Portals to Wonderland: Health portals lead to confusing information about the effects of health care

BACKGROUND: The Internet offers a seemingly endless amount of health information of varying quality. Health portals, which provide entry points to quality-controlled collections of websites, have been hailed as a solution to this problem. The objective of this study is to assess the extent to which government-run health portals provide access to relevant, valid and understandable information about the effects of health care. METHODS: We selected eight clinically relevant questions for which there was a systematic review, searched four portals for answers, and compared the answers we found to the results of the systematic reviews. RESULTS: Our searches resulted in 3400 hits, 155 of which mentioned both the condition and the intervention in one of the eight questions. Sixty-three of the 155 web pages did not give any information about the effect of the intervention. Seventy-seven qualitatively described the effects of the intervention. Twenty-six of these had information that was too unclear to be categorised; 15 were not consistent with the systematic review; and 36 were consistent with the review, but usually did not mention what happens without the intervention, what outcomes have been measured or when they were measured. Fifteen web pages quantitatively described effects. Four of these were abstracts from the systematic review, nine had information that was incomplete and potentially misleading because of a lack of information about people not receiving the intervention and the length of follow-up; one had information that was consistent with the review, but only referred to three trials whereas the review included six; and one was consistent with the review. CONCLUSION: Information accessible through health portals is unlikely to be based on systematic reviews and is often unclear, incomplete and misleading. Portals are only as good as the websites they lead to. Investments in national health portals are unlikely to benefit consumers without investments in the production and maintenance of relevant, valid and understandable information to which the portals lead

Translating research into policy and practice in developing countries: a case study of magnesium sulphate for pre-eclampsia.

BACKGROUND: The evidence base for improving reproductive health continues to grow. However, concerns remain that the translation of this evidence into appropriate policies is partial and slow. Little is known about the factors affecting the use of evidence by policy makers and clinicians, particularly in developing countries. The objective of this study was to examine the factors that might affect the translation of randomised controlled trial (RCT) findings into policies and practice in developing countries. METHODS: The recent publication of an important RCT on the use of magnesium sulphate to treat pre-eclampsia provided an opportunity to explore how research findings might be translated into policy. A range of research methods, including a survey, group interview and observations with RCT collaborators and a survey of WHO drug information officers, regulatory officials and obstetricians in 12 countries, were undertaken to identify barriers and facilitators to knowledge translation. RESULTS: It proved difficult to obtain reliable data regarding the availability and use of commonly used drugs in many countries. The perceived barriers to implementing RCT findings regarding the use of magnesium sulphate for pre-eclampsia include drug licensing and availability; inadequate and poorly implemented clinical guidelines; and lack of political support for policy change. However, there were significant regional and national differences in the importance of specific barriers. CONCLUSION: The policy changes needed to ensure widespread availability and use of magnesium sulphate are variable and complex. Difficulties in obtaining information on availability and use are combined with the wide range of barriers across settings, including a lack of support from policy makers. This makes it difficult to envisage any single intervention strategy that might be used to promote the uptake of research findings on magnesium sulphate into policy across the study settings. The publication of important trials may therefore not have the impacts on health care that researchers hope for

Decision-Making Under Risk in Children, Adolescents, and Young Adults

Adolescents often make risky and impulsive decisions. Such behavior has led to the common assumption that a dysfunction in risk-related decision-making peaks during this age. Differences in how risk has been defined across studies, however, make it difficult to draw conclusions about developmental changes in risky decision-making. Here, we developed a non-symbolic economic decision-making task that can be used across a wide age span and that uses coefficient of variation (CV) in reward as an index of risk. We found that young children showed the strongest preference for risky compared to sure bet options of equal expected value, adolescents were intermediate in their risk preference, and young adults showed the strongest risk aversion. Furthermore, children's preference for the risky option increased for larger CVs, while adolescents and young adults showed the opposite pattern, favoring the sure bet more often as CV increased. Finally, when faced with two gambles in a risk–return tradeoff, all three age groups exhibited a greater preference for the option with the lower risk and return as the disparity in risk between the two options increased. These findings demonstrate clear age-related differences in economic risk preferences that vary with choice set and risk. Importantly, adolescence appears to represent an intermediate decision-making phenotype along the transition from childhood to adulthood, rather than an age of heightened preference for economic risk

