Wallmunk9982

Drawing on a broad literature base and years of experience as a senior humanitarian pharmacist, the author reflects on the barriers, culture and system that contributes to the existence and persistence of substandard and falsified medical products in global assistance projects. ABT-888 cell line The paper offers an in-depth examination of pressures that may arise in four key areas (capacity, supply chain, bureaucracy and quality assurance) and postulates on the myriad ways in which this may alter the attitudes, behaviours and decision-making of iNGOs in a manner that disincentivises the prioritisation of medical product quality. This paper does not seek to excoriate the aid sector, but rather to lend a new perspective that such predicaments are overlooked, real-world ethical dilemmas in urgent need of greater openness, research, debate and guidance, for the benefit of moral decision-making and patient care.

One way to prevent falsified medical products from entering the regulated pharmaceutical supply chain is to implement a pharmaceutical track-and-trace system (PTTS). Such systems in the most extensive versions generally mandate a scan at every point of contact with the medical product from the point of entry to dispensation. There have been several attempts to implement such systems; for example, a 'full' PTTS in Turkey and the more pared-down version offered by the European Union's Falsified Medicines Directive and Delegated Act. This study aims to identify facilitators and barriers to implementing (elements of) a PTTS, with the Turkish system used as a benchmark.

We conducted a 'realist' review, which synthesises literature and aims to establish how a specific technology works, for whom, under which circumstances. We searched Embase, Medline Ovid, Web of Science, Cochrane Central and Google Scholar databases, yielding 2,790 scholarly articles. We selected 21 for review.

Implementation of PTTS elements has been attempted in different compositions in several primarily high-income and middle-income countries. Factors that affected implementation included stakeholders like the government and supply chain actors, the coordination between them, and their awareness, knowledge, and skills, as well as regulation and legislation, monetary investments, and technical and digital requirements.

The interplay between contextual factors is crucial for successful PTTS implementation. Specifically, the findings indicate that aligning the incentives for all actors and allowing for adjustments in a continuous implementation process will likely facilitate implementation.

The interplay between contextual factors is crucial for successful PTTS implementation. Specifically, the findings indicate that aligning the incentives for all actors and allowing for adjustments in a continuous implementation process will likely facilitate implementation.

Indonesia, the world's fourth most populous nation, is close to achieving universal health coverage (UHC). A widely-publicised falsified vaccine case in 2016, coupled with a significant financial deficit in the national insurance system, has contributed to concern that the rapid scale-up of UHC might undermine medicine quality. We investigated the political and economic factors that drive production and trade of poor-quality medicines in Indonesia.

We reviewed academic publications, government regulations, technical agency documents and news reports to develop a semi-structured questionnaire. We interviewed healthcare providers, policy-makers, medicine regulators, pharmaceutical manufacturers, patients and academics (n=31). We included those with in-depth knowledge about the falsified vaccine case or the pharmaceutical business, medicine regulation, prescribing practice and the implementation of UHC. We coded data using NVivo software and analysed by constant comparative method.

The scale-up of UHC has ive markets for substandard and falsified medicines. To protect progress towards UHC, policy-makers must consider the potential impact on medicine quality when formulating rules governing health financing, procurement, taxation and industry.

Market factors, including political pressure to reduce medicine prices and healthcare provider incentives, can drive markets for substandard and falsified medicines. To protect progress towards UHC, policy-makers must consider the potential impact on medicine quality when formulating rules governing health financing, procurement, taxation and industry.In 2012, the WHO launched its Global Surveillance and Monitoring System (GSMS) for substandard and falsified medicines, with the aim of improving the quality of reporting and using the data to inform post-market surveillance and build regulatory capacity. However, from a regulatory governance perspective, its effectiveness depends on the willingness and ability of actors 'on the ground' to identify, report and investigate possible infringements and to enforce penalties. This paper presents findings from 27 interviews with representatives of agencies charged with regulating pharmaceutical markets and 4 interviews with pharmaceutical industry representatives in Tanzania. Their experiences provide important insights into how the theorised mechanism between reporting and a reduction in undesirable behaviours can play out in a low-income context, revealing hidden assumptions about regulator behaviour and motivations. A combination of chronic under-resourcing, information gaps and enforcement challenges conspires to limit the efforts of local regulators to achieve the GSMS goals, shedding new light on the relationship between apparent 'misconduct' and structural constraints.

The host's immune system develops in equilibrium with both cellular self-antigens and non-self-antigens derived from microorganisms which enter the body during lifetime. In addition, during the years, a tumor may arise presenting to the immune system an additional pool of non-self-antigens, namely tumor antigens (tumor-associated antigens, TAAs; tumor-specific antigens, TSAs).

