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Before his incoherent response to the COVID-19 pandemic, the focus of President Trump's health policy agenda was the elimination of the Patient Protection and Affordable Care Act (ACA), which he has called a ‘disaster’. The attacks on the ACA included proposals to repeal the law through the legislative process, to erode it through a series of executive actions, and to ask the courts to declare it unconstitutional. Despite these ongoing challenges, the ACA remains largely intact as the U.S. heads into the 2020 election. The longer term fate of the law, however, is uncertain and the outcome of the 2020 election is likely to have a dramatic effect on the direction of health policy in the U.S.
Background: Measles is a highly contagious virus that reemerged in 2019 with the highest number of reported cases in the United States since 1992. Beginning in March 2019, The Johns Hopkins Hospital (JHH) responded to an influx of patients with concern for measles as a result of outbreaks in Maryland and the surrounding states. We report the JHH Department of Infection Control and Hospital Epidemiology (HEIC) response to this measles outbreak using a multidisciplinary measles incident command system (ICS). Methods: The JHH HEIC and the Johns Hopkins Office of Emergency Management established the HEIC Clinical Incident Command Center and coordinated a multipronged response to the measles outbreak with partners from occupational health services, microbiology, the adult and pediatric emergency departments, marketing and communication and local and state public health departments. The multidisciplinary structure rapidly developed, approved, and disseminated tools to improve the ability of frontline providers to quickly identify, isolate, and determine testing needs for patients suspected to have measles infection and reduce the risk of secondary transmission. The tools included a triage algorithm, visitor signage, staff and patient vaccination guidance and clinics, and standard operating procedures for measles evaluation and testing. The triage algorithms were developed for phone or in-person and assessed measles exposure history, immune status, and symptoms, and provided guidance regarding isolation and the need for testing. The algorithms were distributed to frontline providers in clinics and emergency rooms across the Johns Hopkins Health System. The incident command team also distributed resources to community providers to reduce patient influx to JHH and staged an outdoor measles evaluation and testing site in the event of a case influx that would exceed emergency department resources. Results: From March 2019 through June 2019, 37 patients presented with symptoms or concern for measles. Using the ICS tools and algorithms, JHH rapidly identified, isolated, and tested 11 patients with high suspicion for measles, 4 of whom were confirmed positive. Of the other 26 patients not tested, none developed measles infection. Exposures were minimized, and there were no secondary measles transmissions among patients. Conclusions: Using the ICS and development of tools and resources to prevent measles transmission, including a patient triage algorithm, the JHH team successfully identified, isolated, and evaluated patients with high suspicion for measles while minimizing exposures and secondary transmission. These strategies may be useful to other institutions and locales in the event of an emerging or reemerging infectious disease outbreak.
Disclosures: Aaron Milstone reports consulting for Becton Dickinson.
Terrestrial laser scanning (TLS) provides a means of rapid and highly accurate survey of archaeological excavations and structures at landscape scales, and is particularly valuable for documenting tidal environments. Here, the authors use TLS to record tidal fixed fishing structures and a tide mill within the Léguer Estuary at Le Yaudet, in north-west France. As part of a comprehensive resource-exploitation system, the early medieval (sixth to eighth centuries AD) structures lie within, and exploit different parts of, the tidal frame. The results are used to quantify production within an estuarine landscape associated with seignorial or monastic control of environmental resources.
The principal aim of this study was to optimize the diagnosis of canine neuroangiostrongyliasis (NA). In total, 92 cases were seen between 2010 and 2020. Dogs were aged from 7 weeks to 14 years (median 5 months), with 73/90 (81%) less than 6 months and 1.7 times as many males as females. The disease became more common over the study period. Most cases (86%) were seen between March and July. Cerebrospinal fluid (CSF) was obtained from the cisterna magna in 77 dogs, the lumbar cistern in f5, and both sites in 3. Nucleated cell counts for 84 specimens ranged from 1 to 146 150 cells μL−1 (median 4500). Percentage eosinophils varied from 0 to 98% (median 83%). When both cisternal and lumbar CSF were collected, inflammation was more severe caudally. Seventy-three CSF specimens were subjected to enzyme-linked immunosorbent assay (ELISA) testing for antibodies against A. cantonensis; 61 (84%) tested positive, titres ranging from <100 to ⩾12 800 (median 1600). Sixty-one CSF specimens were subjected to real-time quantitative polymerase chain reaction (qPCR) testing using a new protocol targeting a bioinformatically-informed repetitive genetic target; 53/61 samples (87%) tested positive, CT values ranging from 23.4 to 39.5 (median 30.0). For 57 dogs, it was possible to compare CSF ELISA serology and qPCR. ELISA and qPCR were both positive in 40 dogs, in 5 dogs the ELISA was positive while the qPCR was negative, in 9 dogs the qPCR was positive but the ELISA was negative, while in 3 dogs both the ELISA and qPCR were negative. NA is an emerging infectious disease of dogs in Sydney, Australia.
Presently, evidence guiding clinicians on the optimal approach to safely screen patients for coronavirus disease 2019 (COVID-19) to a nonemergent hospital procedure is scarce. In this report, we describe our experience in screening for SARS-CoV-2 prior to semiurgent and urgent hospital procedures.
Retrospective case series.
A single tertiary-care medical center.
Our study cohort included patients ≥18 years of age who had semiurgent or urgent hospital procedures or surgeries.
Overall, 625 patients were screened for SARS-CoV-2 using a combination of phone questionnaire (7 days prior to the anticipated procedure), RT-PCR and chest computed tomography (CT) between March 1, 2020, and April 30, 2020.
Of the 625 patients, 520 scans (83.2%) were interpreted as normal; 1 (0.16%) had typical features of COVID-19; 18 scans (2.88%) had indeterminate features of COVID-19; and 86 (13.76%) had atypical features of COVID-19. In total, 640 RT-PCRs were performed, with 1 positive result (0.15%) in a patient with a CT scan that yielded an atypical finding. Of the 18 patients with chest CTs categorized as indeterminate, 5 underwent repeat negative RT-PCR nasopharyngeal swab 1 week after their initial swab. Also, 1 patient with a chest CT categorized as typical had a follow-up repeat negative RT-PCR, indicating that the chest CT was likely a false positive. After surgery, none of the patients developed signs or symptoms suspicious of COVID-19 that would indicate the need for a repeated RT-PCR or CT scan.
In our experience, chest CT scanning did not prove provide valuable information in detecting asymptomatic cases of SARS-CoV-2 (COVID-19) in our low-prevalence population.
The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
Improved plasticity models require simultaneous experimental local strain and microstructural evolution data. Microscopy tools, such as electron backscatter diffraction (EBSD), that can monitor transformation at the relevant length-scale, are often incompatible with digital image correlation (DIC) techniques required to determine local deformation. In this paper, the viability of forescatter detector (FSD) images as the basis for the DIC study is investigated. Standard FSD and an integrated EBSD/FSD approach (Pattern Region of Interest Analysis System: PRIAS™) are analyzed. Simultaneous strain and microstructure maps are obtained for tensile deformation of Q&P 1180 steel up to ~14% strain. Tests on an undeformed sample that is simply shifted indicate a standard deviation of error in strain of around 0.4% without additional complications from a deformed surface. The method resolves strain bands at ~2 μm spacing but does not provide significant sub-grain strain resolution. Similar resolution was obtained for mechanically polished and electropolished samples, despite electropolished surfaces presenting a smoother, simpler topography. While the resolution of the PRIAS approach depends upon the EBSD step size, the 80 nm step size used provides seemingly similar resolution as 8,000× (22.7 nm) FSD images. Surface feature evolution prevents DIC analysis across large strain steps (>6% strain), but restarting DIC, using an FSD reference image from an interim strain step, allows reasonable DIC across the stress–strain curve. Furthermore, the data are obtained easily and provide complementary information for EBSD analysis.
ON 24 July 1304, before the gates of Stirling Castle, the last stronghold resisting the rule of Edward I over the kingdom of Scotland was surrendered. The submission of the garrison brought to a close more than seven years of warfare between the English king and his opponents in Scotland and completed Edward's second conquest of the land. In a royal document drawn up to record the capitulation of Stirling, the terms of surrender were prefaced by an account of the wider context. This recalled ‘the presumptuous rebellion which some of the prelates, earls, barons, knights, communities and inhabitants of the kingdom of Scotland … dared to raise against the lord Edward … their lord and king’. Edward entered the kingdom for the correction of their great offences and ‘by brandishing the royal power and extending the royal arm with a strong hand … he led them to a wiser spirit’. The Scottish lords and people acknowledged Edward as their liege lord and, returning to his obedience, will and lordship, sought his pardon and the restoration of their lands.
Edward I's Scottish wars provide one of the defining elements of the king's reign. They confirm both the positive and negative views of the king. Edward is revealed as able and tenacious, a warrior king at the head of his realm, and as harsh and intransigent in his pursuit of dubious rights by force. His apparent victory over his Scottish opponents in both 1304 and in 1296 drew fulsome praise from English contemporaries. However, the king's ultimate failure to secure his authority over the northern kingdom created a poisoned legacy for his successors. Unlike Wales, where he received the name ‘conqueror’, the successes won by Edward in 1296 and 1304 did not produce lasting conquests. Instead armed opposition to the English king's sovereignty was renewed in 1297 and 1306, forcing Edward into fresh conflicts. If Edward twice demonstrated that he possessed the ability and resources to force the surrender of Scotland through warfare, this was clearly not enough. Conquest, in its fullest sense, was a political not a military act. War was the tool but the key was recognition of the obedience owed to the conqueror.
The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
Delirious mania is a life-threatening condition, presenting with symptoms of acute delirium and psychotic mania as a complication of medical or psychiatric condition. It is not recognized as a diagnosis in DSM-V and is under recognized in clinical practice. It was first described by Calmeil (Calmeil, 1832). In 1849 Luther Bell described 40 cases with an associated 75% mortality rate. More recently, Jacobowski et al (2013) compiled a comprehensive review of clinical characteristics, diagnostic work up, and treatment recommendations for delirious mania. In addition to acute onset, clinical course is frequently worsened by psychosis and catatonia. Delirium leads to disequilibrium of neurotransmitters, particularly depletion of acetylcholine and elevation of dopamine.
Lithium has been used for the treatment of mania for many decades. Suppes et al performed a meta-analysis of 14 studies including 257 patients with Bipolar I disorder and concluded that patients relapsed 28 times more when stopping lithium compared to those who continued this medication. Baldessarini et al (1999) completed analysis of 227 patients with Bipolar I and II disorders, dividing the sample into “abrupt” (1-14 days) and “gradual” (15-30 days) discontinuation groups and concluded that the frequency of relapse following “abrupt” cessation was four times higher compared to following “gradual” cessation. In a study of 450 bipolar patients, Baldessarini et al (2003) reviewed the long-term treatment of lithium as monotherapy (86 % of the study’s population) in the context of lithium maintenance population morbidity. Greater pretreatment morbidity lead to larger relative reduction in morbidity as a result of treatment with lithium. A subgroup of bipolar patients with “abrupt” discontinuation became refractory when re-challenged with lithium.
Describing three clinical cases of delirious mania following conclusions can be derived:
• Patients with bipolar disorder and comorbid chronic kidney injury currently or formerly receiving long-term therapy with lithium are at increased risk for delirious mania.
• Abrupt lithium discontinuation in patients with bipolar disorder and comorbid chronic medical conditions (especially chronic kidney disease) increases risk for mania refractory to conventional treatment with medications.
Children with CHD who undergo cardiopulmonary bypass are at an increased risk of acute kidney injury. This study evaluated the association of end-organ specific injury plasma biomarkers for brain: glial fibrillary acidic protein and heart: Galectin 3, soluble suppression of tumorgenicity 2, and N-terminal pro b-type natriuretic peptide with acute kidney injury in children undergoing cardiopulmonary bypass.
Materials and Methods:
We enrolled consecutive children undergoing cardiac surgery with cardiopulmonary bypass. Blood samples were collected pre-bypass in the operating room and in the immediate post-operative period. Acute kidney injury was defined as a rise of serum creatinine ≥50% from pre-operative baseline within 7 days after surgery.
Overall, 162 children (mean age 4.05 years, sd 5.28 years) were enrolled. Post-operative acute kidney injury developed in 55 (34%) children. Post-operative plasma glial fibrillary acidic protein levels were significantly higher in patients with acute kidney injury (median 0.154 (inter-quartile range 0.059–0.31) ng/ml) compared to those without acute kidney injury (median 0.056 (inter-quartile range 0.001–0.125) ng/ml) (p = 0.043). After adjustment for age, weight, and The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category, each natural log increase in post-operative glial fibrillary acidic protein was significantly associated with a higher risk for subsequent acute kidney injury (adjusted odds ratio glial fibrillary acidic protein 1.25; 95% confidence interval 1.01–1.59). Pre/post-operative levels of galectin 3, soluble suppression of tumorgenicity 2, and N-terminal pro b-type natriuretic peptide did not significantly differ between patients with and without acute kidney injury.
Higher plasma glial fibrillary acidic protein levels measured in the immediate post-operative period were independently associated with subsequent acute kidney injury in children after cardiopulmonary bypass. Elevated glial fibrillary acidic protein likely reflects intraoperative brain injury which may occur in the context of acute kidney injury-associated end-organ dysfunction.
A primary barrier to translation of clinical research discoveries into care delivery and population health is the lack of sustainable infrastructure bringing researchers, policymakers, practitioners, and communities together to reduce silos in knowledge and action. As National Institutes of Healthʼs (NIH) mechanism to advance translational research, Clinical and Translational Science Award (CTSA) awardees are uniquely positioned to bridge this gap. Delivering on this promise requires sustained collaboration and alignment between research institutions and public health and healthcare programs and services. We describe the collaboration of seven CTSA hubs with city, county, and state healthcare and public health organizations striving to realize this vision together. Partnership representatives convened monthly to identify key components, common and unique themes, and barriers in academic–public collaborations. All partnerships aligned the activities of the CTSA programs with the needs of the city/county/state partners, by sharing resources, responding to real-time policy questions and training needs, promoting best practices, and advancing community-engaged research, and dissemination and implementation science to narrow the knowledge-to-practice gap. Barriers included competing priorities, differing timelines, bureaucratic hurdles, and unstable funding. Academic–public health/health system partnerships represent a unique and underutilized model with potential to enhance community and population health.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
There is demand for new, effective and scalable treatments for depression, and development of new forms of cognitive bias modification (CBM) of negative emotional processing biases has been suggested as possible interventions to meet this need.
We report two double blind RCTs, in which volunteers with high levels of depressive symptoms (Beck Depression Inventory ii (BDI-ii) > 14) completed a brief course of emotion recognition training (a novel form of CBM using faces) or sham training. In Study 1 (N = 36), participants completed a post-training emotion recognition task whilst undergoing functional magnetic resonance imaging to investigate neural correlates of CBM. In Study 2 (N = 190), measures of mood were assessed post-training, and at 2-week and 6-week follow-up.
In both studies, CBM resulted in an initial change in emotion recognition bias, which (in Study 2) persisted for 6 weeks after the end of training. In Study 1, CBM resulted in increases neural activation to happy faces, with this effect driven by an increase in neural activity in the medial prefrontal cortex and bilateral amygdala. In Study 2, CBM did not lead to a reduction in depressive symptoms on the BDI-ii, or on related measures of mood, motivation and persistence, or depressive interpretation bias at either 2 or 6-week follow-ups.
CBM of emotion recognition has effects on neural activity that are similar in some respects to those induced by Selective Serotonin Reuptake Inhibitors (SSRI) administration (Study 1), but we find no evidence that this had any later effect on self-reported mood in an analogue sample of non-clinical volunteers with low mood (Study 2).
Academic medical centers (AMCs) face challenges in conducting research among traditionally marginalized communities due to long-standing community mistrust. Evidence suggests that some AMC faculty and staff lack an understanding of the history of distrust and social determinants of health (SDH) affecting their communities. Wake Forest Clinical and Translational Science Institute Program in Community Engagement (PCE) aims to build bridges between communities and Wake Forest Baptist Health by equipping faculty, clinicians, administrators, and staff (FCAS) with a better understanding of SDH. The PCE collaborated with community partners to develop and implement community tours to improve cross-community AMC understanding and communication, enhance knowledge of SDH, and build awareness of community needs, priorities, and assets. Nine day-long tours have been conducted with 92 FCAS. Tours included routes through under-resourced neighborhoods and visits to community assets. Participant evaluations assessed program quality; 89% reported enhanced understanding of access-to-care barriers and how SDH affect health; 86% acknowledged the experience would improve future interactions with participants and patients; and 96% agreed they would recommend the tour to colleagues. This work supports the use of community tours as a strategy to improve cross-community AMC communication, build trust, and raise awareness of community needs, priorities, and assets.
