Search

Objective: This systematic review and meta-analysis aimed to quantify the relationship between resilience resources at the individual (e.g., optimism), interpersonal (e.g., social support), and neighborhood (e.g., social environment) levels, and cardiovascular outcomes among adults in the United States. Method: On 9/25/2020, electronic databases (PubMed, Embase, CINAHL, PsycINFO) were systematically searched for randomized controlled trials, nonrandomized intervention studies, and prospective cohort studies that examined the relationship between resilience resources at the individual, interpersonal, or neighborhood level and cardiovascular outcomes. Studies that met the eligibility criteria were summarized narratively and quantitatively. Because relevant search results yielded only observational studies, risk of bias was assessed using an adapted version of the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. Results: From 4,103 unique records, 13 prospective cohort studies with a total of 310,906 participants met the eligibility criteria, and six of these studies were included in the meta-analyses. Most relevant studies found that higher levels of individual-level resilience resources were associated with lower incidence of adverse cardiovascular outcomes, with point estimates ranging from .46 to 1.18. Interpersonal-level resilience resources (i.e., social network) were associated with a lower coronary heart disease risk (risk ratio, .76; 95% CI [.56, 1.02]). Neighborhood-level resilience resources (i.e., perceived social cohesion and residential stability) were associated with a lower odds of stroke (odds ratio, .92; 95% CI [.84, 1.01]). Conclusions: Evidence suggests that higher levels of resilience resources are associated with better cardiovascular outcomes. However, more prospective studies with diverse populations are needed to strengthen the evidence. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objective Reports on the pharmacologic treatment of anxiety, including generalized anxiety disorder (GAD), in individuals with Down syndrome (DS) are lacking. Methods We present the case histories of 1 adolescent and 2 young adults with DS and the treatment course of comorbid GAD with buspirone. Results Treatment with buspirone was safe and well-tolerated and resulted in sustained improvement in symptoms of anxiety for a minimum of 2 years in all 3 cases. Conclusion Buspirone's generally benign adverse effect profile makes it well suited for treating anxiety in individuals with DS in light of their common medical comorbidities.

The energy transition has started. While traditional petroleum exploration and production will become increasingly difficult, the offshore region around the UK, Norway, Denmark and the Netherlands offers many opportunities for companies prepared to embrace low-carbon energy and related activities. We present 19 ideas for new sustainable business. If climate commitments are to be met, the scale of the transformation will be immense. Assuming the economics of floating technologies improve, we envisage the majority of the North Sea (>100,000km2) to be repurposed for renewable power and related activities. In order to fully unlock the future value in wind, solar and ocean energies, as well as in subsurface storage, companies and governments will need to work together to create an integrated energy system.

Overview In 2012, the Institute of Medicine Roundtable on Health Literacy established 10 attributes of a health literate health care organization that, if instated, would improve health information and empower patients to make more informed health decisions. Few studies have assessed how well organizations meet these attributes. Purpose This study sought to describe the extent to which health care systems in North Texas were adopting policies and practices that address the 10 attributes of a health literate health care organization. More specifically, we sought to describe key organizational leaders' and clinicians' perceptions in this regard. Study design and methods This was a mixed-methods study, conducted with a convenience sample of 74 key informants from 13 hospitals across five health care systems. Informants provided demographic data, and their perceptions of the extent to which their hospital met the 10 attributes were measured via the Health Literate Health Care Organization 10-item questionnaire (HLHO-10) and semistructured interviews. Results Mean scores for HLHO-10 items ranged from 3.74 to 5.39, with 7 as a maximum score. Qualitative data provided richer content, elaborating on the survey results. Workforce training in health literacy, patient inclusion in health information development and evaluation, and communication about health care costs were rated the lowest and were described as issues of concern. Conclusion Study findings indicated limited leadership and little systemic promotion of efforts to ensure health literate health care organizations, although individual health literacy champions sometimes stepped up with creative initiatives.

It has been hypothesised that nonsyndromic cleft lip/palate (nsCL/P) and cancer may share aetiological risk factors. Population studies have found inconsistent evidence for increased incidence of cancer in nsCL/P cases, but several genes (e.g., CDH1, AXIN2) have been implicated in the aetiologies of both phenotypes. We aimed to evaluate shared genetic aetiology between nsCL/P and oral cavity/oropharyngeal cancers (OC/OPC), which affect similar anatomical regions. Using a primary sample of 5,048 OC/OPC cases and 5,450 controls of European ancestry and a replication sample of 750 cases and 336,319 controls from UK Biobank, we estimate genetic overlap using nsCL/P polygenic risk scores (PRS) with Mendelian randomization analyses performed to evaluate potential causal mechanisms. In the primary sample, we found strong evidence for an association between a nsCL/P PRS and increased odds of OC/OPC (per standard deviation increase in score, odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.04, 1.13; p = .000053). Although confidence intervals overlapped with the primary estimate, we did not find confirmatory evidence of an association between the PRS and OC/OPC in UK Biobank (OR 1.02; 95% CI: 0.95, 1.10; p = .55). Mendelian randomization analyses provided evidence that major nsCL/P risk variants are unlikely to influence OC/OPC. Our findings suggest possible shared genetic influences on nsCL/P and OC/OPC.

