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

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

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

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

New synchronization method for <i>Plasmodium falciparum</i>

&lt;b&gt;Background&lt;/b&gt;: Plasmodium falciparum is usually asynchronous during in vitro culture. Although various synchronization methods are available, they are not able to narrow the range of ages of parasites. A newly developed method is described that allows synchronization of parasites to produce cultures with an age range as low as 30 minutes. &lt;b&gt;Methods&lt;/b&gt;: Trophozoites and schizonts are enriched using Plasmion. The enriched late stage parasites are immobilized as a monolayer onto plastic Petri dishes using concanavalin A. Uninfected erythrocytes are placed onto the monolayer for a limited time period, during which time schizonts on the monolayer rupture and the released merozoites invade the fresh erythrocytes. The overlay is then taken off into a culture flask, resulting in a highly synchronized population of parasites. &lt;b&gt;Results&lt;/b&gt;: Plasmion treatment results in a 10- to 13-fold enrichment of late stage parasites. The monolayer method results in highly synchronized cultures of parasites where invasion has occurred within a very limited time window, which can be as low as 30 minutes. The method is simple, requiring no specialized equipment and relatively cheap reagents. &lt;b&gt;Conclusions&lt;/b&gt;: The new method for parasite synchronization results in highly synchronized populations of parasites, which will be useful for studies of the parasite asexual cell cycle

Risk factors for UK Plasmodium falciparum cases

Background An increasing proportion of malaria cases diagnosed in UK residents with a history of travel to malaria endemic areas are due to Plasmodium falciparum. Methods In order to identify travellers at most risk of acquiring malaria a proportional hazards model was used to estimate the risk of acquiring malaria stratified by purpose of travel and age whilst adjusting for entomological inoculation rate (EIR) and duration of stay in endemic countries. Results Travellers visiting friends and relatives and business travellers were found to have significantly higher hazard of acquiring malaria (adjusted hazard ratio (HR) relative to that of holiday makers 7.4, 95% CI 6. 4-8. 5, p < 0. 0001 and HR 3.4, 95% CI 2.9-3.8, p < 0. 0001, respectively). All age-groups were at lower risk than children aged 0-15 years. Conclusions These estimates of the increased risk for these groups accounting for exposure should be used to inform programmes to improve awareness of the risks of malaria when travelling

Defining childhood severe falciparum malaria for intervention studies.

Background Clinical trials of interventions designed to prevent severe falciparum malaria in children require a clear endpoint. The internationally accepted definition of severe malaria is sensitive, and appropriate for clinical purposes. However, this definition includes individuals with severe nonmalarial disease and coincident parasitaemia, so may lack specificity in vaccine trials. Although there is no “gold standard” individual test for severe malaria, malaria-attributable fractions (MAFs) can be estimated among groups of children using a logistic model, which we use to test the suitability of various case definitions as trial endpoints. Methods and Findings A total of 4,583 blood samples were taken from well children in cross-sectional surveys and from 1,361 children admitted to a Kenyan District hospital with severe disease. Among children under 2 y old with severe disease and over 2,500 parasites per microliter of blood, the MAFs were above 85% in moderate- and low-transmission areas, but only 61% in a high-transmission area. HIV and malnutrition were not associated with reduced MAFs, but gastroenteritis with severe dehydration (defined by reduced skin turgor), lower respiratory tract infection (clinician's final diagnosis), meningitis (on cerebrospinal fluid [CSF] examination), and bacteraemia were associated with reduced MAFs. The overall MAF was 85% (95% confidence interval [CI] 83.8%–86.1%) without excluding these conditions, 89% (95% CI 88.4%–90.2%) after exclusions, and 95% (95% CI 94.0%–95.5%) when a threshold of 2,500 parasites/μl was also applied. Applying a threshold and exclusion criteria reduced sensitivity to 80% (95% CI 77%–83%). Conclusions The specificity of a case definition for severe malaria is improved by applying a parasite density threshold and by excluding children with meningitis, lower respiratory tract infection (clinician's diagnosis), bacteraemia, and gastroenteritis with severe dehydration, but not by excluding children with HIV or malnutrition