Protein-energy malnutrition, or undernutrition, arising from a deficiency of energy and protein intake, can occur in developed countries both in hospitalised patients and in the primary care/community setting. Oral nutritional supplements (ONS) are an effective method of managing malnutrition if prescribed for patients who are malnourished or at risk of malnutrition. Pooled data of older adults at risk of malnutrition indicate that ONS combined with dietary counselling is the most effective intervention. Previous Irish research has demonstrated that management of patients ‘at risk’ of malnutrition in the primary care/community setting is sub-optimal, with low awareness of the condition and its management among non-dietetic health care professionals. Therefore, the aim of this qualitative study is to explore community nurses’ and dietitians’ experiences and opinions on the management of malnutrition and the prescription of ONS in the primary care/community setting in Ireland. Three focus groups were conducted with primary care dietitians (n = 17) and one focus group with community nurses (n = 5), one of the nurses had prescribing rights. The focus groups explored the following domains; the term malnutrition and patient population presenting as malnourished or at risk of malnutrition, barriers and facilitators in the management of malnutrition, ONS prescribing in the primary care/community setting, and future directions in the management of malnutrition and ONS prescribing. Recorded focus groups were transcribed and analysed using inductive thematic analysis. Both professional groups showed similar perspectives, and three preliminary main themes were identified; i) Malnutrition is a misunderstood term, ii) Delayed treatment of malnutrition, iii) Challenges with ONS prescription in the primary care/community setting. Both dietitians and community nurses agreed that the term malnutrition had negative connotations for patients and preferred not to use it with them. Dietitians identified the need for a multidisciplinary approach to manage patients at risk of malnutrition in the community, and community nurses agreed on their pivotal role identifying the risk of malnutrition and providing first line advice to clients. However, community nurses expressed the urgent need for training to provide first line advice to patients to improve their nutritional status to prevent malnutrition. Both groups also agreed on the need for access to more dietitians in the community, and suggested that giving dietitians prescribing rights would improve appropriate ONS prescribing. Community nurses identified a gap in their knowledge of the different ONS products, and the need to receive independent generic education on nutritional supplements.
Globally, over 1.97 billion adults and 338 million children and adolescents are living with overweight and obesity, increasing the risk of numerous co-morbidities, including at least 12 cancers(1). WCRF/AICR conducted a literature review of diet and physical activity as determinants of weight gain, overweight and obesity in adults and children. We also introduce a novel evidence-based policy framework for promoting physical activity, and linked database, currently in development as part of the EU-funded CO-CREATE project on child and adolescent obesity prevention.
Materials and Methods
Evidence on diet and physical activity as determinants and risk of weight gain, overweight and obesity was systematically extracted from existing reviews and a systematic search for recent meta-analyses, then collated and analysed. The WCRF Continuous Update Project Expert Panel drew conclusions about which exposures influence risk of weight gain, overweight and obesity, using pre-defined criteria that included evidence of biological plausibility.
The Panel identified strong evidence that several diet and physical activity related exposures influence the risk of weight gain, overweight and obesity in adults and children (see table 1). Separate conclusions were drawn for adults and children in relation to screen time, considered a marker of sedentary time.
However, the Panel noted that as exposures tend to cluster, physiologically interact and share common biological mechanisms, they should not be regarded as absolutely ‘singular'but an integrated concept of interrelated exposures within a pattern of lifestyle.
Screen time (adults)‘Fast foods’‘Western type’ diet
For full list of footnotes, see Energy Balance and Body Fatness report(1).
Healthy dietary patterns help prevent excess weight gain. Achieving such patterns requires attention to the broader economic, environmental and social factors that influence and constrain people's behaviour. The findings of this report support the need for evidence-based public health policy to help create health-enabling environments, particularly for children and adolescents. The WCRF International MOVING framework(2) presents a package of policies to promote physical activity, which alongside wider public health policy can help address the multiple drivers of overweight and obesity.
5-HT4 receptor stimulation has pro-cognitive and antidepressant-like effects in animal experimental studies; however, this pharmacological approach has not yet been tested in humans. Here we used the 5-HT4 receptor partial agonist prucalopride to assess the translatability of these effects and characterise, for the first time, the consequences of 5-HT4 receptor activation on human cognition and emotion.
Forty one healthy volunteers were randomised, double-blind, to a single dose of prucalopride (1 mg) or placebo in a parallel group design. They completed a battery of cognitive tests measuring learning and memory, emotional processing and reward sensitivity.
Prucalopride increased recall of words in a verbal learning task, increased the accuracy of recall and recognition of words in an incidental emotional memory task and increased the probability of choosing a symbol associated with a high likelihood of reward or absence of loss in a probabilistic instrumental learning task. Thus acute prucalopride produced pro-cognitive effects in healthy volunteers across three separate tasks.
These findings are a translation of the memory enhancing effects of 5-HT4 receptor agonism seen in animal studies, and lend weight to the idea that the 5-HT4 receptor could be an innovative target for the treatment of cognitive deficits associated with depression and other neuropsychiatric disorders. Contrary to the effects reported in animal models, prucalopride did not reveal an antidepressant profile in human measures of emotional processing.