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).

Validation of gout diagnosis in electronic primary care medical records: A population-based study.

OBJECTIVE: The main objective of the study was to see the concordance between the diagnosis of gout recorded in primary care electronic medical records and the ACR/EULAR 2015 classification criteria. METHODS: A cross-sectional study was conducted using electronic medicals records in 7 primary care centres of Barcelona. Patients' data to study clinical diagnose and management was gathered from the primary care electronic medical records of the Catalonian health institute (Institut Català de la Salut, ICS) and phone interview. Patients were considered to have gout if they scored 8 or more points on the EULAR/ACR 2015 classification criteria for gout. RESULTS: In total, 70.9% of the patients with a gout diagnosis met ACR/EULAR 2015 criteria. Adding a hyperuricemia in a blood test in the EMR increased the percentage to 78.9%. 29.8% of the gout patients were not receiving urate-lowering therapy. 62.3% of the treated patients did not achieve the target uricemia (< 6mg/dL). CONCLUSIONS: The majority of gout patients from primary care electronic medical records fulfil ACR/EULAR gout criteria. This database can be used for observational studies. In most of the gout patients the urate target was not achieved.

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 ).

A programme for early diagnosis of atrial fibrillation: a multi-centre study in primary care.

BACKGROUND: Atrial fibrillation (AF) is a morbid disease whose complications can be prevented if prompt and correctly treated. OBJECTIVE: To assess the usefulness of an early AF diagnosis programme in at-risk individuals in primary care centres. METHODS: In an open-label, multi-centre, controlled interventional study, individuals with one or more risk factors for AF but without known AF were enrolled. They were allocated to intervention and control groups in a 1:2 ratio. Participants in the intervention group had three clinical and educational visits (0, 6 and 12 months). In intervention subgroup A, an electrocardiogram (ECG) was performed at each visit and in subgroup B, only if arrhythmia was detected on auscultation. After 2 years, the medical records of all participants were reviewed. Participants diagnosed with AF were followed for two additional years. RESULTS: Of the total 2231 participants enrolled, 1503 (67.36%) were allocated to the control group and 728 (32.63%) to the intervention groups (355 in subgroup A, 373 subgroup B). The groups showed similar clinical characteristics. New-onset AF was diagnosed in 38 patients. Early detection in subgroup B was similar to subgroup A and superior to control group (3.2% versus 1.2%, hazard ratio 3.149, 95% confidence interval 1.503-6.597, P = 0.002). AF patients in subgroups A and B had similar long-term complications and a tendency for fewer complications than AF patients in the control group. CONCLUSIONS: An intervention programme consisting of health education, systematic auscultation and opportunistic ECG by a primary care provider is a useful method for the early diagnosis of AF.

Use of proton pump inhibitors and risk of fragility hip fracture in a Mediterranean region.

OBJECTIVE: To determine whether there is an increased risk of hip fracture associated with the use of proton pump inhibitors in a Mediterranean area after adjusting for other potential risk factors. METHODS: Retrospective multicenter case-control study carried out in 6 primary health care centers in Catalonia, Spain. Cases were patients aged 50years and over with a fragility hip fracture registered between January 2007 and December 2010, matched with 2 controls by sex and age. DATA COLLECTED: use of proton pump inhibitors (type, dosage) in the 5years previous to the hip fracture, socio-demographic data, body mass index, alcohol and tobacco consumption as well as health conditions and drugs associated with an increase risk of fragility hip fracture. RESULTS: 358 cases were matched with 698 controls. The mean age was 82years old in both groups. Women represented 77.1% in the case group and 76.9% in the control group. Crude association between proton pump inhibitors and hip fracture was 1.44 (95% CI, 1.09-1.89) and adjusted OR was 1.24 (95% CI, 0.93-1.65). No association was found with the continuous or discontinuous use of proton pump inhibitors, OR 1.17 (95% CI, 0.77-1.79), and OR of 1.16 (95% CI, 0.85-1.60) respectively. No association was found when restricting the analysis by sex, OR of 1.19 (95% CI, 0.27-5.14) or by age, younger or older than 80years, OR of 0.72 (95% CI, 0.24-2.15). CONCLUSION: The use of proton pump inhibitors was not associated with an increased risk of hip fracture after adjusting for other risk factors in a Mediterranean area. This result suggests the existence of protective environmental factors linked to this southern area of Europe that eventually could compensate for the potential harm produced by proton pump inhibitors.