Light Scattering Measured with Spatial Frequency Domain Imaging can Predict Stromal Versus Epithelial Proportions in Surgically Resected Breast Tissue

This study aims to determine if light scatter parameters measured with spatial frequency domain imaging (SFDI) can accurately predict stromal, epithelial, and adipose fractions in freshly resected, unstained human breast specimens. An explicit model was developed to predict stromal, epithelial, and adipose fractions as a function of light scattering parameters, which was validated against a quantitative analysis of digitized histology slides for N  =  31 specimens using leave-one-out cross-fold validation. Specimen mean stromal, epithelial, and adipose volume fractions predicted from light scattering parameters strongly correlated with those calculated from digitized histology slides (r  =  0.90, 0.77, and 0.91, respectively, p-value×  10  -  6). Additionally, the ratio of predicted epithelium to stroma classified malignant specimens with a sensitivity and specificity of 90% and 81%, respectively, and also classified all pixels in malignant lesions with 63% and 79%, at a threshold of 1. All specimens and pixels were classified as malignant, benign, or fat with 84% and 75% accuracy, respectively. These findings demonstrate how light scattering parameters acquired with SFDI can be used to accurately predict and spatially map stromal, epithelial, and adipose proportions in fresh unstained, human breast tissue, and suggest that these estimations could provide diagnostic value

Spectral discrimination of breast pathologies in situ using spatial frequency domain imaging

Introduction: Nationally, 25% to 50% of patients undergoing lumpectomy for local management of breast cancer require a secondary excision because of the persistence of residual tumor. Intraoperative assessment of specimen margins by frozen-section analysis is not widely adopted in breast-conserving surgery. Here, a new approach to wide-field optical imaging of breast pathology in situ was tested to determine whether the system could accurately discriminate cancer from benign tissues before routine pathological processing. Methods: Spatial frequency domain imaging (SFDI) was used to quantify near-infrared (NIR) optical parameters at the surface of 47 lumpectomy tissue specimens. Spatial frequency and wavelength-dependent reflectance spectra were parameterized with matched simulations of light transport. Spectral images were co-registered to histopathology in adjacent, stained sections of the tissue, cut in the geometry imaged in situ. A supervised classifier and feature-selection algorithm were implemented to automate discrimination of breast pathologies and to rank the contribution of each parameter to a diagnosis. Results: Spectral parameters distinguished all pathology subtypes with 82% accuracy and benign (fibrocystic disease, fibroadenoma) from malignant (DCIS, invasive cancer, and partially treated invasive cancer after neoadjuvant chemotherapy) pathologies with 88% accuracy, high specificity (93%), and reasonable sensitivity (79%). Although spectral absorption and scattering features were essential components of the discriminant classifier, scattering exhibited lower variance and contributed most to tissue-type separation. The scattering slope was sensitive to stromal and epithelial distributions measured with quantitative immunohistochemistry. Conclusions: SFDI is a new quantitative imaging technique that renders a specific tissue-type diagnosis. Its combination of planar sampling and frequency-dependent depth sensing is clinically pragmatic and appropriate for breast surgical-margin assessment. This study is the first to apply SFDI to pathology discrimination in surgical breast tissues. It represents an important step toward imaging surgical specimens immediately ex vivo to reduce the high rate of secondary excisions associated with breast lumpectomy procedures

Calibration and Analysis of a Multimodal Micro-CT and Structured Light Imaging System for the Evaluation of Excised Breast Tissue.

