Inflammatory bowel disease in the United Kingdom: Epidemiological trends in primary care and associations with contraception

Background: The epidemiology of inflammatory bowel disease (IBD) in the UK is poorly described. Primary care contraceptive prescribing data published by the NHS are not linked to individual patients. Studies have linked contraceptive pills to the development of IBD. However, there is a paucity of literature on how contraceptive formulation and duration of therapy affect IBD risk. Aims: To describe changes in the incidence and prevalence of IBD in the UK from 2000-2018. To describe non-barrier contraceptive prescribing patterns in primary care over the same period. To investigate the associations between exposure to contraception and development of IBD. Methods: Three epidemiological studies using IQVIATM Medical Research Data; a cohort study examining temporal trends in IBD incidence and prevalence, a repeated cross-sectional study exploring trends in contraceptive prescribing, a nested case-control study investigating the associations between a range of contraceptives and development of IBD. Results: Overall, the incidence of IBD is falling, but prevalence continues to rise. Some of the highest recorded incidence and prevalence rates globally were observed, with a 94% rise in incidence in adolescents since the year 2000. Over the same period, combined hormonal contraception prescribing has halved whereas progestogen-only pill prescribing has more than doubled. Methods of contraception prescribed by GPs are influenced by social deprivation. Withdrawal of a pay-for-performance incentive may have adversely affected adolescent long-acting reversible contraception uptake. Results suggest that oestrogen-containing contraception is associated with development of IBD whereas progestogen-only methods have minimal to no effect. Conclusion: This thesis provides evidence relating to a wide range of temporal trends in the epidemiology of IBD and patterns of contraceptive prescribing in the UK. Although previous associations between oral contraceptive pills and IBD have been made, this thesis provides the first epidemiological evidence that oestrogen-containing contraceptives, but not progestogen-only methods, are associated with development of IBD

Time trends in contraceptive prescribing in UK primary care 2000–2018: a repeated cross-sectional study

BACKGROUND: Over the last 20 years, new contraceptive methods became available and incentives to increase contraceptive uptake were introduced. We aimed to describe temporal trends in non-barrier contraceptive prescribing in UK primary care for the period 2000-2018. METHODS: A repeated cross-sectional study using patient data from the IQVIA Medical Research Data (IMRD) database. The proportion (95% CI) of women prescribed non-barrier contraception per year was captured. RESULTS: A total of 2 705 638 women aged 15-49 years were included. Between 2000 and 2018, the proportion of women prescribed combined hormonal contraception (CHC) fell from 26.2% (26.0%-26.3%) to 14.3% (14.2%-14.3%). Prescriptions for progestogen-only pills (POPs) and long-acting reversible contraception (LARC) rose from 4.3% (4.3%-4.4%) to 10.8% (10.7%-10.9%) and 4.2% (4.1%-4.2%) to 6.5% (6.5%-6.6%), respectively. Comparing 2018 data for most deprived versus least deprived areas, women from the most deprived areas were more likely to be prescribed LARC (7.7% (7.5%-7.9%) vs 5.6% (5.4%-5.8%)) while women from the least deprived areas were more likely to be prescribed contraceptive pills (20.8% (21.1%-21.5%) vs 26.2% (26.5%-26.9%)). In 2009, LARC prescriptions increased irrespective of age and social deprivation in line with a pay-for-performance incentive. However, following the incentive's withdrawal in 2014, LARC prescriptions for adolescents aged 15-19 years fell from 6.8% (6.6%-7.0%) in 2013 to 5.6% (5.4%-5.8%) in 2018. CONCLUSIONS: CHC prescribing fell by 46% while POP prescribing more than doubled. The type of contraception prescribed was influenced by social deprivation. Withdrawal of a pay-for-performance incentive may have adversely affected adolescent LARC uptake, highlighting the need for further intervention to target this at-risk group

Bone mineral density optimisation in adults with perinatally acquired HIV infection in routine care

We report on BMD and factors associated with reductions in BMD for all adults with perinatally acquired HIV who attended a London clinic between May 2014 and October 2016. We observed a high prevalence of reductions in BMD and a higher than expected prevalence of factors associated with adverse bone health, namely vitamin D deficiency

Bone mineral density optimisation in adults with perinatally acquired HIV infection in routine care.

We report on BMD and factors associated with reductions in BMD for all adults with perinatally acquired HIV who attended a London clinic between May 2014 and October 2016. We observed a high prevalence of reductions in BMD and a higher than expected prevalence of factors associated with adverse bone health, namely vitamin D deficiency

Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in mycobacterium tuberculosis–infected individuals

Copyright © 2009 by the American Thoracic Society.Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas.Oxford Biomedical Research Centre, Wellcome Trust, and AFTBVAC

Use of contraceptives and risk of inflammatory bowel disease: A nested case–control study

