Simon Crouch

Estimation of the impact of genital warts on health-related quality of life

Objectives: One of the two new human papillomavirus (HPV) vaccines protects against HPV types 6 and 11, which cause over 95% of genital warts, in addition to protecting against HPV types 16 and 18. In anticipation of HPV vaccine implementation, the impact of genital warts on health-related quality of life (HRQoL) was measured to assess the potential benefits of the quadrivalent over the bivalent vaccine. Methods: Genitourinary medicine clinic patients aged 18 years and older with a current diagnosis of genital warts were eligible; 81 consented and were interviewed by a member of the research team. A generic HRQoL questionnaire, the EQ-5D (comprising EQ-5D index and EQ visual analogue scale (VAS) scores) and a disease-specific HRQoL instrument, the CECA10, were administered. Previously established UK population norms were used as a control group for EQ-5D comparisons. Results: Cases (with genital warts) had lower EQ VAS and EQ-5D index scores than controls. After adjusting for age a mean difference between cases and controls 30 years of age and under (n  =  70) of 13.9 points (95% CI 9.9 to 17.6, p<0.001) for the EQ VAS and 0.039 points (95% CI 0.005 to 0.068, p = 0.02) on the EQ-5D index (also adjusted for sex) was observed. The difference between cases and controls for the EQ VAS was especially notable in young women. Conclusions: Genital warts are associated with a significant detriment to HRQoL. The potential added benefit of preventing most cases of genital warts by HPV vaccination should be considered in decisions about which HPV vaccine to implement in the United Kingdom.

Lymphoma incidence, survival and prevalence 2004–2014: sub-type analyses from the UK’s Haematological Malignancy Research Network

Background:Population-based information about cancer occurrence and survival are required to inform clinical practice and research; but for most lymphomas data are lacking.Methods:Set within a socio-demographically representative UK population of nearly 4 million, lymphoma data (N=5796) are from an established patient cohort.Results:Incidence, survival (overall and relative) and prevalence estimates for >20 subtypes are presented. With few exceptions, males tended to be diagnosed at younger ages and have significantly (P<0.05) higher incidence rates. Differences were greatest at younger ages: the <15 year male/female rate ratio for all subtypes combined being 2.2 (95% CI 1.3–3.4). These gender differences impacted on prevalence; most subtype estimates being significantly (P<0.05) higher in males than females. Outcome varied widely by subtype; survival of patients with nodular lymphocyte predominant Hodgkin lymphoma approached that of the general population, whereas less than a third of those with other B-cell (e.g., mantle cell) or T-cell (e.g., peripheral-T) lymphomas survived for ≥5 years. No males/female survival differences were detected.Conclusions:Major strengths of our study include completeness of ascertainment, world-class diagnostics and generalisability. The marked variations demonstrated confirm the requirement for ‘real-world’ data to inform aetiological hypotheses, health-care planning and the future monitoring of therapeutic changes.

Targeted sequencing identifies patients with preclinical MDS at high risk of disease progression.

The diagnosis of myelodysplastic syndromes (MDS) remains problematic due to the subjective nature of morphologic assessment. The reported high frequency of somatic mutations and increased structural variants by array-based cytogenetics have provided potential objective markers of disease; however, this has been complicated by reports of similar abnormalities in the healthy population. We aimed to identify distinguishing features between those with early MDS and reported healthy individuals by characterizing 69 patients who, following a nondiagnostic marrow, developed progressive dysplasia or acute myeloid leukemia. Targeted sequencing and array-based cytogenetics identified a driver mutation and/or structural variant in 91% (63/69) of prediagnostic samples with the mutational spectrum mirroring that in the MDS population. When compared with the reported healthy population, the mutations detected had significantly greater median variant allele fraction (40% vs 9% to 10%), and occurred more commonly with additional mutations (≥2 mutations, 64% vs 8%). Furthermore, mutational analysis identified a high-risk group of patients with a shorter time to disease progression and poorer overall survival. The mutational features in our cohort are distinct from those seen in the healthy population and, even in the absence of definitive disease, can predict outcome. Early detection may allow consideration of intervention in poor-risk patients.

Whole genome expression profiling based on paraffin embedded tissue can be used to classify diffuse large B‐cell lymphoma and predict clinical outcome

This study tested the validity of whole‐genome expression profiling (GEP) using RNA from formalin‐fixed, paraffin‐embedded (FFPE) tissue to sub‐classify Diffuse Large B‐cell Lymphoma (DLBCL), in a population based cohort of 172 patients. GEP was performed using Illumina Whole Genome cDNA‐mediated Annealing, Selection, extension & Ligation, and tumours were classified into germinal centre (GCB), activated B‐cell (ABC) and Type‐III subtypes. The method was highly reproducible and reliably classified cell lines of known phenotype. GCB and ABC subtypes were each characterized by unique gene expression signatures consistent with previously published data. A significant relationship between subtype and survival was observed, with ABC having the worst clinical outcome and in a multivariate survival model only age and GEP class remained significant. This effect was not seen when tumours were classified by immunohistochemistry. There was a significant association between age and subtype (mean ages ABC – 72·8 years, GC – 68·4 years, Type‐III – 64·5 years). Older patients with ABC subtype were also over‐represented in patients who died soon after diagnosis. The relationship between prognosis and subtype improved when only patients assigned to the three categories with the highest level of confidence were analysed. This study demonstrates that GEP‐based classification of DLBCL can be applied to RNA extracted from routine FFPE samples and has potential for use in stratified medicine trials and clinical practice.

