Telemedicine interventions in six conflict-affected countries in the WHO Eastern Mediterranean region: a systematic review

Background: The COVID-19 pandemic has escalated the use of telemedicine in both high and low resource settings however its use has preceded this, particularly in conflict-affected settings. Several countries in the WHO Eastern Mediterranean (EMR) region are affected by complex, protracted crises. Though telemedicine has been used in such settings, there has been no comprehensive assessment of what interventions are used, their efficacy, barriers, or current research gaps. Objectives: To perform a systematic review of academic and grey literature, identifying telemedicine interventions in select, EMR conflict-affected settings and relevant enablers and barriers to their implementation. Methods: A systematic search of ten academic databases and 3 grey literature sources from January 1st 2000 to December 31st 2020 was completed. Included articles reported on telemedicine use in six conflict-affected EMR countries (or territories) graded as WHO Health Emergencies: Afghanistan, Gaza, Iraq, Libya, Syria and Yemen. Data were extracted and narratively synthesised due to heterogeneity in study design and outcomes. Results: Of 3419 articles identified, twenty-one peer-reviewed and three grey literature sources met the inclusion criteria. We analysed these by context, intervention, and evaluation. Context: eight related to Afghanistan, eight to Syria and seven to Iraq with one each in Yemen and Gaza. Most were implemented by humanitarian or academic organisations with projects mostly initiated in the United States or Europe and mostly by physicians. The in-country links were mostly health professionals rather than patients seeking specialist inputs for specialities not locally available. Interventions: These included both SAF (store and forward) and RT (real-time) with a range of specialities represented including radiology, histopathology, dermatology, mental health, and intensive care. Evaluation: most papers were observational or descriptive with few describing quality measures of interventions. Conclusions: Telemedicine interventions are feasible in conflict-affected settings in EMR using low-cost, accessible technologies. However, few implemented interventions reported on evaluation strategies or had these built in. The ad hoc nature of some of the interventions, which relied on volunteers without sustained financial or academic investment, could pose challenges to quality and sustainability. There was little exploration of confidentiality, ethical standards, data storage or local healthcare worker and patient acceptability

Challenges of providing healthcare worker education and training in protracted conflict: a focus on non-government controlled areas in north west Syria

Without healthcare workers (HCWs), health and humanitarian provision in Syria cannot be sustained either now or in the post-conflict phase. The protracted conflict has led to the exodus of more than 70% of the healthcare workforce. Those remaining work in dangerous conditions with insufficient resources and a healthcare system that has been decimated by protracted conflict. For many HCWs, particularly those in non-government-controlled areas (NGCAs) of Syria, undergraduate education and postgraduate training has been interrupted with few opportunities to continue. In this manuscript, we explore initiatives present in north west Syria at both undergraduate and postgraduate level for physician and non-physician HCWs. Conclusion: Challenges to HCW education in north west Syria can be broadly divided into 1. Organisational (local healthcare leadership and governance, coordination and collaboration between stakeholders, competition between stakeholders and insufficient funding.) 2. Programmatic (lack of accreditation or recognition of qualifications, insufficient physical space for teaching, exodus of faculty affecting teaching and training, prioritisation of physicians over non-physicians, informally trained healthcare workers.) 3. Healthcare system related (politicisation of healthcare system, changing healthcare needs of the population, ongoing attacks on healthcare.) Locally implementable strategies including dedicated funding are key to supporting retention of HCWs and return during post-conflict reconstruction

Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity

Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T cells against leukemia and lymphoma with promising clinical results. Extending this approach to allogeneic T cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen-specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy. We transduced CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9), and demonstrated efficient killing of CD19-expressing cell lines and primary leukemia cells in vitro, with marked prolongation of survival in a xenograft Raji lymphoma murine model. Interleukin-15 (IL-15) production by the transduced CB-NK cells critically improved their function. Moreover, iC9/CAR.19/IL-15 CB-NK cells were readily eliminated upon pharmacologic activation of the iC9 suicide gene. In conclusion, we have developed a novel approach to immunotherapy using engineered CB-derived NK cells, which are easy to produce, exhibit striking efficacy and incorporate safety measures to limit toxicity. This approach should greatly improve the logistics of delivering this therapy to large numbers of patients, a major limitation to current CAR-T-cell therapies

Large-scale GMP-compliant CRISPR-Cas9-mediated deletion of the glucocorticoid receptor in multivirus-specific T cells

Virus-specific T cells have proven highly effective for the treatment of severe and drugrefractory infections after hematopoietic stem cell transplant (HSCT). However, the efficacy of these cells is hindered by the use of glucocorticoids, often given to patients for the management of complications such as graft-versus-host disease. To address this limitation, we have developed a novel strategy for the rapid generation of good manufacturing practice (GMP)-grade glucocorticoid-resistant multivirus-specific T cells (VSTs) using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) gene-editing technology. We have shown that deleting the nuclear receptor subfamily 3 group C member 1 (NR3C1; the gene encoding for the glucocorticoid receptor) renders VSTs resistant to the lymphocytotoxic effect of glucocorticoids. NR3C1-knockout (KO) VSTs kill their targets and proliferate successfully in the presence of high doses of dexamethasone both in vitro and in vivo. Moreover, we developed a protocol for the rapid generation of GMP-grade NR3C1 KO VSTs with high on-target activity and minimal off-target editing. These genetically engineered VSTs promise to be a novel approach for the treatment of patients with life-threatening viral infections post-HSCT on glucocorticoid therapy