Julia Snowball

Evaluating the Hazard of Foetal Death following H1N1 Influenza Vaccination; A Population Based Cohort Study in the UK GPRD

Background To evaluate the risk of foetal loss associated with pandemic influenza vaccination in pregnancy. Retrospective cohort study. UK General Practice Research Database Pregnancies ending in delivery or spontaneous foetal death after 21 October 2009 and starting before 01 January 2010. Methodology/Principal Findings Hazard ratios of foetal death for vaccinated compared to unvaccinated pregnancies were estimated for gestational weeks 9 to 12, 13 to 24 and 25 to 43 using discrete-time survival analysis. Separate models were specified to evaluate whether the potential effect of vaccination on foetal loss might be transient (for ∼4 weeks post vaccination only) or more permanent (for the duration of the pregnancy). 39,863 pregnancies meeting our inclusion criteria contributed a total of 969,322 gestational weeks during the study period. 9,445 of the women were vaccinated before or during pregnancy. When the potential effect of vaccination was assumed to be transient, the hazard of foetal death during gestational weeks 9 through 12 (HRunadj 0.56; CI95 0.43 to 0.73) and 13 through 24 (HRunadj 0.45; CI95 0.28 to 0.73) was lower in the 4 weeks after vaccination than in other weeks. Where the more permanent exposure definition was specified, vaccinated pregnancies also had a lower hazard of foetal loss than unvaccinated pregnancies in gestational weeks 9 through 12 (HRunadj 0.74; CI95 0.62 to 0.88) and 13 through 24 (HRunadj 0.59; CI95 0.45 to 0.77). There was no difference in the hazard of foetal loss during weeks 25 to 43 in either model. Sensitivity analyses suggest the strong protective associations observed may be due in part to unmeasured confounding. Conclusions/Significance Influenza vaccination during pregnancy does not appear to increase the risk of foetal death. This study therefore supports the continued recommendation of influenza vaccination of pregnant women.

Factors associated with uptake of seasonal and pandemic influenza vaccine among clinical risk groups in the UK: an analysis using the General Practice Research Database.

BACKGROUND Influenza vaccine uptake rates are low compared with uptake rates of many other vaccines. It is unclear how this differs between risk groups in the population and between pandemic and non-pandemic influenza vaccines. AIM This study sought to estimate uptake rates of pandemic and seasonal influenza vaccines among clinical risk groups in the UK during the 2009/2010 influenza season and to identify predictors of vaccine uptake in this cohort. METHODS Uptake rates were calculated using data from the UK General Practice Research Database (GPRD). Predictors of vaccination were identified using a modified Poisson regression with robust standard error estimates. RESULTS Uptake of pandemic influenza vaccine in clinical risk groups was 40.3% and uptake of seasonal influenza vaccine was 61.3%. Factors found to be predictive of seasonal and pandemic influenza vaccination included age and the total number of underlying health conditions an individual had. At risk individuals in those age groups in which universal vaccination of the general population was recommended were more likely to have been vaccinated than individuals in age groups in which only clinical risk groups were recommended for vaccination; hence children in clinical risk groups were more likely to receive pandemic than seasonal influenza vaccine. In older people, having a history of Guillain Barré syndrome was associated with a reduced likelihood of receipt of both seasonal (IRR(adj) 0.83, CI(95) 0.77-0.90) and pandemic influenza vaccines (IRR(adj) 0.82, CI(95) 0.73-0.92). DISCUSSION Uptake of pandemic influenza vaccine was lower than that of seasonal influenza vaccine among those at a clinically high risk of influenza related morbidity. This suggests that vaccination strategies may need to be altered during future pandemics. Recommending universal vaccination within age categories in which there is a large proportion of high risk individuals could be considered as this may result in higher uptake among clinical risk groups.