Survival from childhood acute lymphoblastic leukaemia: the impact of social inequality in the United Kingdom

BACKGROUND Survival from childhood acute lymphoblastic leukaemia (ALL) has continued to improve in economically-developed regions of the world, but 20% of patients still die within 5-years of diagnosis. Treatment is prolonged and complex; and as survival rates plateau, factors relating to socio-economic status and/or treatment adherence are increasingly scrutinised as potentially important determinants of outcome. METHODS Predicated on the frame-work of the United Kingdom (UK) NHS, the relationship between socio-demographic factors and ALL survival is examined here using data from a large follow-up study conducted in the 1990s. One thousand five hundred and fifty nine children (0-14 years) diagnosed in England, Scotland &Wales during the era of the national UKALL XI randomized-controlled trial (RCT) were followed-up for an average of 15.9 years (20,826.3 person-years). Area-based deprivation scores and fathers occupational social class at the time of the childs birth were used as markers of socio-economic status. Information on deaths was obtained from the NHS Information Centre for Health and Social Care. All children were included in the analyses, irrespective of RCT enrolment or participation in the founding epidemiological study (www.UKCCS.org).Survival effects were assessed using proportional hazards regressions models. RESULTS Survival varied with both area-based deprivation at diagnosis (hazard ratio (HR) 1.29; 95% confidence interval (CI) 1.05-1.57) and fathers occupational social class at birth (HR 1.12; 95% CI 0.97-1.29); the divergence beginning 6-9 months after diagnosis, and widening thereafter during home-administered therapy. The findings became more marked when analyses were restricted to those enrolled in UKALL XI (n = 1341). As expected, survival differences were also observed with sex, and age at diagnosis. CONCLUSION The existence of significant social disparities in ALL survival, which are not due to treatment accessibility, is of major clinical importance. Trends should be monitored and further research into potentially modifiable risk factors conducted.

Infectious Illness in Children Subsequently Diagnosed With Acute Lymphoblastic Leukemia: Modeling the Trends From Birth to Diagnosis

Although there is increasing evidence that immune dysregulation in children who develop acute lymphoblastic leukemia (ALL) is detectable from birth, debate about the role of infectious exposures in infancy continues. With the aim of quantifying childrens infectious exposures, investigators have used a number of infection exposure proxies, but there is a lack of consistency in findings, with some markers indicating increased ALL risks and others decreased risks, the disparity being evident both within and between studies. Accordingly, the authors conducted an in-depth analysis of key infection exposure proxies used in the United Kingdom Childhood Cancer Study, a national population-based case-control study conducted over the period 1991-1996, which combined data from medical records, parental interview, and population census. This longitudinal approach revealed the marked deterioration in immune response that emerged around 5 months prior to ALL diagnosis and confirmed that infectious diagnoses in the first year of life were significantly increased (P < 0.05) in children who developed leukemia between 2 and 14 years of age, as well as in those who had birth orders >1, were not breastfed, lived in deprived areas, or were diagnosed with eczema. By contrast, no association between infectious illness and preschool activity was detected, the lower infection levels among controls whose mothers reported attendance contributing to a significantly reduced ALL odds ratio.

Cost of treatment and QALYs lost due to genital warts: data for the economic evaluation of HPV vaccines in the United Kingdom.

Background: Data on the burden of genital warts in terms of treatment costs and detriment to quality of life (QoL) are required to assess cost-effectiveness of quadrivalent human papillomavirus vaccination. We investigated the cost of treatment and period of time for which QoL is affected to obtain estimates of quality-adjusted life year (QALY) loss associated with an episode of genital warts. Methods: Adults diagnosed with genital warts attending the York sexually transmitted disease clinic during two 3-month periods in 2006 and 2007 were enrolled (n = 189). Data on cost of treatment and duration of episode of care were collected from a retrospective case note review. QALY loss was calculated by applying estimates of the duration of time for which QoL was affected to the previously reported detriment to QoL associated with genital warts. Results: The average cost per episode of care was

Brain Tumor Signs and Symptoms: Analysis of Primary Health Care Records From the UKCCS

286 (£139, 95% CI:

Exercise-based cardiac rehabilitation in patients with heart failure: a meta-analysis of randomised controlled trials between 1999 and 2013

246–

Myeloid malignancies in the real-world: Occurrence, progression and survival in the UK’s population-based Haematological Malignancy Research Network 2004–15

327). Estimated loss of QALYs ranged from 0.0045 (95% CI: 0.0014–0.0078) to 0.023 (95% CI: 0.0072–0.039). Conclusions: Genital warts present a significant burden both to individuals and to the health service. Data on the burden of genital warts should be incorporated into economic evaluations of human papillomavirus vaccination strategies.