Jemma Walker

Impact of the national rotavirus vaccination programme on acute gastroenteritis in England and associated costs averted.

Highlights • Acute gastroenteritis primary care visits fell sharply after vaccine introduction.• Decreases were most marked in the age groups targeted for vaccination.• Decreases were also seen in older children and adults, indicating herd immunity.• An estimated 87,376 healthcare visits by young children were averted.• There was an estimated £12.5 million reduction in healthcare costs across settings.

Do Genetic Susceptibility Variants Associate with Disease Severity in Early Active Rheumatoid Arthritis

Objective. Genetic variants affect both the development and severity of rheumatoid arthritis (RA). Recent studies have expanded the number of RA susceptibility variants. We tested the hypothesis that these associated with disease severity in a clinical trial cohort of patients with early, active RA. Methods. We evaluated 524 patients with RA enrolled in the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trials. We tested validated susceptibility variants — 69 single-nucleotide polymorphisms (SNP), 15 HLA-DRB1 alleles, and amino acid polymorphisms in 6 HLA molecule positions — for their associations with progression in Larsen scoring, 28-joint Disease Activity Scores, and Health Assessment Questionnaire (HAQ) scores over 2 years using linear mixed-effects and latent growth curve models. Results. HLA variants were associated with joint destruction. The *04:01 SNP (rs660895, p = 0.0003), *04:01 allele (p = 0.0002), and HLA-DRβ1 amino acids histidine at position 13 (p = 0.0005) and valine at position 11 (p = 0.0012) significantly associated with radiological progression. This association was only significant in anticitrullinated protein antibody (ACPA)-positive patients, suggesting that while their effects were not mediated by ACPA, they only predicted joint damage in ACPA-positive RA. Non-HLA variants did not associate with radiograph damage (assessed individually and cumulatively as a weighted genetic risk score). Two SNP — rs11889341 (STAT4, p = 0.0001) and rs653178 (SH2B3-PTPN11, p = 0.0004) — associated with HAQ scores over 6–24 months. Conclusion. HLA susceptibility variants play an important role in determining radiological progression in early, active ACPA-positive RA. Genome-wide and HLA-wide analyses across large populations are required to better characterize the genetic architecture of radiological progression in RA.

Verteporfin Photodynamic Therapy Cohort Study: Report 2: Clinical Measures of Vision and Health-Related Quality of Life

PURPOSE To quantify decreases in health-related quality of life (HRQoL) for given deterioration in clinical measures of vision; to describe the shape of these relationships; and to test whether the gradients of these relationships change with duration of visual loss. DESIGN A prospective, longitudinal study of patients treated with verteporfin photodynamic therapy in the United Kingdom National Health Service. PARTICIPANTS Patients with neovascular age-related macular degeneration (AMD) treated in 18 ophthalmology departments in the United Kingdom with expertise in management of neovascular AMD. METHODS Responses to HRQoL questionnaires (Short Form 36 [SF-36] and National Eye Institute Visual Functioning Questionnaire [NEIVFQ]) and clinical measures of vision were recorded at baseline and at follow-up visits. Mixed regression models were used to characterize the relationships of interest. MAIN OUTCOME MEASURES Measures of vision were best-corrected visual acuity (BCVA) and contrast sensitivity (CS). The SF-36 physical and mental component scores (PCS and MCS), SF-6D utility, and distance, near, and composite NEIVFQ scores were derived to characterize HRQoL. RESULTS The SF-6D, PCS, and MCS were linearly associated with BCVA; predicted decreases for a 5-letter drop in BCVA in the better-seeing eye were 0.0058, 0.245, and 0.546, respectively (all P<0.0001). Gradients were not influenced by duration of follow-up. Models predicting distance, near, and composite NEIVFQ scores from BCVA were quadratic; predicted decreases for a 5-letter drop in BCVA in the better-seeing eye were 5.08, 5.48, and 3.90, respectively (all P<0.0001). The BCVA predicted HRQoL scores more strongly than CS. CONCLUSIONS Clinically significant deterioration in clinical measures of vision is associated with small decreases in generic and vision-specific HRQoL. Our findings are important for further research modeling the cost effectiveness of current and future interventions for neovascular AMD.

Verteporfin Photodynamic Therapy Cohort Study: Report 3: Cost Effectiveness and Lessons for Future Evaluations

PURPOSE To report (1) the costs of verteporfin photodynamic therapy (VPDT) in routine treatment of neovascular age-related macular degeneration (nAMD), (2) the relationship between health and social service costs and best-corrected visual acuity (BCVA), (3) the cost-effectiveness of VPDT versus a best supportive care (BSC) group who were assumed to have no active treatment, and (4) lessons for future cost-effectiveness analyses (CEAs). DESIGN The CEA of VPDT versus BSC that uses health-related quality of life (HrQoL), resource use, and visual acuity data from the United Kingdom (UK) VPDT Cohort Study. PARTICIPANTS Data on VPDT use were collected from patients attending 45 ophthalmology provider units in the UK National Health Service, 15 units collected data on self-reported use of services. METHODS Incremental costs of VPDT versus BSC were calculated from treatment costs, change in cost associated with declining BCVA, and difference in BCVA previously attributed to VPDT. Similarly, incremental quality-adjusted life years (QALYs) were calculated from change in HRQoL associated with declining BCVA, giving an incremental cost per QALY of VPDT versus BSC over 2 years. MAIN OUTCOME MEASURES Incremental costs (UK pounds [ pound]; United States dollars [

Verteporfin Photodynamic Therapy Cohort Study: Report 1: Effectiveness and Factors Influencing Outcomes

]); incremental QALYs; costs per QALY. RESULTS The treatment costs of VDPT were pound 3026 (

Effectiveness of herpes zoster vaccination in an older United Kingdom population

4544) in year 1 and pound 845 (

Identifying social factors amongst older individuals in linked electronic health records: An assessment in a population based study.

1269) in year 2. For patients who used services, a 5-letter decrease in BCVA was associated with an increase in annual costs of approximately pound 110 (

Exome array analysis of adverse reactions to fluoropyrimidine-based therapy for gastrointestinal cancer

165; 95% confidence intervals, approximately pound 48 [

Tu1925 Novel Pathway-Centric Analysis Reveals Variants Associated With Toxicity and Response to Thiopurines in Patients With Inflammatory Bowel Disease

72] to pound 174 [

Seasonal and Regional Short-term Effects of Fine Particles on Hospital Admissions in 202 US Counties, 1999–2005

261]). The incremental costs and QALYs for VPDT were pound 3514 (