The Neural Correlates of the Clock-Drawing Test in Healthy Aging

Importance: The clock-drawing test (CDT) is an important neurocognitive assessment tool, widely used as a screening test for dementia. Behavioral performance on the test has been studied extensively, but there is scant literature on the underlying neural correlates.Purpose: To administer the CDT naturalistically to a healthy older aging population in an MRI environment, and characterize the brain activity associated with test completion.Main Outcome and Measure: Blood-oxygen-level dependent (BOLD) functional MRI was conducted as participants completed the CDT using novel tablet technology. Brain activity during CDT performance was contrasted to rest periods of visual fixation. Performance on the CDT was evaluated using a standardized scoring system (Rouleau score) and time to test completion. To assess convergent validity, performance during fMRI was compared to performance on a standard paper version of the task, administered in a psychometric testing room.Results: Study findings are reported for 33 cognitively healthy older participants aged 52–85. Activation was observed in the bilateral frontal, occipital and parietal lobes as well as the supplementary motor area and precentral gyri. Increased age was significantly correlated with Rouleau scores on the clock number drawing (R2) component (rho = -0.55, p < 0.001); the clock hand drawing (R3) component (rho = -0.50, p < 0.005); and the total clock (rho = -0.62, p < 0.001). Increased age was also associated with decreased activity in the bilateral parietal and occipital lobes as well as the right temporal lobe and right motor areas.Conclusion and Relevance: This imaging study characterizes the brain activity underlying performance of the CDT in a healthy older aging population using the most naturalistic version of the task to date. The results suggest that the functions of the occipital and parietal lobe are significantly altered by the normal aging process, which may lead to performance decrements

Call volume, triage outcomes and protocols during the first wave of the COVID-19 pandemic in the UK : results of a national survey

Objectives During the first wave of the COVID-19 pandemic in the United Kingdom (UK), to describe volume and pattern of calls to emergency ambulance services, proportion of calls where an ambulance was dispatched, proportion conveyed to hospital, and features of triage used. Methods Semistructured electronic survey of all UK ambulance services (n = 13) and a request for routine service data on weekly call volumes for 22 weeks (February 1–July 3, 2020). Questionnaires and data request were emailed to chief executives and research leads followed by email and telephone reminders. The routine data were analyzed using descriptive statistics, and questionnaire data using thematic analysis. Results Completed questionnaires were received from 12 services. Call volume varied widely between services, with a UK peak at week 7 at 13.1% above baseline (service range -0.5% to +31.4%). All services ended the study period with a lower call volume than at baseline (service range -3.7% to -25.5%). Suspected COVID-19 calls across the UK totaled 604,146 (13.5% of all calls), with wide variation between services (service range 3.7% to 25.7%), and in service peaks of 11.4% to 44.5%. Ambulances were dispatched to 478,638 (79.2%) of these calls (service range 59.0% to 100.0%), with 262,547 (43.5%) resulting in conveyance to hospital (service range 32.0% to 53.9%). Triage models varied between services and over time. Two primary call triage systems were in use across the UK. There were a large number of products and arrangements used for secondary triage, with services using paramedics, nurses, and doctors to support decision making in the call center and on scene. Frequent changes to triage processes took place. Conclusions Call volumes were highly variable. Case mix and workload changed significantly as COVID-19 calls displaced other calls. Triage models and prehospital outcomes varied between services. We urgently need to understand safety and effectiveness of triage models to inform care during further waves and pandemics

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Dataset for: Tobacco Industry Messaging around Harm: Narrative Framing in PMI and BAT Press Releases and Annual Reports 2011 to 2021

This dataset includes Annual Reports and Press releases from British American Tobacco and Philip Morris International published between 2011 and 2021 containing one or more of the keywords: harm, risk, HTP, heat, e-cig/e-cigarette, vap and any of their variants. The data was qualitatively coded using an existing codebook, which is also included in the dataset. The dataset relates to corporate communications around harm and risk, and was collected in order to understand how particular narrative frames might interfere with public health policy relating to tobacco.PMI and BAT were selected based on their market value - largest and second largest transnational tobacco companies worldwide in 2021. All annual reports were saved. Press releases were filtered for inclusion based on the use of any of researcher-identified key words relating to harm reduction, these were risk, htp, harm, heat, e-cig/e-cigarette and vap. Press releases and annual reports covering the relevant date range (2011–2020) containing any of the pre-identified keywords were downloaded directly from company webpages. Boydstun et al.’s Policy Frames Codebook was used as a framework to code paragraphs that contained any of the target keywords. Relevant text was coded in paragraphs and undertaken by four coders. All relevant text was double coded.Duplicated press releases were deleted prior to the start of analysisNVivo AntCon

Understanding the long-term policy influence strategies of the tobacco industry:two contemporary case studies

Objective: This paper explores transnational tobacco companies’ (TTCs) long-term policy influence strategies using two case studies, harm reduction and illicit tobacco, to identify lessons for the tobacco control movement and wider efforts to address the commercial determinants of health.Methods: Evidence from a broad combination of sources including leaked documents and findings from over two decades of TTC monitoring were reviewed for each case study and categorised using the Policy Dystopia Model, focusing on the primary discursive strategy and key instrumental (action-based) strategies used.Results: In both case studies, TTCs seek to advance their interests by engaging primarily in reputation management, coalition management and information management strategies over the long-term to propagate their over-riding discursive strategy—‘we’ve changed, we are part of the solution’—despite clear evidence from both case studies that this is not the case. These strategies are globally coordinated and attempt primarily to reshape norms towards TTC involvement in tobacco control policy and delivery. Findings also suggest that industry denormalisation and the advent of Article 5.3 have led to the TTCs growing use of increasingly complex and opaque ‘webs of influence’.Conclusions: The tobacco control community must develop its own proactive long-term strategies which should include industry denormalisation, new ways to fund research that reduce industry control, and improved transparency measures for research and policy. These findings, including TTC adaptations to Article 5.3, also indicate the need for more structural solutions, addressing corporate power and the underlying political and economic system. These lessons can be applied to other unhealthy commodity industries