Background Previous studies have found that children born with a non-syndromic orofacial cleft have lower-than-average educational attainment. Differences could be due to a genetic predisposition to low intelligence and academic performance, factors arising due to the cleft phenotype (such as social stigmatization, impaired speech/language development) or confounding by the prenatal environment. A clearer understanding of this mechanism will inform interventions to improve educational attainment in individuals born with a cleft, which could substantially improve their quality of life. We assessed evidence for the hypothesis that common variant genetic liability to non-syndromic cleft lip with or without cleft palate (nsCL/P) influences educational attainment. Methods We performed a genome-wide association study (GWAS) meta-analysis of nsCL/P with 1692 nsCL/P cases and 4259 parental and unrelated controls. Using GWAS summary statistics, we performed Linkage Disequilibrium (LD)-score regression to estimate the genetic correlation between nsCL/P, educational attainment (GWAS n = 766 345) and intelligence (GWAS n = 257 828). We used two-sample Mendelian randomization to evaluate the causal effects of genetic liability to nsCL/P on educational attainment and intelligence. Results There was limited evidence for shared genetic aetiology or causal relationships between nsCL/P and educational attainment [genetic correlation (rg) −0.05, 95% confidence interval (CI) −0.12 to 0.01, P 0.13; MR estimate (βMR) −0.002, 95% CI −0.009 to 0.006, P 0.679) or intelligence (rg −0.04, 95% CI −0.13 to 0.04, P 0.34; βMR −0.009, 95% CI −0.02 to 0.002, P 0.11). Conclusions Common variants are unlikely to predispose individuals born with nsCL/P to low educational attainment or intelligence. This is an important first step towards understanding the aetiology of low educational attainment in this group.

Sprint interval training (SIT) has demonstrated reductions in fat mass through potential alterations in postexercise metabolism. This study examined whether exercising in the fasted or fed state affects postexercise metabolism following acute SIT. Ten active males performed a bout of modified SIT (8 × 15-s sprints; 120 s recovery) in both a fasted (FAST) and fed (FED) state. Gas exchange was collected through 3 h postexercise, appetite perceptions were measured using a visual analog scale, and energy intake was recorded using dietary food logs. There was no difference in energy expenditure between conditions at any time point (p > 0.329) or in total session energy expenditure (FED: 514.8 ± 54.9 kcal, FAST: 504.0 ± 74.3 kcal; p = 0.982). Fat oxidation at 3 h after exercise was higher in FED (0.110 ± 0.04 g·min−1) versus FAST (0.069 ± 0.02 g·min−1; p = 0.013) though not different between conditions across time (p > 0.340) or in total postexercise fat oxidation (FED: 0.125 ± 0.04 g·min−1, FAST: 0.105 ± 0.02 g·min−1; p = 0.154). Appetite perceptions were lower in FED (–4815.0 ± 4098.7 mm) versus FAST (–707.5 ± 2010.4 mm, p = 0.022); however, energy intake did not differ between conditions (p = 0.429). These results demonstrate the fasted or fed state does not augment postexercise metabolism following acute SIT in a way that would favour fat loss following training. Novelty Energy expenditure was similar between conditions, while fat oxidation was significantly greater in FED at 3 h after exercise. Appetite perceptions were significantly lower in FED; however, energy intake was not different between conditions. Current findings suggest that performing SIT in the fed or fasted state would not affect fat loss following training.

BACKGROUND: Epidemiologic studies suggest cadmium exposure is associated with cardiovascular disease risk, including heart failure. However, prior findings may be influenced by tobacco smoking, a dominant source of cadmium exposure and risk factor for heart failure. The present study leverages up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to examine the relationship between urinary cadmium and incident heart failure among people who never smoked.METHODS: Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 men and 600 women and identified 958 incident heart failure cases occurring between baseline and 2015. Using a case-cohort approach, we estimated adjusted hazard ratios (aHR) for heart failure in Cox proportional hazards models with age as the time scale.RESULTS: Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median= 0.20; 25th, 75th= 0.13, 0.32 µg cadmium/g creatinine). In adjusted models, we found that higher urinary cadmium was associated with a higher rate of incident heart failure overall (aHR=1.1 per interquartile range difference; 95% CI= 1.0 - 1.2). In sex-stratified analyses the association seemed restricted to men (aHR= 1.5; 95% CI= 1.2 - 1.9).CONCLUSION: In this cohort of people who never smoked tobacco, environmental cadmium was positively associated with incident heart failure, especially among men.

Social epidemiology is concerned with how social forces influence population health. Rather than focusing on a single disease (as in cancer or cardiovascular epidemiology) or a single type of exposure (e.g., nutritional epidemiology), social epidemiology encompasses all the social and economic determinants of health, both historical and contemporary. These include features of social and physical environments, the network of relationships in a society, and the institutions, politics, policies, norms and cultures that shape all of these forces. This commentary presents the perspective of several editors at the Journal with expertise in social epidemiology. We articulate our thinking to encourage submissions to the Journal that: 1) expand knowledge of emerging and underresearched social determinants of population health; 2) advance new empirical evidence on the determinants of health inequities and solutions to advance health equity; 3) generate evidence to inform the translation of research on social determinants of health into public health impact; 4) contribute to innovation in methods to improve the rigor and relevance of social epidemiology; and 5) encourage critical self-reflection on the direction, challenges, successes, and failures of the field.

Synthetic biology research and its industrial applications rely on the deterministic spatiotemporal control of gene expression. Recently, electrochemical control of gene expression has been demonstrated in electrogenetic systems (redox-responsive promoters used alongside redox inducers and an electrode), allowing for the direct integration of electronics with complex biological processes for a variety of new applications. However, the use of electrogenetic systems is limited by poor activity, tunability and standardisation. Here, we have developed a variety of genetic and electrochemical tools that facilitate the design and vastly improve the performance of electrogenetic systems. We developed a strong, unidirectional, redox-responsive promoter before deriving a mutant promoter library with a spectrum of strengths. We then constructed genetic circuits with these parts and demonstrated their activation by multiple classes of redox molecules. Finally, we demonstrated electrochemical activation of gene expression in aerobic conditions utilising a novel, modular bioelectrochemical device. This toolset provides researchers with all the elements needed to design and build optimised electrogenetic systems for specific applications.