Background: How contraceptive formulation, dose, duration of therapy and mode of delivery affects the risk of inflammatory bowel disease (IBD) is poorly described. // Aim: To examine associations between types of hormonal contraception and development of IBD. // Methods: This was a nested case–control study using IQVIA Medical Research Data. Women aged 15-49 years with a new diagnosis of IBD were matched with up to six controls by age, practice and year. Odds ratios (OR) and 95% confidence intervals (95% CI) for incident IBD and use of contraception were calculated. // Results: 4932 incident cases of IBD were matched to 29 340 controls. Use of combined oral contraceptive pills (COCPs) was associated with the development of Crohn's disease and ulcerative colitis (OR 1.60 [1.41-1.82] and 1.30 [1.15-1.45], respectively). Each additional month of COCP exposure per year of follow-up increased risk of Crohn's disease by 6.4% (5.1%-7.7%) and ulcerative colitis by 3.3% (2.1%-4.4%). Progestogen-only pills had no effect on Crohn's disease risk (OR 1.09 [0.84-1.40]) but there was a modest association with ulcerative colitis (OR 1.35 [1.12-1.64]). Parenteral contraception was not associated with the development of Crohn's disease or ulcerative colitis (OR 1.15 [0.99-1.47] and 1.17 [0.98-1.39], respectively). // Conclusions: We observed an increase in the risk of IBD with increasing duration of exposure to COCPs. Progestogen-only pills were not associated with Crohn's disease but there was a modest association with ulcerative colitis. There was no association between parenteral progestogen-only contraception and IBD. These findings are broadly consistent with a hypothesis that the oestrogen component of contraception may drive IBD pathogenesis

Clinical outcomes post transition to adult services in young adults with perinatally acquired HIV infection: mortality, retention in care, and viral suppression

OBJECTIVE: Adolescence is the only age group globally where HIV associated mortality is rising, with poorer outcomes at all stages of the care cascade compared to adults. We examined post-transition outcomes for young adults living with perinatal HIV (YAPaHIV). DESIGN: Retrospective cohort analysis. SETTING: A tertiary Youth Friendly Service (YFS) London, UK. PARTICIPANTS: 180 YAPaHIV registered between 01.01.06 and 31.12.17 contributed 921 person-years of follow up post-transition to adult services. INTERVENTION: YFS with multidisciplinary care and walk-in access. MAIN OUTCOME MEASURES: mortality, morbidity, retention in care, antiretroviral (ART) uptake and HIV-viral load (HIV-VL) suppression. Crude incidence rates (CIR) are reported per 1000 person-years. RESULTS: Of 180 youth registered; 4 (2.2%) died, 14 (7.8%) transferred care and 4 (2.2%) were lost to follow up. For the 158 retained in care the median age was 22.9 years (IQR 20.3-25.4), 56% were female, 85% Black African, with a median length of follow up in adult care of 5.5 years (IQR 2.9-7.3). 157 (99.4%) ever received an ART prescription, 127/157 (81%) with a latest HIV-VL < 200 copies RNA/ml, median CD4 count of 626 cells/ul (IQR 441-820). The all-cause mortality was 4.3/1000 person-years (95% CI 1.2 - 11.1), ten fold the aged-matched UK HIV-negative population (0.43/1000 person-years (95% CI 0.41 - 0.44). Post-transition, 17/180 (9.4%) developed a new AIDS diagnosis; CIR 18.5/1000 person-years (95% CI 10.8 - 29.6). CONCLUSION: Whilst this youth-friendly multi-disciplinary service achieved high engagement and coverage of suppressive ART, mortality remains markedly increased compared to the general UK population

Incidence and prevalence of inflammatory bowel disease in UK primary care: a population-based cohort study

OBJECTIVES: We describe temporal trends in the recorded incidence of inflammatory bowel disease (IBD) in UK primary care patients between 2000 and 2018. DESIGN: A cohort study. SETTING: The IQVIA Medical Research data (IMRD) primary care database. PARTICIPANTS: All individuals registered with general practices contributing to IMRD during the period 01 January 2000-31 December 2018. MAIN OUTCOME MEASURES: The primary outcome was the recorded diagnosis of IBD. RESULTS: 11 325 025 individuals were included and 65 700 IBD cases were identified, of which 22 560 were incident diagnoses made during the study period. Overall, there were 8077 incident cases of Crohn's disease (CD) and 12 369 incident cases of ulcerative colitis (UC). Crude incidence estimates of 'IBD overall', CD and UC were 28.6 (28.2 to 28.9), 10.2 (10.0 to 10.5) and 15.7 (15.4 to 15.9)/100 000 person years, respectively. No change in IBD incidence was observed for adults aged 17-40 years and children aged 0-9 years. However, for adults aged over 40 years, incidence fell from 37.8 (34.5 to 41.4) to 23.6 (21.3 to 26.0)/100 000 person years (average decrease 2.3% (1.9 to 2.7)/year (p<0.0001)). In adolescents aged 10-16 years, incidence rose from 13.1 (8.4 to 19.5) to 25.4 (19.5 to 32.4)/100 000 person years (average increase 3.0% (1.7 to 4.3)/year (p<0.0001)). Point prevalence estimates on 31 December 2018 for IBD overall, CD and UC were 725, 276 and 397 per 100 000 people, respectively. CONCLUSIONS: This is one of the largest studies ever undertaken to investigate trends in IBD epidemiology. Although we observed stable or falling incidence of IBD in adults, our results are consistent with some of the highest reported global incidence and prevalence rates for IBD, with a 94% rise in incidence in adolescents. Further investigation is required to understand the aetiological drivers

Does α (+)-Thalassaemia Protect against Malaria?

Pasvol discusses a new study in PLoS Medicine that shows that α (+)-thalassemia protects against severe but not mild malaria