A Case–Control Study Investigating Simulated Driving Errors in Ischemic Stroke and Subarachnoid Hemorrhage

BackgroundStroke can affect a variety of cognitive, perceptual, and motor abilities that are important for safe driving. Results of studies assessing post-stroke driving ability are quite variable in the areas and degree of driving impairment among patients. This highlights the need to consider clinical characteristics, including stroke subtype, when assessing driving performance.MethodsWe compared the simulated driving performance of 30 chronic stroke patients (>3 months), including 15 patients with ischemic stroke (IS) and 15 patients with subarachnoid hemorrhage (SAH), and 20 age-matched controls. A preliminary analysis was performed, subdividing IS patients into right (n = 8) and left (n = 6) hemispheric lesions and SAH patients into middle cerebral artery (MCA, n = 5) and anterior communicating artery (n = 6) territory. A secondary analysis was conducted to investigate the cognitive correlates of driving.ResultsNine patients (30%) exhibited impaired simulated driving performance, including four patients with IS (26.7%) and five patients with SAH (33.3%). Both patients with IS (2.3 vs. 0.3, U = 76, p < 0.05) and SAH (1.5 vs. 0.3, U = 45, p < 0.001) exhibited difficulty with lane maintenance (% distance out of lane) compared to controls. In addition, patients with IS exhibited difficulty with speed maintenance (% distance over speed limit; 8.9 vs. 4.1, U = 81, p < 0.05), whereas SAH patients exhibited difficulty with turning performance (total turning errors; 5.4 vs. 1.6, U = 39.5, p < 0.001). The Trail Making Test (TMT) and Useful Field of View test were significantly associated with lane maintenance among patients with IS (rs > 0.6, p < 0.05). No cognitive tests showed utility among patients with SAH.ConclusionBoth IS and SAH exhibited difficulty with lane maintenance. Patients with IS additionally exhibited difficulty with speed maintenance, whereas SAH patients exhibited difficulty with turning performance. Current results support the importance of differentiating between stroke subtypes and considering other important clinical characteristics (e.g., side of lesion, vascular territory) when assessing driving performance and reinforce the importance of physicians discussing driving safety with patients after stroke

Affective Speech Elicited With a Computer Game.

To determine the degree to which emotional changes in speech reflect factors other than arousal, such as valence, the authors used a computer game to induce natural emotional speech. Voice samples were elicited following game events that were either conducive or obstructive to the goal of winning and were accompanied by either pleasant or unpleasant sounds. Acoustic analysis of the speech recordings of 30 adolescents revealed that mean energy, fundamental-frequency level, utterance duration, and the proportion of an utterance that was voiced varied with goal conduciveness; spectral energy distribution depended on manipulations of pleasantness; and pitch dynamics depended on the interaction of pleasantness and goal conduciveness. The results suggest that a single arousal dimension does not adequately characterize a number of emotion-related vocal changes, lending weight to multidimensional theories of emotional response patterning

Advocacy counterstrategies to tobacco industry interference in policymaking: a scoping review of peer-reviewed literature

Abstract Background There has been remarkable tobacco control progress in many places around the globe. Tobacco industry interference (TII) has been identified as the most significant barrier to further implementation of the World Health Organization Framework Convention on Tobacco Control (WHO FCTC). Civil society has been recognised as a key actor in countering TII. While TII has been extensively studied for several decades now, there is little research that focuses on counteractions to limit it and their effectiveness to do so. This scoping review seeks to map the peer-reviewed literature on civil society’s activities of countering TII in policymaking to identify common counterstrategies and assess their effectiveness. Methods Data sources: We searched Embase, IBSS, JSTOR, PubMed, Science Direct, Scopus and Web of Science using the following terms: (“Tobacco industry” OR “Tobacco compan*”) AND. (“corporate political activity” OR “CPA” OR “lobbying” OR “interference”) AND (“advoca*” OR “counter*” OR “activi*”), without time or language restrictions. Study selection: Our selection criteria included peer-reviewed studies that were written in English, German, or Spanish that drew on primary data and/or legal and policy documents and reported at least one specific example of civil society members or organisations countering tobacco industry action-based strategies. Data extraction: Advocates’ counterstrategies were analysed inductively and countered industry strategies were analysed using the Policy Dystopia Model (PDM). Perceptions of effectiveness of countering attempts were analysed descriptively. Results We found five common counterstrategies among 30 included papers covering five WHO regions; 1. Exposing industry conduct and false claims; 2. Accessing decision-makers; 3. Generating and using evidence; 4. Filing a complaint or taking legal action; 5. Mobilising coalition and potential supporters. These counterstrategies were used to work against a wide range of industry strategies, which are captured by five action-based strategies described in the PDM (Coalition Management, Information Management, Direct Access and Influence, Litigation, Reputation Management). While some studies reported the outcome of the countering activities, their impact remained largely underexplored. Conclusion The review shows that peer-reviewed literature documenting how civil society actors counter TII is scarce. It suggests that advocates employ a range of strategies to counter TII in its different forms and use them flexibly. More work is needed to better understand the effects of their actions. This could stimulate discussions about, and facilitate learning from, past experiences and help to further enhance advocates’ capacity