Following traumatic brain injury (TBI), raised cerebral lactate/pyruvate ratio (LPR) reflects impaired energy metabolism. Raised LPR correlates with poor outcome and mortality following TBI. We prospectively recruited patients with TBI requiring neurocritical care and multimodal monitoring, and utilised a tiered management protocol targeting LPR. We identified patients with persistent raised LPR despite adequate cerebral glucose and oxygen provision, which we clinically classified as cerebral ‘mitochondrial dysfunction’ (MD). In patients with TBI and MD, we administered disodium 2,3-13C2 succinate (12 mmol/L) by retrodialysis into the monitored region of the brain. We recovered 13C-labelled metabolites by microdialysis and utilised nuclear magnetic resonance spectroscopy (NMR) for identification and quantification. Of 33 patients with complete monitoring, 73% had MD at some point during monitoring. In 5 patients with multimodality-defined MD, succinate administration resulted in reduced LPR(−12%) and raised brain glucose(+17%). NMR of microdialysates demonstrated that the exogenous 13C-labelled succinate was metabolised intracellularly via the tricarboxylic acid cycle. By targeting LPR using a tiered clinical algorithm incorporating intracranial pressure, brain tissue oxygenation and microdialysis parameters, we identified MD in TBI patients requiring neurointensive care. In these, focal succinate administration improved energy metabolism, evidenced by reduction in LPR. Succinate merits further investigation for TBI therapy.

Taller people have lower risk of coronary heart disease but higher risk of many cancers. Mendelian randomization studies in unrelated individuals have suggested that these relationships are potentially causal. However, Mendelian randomization estimates from samples of unrelated individuals are sensitive to demography (population stratification, assortative mating) and familial (indirect genetic) effects. Height could influence disease risk via anatomic and physiological effects of height (e.g., number of cells or the bore of arteries) or previous results may have been confounded by early-life environmental factors (e.g., parental socioeconomic position and nutrition).In this study, we performed within-sibship Mendelian randomization analyses using 77,757 siblings, a design robust against demography and indirect genetic effects of parents. Within-sibship Mendelian randomization estimated that one SD taller height lowers odds of coronary heart disease by 14% (95% CI: 3% to 23%) but increases odds of cancer by 18% (95% CI: 3% to 34%). There was some evidence that taller height reduces systolic blood pressure and LDL cholesterol, which may mediate some of the protective effect of taller height on coronary heart disease risk.For the first time, we have demonstrated that purported effects of height on adulthood disease risk are unlikely to be explained by demographic or familial factors, and so likely reflect an individual-level causal effect. Disentangling the mechanisms via which height affects disease risk may improve understanding of the aetiologies of atherosclerosis and carcinogenesis.

The re-wiring of photosynthetic bio-machineries to electrodes is a forward-looking semi-artificial route for sustainable bio-electricity and fuel generation. Currently, it is unclear how the bio-material interface can be designed to meet the complex requirements for high bio-photoelectrochemical performance. Here, we developed an aerosol jet printing method for generating hierarchical electrode structures using indium tin oxide nanoparticles. We printed libraries of micropillar array electrodes varying in height and sub-micron surface features and studied the energy/electron transfer processes across the bio-electrode interfaces. When wired to the cyanobacterium Synechocysis sp. PCC 6803, micropillar array electrodes with micro-branches exhibited favourable biocatalyst loading, light utilisation and electron flux output, ultimately almost doubling the photocurrent of state-of-the-art porous structures of the same height. When the micropillars’ heights were increased from 50 to 600 µm, milestone mediated photocurrent densities of 245 µA cm–2 (the closest thus far to theoretical predictions) and external quantum efficiencies of up to 29% could be reached. This study demonstrates how bioenergy from photosynthesis could be more efficiently harnessed in the future and provide new tools for 3D electrode design.

Background Increasing evidence suggests that psychological well-being (PWB) is associated with lower disease and mortality risk, and may be enhanced with relatively low-cost interventions. Yet, dissemination of these interventions remains limited, in part because insufficient attention has been paid to distinct PWB dimensions, which may impact physical health outcomes differently. Methods This essay first reviews the empirical evidence regarding differential relationships between all-cause mortality and multiple dimensions of PWB (e.g., life purpose, mastery, positive affect, life satisfaction, optimism). Then, individual-level positive psychology interventions aimed at increasing PWB and tested in randomized-controlled trials are reviewed as these allow for easy implementation and potentially broad outreach to improve population well-being, in concert with efforts targeting other established social determinants of health. Results Several PWB dimensions relate to mortality, with varying strength of evidence. Many of positive psychology trials indicate small-to-moderate improvements in PWB; rigorous institution-level interventions are comparatively few, but preliminary results suggest benefits as well. Examples of existing health policies geared towards the improvement of population well-being are also presented. Future avenues of well-being epidemiological and intervention research, as well as policy implications, are discussed. Conclusions Although research in the fields of behavioral and psychosomatic medicine, as well as health psychology have substantially contributed to the science of PWB, this body of work has been somewhat overlooked by the public health community. Yet, the growing interest in documenting well-being, in addition to examining its determinants and consequences at a population level may provoke a shift in perspective. To cultivate optimal well-being—mental, physical, social, and spiritual—consideration of a broader set of well-being measures, rigorous studies, and interventions that can be disseminated is critically needed.

The Dietary Guidelines for Americans serve as a basis for developing federal nutrition education materials for the public, such as MyPlate. MyPlate is a visual cue that uses food groups as a guide to building healthy plates at mealtime. The objective of this study was to determine factors associated with child familiarity with MyPlate guidelines and to determine if typical meals met MyPlate guidelines using food models. A convenience sample of 250 children (aged 7-13 years) and their parent/guardian were recruited at a local science and history museum. Children viewed a picture of the MyPlate icon and were asked to identify the picture. Next, participants used a nine-inch plate to build a typical meal (meals that they would regularly consume) from a buffet of food and beverages models (>65 items to choose from). Research team members took photographs of the plates. A Registered Dietitian Nutritionist determined the percentage of plates that met MyPlate guidelines. Eighty-six percent of children recognized the MyPlate icon upon viewing the image; 7.6% could accurately identify the icon by name. When participants were asked to build a typical meal, however, only 3.43% met MyPlate guidelines. The results of this study suggest that despite being familiar with MyPlate, children built typical meals that did not meet MyPlate guidelines.

ObjectiveElectronic health records (EHRs) are a rich source of information on human diseases, but the information is variably structured, fragmented, curated using different coding systems, and collected for purposes other than medical research. We describe an approach for developing, validating, and sharing reproducible phenotypes from national structured EHR in the United Kingdom with applications for translational research.Materials and MethodsWe implemented a rule-based phenotyping framework, with up to 6 approaches of validation. We applied our framework to a sample of 15 million individuals in a national EHR data source (population-based primary care, all ages) linked to hospitalization and death records in England. Data comprised continuous measurements (for example, blood pressure; medication information; coded diagnoses, symptoms, procedures, and referrals), recorded using 5 controlled clinical terminologies: (1) read (primary care, subset of SNOMED-CT [Systematized Nomenclature of Medicine Clinical Terms]), (2) International Classification of Diseases–Ninth Revision and Tenth Revision (secondary care diagnoses and cause of mortality), (3) Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures, Fourth Revision (hospital surgical procedures), and (4) DM+D prescription codes.ResultsUsing the CALIBER phenotyping framework, we created algorithms for 51 diseases, syndromes, biomarkers, and lifestyle risk factors and provide up to 6 validation approaches. The EHR phenotypes are curated in the open-access CALIBER Portal (https://www.caliberresearch.org/portal) and have been used by 40 national and international research groups in 60 peer-reviewed publications.ConclusionsWe describe a UK EHR phenomics approach within the CALIBER EHR data platform with initial evidence of validity and use, as an important step toward international use of UK EHR data for health research.

Recent advances in synthetic biology research have been underpinned by an exponential increase in available genomic information and a proliferation of advanced DNA assembly tools. The adoption of plasmid vector assembly standards and parts libraries has greatly enhanced the reproducibility of research and exchange of parts between different labs and biological systems. However, a standardised Modular Cloning (MoClo) system is not yet available for cyanobacteria, which lag behind other prokaryotes in synthetic biology despite their huge potential in biotechnological applications. By building on the assembly library and syntax of the Plant Golden Gate MoClo kit, we have developed a versatile system called CyanoGate that unites cyanobacteria with plant and algal systems. Here we have generated a suite of parts and acceptor vectors for making i) marked/unmarked knock-outs or integrations using an integrative acceptor vector, and ii) transient multigene expression and repression systems using known and novel replicative vectors. We have tested and compared the CyanoGate system in the established model cyanobacterium Synechocystis sp. PCC 6803 and the more recently described fast-growing strain Synechococcus elongatus UTEX 2973. We observed that fast-growth phenotype in UTEX 2973 is only evident under specific growth conditions, but that UTEX 2973 can accumulate high levels of proteins with strong native or synthetic promoters. The system is publicly available and can be readily expanded to accommodate other standardised MoClo parts to accelerate the development of reliable synthetic biology tools for the cyanobacterial community.

Introduction: Myotonic dystrophy (DM) is a chronic, multisystemic, neurological condition. Patients and caregivers are uniquely suited to identify what symptoms are most important and highlight the unmet needs that are most relevant to DM. Methods: We conducted a North American, cross‐sectional study of people with DM type‐1, congenital DM, and DM type‐2 and their family members. We sent patients and caregivers separate surveys to identify and quantitate the issues of greatest importance, examine the differences between groups, and identify the most important challenges experienced by this population. Results: 1,180 people with DM and 402 family members/caregivers responded to the surveys. They reported considerable physical and cognitive symptoms, extensive diagnostic delays, and varying clinical phenotypes on the basis of DM type. Discussion: Marked disease burden and numerous unmet needs exist in DM. These needs vary based on DM type and highlight the complex clinical phenotypes of these neurological disorders. Muscle Nerve 59:457–464, 2019

Background: Low health literacy impacts individual health and the health care system. The Health Literacy Knowledge and Experience Survey (HLKES) was created to evaluate preparedness of nurses to provide health literate care. However, the instrument was developed a decade ago and needs revision. The purpose of this study was to update and shorten the HLKES into a feasible, valid, and reliable instrument. Method: The HLKES was refined into a 14-item instrument (10 knowledge questions and four experience questions). Expert review was obtained. Face validity was assessed, and pilot and field testing with students was conducted. Results: Scale content validity index was 0.95, and individual questions demonstrated appropriate item difficulty and discrimination. Cronbach's alpha coefficient was .565 for the 10 multiple choice questions and .843 for the four Likert-type questions, indicating good reliability. Conclusion: A reliable and valid HLKES-2 was developed to evaluate health literacy knowledge and experiences in a contemporary setting. [ J Nurs Educ . 2019;58(2):86–92.]

