Sample selection, recruitment and participation rates in health examination surveys in Europe--experience from seven national surveys.

BACKGROUND: Health examination surveys (HESs), carried out in Europe since the 1950's, provide valuable information about the general population's health for health monitoring, policy making, and research. Survey participation rates, important for representativeness, have been falling. International comparisons are hampered by differing exclusion criteria and definitions for non-response. METHOD: Information was collected about seven national HESs in Europe conducted in 2007-2012. These surveys can be classified into household and individual-based surveys, depending on the sampling frames used. Participation rates of randomly selected adult samples were calculated for four survey modules using standardised definitions and compared by sex, age-group, geographical areas within countries, and over time, where possible. RESULTS: All surveys covered residents not just citizens; three countries excluded those in institutions. In two surveys, physical examinations and blood sample collection were conducted at the participants' home; the others occurred at examination clinics. Recruitment processes varied considerably between surveys. Monetary incentives were used in four surveys. Initial participation rates aged 35-64 were 45% in the Netherlands (phase II), 54% in Germany (new and previous participants combined), 55% in Italy, and 65% in Finland. In Ireland, England and Scotland, household participation rates were 66%, 66% and 63% respectively. Participation rates were generally higher in women and increased with age. Almost all participants attending an examination centre agreed to all modules but surveys conducted in the participants' home had falling responses to each stage. Participation rates in most primate cities were substantially lower than the national average. Age-standardized response rates to blood pressure measurement among those aged 35-64 in Finland, Germany and England fell by 0.7-1.5 percentage points p.a. between 1998-2002 and 2010-2012. Longer trends in some countries show a more marked fall. CONCLUSIONS: The coverage of the general population in these seven national HESs was good, based on the sampling frames used and the sample sizes. Pre-notification and reminders were used effectively in those with highest participation rates. Participation rates varied by age, sex, geographical area, and survey design. They have fallen in most countries; the Netherlands data shows that they can be maintained at higher levels but at much higher cost.

Sulfur Amino Acid Restriction Enhances Exercise Capacity in Mice by Boosting Fat Oxidation in Muscle.

Dietary restriction of the sulfur-containing amino acids methionine and cysteine (SAAR) improves body composition, enhances insulin sensitivity, and extends lifespan; benefits seen also with endurance exercise. Yet, the impact of SAAR on skeletal muscle remains largely unexplored. Here we demonstrate that one week of SAAR in sedentary, young, male mice increases endurance exercise capacity. Indirect calorimetry showed that SAAR increased lipid oxidation at rest and delayed the onset of carbohydrate utilization during exercise. Transcriptomic analysis revealed increased expression of genes involved in fatty acid catabolism especially in glycolytic muscle following SAAR. These findings were functionally supported by increased fatty acid circulatory turnover flux and muscle ß-oxidation. Reducing lipid uptake from circulation through endothelial cell (EC)-specific CD36 deletion attenuated the running phenotype. Mechanistically, VEGF-signaling inhibition prevented exercise increases following SAAR, without affecting angiogenesis, implicating noncanonical VEGF signaling and EC CD36-dependent fatty acid transport in regulating exercise capacity by influencing muscle substrate availability.

Multiomics assessment of dietary protein titration reveals altered hepatic glucose utilization.

Dietary protein restriction (PR) has rapid effects on metabolism including improved glucose and lipid homeostasis, via multiple mechanisms. Here, we investigate responses of fecal microbiome, hepatic transcriptome, and hepatic metabolome to six diets with protein from 18% to 0% of energy in mice. PR alters fecal microbial composition, but metabolic effects are not transferable via fecal transplantation. Hepatic transcriptome and metabolome are significantly altered in diets with lower than 10% energy from protein. Changes upon PR correlate with calorie restriction but with a larger magnitude and specific changes in amino acid (AA) metabolism. PR increases steady-state aspartate, serine, and glutamate and decreases glucose and gluconeogenic intermediates. 13C6 glucose and glycerol tracing reveal increased fractional enrichment in aspartate, serine, and glutamate. Changes remain intact in hepatic ATF4 knockout mice. Together, this demonstrates an ATF4-independent shift in gluconeogenic substrate utilization toward specific AAs, with compensation from glycerol to promote a protein-sparing response.

Assessment and Treatment of Prosody Behavior in Individuals with Level 1 Autism: A Review and Call for Research.

Differences in prosody behavior between individuals with autism spectrum disorder (ASD) and their typically developing peers have been considered a central feature of ASD since the earliest clinical descriptions of the disorder (e.g., Kanner, 1943/1973). Prosody includes pitch and volume among other dimensions of vocal-verbal behavior that discriminate responses of the listener; thus, people with ASD whose prosody has confusing or off-putting effects may have fewer social opportunities at work, at school, or in the community. The purpose of this review is to examine the state of the literature intervening on prosody with individuals with ASD and to provide recommendations for researchers who are interested in contributing to the scientific understanding of prosody.

