Socioeconomic deprivation is associated with worse patient and graft survival following adult liver transplantation.

BACKGROUND: The impact of social determinants of health (SDOH) on adult liver transplant recipient outcomes is not clear at a national level. Further understanding of the impact of SDOH on patient outcomes can inform effective equitable healthcare delivery. METHODS: Unadjusted and multivariable models were used to analyze the Scientific Registry of Transplant Recipients to evaluate the association between the Social Deprivation Index (SDI) based on liver transplant recipient's residential location and patient and graft survival. We included adult recipients between 1/1/2008-12/1/2021. RESULTS: Patient and graft survival were lower in adults living in areas with deprivation scores above the median. Five-year patient and graft survival were 78.7% and 76.5% respectively in the cohort above median SDI compared to 80.5% and 78.3% below median SDI. Compared to the recipients in low deprivation residential areas, recipients residing in highest deprivation (SDI quintile=5) cohort had 6% higher adjusted risk of mortality (Adjusted Hazard Ratio [AHR]=1.06,95%C.I. 1.01-1.13) and 6% higher risk of graft failure (AHR=1.06,95% C.I. 1.001-1.11). The increased risks for recipients residing in more vulnerable residential areas were higher (AHR=1.11,95% CI 1.03-1.20 for both death and graft loss) following the first-year post-transplantation. Importantly, overall risk for graft loss associated with SDI was not linear but instead accelerated above the median level of deprivation. DISCUSSION: In the United States, SDOH, as reflected by residential distress, significantly impact 5-year patient and graft survival. The overall effect of residential deprivation are modest, but importantly, results illustrate they are more strongly associated with longer-term follow up and accelerate at higher deprivation levels. Further research is needed to evaluate effective interventions and policies to attenuate disparities in outcomes among recipients in highly disadvantaged areas.

Short-Term Cannabidiol with Δ-9-Tetrahydrocannabinol in Parkinson's Disease: A Randomized Trial.

BACKGROUND: Cannabis use is frequent in Parkinson's disease (PD), despite inadequate evidence of benefits and risks. OBJECTIVE: The aim is to study short-term efficacy and tolerability of relatively high cannabidiol (CBD)/low Δ-9-tetrahydrocannabinol (THC) to provide preliminary data for a longer trial. METHODS: Persons with PD with ≥20 on motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) who had negative cannabis testing took cannabis extract (National Institute of Drug Abuse) oral sesame oil solution for 2 weeks, increasing to final dose of 2.5 mg/kg/day. Primary outcome was change in motor MDS-UPDRS from baseline to final dose. RESULTS: Participants were randomized to CBD/THC (n = 31) or placebo (n = 30). Mean final dose (CBD/THC group) was 191.8 ± 48.9 mg CBD and 6.4 ± 1.6 mg THC daily. Motor MDS-UPDRS was reduced by 4.57 (95% CI, -8.11 to -1.03; P = 0.013) in CBD/THC group, and 2.77 (-4.92 to -0.61; P = 0.014) in placebo; the difference between groups was non-significant: -1.80 (-5.88 to 2.27; P = 0.379). Several assessments had a strong placebo response. Sleep, cognition, and activities of daily living showed a treatment effect, favoring placebo. Overall adverse events were mild and reported more in CBD/THC than placebo group. On 2.5 mg/kg/day CBD plasma level was 54.0 ± 33.8 ng/mL; THC 1.06 ± 0.91 ng/mL. CONCLUSIONS: The brief duration and strong placebo response limits interpretation of effects, but there was no benefit, perhaps worsened cognition and sleep, and there was many mild adverse events. Longer duration high quality trials that monitor cannabinoid concentrations are essential and would require improved availability of research cannabinoid products in the United States. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis.

