A retrospective observational study to evaluate the clinical outcomes and routine management of patients with chronic lymphocytic leukaemia treated with idelalisib and rituximab in the UK and Ireland (RETRO-idel).

Idelalisib (IDL) is an oral first-in-class phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor approved for chronic lymphocytic leukaemia (CLL) alongside rituximab (R) since 2014. However, little data exist on routine practice. The RETRO-idel was a protocol-led, retrospective study of 110 patients [n = 27 front-line (1L)] who received IDL-R. The primary end-point was clinical overall response rate (ORR). The median (range) follow-up of the whole cohort was 30·2 (0·1-51·9) months. The median (range) age was 72 (48-89) years. Tumour protein p53-disruption was common [100% 1L, 32·5% relapsed/refractory (R/R)]. The best ORR (intention-to-treat) was 88·2% (1L 96·3%, R/R 85·5%). Overall, the median event-free survival (mEFS) was 20·3 months and time-to-next treatment was 29·2 months. The mEFS for 1L patients was 18·7 months and R/R patients was 21·7 months. The 3-year overall survival was 56·1% (95% confidence interval 45·7-65·3). IDL was discontinued in 87·3% (n = 96). More patients discontinued due to adverse events in the front-line setting (1L 63·0% vs. R/R 44·6%) and due to progressive disease in R/R patients (20·5% vs. 3·7% in 1L). Lower respiratory tract infection/pneumonia were reported in 34·5% (Grade ≥3, 19·1%), diarrhoea in 30·9% (Grade ≥3, 6·4%), and colitis in 9·1% (Grade ≥3, 5·5%). Overall, these data describe clear efficacy for IDL-R in routine practice. No new safety signals were identified, although careful management of known toxicities is required.

An Update on COVID-19 Vaccine Induced Thrombotic Thrombocytopenia Syndrome and Some Management Recommendations.

The thrombotic thrombocytopenia syndrome (TTS), a complication of COVID-19 vaccines, involves thrombosis (often cerebral venous sinus thrombosis) and thrombocytopenia with occasional pulmonary embolism and arterial ischemia. TTS appears to mostly affect females aged between 20 and 50 years old, with no predisposing risk factors conclusively identified so far. Cases are characterized by thrombocytopenia, higher levels of D-dimers than commonly observed in venous thromboembolic events, inexplicably low fibrinogen levels and worsening thrombosis. Hyper fibrinolysis associated with bleeding can also occur. Antibodies that bind platelet factor 4, similar to those associated with heparin-induced thrombocytopenia, have also been identified but in the absence of patient exposure to heparin treatment. A number of countries have now suspended the use of adenovirus-vectored vaccines for younger individuals. The prevailing opinion of most experts is that the risk of developing COVID-19 disease, including thrombosis, far exceeds the extremely low risk of TTS associated with highly efficacious vaccines. Mass vaccination should continue but with caution. Vaccines that are more likely to cause TTS (e.g., Vaxzevria manufactured by AstraZeneca) should be avoided in younger patients for whom an alternative vaccine is available.

Beyond Information Provision: Analysis of the Roles of Structure and Agency in COVID-19 Vaccine Confidence in Ethnic Minority Communities.

People from Black and Asian backgrounds are more likely to die from COVID-19 but less likely to be vaccinated, threatening to exacerbate health inequalities already experienced by ethnic minority groups. The literature suggests that mistrust rooted in structural inequality (including socioeconomic position and experience of racism) may be a key barrier to COVID-19 vaccine uptake. Understanding and addressing structural inequality is likely to lead to longer-term impacts than information alone. The aim of this study is to draw on health and sociological theories of structure and agency to inform our understanding of how structural factors influence vaccine confidence. We conducted qualitative interviews and focus groups with 22 people from London and the surrounding areas from December 2021 to March 2022. Fourteen participants were members of the public from ethnic minority backgrounds, and seven were professionals working with the public to address concerns and encourage vaccine uptake. Our findings suggest that people from ethnic minority backgrounds make decisions regarding COVID-19 vaccination based on a combination of how they experience external social structures (including lack of credibility and clarity from political authority, neglect by health services, and structural racism) and internal processes (weighing up COVID-19 vaccine harms and benefits and concerns about vaccine development and deployment). We may be able to support knowledge accumulation through the provision of reliable and accessible information, particularly through primary and community care, but we recommend a number of changes to research, policy and practice that address structural inequalities. These include working with communities to improve ethnicity data collection, increasing funding allocation to health conditions where ethnic minority communities experience poorer outcomes, greater transparency and public engagement in the vaccine development process, and culturally adapted research recruitment processes.

Coagulopathy of Dengue and COVID-19: Clinical Considerations.

Thrombocytopenia and platelet dysfunction commonly occur in both dengue and COVID-19 and are related to clinical outcomes. Coagulation and fibrinolytic pathways are activated during an acute dengue infection, and endothelial dysfunction is observed in severe dengue. On the other hand, COVID-19 is characterised by a high prevalence of thrombotic complications, where bleeding is rare and occurs only in advanced stages of critical illness; here thrombin is the central mediator that activates endothelial cells, and elicits a pro-inflammatory reaction followed by platelet aggregation. Serological cross-reactivity may occur between COVID-19 and dengue infection. An important management aspect of COVID-19-induced immunothrombosis associated with thrombocytopenia is anticoagulation with or without aspirin. In contrast, the use of aspirin, nonsteroidal anti-inflammatory drugs and anticoagulants is contraindicated in dengue. Mild to moderate dengue infections are treated with supportive therapy and paracetamol for fever. Severe infection such as dengue haemorrhagic fever and dengue shock syndrome often require escalation to higher levels of support in a critical care facility. The role of therapeutic platelet transfusion is equivocal and should not be routinely used in patients with dengue with thrombocytopaenia and mild bleeding. The use of prophylactic platelet transfusion in dengue fever has strained financial and healthcare systems in endemic areas, together with risks of transfusion-transmitted infections in low- and middle-income countries. There is a clear research gap in the management of dengue with significant bleeding.

The COVID-19 Pandemic: Disproportionate Thrombotic Tendency and Management Recommendations.

COVID-19 is an infectious disease caused by the SARS COV-2 virus. Patients with COVID-19 are susceptible to thrombosis due to excessive inflammation, platelet activation, endothelial dysfunction, and circulatory stasis, resulting in an increased risk of death due to associated coagulopathies. In addition, many patients receiving antithrombotic therapy for pre-existing thrombotic diseases can develop COVID-19, which can further complicate dose adjustment, choice and laboratory monitoring of antithrombotic treatment. This review summarizes the laboratory findings, the prohemostatic state, incidence of thromboembolic events and some potential therapeutic interventions of COVID-19 associated coagulopathy. We explore the roles of biomarkers of thrombosis and inflammation according to the severity of COVID-19. While therapeutic anticoagulation has been used empirically in some patients with severe COVID-19 but without thrombosis, it may be preferable to provide supportive care based on evidence-based randomized clinical trials. The likely lifting of travel restrictions will accelerate the spread of COVID-19, increasing morbidity and mortality across nations. Many individuals will continue to receive anticoagulation therapy regardless of their location, requiring on-going treatment with low-molecular weight heparin, vitamin K antagonist or direct-acting anticoagulants.