Humanity & Health

Globally, immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1) are rapidly becoming the backbone of first-line systemic therapy for hepatocellular carcinoma (HCC). This is supported by large-scale global phase 3 studies which demonstrated that the use of ICIs-based therapy could markedly improve the overall survival with quality in patients who suffered from unresectable HCC [1]. However, with the use of anti-PD-1/anti-PD-L1-based therapy in patients with HCC, it is not uncommon to encounter primary resistant to or become resistant with disease progression following initial response. There are also patients who were discontinued from further ICIs treatment owing to immune-related adverse events (irAEs) [2] [3] [4] [5] . According to the current management guidelines, for grade 2 or grade 3 irAEs, ICIs can be resumed when symptoms and/or laboratory values revert to grade 1 or less [1, 6, 7] . Recent studies have shown that the occurrence of imAEs may predict ICIs response across tumor types, including melanoma, renal cell carcinoma, and HCC. This is of great clinical relevance as irAEs activate exhausted immune cells that attack both tumors and normal tissues, and it is theoretically possible that irAEs may signal a better response to ICIs therapy [8] . In a metaanalysis which included 30 trials covering various cancer types, patients who developed irAEs experienced a significant benefit in OS compared with those who did not develop irAEs [9] . In keeping with this, in the HIMALAYA study, patients with uHCC treated with ≥ 1 dose of STRIDE and experienced irAE had a numerical improvement in overall * George Lau

About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV. In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed. Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV. High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.

Person-centered care (PCC) within HIV treatment services has demonstrated potential to overcome inequities in HIV service access while improving treatment outcomes. Despite PCC being widely considered a best practice, no consensus exists on its assessment and measurement. This study in Zambia builds upon previous research that informed development of a framework for PCC and a PCC assessment tool (PCC-AT). This mixed methods study aims to examine the preliminary effectiveness of the PCC-AT through assessing the association between client HIV service delivery indicators and facility PCC-AT scores. We hypothesize that facilities with higher PCC-AT scores will demonstrate more favorable HIV treatment continuity, viral load (VL) coverage, and viral suppression in comparison to those of facilities with lower PCC-AT scores. We will implement the PCC-AT at 30 randomly selected health facilities in the Copperbelt and Central provinces of Zambia. For each study facility, data will be gathered from 3 sources: (1) PCC-AT scores, (2) PCC-AT action plans, and (3) facility characteristics, along with service delivery data. Quantitative analysis, using STATA, will include descriptive statistics on the PCC-AT results stratified by facility characteristics. Cross-tabulations and/or regression analysis will be used to determine associations between scores and treatment continuity, VL coverage, and/or viral suppression.Qualitative data will be collected via action planning, with detailed notes collected and recorded into an action plan template. Descriptive coding and emerging themes will be analyzed with NVivo software. As of May 2024, we enrolled 29 facilities in the study and data analysis from the key informant interviews is currently underway. Results are expected to be published by September 2024. Assessment and measurement of PCC within HIV treatment settings is a novel approach that offers HIV treatment practitioners the opportunity to examine their services and identify actions to improve PCC performance. Study results and the PCC-AT will be broadly disseminated for use among all project sites in Zambia as well as other HIV treatment programs, in addition to making the PCC-AT publicly available to global HIV practitioners. DERR1-10.2196/54129.

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.

In this book we analyze the topic of Intellectual Property Rights<br> (IPR) from a new perspective. The topic of restriction of polyexistentials and<br> Western IPR are one and the same. Yet, the concept of polyexistentials has not<br> appeared in prior discussions of this topic. This is the very first time that<br> the concept and the word “polyexistetials” are being introduced. Knowledge, know-how, uses of know-how, ideas and information are inherently<br> non-scarce. They are polyexistentials. Unlike monoexistentials which exist in<br> singular, polyexistentials naturally exist in multiples and are inherently not<br> scarce. What is abundant in nature is being made artificially scarce through<br> man-made ownership rules called copyright and patents. These ownership rules<br> then permit a certain group which usually take the form of corporations to<br> economically profit from these unnatural and economically motivated artificial<br> scarcities. The model of polyexistence makes it easy to demonstrate that the<br> concept of Intellectual Property is invalid. This proof is based on logic that<br> is rooted in nature of existence and nature of possession and the requirement<br> for ownership to be in harmony with nature of possession and existence. Having rejected the Western IPR regime as an erroneous model for govenrnance of<br> polyexistentials, we introduce the Libre-Halaal model of governance of<br> polyexistentials towards facilitating conviviality of tools. We then focus on<br> the digital world and introduce the The Libre-Halaal By* (ByStar) Digital<br> Ecosystem, as a moral alternative to the existing proprietary American digital<br> ecosystem. Equipped with a multidisciplinary blueprint, we offer our initial<br> implementation of the ByStar digital ecosystem as a starting point towards<br> concrete solutions. Todays’s American Internet is mostly a business construct.<br> The current basic model of internet is rooted in the rise-of-the-middle model of<br> corporations exploiting the individual. The engineering architecture of the<br> proprietary internet application services is very central. Proprietary American<br> corporations the likes of Google, Facebook, Amazon, Microsoft and Apple are<br> positioned in the middle and monitor, control and expolit citizens of the world.<br> The engineering architecture of Libre-Halaal ByStar Digital Ecosystem is<br> distinctly different. The multidisciplinary blue print that we have provided can<br> be the basis for de-Americanization, de-IPR-ization and redecentralization of<br> internet application services. We are pro-business. We are devout monoexistential bounded-corporations<br> capitalists. The existing capitalist model for monoexistentials is generally<br> correct, in both philosophical and economic terms. But the extension of the<br> monoexistential capitalist model into the domain of polyexistentials, based on<br> the Western IPR regime, is a grave mistake. To address this mistake of American<br> Capitalism, we introduce the model of Global Polyexistential Capitalism as an<br> Attribution Based Economy towards correcting the existing IPR rooted Ownership<br> Based Economy of American Capitalism. Deep understanding of the strategy that we<br> outline in this book, makes it clear that Polyexistential American Capitalism is<br> very vulnerable. Our ultimate goal for all of this has been to influence<br> societal policies towards adoption of halaal manner of-existence of<br> polyexistentials. We recognize that adoption of such societal policies in<br> America is likely not possible and their adoption in the West is likely very<br> difficult. Therefore, we focus on Eastern societies in general and Iran and<br> China in particular. It is only through full rejection of Western IPR regime and<br> its deep roots in Americanism that humanity can be rescued.<br>

4073 Background: In the Phase 3 HIMALAYA study (NCT03298451) in uHCC, STRIDE (Single T Regular Interval D) significantly improved overall survival versus sorafenib (S) and had manageable safety (Abou-Alfa et al. NEJM Evid 2022). STRIDE is approved for uHCC in the United States and Japan and is recommended for approval by the European Medicines Agency. In this exploratory post hoc analysis, we assessed temporal patterns of imAEs for the STRIDE regimen in HIMALAYA. Methods: Safety was assessed in participants (pts) who received ≥1 dose of STRIDE (T 300 mg [one dose] plus D 1500 mg once every 4 weeks) or S (400 mg twice daily). Treatment causality was investigator-assessed. imAEs were defined as AEs of special interest associated with drug exposure and consistent with an immune-mediated mechanism of action for which no alternate etiology was clear. Safety was summarized descriptively overall and at specific time points after the start of treatment. Results: In total, 388 (STRIDE) and 374 (S) pts were included in the safety analysis. Median (range) duration of exposure was 5.5 (0.4–41.9) months for STRIDE (D exposure in STRIDE) and 4.1 (0.1–38.6) months for S. Any grade treatment-related AEs (TRAEs) and Grade 3 or 4 TRAEs were less frequent for STRIDE (75.8% and 25.8%, respectively) versus S (84.8% and 36.9%, respectively). Any grade imAEs and max Grade 3 or 4 imAEs occurred in 35.8% and 12.6% of pts, respectively for STRIDE. Any grade imAEs and max Grade 3 or 4 imAEs with STRIDE occurred at all time points assessed and were most likely to occur within the first three months after treatment. For STRIDE, any grade imAEs of gastrointestinal disorders and skin and subcutaneous tissue disorders were most common within the first month after treatment (3.9% and 3.1%, respectively), whereas any grade imAEs of endocrine disorders were most common between &gt;1 and ≤2 months (6.7%). Conclusions: In HIMALAYA, AEs with STRIDE were manageable and generally low grade. Any grade TRAEs and Grade 3 or 4 TRAEs were less frequent for STRIDE versus S. Although imAEs with STRIDE could occur at any time, most were observed within the first three months after treatment. These findings continue to support STRIDE for the treatment of uHCC. Clinical trial information: NCT03298451 . [Table: see text]

Mental health is an increasing concern around the world, but there is a substantial gap between Western and non-Western countries in terms of access to quality mental healthcare. To help close this gap and improve the delivery of mental health and psychosocial support services (MHPSS), the UN’s 2016 Grand Bargain declared a new approach of prioritising the localisation of these services. This paper examines the effects of the Grand Bargain on the localisation of mental health and psychosocial support services in non-Western countries, as a means to decolonise mental health. An outcome evaluation was carried out to measure the amount of funding received by local and national agencies that provide MHPSS services in less economically developed countries. All data was gathered from the UN Financing Track System (FTS) and looked at financial contributions over time in six humanitarian sectors: health; water, sanitation and hygiene (WASH); gender-based violence; nutrition; protection, and shelter. The results show that local and national agencies received only 3% of international donors' MHPSS-related humanitarian funding between 2017 and 2021. Most localised MHPSS-related funding is driven by country-based pooled funds, with Middle Eastern countries as the primary beneficiaries, and localised MHPSS funding predominantly went to the health, WASH, and protection sectors. The study found limited localisation of MHPSS services in less economically developed countries, and a limited focus on community capacity building through associated humanitarian sectors. Based on this study, it is recommended that humanitarians should advocate for increased localisation and culturally competent practices in the MHPSS space.