Non-pharmaceutical interventions (NPIs) remain the only widely available tool for controlling the ongoing SARS-CoV-2 pandemic. We estimated weekly values of the effective basic reproductive number (Reff) using a mechanistic metapopulation model and associated these with county-level characteristics and NPIs in the United States (US). Interventions that included school and leisure activities closure and nursing home visiting bans were all associated with a median Reff below 1 when combined with either stay at home orders (median Reff 0.97, 95% confidence interval (CI) 0.58–1.39) or face masks (median Reff 0.97, 95% CI 0.58–1.39). While direct causal effects of interventions remain unclear, our results suggest that relaxation of some NPIs will need to be counterbalanced by continuation and/or implementation of others., Disentangling the impacts of non-pharmaceutical interventions on COVID-19 transmission is challenging as they have been used in different combinations across time and space. This study shows that, early in the epidemic, school/daycare closures and stopping nursing home visits were associated with the biggest reduction in transmission in the United States.

Cadmium exposure has been associated with cardiovascular disease. Cigarette smoking is a key source of cadmium exposure and thus a potential confounder in observational studies of environmental cadmium and cardiovascular disease that include tobacco smokers. We leveraged up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to test the hypothesis that cadmium exposure is associated with acute myocardial infarction (AMI) among people who never smoked. Between 1993 and 1997, 19,394 never-smoking participants (ages 50–64 years) were enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 males and 600 females. We identified 809 AMI cases occurring between baseline and the end of 2015 using the Danish National Patient Registry. We quantified cadmium, creatinine, and osmolality in baseline urine samples. Using an unweighted case-cohort approach, we estimated adjusted hazard ratios (aHR) for AMI in Cox proportional hazards models with age as the time axis. Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 μg cadmium/g creatinine). We did not find strong evidence to support an association between higher urinary cadmium and AMI when comparing the highest versus lowest quartile (aHR = 1.16; 95% CI: 0.86 – 1.56) and per IQR increment in cadmium concentration (aHR = 1.02; 95% CI: 0.93 – 1.12). Results were not materially different across strata defined by sex. Results were generally similar using creatinine or osmolality to account for differences in urine dilution. While cadmium exposure has been identified as a risk factor for cardiovascular disease, we did not find strong evidence that urinary cadmium at relatively low-levels is associated with AMI among people who have never smoked.

Introduction: Designed in 1972 the Abbreviated Mental Test Score (AMTS) is widely used to assess a cognition on hospital admission. The Nottingham Hip Fracture Score uses this in predicting morbidity/mortality in neck of femur fracture. The consequences of misappropriating cognitive impairment could have lasting implications. Questions about the monarchy or World War One and Two may be inappropriate for today’s diverse society. Materials and Methods: 100 patients were questioned during routine fracture clinic appointments. Patients were asked: In what year did WWII start? Who is the current monarch? Please state a memorable event in your lifetime that you would not expect another person of the same age to forget. Two-tailed Z-tests were performed between the observed proportions and those from the original AMTS validation study. Results: Only 47% (n = 47) were able to correctly answer the year in which WW2 started. A statistically significant difference when compared to the upper and lower limits from the original study (z = -4.191, p < .001.). Significance was not seen in the second question, with 97% (n-97) identifying the monarch correctly. 51% (n = 51) of participants suggested the terrorist attack on the World Trade Centre in New York as an alternative memorable event. Discussion: Some hospitals now use the 4 “A”s Test (4-AT) as a screening tool for delirium. Without amendments to the Nottingham Hip Fracture Score, AMTS use is likely to continue in orthogeriatric patients. Over time there will be a need for the AMTS to be reviewed so that it remains a true assessment of cognition. Its limitations regarding language and culture is widely acknowledged and several validated variants have been published in the literaure. Conclusions: We highlight a potential future issue with the AMTS and raise considerations for the development of an alternative question to better meet the needs of the orthogeriatric population.

Aims While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation. Methods and results We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro. Conclusions A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.

Assays of urine biomarkers often use urine creatinine to account for urinary dilution, even though creatinine levels are influenced by underlying physiology and muscle catabolism. Urine osmolality—a measure of dissolved particles including ions, glucose, and urea—is thought to provide a more robust marker of urinary dilution but is seldom measured. The relationship between urine osmolality and creatinine is not well understood. We calculated correlation coefficients between urine creatinine and osmolality among 1375 members of a subcohort of the Danish Diet, Cancer, and Health Cohort, and within different subgroups. We used linear regression to relate creatinine with osmolality, and a lasso selection procedure to identify other variables that explain remaining variability in osmolality. Spearman correlation between urine creatinine and osmolality was strong overall (ρ = 0.90; 95% CI: 0.89–0.91) and in most subgroups. Linear regression showed that urine creatinine explained 60% of the variability in urine osmolality, with another 9% explained by urine thallium (Tl), cesium (Cs), and strontium (Sr). Urinary creatinine and osmolality are strongly correlated, although urine Tl, Cs, and Sr might help supplement urine creatinine for purposes of urine dilution adjustment when osmolality is not available.

