Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721.

Applying an equity lens to liver health and research in Europe.

Liver disease is a major cause of premature death and disability in Europe. However, morbidity and mortality are not equally distributed in the population. In spite of this, there are few studies addressing the issue of health inequalities in Europe. In this Public Health Corner article, we compare the research conducted on health inequalities in Europe to other settings and highlight the main differences based upon an extensive review of the literature. We report that only 10.2% of studies were led by European institutions or conducted in European populations and that certain topics such as alcohol-related liver disease are largely overlooked. In addition, we discuss the relevance of including a health equity lens when conducting clinical, epidemiological and health systems' research in liver disease and set out the basic requirements to tackle health inequalities in liver disease in Europe.

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 ).

What do we know about the impact of economic recessions on mortality inequalities? A critical review.

Historically, there has been a debate on the effects of recessions on population health, and especially on mortality and its distribution across different social groups. This paper contributes to this discussion by means of a critical review of the research on the impact of economic recessions on mortality inequalities in the period 1980-2020. We analyzed 19 studies according to their mortality outcomes, socioeconomic indicators, design, analysis, and main findings. Twelve studies focused on European countries or urban areas, two on Asian countries, two on Russia, one on Asia and Europe, one on the USA, and one in Somalia. Five articles included cross-country comparisons (four between European countries or cities and one between Asian and European countries). The Great Recession of 2008 was the most researched economic crisis, followed by country-specific crises in the 90s, the fall of the Soviet Union, and some crises during the 80s. Most studies (n = 15) showed an overall or partial increase in mortality inequalities after an economic recession. However, two papers found a decrease in mortality inequalities due to the worsening of the health of the upper and middle classes, one article found a decrease in inequalities due to a general improvement in population health, and a study found a "slow-down" effect of pre-existent mortality inequalities.

The case for planetary health prevention.

The lack of preparedness and the adoption of a reactive approach underlie many mistakes in handling the COVID-19 pandemic. We need a vision with a proactive approach to planetary health prevention, that is suited for addressing the neglected systemic determinants of health which generate disease, inequality and environmental degradation, and capable of anticipating known and unknown risks, and foreseeing possible threatening scenarios. To achieve a healthy, equitable and sustainable future, it is time to make health prevention planetary.

What Do We Know about Inequalities in NAFLD Distribution and Outcomes? A Scoping Review.

With prevalence high and rising given the close relationship with obesity and diabetes mellitus, non-alcoholic fatty liver disease (NAFLD) is progressively becoming the most common chronic liver condition worldwide. However, little is known about the health inequalities in NAFLD distribution and outcomes. This review aims to analyze health inequalities in NAFLD distribution globally and to assess the health disparities in NAFLD-related outcomes. We conducted a scoping review of global health inequalities in NAFLD distribution and outcomes according to gender/sex, ethnicity/race, and socioeconomic position from PubMed's inception to May 2021. Ultimately, 20 articles were included in the review, most (75%) of them carried out in the United States. Males were found to have a higher NAFLD prevalence (three articles), while available evidence suggests that women have an overall higher burden of advanced liver disease and complications (four articles), whereas they are less likely to be liver-transplanted once cirrhosis develops (one article). In the US, the Hispanic population had the highest NAFLD prevalence and poorer outcomes (seven articles), whereas Whites had fewer complications than other ethnicities (two articles). Patients with low socioeconomic status had higher NAFLD prevalence (four articles) and a higher likelihood of progression and complications (five articles). In conclusion, globally there is a lack of studies analyzing NAFLD prevalence and outcomes according to various axes of inequality through joint intersectional appraisals, and most studies included in our review were based on the US population. Available evidence suggests that NAFLD distribution and outcomes show large inequalities by social group. Further research on this issue is warranted.

Health Inequalities in the Time of COVID-19: The Globally Reinforcing Need to Strengthen Health Inequalities Research Capacities.

