Suboptimal SVR rates in African patients with atypical genotype 1 subtypes: Implications for global elimination of hepatitis C.

BACKGROUND & AIMS: HCV subtypes which are unusual in Europe are more prevalent in the African region, but little is known of their response to direct-acting antivirals (DAAs). These include non-1a/1b/ non-subtypeable genotype 1 (G1) or non-4a/4d (G4). In this report we aimed to describe the genotype distribution and treatment outcome in a south London cohort of African patients. METHODS: We identified all patients born in Africa who attended our clinic from 2010-2018. Information on HCV genotype, treatment regimen and outcome were obtained. Non-subtypeable samples were analysed using Glasgow NimbleGen next-generation sequencing (NGS). Phylogenetic analysis was carried out by generating an uncorrected nucleotide p-distance tree from the complete coding regions of our sequences. RESULTS: Of 91 African patients, 47 (52%) were infected with an unusual subtype. Fourteen novel, as yet undesignated subtypes (G1*), were identified by NGS. Three individuals were infected with the same subtype, now designated as subtype 1p. Baseline sequences were available for 22 patients; 18/22 (82%) had baseline NS5A resistance-associated substitutions (RASs). Sustained virological response (SVR) was achieved in 56/63 (89%) overall, yet only in 21/28 (75%) of those with unusual G1 subtypes, with failure in 3/16 G1*, 1/2 G1p and 3/3 in G1l. Six treatment failures occurred with sofosbuvir/ledipasvir compared to 1 failure on a PI-based regimen. The SVR rate for all other genotypes and subtypes was 35/35 (100%). CONCLUSIONS: Most individuals in an unselected cohort of African patients were infected with an unusual genotype, including novel subtype 1p. The SVR rate of those with unusual G1 subtypes was 75%, raising concern about expansion of DAAs across Africa. Depending on the regimen used, higher failure rates in African cohorts could jeopardise HCV elimination. LAY SUMMARY: Direct-acting antiviral medications are able to cure hepatitis C in the majority of patients. The most common genotype of hepatitis C in Europe and the United States is genotype 1a or 1b and most clinical trials focused on these genotypes. We report that in a group of African patients, most of them had unusual (non-1a/1b) genotype 1 subtypes, and that the cure rate in these unusual genotypes was lower than in genotypes 1a and 1b

Thalassaemia Prior and Consequent to COVID-19 Pandemic. The Perspective of Thalassaemia International Federation (TIF)

Patients with haemoglobin disorders, particularly β-thalassaemia or sickle cell disease (SCD) or combined forms, on account of their underlying disease pathology and associated (iron load mainly in the case of thalassaemia) co-morbidities are defined as high-risk individuals prone to develop more severe complications from coronavirus disease-2019 (COVID-19). Despite the fact that epidemiological evidence concerning severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection in these patients is currently limited across the world, it is expected that COVID-19 pandemic will have a very serious, negative impact on national economies, healthcare and social systems and consequently significant respective repercussions on the patients particularly chronic ones, and their families. Although this may be a temporary challenge in some countries of high HDI and robust health, public health and social infrastructures, this can be a long term challenge with serious to tragic consequences in countries particularly devoid of universally covered heath care systems. Thalassaemia International Federation (TIF) in this present paper summarises the key challenges as expressed by the patients, their families and involved health care professionals themselves prior and consequent to COVID-19 pandemic, describes its response during the pandemic and expresses its position in support of its global patient community

Hemoglobin Disorders in Europe: A Systematic Effort of Identifying and Addressing Unmet Needs and Challenges by the Thalassemia International Federation

Hemoglobin disorders (thalassemia and sickle cell disease) are a group of hereditary anemias that today occur across the world. The recent population movement has led to a steady increase of carriers and patients in all countries of the European Union. Requiring complex monitoring and treatment and, as a consequence, well-organized and nationally coordinated, supported and funded services, these lifelong conditions are now visible to healthcare services in the EU. The purpose of this study is to provide an overview of the current situation pertaining to these disorders, as perceived by the patient/parent community that the Thalassemia International Federation (TIF) represents. The aim is to establish a comprehensive understanding of the situation and unmet needs faced by migrants with thalassemia. The implementation of activities by TIF in 2018–2020 to identify and address these challenges, paves the way to increased awareness, education and policy changes building on international expertise and knowledge that will enable the provision of state-of-art clinical management services thus guaranteeing an improved quality of life. A bird’s eye view of the prevalence of these disorders is presented contributing to the further understanding of challenges met by both patients and healthcare professionals in the receipt and provision of quality healthcare respectively

