Vaccination against viruses has rarely been associated with Guillain-Barré syndrome (GBS). An association with the COVID-19 vaccine is unknown. We performed a population-based study of National Health Service data in England and a multicentre surveillance study from UK hospitals, to investigate the relationship between COVID-19 vaccination and GBS. Firstly, case dates of GBS identified retrospectively in the National Immunoglobulin Database from 8 December 2021 to 8 July 2021 were linked to receipt dates of a COVID-19 vaccines using data from the National Immunisation Management System in England. For the linked dataset, GBS cases temporally associated with vaccination within a 6-week risk window of any COVID-19 vaccine were identified. Secondly, we prospectively collected incident UK-wide (four nations) GBS cases from 1 January 2021 to 7 November 2021 in a separate UK multicentre surveillance database. For this multicentre UK-wide surveillance dataset, we explored phenotypes of reported GBS cases to identify features of COVID-19 vaccine-associated GBS. 996 GBS cases were recorded in the National Immunoglobulin Database from January to October 2021. A spike of GBS cases above the 2016-2020 average occurred in March-April 2021. 198 GBS cases occurred within 6 weeks of the first-dose COVID-19 vaccination in England (0.618 cases per 100,000 vaccinations, 176 ChAdOx1 nCoV-19 (AstraZeneca), 21 tozinameran (Pfizer), 1 mRNA-1273 (Moderna)). The 6-week excess of GBS (compared to the baseline rate of GBS cases 6-12 weeks after vaccination) occurs with a peak at 24 days post-vaccination; first-doses of ChAdOx1 nCoV-19 accounted for the excess. No excess was seen for second-dose vaccination. The absolute number of excess GBS cases from January-July 2021 was between 98-140 cases for first-dose ChAdOx1 nCoV-19 vaccination. First-dose tozinameran and second-dose of any vaccination showed no excess GBS risk. Detailed clinical data from 121 GBS patients were reported in the separate multicentre surveillance dataset during this timeframe. No phenotypic or demographic differences identified between vaccine-associated and non-vaccinated GBS cases occurring in the same timeframe. Analysis of the linked NID/NIMS dataset suggests that first-dose ChAdOx1 nCoV-19 vaccination is associated with an excess GBS risk of 0.576 (95%CI 0.481-0.691) cases per 100,000 doses. However, examination of a multicentre surveillance dataset suggests that no specific clinical features, including facial weakness, are associated with vaccination-related GBS compared to non-vaccinated cases. The pathogenic cause of the ChAdOx1 nCoV-19 specific first dose link warrants further study.

Introduction

Purpose The purpose of this study is to characterise how Type 2 Diabetes Mellitus (T2DM) is treated in England and Wales and whether this adheres to 2009 National Institute for Health and Care Excellence (NICE) guidance on management of T2DM. Methods Data for T2DM patients aged 18+ years prescribed at least one anti-diabetic drug between 01/01/2000-30/06/2012 were extracted from the Clinical Practice Research Datalink.We examined the sequences in which anti-diabetic drugs were prescribed and, for patients on the most common anti-diabetic drug pathways, evaluated average HbA1c values at treatment initiation and at progression to a second or third-line anti-diabetic drug class, including insulin.Results The cohort included 123 671 patients, 56% males, 95% aged 40+ and 79% with at least one recorded HbA1c level. Metformin was the first prescription for 98 957 (80%) patients, with mean HbA1c of 8.68% prior to initiation (95% confidence interval [CI] 8.67, 8.69). A total of 19 890 (16%) patients received sulphonylureas first-line (mean HbA1c = 9.31%, 95%CI 9. 27, 9.35). 1402 (12%) insulin users were prescribed insulin first-line (mean HbA1c = 9.89%, 95%CI 9.59, 10.19). A total of 96 895 (78%) patients were managed in line with one of the treatment pathways recommended by NICE.Patients prescribed insulin second-line after metformin had a mean HbA1c of 10.11% (95%CI 9.83, 10.38) prior to first prescription of insulin and 9.98% (95%CI 9.73, 10.23) at baseline. Both values were significantly higher than other groups initiating new treatment. Conclusions In over three-quarters of patients, anti-diabetic drugs are being prescribed per NICE guidance. When insulin is being used earlier than recommended, there appears to be a need for urgent and rapid glycaemic control.