Protocol - Evaluating the Effect of ACA Medicaid Expansion on Mortality During the COVID-19 Pandemic Using County-level Matching.

States are able to choose whether to expand Medicaid as part of the Affordable Care Act (ACA); thus it is of interest to understand the impact of this policy choice. In this protocol, we outline a study on the impact of Medicaid expansion as part of the ACA on mortality during the COVID-19 pandemic in the United States. County-level matching using full, optimal matching with a propensity score model is used to estimate causal effects in this observational study. Due to the provisional nature of mortality data in 2020 as reported by the CDC, we outline a modified aligned rank test to account for censored data as well as reporting lags for different states. We aim to make connections between statistical and ethnographic methodologies by particularly examining adjacent counties and similar counties that are in the same region of the US and in vastly different regions of the US. Finally, we aim to add to the growing literature about the effect of ACA Medicaid expansion on mortality by calculating effects, disaggregating by race.

Derivation and external validation of a simple risk score to predict in-hospital mortality in patients hospitalized for COVID-19: A multicenter retrospective cohort study.

ABSTRACT: As severe acute respiratory syndrome coronavirus 2 continues to spread, easy-to-use risk models that predict hospital mortality can assist in clinical decision making and triage. We aimed to develop a risk score model for in-hospital mortality in patients hospitalized with 2019 novel coronavirus (COVID-19) that was robust across hospitals and used clinical factors that are readily available and measured standardly across hospitals.In this retrospective observational study, we developed a risk score model using data collected by trained abstractors for patients in 20 diverse hospitals across the state of Michigan (Mi-COVID19) who were discharged between March 5, 2020 and August 14, 2020. Patients who tested positive for severe acute respiratory syndrome coronavirus 2 during hospitalization or were discharged with an ICD-10 code for COVID-19 (U07.1) were included. We employed an iterative forward selection approach to consider the inclusion of 145 potential risk factors available at hospital presentation. Model performance was externally validated with patients from 19 hospitals in the Mi-COVID19 registry not used in model development. We shared the model in an easy-to-use online application that allows the user to predict in-hospital mortality risk for a patient if they have any subset of the variables in the final model.Two thousand one hundred and ninety-three patients in the Mi-COVID19 registry met our inclusion criteria. The derivation and validation sets ultimately included 1690 and 398 patients, respectively, with mortality rates of 19.6% and 18.6%, respectively. The average age of participants in the study after exclusions was 64 years old, and the participants were 48% female, 49% Black, and 87% non-Hispanic. Our final model includes the patient's age, first recorded respiratory rate, first recorded pulse oximetry, highest creatinine level on day of presentation, and hospital's COVID-19 mortality rate. No other factors showed sufficient incremental model improvement to warrant inclusion. The area under the receiver operating characteristics curve for the derivation and validation sets were .796 (95% confidence interval, .767-.826) and .829 (95% confidence interval, .782-.876) respectively.We conclude that the risk of in-hospital mortality in COVID-19 patients can be reliably estimated using a few factors, which are standardly measured and available to physicians very early in a hospital encounter.

Plasma Hydrogen Sulfide Is Positively Associated With Post-operative Survival in Patients Undergoing Surgical Revascularization.

Objective: Hydrogen sulfide (H2S) is a gaseous signaling molecule and redox factor important for cardiovascular function. Deficiencies in its production or bioavailability are implicated in atherosclerotic disease. However, it is unknown if circulating H2S levels differ between vasculopaths and healthy individuals, and if so, whether H2S measurements can be used to predict surgical outcomes. Here, we examined: (1) Plasma H2S levels in patients undergoing vascular surgery and compared these to healthy controls, and (2) the association between H2S levels and mortality in a cohort of patients undergoing surgical revascularization. Methods: One hundred and fifteen patients undergoing carotid endarterectomy, open lower extremity revascularization or lower leg amputation were enrolled at a single institution. Peripheral blood was also collected from a matched control cohort of 20 patients without peripheral or coronary artery disease. Plasma H2S production capacity and sulfide concentration were measured using the lead acetate and monobromobimane methods, respectively. Results: Plasma H2S production capacity and plasma sulfide concentrations were reduced in patients with PAD (p < 0.001, p = 0.013, respectively). Patients that underwent surgical revascularization were divided into high vs. low H2S production capacity groups by median split. Patients in the low H2S production group had increased probability of mortality (p = 0.003). This association was robust to correction for potentially confounding variables using Cox proportional hazard models. Conclusion: Circulating H2S levels were lower in patients with atherosclerotic disease. Patients undergoing surgical revascularization with lower H2S production capacity, but not sulfide concentrations, had increased probability of mortality within 36 months post-surgery. This work provides insight on the role H2S plays as a diagnostic and potential therapeutic for cardiovascular disease.

Efficacy and social validity of procedures for improving conversational skills of college students with autism.

