjects older than 50, without a prior history of stroke or coronary disease and with a moderate to high vascular risk (mean age, 66 years; 34.1% women). Three cognitive domains were derived from factoral analysis: visuospatial skills/speed, verbal memory and verbal fluency. Multiple linear regression was used to assess relationships between cognitive performance (multiple domains) and a panel of circulating biomarkers, including indicators of inflammation, C-reactive protein (CRP) and resistin, endothelial dysfunction, asymmetric dimethylarginine (ADMA), thrombosis, plasminogen activator inhibitor 1 (PAI-1), as well as traditional VRF, metabolic syndrome and insulin resistance (homeostatic model assessment for insulin resistance index). Analyses were adjusted for age, gender, years of education and depressive symptoms. RESULTS: Traditional VRF were related to lower performance in verbal fluency, insulin resistance accounted for lower performance in visuospatial skills/speed and the metabolic syndrome predicted lower performance in both cognitive domains. From the biomarkers of CVD, CRP was negatively related to verbal fluency performance and increasing ADMA levels were associated with lower performance in verbal memory. Resistin and PAI-1 did not relate to cognitive function performance. CONCLUSION: Vascular risk factors, and markers of inflammation and endothelial dysfunction predicted lower performance in several cognitive domains. Specifically, cognitive functions associated with CRP are typically affected in VCI and overlap those related to VRF. ADMA indicated a dissociation in the cognitive profile involving verbal memory. These findings suggest that inflammation and endothelial dysfunction might play a role in the predementia cognitive impairment stages.

Measurement of the ankle brachial index with a non-mercury sphygmomanometer in diabetic patients: a concordance study.

BACKGROUND: The removal of mercury sphygmomanometers from health centers requires the validation of other instruments to measure blood pressure in the limbs to calculate the ankle-brachial index (ABI). METHODS: Descriptive cross-sectional study of agreement between two measurement methods in type 2 diabetes patients from three urban primary healthcare centres in the Barcelonès Nord i Maresme area (Catalonia, Spain). RESULTS: 211 patients were included, from these, 421 limbs were available for study. The mean age of the participants was 67 years (SD = 10), 51.7% were women. CONCLUSION: The combination of a Doppler device with the hybrid sphygmomanometer is a simple and reliable method to measure ABI showing that hybrid sphygmomanometer is a good alternative to the use of mercury sphygmomanometers.