Country planning for health interventions under development: lessons from the malaria vaccine decision-making framework and implications for other new interventions

Traditionally it has taken years or decades for new public health interventions targeting diseases found in developing countries to be accessible to those most in need. One reason for the delay has been insufficient anticipation of the eventual processes and evidence required for decision making by countries. This paper describes research into the anticipated processes and data needed to inform decision making on malaria vaccines, the most advanced of which is still in phase 3 trials. From 2006 to 2008, a series of country consultations in Africa led to the development of a guide to assist countries in preparing their malaria vaccine decision-making frameworks. The guide builds upon the World Health Organization's Vaccine Introduction Guidelines. It identifies the processes and data for decisions, when they would be needed relative to the development timelines of the intervention, and where they will come from. Policy development will be supported by data (e.g. malaria disease burden; roles of other malaria interventions; malaria vaccine impact; economic and financial issues; malaria vaccine efficacy, quality and safety) as will implementation decisions (e.g. programmatic issues and socio-cultural environment). This generic guide can now be applied to any future malaria vaccine. The paper discusses the opportunities and challenges to early planning for country decision-making—from the potential for timely, evidence-informed decisions to the risks of over-promising around an intervention still under development. Careful and well-structured planning by countries is an important way to ensure that new interventions do not remain unused for years or decades after they become availabl

Country planning for health interventions under development: lessons from the malaria vaccine decision-making framework and implications for other new interventions

Traditionally it has taken years or decades for new public health interventions targeting diseases found in developing countries to be accessible to those most in need. One reason for the delay has been insufficient anticipation of the eventual processes and evidence required for decision making by countries. This paper describes research into the anticipated processes and data needed to inform decision making on malaria vaccines, the most advanced of which is still in phase 3 trials. From 2006 to 2008, a series of country consultations in Africa led to the development of a guide to assist countries in preparing their malaria vaccine decision-making frameworks. The guide builds upon the World Health Organization’s Vaccine Introduction Guidelines. It identifies the processes and data for decisions, when they would be needed relative to the development timelines of the intervention, and where they will come from. Policy development will be supported by data (e.g. malaria disease burden; roles of other malaria interventions; malaria vaccine impact; economic and financial issues; malaria vaccine efficacy, quality and safety) as will implementation decisions (e.g. programmatic issues and socio-cultural environment). This generic guide can now be applied to any future malaria vaccine. The paper discusses the opportunities and challenges to early planning for country decision-making—from the potential for timely, evidence-informed decisions to the risks of over-promising around an intervention still under development. Careful and well-structured planning by countries is an important way to ensure that new interventions do not remain unused for years or decades after they become available

The comprehensive cohort model in a pilot trial in orthopaedic trauma

Background: The primary aim of this study was to provide an estimate of effect size for the functional outcome of operative versus non-operative treatment for patients with an acute rupture of the Achilles tendon using accelerated rehabilitation for both groups of patients. The secondary aim was to assess the use of a comprehensive cohort research design (i.e. a parallel patient-preference group alongside a randomised group) in improving the accuracy of this estimate within an orthopaedic trauma setting. Methods: Pragmatic randomised controlled trial and comprehensive cohort study within a level 1 trauma centre. Twenty randomised participants (10 operative and 10 non-operative) and 29 preference participants (3 operative and 26 non-operative). The ge range was 22-72 years and 37 of the 52 patients were men. All participants had an acute rupture of their Achilles tendon and no other injuries. All of the patients in the operative group had a simple end-to-end repair of the tendon with no augmentation. Both groups then followed the same eight-week immediate weight-bearing rehabilitation programme using an off-the-shelf orthotic. The disability rating index (DRI; primary outcome), EQ-5D, Achilles Total Rupture Score and complications were assessed ed at two weeks, six weeks, three months, six months and nine months after initial injury. Results: At nine months, there was no significant difference in DRI between patients randomised to operative or non-operative management. There was no difference in DRI between the randomised group and the parallel patient preference group. The use of a comprehensive cohort of patients did not provide useful additional information as to the treatment effect size because the majority of patients chose non-operative management. Conclusions: Recruitment to clinical trials that compare operative and non-operative interventions is notoriously difficult; especially within the trauma setting. Including a parallel patient preference group to create a comprehensive cohort of patients has been suggested as a way of increasing the power of such trials. In our study, the comprehensive cohort model doubled the number of patients involved in the study. However, a strong preference for non-operative treatment meant that the increased number of patients did not significantly increase the ability of the trial to detect a difference between the two interventions