Pandemic influenza vaccination during pregnancy: An investigation of vaccine uptake during the 2009/10 pandemic vaccination campaign in Great Britain

Background: Pregnant women in Great Britain were recommended to receive influenza A(H1N1)pdm09 vaccines during the 2009/10 influenza pandemic, however uptake of the vaccines by pregnant women was reported to have been very low. Aim: We sought to estimate uptake of influenza A(H1N1)pdm09 vaccines and to investigate predictors of vaccine uptake in pregnant women in Great Britain during the 2009/10 pandemic. Methods: Uptake rates were calculated using data from the UK General Practice Research Database (GPRD). Predictors of vaccination were identified using a Cox proportional hazards model. Results: Uptake of influenza A(H1N1)pdm09 vaccines by pregnant women was 21.6%. Pregnant women with an underlying health condition increasing the risk of influenza-related complications had a higher vaccination rate than pregnant women without such conditions. The hazard ratio comparing these two groups decreased logarithmically throughout pregnancy from 9.3 in the first week to 1.3 by the end of pregnancy. Increasing maternal age (HR 1.01, CI95 1.01–1.01), having a previous delivery recorded (HR 1.21, CI95 1.16–1.27) and living in Scotland (HR 2.58, CI95 2.34–2.85) or Wales (HR 1.37, CI95 1.20–1.57) as opposed to England were all also associated with an increase in vaccination uptake rates throughout pregnancy. Discussion: Uptake of influenza A(H1N1)pdm09 vaccines by pregnant women was low. None of the potential predictors evaluated in this study were strong enough to account for this, however information on health beliefs and GP recommendation were not available. If the low rates reported here are to be improved new strategies to increase uptake of influenza vaccine in pregnant women need to be identified, evaluated and implemented.

Pregnancy losses in women with type 1 or type 2 diabetes in the UK: an investigation using primary care records

This study aims to investigate pregnancy losses in women with Type 1 or Type 2 diabetes and compare this with the general population.

Colorectal cancer incidence on the General Practice Research Database

The General Practice Research Database (GPRD) contains longitudinal patient medical records collected within UK primary care. This study aimed to identify incident cases of colorectal cancer on the GPRD and to compare incidence rates for 2007 with those reported by the UK cancer registries.

Colorectal cancer risk reduction following macrogol exposure: a cohort and nested case control study in the UK.

Background and Aims Animal studies have demonstrated macrogol laxatives may reduce colorectal cancer (CRC) risk. This study aimed to investigate the association between macrogol prescribing and CRC risk. Methods A case-control study nested within a cohort of laxative users was conducted using data from the UK General Practice Research Database. Six controls per case were identified and to account for the lead time of CRC, additional control sets were selected on the index date backdated by 1 to 5 years. Exposure to macrogols and covariate status before each of the backdated index dates was established. Conditional logistic regression was used to calculate the risk of CRC following macrogol prescribing adjusted for potential confounders. Results 4734 incident CRC cases were identified; 2722, 2195, 1789, 1481 and 1214 had received a laxative prescription before the index dates backdated by 1 to 5 years. A suggestion of a non-significant reduction in CRC risk associated with ‘macrogol after other laxative’ prescribing was observed when the index date was backdated by 1 and 2 years, ORadj = 0.87 (CI950.74–1.03) and ORadj = 0.80 (CI950.65–1.00) compared to non-macrogol laxative exposure. The odds ratios reduced further and were significant when backdated by 3, 4 and 5 years, ORadj = 0.68 (CI950.50–0.92), ORadj = 0.60 (CI950.40–0.90) and ORadj = 0.30 (CI950.14–0.64) respectively. This reduction in risk was not observed, however, for ‘macrogol only’ and ‘macrogol before other laxative’ exposure categories. Conclusions In this study we observed a reduced CRC risk associated with macrogol prescribing after accounting for the lead time for CRC. Further studies are required to determine whether the association is causal and whether it can partly be explained by selective prescribing.

Interval between onset of psoriasis and psoriatic arthritis comparing the UK Clinical Practice Research Datalink with a hospital-based cohort.