A multimodal micro-computed tomography (CT) and multi-spectral structured light imaging (SLI) system is introduced and systematically analyzed to test its feasibility to aid in margin delineation during breast conserving surgery (BCS). Phantom analysis of the micro-CT yielded a signal-to-noise ratio of 34, a contrast of 1.64, and a minimum detectable resolution of 240 ?m for a 1.2?min scan. The SLI system, spanning wavelengths 490?nm to 800?nm and spatial frequencies up to 1.37 , was evaluated with aqueous tissue simulating phantoms having variations in particle size distribution, scatter density, and blood volume fraction. The reduced scattering coefficient, and phase function parameter, ?, were accurately recovered over all wavelengths independent of blood volume fractions from 0% to 4%, assuming a flat sample geometry perpendicular to the imaging plane. The resolution of the optical system was tested with a step phantom, from which the modulation transfer function was calculated yielding a maximum resolution of 3.78 cycles per mm. The three dimensional spatial co-registration between the CT and optical imaging space was tested and shown to be accurate within 0.7?mm. A freshly resected breast specimen, with lobular carcinoma, fibrocystic disease, and adipose, was imaged with the system. The micro-CT provided visualization of the tumor mass and its spiculations, and SLI yielded superficial quantification of light scattering parameters for the malignant and benign tissue types. These results appear to be the first demonstration of SLI combined with standard medical tomography for imaging excised tumor specimens. While further investigations are needed to determine and test the spectral, spatial, and CT features required to classify tissue, this study demonstrates the ability of multimodal CT/SLI to quantify, visualize, and spatially navigate breast tumor specimens, which could potentially aid in the assessment of tumor margin status during BCS

A comparative evaluation of PDQ-Evidence

BACKGROUND: A strategy for minimising the time and obstacles to accessing systematic reviews of health system evidence is to collect them in a freely available database and make them easy to find through a simple ‘Google-style’ search interface. PDQ-Evidence was developed in this way. The objective of this study was to compare PDQ-Evidence to six other databases, namely Cochrane Library, EVIPNet VHL, Google Scholar, Health Systems Evidence, PubMed and Trip. METHODS: We recruited healthcare policy-makers, managers and health researchers in low-, middle- and highincome countries. Participants selected one of six pre-determined questions. They searched for a systematic review that addressed the chosen question and one question of their own in PDQ-Evidence and in two of the other six databases which they would normally have searched. We randomly allocated participants to search PDQ-Evidence first or to search the two other databases first. The primary outcomes were whether a systematic review was found and the time taken to find it. Secondary outcomes were perceived ease of use and perceived time spent searching. We asked open-ended questions about PDQ-Evidence, including likes, dislikes, challenges and suggestions for improvements. RESULTS: A total of 89 people from 21 countries completed the study; 83 were included in the primary analyses and 6 were excluded because of data errors that could not be corrected. Most participants chose PubMed and Cochrane Library as the other two databases. Participants were more likely to find a systematic review using PDQ-Evidence than using Cochrane Library or PubMed for the pre-defined questions. For their own questions, this difference was not found. Overall, it took slightly less time to find a systematic review using PDQ-Evidence. Participants perceived that it took less time, and most participants perceived PDQ-Evidence to be slightly easier to use than the two other databases. However, there were conflicting views about the design of PDQ-Evidence. CONCLUSIONS: PDQ-Evidence is at least as efficient as other databases for finding health system evidence. However, using PDQ-Evidence is not intuitive for some people

Abnormal RNA Stability in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share key features, including accumulation of the RNA-binding protein TDP-43. TDP-43 regulates RNA homeostasis, but it remains unclear whether RNA stability is affected in these disorders. We use Bru-seq and BruChase-seq to assess genome-wide RNA stability in ALS patient-derived cells, demonstrating profound destabilization of ribosomal and mitochondrial transcripts. This pattern is recapitulated by TDP-43 overexpression, suggesting a primary role for TDP-43 in RNA destabilization, and in postmortem samples from ALS and FTD patients. Proteomics and functional studies illustrate corresponding reductions in mitochondrial components and compensatory increases in protein synthesis. Collectively, these observations suggest that TDP-43 deposition leads to targeted RNA instability in ALS and FTD, and may ultimately cause cell death by disrupting energy production and protein synthesis pathways

