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Author(s): Darren M. Lipnicki 1,*, Steve R. Makkar 1, John D. Crawford 1, Anbupalam Thalamuthu 1, Nicole A. Kochan 1, Maria Fernanda Lima-Costa 2, Erico Castro-Costa 2, Cleusa Pinheiro Ferri [...], Background With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. Methods and findings We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E [epsilon]4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. Conclusions These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

Background: Cerebral small vessel disease (SVD) and Alzheimer's disease pathology, namely amyloid-β (Aβ) deposition, commonly co-occur. Exactly how they interact remains uncertain.Objective: Using participants from the Alzheimer's Disease Neuroimaging Initiative (n = 216; mean age 73.29±7.08 years, 91 (42.1%) females), we examined whether the presence of vascular risk factors and/or baseline cerebral SVD was related to a greater burden of Aβ cross-sectionally, and at 24 months follow-up.Method: Amyloid burden, assessed using 18F-florbetapir PET, was quantified as the global standardized uptake value ratio (SUVR). Multimodal imaging was used to strengthen the quantification of baseline SVD as a composite variable, which included white matter hyperintensity volume using MRI, and peak width of skeletonized mean diffusivity using diffusion tensor imaging. Structural equation modeling was used to analyze the associations between demographic factors, Apolipoprotein E ɛ4 carrier status, vascular risk factors, SVD burden and cerebral amyloid.Results: SVD burden had a direct association with Aβ burden cross-sectionally (coeff. = 0.229, p = 0.004), and an indirect effect over time (indirect coeff. = 0.235, p = 0.004). Of the vascular risk factors, a history of hypertension (coeff. = 0.094, p = 0.032) and a lower fasting glucose at baseline (coeff. = -0.027, p = 0.014) had a direct effect on Aβ burden at 24 months, but only the direct effect of glucose persisted after regularization.Conclusion: While Aβ and SVD burden have an association cross-sectionally, SVD does not appear to directly influence the accumulation of Aβ longitudinally. Glucose regulation may be an important modifiable risk factor for Aβ accrual over time. [ABSTRACT FROM AUTHOR]

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity. [ABSTRACT FROM AUTHOR]

Background: Besides physical activity as a target for dementia prevention, sedentary behaviour is hypothesized to be a potential target in its own right. The rising number of persons with dementia and lack of any effective treatment highlight the urgency to better understand these modifiable risk factors. Therefore, we aimed to investigate whether higher levels of sedentary behaviour are associated with reduced global cognitive functioning and slower cognitive decline in older persons without dementia. Methods: We used five population cohorts from Greece, Australia, USA, Japan, and Singapore (HELIAD, PATH, SALSA, SGS, and SLAS2) from the Cohort Studies of Memory in an International Consortium. In a coordinated analysis, we assessed the relationship between sedentary behaviour and global cognitive function with the use of linear mixed growth model analysis (mean follow-up range of 2.0–8.1 years). Results: Baseline datasets combined 10,450 older adults without dementia with a mean age range between cohorts of 66.7–75.1 years. After adjusting for multiple covariates, no cross-sectional association between sedentary behaviour and cognition was found in four studies. One association was detected where more sedentary behaviour was cross-sectionally linked to higher cognition levels (SLAS2, B = 0.118 (0.075; 0.160), P < 0.001). Longitudinally, there were no associations between baseline sedentary behaviour and cognitive decline (P > 0.05). Conclusions: Overall, these results do not suggest an association between total sedentary time and lower global cognition in older persons without dementia at baseline or over time. We hypothesize that specific types of sedentary behaviour may differentially influence cognition which should be investigated further. For now, it is, however, too early to establish undifferentiated sedentary time as a potential effective target for minimizing cognitive decline in older adults without dementia. [ABSTRACT FROM AUTHOR]

