Assessment of thyroiditis risk associated with HPV vaccination among girls aged 9-18 years: A time-varying cohort study.

BACKGROUND: Previous studies have suggested a relationship between human papillomavirus vaccine and autoimmune diseases, including thyroiditis. Thus, we aimed to evaluate the risk of thyroiditis associated with HPV vaccination among girls using the Primary Care Database For Pharmacoepidemiological Research (BIFAP) in Spain. METHODS: In this retrospective cohort study, girls in BIFAP aged 9-18 years from 2007 to 2016, free of past thyroiditis and HPV vaccination, were included. Hazard Ratios (HRs; 95% CI) of thyroiditis were calculated within exposed periods (up to 2 years of vaccination) and post-exposed periods (from 2 years after vaccination onwards) compared with non-exposed periods, overall, by dose and by type of vaccine, adjusted for potential confounders collected at different times. In a post-hoc analysis, we moved back the thyroiditis date (30 days) as a theoretical delay in diagnosis. RESULTS: Out of the 388,411 girls included in the cohort, 153,924 were vaccinated against HPV and 480 thyroiditis (253 autoimmune) cases were identified (334 non-exposed; 103 exposed; 43 post-exposed). Adjusted HR was 1.18 [95% CI: 0.79-1.76] for exposed (1.25 [0.77-2.04] for bi- and 1.15 [0.76-1.76] for quadri-valent vaccines) and 1.26 [0.74-2.14] for post-exposed periods. HR was 1.50 [0.87-2.59] for the 1st dose, 1.13 [0.66-1.91] for the 2nd and 1.11 [0.71-1.72] for the 3rd one. When the diagnosis date was moved back, the risk was 1.14 [0.76-1.70] for exposed period, being 1.80 [0.86-3.76] and 1.40 [0.74-2.66] after 1st dose of bi- and quadri-valent, respectively. CONCLUSIONS: We did not observe an increased risk of thyroiditis following HPV vaccination (whether bi- or quadri-valent). Even though the point estimate was higher after 1st HPV vaccination dose than after subsequent doses, a dose-effect was not confirmed. Results remained similar after applying a lag time.

ADVANCE database characterisation and fit for purpose assessment for multi-country studies on the coverage, benefits and risks of pertussis vaccinations.

INTRODUCTION: The public-private ADVANCE consortium (Accelerated development of vaccine benefit-risk collaboration in Europe) aimed to assess if electronic healthcare databases can provide fit-for purpose data for collaborative, distributed studies and monitoring of vaccine coverage, benefits and risks of vaccines. OBJECTIVE: To evaluate if European healthcare databases can be used to estimate vaccine coverage, benefit and/or risk using pertussis-containing vaccines as an example. METHODS: Characterisation was conducted using open-source Java-based (Jerboa) software and R scripts. We obtained: (i) The general characteristics of the database and data source (meta-data) and (ii) a detailed description of the database population (size, representatively of age/sex of national population, rounding of birth dates, delay between birth and database entry), vaccinations (number of vaccine doses, recording of doses, pattern of doses by age and coverage) and events of interest (diagnosis codes, incidence rates). A total of nine databases (primary care, regional/national record linkage) provided data on events (pertussis, pneumonia, death, fever, convulsions, injection site reactions, hypotonic hypo-responsive episode, persistent crying) and vaccines (acellular pertussis and whole cell pertussis) related to the pertussis proof of concept studies. RESULTS: The databases contained data for a total population of 44 million individuals. Seven databases had recorded doses of vaccines. The pertussis coverage estimates were similar to those reported by the World Health Organisation (WHO). Incidence rates of events were comparable in magnitude and age-distribution between databases with the same characteristics. Several conditions (persistent crying and somnolence) were not captured by the databases for which outcomes were restricted to hospital discharge diagnoses. CONCLUSION: The database characterisation programs and workflows allowed for an efficient, transparent and standardised description and verification of electronic healthcare databases which may participate in pertussis vaccine coverage, benefit and risk studies. This approach is ready to be used for other vaccines/events to create readiness for participation in other vaccine related studies.

ADVANCE system testing: Benefit-risk analysis of a marketed vaccine using multi-criteria decision analysis and individual-level state transition modelling.

