Building an international network for a primary care research program: reflections on challenges and solutions in the set-up and delivery of a prospective observational study of acute cough in 13 European countries

BACKGROUND: Implementing a primary care clinical research study in several countries can make it possible to recruit sufficient patients in a short period of time that allows important clinical questions to be answered. Large multi-country studies in primary care are unusual and are typically associated with challenges requiring innovative solutions. We conducted a multi-country study and through this paper, we share reflections on the challenges we faced and some of the solutions we developed with a special focus on the study set up, structure and development of Primary Care Networks (PCNs).METHOD: GRACE-01 was a multi-European country, investigator-driven prospective observational study implemented by 14 Primary Care Networks (PCNs) within 13 European Countries. General Practitioners (GPs) recruited consecutive patients with an acute cough. GPs completed a case report form (CRF) and the patient completed a daily symptom diary. After study completion, the coordinating team discussed the phases of the study and identified challenges and solutions that they considered might be interesting and helpful to researchers setting up a comparable study.RESULTS: The main challenges fell within three domains as follows:i) selecting, setting up and maintaining PCNs;ii) designing local context-appropriate data collection tools and efficient data management systems; andiii) gaining commitment and trust from all involved and maintaining enthusiasm.The main solutions for each domain were:i) appointing key individuals (National Network Facilitator and Coordinator) with clearly defined tasks, involving PCNs early in the development of study materials and procedures.ii) rigorous back translations of all study materials and the use of information systems to closely monitor each PCNs progress;iii) providing strong central leadership with high level commitment to the value of the study, frequent multi-method communication, establishing a coherent ethos, celebrating achievements, incorporating social events and prizes within meetings, and providing a framework for exploitation of local data.CONCLUSIONS: Many challenges associated with multi-country primary care research can be overcome by engendering strong, effective communication, commitment and involvement of all local researchers. The practical solutions identified and the lessons learned in implementing the GRACE-01 study may assist in establishing other international primary care clinical research platforms

Twitter mood predicts the stock market

Behavioral economics tells us that emotions can profoundly affect individual behavior and decision-making. Does this also apply to societies at large, i.e., can societies experience mood states that affect their collective decision making? By extension is the public mood correlated or even predictive of economic indicators? Here we investigate whether measurements of collective mood states derived from large-scale Twitter feeds are correlated to the value of the Dow Jones Industrial Average (DJIA) over time. We analyze the text content of daily Twitter feeds by two mood tracking tools, namely OpinionFinder that measures positive vs. negative mood and Google-Profile of Mood States (GPOMS) that measures mood in terms of 6 dimensions (Calm, Alert, Sure, Vital, Kind, and Happy). We cross-validate the resulting mood time series by comparing their ability to detect the public's response to the presidential election and Thanksgiving day in 2008. A Granger causality analysis and a Self-Organizing Fuzzy Neural Network are then used to investigate the hypothesis that public mood states, as measured by the OpinionFinder and GPOMS mood time series, are predictive of changes in DJIA closing values. Our results indicate that the accuracy of DJIA predictions can be significantly improved by the inclusion of specific public mood dimensions but not others. We find an accuracy of 87.6% in predicting the daily up and down changes in the closing values of the DJIA and a reduction of the Mean Average Percentage Error by more than 6%

Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

<div><p>Background</p><p>Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.</p><p>Methodology</p><p>497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.</p><p>Principal Findings</p><p>Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).</p><p>Significance</p><p>These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.</p></div

Multisensory effects on somatosensation: a trimodal visuo-vestibular-tactile interaction

Vestibular information about self-motion is combined with other sensory signals. Previous research described both visuo-vestibular and vestibular-tactile bilateral interactions, but the simultaneous interaction between all three sensory modalities has not been explored. Here we exploit a previously reported visuo-vestibular integration to investigate multisensory effects on tactile sensitivity in humans. Tactile sensitivity was measured during passive whole body rotations alone or in conjunction with optic flow, creating either purely vestibular or visuo-vestibular sensations of self-motion. Our results demonstrate that tactile sensitivity is modulated by perceived self-motion, as provided by a combined visuo-vestibular percept and not by the visual and vestibular cues independently. We propose a hierarchical multisensory interaction that underpins somatosensory modulation: visual and vestibular cues are first combined to produce a multisensory self-motion percept. Somatosensory processing is then enhanced according to the degree of perceived self-motion