BACKGROUND: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood. METHODS: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code. RESULTS: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4-15.2 vs. 15.1, 14.1-15.7, p=0.002), but Mayo risk score (0.03, -0.8 to 1.1 vs. 0.02, -0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8-10.7 vs. 6.4, 2.6-10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02-1.06, p<0.0001), total bilirubin (1.06, 1.04-1.08, p<0.0001), and albumin (0.44, 0.33-0.61, p<0.0001). AA race did not affect the performance of prognostic models. CONCLUSIONS: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs.

Interdependent Determinants of Health and Death? Examining the Linkages between Health Equity, Human Rights, and Democracy during COVID-19.

Background: The COVID-19 pandemic has been characterised by health inequities in differential rates of COVID-19-related morbidity and mortality and differential access to essential COVID-19-related health care interventions such as vaccines. Inequities through the pandemic have deeply illuminated the interdependence between health inequities, human rights, and democratic leadership and the imperative to delve more deeply into these key determinants of health, illness, and death. Methods: In this paper, we consider what COVID-19 suggests we should be learning about the relationships between democracy, human rights, and health equity. We first elaborate on the growing prominence of the framework and discourse of health equity. We turn to elaborate on a longer-standing trend of democratic backsliding and populist leadership during COVID-19. We consider human rights violations and domestic and global inequities that have characterised COVID-19 and COVID responses. Findings and conclusions: The pandemic has illustrated how rights-violating, negligent, and inequitable political leadership can deeply determine health outcomes. It has equally shown how democratic norms and institutions, including human rights and equity, offer discourse, standards, and tools that can be effectively used to challenge inequitable leadership on health. More fundamentally, it underscores how great the need is for approaches to public health emergencies rooted in human rights, equity, and good governance, including through a pandemic treaty in negotiation.

Can we move beyond vaccine apartheid? Examining the determinants of the COVID-19 vaccine gap.

While global health leaders call disparities in access to COVID-19 vaccines an 'apartheid,' this gap is not the first such disparity. The recurrence of these gaps in low and middle-income countries and especially in Africa, raises questions about their determinants and about the persistent failures of global health institutions to remediate them. We interrogate these determinants and questions by examining: (1) the distribution of COVID-19 vaccines; (2) primary determinants of vaccine access including availability and affordability; (3) factors affecting availability (hoarding, COVAX, and manufacturing capacity); and (4) factors affecting affordability (pricing, intellectual property rights (IPR), the TRIPS waiver and a potential pandemic treaty). We conclude that IPR constrained the affordability and availability of COVID-19 vaccines in ways inadequately addressed by COVAX and a waiver compromise thwarted by political, corporate, and philanthropic interests. While stronger limits to IPR in a pandemic treaty and a reformed International Health Regulations will not resolve structural inequities, they could meaningfully expand LMIC autonomy to protect public health. We urge equity-seeking Global South and North actors to fight for such IPR reforms as small and meaningful steps towards a more equitable global health order. Otherwise, criminally racist 'apartheids' will continue to be the norm when it comes to the distribution of essential health goods during global health emergencies.

Promoting children's rights to health and well-being in the United States.

The United States has a highly sophisticated pediatric healthcare system and spends more than any other country per capita on children's healthcare. However, not all children have access to needed and affordable health care and the life expectancy and health outcomes of children in the country are worse than in any other industrialized nation. These nations typically offer universal healthcare for children as part of a robust recognition of a children's rights framework. In 1989 the United Nations adopted the Convention on the Rights of the Child that recognizes the right of the child to the highest attainable standard of health and to facilities for the treatment of illness and rehabilitation of health. Currently the United States is the only United Nations member country that has not ratified the Convention on the Rights of the Child. This paper outlines the potential benefits of adopting a child rights approach based on the principles and provisions of the Convention on the Rights of the Child. The fact that countries who invest much less in healthcare compared to the United States can achieve better health outcomes provides the certainty that a solution is possible and within reach.

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study.

BACKGROUND AND AIMS: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA). APPROACH AND RESULTS: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events. CONCLUSIONS: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.

Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: Open-label pilot study.

BACKGROUND: Primary sclerosing cholangitis (PSC) is frequently associated with pruritus, which significantly impairs quality of life. Maralixibat is a selective ileal bile acid transporter (IBAT) inhibitor that lowers circulating bile acid (BA) levels and reduces pruritus in cholestatic liver diseases. This is the first proof-of-concept study of IBAT inhibition in PSC. METHODS: This open-label study evaluated the safety and tolerability of maralixibat ≤10 mg/d for 14 weeks in adults with PSC. Measures of pruritus, biomarkers of BA synthesis, cholestasis, and liver function were also assessed. RESULTS: Of 27 enrolled participants, 85.2% completed treatment. Gastrointestinal treatment-emergent adverse events (TEAEs) occurred in 81.5%, with diarrhea in 51.9%. TEAEs were mostly mild or moderate (63.0%); 1 serious TEAE (cholangitis) was considered treatment related. Mean serum BA (sBA) levels decreased by 16.7% (-14.84 µmol/L; 95% CI, -27.25 to -2.43; p = 0.0043) by week 14/early termination (ET). In participants with baseline sBA levels above normal (n = 18), mean sBA decreased by 40.0% (-22.3 µmol/L, 95% CI, -40.38 to -4.3; p = 0.004) by week 14/ET. Liver enzyme elevations were not significant; however, increases of unknown clinical significance in conjugated bilirubin levels were observed. ItchRO weekly sum scores decreased from baseline to week 14/ET by 8.4% (p = 0.0495), by 12.6% (p = 0.0275) in 18 participants with pruritus at baseline, and by 70% (p = 0.0078) in 8 participants with ItchRO daily average score ≥3 at baseline. CONCLUSIONS: Maralixibat was associated with reduced sBA levels in adults with PSC. In participants with more severe baseline pruritus, pruritus improved significantly from baseline. TEAEs were mostly gastrointestinal related. These results support further investigation of IBAT inhibitors for adults with PSC-associated pruritus. ClinicalTrials.gov: NCT02061540.

COVID-19 vaccine equity and the right to health for displaced Venezuelans in Latin America.

Given the magnitude of Venezuelan displacement in Latin America, there is a need to assess how migrants were, and will continue to be, addressed in COVID-19 vaccination policies. To explore migration status as a dimension of vaccine equity in Latin America and in relation to international human rights, we assessed national vaccination plans, peer-reviewed, and gray literature published between January 2020 and June 2021. Three key rights-related concerns were found to restrict the health rights of migrants in the region: 1) lack of prioritization of migrants in vaccine distribution; 2) onerous documentation requirements to be eligible for COVID-19 vaccination; and (3) how pervasive anti-migrant discrimination limited equitable health care access. While international human rights law prohibits against discrimination based on migration status, few countries analyzed realized their obligations to provide equal access to COVID-19 vaccines to non-citizens, including displaced Venezuelans. Especially for migrants and displaced people, effective and sustainable vaccination strategies for COVID-19 and future pandemics in Latin America must be guided not only by epidemiological risk but also seek to align with human rights obligations. To achieve this, States must also take special measures to facilitate vaccine access for communities facing systemic discrimination, exclusion, and marginalization.

Structural violence and the uncertainty of viral undetectability for African, Caribbean and Black people living with HIV in Canada: an institutional ethnography.

Biomedical advances in healthcare and antiretroviral treatment or therapy (ART) have transformed HIV/AIDS from a death sentence to a manageable chronic disease. Studies demonstrate that people living with HIV who adhere to antiretroviral therapy can achieve viral suppression or undetectability, which is fundamental for optimizing health outcomes, decreasing HIV-related mortality and morbidity, and preventing HIV transmission. African, Caribbean, and Black (ACB) communities in Canada remain structurally disadvantaged and bear a disproportionate burden of HIV despite biomedical advancements in HIV treatment and prevention. This institutional ethnography orients to the concept of 'structural violence' to illuminate how inequities shape the daily experiences of ACB people living with HIV across the HIV care cascade. We conducted textual analysis and in-depth interviews with ACB people living with HIV (n = 20) and health professionals including healthcare providers, social workers, frontline workers, and health policy actors (n = 15). Study findings produce a cumulative understanding that biomedical HIV discourses and practices ignore structural violence embedded in Canada's social fabric, including legislation, policies and institutional practices that produce inequities and shape the social world of Black communities. Findings show that inequities in structural and social determinants of health such as food insecurity, financial and housing instability, homelessness, precarious immigration status, stigma, racial discrimination, anti-Black racism, criminalization of HIV non-disclosure, health systems barriers and privacy concerns intersect to constrain engagement and retention in HIV healthcare and ART adherence, contributing to the uncertainty of achieving and maintaining undetectability and violating their right to health. Biomedical discourses and practices, and inequities reduce Black people to a stigmatized, pathologized, and impoverished detectable viral underclass. Black people perceived as nonadherent to ART and maintain detectable viral loads are considered "bad" patients while privileged individuals who achieve undetectability are considered "good" patients. An effective response to ending HIV/AIDS requires implementing policies and institutional practices that address inequities in structural and social determinants of health among ACB people.

An Inquiry into State Agreement and Practice on the International Law Status of the Human Right to Medicines.

Global disparities in access to COVID-19 vaccines have brought back into focus questions about whether the right to medicines has assumed any level of binding legality within international law. In this paper, we attempt to answer this question by considering if there is evidence of subsequent state agreement and practice to read the right to medicines into the rights to health and science protected in the International Covenant on Economic, Social and Cultural Rights. We adopt the interpretive framework in the Vienna Convention on the Law of Treaties and the International Law Commission's 2018 report to analyze the work of the United Nations Committee on Economic, Social, and Cultural Rights relevant to medicines, and its relationship to the content and voting in successive resolutions of the United Nations General Assembly. We find that these resolutions provide some evidence of state agreement that the rights to health and science, as enshrined in the International Covenant on Economic, Social and Cultural Rights, include access to affordable medicines. Yet the legal implications of this right remain highly contested, particularly when it comes to trade-related intellectual property rights. The negotiation of a pandemic treaty offers possibilities for codifying this right beyond these discursive instances, while political opposition remains likely to continue to undercut this emerging legal norm.

A Randomized, Dose-Finding, Proof-of-Concept Study of Berberine Ursodeoxycholate in Patients With Primary Sclerosing Cholangitis.

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a fibroinflammatory disease of the bile ducts leading to cirrhosis and hepatic decompensation. There are no approved pharmaceutical therapies for PSC. Berberine ursodeoxycholate (HTD1801) is an ionic salt of berberine and ursodeoxycholic acid with pleiotropic mechanisms of action. METHODS: An 18-week proof-of-concept study was conducted to assess the safety and efficacy of HTD1801 in PSC. This study had three 6-week periods: (i) a placebo-controlled period, (ii) a treatment extension period, and (iii) a randomized treatment withdrawal period. The primary end point was change from baseline in alkaline phosphatase (ALP) at week 6. RESULTS: Fifty-five patients were randomized and treated; 35 (64%) had inflammatory bowel disease and 22 (40%) had previously received ursodeoxycholic acid. Patients were initially randomized to placebo (n = 16), HTD1801 500 mg BID (n = 15), or HTD1801 1000 mg BID (n = 24). At baseline, mean (range) ALP values were 414 U/L (138-1,048), 397 U/L (237-773), and 335 U/L (122-882) for the placebo, HTD1801 500 mg BID, and HTD1801 1,000 mg BID groups, respectively. At week 6, a significant decrease in ALP was observed with HTD1801 (least square mean; HTD1801 500 mg BID = -53 U/L, P = 0.016; HTD1801 1000 mg BID = -37 U/L, P = 0.019) compared with placebo (98 U/L). ALP reductions were sustained through week 18 in those who remained on therapy, whereas ALP increased in those who crossed over to placebo during period 3. HTD1801 was generally well tolerated; 4 patients experienced serious adverse events, none attributed to HTD1801. DISCUSSION: HTD1801 is associated with significant improvement in ALP and warrants further study as a treatment for PSC.

Statin-Induced Rhabdomyolysis Associated With Transjugular Intrahepatic Portosystemic Shunt Placement.

Rhabdomyolysis is a known rare and potentially lethal complication of statin use. This toxic effect is potentiated by alterations in hepatic physiology in patients with cirrhosis. Transjugular intrahepatic portosystemic shunt placement has the potential to further compound this effect; yet, examples of this have not previously been described in the literature. We present a case of a patient who experienced statin-induced rhabdomyolysis likely as a direct consequence of transjugular intrahepatic portosystemic shunt placement.

Legislatively Excluded, Medically Uninsured and Structurally Violated: The Social Organization of HIV Healthcare for African, Caribbean and Black Immigrants with Precarious Immigration Status in Toronto, Canada.

African, Caribbean and Black immigrants face persistent legislative barriers to accessing healthcare services in Canada. This Institutional Ethnography examines how structural violence and exclusionary legislative frameworks restrict the right to HIV healthcare access for many Black immigrants. We conducted semi-structured interviews with Black immigrants living with HIV (n = 20) and healthcare workers in Toronto, Canada (n = 15), and analyzed relevant policy texts. Findings revealed that exclusionary immigration and healthcare legislation shaping and regulating immigrants' right to health restricted access to public resources, including health insurance and HIV healthcare and related services, subjecting Black immigrants with precarious status to structural violence. Healthcare providers and administrative staff worked as healthcare gatekeepers. These barriers undermine public health efforts of advancing health equity and ending HIV "while leaving no one behind." We urge continued policy reforms in Canada's immigration and healthcare systems regarding HIV care access for Canada's precarious status immigrants.

Unmasking legislative constraints: An institutional ethnography of linkage and engagement in HIV healthcare for African, Caribbean, and Black people in Ontario, Canada.

The Human Immunodeficiency Virus (HIV) epidemic significantly impacts African, Caribbean, and Black (ACB) immigrants in Canada. Health scholarship has revealed striking injustices within Canada's public healthcare system that restrict access to healthcare and violate the human rights of ACB immigrants living with HIV who are marginalized. We conducted an institutional ethnography to comprehensively understand how HIV healthcare in Ontario is organized and experienced by ACB immigrants, focusing on unjust and discriminatory legislative frameworks and institutional practices regulating access to publicly funded healthcare resources and services. We interviewed 20 ACB immigrants and 15 healthcare workers, including specialists, primary care providers, immigration physicians, and social workers. We found a disjuncture between the organization of HIV healthcare in Ontario and how ACB immigrants experienced access to care. We uncovered how immigration, public health and healthcare laws and related institutional practices intersect to produce structural violence which create barriers and missed opportunities to timely linkage and engagement in HIV healthcare. Black immigrants' accounts revealed that they underwent mandatory HIV under the Immigration Medical Examination policy (IME) without providing informed consent and receiving pre and post-test counselling. Furthermore, Black immigrants did not receive referrals and were not adequately linked to care following HIV diagnosis. Troubling encounters with immigration and public health state agents and healthcare legislative barriers including difficulty finding a physician, the 3-month waiting period under the Ontario Health Insurance Plan (OHIP), long wait times, lack of drug coverage, and stigma, discrimination, and anti-Black racism shaped and affected Black people's linkage and engagement in HIV care. We elucidate how the legislative and structural organization of healthcare regulated and constrained health service access for ACB immigrants living with HIV, including their ability to "achieve" HIV undetectability.