Background: There is widespread consumer concern that statin use may be associated with impaired memory and cognitive decline.Objectives: This study sought to examine the association between statin use and changes in memory and global cognition in the elderly population over 6 years and brain volumes over 2 years. Interactions between statin use and known dementia risk factors were examined.Methods: Prospective observational study of community-dwelling elderly Australians age 70 to 90 years (the MAS [Sydney Memory and Ageing Study], n = 1,037). Outcome measures were memory and global cognition (by neuropsychological testing every 2 years) and total brain, hippocampal and parahippocampal volumes (by magnetic resonance) in a subgroup (n = 526). Analyses applied linear mixed modeling, including the covariates of age, sex, education, body mass index, heart disease, diabetes, hypertension, stroke, smoking, and apolipoprotein Eε4 carriage. Interactions were sought between statin use and dementia risk factors.Results: Over 6 years there was no difference in the rate of decline in memory or global cognition between statin users and never users. Statin initiation during the observation period was associated with blunting the rate of memory decline. Exploratory analyses found statin use was associated with attenuated decline in specific memory test performance in participants with heart disease and apolipoprotein Eε4 carriage. There was no difference in brain volume changes between statin users and never users.Conclusions: In community-dwelling elderly Australians, statin therapy was not associated with any greater decline in memory or cognition over 6 years. These data are reassuring for consumers concerned about statin use and risk of memory decline. [ABSTRACT FROM AUTHOR]

Background: Hypertension is an established risk factor for stroke and vascular dementia but recent meta-analyses examining the association between Alzheimer's disease (AD) and hypertension have found no significant association. These meta-analyses included short term studies starting in late life which may have obscured the real effect of midlife hypertension.Objective: To examine the association of AD with midlife hypertension, by including only studies with a sufficiently long follow up duration.Methods: Relevant studies were found by searches of MEDLINE, EMBASE, and PubMed. Study outcomes were grouped by measures of blood pressure and definition of hypertension (e.g., systolic hypertension > 140 mmHg or > 160 mmHg). We assessed pooled effect estimates using random effects models and heterogeneity of pooled estimates through the I2 statistic.Results: Literature search found 3,426 publications of which 7 were eligible studies. There was a significant association between systolic hypertension (>160 mm Hg) and AD (HR 1.25, 95CI 1.06 - 1.47, p = 0.0065). Similarly, for systolic hypertension > 140 mm Hg, there was a smaller but still significant association (HR 1.18, 95CI 1.02 - 1.35, p = 0.021). For diastolic hypertension, all four studies found no significant associations between diastolic hypertension and AD, and these data could not be pooled due to heterogeneity in reporting.Conclusions: Our study found that midlife stage 1 and stage 2 systolic hypertension is associated with increased risk of AD by 18 and 25%, respectively, although no association was found for diastolic hypertension. It is likely that assertive control of systolic hypertension starting in midlife is important to preventing AD. [ABSTRACT FROM AUTHOR]

There are calls for policymakers to make greater use of research when formulating policies. Therefore, it is important that policy organisations have a range of tools and systems to support their staff in using research in their work. The aim of the present study was to measure the extent to which a range of tools and systems to support research use were available within six Australian agencies with a role in health policy, and examine whether this was related to the extent of engagement with, and use of research in policymaking by their staff. The presence of relevant systems and tools was assessed via a structured interview called ORACLe which is conducted with a senior executive from the agency. To measure research use, four policymakers from each agency undertook a structured interview called SAGE, which assesses and scores the extent to which policymakers engaged with (i.e., searched for, appraised, and generated) research, and used research in the development of a specific policy document. The results showed that all agencies had at least a moderate range of tools and systems in place, in particular policy development processes; resources to access and use research (such as journals, databases, libraries, and access to research experts); processes to generate new research; and mechanisms to establish relationships with researchers. Agencies were less likely, however, to provide research training for staff and leaders, or to have evidence-based processes for evaluating existing policies. For the majority of agencies, the availability of tools and systems was related to the extent to which policymakers engaged with, and used research when developing policy documents. However, some agencies did not display this relationship, suggesting that other factors, namely the organisation’s culture towards research use, must also be considered. [ABSTRACT FROM AUTHOR]

Background: Few measures of research use in health policymaking are available, and the reliability of such measures has yet to be evaluated. A new measure called the Staff Assessment of Engagement with Evidence (SAGE) incorporates an interview that explores policymakers' research use within discrete policy documents and a scoring tool that quantifies the extent of policymakers' research use based on the interview transcript and analysis of the policy document itself. We aimed to conduct a preliminary investigation of the usability, sensitivity, and reliability of the scoring tool in measuring research use by policymakers.Methods: Nine experts in health policy research and two independent coders were recruited. Each expert used the scoring tool to rate a random selection of 20 interview transcripts, and each independent coder rated 60 transcripts. The distribution of scores among experts was examined, and then, interrater reliability was tested within and between the experts and independent coders. Average- and single-measure reliability coefficients were computed for each SAGE subscales.Results: Experts' scores ranged from the limited to extensive scoring bracket for all subscales. Experts as a group also exhibited at least a fair level of interrater agreement across all subscales. Single-measure reliability was at least fair except for three subscales: Relevance Appraisal, Conceptual Use, and Instrumental Use. Average- and single-measure reliability among independent coders was good to excellent for all subscales. Finally, reliability between experts and independent coders was fair to excellent for all subscales.Conclusions: Among experts, the scoring tool was comprehensible, usable, and sensitive to discriminate between documents with varying degrees of research use. Secondly, the scoring tool yielded scores with good reliability among the independent coders. There was greater variability among experts, although as a group, the tool was fairly reliable. The alignment between experts' and independent coders' ratings indicates that the independent coders were scoring in a manner comparable to health policy research experts. If the present findings are replicated in a larger sample, end users (e.g. policy agency staff) could potentially be trained to use SAGE to reliably score research use within their agencies, which would provide a cost-effective and time-efficient approach to utilising this measure in practice. [ABSTRACT FROM AUTHOR]

Background: An intervention's success depends on how participants interact with it in local settings. Process evaluation examines these interactions, indicating why an intervention was or was not effective, and how it (and similar interventions) can be improved for better contextual fit. This is particularly important for innovative trials like Supporting Policy In health with Research: an Intervention Trial (SPIRIT), where causal mechanisms are poorly understood. SPIRIT was testing a multi-component intervention designed to increase the capacity of health policymakers to use research.Methods: Our mixed-methods process evaluation sought to explain variation in observed process effects across the six agencies that participated in SPIRIT. Data collection included observations of intervention workshops (n = 59), purposively sampled interviews (n = 76) and participant feedback forms (n = 553). Using a realist approach, data was coded for context-mechanism-process effect configurations (retroductive analysis) by two authors.Results: Intervention workshops were very well received. There was greater variation of views regarding other aspects of SPIRIT such as data collection, communication and the intervention's overall value. We identified nine inter-related mechanisms that were crucial for engaging participants in these policy settings: (1) Accepting the premise (agreeing with the study's assumptions); (2) Self-determination (participative choice); (3) The Value Proposition (seeing potential gain); (4) 'Getting good stuff' (identifying useful ideas, resources or connections); (5) Self-efficacy (believing 'we can do this!'); (6) Respect (feeling that SPIRIT understands and values one's work); (7) Confidence (believing in the study's integrity and validity); (8) Persuasive leadership (authentic and compelling advocacy from leaders); and (9) Strategic insider facilitation (local translation and mediation). These findings were used to develop tentative explanatory propositions and to revise the programme theory.Conclusion: This paper describes how SPIRIT functioned in six policy agencies, including why strategies that worked well in one site were less effective in others. Findings indicate a complex interaction between participants' perception of the intervention, shifting contextual factors, and the form that the intervention took in each site. Our propositions provide transferable lessons about contextualised areas of strength and weakness that may be useful in the development and implementation of similar studies. [ABSTRACT FROM AUTHOR]