Harnessing genomics to improve health in the Eastern Mediterranean Region – an executive course in genomics policy

BACKGROUND: While innovations in medicine, science and technology have resulted in improved health and quality of life for many people, the benefits of modern medicine continue to elude millions of people in many parts of the world. To assess the potential of genomics to address health needs in EMR, the World Health Organization's Eastern Mediterranean Regional Office and the University of Toronto Joint Centre for Bioethics jointly organized a Genomics and Public Health Policy Executive Course, held September 20(th)–23(rd), 2003, in Muscat, Oman. The 4-day course was sponsored by WHO-EMRO with additional support from the Canadian Program in Genomics and Global Health. The overall objective of the course was to collectively explore how to best harness genomics to improve health in the region. This article presents the course findings and recommendations for genomics policy in EMR. METHODS: The course brought together senior representatives from academia, biotechnology companies, regulatory bodies, media, voluntary, and legal organizations to engage in discussion. Topics covered included scientific advances in genomics, followed by innovations in business models, public sector perspectives, ethics, legal issues and national innovation systems. RESULTS: A set of recommendations, summarized below, was formulated for the Regional Office, the Member States and for individuals. • Advocacy for genomics and biotechnology for political leadership; • Networking between member states to share information, expertise, training, and regional cooperation in biotechnology; coordination of national surveys for assessment of health biotechnology innovation systems, science capacity, government policies, legislation and regulations, intellectual property policies, private sector activity; • Creation in each member country of an effective National Body on genomics, biotechnology and health to: - formulate national biotechnology strategies - raise biotechnology awareness - encourage teaching and training of biotechnology - devise integration of biotechnology within national health systems. CONCLUSION: The recommendations provide the basis for a road map for EMR to take steps to harness biotechnology for better and more equitable health. As a result of these recommendations, health ministers from the region, at the 50th Regional Committee Meeting held in October 2003, have urged Member States to establish national bodies of biotechnology to formulate a strategic vision for developing biotechnology in the service of the region's health. These efforts promise to raise the profile of genomics in EMR and increase regional cooperation in this exciting new field

Mutation Detection with Next-Generation Resequencing through a Mediator Genome

The affordability of next generation sequencing (NGS) is transforming the field of mutation analysis in bacteria. The genetic basis for phenotype alteration can be identified directly by sequencing the entire genome of the mutant and comparing it to the wild-type (WT) genome, thus identifying acquired mutations. A major limitation for this approach is the need for an a-priori sequenced reference genome for the WT organism, as the short reads of most current NGS approaches usually prohibit de-novo genome assembly. To overcome this limitation we propose a general framework that utilizes the genome of relative organisms as mediators for comparing WT and mutant bacteria. Under this framework, both mutant and WT genomes are sequenced with NGS, and the short sequencing reads are mapped to the mediator genome. Variations between the mutant and the mediator that recur in the WT are ignored, thus pinpointing the differences between the mutant and the WT. To validate this approach we sequenced the genome of Bdellovibrio bacteriovorus 109J, an obligatory bacterial predator, and its prey-independent mutant, and compared both to the mediator species Bdellovibrio bacteriovorus HD100. Although the mutant and the mediator sequences differed in more than 28,000 nucleotide positions, our approach enabled pinpointing the single causative mutation. Experimental validation in 53 additional mutants further established the implicated gene. Our approach extends the applicability of NGS-based mutant analyses beyond the domain of available reference genomes

Financing of U.S. Biomedical Research and New Drug Approvals across Therapeutic Areas