Objectives To describe the time interval between the onset of psoriasis and PsA in the UK primary care setting and compare with a large, well-classified secondary care cohort. Methods Patients with PsA and/or psoriasis were identified in the UK Clinical Practice Research Datalink (CPRD). The secondary care cohort comprised patients from the Bath PsA longitudinal observational cohort study. For incident PsA patients in the CPRD who also had a record of psoriasis, the time interval between PsA diagnosis and first psoriasis record was calculated. Comparisons were made with the time interval between diagnoses in the Bath cohort. Results There were 5272 eligible PsA patients in the CPRD and 815 in the Bath cohort. In both cohorts, the majority of patients (82.3 and 61.3%, respectively) had psoriasis before their PsA diagnosis or within the same calendar year (10.5 and 23.8%), with only a minority receiving their PsA diagnosis first (7.1 and 14.8%). Excluding those who presented with arthritis before psoriasis, the median time between diagnoses was 8 years [interquartile range (IQR) 2-15] in the CPRD and 7 years (IQR 0-20) in the Bath cohort. In the CPRD, 60.1 and 75.1% received their PsA diagnosis within 10 and 15 years of their psoriasis diagnosis, respectively; this was comparable with 57.2 and 67.7% in the Bath cohort. Conclusion A similar distribution for the time interval between psoriasis and arthritis was observed in the CPRD and secondary care cohort. These data can inform screening strategies and support the validity of data from each cohort.

The Clinical Practice Research Datalink for drug safety in pregnancy research: an overview.

Medicine use during pregnancy is common; however the safety of medicine use during pregnancy is largely unknown when a medicine comes to market. Electronic healthcare databases, including the Clinical Practice Research Datalink (CPRD), are increasingly being used for post-marketing surveillance in this field. The CPRD contains anonymised, longitudinal medical records routinely collected in primary care. Using CPRD data it is possible to identify medical records indicative of pregnancy, including pregnancy losses. Data on prescriptions issued can be used to determine maternal exposure and for about 80% of pregnancies it is possible to link the mothers medical record to the medical record of the child. Data in the medical records of the mother and child can then be used to identify adverse pregnancy outcomes, including congenital malformations. This paper describes some of the complexities involved in using CPRD data for pregnancy related research and discusses some of its strengths and limitations.

Risk of uveitis and inflammatory bowel disease in people with psoriatic arthritis: a population-based cohort study

Objectives To determine the risk of uveitis and inflammatory bowel disease (IBD) in patients with psoriatic arthritis (PsA) compared with the general population and patients with psoriasis. Methods A cohort study using data from the UK Clinical Practice Research Datalink between 1998 and 2014. Patients with incident PsA aged 18–89 years were identified and matched to a cohort of patients with psoriasis and a general population cohort. The incidence of uveitis, all IBD, Crohn’s disease and ulcerative colitis was calculated for each study cohort and adjusted relative risks (RRadj) were calculated using conditional Poisson regression. Results 6783 incident cases of PsA were identified with a median age of 49 years. The risk of uveitis was significantly higher in the PsA cohort than in the general population and psoriasis cohorts (RRadj 3.55, 95% CI 2.21 to 5.70 and RRadj 2.13, 95% CI 1.40 to 3.24, respectively). A significant increase was observed for Crohn’s disease (RRadj 2.96, 95% CI 1.46 to 6.00 and RRadj3.60, 95% CI 1.83 to 7.10) but not for ulcerative colitis (RRadj1.30, 95% CI 0.66 to 2.56 and RRadj0.98, 95% CI 0.50 to 1.92). Conclusions In a primary care-based incidence cohort of patients with PsA, there were substantial risks of developing uveitis and/or Crohn’s disease, but not ulcerative colitis, when compared with the general population and psoriasis controls.

Statins during pregnancy: A cohort study using the General Practice Research Database to investigate pregnancy loss

The aim of this study was to determine if there are any differences between the types of pregnancy loss experienced by women who have been prescribed a statin just before or early in pregnancy compared with those who have not.