The full impact of coronavirus disease 2019 (COVID-19) is yet to be well established; however, as the pandemic spreads, and early results emerge, unmet needs are being revealed, and pressing questions are being asked about who is most affected, how, where, and in what ways government responses might be exacerbating inequalities. A number of scholars have called for more in-depth critical research on COVID-19 and health inequalities to produce a strong empirical evidence based on these issues. There are also justifiable concerns about the scarcity of health-equity actions oriented analyses of the situation and calls for more empirical evidence on COVID-19 and health inequalities. A preliminary condition to establish this type of information is strong capacity to conduct health inequalities research. Worldwide, however, this type of capacity is limited, which, alongside other challenges, will likely hinder capacities of many countries to develop comprehensive equity-oriented COVID-19 analyses, and adequate responses to present and future crises. The current pandemic reinforces the pending need to invest in and strengthen these research capacities. These capacities must be supported by widespread recognition and concern, cognitive social capital, and greater commitment to coordinated, transparent action, and responsibility. Otherwise, we will remain inadequately prepared to respond and meet our society's unmet needs.

Going 'trans-E-3-ve': Educational principles for a new generation of medical students.

Educating medical students represents a thrilling yet challenging task. In an era of research breakthroughs but also global health setbacks, there is a risk that scientists and educators focus on highly specialized areas of knowledge, neglecting interrelated systemic issues. Here, we argue that the education of medical students should be embraced using a different strategy remodeled through what we call a 'tranS-E-3-ve' lens. In this new approach, there is no room for scientific reductionism. Instead, health disciplines should be seen from a translational, trans-disciplinary and trans-territorial scope, and should be sensitive to problems and pathways that link global phenomena to health. While current health issues cannot be approached without an equity lens, there are three interconnected dimensions of health that should pervade the content, goals, and design of academic curricula in medical schools: (1) exposome, or the understanding of the environmental contributors to health and disease; (2) identification of the mechanisms involved in the interactions between the elements that constitute complex systems; and (3) 'inner space', or the study of how cells communicate within the human body.

A cross-sectional study of the public health response to non-alcoholic fatty liver disease in Europe.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a growing public health problem worldwide and has become an important field of biomedical inquiry. We aimed to determine whether European countries have mounted an adequate public health response to NAFLD and non-alcoholic steatohepatitis (NASH). METHODS: In 2018 and 2019, NAFLD experts in 29 European countries completed an English-language survey on policies, guidelines, awareness, monitoring, diagnosis and clinical assessment in their country. The data were compiled, quality checked against existing official documents and reported descriptively. RESULTS: None of the 29 participating countries had written strategies or action plans for NAFLD. Two countries (7%) had mentions of NAFLD or NASH in related existing strategies (obesity and alcohol). Ten (34%) reported having national clinical guidelines specifically addressing NAFLD and, upon diagnosis, all included recommendations for the assessment of diabetes and liver cirrhosis. Eleven countries (38%) recommended screening for NAFLD in all patients with either diabetes, obesity and/or metabolic syndrome. Five countries (17%) had referral algorithms for follow-up and specialist referral in primary care, and 7 (24%) reported structured lifestyle programmes aimed at NAFLD. Seven (24%) had funded awareness campaigns that specifically included prevention of liver disease. Four countries (14%) reported having civil society groups which address NAFLD and 3 countries (10%) had national registries that include NAFLD. CONCLUSIONS: We found that a comprehensive public health response to NAFLD is lacking in the surveyed European countries. This includes policy in the form of a strategy, clinical guidelines, awareness campaigns, civil society involvement, and health systems organisation, including registries. LAY SUMMARY: We conducted a survey on non-alcoholic fatty liver disease with experts in European countries, coupled with data extracted from official documents on policies, clinical guidelines, awareness, and monitoring. We found a general lack of national policies, awareness campaigns and civil society involvement, and few epidemiological registries.

Evaluation of the effectiveness and equity of the maternity protection reform in Chile from 2000 to 2015.

INTRODUCTION: According to the International Labor Organization, Maternity Protection (MP) policies try to harmonize child care and women's paid work, without affecting family health and economic security. Chile Law 20.545 (2011) increased benefits for economically active women and reduced requirements for accessing these benefits. The goals of the reform included: 1) to increase MP coverage; and 2) to reduce inequities in access to the benefits. METHOD: This study uses two data sources. First, using individual data routinely collected from 2000 to 2015, yearly MP coverage access over time was calculated. Second, using national representative household surveys collected before and after the Law (2009 and 2013), coverage and a set of measures of inequality were estimated. To compare changes over time, we used non-experimental, before-after intervention design for independent samples. For each variable, we estimated comparative proportions at 95% confidence interval before and after the intervention. Additionally, we included multivariate and propensity score analysis. RESULTS: Between 2000 and 2015, MP coverage grew from 24.4% to 44.8%. Using comparable 2009 and 2013 survey data, we observed the same trend, with 31.6% of estimated MP coverage in 2009, escalating to 39.5% in 2013. We conclude that: 1) after the reform, there was an increase in MP coverage; and, 2) there was no significant reduction of inequities in the distribution of MP benefits. DISCUSSION/CONCLUSION: Few scientific evaluations of MP reforms have been conducted worldwide; even fewer including an equity analysis. This study provides an empirically-based evaluation of MP reform from both a population-level and an equity-focused perspective. We conclude that this reform needs to be complemented with other policies to ensure maternity protection in terms of access and equity in a country with deep socioeconomic stratification.

Hepatitis C services at harm reduction centres in the European Union: a 28-country survey.

BACKGROUND: In the context of the WHO's 2016 Viral Hepatitis Strategy and the introduction of treatment that can cure more than 95% of cases with hepatitis C virus (HCV) infection, the European Joint Action on HIV and Co-infection Prevention and Harm Reduction (HA-REACT) undertook a study in the member states of the European Union (EU). It aimed to determine service providers' understanding of the current services in their respective countries and the barriers experienced by PWID in accessing HCV testing, care and treatment services in their country. METHODS: In 2017, 38 purposively selected harm reduction service providers completed a 26-item English-language online survey addressing the availability, accessibility and funding of HCV services at harm reduction centres. HCV-related data and reported findings were extracted by country or by responding organization. RESULTS: Responses were received from all EU member states. Respondents from 23 countries reported that HCV tests are offered by harm reduction services in their countries, and eight countries reported that addiction specialists in their countries are able to prescribe HCV therapy. Almost half of the respondents (45%) said that their respective organizations had established referral systems with centres providing HCV treatment. CONCLUSIONS: Not all EU member states have harm reduction services that provide HCV tests, and many do not have established referral systems with treatment providers. Moreover, the inability of addiction specialists to prescribe HCV treatment points to missed opportunities to make treatment more accessible. Further, discrepancies were noted between the available HCV services and stakeholders' knowledge about their availability.

Systemic Factors and Barriers That Hamper Adequate Data Collection on the HIV Epidemic and Its Associated Inequalities in Countries With Long-Term Armed Conflicts: Lessons From Colombia.

Although advances in treatment and diagnosis have transformed HIV into a chronic disease in high-income countries, a spectrum of structural, political, sociocultural, and health system barriers hamper early diagnosis and timely treatment of HIV in many middle- and low-income countries. In most Latin American countries, in spite of the great improvement in access to antiretroviral therapy, a large proportion of individuals infected with HIV do not know their status. In Colombia, the Joint United Nations Programme on HIV/AIDS currently estimates a much larger number of HIV cases than the number reported by Colombian authorities. Potential reasons for underdiagnosis and underreporting include sociocultural factors such as social stigma, restrictions in access to health care, a lack of public health research and robust surveillance systems, and the particular recent history and social situation related to the armed conflict the country has suffered through for several decades. Lessons from Colombia may be helpful in monitoring, understanding, and tackling the HIV epidemic in countries with long-term armed conflicts.

Inequalities in global health inequalities research: A 50-year bibliometric analysis (1966-2015).

