Reducing the Social Gradient in Uptake of the NHS Colorectal Cancer Screening Programme Using a Narrative-Based Information Leaflet: A Cluster-Randomised Trial

Objective: To test the effectiveness of adding a narrative leaflet to the current information material delivered by the NHS English colorectal cancer (CRC) screening programme on reducing socioeconomic inequalities in uptake. / Participants: 150,417 adults (59-74 years) routinely invited to complete the guaiac Faecal Occult Blood test (gFOBt) in March 2013. / Design: A cluster randomised controlled trial (ISRCTN74121020) to compare uptake between two arms. The control arm received the standard NHS CRC screening information material (SI) and the intervention arm received the standard information plus a supplementary narrative leaflet, which had previously been shown to increase screening intentions (SI+N). Between group comparisons were made for uptake overall and across socioeconomic status (SES). Results: Uptake was 57.7% and did not differ significantly between the two trial arms (SI: 58.5%; SI+N: 56.7%; Odds Ratio = 0.93, 95% confidence interval: 0.81-1.06, p = 0.27). There was no interaction between group and SES quintile (p = 0.44). / Conclusions: Adding a narrative leaflet to existing information materials does not reduce the SES gradient in uptake. Despite the benefits of using a pragmatic trial design, the need to add to, rather than replace existing information may have limited the true value of an evidence-based intervention on behaviour

Modelers' Perception of Mathematical Modeling in Epidemiology: A Web-Based Survey

International audienceBackground: Mathematical modeling in epidemiology (MME) is being used increasingly. However, there are many uncertainties in terms of definitions, uses and quality features of MME. Methodology/Principal Findings: To delineate the current status of these models, a 10-item questionnaire on MME was devised. Proposed via an anonymous internet-based survey, the questionnaire was completed by 189 scientists who had published in the domain of MME. A small minority (18%) of respondents claimed to have in mind a concise definition of MME. Some techniques were identified by the researchers as characterizing MME (e.g. Markov models), while others–at the same level of sophistication in terms of mathematics–were not (e.g. Cox regression). The researchers' opinions were also contrasted about the potential applications of MME, perceived as higly relevant for providing insight into complex mechanisms and less relevant for identifying causal factors. The quality criteria were those of good science and were not related to the size and the nature of the public health problems addressed. Conclusions/Significance: This study shows that perceptions on the nature, uses and quality criteria of MME are contrasted, even among the very community of published authors in this domain. Nevertheless, MME is an emerging discipline in epidemiology and this study underlines that it is associated with specific areas of application and methods. The development of this discipline is likely to deserve a framework providing recommendations and guidance at various steps of the studies, from design to report

Effects of evidence-based strategies to reduce the socioeconomic gradient of uptake in the English NHS Bowel Cancer Screening Programme (ASCEND): four cluster-randomised controlled trials

This study is funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research Programme ( RP-PG-0609-10106 ) and partly supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North Thames (MCT and RR

Brief Review Renal Aging. Causes and consequences

Individuals age >65 years old are the fastest expanding population demographic throughout the developed world. Consequently, more aged patients than before are receiving diagnoses of impaired renal function and nephrosclerosis—age–associated histologic changes in the kidneys. Recent studies have shown that the aged kidney undergoes a range of structural changes and has altered transcriptomic, hemodynamic, and physiologic behavior at rest and in response to renal insults. These changes impair the ability of the kidney to withstand and recover from injury, contributing to the high susceptibility of the aged population to AKI and their increased propensity to develop subsequent progressive CKD. In this review, we examine these features of the aged kidney and explore the various validated and putative pathways contributing to the changes observed with aging in both experimental animal models and humans. We also discuss the potential for additional study to increase understanding of the aged kidney and lead to novel therapeutic strategies