ObjectivesTo compare mean birth weights, gestational ages and odds of preterm birth and low birth weight of live singleton babies of black African or Caribbean ethnicity born in 2005 or 2006 by mother's country of birth.DesignSecondary analysis of data from linked birth registration and NHS Numbers for Babies data set.SettingBirths to women in England and Wales in 2005 and 2006.ParticipantsBabies of African and Caribbean ethnicity born in England and Wales in 2005–2006, whose mothers were born in African and Caribbean countries or the UK. Birth outcomes for 51 599 singleton births were analysed.Main outcome measuresGestational age and birth weight.ResultsMothers born in Eastern or Northern Africa had babies at higher mean gestational ages (39.38 and 39.41 weeks, respectively) and lower odds of preterm birth (OR=0.80 and 0.65, respectively) compared with 39.00 weeks for babies with mothers born in the UK. Babies of African ethnicity whose mothers were born in Middle or Western Africa had mean birth weights of 3327 and 3311 g, respectively. These were significantly higher than the mean birth weight of 3257 g for babies of the UK-born mothers. Their odds of low birth weight (OR=0.75 and 0.72, respectively) were significantly lower. Babies of Caribbean ethnicity whose mothers were born in the Caribbean had higher mean birth weight and lower odds of low birth weight than those whose mothers were born in the UK.ConclusionsThe study shows that in babies of African and Caribbean ethnicity, rates of low birth weight and preterm birth varied by mothers' countries of birth. Ethnicity and country of birth are important factors associated with perinatal health, but assessing them singly can mask important heterogeneity in birth outcomes within categories particularly in relation to African ethnicity. These differences should be explored further.

The precise effects of CD34 þ cell dose on the outcome of allogeneic transplantation for aplastic anaemia (AA) are not known. Previous studies have used the total mononuclear cell count to quantify stem cell dose. We evaluated the effects of CD34 þ cell dose on the clinical and haematological end points of transplantation. The transplant variables and outcome parameters on 46 patients with acquired AA were assessed by comparing low vs high CD34 þ cell doses. Infusion of less than 2 Â 10 6 /kg of CD34 þ cells was associated with an increased incidence of graft failures (P ¼ 0.03), higher incidence of bacterial infections (P ¼ 0.006) and a delay in the engraftment of neutrophils (P ¼ 0.046). The latter was found to be an effect of stem cell source (non-PBSC) rather than the CD34 þ count. Other parameters, such as plt engraftment (P ¼ 0.63), red cell (P ¼ 0.94) and plt (P ¼ 0.31) transfusion independence, chimerism, acute and chronic GVHD (P ¼ 1.0) and OS (P ¼ 0.57), were not significantly influenced by the CD34 þ cell dose. These findings are different to the published studies on the relevance of CD34 þ cell dose in allogeneic transplantation for haematological cancers.

Vaccination against viruses has rarely been associated with Guillain-Barré syndrome (GBS). An association with the COVID-19 vaccine is unknown. We performed a population-based study of National Health Service (NHS) data in England and a multicentre surveillance study from UK hospitals, to investigate the relationship between COVID-19 vaccination and GBS.Firstly, we present a retrospective analysis of every GBS patient in England in the National Immunoglobulin Database (NID) linked with their COVID-19 vaccination data. Cases of GBS identified in the National Immunoglobulin Database (NID) from 8 December 2021 to 8 July 2021 were linked to data from the National Immunisation Management System (NIMS) in England to identify exposure to a COVID-19 vaccine. For the NID/NIMS linked dataset, GBS cases temporally associated with vaccination within a 6-week risk window of any COVID-19 vaccine were identified. Secondly, we prospectively collected incident UK GBS cases from 1 January 2021 to 7 November 2021 in a separate UK multicentre surveillance database, regardless of vaccine exposure, with vaccine timings and GBS phenotypic data. For this multicentre UK surveillance dataset, we explored phenotypes of reported GBS cases to identify features of COVID-19 vaccine-associated GBS.996 GBS cases were recorded in the NID from January to October 2021. A spike of GBS cases above the 2016-2020 average occurred in March-April 2021. In England, among all cases of GBS, 198 occurred within 6 weeks of the first-dose COVID-19 vaccination (0.618 cases per 100,000 vaccinations, 176 ChAdOx1 nCoV-19 (AstraZeneca), 21 tozinameran (Pfizer), 1 mRNA-1273 (Moderna)). The excess of GBS occurs with a peak at 24 days; first-doses of ChAdOx1 nCoV-19 accounted for the excess. No excess was seen for second-dose vaccination. The absolute number of excess GBS cases was between 98-140 cases for first-dose ChAdOx1 nCoV-19 vaccination from January-July 2021. First-dose tozinameran and second-dose of any vaccination showed no excess GBS risk. 121 patients were reported in the separate multicentre surveillance dataset with no phenotypic or demographic differences identified between vaccinated and non-vaccinated GBS cases.Data from the linked NID/NIMS dataset suggest that first-dose ChAdOx1 nCoV-19vaccination is associated with an excess GBS risk of 0.576 (95%CI 0.481-0.691) cases per 100,000 doses. However, further data reported from a multicentre surveillance dataset suggest that no specific clinical features, including facial weakness, are associated with vaccination-related GBS compared to non-vaccinated cases. The pathogenic cause of the ChAdOx1 nCoV-19specific first dose link warrants further study.

Hematological cancers and non-malignant hematological disorders are biologically diverse conditions and are treated differently. We compared the pattern of EBV infections following allogeneic stem cell transplantation between the above two groups of hematological disorders. Eighty-three transplants were evaluated over a consecutive 7-year period at a single center. No difference was found in the incidence of post-transplant EBV infections between the two groups, though a higher median peak viral load was noted in the non-malignant group (P=0·04). Pre-transplant immunosuppressive therapy with antithymocyte globulin (ATG) significantly increased the risk of post-transplant EBV infections (P=0·04) in the non-malignant group patients. No significance was found for prior cytotoxic chemotherapy among the malignant group of patients. Alemtuzumab based conditioning was not associated with an increased risk for EBV infections in either of the groups. Treatment with two or more courses of ATG was found to be significantly associated with post-transplant EBV-related PTLD (P=0·01). Post-transplant EBV infections did not influence overall survival (non-malignant, P=0·66; malignant, P=0·41) in either of the subgroups. There were no deaths directly attributable to EBV infections.

PurposeTo develop a cohort of patients with T2DM treated with insulin using CPRD to obtain an accurate diagnosis date. This was used to analyse time from T2DM diagnosis to first ever insulin prescription between 01/01/2000 and 30/06/2012, for patients in England and Wales.MethodsPatients aged 18 years and over at diagnosis, were included if prescribed an anti-diabetic drug and were excluded if first diagnosis-specific code was inconsistent with a T2DM diagnosis. Diagnosis codes were split into 8 categories based on whether they related to specific T2DM or non-specific diabetes codes. Patients were excluded if they had non-specific diagnosis codes and were prescribed insulin as their first-ever treatment for diabetes. Descriptive statistics for time from T2DM diagnosis to insulin initiation were calculated.ResultsTwo hundred and fifty-six codes were identified which were consistent with a first-ever diagnosis of T2DM. 7 codes were considered to clearly define a diagnosis of T2DM, which were reported for 64% of patients. The final cohort comprised 11,917 patients and the median time to first insulin prescription from the date of diagnosis was 4.4 years.ConclusionsA clear definition of cohort development is required to compare and interpret results from studies. Use of diagnosis and product codes is essential when examining use of drugs such as insulin, where competing diagnoses need to be considered separately.