Migrants' primary care utilisation before and during the COVID-19 pandemic in England: An interrupted time series analysis.

Background: How international migrants access and use primary care in England is poorly understood. We aimed to compare primary care consultation rates between international migrants and non-migrants in England before and during the COVID-19 pandemic (2015-2020). Methods: Using data from the Clinical Practice Research Datalink (CPRD) GOLD, we identified migrants using country-of-birth, visa-status or other codes indicating international migration. We linked CPRD to Office for National Statistics deprivation data and ran a controlled interrupted time series (ITS) using negative binomial regression to compare rates before and during the pandemic. Findings: In 262,644 individuals, pre-pandemic consultation rates per person-year were 4.35 (4.34-4.36) for migrants and 4.60 (4.59-4.60) for non-migrants (RR:0.94 [0.92-0.96]). Between 29 March and 26 December 2020, rates reduced to 3.54 (3.52-3.57) for migrants and 4.2 (4.17-4.23) for non-migrants (RR:0.84 [0.8-0.88]). The first year of the pandemic was associated with a widening of the gap in consultation rates between migrants and non-migrants to 0.89 (95% CI 0.84-0.94) times the ratio before the pandemic. This widening in ratios was greater for children, individuals whose first language was not English, and individuals of White British, White non-British and Black/African/Caribbean/Black British ethnicities. It was also greater in the case of telephone consultations, particularly in London. Interpretation: Migrants were less likely to use primary care than non-migrants before the pandemic and the first year of the pandemic exacerbated this difference. As GP practices retain remote and hybrid models of service delivery, they must improve services and ensure primary care is accessible and responsive to migrants' healthcare needs. Funding: This study was funded by the Medical Research Council (MC_PC 19070 and MR/V028375/1) and a Wellcome Clinical Research Career Development Fellowship (206602).

Health on the Move (HOME) Study: Using a smartphone app to explore the health and wellbeing of migrants in the United Kingdom.

Background/Aim: We have a limited understanding of the broader determinants of health of international migrants and how these change over time since migration to the United Kingdom (UK). To address this knowledge gap, we aim to conduct a prospective cohort study with data acquisition via a smartphone application (app). In this pilot study, we aim to 1) determine the feasibility of the use of an app for data collection in international migrants, 2) optimise app engagement by quantifying the impact of specific design features on the completion rates of survey questionnaires and on study retention, 3) gather preliminary profile health status data, to begin to examine how risk factors for health are distributed among migrants. Methods: We will recruit 275 participants through a social media campaign and through third sector organisations that work with or support migrants in the UK. Following consent and registration, data will be collected via surveys. To optimise app engagement and study retention, we will quantify the impact of specific design features (i.e. the frequency of survey requests, the time of day for app notifications, the frequency of notifications, and the wording of notifications) via micro-randomised process evaluations. The primary outcome for this study is survey completion rates with numerator as the number of surveys completed and denominator as the total number of available surveys. Secondary outcomes are study retention rates and ratings of interest after app usage. Ethics and dissemination: We have obtained approval to use consented patient identifiable data from the University College London Ethics Committee. Improving engagement with the app and gathering preliminary health profile data will help us identify accessibility and usability issues and other barriers to app and study engagement prior to moving to a larger study.

Thromboelastography does not predict outcome in different etiologies of cirrhosis.

BACKGROUND: New laboratory tests that measure global hemostasis indicate generally preserved hemostatic function in patients with cirrhosis. It is not known whether normal hemostatic function is maintained across various subsets of patients. OBJECTIVES: In the present study, we investigated clot generation and clot lysis kinetics in a large group of patients with different etiologies of disease. PATIENTS/METHODS: Blood samples of 270 patients with cirrhosis were studied using thromboelastography (TEG), which measures the dynamic and physical properties of clot formation and lysis in whole blood. TEG parameters of different subsets of the patient population were compared. Correlations with routine laboratory tests as well as clinical outcomes were explored. RESULTS: Overall, TEG parameters were normal and similar between underlying disease etiologies. A proportion of subjects showed hypocoagulable features, with the exception of patients with cholestatic cirrhosis in whom TEG readings showed hypercoagulable features. In all groups, K-time, α-Angle, and MA correlated well with platelet counts and fibrinogen plasma levels. After a mean follow-up of 2 years and 11 months, 31 patients had experienced a bleeding event, 8 had developed thrombosis, and 173 patients (64%) had undergone liver transplantation and/or had died. TEG baseline parameters were similar between patients subdivided according to outcome. CONCLUSIONS: TEG parameters reflected generally preserved function of the hemostatic system in patients with cirrhosis, with hypo- and hypercoagulable features in subsets of patients with specific underlying disease etiologies. Abnormalities in TEG parameters did however not predict bleeding, thrombosis, or risk of liver transplantation and/or death.