Personal experience with the procurement of 132 liver allografts

A single donor surgeon's experience procuring the livers from 132 donors is described. Thirty-seven grafts (28.9%) had hepatic arterial anomalies, 19 (14.4%) of which required arterial reconstruction prior to transplantation. Of the 121 grafts evaluated for early function, 103 grafts (85.2%) functioned well, whereas 14 grafts (11.6%) functioned poorly and 4 grafts (3.3%) failed to function at all. The variables associated with less than optimal function of the graft consisted of donor age (P<0.05), duration of donor's stay in the intensive care unit (P<0.005), abnormal graft appearance (P<0.05), and such recipient problems as vascular thromboses during or immediately following transplantation (P<0.005). A new preservation fluid, University of Wisconsin solution, allowed safe and longer cold storage of the liver allograft than did Euro-Collins' solution (P<0.0001). A parameter of liver allograft viability, which is simple and predictive of allograft function prior to the actual transplant procedure, is urgently needed. © 1989 Springer-Verlag

Effective, Robust Design of Community Mitigation for Pandemic Influenza: A Systematic Examination of Proposed US Guidance

BACKGROUND: The US government proposes pandemic influenza mitigation guidance that includes isolation and antiviral treatment of ill persons, voluntary household member quarantine and antiviral prophylaxis, social distancing of individuals, school closure, reduction of contacts at work, and prioritized vaccination. Is this the best strategy combination? Is choice of this strategy robust to pandemic uncertainties? What are critical enablers of community resilience? METHODS AND FINDINGS: We systematically simulate a broad range of pandemic scenarios and mitigation strategies using a networked, agent-based model of a community of explicit, multiply-overlapping social contact networks. We evaluate illness and societal burden for alterations in social networks, illness parameters, or intervention implementation. For a 1918-like pandemic, the best strategy minimizes illness to <1% of the population and combines network-based (e.g. school closure, social distancing of all with adults' contacts at work reduced), and case-based measures (e.g. antiviral treatment of the ill and prophylaxis of household members). We find choice of this best strategy robust to removal of enhanced transmission by the young, additional complexity in contact networks, and altered influenza natural history including extended viral shedding. Administration of age-group or randomly targeted 50% effective pre-pandemic vaccine with 7% population coverage (current US H5N1 vaccine stockpile) had minimal effect on outcomes. In order, mitigation success depends on rapid strategy implementation, high compliance, regional mitigation, and rigorous rescinding criteria; these are the critical enablers for community resilience. CONCLUSIONS: Systematic evaluation of feasible, recommended pandemic influenza interventions generally confirms the US community mitigation guidance yields best strategy choices for pandemic planning that are robust to a wide range of uncertainty. The best strategy combines network- and case-based interventions; network-based interventions are paramount. Because strategies must be applied rapidly, regionally, and stringently for greatest benefit, preparation and public education is required for long-lasting, high community compliance during a pandemic

A Biological Model for Influenza Transmission: Pandemic Planning Implications of Asymptomatic Infection and Immunity

Background: The clinical attack rate of influenza is influenced by prior immunity and mixing patterns in the host population, and also by the proportion of infections that are asymptomatic. This complexity makes it difficult to directly estimate R0 from the attack rate, contributing to uncertainty in epidemiological models to guide pandemic planning. We have modelled multiple wave outbreaks of influenza from different populations to allow for changing immunity and asymptomatic infection and to make inferences about R0. \ud \ud Data and Methods. On the island of Tristan da Cunha (TdC), 96% of residents reported illness during an H3N2 outbreak in 1971, compared with only 25% of RAF personnel in military camps during the 1918 H1N1 pandemic. Monte Carlo Markov Chain (MCMC) methods were used to estimate model parameter distributions. \ud \ud Findings. We estimated that most islanders on TdC were non-immune (susceptible) before the first wave, and that almost all exposures of susceptible persons caused symptoms. The median R0 of 6.4 (95% credibility interval 3.7–10.7) implied that most islanders were exposed twice, although only a minority became ill in the second wave because of temporary protection following the first wave. In contrast, only 51% of RAF personnel were susceptible before the first wave, and only 38% of exposed susceptibles reported symptoms. R0 in this population was also lower [2.9 (2.3–4.3)], suggesting reduced viral transmission in a partially immune population. \ud \ud Interpretation: Our model implies that the RAF population was partially protected before the summer pandemic wave of 1918, arguably because of prior exposure to interpandemic influenza. Without such protection, each symptomatic case of influenza would transmit to between 2 and 10 new cases, with incidence initially doubling every 1–2 days. Containment of a novel virus could be more difficult than hitherto supposed