Background: There is a need to develop innovations that can help bridge the gap between research and policy. Web CIPHER is an online tool designed to help policymakers better engage with research in order to increase its use in health policymaking. The aim of the present study was to test interventions in order to increase policymakers' usage of Web CIPHER. Namely, the impact of posting articles and blogs on topics relevant to the missions and scope of selected policy agencies in the Web CIPHER community. Methods: Five policy agencies were targeted for the intervention. Web CIPHER usage data was gathered over a 30-month period using Google Analytics. Time series analysis was used to evaluate whether publication of tailored articles and blogs led to significant changes in usage for all Web CIPHER members from policy agencies, including those from the five target agencies. We further evaluated whether these users showed greater increases in usage following publication of articles and blogs directly targeted at their agency, and if these effects were moderated by the blog author. Results: Web CIPHER usage gradually increased over time and was significantly predicted by the number of articles but not blogs that were posted throughout the study period. Publication of articles on sexual and reproductive health was followed by sustained increases in usage among all users, including users from the policy agency that targets this area. This effect of topic relevance did not occur for the four remaining target agencies. Finally, page views were higher for articles targeted at one's agency compared to other agencies. This effect also occurred for blogs, particularly when the author was internal to one's agency. Conclusion: The findings suggest that Web CIPHER usage in general was motivated by general interest, engagement and appeal, as opposed to the agency specificity of content and work relevance. Blogs in and of themselves may not be effective at promoting usage. Thus, in order to increase policymakers' engagement with research through similar online platforms, a potentially effective approach would be to post abundant, frequently updated, engaging, interesting and widely appealing content irrespective of form. [ABSTRACT FROM AUTHOR]

It is essential that health policies are based on the best available evidence including that from research, to ensure their effectiveness in terms of both cost and health outcomes for the wider community. The present study describes the development of SAGE (Staff Assessment of enGagement with Evidence), a measure that combines an interview and document analysis to evaluate how policymakers engaged with research (i.e., how research was searched for, appraised, or generated, and whether interactions with researchers occurred), how policymakers used research (i.e., conceptually, instrumentally, tactically, or imposed), and what barriers impacted upon the use of research, in the development of a specific policy product. A multifaceted strategy was used to develop the SAGE interview and the accompanying interview-scoring tool. These included consultations with experts in health policy and research, review and analysis of the literature on evidence-informed policymaking and previous measures of research use, qualitative analysis of interviews with policymakers, and pilot-testing with senior policymakers. These steps led to the development of a comprehensive interview and scoring tool that captures and evaluates a broad range of key actions policymakers perform when searching for, appraising, generating, and using research to inform a specific policy product. Policy organizations can use SAGE to not only provide a thorough evaluation of their current level of research engagement and use, but to help shed light on programs to improve their research use capacity, and evaluate the success of these programs in improving the development of evidence-informed policies. [ABSTRACT FROM AUTHOR]

Background: Evidence-informed policymaking is more likely if organisations have cultures that promote research use and invest in resources that facilitate staff engagement with research. Measures of organisations' research use culture and capacity are needed to assess current capacity, identify opportunities for improvement, and examine the impact of capacity-building interventions. The aim of the current study was to develop a comprehensive system to measure and score organisations' capacity to engage with and use research in policymaking, which we entitled ORACLe (Organisational Research Access, Culture, and Leadership).Method: We used a multifaceted approach to develop ORACLe. Firstly, we reviewed the available literature to identify key domains of organisational tools and systems that may facilitate research use by staff. We interviewed senior health policymakers to verify the relevance and applicability of these domains. This information was used to generate an interview schedule that focused on seven key domains of organisational capacity. The interview was pilot-tested within four Australian policy agencies. A discrete choice experiment (DCE) was then undertaken using an expert sample to establish the relative importance of these domains. This data was used to produce a scoring system for ORACLe.Results: The ORACLe interview was developed, comprised of 23 questions addressing seven domains of organisational capacity and tools that support research use, including (1) documented processes for policymaking; (2) leadership training; (3) staff training; (4) research resources (e.g. database access); and systems to (5) generate new research, (6) undertake evaluations, and (7) strengthen relationships with researchers. From the DCE data, a conditional logit model was estimated to calculate total scores that took into account the relative importance of the seven domains. The model indicated that our expert sample placed the greatest importance on domains (2), (3) and (4).Conclusion: We utilised qualitative and quantitative methods to develop a system to assess and score organisations' capacity to engage with and apply research to policy. Our measure assesses a broad range of capacity domains and identifies the relative importance of these capacities. ORACLe data can be used by organisations keen to increase their use of evidence to identify areas for further development. [ABSTRACT FROM AUTHOR]

Background: The importance of utilising the best available research evidence in the development of health policies, services, and programs is increasingly recognised, yet few standardised systems for quantifying policymakers' research use are available. We developed a comprehensive measurement and scoring tool that assesses four domains of research use (i.e. instrumental, conceptual, tactical, and imposed). The scoring tool breaks down each domain into its key subactions like a checklist. Our aim was to develop a tool that assigned appropriate scores to each subaction based on its relative importance to undertaking evidence-informed health policymaking. In order to establish the relative importance of each research use subaction and generate this scoring system, we conducted conjoint analysis with a sample of knowledge translation experts. Methods: Fifty-four experts were recruited to undertake four choice surveys. Respondents were shown combinations of research use subactions called profiles, and rated on a 1 to 9 scale whether each profile represented a limited (1–3), moderate (4–6), or extensive (7–9) example of research use. Generalised Estimating Equations were used to analyse respondents' choice data, which calculated a utility coefficient for each subaction. A large utility coefficient indicated that a subaction was particularly influential in guiding experts' ratings of extensive research use. Results: Utility coefficients were calculated for each subaction, which became the points assigned to the subactions in the scoring system. The following subactions yielded the largest utilities and were regarded as the most important components of each research use domain: using research to directly influence the core of the policy decision; using research to inform alternative perspectives to deal with the policy issue; using research to persuade targeted stakeholders to support a predetermined decision; and using research because it was a mandated requirement by the policymaker's organisation. Conclusions: We have generated an empirically derived and context-sensitive means of measuring and scoring the extent to which policymakers used research to inform the development of a policy document. The scoring system can be used by organisations to not only quantify the extent of their research use, but also to provide them with insights into potential strategies to improve subsequent research use. [ABSTRACT FROM AUTHOR]

Objective: The aim of this review was to explore what is known about the effectiveness of strategies to increase the use of research in mental health policies. Methods: PsycINFO, MEDLINE, PubMed and EMBASE were searched for peer-reviewed journal articles by using the terms information dissemination OR knowledge OR diffusion of innovation OR knowledge transfer OR knowledge exchange OR evidence based OR evidence informed AND mental health policy OR decision makers. Searches were limited to articles pertaining to humans, written in English, and published from 1995 to 2013. Studies were excluded if they did not include a component related either to mental health policy or to mental health policy and decision makers or did not describe the development, implementation, or evaluation of an intervention that included a component aimed at increasing use of evidence. Reference lists were scanned to identify additional papers. Results: The search returned 2,677 citations. Fifty additional papers were identified via reference lists of relevant articles. Nine separate intervention studies were identified that included a component aimed at increasing use of evidence in mental health policy. All employed at least three strategies to increase evidence use, mostly in regard to implementation of a particular evidence-based policy. Methodologies of the identified studies did not enable estimation of the effectiveness of individual strategies to increase evidence use. Conclusions: Little research has examined how to increase the use of evidence in mental health policy. Available research suggests a number of potentially effective strategies for increasing the use of evidence that warrant further examination. [ABSTRACT FROM AUTHOR]

