Health Equity Impacts of Medical Tourism in the Caribbean: The Need to Provide Actionable Guidance Regarding Balancing Local and Foreign Interests

Medical tourism is a practice where individuals cross international borders with the intention of privately purchasing healthcare. Caribbean countries are increasingly entering into the medical tourism market, which presents both opportunities and dangers. Our previous fieldwork shows that medical tourism requires host countries to balance the interests of private developers and domestic actors, including those accessing healthcare locally. Discussions with stakeholders in Jamaica, Cayman Islands, Barbados and St Lucia demonstrate concrete instances of this problem. Firstly, medical tourism can enhance training and employment opportunities for domestic health-workers. In doing so, it may exacerbate the inequitable distribution of these workers between the public and private sectors. Secondly, the expansion of private medical services can provide locals with more care options. These facilities may also crowd out existing local operators and price out local consumers. Thirdly, medical tourism is hailed as potentially cross subsidizing and strengthening the local public health system. It may also heighten health inequities and distract local attention from the needs of the public health sector. Caribbean stakeholders are aware of the promise and dangers of medical tourism. However, they lack clear advice from medical tourism researchers about how to navigate these issues, and specifically balancing local and foreign interests. We call on researchers to shift focus from highlighting the theoretical problems associated with medical tourism to providing concrete guidance to stakeholders in a position to decide whether or not to pursue medical tourism development and to shape this development when it takes place

The ability of Hepascore to predict liver fibrosis in chronic liver disease: A meta-analysis

Background & Aims: Hepascore is a serum model that was developed to assess the severity of liver fibrosis. It has been well validated in common causes of chronic liver disease. This study performed a meta-analysis to evaluate the pooled diagnostic performance of Hepascore and to compare it for different aetiologies of chronic liver disease. Methods: Two reviewers searched electronic databases from October 2005 to September 2015 for studies that evaluated the diagnostic performance of Hepascore for liver fibrosis in chronic liver disease. Results: 21 studies were included. The AUROC was adjusted according to the distribution of fibrosis stages. The mean adjusted AUROC was 0.83 (95%CI, 0.81-0.85) for significant fibrosis, 0.89 (95%CI, 0.85-0.92) for advance fibrosis and 0.93 (95%CI, 0.91-0.95) for cirrhosis. A cut point of 0.50-0.55 achieved a summary sensitivity of 70% and a summary specificity of 79% to predict significant fibrosis. A cut point of 0.50-0.61 had a summary sensitivity of 81% and a summary specificity of 74% to predict advanced fibrosis. A cut point of 0.80-0.84 had a summary sensitivity of 72% and a summary specificity of 0.88% to predict cirrhosis. The accuracy of Hepascore was similar among all disease aetiologies for the prediction of cirrhosis. However, Hepascore had better diagnostic ability for significant and advanced fibrosis in chronic hepatitis C, chronic hepatitis B and alcoholic liver disease than for non-alcoholic fatty liver disease and HIV co-infected viral hepatitis. Conclusions: Hepascore is a clinically useful measure of liver fibrosis in patients with common causes of chronic liver disease

Alcohol consumption and cardiovascular outcomes in patients with nonalcoholic fatty liver disease: A population-based cohort study

Low-level alcohol consumption is associated with reduced cardiovascular disease (CVD) in the general population. It is unclear whether this association is seen in patients with nonalcoholic fatty liver disease (NAFLD) who have an increased risk of CVD. We examined the association between alcohol consumption and CVD-related outcomes in subjects with NAFLD from a general population cohort. Subjects participating in the 1994-1995 Busselton Health survey underwent clinical and biochemical assessment. NAFLD was identified using the Fatty Liver Index of \u3e60, and alcohol consumption quantified using a validated questionnaire. CVD hospitalizations and death during the ensuing 20 years were ascertained using the Western Australian data linkage system. A total of 659 of 4,843 patients were diagnosed with NAFLD. The average standard drinks per week was 8.0 for men and 4.0 for women. Men consuming 8-21 drinks per week had a 38% (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.43-0.90) lower risk of CVD hospitalization as compared with men consuming 1-7 drinks per week. With both men and women combined, consumption of 8-21 drinks per week was associated with a 32% (HR 0.68, 95% CI 0.49-0.93) reduction in CVD hospitalization in minimally adjusted and 29% (HR 0.71, 95% CI 0.51-0.99) in fully adjusted models. No protective association was observed with binge drinking. There was no association between alcohol consumption and CVD death. Conclusion: Low to moderate alcohol consumption is associated with fewer CVD hospitalizations but not CVD death in subjects with NAFLD

Association between remnant lipoprotein cholesterol levels and non-alcoholic fatty liver disease in adolescents

Background & Aims: Remnant lipoprotein cholesterol (RLP-C) is an atherogenic lipid profile associated with non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). With increased rates of CVD seen in adults with NAFLD, RLP-C has the potential to identify individuals with NAFLD who are at increased risk of CVD. This study examined in adolescents sex-different associations among RLP-C, NAFLD, and cardiometabolic risk factors, and whether RLP-C is associated with NAFLD beyond traditional cardiometabolic risk factors. Methods: Adolescents in the Raine Study had anthropometry, clinical, biochemistry and arterial stiffness measurements recorded at 17 years of age. Fatty liver, subcutaneous and visceral adipose thickness were assessed using abdominal ultrasound. Relationships among RLP-C, NAFLD, liver biochemistry, insulin resistance, adipokines, adiposity and arterial stiffness were assessed. Results: NAFLD was diagnosed in 15.1% (19.6% females and 10.7% males) of adolescents. Increasing RLP-C levels were associated with increasing severity of hepatic steatosis and metabolic syndrome. Adolescents with NAFLD and serum RLP-C levels in the highest quartile compared with the lowest quartile, had higher serum leptin, homeostatic model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein, low-density-lipoprotein cholesterol, triglycerides, BMI, subcutaneous and visceral adipose thickness, systolic blood pressure and arterial stiffness, but lower adiponectin and high-density-lipoprotein cholesterol. Using multivariable logistic regression, RLP-C in the lowest quartile compared with the highest quartile was associated with 85% lower odds of NAFLD in males and 55% in females, after adjusting for waist circumference, leptin, ALT, adiponectin and HOMA-IR. Conclusions: There is an association between RLP-C and NAFLD beyond traditional risk factors of adiposity and insulin resistance in adolescents. Although raised serum RLP-C levels were associated with the severity of hepatic steatosis and markers of cardiometabolic risk, lower serum RLP-C might reflect reduced cardiovascular risk. Lay summary: Remnant lipoprotein cholesterol (RLP-C) is a part of the blood cholesterol that is linked with heart disease and non-alcoholic fatty liver disease (NAFLD) in adults. In the Raine Study, teenagers with high RLP-C levels had more severe fat accumulation in their liver. Thus, RLP-C might be the hidden link between NAFLD and future risk of heart disease

Mistranslation drives alterations in protein levels and the effects of a synonymous variant at the fibroblast growth factor 21 locus

Fibroblast growth factor 21 (FGF21) is a liver-derived hormone with pleiotropic beneficial effects on metabolism. Paradoxically, FGF21 levels are elevated in metabolic diseases. Interventions that restore metabolic homeostasis reduce FGF21. Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor in altering FGF21 levels and function in humans is unknown. A genetic approach is used to help resolve this paradox. The authors demonstrate that the primary event in dysmetabolic phenotypes is the elevation of FGF21 secretion. The latter is regulated by translational reprogramming in a genotype- and context-dependent manner. To relate the findings to tissues outcomes, the minor (A) allele of rs838133 is shown to be associated with increased hepatic inflammation in patients with metabolic associated fatty liver disease. The results here highlight a dominant role for translation of the FGF21 protein to explain variations in blood levels that is at least partially inherited. These results provide a framework for translational reprogramming of FGF21 to treat metabolic diseases

Copy number variation and expression of exportin-4 associates with severity of fibrosis in metabolic associated fatty liver disease

Background Liver fibrosis risk is a heritable trait, the outcome of which is the net deposition of extracellular matrix by hepatic stellate cell-derived myofibroblasts. Whereas nucleotide sequence variations have been extensively studied in liver fibrosis, the role of copy number variations (CNV) in which genes exist in abnormal numbers of copies (mostly due to duplication or deletion) has had limited exploration. Methods The impact of the XPO4 CNV on histological liver damage was examined in a cohort comprised 646 Caucasian patients with biopsy-proven MAFLD and 170 healthy controls. XPO4 expression was modulated and function was examined in human and animal models. Findings Here we demonstrate in a cohort of 816 subjects, 646 with biopsy-proven metabolic associated liver disease (MAFLD) and 170 controls, that duplication in the exportin 4 (XPO4) CNV is associated with the severity of liver fibrosis. Functionally, this occurs via reduced expression of hepatic XPO4 that maintains sustained activation of SMAD3/SMAD4 and promotes TGF-β1-mediated HSC activation and fibrosis. This effect was mediated through termination of nuclear SMAD3 signalling. XPO4 demonstrated preferential binding to SMAD3 compared to other SMADs and led to reduced SMAD3-mediated responses as shown by attenuation of TGFβ1 induced SMAD transcriptional activity, reductions in the recruitment of SMAD3 to target gene promoters following TGF-β1, as well as attenuation of SMAD3 phosphorylation and disturbed SMAD3/SMAD4 complex formation. Interpretation We conclude that a CNV in XPO4 is a critical mediator of fibrosis severity and can be exploited as a therapeutic target for liver fibrosis

Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases

Key physiological functions of the liver, including glucose and lipid metabolism, become disturbed in the setting of non-alcoholic fatty liver disease (NAFLD) and may be associated with a systemic inflammatory 'milieu' initiated in part by liver-secreted cytokines and molecules. Consequently, the pathophysiological effects of NAFLD extend beyond the liver with a large body of clinical evidence demonstrating NAFLD to be independently associated with both prevalent and incident cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). The magnitude of risk of developing these extrahepatic diseases parallels the underlying severity of NAFLD, such that patients with non-alcoholic steatohepatitis (NASH) appear to be at greater risk of incident CVD, CKD and T2DM than those with simple steatosis. Other modifiers of risk may include genetic variants (eg, patatin-like phospholipase domain-containing 3 and trans-membrane 6 superfamily member 2 polymorphisms), visceral adipose tissue accumulation, dietary intake and the gut microbiome. Emerging data also suggest that NAFLD may be a risk factor for colonic neoplasia and reduced bone mineral density, especially among men. Importantly, improvement/resolution of NAFLD is associated with a reduced incidence of T2DM and improved kidney function, adding weight to causality and suggesting liver focused treatments may reduce risk of extrahepatic complications. Awareness of these associations is important for the clinicians such that CVD risk factor management, screening for T2DM and CKD are part of the routine management of patients with NAFLD

The relationship between abdominal pain and emotional wellbeing in children and adolescents in the Raine Study

Abdominal pain is a common reason for medical visits. We examined the prevalence, gastrointestinal, and emotional significance of abdominal pain in a population-based cohort serially followed up from birth to 17 years. Children and adolescents from Generation 2 of the Raine Study participated in comprehensive cross-sectional assessments at ages 2, 5, 8, 10, 14 and 17 years. At 17 years, medical history, general health, gastrointestinal symptoms, medications, health practitioner attendance, and self-rated unhappiness were recorded. Longitudinal data regarding abdominal pain or unhappiness, from serial questionnaires, were analysed to identify factors associated with abdominal pain and adverse emotional health at age 17 years. Females experienced more abdominal pain than males at all ages (p \u3c 0.05). Seventeen-year-old adolescents with abdominal pain reported a higher prevalence of depression, anxiety, being bullied at school, and poorer health status than those without abdominal pain (p \u3c 0.05 for all). Abdominal pain and unhappiness during childhood and mid-adolescence were prospectively associated with recurrent abdominal pain, anxiety, depression and unhappiness during late adolescence (p \u3c 0.05 for all). In conclusion, abdominal pain in children and adolescents associates with depression, anxiety, being bullied, unhappiness and reduced overall health-rating during adolescence. Awareness of these factors may guide management decisions

Prospective dietary polyunsaturated fatty acid intake is associated with trajectories of fatty liver disease: An 8 year follow-up study from adolescence to young adulthood

Background and aim: Dietary fat intake has long been associated with fatty liver. Our study aimed to determine the effect of dietary fats on longitudinal fatty liver index (FLI) trajectories from adolescence to young adulthood. Methods: Nine hundred eighty-five participants in the Raine Study, Perth, Western Australia, Australia, had cross-sectional assessments at ages 14, 17, 20 and 22 years, during which anthropometric measurements and blood tests were obtained. FLI trajectories were derived from the longitudinal FLI results. Dietary fat intake was measured with a semi-quantitative food frequency questionnaire at 14 years and log multinominal regression analyses were used to estimate relative risks. Results: Three FLI trajectories were identified and labelled as stable-low (79.1%, N = 782), low-to-high (13.9%, N = 132), and stable-high (7%, N = 71). The low-to-high group associated with an increased intake of the long-chain polyunsaturated fatty acids EPA, DPA and DHA (RR 1.27, 95% CI 1.10–1.48) relative to the stable-low group. Compared to the stable-low group, omega-6 and the ratio of omega-6 to omega-3 in the stable-high group were associated with an increased relative risk of 1.34 (95% CI 1.02–1.76) and 1.10 (95% CI 1.03–1.16), respectively. Conclusion: For those at high risk of fatty liver in early adolescence, high omega-6 fatty acid intake and a high ratio of omega-6 to omega-3 fatty acids are associated with increased risk of fatty liver. There should be caution in assuming these associations are causal due to possible undetected and underestimated confounding factors