Hemoglobin disorders in Europe: a systematic effort of identifying and addressing unmet needs and challenges by the Thalassemia International Federation

Hemoglobin disorders (thalassemia and sickle cell disease) are a group of hereditary anemias that today occur across the world.The recent population movement has led to a steady increase of carriers and patients in all countries of the European Union.Requiring complex monitoring and treatment and, as a consequence, well-organized and nationally coordinated, supported and funded services, these lifelong conditions are now visible to healthcare services in the EU. The purpose of this study is to provide an overview of the current situation pertaining to these disorders, as perceived by the patient/parent community that the Thalassemia International Federation (TIF)represents. The aim is to establish a comprehensive understanding of the situation and unmet needs faced by migrants with thalassemia. The implementation of activities by TIF in 2018-2020 to identify and address these challenges, paves the way to increased awareness, education and policy changes building on international expertise and knowledge that will enable the provision of state-of-art clinical management services thus guaranteeing an improved quality of life. A bird's eye view of the prevalence of these disorders is presented contributing to the further understanding of challenges met by both patients and healthcare professionals in the receipt and provision of quality healthcare respectively

Architecture of the human interactome defines protein communities and disease networks

The physiology of a cell can be viewed as the product of thousands of proteins acting in concert to shape the cellular response. Coordination is achieved in part through networks of protein-protein interactions that assemble functionally related proteins into complexes, organelles, and signal transduction pathways. Understanding the architecture of the human proteome has the potential to inform cellular, structural, and evolutionary mechanisms and is critical to elucidation of how genome variation contributes to disease1–3. Here, we present BioPlex 2.0 (Biophysical Interactions of ORFEOME-derived complexes), which employs robust affinity purification-mass spectrometry (AP-MS) methodology4 to elucidate protein interaction networks and co-complexes nucleated by more than 25% of protein coding genes from the human genome, and constitutes the largest such network to date. With >56,000 candidate interactions, BioPlex 2.0 contains >29,000 previously unknown co-associations and provides functional insights into hundreds of poorly characterized proteins while enhancing network-based analyses of domain associations, subcellular localization, and co-complex formation. Unsupervised Markov clustering (MCL)5 of interacting proteins identified more than 1300 protein communities representing diverse cellular activities. Genes essential for cell fitness6,7 are enriched within 53 communities representing central cellular functions. Moreover, we identified 442 communities associated with more than 2000 disease annotations, placing numerous candidate disease genes into a cellular framework. BioPlex 2.0 exceeds previous experimentally derived interaction networks in depth and breadth, and will be a valuable resource for exploring the biology of incompletely characterized proteins and for elucidating larger-scale patterns of proteome organization

Six habits to enhance MET performance under stress: a discussion paper reviewing team mechanisms for improved patient outcomes

Effective team decision making has the potential to improve the quality of health care outcomes. Medical Emergency Teams (METs), a specific type of team led by either critical care nurses or physicians, must respond to and improve the outcomes of deteriorating patients. METs routinely make decisions under conditions of uncertainty and suboptimal care outcomes still occur. In response, the development and use of Shared Mental Models (SMMs), which have been shown to promote higher team performance under stress, may enhance patient outcomes. This discussion paper specifically focuses on the development and use of SMMs in the context of METs. Within this process, the psychological mechanisms promoting enhanced team performance are examined and the utility of this model is discussed through the narrative of six habits applied to MET interactions. A two stage, reciprocal model of both nonanalytic decision making within the acute care environment and analytic decision making during reflective action learning was developed. These habits are explored within the context of a MET, illustrating how applying SMMs and action learning processes may enhance team-based problem solving under stress. Based on this model, we make recommendations to enhance MET decision making under stress. It is suggested that the corresponding habits embedded within this model could be imparted to MET members and tested by health care researchers to assess the efficacy of this integrated decision making approach in respect to enhanced team performance and patient outcomes