[Adverse effects of antiarrhythmic drugs in patients with atrial fibrillation in primary care]. / Estudio sobre los efectos adversos de los fármacos antiarrítmicos en pacientes con fibrilación auricular atendidos en un Centro de Atención Primaria.

BACKGROUND AND OBJECTIVE: To determine the adverse effects (AE) of antiarrhythmic drugs used to treat atrial fibrillation (AF) in routine clinical practice. PATIENTS AND METHODS: A retrospective, observational, population-based study of all patients diagnosed of AF requiring long-term treatment with antiarrhythmic drugs. We performed also a descriptive analysis of the type of EA, and their management (diagnostic techniques, laboratory tests, drug treatment, number of visits to health services, emergency visits, hospitalizations and surgeries). RESULTS: We included 400 patients. Overall, 688 treatments were started, 34 of which (4.9%) were implied in 32 EA in 30 patients. The most frequent EA were hypothyroidism (28.1%), hyperthyroidism (25%) and bradycardia (9.38%). In absolute numbers, class III drugs (Vaughan-Williams classification) were associated with a higher number of AE (p=0.001). The number of AE/100 patients-year was: class I 0.42 (0.01-1.15%), class II 2.55 (0.68-5.13%), class III 4.70 (2.98-6.64%), class IV 1.18 (0.14-2.80%), digoxin 0.41 (0.08-1.19). Individually, the drugs with a higher rate were sotalol, bisoprolol and amiodarone (5.70, 5.37 and 4.59 respectively). 93.75% of EA required visits to health services, 59.38% laboratory tests and 56.25% diagnostic techniques. The most frequent visits were scheduled for primary care (75%), followed by scheduled visits to outpatient cardiology (21.9%). 71.9% of EA were resolved without any sequel and one patient died. CONCLUSIONS: Antiarrhythmic drugs for the management of AF are associated with the presence of AE, mainly class III drugs. In most cases they are not serious, but imply important health resources.

Sex differences in the treatment of patients with atrial fibrillation: population-based study in a local health district.

Differences in the treatment of atrial fibrillation between men and women were investigated by using patients in a local health district as a reference population. The study included 688 patients (359 female) who presented with atrial fibrillation. Women were older, more frequently had heart failure, and were more often functionally dependent than men. With regards to the management of atrial fibrillation, women were prescribed digoxin more frequently than men, but underwent electrical cardioversion less often, were less frequently seen by a cardiologist, and understood less about their treatment. After stratifying the findings by age and adjusting for heart failure and the degree of functional dependence, it was observed that women aged over 85 years were prescribed digoxin more often than men, while women aged under 65 years underwent cardioversion less often than men. In conclusion, gender differences observed in the treatment of atrial fibrillation cannot be fully explained by differences in clinical characteristics between men and women in the population.

[Impact of implementing common guidelines at different care levels in a healthcare area on the improvement of atrial fibrillation treatment]. / Impacto de la instauración de un protocolo común en los distintos niveles asistenciales de un área sanitaria para la mejora del tratamiento de la fibrilación auricular.

INTRODUCTION AND OBJECTIVES: Atrial fibrillation (AF) is treated in different settings by different specialists. The objective of the study was to analyze the impact of the implementation of a practice guideline about AF treatment common to the different levels of health attention on the adequacy of AF treatment and on corrective interventions. METHODS: The study was performed in two periods, before and after the implementation of a practice guideline common to all health care levels. In each period, patients with AF who consulted to any of the health care attention levels of a sanitary area were included. Data referring to treatment and compliance of guidelines before and after the visit were recorded prospectively. RESULTS: 293 patients were included in the first period and 267 in the second one. After the guideline implementation, adequacy before the visit, both of antiarrythmic treatment and of antithrombotic prophylaxis were superior than in the first period (80% vs 71%, P=.009 and 81% vs 67%, P<.001, respectively). The percentage of improvement in case of a previous inadequacy of antithrombotic prophylaxis was significantly better in the second period than in the first one (35% vs 9%, P<.001), but the percentage of corrective interventions on antiarrhythmic treatment was similar in both periods. CONCLUSIONS: The implementation of a common practice guideline in the different levels of health care attention is useful to improve adequacy of AF treatment, although there is still some reluctance to change an inadequate antiarrythmic treatment.