BACKGROUND: Increasing evidence shows that health inequalities exist between and within countries, and emphasis has been placed on strengthening the production and use of the global health inequalities research, so as to improve capacities to act. Yet, a comprehensive overview of this evidence base is still needed, to determine what is known about the global and historical scientific production on health inequalities to date, how is it distributed in terms of country income groups and world regions, how has it changed over time, and what international collaboration dynamics exist. METHODS: A comprehensive bibliometric analysis of the global scientific production on health inequalities, from 1966 to 2015, was conducted using Scopus database. The historical and global evolution of the study of health inequalities was considered, and through joinpoint regression analysis and visualisation network maps, the preceding questions were examined. FINDINGS: 159 countries (via authorship affiliation) contributed to this scientific production, three times as many countries than previously found. Scientific output on health inequalities has exponentially grown over the last five decades, with several marked shift points, and a visible country-income group affiliation gradient in the initiation and consistent publication frequency. Higher income countries, especially Anglo-Saxon and European countries, disproportionately dominate first and co-authorship, and are at the core of the global collaborative research networks, with the Global South on the periphery. However, several country anomalies exist that suggest that the causes of these research inequalities, and potential underlying dependencies, run deeper than simply differences in country income and language. CONCLUSIONS: Whilst the global evidence base has expanded, Global North-South research gaps exist, persist and, in some cases, are widening. Greater understanding of the structural determinants of these research inequalities and national research capacities is needed, to further strengthen the evidence base, and support the long term agenda for global health equity.

AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis.

The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) (P = 0.343), while the medians (interquartile ranges [IQRs]) for log10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) (P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis.

Financial, nonfinancial and editors' conflicts of interest in high-impact biomedical journals.

PURPOSE: To assess financial, nonfinancial and editors' conflicts of interest (COI) disclosure policies among the most influential biomedical journals publishing original research. MATERIALS AND METHODS: We conducted a cross-sectional study of 399 high-impact biomedical journals in 27 biomedical categories of the Journal Citation Reports (JCR) in December 2011. Information relevant to COI and requirements for disclosures that was publicly available on journal websites was collected. RESULTS: While financial COI disclosures were required by 358 (89.7%) and nonfinancial by 280 (70.2%) journals, 155 (38.8%) required editors' disclosures. Journals in the first decile of the JCR classification scored significantly higher than those in the second decile for all disclosure policies. Ninety (22.6%) journals were published by Elsevier and 59 (14.8%) by Wiley-Blackwell, with Elsevier scoring significantly better in financial disclosure policies (P = 0.022). Clinical journals scored significantly higher than basic journals for all disclosure policies. No differences were observed between open-access (n = 25) and nonopen-access (n = 374) journals for any type of disclosure. Somewhat incoherently, authors' disclosure statements were included in some published manuscript in 57.1% of journals without any COI disclosure policies. CONCLUSIONS: Authors' financial COI disclosures were required by about 90% of high-impact clinical and basic journals publishing original research. Unlike recent studies showing a significantly lower prevalence of nonfinancial compared with financial disclosures, the former were required by about 70% of journals, suggesting that editors are increasingly concerned about nonfinancial competing interests. Only 40% of journals required disclosure of editors' COI, in conflict with the recommendations of the most influential editors' associations.

Should alternatives to conventional hospitalisation be promoted in an era of financial constraint?

BACKGROUND: Because the current economic crisis has led to austerity in health policies, with severe restrictions on public health care, avoiding unnecessary admissions and shortening hospital stays is rapidly becoming an urgent priority. Alternatives to hospitalisation replace or shorten hospital processes, including diagnosis, monitoring, treatment and follow-up. This review aims to present the available evidence on alternatives to conventional hospitalisation for medical disorders; options for surgery, psychiatry and palliative care are largely excluded. MATERIALS AND METHODS: Narrative review. RESULTS: The main alternatives to conventional hospitalisation include day centres (DC), quick diagnosis units (QDU), hospital at home (HaH) and, in some circumstances, telemonitoring. DC increase patient comfort, reduce costs and can improve efficiency. In generally healthy patients with suspected severe disease, QDU may be a good alternative to hospitalisation for diagnostic procedures. However, their cost-effectiveness remains to be clearly proven. Randomised controlled trials have shown that hospital-at-home (HaH) can lead to earlier hospital discharges, improve outcomes and reduce costs in patients with prevalent chronic diseases. Although telemonitoring seems to be promising and its use is increasing, methodologically sounder studies with a higher level of evidence are needed to assess its clinical effectiveness. CONCLUSIONS: Factors such as ageing, the need for an earlier diagnosis of suspected severe disease, the increasing complexity of medical care and the increasing costs of hospitalisation mean that, whenever possible, giving priority to less expensive alternatives to hospital admission, such as QDU, DC, HaH and telemedicine, is an urgent task in the current economic crisis.