BACKGROUND: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines using electronic health record (eHR) databases in Europe. Proof-of-concept studies were designed to assess the proposed processes and system for generating the required evidence to perform B/R assessment and near-real time monitoring of vaccines. We aimed to test B/R methodologies for vaccines, using the comparison of the B/R profiles of whole-cell (wP) and acellular pertussis (aP) vaccine formulations in children as an example. METHODS: We used multi-criteria decision analysis (MCDA) to structure the B/R assessment combined with individual-level state transition modelling to build the B/R effects table. In the state transition model, we simulated the number of events in two hypothetical cohorts of 1 million children followed from first pertussis dose till pre-school-entry booster (or six years of age, whichever occurred first), with one cohort receiving wP, and the other aP. The benefits were reductions in pertussis incidence and complications. The risks were increased incidences of febrile convulsions, fever, hypotonic-hyporesponsive episodes, injection-site reactions and persistent crying. Most model parameters were informed by estimates (coverage, background incidences, relative risks) from eHR databases from Denmark (SSI), Spain (BIFAP and SIDIAP), Italy (Pedianet) and the UK (RCGP-RSC and THIN). Preferences were elicited from clinical and epidemiological experts. RESULTS: Using state transition modelling to build the B/R effects table facilitated the comparison of different vaccine effects (e.g. immediate vaccine risks vs long-term vaccine benefits). Estimates from eHR databases could be used to inform the simulation model. The model results could be easily combined with preference weights to obtain B/R scores. CONCLUSION: Existing B/R methodology, modelling and estimates from eHR databases can be successfully used for B/R assessment of vaccines.

Risk factors for diabetic retinopathy in people with Type 2 diabetes: A case-control study in a UK primary care setting.

AIM: To identify risk factors of diabetic retinopathy (DR) among people with Type 2 diabetes mellitus in UK primary care. METHODS: A case-control study nested in a cohort of incident Type 2 diabetes identified in The Health Improvement Network database from 2000 to 2007. Cases were people with DR (N=7735) and controls were a DR-free sample (N=9395). No age restrictions were applied. Adjusted odds ratios and 95% CIs were estimated. RESULTS: 21% of DR cases were identified during the first semester after Type 2 diabetes diagnosis. After controlling for delay on the Type 2 diabetes diagnosis, the DR risk increased with the duration of diabetes. DR increased with a mean systolic BP ≥150mmHg (1.18; 1.10-1.27), high alcohol consumption (1.34; 1.11-1.61), glycated haemoglobin (≥75 to <86: 1.14; 1.00-1.31; ≥86 to <97mmol/mol: 1.25; 1.07-1.45; ≥97mmol/mol: 1.21; 1.07-1.37), microalbuminuria (1.16; 1.06-1.27), and retinal vein occlusion (2.47; 1.67-3.66). Glaucoma and retinal arterial occlusion showed an OR of 0.71 (0.60-0.84) and 0.63 (0.40-1.01), respectively. HDL ≥1.55mmol/l (0.88; 0.80-0.98), high triglycerides (2.3-5.6mmol/l: 0.90; 0.82-0.99; >5.6mmol/l: 0.85; 0.64-1.13) or smoking (0.89; 0.81-0.97) had a slightly reduced DR risk. Users of hypoglycaemic agents had an increased DR risk. CONCLUSION: Some DR cases were identified near the diabetes diagnosis date suggesting that a delayed diabetes diagnosis is still common. Glaucoma, retinal arterial occlusion and high HDL levels were inversely associated with DR, while retinal vein occlusion, alcohol and other well-known risk factors were positively associated.

The incidence of hysterectomy, uterus-preserving procedures and recurrent treatment in the management of uterine fibroids.

OBJECTIVE: To determine the incidence of hysterectomy and uterus-preserving procedures (UPPs) among women with uterine fibroids (UFs) and the incidence of further procedures after a UPP. STUDY DESIGN: This was an observational study using a primary care database, The Health Improvement Network (THIN). Women in THIN with UFs aged 15-54 years between January 2000 and December 2009 were eligible for study. The UPPs examined were myomectomy, endometrial ablation (EA) and uterine artery embolization (UAE). Using Read codes, women were followed up until one of the following was met: there was a record of hysterectomy or UPPs, they died or the study ended (end of 2010). RESULTS: The cumulative incidence of hysterectomy or UPPs was 23.6% at 1 year, and 40.9% after the follow-up period (median 3.6 years). At the end of the follow-up period, the cumulative incidences of hysterectomy, myomectomy, EA and UAE were 33.0%, 3.9%, 6.4% and 1.9%, respectively. For women initially treated with a UPP, the cumulative incidence of second procedures was 11.5% at 1 year. At the end of the follow-up period (median 2.7 years), the cumulative incidence of further procedures was 26.1%, and the cumulative incidences of women undergoing hysterectomy, myomectomy, EA and UAE were 19.0%, 4.3%, 3.4% and 1.4%, respectively. CONCLUSIONS: Women considering UPPs for the management of UFs should be made aware that the incidence of further treatments is high, with hysterectomy being the most frequent procedure undergone.