Modelling the Effects of Population Structure on Childhood Disease: The Case of Varicella

Realistic, individual-based models based on detailed census data are increasingly used to study disease transmission. Whether the rich structure of such models improves predictions is debated. This is studied here for the spread of varicella, a childhood disease, in a realistic population of children where infection occurs in the household, at school, or in the community at large. A methodology is first presented for simulating households with births and aging. Transmission probabilities were fitted for schools and community, which reproduced the overall cumulative incidence of varicella over the age range of 0–11 years old

Modeling influenza epidemics and pandemics: insights into the future of swine flu (H1N1)

Here we present a review of the literature of influenza modeling studies, and discuss how these models can provide insights into the future of the currently circulating novel strain of influenza A (H1N1), formerly known as swine flu. We discuss how the feasibility of controlling an epidemic critically depends on the value of the Basic Reproduction Number (R0). The R0 for novel influenza A (H1N1) has recently been estimated to be between 1.4 and 1.6. This value is below values of R0 estimated for the 1918–1919 pandemic strain (mean R0~2: range 1.4 to 2.8) and is comparable to R0 values estimated for seasonal strains of influenza (mean R0 1.3: range 0.9 to 2.1). By reviewing results from previous modeling studies we conclude it is theoretically possible that a pandemic of H1N1 could be contained. However it may not be feasible, even in resource-rich countries, to achieve the necessary levels of vaccination and treatment for control. As a recent modeling study has shown, a global cooperative strategy will be essential in order to control a pandemic. This strategy will require resource-rich countries to share their vaccines and antivirals with resource-constrained and resource-poor countries. We conclude our review by discussing the necessity of developing new biologically complex models. We suggest that these models should simultaneously track the transmission dynamics of multiple strains of influenza in bird, pig and human populations. Such models could be critical for identifying effective new interventions, and informing pandemic preparedness planning. Finally, we show that by modeling cross-species transmission it may be possible to predict the emergence of pandemic strains of influenza

Defects in ErbB-Dependent Establishment of Adult Melanocyte Stem Cells Reveal Independent Origins for Embryonic and Regeneration Melanocytes

Adult stem cells are responsible for maintaining and repairing tissues during the life of an organism. Tissue repair in humans, however, is limited compared to the regenerative capabilities of other vertebrates, such as the zebrafish (Danio rerio). An understanding of stem cell mechanisms, such as how they are established, their self-renewal properties, and their recruitment to produce new cells is therefore important for the application of regenerative medicine. We use larval melanocyte regeneration following treatment with the melanocytotoxic drug MoTP to investigate these mechanisms in Melanocyte Stem Cell (MSC) regulation. In this paper, we show that the receptor tyrosine kinase, erbb3b, is required for establishing the adult MSC responsible for regenerating the larval melanocyte population. Both the erbb3b mutant and wild-type fish treated with the ErbB inhibitor, AG1478, develop normal embryonic melanocytes but fail to regenerate melanocytes after MoTP-induced melanocyte ablation. By administering AG1478 at different time points, we show that ErbB signaling is only required for regeneration prior to MoTP treatment and before 48 hours of development, consistent with a role in establishing MSCs. We then show that overexpression of kitla, the Kit ligand, in transgenic larvae leads to recruitment of MSCs, resulting in overproliferation of melanocytes. Furthermore, kitla overexpression can rescue AG1478-blocked regeneration, suggesting that ErbB signaling is required to promote the progression and specification of the MSC from a pre–MSC state. This study provides evidence that ErbB signaling is required for the establishment of adult MSCs during embryonic development. That this requirement is not shared with the embryonic melanocytes suggests that embryonic melanocytes develop directly, without proceeding through the ErbB-dependent MSC. Moreover, the shared requirement of larval melanocyte regeneration and metamorphic melanocytes that develops at the larval-to-adult transition suggests that these post-embryonic melanocytes develop from the same adult MSC population. Lastly, that kitla overexpression can recruit the MSC to develop excess melanocytes raises the possibility that Kit signaling may be involved in MSC recruitment during regeneration