Background: Effective use of research to inform policymaking can be strengthened by policymakers undertaking various research engagement actions (e.g., accessing, appraising, and applying research). Consequently, we developed a thorough measurement and scoring tool to assess whether and how policymakers undertook research engagement actions in the development of a policy document. This scoring tool breaks down each research engagement action into its key 'subactions' like a checklist. The primary aim was to develop the scoring tool further so that it assigned appropriate scores to each subaction based on its effectiveness for achieving evidence-informed policymaking. To establish the relative effectiveness of these subactions, we conducted a conjoint analysis, which was used to elicit the opinions and preferences of knowledge translation experts. Method: Fifty-four knowledge translation experts were recruited to undertake six choice surveys. Respondents were exposed to combinations of research engagement subactions called 'profiles', and rated on a 1-9 scale whether each profile represented a limited (1-3), moderate (4-6), or extensive (7-9) example of each research engagement action. Generalised estimating equations were used to analyse respondents' choice data, where a utility coefficient was calculated for each subaction. A large utility coefficient indicates that a subaction was influential in guiding experts' ratings of extensive engagement with research. Results: The calculated utilities were used as the points assigned to the subactions in the scoring system. The following subactions yielded the largest utilities and were regarded as the most important components of engaging with research: searching academic literature databases, obtaining systematic reviews and peer-reviewed research, appraising relevance by verifying its applicability to the policy context, appraising quality by evaluating the validity of the method and conclusions, engaging in thorough collaborations with researchers, and undertaking formal research projects to inform the policy in question. Conclusions: We have generated an empirically-derived and context-sensitive method of measuring and scoring the extent to which policymakers engaged with research to inform policy development. The scoring system can be used by organisations to quantify staff research engagement actions and thus provide them with insights into what types of training, systems, and tools might improve their staff's research use capacity. [ABSTRACT FROM AUTHOR]

Background: There is a need to develop innovations that help policymakers better engage with research in order to increase its use in policymaking. As part of the Centre for Informing Policy in Health with Evidence from Research (CIPHER), we established Web CIPHER, an online tool with dynamic interactive elements such as hot topics, research summaries, blogs from trusted figures in health policy and research, a community bulletin board, multimedia section and research portal. The aim of this study was to examine policymakers' use of the website, and determine which sections were key drivers of use. Methods: Google Analytics (GA) was used to gather usage data during a 16-month period. Analysis was restricted to Web CIPHER members from policy agencies. We examined descriptive statistics including mean viewing times, number of page visits and bounce rates for each section and performed analyses of variance to compare usage between sections. Repeated measures analyses were undertaken to examine whether a weekly reminder email improved usage of Web CIPHER, particularly for research-related content. Results: During the measurement period, 223 policymakers from more than 32 organisations joined Web CIPHER. Users viewed eight posts on average per visit and stayed on the site for approximately 4 min. The bounce rate was less than 6%. The Blogs and Community sections received more unique views than all other sections. Blogs relating to improving policymakers' skills in applying research to policy were particularly popular. The email reminder had a positive effect on improving usage, particularly for research-related posts. Conclusions: The data indicated a relatively small number of users. However, this sample may not be representative of policymakers since membership to the site and usage was completely voluntarily. Nonetheless, those who used the site appeared to engage well with it. The findings suggest that providing blog-type content written by trusted experts in health policy and research as well as regular email reminders may provide an effective means of disseminating the latest research to policymakers through an online web portal. [ABSTRACT FROM AUTHOR]

Background:Socially anxious individuals are theorized to avoid social cues and engage in safety behaviors to prevent negative evaluation, which prevents disconfirmation of social fears. Cognitive models propose that this avoidance is driven by (1) self-focused attention (SFA) and (2) physiological arousal.Design:To examine these proposed mechanisms, we compared high socially anxious (HSA;n=29) and low socially anxious (LSA;n= 28) participants on a view-time task involving faces.Method:Participants engaged in a task in which they viewed socially threatening (i.e., disgust, anger) and nonthreatening (i.e., happy, neutral) faces.Results:Results revealed that HSA participants endorsed greater SFA during the view-time task and spent less time viewing angry, disgusted, and neutral facial expressions relative to LSA participants. Regression analyses revealed that arousal, as indexed by salivary α-amylase, was a unique predictor of increased face-viewing time among HSA participants. In contrast, arousal predicted decreased face-viewing time among LSA participants.Conclusions:Findings underscore the need for further investigation of avoidance mechanisms in social anxiety. [ABSTRACT FROM PUBLISHER]