Which older people decline participation in a primary care trial of physical activity and why: insights from a mixed methods approach

This article is available through the Brunel Open Access Publishing Fund. Copyright 2014 Rogers et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Physical activity is of vital importance to older peoples’ health. Physical activity intervention studies with older people often have low recruitment, yet little is known about non-participants. Methods: Patients aged 60–74 years from three UK general practices were invited to participate in a nurse-supported pedometer-based walking intervention. Demographic characteristics of 298 participants and 690 non-participants were compared. Health status and physical activity of 298 participants and 183 non-participants who completed a survey were compared using age, sex adjusted odds ratios (OR) (95% confidence intervals). 15 non-participants were interviewed to explore perceived barriers to participation. Results: Recruitment was 30% (298/988). Participants were more likely than non-participants to be female (54% v 47%; p = 0.04) and to live in affluent postcodes (73% v 62% in top quintile; p < 0.001). Participants were more likely than non-participants who completed the survey to have an occupational pension OR 2.06 (1.35-3.13), a limiting longstanding illness OR 1.72 (1.05-2.79) and less likely to report being active OR 0.55 (0.33-0.93) or walking fast OR 0.56 (0.37-0.84). Interviewees supported general practice-based physical activity studies, particularly walking, but barriers to participation included: already sufficiently active, reluctance to walk alone or at night, physical symptoms, depression, time constraints, trial equipment and duration. Conclusion: Gender and deprivation differences suggest some selection bias. However, trial participants reported more health problems and lower activity than non-participants who completed the survey, suggesting appropriate trial selection in a general practice population. Non-participant interviewees indicated that shorter interventions, addressing physical symptoms and promoting confidence in pursuing physical activity, might increase trial recruitment and uptake of practice-based physical activity endeavours.The National Institute for Health Research (NIHR) under its Research for Patient Benefit Programme (Grant Reference Number PB-PG-0909-20055)

Chiropractic wellness on the web: the content and quality of information related to wellness and primary prevention on the Internet

<p>Abstract</p> <p>Background</p> <p>The Internet has become a common source of information for patients wishing to learn about health information. Previous studies found information related to back pain poor and often contradictory to current guidelines. Wellness has become a common topic in the field of chiropractic and accrediting agencies have standards on delivery of wellness-based content in college curricula as well as directives for clinical applications. The purpose of this study was to evaluate the quality of the information on the Internet using the terms "chiropractic wellness," or "wellness chiropractic".</p> <p>Methods</p> <p>Five commonly used search engines were selected and the first 10 sites found using the strategy above were evaluated by two raters. Demographic assessments of the sites were made along with whether they were Health on the Net Foundation (HON) certified, contained standard wellness content, mentioned any Healthy People Focus Areas, and other chiropractic topics. Kappa statistics compared inter-rater agreement.</p> <p>Results</p> <p>Potential patients appeared to be the audience 87% of the time and a private doctor of chiropractic appeared to be the typical site owner. The sites usually promoted the provider. No sites displayed HON certification logo nor did any appear to meet the HON certification criteria. Twenty-six sites (55%) promoted regular physical activity in some manner and 18 (38%) had information on health risks of tobacco. Four (9%) had mental health or stress-reduction content but none had information supportive of vaccination. Some had information contradictory to common public health measures.</p> <p>Conclusions</p> <p>Patients searching the Internet for chiropractic wellness information will often find useless information that will not help them maintain health or become well. Most simply market the chiropractic practice or allow for a patients to provide personal information in exchange for more 'wellness' information. More research should be done on how providers determine site content, pay any attention to the details on their sites, or agree with content as some appear to be prefabricated sites. Website content could be enhanced by sharing of information from reputable sources like US Centers for Disease Control, the National Institutes of Health and other authoritative sources. HON certification should also be sought.</p

Microbes in the neonatal intensive care unit resemble those found in the gut of premature infants

Background: The source inoculum of gastrointestinal tract (GIT) microbes is largely influenced by delivery mode in full-term infants, but these influences may be decoupled in very low birth weight (VLBW, <1,500 g) neonates via conventional broad-spectrum antibiotic treatment. We hypothesize the built environment (BE), specifically room surfaces frequently touched by humans, is a predominant source of colonizing microbes in the gut of premature VLBW infants. Here, we present the first matched fecal-BE time series analysis of two preterm VLBW neonates housed in a neonatal intensive care unit (NICU) over the first month of life.Results: Fresh fecal samples were collected every 3 days and metagenomes sequenced on an Illumina HiSeq2000 device. For each fecal sample, approximately 33 swabs were collected from each NICU room from 6 specified areas: sink, feeding and intubation tubing, hands of healthcare providers and parents, general surfaces, and nurse station electronics (keyboard, mouse, and cell phone). Swabs were processed using a recently developed 'expectation maximization iterative reconstruction of genes from the environment' (EMIRGE) amplicon pipeline in which full-length 16S rRNA amplicons were sheared and sequenced using an Illumina platform, and short reads reassembled into full-length genes. Over 24,000 full-length 16S rRNA sequences were produced, generating an average of approximately 12,000 operational taxonomic units (OTUs) (clustered at 97% nucleotide identity) per room-infant pair. Dominant gut taxa, including Staphylococcus epidermidis, Klebsiella pneumoniae, Bacteroides fragilis, and Escherichia coli, were widely distributed throughout the room environment with many gut colonizers detected in more than half of samples. Reconstructed genomes from infant gut colonizers revealed a suite of genes that confer resistance to antibiotics (for example, tetracycline, fluoroquinolone, and aminoglycoside) and sterilizing agents, which likely offer a competitive advantage in the NICU environment.Conclusions: We have developed a high-throughput culture-independent approach that integrates room surveys based on full-length 16S rRNA gene sequences with metagenomic analysis of fecal samples collected from infants in the room. The approach enabled identification of discrete ICU reservoirs of microbes that also colonized the infant gut and provided evidence for the presence of certain organisms in the room prior to their detection in the gut

An exact expression to calculate the derivatives of position-dependent observables in molecular simulations with flexible constraints

In this work, we introduce an algorithm to compute the derivatives of physical observables along the constrained subspace when flexible constraints are imposed on the system (i.e., constraints in which the hard coordinates are fixed to configuration-dependent values). The presented scheme is exact, it does not contain any tunable parameter, and it only requires the calculation and inversion of a sub-block of the Hessian matrix of second derivatives of the function through which the constraints are defined. We also present a practical application to the case in which the sought observables are the Euclidean coordinates of complex molecular systems, and the function whose minimization defines the constraints is the potential energy. Finally, and in order to validate the method, which, as far as we are aware, is the first of its kind in the literature, we compare it to the natural and straightforward finite-differences approach in three molecules of biological relevance: methanol, N-methyl-acetamide and a tri-glycine peptideComment: 13 pages, 8 figures, published versio

Illuminating subduction zone rheological properties in the wake of a giant earthquake

Deformation associated with plate convergence at subduction zones is accommodated by a complex system involving fault slip and viscoelastic flow. These processes have proven difficult to disentangle. The 2010 Mw 8.8 Maule earthquake occurred close to the Chilean coast within a dense network of continuously recording Global Positioning System stations, which provide a comprehensive history of surface strain. We use these data to assemble a detailed picture of a structurally controlled megathrust fault frictional patchwork and the three-dimensional rheological and time-dependent viscosity structure of the lower crust and upper mantle, all of which control the relative importance of afterslip and viscoelastic relaxation during postseismic deformation. These results enhance our understanding of subduction dynamics including the interplay of localized and distributed deformation during the subduction zone earthquake cycle

GalNAc glycoprotein expression by breast cell lines, primary breast cancer and normal breast epithelial membrane

Over-expression of N-acetylgalactosamine glycoproteins as detected by binding of the lectin from Helix pomatia (HPA), is associated with metastatic competence and poor patient prognosis in a range of human adenocarcinomas. These glycoproteins remain poorly characterised, and their functional role has yet to be elucidated. This study describes characterisation of a range of human breast/breast cancer cell lines for the expression of the N-acetylgalactosaminylated glycoproteins of interest, and their comparison with normal breast epithelium and a range of clinical breast carcinoma samples. Confocal and light microscopy studies revealed cytochemical HPA-binding patterns consistent with a fundamental disruption in normal glycobiosynthetic pathways attending increasing metastatic potential. We report the most complete comparative analysis of HPA-binding ligands from cultured breast cells, clinical breast carcinoma samples and normal breast epithelium to date. Lectin blotting identified 11 major HPA-binding glycoprotein bands common to both clinical tumour samples and breast cell lines and 6 of these bands were also expressed by samples of normal breast epithelium, albeit at much lower levels. Moreover, very marked quantitative but not qualitative differences in levels of expression consistent with metastatic capability were noted. © 2001 Cancer Research Campaignhttp://www.bjcancer.co