Is there a rationale for treatment of chronic liver disease with antithrombotic therapy?

Recent advances in the understanding of the coagulopathy in chronic liver disease have provided a strong support for anticoagulation as a new therapeutic paradigm for patients with cirrhosis. Laboratory studies indicate that the net effect of changes in hemostasis in many patients with chronic liver disease is a hypercoagulable status. In turn, clinical thrombosis is increasingly recognized as a complication of liver disease. When occurring within the liver, thrombosis may even progress the disease course. Exciting preliminary data regarding the potential of low-molecular-weight heparin to slow down the progression of liver disease indicate that this class of drugs may improve outcome without a major increase in bleeding risk. However, this new era for antithrombotic therapy in chronic liver disease is still hindered by a persistent false notion that patients with cirrhosis are "auto-anticoagulated" by their underlying liver disease. In addition, there is insufficient clinical evidence on safety and efficacy of anticoagulant therapy in cirrhosis and the studies conducted so far are limited by small sample sizes, uncontrolled treatment arms, or by their retrospective nature. Finally, a lack of knowledge on how or when to monitor antithrombotic treatment to optimize the risk-benefit ratio has restricted a widespread application of anticoagulant treatment in clinical management algorithms. Nonetheless, by systematically covering possibilities and pitfalls, this review highlights the potential of antithrombotic therapy to improve the quality of life and the clinical outcome of patients with chronic liver disease.

An unbalance between von Willebrand factor and ADAMTS13 in acute liver failure: implications for hemostasis and clinical outcome.

UNLABELLED: Emerging evidence supports the concept of a rebalanced hemostatic state in liver disease as a result of a commensurate decline in prohemostatic and antihemostatic drivers. In the present study, we assessed levels and functionality of the platelet-adhesive protein von Willebrand factor (VWF) and its cleaving protease ADAMTS13 in the plasma of patients with acute liver injury and acute liver failure (ALI/ALF). Furthermore, we explored possible associations between VWF, ADAMTS13, and disease outcome. We analyzed the plasma of 50 patients taken on the day of admission for ALI/ALF. The plasma of 40 healthy volunteers served as controls. VWF antigen levels were highly elevated in patients with ALI/ALF. In contrast, the collagen-binding activity and the ratio of the VWF ristocetin cofactor activity and VWF antigen was significantly decreased when compared with healthy controls. Also, the proportion of high molecular weight VWF multimers was reduced, despite severely decreased ADAMTS13 levels. In spite of these functional defects, platelet adhesion and aggregation were better supported by plasma of patients with ALI/ALF when compared with control plasma. Low ADAMTS13 activity, but not high VWF antigen, was associated with poor outcome in patients with ALI/ALF as evidenced by higher grades of encephalopathy, higher transplantation rates, and lower survival. VWF or ADAMTS13 levels were not associated with bleeding or thrombotic complications. CONCLUSION: Highly elevated levels of VWF in plasma of patients with ALI/ALF support platelet adhesion, despite a relative loss of function of the molecule. Furthermore, low ADAMTS13 activity is associated with progressive liver failure in the patient cohort, which might be attributed to platelet-induced microthrombus formation in the diseased liver resulting from a substantially unbalanced VWF/ADAMTS13 ratio.

Susceptibility of human pancreatic ß cells for cytomegalovirus infection and the effects on cellular immunogenicity.

OBJECTIVES: Human cytomegalovirus (HCMV) infection has been suggested to be a causal factor in the development of type 1 diabetes, posttransplantation diabetes, and the failure of islet allografts. This effect of CMV has been interpreted as an indirect effect on the immune system rather than direct infection-induced cell death. In the present study, we investigated (i) the susceptibility of ß cells to HCMV infection, (ii) regulation of immune cell-activating ligands, (iii) release of proinflammatory cytokines, and (iv) the effects on peripheral blood mononuclear cell (PBMC) activation. METHODS: CM insulinoma cells and primary ß cells were HCMV-infected in vitro using a laboratory and a clinical HCMV strain. The susceptibility to infection was measured by the expression of viral genes and proteins. Furthermore, expression levels of Major Histocompatibility Complex I, Intracellular Adhesion Molecule-1, and Lymphocyte Function Associated Antigen-3 and the release of proinflammatory cytokines were determined. In addition, PBMC activation to HCMV-infected ß cells was determined. RESULTS: ß Cells were susceptible to HCMV infection. Moreover, the infection increased the cellular immunogenicity, as demonstrated by an increased MHC I and ICAM-1 expression and an increased proinflammatory cytokine release. Human cytomegalovirus-infected CM cells potently activated PBMCs. The infection-induced effects were dependent on both viral "sensing" and viral replication. CONCLUSIONS: In vivo ß-cell HCMV infection and infection-enhanced cellular immunogenicity may have important consequences for native or transplanted ß-cell survival.