The current review systematically documents the role of γ-amino-butyric acid (GABA) in different aspects of fear memory—acquisition and consolidation, reconsolidation, and extinction, and attempts to resolve apparent contradictions in the data in order to identify the function of GABAA receptors in fear memory. First, numerous studies have shown that pre- and post-training administration of drugs that facilitate GABAergic transmission disrupt the initial formation of fear memories, indicating a role for GABAA receptors, possibly within the amygdala and hippocampus, in the acquisition and consolidation of fear memories. Similarly, recent evidence indicates that these drugs are also detrimental to the restorage of fear memories after their reactivation. This suggests a role for GABAA receptors in the reconsolidation of fear memories, although the precise neural circuits are yet to be identified. Finally, research regarding the role of GABA in extinction has shown that GABAergic transmission is also disruptive to the formation of newly acquired extinction memories. We argue that contradictions to these patterns are the result of variations in (a) the location of drug infusion, (b) the dosage of the drug and/or (c) the time point of drug administration. The question of whether these GABA-induced memory deficits reflect deficits in retrieval is discussed. Overall, the evidence implies that the processes mediating memory stability consequent to initial fear learning, memory reactivation, and extinction training are dependent on a common mechanism of reduced GABAergic neurotransmission. [ABSTRACT FROM AUTHOR]

A correction to the article "Behavioral and Neural Analysis of GABA in the Acquisition, Consolidation, Reconsolidation, and Extinction of Fear Memory," published in a previous issue of the journal is presented.

Importance: COVID-19 has placed a monumental burden on the health care system globally. Although no longer a public health emergency, there is still a pressing need for effective treatments to prevent hospitalization and death. Paxlovid (nirmatrelvir/ritonavir) is a promising and potentially effective antiviral that has received emergency use authorization by the U.S. FDA., Objective: Determine real world effectiveness of Paxlovid nationwide and investigate disparities between treated and untreated eligible patients., Design/setting/participants: Population-based cohort study emulating a target trial, using inverse probability weighted models to balance treated and untreated groups on baseline confounders. Participants were patients with a SARS-CoV-2 positive test or diagnosis (index) date between December 2021 and February 2023 selected from the National COVID Cohort Collaborative (N3C) database who were eligible for Paxlovid treatment. Namely, adults with at least one risk factor for severe COVID-19 illness, no contraindicated medical conditions, not using one or more strictly contraindicated medications, and not hospitalized within three days of index. From this cohort we identified patients who were treated with Paxlovid within 5 days of positive test or diagnosis (n = 98,060) and patients who either did not receive Paxlovid or were treated outside the 5-day window (n = 913,079 never treated; n = 1,771 treated after 5 days)., Exposures: Treatment with Paxlovid within 5 days of positive COVID-19 test or diagnosis., Main Outcomes and Measures: Hospitalization and death in the 28 days following COVID-19 index date., Results: A total of 1,012,910 COVID-19 positive patients at risk for severe COVID-19 were included, 9.7% of whom were treated with Paxlovid. Uptake varied widely by geographic region and timing, with top adoption areas near 50% and bottom near 0%. Adoption increased rapidly after EUA, reaching steady state by 6/2022. Participants who were treated with Paxlovid had a 26% (RR, 0.742; 95% CI, 0.689-0.812) reduction in hospitalization risk and 73% (RR, 0.269, 95% CI, 0.179-0.370) reduction in mortality risk in the 28 days following COVID-19 index date., Conclusions/relevance: Paxlovid is effective in preventing hospitalization and death in at-risk COVID-19 patients. These results were robust to a large number of sensitivity considerations., Disclosure: The authors report no disclosures., Key Points: Question: Is treatment with Paxlovid (nirmatrelvir/ritonavir) associated with a reduction in 28-day hospitalization and mortality in patients at risk for severe COVID-19? Findings: In this multi-institute retrospective cohort study of 1,012,910 patients, Paxlovid treatment within 5 days after COVID-19 diagnosis reduced 28-day hospitalization and mortality by 26% and 73% respectively, compared to no treatment with Paxlovid within 5 days. Paxlovid uptake was low overall (9.7%) and highly variable. Meaning: In Paxlovid-eligible patients, treatment was associated with decreased risk of hospitalization and death. Results align with prior randomized trials and observational studies, thus supporting the real-world effectiveness of Paxlovid.

Introduction: There are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100., Methods: Participant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed., Results: The mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI)., Discussion: Among the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)