Non-pharmaceutical interventions (NPIs) remain the only widely available tool for controlling the ongoing SARS-CoV-2 pandemic. We estimated weekly values of the effective basic reproductive number (Reff) using a mechanistic metapopulation model and associated these with county-level characteristics and NPIs in the United States (US). Interventions that included school and leisure activities closure and nursing home visiting bans were all associated with an Reff below 1 when combined with either stay at home orders (median Reff 0.97, 95% confidence interval (CI) 0.58-1.39)* or face masks (median Reff 0.97, 95% CI 0.58-1.39)*. While direct causal effects of interventions remain unclear, our results suggest that relaxation of some NPIs will need to be counterbalanced by continuation and/or implementation of others.

ObjectivesInforming research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.DesignIn the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.SettingUK stroke services.Participants3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.ResultsOf those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.ConclusionIt is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration numberISRCTN83290762; Post-results.

High-intensity exercise inhibits appetite, in part, via alterations in the peripheral concentrations of the appetite-regulating hormones acylated ghrelin, active glucagon-like peptide-1 (GLP-1), and active peptide tyrosine-tyrosine (PYY). Given lactate may mediate these effects, we used sodium bicarbonate (NaHCO(3)) supplementation in a double-blind, placebo-controlled, crossover design to investigate lactate’s purported role in exercise-induced appetite suppression. Eleven males completed two identical high-intensity interval training sessions (10 × 1 min cycling bouts at ~90% heart rate maximum interspersed with 1-min recovery), where they ingested either NaHCO(3) (BICARB) or sodium chloride (NaCl) as a placebo (PLACEBO) preexercise. Blood lactate, acylated ghrelin, GLP-1, and PYY concentrations, as well as overall appetite were assessed preexercise and 0, 30, 60, and 90 min postexercise. Blood lactate was greater immediately (P < 0.001) and 30 min postexercise (P = 0.049) in the BICARB session with an increased (P = 0.009) area under the curve (AUC). The BICARB session had lower acylated ghrelin at 60 (P = 0.014) and 90 min postexercise (P = 0.016), with a decreased AUC (P = 0.039). The BICARB session had increased PYY (P = 0.034) with an increased AUC (P = 0.031). The BICARB session also tended (P = 0.060) to have increased GLP-1 at 30 (P = 0.003) and 60 min postexercise (P < 0.001), with an increased AUC (P = 0.030). The BICARB session tended (P = 0.059) to reduce overall appetite, although there was no difference in AUC (P = 0.149). These findings support a potential role for lactate in the high-intensity exercise-induced appetite-suppression. NEW & NOTEWORTHY We used sodium bicarbonate to increase lactate accumulation or sodium chloride as a placebo. Our findings further implicate lactate as a mediator of exercise-induced appetite suppression, given exercise-induced increases in lactate during the sodium bicarbonate session altered peripheral concentrations of appetite-regulating hormones, culminating in a reduction of appetite. This supports a lactate-dependent mechanism of appetite suppression following high-intensity exercise and highlights the potential of using lactate as a means of inducing a caloric deficit.

Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. Results: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92–1.16]; I 2 =28%; P -heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity. Conclusions: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.

Receiving regular HIV care is crucial for maintaining good health among persons with HIV. However, racial and gender disparities in HIV care receipt exist. Discrimination and its impact may vary by race/ethnicity and gender, contributing to disparities. Data from 1578 women in the Women’s Interagency HIV Study ascertained from 10/1/2012 to 9/30/2016 were used to: (1) estimate the relationship between discrimination and missing any scheduled HIV care appointments and (2) assess whether this relationship is effect measure modified by race/ethnicity. Self-reported measures captured discrimination and the primary outcome of missing any HIV care appointments in the last 6 months. Log-binomial models accounting for measured sources of confounding and selection bias were fit. For the primary outcome analyses, women experiencing discrimination typically had a higher prevalence of missing an HIV care appointment. Moreover, there was no statistically significant evidence for effect measure modification by race/ethnicity. Interventions to minimize discrimination or its impact may improve HIV care engagement among women.

People living with Human Immunodeficiency Virus (PLWH) face numerous adversities at the individual, interpersonal, and neighborhood levels, which have been linked to negative health behaviors and outcomes. Therefore, there is a growing interest in studying resilience among PLWH to inform future research and intervention efforts. We use a socioecological model of health to define resilience, review the definition and study of resilience among PLWH in the existing peer-reviewed literature, and discuss the strengths and limitations of how resilience is defined and studied in HIV research. We conducted a review of resilience research among for HIV-related behaviors/outcomes of antiretroviral therapy (ART) adherence, clinic attendance, CD4 cell count, viral load, viral suppression, and/or immune functioning among PLWH. We performed searches using PubMed, PsycINFO and Google Scholar databases. The initial search generated 14,296 articles across the three databases, but based on our screening of these articles and inclusion criteria, n = 54 articles were included for review. The majority of HIV resilience research defines resilience only at the individual (i.e., psychological) level or studies individual and limited interpersonal resilience (e.g., social support). The exclusion of neighborhood resilience and more interpersonal factors contrasts with qualitative and quantitative evidence that describes these factors as resilience resources for PLWH. Furthermore, the preponderance of HIV resilience research uses general measures of psychological or interpersonal resilience; these measures have not been developed with or tailored to the needs of PLWH. Our review suggests that a socioecological model of health approach can more fully represent the construct of resilience. Furthermore, measures specific to PLWH that capture individual, interpersonal, and neighborhood resilience are needed. Future research should develop and test multilevel resilience measures for PLWH.

