COVID-19 vaccination and Guillain-Barré syndrome: analyses using the National Immunoglobulin Database.

Vaccination against viruses has rarely been associated with Guillain-Barré syndrome (GBS), and 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 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. Nine hundred and ninety-six 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. One hundred and ninety-eight 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) and one mRNA-1273 (Moderna)]. The 6-week excess of GBS (compared to the baseline rate of GBS cases 6-12 weeks after vaccination) occurred 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 suggested that first-dose ChAdOx1 nCoV-19 vaccination is associated with an excess GBS risk of 0.576 (95% confidence interval 0.481-0.691) cases per 100 000 doses. However, examination of a multicentre surveillance dataset suggested 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.

Patterns of anti-diabetic medication use in patients with type 2 diabetes mellitus in England and Wales.

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. © 2016 Crown Copyright. Pharmacoepidemiology and Drug Safety © 2016 John Wiley & Sons, Ltd.

Opportunities and Challenges in Developing a Cohort of Patients with Type 2 Diabetes Mellitus Using Electronic Primary Care Data.

PURPOSE: To 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. METHODS: Patients 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. RESULTS: Two 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. CONCLUSIONS: A 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.

Birth outcomes for African and Caribbean babies in England and Wales: retrospective analysis of routinely collected data.

OBJECTIVES: To 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. DESIGN: Secondary analysis of data from linked birth registration and NHS Numbers for Babies data set. SETTING: Births to women in England and Wales in 2005 and 2006. PARTICIPANTS: Babies 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 MEASURES: Gestational age and birth weight. RESULTS: Mothers 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. CONCLUSIONS: The 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.

Linking maternity data for England, 2005-06: methods and data quality.

INTRODUCTION: Maternity Hospital Episode Statistics (HES) data were linked to birth registration and NHS Numbers for Babies (NN4B) data to bring together some key demographic and clinical data items not otherwise available at a national level. This project added to earlier work involving linkage of birth registration records to NN4B records. METHODS: Birth registration and NN4B records were linked to Maternity HES delivery records and also Maternity HES baby records using the NHS Number or other indirect identifiers if NHS Number was missing.Data quality and completeness of Maternity HES were assessed in relation to birth registration data wherever possible. For information not collected at registration, NN4B data were used to validate quality of Maternity HES. RESULTS: Overall, 91 per cent of Maternity HES delivery records could be linked to the birth registration/NHS Numbers for Babies records and 84 per cent of Maternity HES baby records were linked.In 2005 only 3 per cent of Maternity HES records had mother's NHS number missing, compared with 30 per cent in the NN4B dataset. This did not reflect the extent to which Maternity HES data items were missing or discordant. Over a quarter of all linked Maternity HES records for singleton babies had one or more of the following data items missing: birthweight, gestational age, birth status, sex, and date of birth of the baby. On the other hand, for data items where information was stated such as birthweight, birth status, and sex for singleton babies, there was good agreement between Maternity HES and linked birth registration and NN4B data.Although NN4B records the ethnic category of the baby as defined by the mother, and Maternity HES records mother's ethnic category, 87 per cent of the linked records had the same ethnic group. CONCLUSION: Even though a good linkage rate was obtained, the method used will be simplified before data for 2007 are linked. To gain the maximum benefit from this linkage in future years, improvements are urgently needed in the quality and completeness of the data contained in Maternity HES.List of Tables, 55.

Epstein-Barr virus infections after allogeneic stem cell transplantation: a comparison between non-malignant and malignant hematological disorders.

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.

Early cytomegalovirus infections following allogeneic stem cell transplantation: a comparison between non-malignant and malignant haematological disorders.

The haematological indications for allogeneic stem cell transplantation can be broadly divided into non-malignant and malignant disorders. We compared the incidence and risk factors for post-transplant cytomegalovirus (CMV) infections between these two biologically diverse subgroups of haematological conditions. Out of 105 allogeneic transplants, 64 and 41 were for underlying non-malignant and malignant indications respectively. CMV infections were significantly more frequent (P=0.016) in the malignant subgroup. Pre-transplant recipient CMV seropositivity in both subgroups (negative versus positive; non-malignant,P=0.023; malignant, p<0.001), donor seropositivity (P=0.002) and acute graft-versus-host disease (GVHD) (P=0.02) in the non-malignant subgroup and > or =3 courses of previous cytotoxic therapy (P=0.023) in the malignant subgroup were found to be associated with an increased risk of CMV infections. On multivariate analysis, donor seropositivity in the non-malignant patients (negative versus positive,P=0.022; odds ratio: 0.18) and recipient seropositivity in patients with malignancies (negative versus positive; P=0.001, odds ratio: 0.01) were identified to be significant factors for risk of CMV infection.