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 ).

Impact of Dietary Habit, Iodine Supplementation and Smoking Habit on Urinary Iodine Concentration During Pregnancy in a Catalonia Population.

(1) Background: The nutritional status of women during pregnancy can have a considerable effect on maternal and fetal health, and on the perinatal outcome. Aim: to assess the changes occurring in dietary iodine intake, potassium iodide supplementation, and smoking habit, and the impact of these changes on the urinary iodine concentration (UIC) during pregnancy in a population of women in Catalonia (Spain). (2) Methods: Between 2009-2011, an observational study included a cohort of women whose pregnancies were monitored in the public health system in the Central and North Metropolitan areas of Catalonia. Women received individual educational counseling, a dietary questionnaire was completed, and a urine sample was collected for iodine determination at each trimester visit. (3) Results: 633 (67.9%) women answered the questionnaire at all 3 visits. The percentage of women with a desirable UIC (≥150 µg/L) increased from the first to the second trimester and remained stable in the third (57.3%, 68.9%, 68%; p < 0.001). Analysis of the relationship between UIC≥150 µg/L and the women's dietary habits showed that the percentage with UIC ≥150 µg/L increased with greater consumption of milk in the first trimester, and the same was true for iodized salt use in all three trimesters and iodine supplementation in all three. (4) Conclusion: During pregnancy, increased intake of milk, iodized salt, and iodine supplements were associated with an increase in the UIC.

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.

Economic evaluation of three populational screening strategies for cervical cancer in the county of Valles Occidental: CRICERVA clinical trial.

BACKGROUND: A high percentage of cervical cancer cases have not undergone cytological tests within 10 years prior to diagnosis. Different population interventions could improve coverage in the public system, although costs will also increase. The aim of this study was to compare the effectiveness and the costs of three types of population interventions to increase the number of female participants in the screening programmes for cancer of the cervix carried out by Primary Care in four basic health care areas. METHODS/DESIGN: A cost-effectiveness analysis will be performed from the perspective of public health system including women from 30 to 70 years of age (n = 20,994) with incorrect screening criteria from four basic health care areas in the Valles Occidental, Barcelona, Spain. The patients will be randomly distributed into the control group and the three intervention groups (IG1: invitation letter to participate in the screening; IG2: invitation letter and informative leaflet; IG3: invitation letter, informative leaflet and a phone call reminder) and followed for three years. Clinical effectiveness will be measured by the number of HPV, epithelial lesions and cancer of cervix cases detected. The number of deaths avoided will be secondary measures of effectiveness. The temporal horizon of the analysis will be the life expectancy of the female population in the study. Costs and effectiveness will be discounted at 3%. In addition, univariate and multivariate sensitivity analysis will be carried out. DISCUSSION: IG3 is expected to be more cost-effective intervention than IG1 and IG2, with greater detection of HPV infections, epithelial lesions and cancer than other strategies, albeit at a greater cost. TRIAL REGISTRATION: Clinical Trials.gov Identifier NCT01373723.

[Validity of the MONICA cardiovascular questionnaire compared with clinical records]. / Validez del cuestionario cardiovascular MONICA comparado con la historia clínica.

OBJECTIVE: To assess the validity of the questionnaire Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) compared with clinical records. METHODS: A descriptive, prospective, multicenter study was performed within the framework of the Peripheral Arterial Disease Study (PERART) in 3,329 persons aged >50 years old. The sample was selected by simple random sampling in 32 primary health care centers. The diagnoses included were acute myocardial infarction, angina pectoris, cerebrovascular disease, hypertension, diabetes mellitus, and hypercholesterolemia. Treatment variables were also considered (antihypertensive, lipid-lowering and hypoglycemic agents or insulin, as well as antiplatelet or anticoagulant agents). The sensitivity, specificity, predictive values, and kappa index were computed to test the validity of the MONICA questionnaire. RESULTS: The mean age was 65 years (SD 8.9) and 54.8% were women. The sensitivity of the questionnaire was >90% for all the variables apart from angina pectoris (89.9%) and cerebrovascular disease (86.5%). Specificity was also >90%, except for angina pectoris (88.3%) and hypercholesterolemia (77.5%). The positive predictive value was >90% for all the treatments; >80% for angina pectoris, acute myocardial infarction and hypertension; 79.4% for cerebrovascular disease; 79.1% for hypercholesterolemia and 73.4% for diabetes mellitus. The negative predictive value was >90% for all the variables. The kappa indexes were >0.80 for all the variables apart from hypercholesterolemia (0.69) and diabetes mellitus (0.79). CONCLUSIONS: The MONICA cardiovascular questionnaire is valid in the assessment of cardiovascular disease, risk factors and treatments in patients aged >50 years old.

Contribution of C-reactive protein to the diagnosis and assessment of severity of community-acquired pneumonia.

STUDY OBJECTIVE: To assess the usefulness of serum C-reactive protein (CRP) in the diagnosis and treatment approach of patients with community-acquired pneumonia (CAP). DESIGN: Population-based case-control study. SETTING: A mixed residential-industrial urban area of 74,368 adult inhabitants in the Maresme region (Barcelona, Spain). PATIENTS: From December 1993 to November 1995, all subjects who were > 14 years of age, were living in the area, and had received a diagnosis of CAP, which had been confirmed by chest radiographs and compatible clinical outcome, were registered. Patients from residential care facilities were excluded. Serum samples were assayed for CRP in the acute phase of the disease. Data from 201 patients with CAP were compared with 84 healthy control subjects matched by age, sex, and municipality, as well as with 25 patients with initially suspected pneumonia that was not confirmed at follow-up. Median CRP levels were 110.7, 1.9, and 31.9 mg/L, respectively. The thresholds of the test for discriminating among these three groups of subjects were 11.0 and 33.15 mg/L. RESULTS: Eighty-nine patients (44.8%) had an identifiable etiology. The most common pathogens were Streptococcus pneumoniae, viruses, and Chlamydia pneumoniae, followed by Mycoplasma pneumoniae, Legionella pneumophila, and Coxiella burnetii. There were statistically significant differences in the median CRP levels in pneumococcal (166.0 mg/L) and L pneumophila (178.0 mg/L) etiologies compared to other causative pathogens. Lower levels of CRP were found in pneumonia caused by viruses and C burnetii as well as in negative microbiological findings. The median CRP levels in hospitalized patients were significantly higher than in outpatients (132.0 vs 76.9 mg/L, respectively; p < 0.001). Considering a cut point of 106 mg/L in men and 110 mg/L in women for deciding about the appropriateness of inpatient care, CRP levels showed a sensitivity of 80.51% and a specificity of 80.72%. CONCLUSIONS: Serum CRP level is a useful marker for establishing the diagnosis of CAP in adult patients with lower respiratory tract infections. High CRP values are especially high in patients with pneumonias caused by S pneumoniae or L pneumophila. Moreover, high CRP values are suggestive of severity, which may be of value in deciding about the appropriateness of inpatient care.