We estimated U.S. biomedical research funding across therapeutic areas, determined the association with disease burden, and evaluated new drug approvals that resulted from this investment.We calculated funding from 1995 to 2005 and totaled Food and Drug Administration approvals in eight therapeutic areas (cardiovascular, endocrine, gastrointestinal, genitourinary, HIV/AIDS, infectious disease excluding HIV, oncology, and respiratory) primarily using public data. We then calculated correlations between funding, published estimates of disease burden, and drug approvals. Financial support for biomedical research from 1995 to 2005 increased across all therapeutic areas between 43% and 369%. Industry was the principal funder of all areas except HIV/AIDS, infectious disease, and oncology, which were chiefly sponsored by the National Institutes of Health (NIH). Total (rho = 0.70; P = .03) and industry funding (rho = 0.69; P = .04) were correlated with projected disease burden in high income countries while NIH support (rho = 0.80; P = .01) was correlated with projected disease burden globally. From 1995 to 2005 the number of new approvals was flat or declined across therapeutic areas, and over an 8-year lag period, neither total nor industry funding was correlated with future approvals.Across therapeutic areas, biomedical research funding increased substantially, appears aligned with disease burden in high income countries, but is not linked to new drug approvals. The translational gap between funding and new therapies is affecting all of medicine, and remedies must include changes beyond additional financial investment

Testing for sexually transmitted infections and blood borne viruses on admission to Western Australian prisons

<p>Abstract</p> <p>Background</p> <p>Prison populations are known to be at high risk of sexually transmitted infections (STIs) and blood borne viruses (BBVs). In accordance with State health guidelines, the Western Australian Department of Correctional Services' policy is to offer testing for STIs and BBVs to all new prison entrants. This audit was undertaken to assess the completeness and timeliness of STI and BBV testing among recent prison entrants in Western Australia, and estimate the prevalence of STIs and BBVs on admission to prison.</p> <p>Methods</p> <p>A retrospective audit of prison medical records was conducted among 946 individuals admitted to prison in Western Australia after the 1^stJanuary 2005, and discharged between the 1^stJanuary and 31^stDecember 2007 inclusive. Quota sampling was used to ensure adequate sampling of females, juveniles, and individuals from regional prisons. Main outcomes of interest were the proportion of prisoners undergoing STI and BBV testing, and the prevalence of STIs and BBVs.</p> <p>Results</p> <p>Approximately half the sample underwent testing for the STIs chlamydia and gonorrhoea, and almost 40% underwent testing for at least one BBV. Completeness of chlamydia and gonorrhoea testing was significantly higher among juveniles (84.1%) compared with adults (39.8%; p < 0.001), and Aboriginal prisoners (58.3%) compared with non-Aboriginal prisoners (40.4%; p < 0.001). Completeness of BBV testing was significantly higher among adults (46.5%) compared with juveniles (15.8%; p < 0.001) and males (43.3%) compared with females (33.1%; p = 0.001). Among prisoners who underwent testing, 7.3% had a positive chlamydia test result and 24.8% had a positive hepatitis C test result.</p> <p>Conclusion</p> <p>The documented coverage of STI and BBV testing among prisoners in Western Australia is not comprehensive, and varies significantly by age, gender and Aboriginality. Given the high prevalence of STIs and BBVs among prisoners, increased test coverage is required to ensure optimal use of the opportunity that prison admission presents for the treatment and control of STIs and BBVs among this high risk group.</p

Investing in the future: lessons learnt from communicating the results of HSV/ HIV intervention trials in South Africa

<p>Abstract</p> <p>Background</p> <p>Communicating the results of randomised controlled trials may present challenges for researchers who have to work with communities and policy-makers to anticipate positive outcomes, while being aware that results may show no effect or harm.</p> <p>Methods</p> <p>We present a case study from the perspective of researchers in South Africa about the lessons learnt from communicating the results of four trials evaluating treatment for herpes simplex virus type 2 (HSV-2) as a new strategy for HIV prevention.</p> <p>Results</p> <p>We show that contextual factors such as misunderstandings and mistrust played an important role in defining the communications response. Use of different approaches in combination was found to be most effective in building understanding, credibility and trust in the research process. During the communication process, researchers acted beyond their traditional role of neutral observers and became agents of social change. This change in role is in keeping with a global trend towards increased communication of research results and presents both opportunities and challenges for the conduct of future research.</p> <p>Conclusions</p> <p>Despite disappointing trial results which showed no benefit of HSV-2 treatment for HIV prevention, important lessons were learnt about the value of the communication process in building trust between researchers, community members and policy-makers, and creating an enabling environment for future research partnerships.</p

Neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives

There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations.We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence.13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n=15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n=221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n=21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n=13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n=66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n=43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n=64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n=42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n=49 326, 19 studies). Heterogeneity for most clinical manifestations was high.Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic's early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers