"For us, whatever we do is wrong, until we do something really good" : a qualitative study of the lived experiences of doctors from minority ethnic backgrounds in Scotland

Acknowledgments We remain very grateful to all the participants for giving us their time and sharing their thoughts and experiences with us. Funding The study received a research grant from the Scottish Medical Education Research Consortium (SMERC).Peer reviewedPublisher PD

Evaluation of SARS-CoV-2 antibody point of care devices in the laboratory and clinical setting

SARS-CoV-2 antibody tests have been marketed to diagnose previous SARS-CoV-2 infection and as a test of immune status. There is a lack of evidence on the performance and clinical utility of these tests. We aimed to carry out an evaluation of 14 point of care (POC) SARS-CoV-2 antibody tests. Serum from participants with previous RT-PCR (real-time polymerase chain reaction) confirmed SARS-CoV-2 infection and pre-pandemic serum controls were used to determine specificity and sensitivity of each POC device. Changes in sensitivity with increasing time from infection were determined on a cohort of study participants. Corresponding neutralising antibody status was measured to establish whether the detection of antibodies by the POC device correlated with immune status. Paired capillary and serum samples were collected to ascertain whether POC devices performed comparably on capillary samples. Sensitivity and specificity varied between the POC devices and in general did not meet the manufacturers’ reported performance characteristics, which signifies the importance of independent evaluation of these tests. The sensitivity peaked at ≥20 days following onset of symptoms, however sensitivity of 3 of the POC devices evaluated at extended time points showed that sensitivity declined with time. This was particularly marked at >140 days post infection. This is relevant if the tests are to be used for sero-prevalence studies. Neutralising antibody data showed that positive antibody results on POC devices did not necessarily confer high neutralising antibody titres, and that these POC devices cannot be used to determine immune status to the SARS-CoV-2 virus. Comparison of paired serum and capillary results showed that there was a decline in sensitivity using capillary blood. This has implications in the utility of the tests as they are designed to be used on capillary blood by the general population

A National Survey of Hereditary Angioedema and Acquired C1 Inhibitor Deficiency in the United Kingdom

Background: Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better demographic data would be beneficial in planning service provision, identifying areas of improvement, and improving care./ Objective: To obtain more accurate data on the demographics of HAE and acquired C1 inhibitor deficiency in the United Kingdom, including treatment modalities and services available to patients./ Methods: A survey was distributed to all centers in the United Kingdom that look after patients with HAE and acquired C1 inhibitor deficiency to collect these data./ Results: The survey identified 1152 patients with HAE-1/2 (58% female and 92% type 1), 22 patients with HAE with normal C1 inhibitor, and 91 patients with acquired C1 inhibitor deficiency. Data were provided by 37 centers across the United Kingdom. This gives a minimum prevalence of 1:59,000 for HAE-1/2 and 1:734,000 for acquired C1 inhibitor deficiency in the United Kingdom. A total of 45% of patients with HAE were on long-term prophylaxis (LTP) with the most used medication being danazol (55% of all patients on LTP). Eighty-two percent of patients with HAE had a home supply of acute treatment with C1 inhibitor or icatibant. A total of 45% of patients had a supply of icatibant and 56% had a supply of C1 inhibitor at home./ Conclusions: Data obtained from the survey provide useful information about the demographics and treatment modalities used in HAE and acquired C1 inhibitor deficiency in the United Kingdom. These data are useful for planning service provision and improving services for these patients

Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK

In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to the hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir, and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count, and the presence of co-morbidities are additional risk factors for poor outcome in this cohort

Triggering mechanism and brittle-ductile dynamics of active faults in the south-central Saurashtra horst, Gujarat, western India: A geospatial, geological, and geophysical approach

The seismically active Saurashtra horst is located within the intraplate volcanic continental margin of western India. The region is prone to moderate and low-magnitude earthquakes within the depth range of ∼ 3 to ∼ 24 km. We observed that the earthquakes in this region are associated with seismically active brittle and ductile crustal layers. To understand the dynamics of the earthquake generation process, we applied an integrated geological and geomorphological approach, supplemented by subsurface geophysical (magnetotelluric) studies. Additionally, the active surface deformation has been measured using the PSInSAR and GLA techniques. Based on the stream offset and geomorphic landform development pattern several NW-SE and NE-SW oriented strike-slip faults have been identified. The PSI-derived displacement analysis reveals that the area is deforming at the rate of ± 5 mm/yr. Furthermore, subsurface crustal heterogeneity with increasing depth has been identified using the magnetotelluric technique, which is reflected in the form of basaltic lava flows, plutonic emplacement within the granitic basement, and the presence of semi-crystallized magmatic bodies below the brittle-ductile level. Additionally, we proposed a model to depict the plutonic emplacement within the highly fractured/faulted granitic basement and their relationship to the earthquake generation process. Our model shows that crustal heterogeneity and the migration of hydrothermal fluid from the semi-crystallized magmatic body along the active fault cause earthquake nucleation processes within the brittle and ductile layers. We concluded that the upwelling magmatic fluid above the brittle-ductile transition (BDT) acted as a lubricant for the nucleation and triggering of the earthquake along the active faults. Similarly, the fractured ductile crust is weakened by fluid migration, which causes high fluid pressure in the ductile crust thereby decreasing the confining pressure and endorsing the velocity weakening in the aseismic layer, responsible for the shear instability that causes deep crustal earthquakes. More specifically, the lithological heterogeneity at brittle and ductile regimes is an important factor for the earthquake nucleation process in this part of the Indian plate