Evidence-informed health policy 1 – Synthesis of findings from a multi-method study of organizations that support the use of research evidence

Background: Organizations have been established in many countries and internationally to support the use of research evidence by producing clinical practice guidelines, undertaking health technology assessments, and/or directly supporting the use of research evidence in developing health policy on an international, national, and state or provincial level. Learning from these organizations can reduce the need to 'reinvent the wheel' and inform decisions about how best to organize support for such organizations, particularly in low- and middle-income countries (LMICs). Methods: We undertook a multi-method study in three phases – a survey, interviews, and case descriptions that drew on site visits – and in each of the second and third phases we focused on a purposive sample of those involved in the previous phase. We used the seven main recommendations that emerged from the advice offered in the interviews to organize much of the synthesis of findings across phases and methods. We used a constant comparative method to identify themes from across phases and methods. Results: Seven recommendations emerged for those involved in establishing or leading organizations that support the use of research evidence in developing health policy: 1) collaborate with other organizations; 2) establish strong links with policymakers and involve stakeholders in the work; 3) be independent and manage conflicts of interest among those involved in the work; 4) build capacity among those working in the organization; 5) use good methods and be transparent in the work; 6) start small, have a clear audience and scope, and address important questions; and 7) be attentive to implementation considerations, even if implementation is not a remit. Four recommendations emerged for the World Health Organization (WHO) and other international organizations and networks: 1) support collaborations among organizations; 2) support local adaptation efforts; 3) mobilize support; and 4) create global public goods. Conclusion: This synthesis of findings from a multi-method study, along with the more detailed findings from each of the three phases of the study (which are reported in the three following articles in the series), provide a strong basis on which researchers, policymakers, international organizations (and networks) like WHO can respond to the growing chorus of voices calling for efforts to support the use of research evidence in developing health policy

Evidence-informed health policy 3 – Interviews with the directors of organizations that support the use of research evidence

Background: Previous surveys of organizations that support the development of evidence-informed health policies have focused on organizations that produce clinical practice guidelines (CPGs) or undertake health technology assessments (HTAs). Only rarely have surveys focused at least in part on units that directly support the use of research evidence in developing health policy on an international, national, and state or provincial level (i.e., government support units, or GSUs) that are in some way successful or innovative or that support the use of research evidence in low- and middle-income countries (LMICs). Methods: We drew on many people and organizations around the world, including our project reference group, to generate a list of organizations to survey. We modified a questionnaire that had been developed originally by the Appraisal of Guidelines, Research and Evaluation in Europe (AGREE) collaboration and adapted one version of the questionnaire for organizations producing CPGs and HTAs, and another for GSUs. We sent the questionnaire by email to 176 organizations and followed up periodically with non-responders by email and telephone. Results: We received completed questionnaires from 152 (86%) organizations. More than one-half of the organizations (and particularly HTA agencies) reported that examples from other countries were helpful in establishing their organization. A higher proportion of GSUs than CPG-or HTA-producing organizations involved target users in the selection of topics or the services undertaken. Most organizations have few (five or fewer) full-time equivalent (FTE) staff. More than four-fifths of organizations reported providing panels with or using systematic reviews. GSUs tended to use a wide variety of explicit valuation processes for the research evidence, but none with the frequency that organizations producing CPGs, HTAs, or both prioritized evidence by its quality. Between one-half and two-thirds of organizations do not collect data systematically about uptake, and roughly the same proportions do not systematically evaluate their usefulness or impact in other ways. Conclusion: The findings from our survey, the most broadly based of its kind, both extend or clarify the applicability of the messages arising from previous surveys and related documentary analyses, such as how the 'principles of evidence-based medicine dominate current guideline programs' and the importance of collaborating with other organizations. The survey also provides a description of the history, structure, processes, outputs, and perceived strengths and weaknesses of existing organizations from which those establishing or leading similar organizations can draw