Retention in care and viral suppression are critical to delaying HIV progression and reducing transmission. Neighborhood socioeconomic context (NSEC) may affect HIV care receipt. We therefore assessed NSEC's impact on retention and viral suppression in a diverse HIV clinical cohort. HIV-positive adults with ≥1 visit at the Vanderbilt Comprehensive Care Clinic and 5-digit ZIP code tabulation area (ZCTA) information between 2008 and 2012 contributed. NSEC z-score indices used neighborhood-level socioeconomic indicators for poverty, education, labor-force participation, proportion of males, median age, and proportion of residents of black race by ZCTA. Retention was defined as ≥2 HIV care visits per calendar year,90 days apart. Viral suppression was defined as an HIV-1 RNA200 copies/mL at last measurement per calendar year. Modified Poisson regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI). Among 2272 and 2541 adults included for retention and viral suppression analyses, respectively, median age and CD4 count at enrollment were approximately 38 (1st and 3rd quartile: 30, 44) years and 351 (176, 540) cells/μL, respectively, while 24% were female, and 39% were black. Across 243 ZCTAs, median NSEC z-score was 0.09 (-0.66, 0.48). Overall, 79% of person-time contributed was retained and 74% was virally suppressed. In adjusted models, NSEC was not associated with retention, though being in the 4th vs. 1st NSEC quartile was associated with lack of viral suppression (RR = 0.88; 95% CI: 0.80-0.97). Residing in the most adverse NSEC was associated with lack of viral suppression. Future studies are needed to confirm this finding.

This study examined the validity and reliability of a 30-second running sprint test using two non-motorized treadmills compared to the established Wingate Anaerobic Test. Twenty-four participants completed three sessions in a randomized order on a: (1) manual mode treadmill (Woodway); (2) specialized interval training treadmill (HiTrainer); and (3) Wingate cycle ergometer. In a subset of 15 participants, 2 additional sessions were completed on both treadmills to establish the test–retest reliability. Peak (Woodway: r = .68; HiTrainer: r = .58; p .75). Fatigue index during the Wingate Anaerobic Test (51.20 ± 7.14%) was moderately correlated with the Woodway (32.9 ± 10.9%, r = .55, p ...

Introduction Stroke-associated pneumonia (SAP) is common, however, data on the economic impact of SAP are scarce. This study aimed to prospectively evaluate the impact of SAP on acute stroke care costs in a UK setting. Methods Prospective cohort study of 213 consecutive patients with stroke (196 ischemic, 17 hemorrhagic) was admitted to a UK hospital over 1 year. Socio demographic and clinical characteristics were recorded along with all treatments and rehabilitation activity. Patients were classified as having SAP if they fulfilled criteria for "probable" or "definite" respiratory tract infection according to the Centres for Disease Control and Prevention definition, within the first seven days following stroke. Resource use was calculated using a "bottom up" approach of cumulative unit costs. Univariate and multivariate regression analyses were used to establish independent predictors of direct costs. Results Probable or definite SAP occurred in 13.2% (28/213) of patients. Patients with SAP experienced greater inpatient stays (31 days vs. 9 days, p ≤ 0.001) and higher in-hospital mortality (29.2% vs. 10.2%, p = 0.007). Mean (SD) acute care costs per patient was £7035 (6767), but costs were significantly greater for patients with SAP than without [£14,371 (9484) versus £6,103 (5,735); p ≤ 0.001]. SAP was an independent predictor of costs along with increasing stroke severity (NIHSS) and age. Occurrence of SAP resulted in an adjusted incremental additional cost of £5817 (95% CI 4945-6689; p = 0.001) per patient. Conclusions SAP increased acute care costs for stroke by approximately 80%. This provides further impetus for research aimed at reducing SAP, and will inform cost-effectiveness analyses of potential therapeutic strategies.

Purpose Obesity prevention efforts may be ineffective if parents lack awareness of their children's overweight status. This study examined the factors that predicted parents' underestimation of child weight status. Design and Methods Using a cross sectional design, researchers recruited children and parents in a local children's museum. Parents completed a demographic questionnaire, the Newest Vital Sign, and the Child Body Image Scale. Children's height and weight were measured to calculate child BMI. Random effects modeling examined the association between predictor variables (parent race/ethnicity, income, education, and health literacy, and child BMI percentile, gender, and age) and the dependent variable, parent underestimation of child weight status. Results Participants included 160 parents (213 children aged 7–12 years) representing a racially and ethnically diverse sample who were affluent, educated, and with 36.6% of parents assessed with limited health literacy. Although 45.1% of children were overweight/obese, only 7.5% of parents chose this weight status; 80% of parents underestimated the weight of their normal weight children, 96% underestimated their overweight children, and 72% underestimated their obese children. Parents were more likely to underestimate weight of older children and those under 81st percentile of BMI. No other predictors were significant. Conclusions Parent underestimation of child weight status appears to be a widespread phenomenon in this sample, regardless of race, ethnicity, income, education, and health literacy. Practice Implications The consistent underestimation of child weight suggests that parents' misperception of weight status represents a critical pathway for intervention. Methods to improve parents' perception of child weight need be developed and tested.

Highlights • Smoking has been shown to affect body weight but evidence for the converse is limited. • Higher body mass index (BMI) was associated with smoking initiation in adolescent females but not males. • Body dissatisfaction was associated with smoking initiation in both sexes. • BMI genetic risk score did not predict smoking, but estimates were imprecise. • BMI and body dissatisfaction may be important considerations for smoking prevention., Background Smoking influences body weight, but there is little evidence as to whether body mass index (BMI) and body dissatisfaction increase smoking initiation in adolescents. Methods We evaluated the association between measured BMI, body dissatisfaction and latent classes of smoking initiation (never smokers, experimenters, late onset regular smokers, early onset regular smokers) in the Avon Longitudinal Study of Parents and Children. In observational analyses we used BMI (N = 3754) and body dissatisfaction at age 10.5 years (N = 3349). In Mendelian randomisation (MR) analysis, we used a BMI genetic risk score of 76 single nucleotide polymorphisms (N = 4017). Results In females, higher BMI was associated with increased odds of early onset regular smoking (OR: 1.11, 95% CI: 1.04, 1.18) compared to being a never smoker, but not clearly associated with experimenting with smoking (OR: 1.04, 95% CI: 0.99, 1.10) or late onset regular smoking (OR: 1.01, 95% CI: 0.94, 1.09). No clear evidence was found for associations between BMI and smoking initiation classes in males (p-value for sex interaction ≤ 0.001). Body dissatisfaction was associated with increased odds of late-onset regular smoking (OR: 1.71, 95% CI: 1.32, 1.99) in males and females combined (P-value for sex interaction = 0.32). There was no clear evidence for an association between the BMI genetic risk score and smoking latent classes in males or females but estimates were imprecise. Conclusions BMI in females and body dissatisfaction in males and females are associated with increased odds of smoking initiation, highlighting these as potentially important factors for consideration in smoking prevention strategies.

Fatty acids (FAs) are essential components of cell membranes and play an integral role in membrane fluidity. The lipophilic index [LI, defined as the sum of the products between FA levels and melting points (°C), divided by the total amount of FA: $${\text{LI}} = \frac{{\mathop \sum \nolimits_{k} [{\text{fatty acid}} \times {\text{melting point}}]}}{{\mathop \sum \nolimits_{k} {\text{fatty acid}} }}$$ ] is thought to reflect membrane and lipoprotein fluidity and may be associated with the risk of coronary heart disease (CHD). Therefore, we examined the associations of dietary and plasma phospholipid (PL) LI with CHD risk among postmenopausal women. We determined dietary LI for the cohort with completed baseline food frequency questionnaires and free of prevalent cardiovascular diseases in the Women’s Health Initiative (WHI) observational study (N = 85,563). We additionally determined plasma PL LI in a matched case-control study (N = 2428) nested within the WHI observational cohort study. Cox proportional hazard regression and multivariable conditional logistic regression were used to calculate HRs/ORs for CHD risk between quartiles of LI after adjusting for potential sources of confounding and selection bias. Higher dietary LI in the cohort study and plasma PL LI in the case-control study were significantly associated with increased risk of CHD: HR = 1.18 (95% CI 1.07–1.31, P for trend

Empirical evidence indicates that aspects of the neighborhood environment may affect HIV prevention efforts. Therefore, the neighborhood environment should be considered when implementing prevention interventions. However, much of the empirical evidence is derived from studies conducted among drug users, men, or adolescents. Such evidence may not be as applicable to adult women whose primary risk for HIV infection is via heterosexual sexual behavior. Therefore, a systematic review examining the relationship between neighborhood environments and HIV sexual risk behaviors among adult U.S. women was conducted. Three databases were searched for articles published in English in peer-reviewed journals between 1/1/1980 and 12/31/2016 meeting relevant criteria. Seven articles identified from the three databases or additional hand searches met inclusion criteria and were summarized. Findings were mixed with several studies indicating associations between neighborhood environments and HIV sexual risk behaviors. However, all summarized studies were cross-sectional. Longitudinal studies conducted among women are needed.

BackgroundThere is growing evidence that polygenic risk scores (PRS) can be used to identify individuals at high lifetime risk of coronary artery disease (CAD). Whether they can also be used to stratify risk of subsequent events among those surviving a first CAD event remains uncertain.MethodsUsing two subsamples of UK Biobank, defined at baseline as prevalent CAD (N=10,287) and without CAD (N=393,108), we evaluated associations between a CAD PRS and incident cardiovascular and fatal outcomes, during a median follow up of 7.8 years.ResultsA 1 S.D. higher PRS was associated with increased risk of incident MI in participants without CAD (OR 1.33; 95% C.I. 1.29, 1.38), but the effect estimate was markedly attenuated in those with prevalent CAD (OR 1.15; 95% C.I. 1.06, 1.25); heterogeneity P =0.0012. Additionally, among prevalent CAD cases, we found evidence of an inverse association between the CAD PRS and risk of all-cause death (OR 0.91; 95% C.I. 0.85, 0.98) compared to those without CAD (OR 1.01; 95% C.I. 0.99, 1.03); heterogeneity P =0.0041. A similar inverse association was found for ischaemic stroke (Prevalent CAD (OR 0.78; 95% C.I. 0.67, 0.90); without CAD (OR 1.09; 95% C.I. 1.04, 1.15), heterogeneity P ConclusionsBias induced by case stratification and survival into UK Biobank may attenuate, or reverse, associations of polygenic risk scores derived from case-control studies or populations initially free of disease. Polygenic risk scores for subsequent events should be derived from new genome wide association studies conducted in patients with established disease.Key messagesCAD PRS are positively associated with incident myocardial infarction risk amongst established CAD cases.However, the effect size is attenuated compared to estimates from CAD-free populations.CAD PRS are inversely associated with mortality and stroke risk amongst established CAD cases.These associations may reflect index event bias induced by stratifying on case status.Dedicated GWAS of coronary disease progression are required to improve prediction of subsequent event risk.