In the present study, we looked for homology between published TAAs and non-self-viral-derived epitopes. Bioinformatics analyses and ex vivo immunological validations have been performed.

Surprisingly, several of such homologies have been found. Moreover, structural similarities between paired TAAs and viral peptides as well as comparable patterns of contact with HLA and T cell receptor (TCR) α and β chains have been observed. Therefore, the two classes of non-self-antigens (viral antigens and tumor antigens) may converge, eliciting cross-reacting CD8

T cell responses which possibly drive the fate of cancer development and progression.

An established antiviral T cell memory may turn out to be an anticancer T cell memory, able to control the growth of a cancer developed during the lifetime if the expressed TAA is similar to the viral epitope. This may ultimately represent a relevant selective advantage for patients with cancer and may lead to a novel preventive anticancer vaccine strategy.

An established antiviral T cell memory may turn out to be an anticancer T cell memory, able to control the growth of a cancer developed during the lifetime if the expressed TAA is similar to the viral epitope. This may ultimately represent a relevant selective advantage for patients with cancer and may lead to a novel preventive anticancer vaccine strategy.Many adverse reactions associated with immune checkpoint inhibitor (ICI) treatments are immunologically driven and may necessitate discontinuation of the ICI. Herein, we present a patient who had been administered the radio contrast media amidotrizoate multiple times without issue but who then developed a Stevens-Johnson syndrome reaction after coadministration of atezolizumab. Causality was confirmed by a positive re-challenge with amidotrizoate and laboratory investigations that implicated T cells. Importantly, the introduction of atezolizumab appears to have altered the immunologic response to amidotrizoate in terms of the tolerance-elicitation continuum. Proof of concept studies demonstrated enhancement of recall responses to a surrogate antigen panel following in-vitro (healthy donors) and in-vivo (ICI patients) administrations of ICIs. Our findings highlight the importance of considering all concomitant medications in patients on ICIs who develop immune-mediated adverse reactions. In the event of some immune-related adverse reactions, it may be critical to identify the culprit antigen-forming entity that the ICIs have altered the perception of rather than simply attribute causality to the ICI itself in order to optimize both patient safety and treatment of malignancies.

Dendritic cells (DCs) are a promising therapeutic target in cancer immunotherapy given their ability to prime antigen-specific T cells, and initiate antitumor immune response. A major obstacle for DC-based immunotherapy is the difficulty to obtain a sufficient number of functional DCs. Theoretically, this limitation can be overcome by using induced pluripotent stem cells (iPSCs); however, therapeutic strategies to engage iPSC-derived DCs (iPSC-DCs) into cancer immunotherapy remain to be elucidated. Accumulating evidence showing that induction of tumor-residing DCs enhances immunomodulatory effect of radiotherapy (RT) prompted us to investigate antitumor efficacy of combining intratumoral administration of iPSC-DCs with local RT.

Mouse iPSCs were differentiated to iPSC-DCs on OP9 stromal cells expressing the notch ligand delta-like 1 in the presence of granulocyte macrophage colony-stimulating factor. Phenotype and the capacities of iPSC-DCs to traffic tumor-draining lymph nodes (TdLNs) and prime antigen-sd PD-L1 expression in tumor-associated macrophages and DCs. Consequently, combined therapy rendered poorly immunogenic tumors responsive to anti-PD-L1 therapy along with the development of tumor-specific immunological memory.

Our findings illustrate the translational potential of iPSC-DCs, and identify the therapeutic efficacy of a combinatorial platform to engage them for overcoming resistance to anti-PD-L1 therapy in poorly immunogenic tumors.

Our findings illustrate the translational potential of iPSC-DCs, and identify the therapeutic efficacy of a combinatorial platform to engage them for overcoming resistance to anti-PD-L1 therapy in poorly immunogenic tumors.

Current immunotherapy for patients with high-risk neuroblastoma involves the therapeutic antibody dinutuximab that targets GD2, a ganglioside expressed on the majority of neuroblastoma tumors. Opsonized tumor cells are killed through antibody-dependent cellular cytotoxicity (ADCC), a process mediated by various immune cells, including neutrophils. The capacity of neutrophils to kill dinutuximab-opsonized tumor cells can be further enhanced by granulocyte-macrophage colony-stimulating factor (GM-CSF), which has been shown in the past to improve responses to anti-GD2 immunotherapy. However, access to GM-CSF (sargramostim) is limited outside of Northern America, creating a high clinical need for an alternative method to stimulate dinutuximab responsiveness in the treatment of neuroblastoma. In this in vitro study, we have investigated whether clinically well-established granulocyte colony-stimulating factor (G-CSF) can be a potentially suitable alternative for GM-CSF in the dinutuximab immunotherapy regimen of patients with neuroblastoma.