Better conversational skills correspond to a higher quality of life for adults diagnosed with autism spectrum disorder (ASD). In this study, we taught vocal-verbal responses discriminated by compound arrangements of concealed conversation partner mands to two college students with ASD. Participants learned to engage in self-questioning about their conversation partner's behavior and to reinforce three concealed mands for termination of an aversive conversation scenario. We assessed generalization to conversation probes with trained confederates and to interactions with untrained conversational partners (e.g., peers, professors). Finally, we collected peer ratings of the social validity of changes in conversational behavior as well as participants' ratings of study goals, procedures, and outcomes.

Periprocedural Hydrogen Sulfide Therapy Improves Vascular Remodeling and Attenuates Vein Graft Disease.

Background Failure rates after revascularization surgery remain high, both in vein grafts (VG) and arterial interventions. One promising approach to improve outcomes is endogenous upregulation of the gaseous transmitter-molecule hydrogen sulfide, via short-term dietary restriction. However, strict patient compliance stands as a potential translational barrier in the vascular surgery patient population. Here we present a new therapeutic approach, via a locally applicable gel containing the hydrogen sulfide releasing prodrug (GYY), to both mitigate graft failure and improve arterial remodeling. Methods and Results All experiments were performed on C57BL/6 (male, 12 weeks old) mice. VG surgery was performed by grafting a donor-mouse cava vein into the right common carotid artery of a recipient via an end-to-end anastomosis. In separate experiments arterial intimal hyperplasia was assayed via a right common carotid artery focal stenosis model. All mice were harvested at postoperative day 28 and artery/graft was processed for histology. Efficacy of hydrogen sulfide was first tested via GYY supplementation of drinking water either 1 week before VG surgery (pre-GYY) or starting immediately postoperatively (post-GYY). Pre-GYY mice had a 36.5% decrease in intimal/media+adventitia area ratio compared with controls. GYY in a 40% Pluronic gel (or vehicle) locally applied to the graft/artery had decreased intimal/media area ratios (right common carotid artery) and improved vessel diameters. GYY-geltreated VG had larger diameters at both postoperative days 14 and 28, and a 56.7% reduction in intimal/media+adventitia area ratios. Intimal vascular smooth muscle cell migration was decreased 30.6% after GYY gel treatment, which was reproduced in vitro. Conclusions Local gel-based treatment with the hydrogen sulfide-donor GYY stands as a translatable therapy to improve VG durability and arterial remodeling after injury.

Teaching multiply controlled intraverbals to children and adolescents with autism spectrum disorders.

Reciprocal conversations, instructional activities, and other social interactions are replete with multiply controlled intraverbals, examples of which have been conceptualized in terms of conditional discriminations. Although the acquisition of conditional discriminations has been examined extensively in the behavior-analytic literature, little research has evaluated procedures to establish multiply controlled intraverbals. Thus, the purpose of this investigation was to evaluate the effects of procedures based on conditional discrimination training on the acquisition of multiply controlled intraverbals with 7 participants who had been diagnosed with autism spectrum disorders. We evaluated the effects of prompt delay with error correction, a differential observing response (DOR), and a DOR plus blocked trials on the acquisition of intraverbals using a multiple baseline design. Accuracy of intraverbal performance increased for at least 1 set of stimuli for all participants under prompt delay with error correction conditions; however, 4 participants required additional teaching (i.e., DOR, modified DOR, modified prompt delay with error correction). Based on these findings, when prompt delay with error correction is not sufficient to establish multiply controlled intraverbals, prompted DORs may be an effective alternative.

Sepsis Prevalence and Outcome on the General Wards and Emergency Departments in Wales: Results of a Multi-Centre, Observational, Point Prevalence Study.

Data on sepsis prevalence on the general wards is lacking on the UK and in the developed world. We conducted a multicentre, prospective, observational study of the prevalence of patients with sepsis or severe sepsis on the general wards and Emergency Departments (ED) in Wales. During the 24-hour study period all patients with NEWS≥3 were screened for presence of 2 or more SIRS criteria. To be eligible for inclusion, patients had to have a high clinical suspicion of an infection, together with a systemic inflammatory response (sepsis) and evidence of acute organ dysfunction and/or shock (severe sepsis). There were 5317 in-patients in the 24-hour study period. Data were returned on 1198 digital data collection forms on patients with NEWS≥3 of which 87 were removed, leaving 1111 for analysis. 146 patients had sepsis and 144 patients had severe sepsis. Combined prevalence of sepsis and severe sepsis was 5.5% amongst all in-patients. Patients with sepsis had significantly higher NEWS scores (3 IQR 3-4 for non-sepsis and 4 IQR 3-6 for sepsis patients, respectively). Common organ dysfunctions in severe sepsis were hypoxia (47%), hypoperfusion (40%) and acute kidney injury (25%). Mortality at 90 days was 31% with a median (IQR) hospital free stay of 78 (36-85) days. Screening for sepsis, referral to Critical Care and completion of Sepsis 6 bundle was low: 26%, 16% and 12% in the sepsis group. Multivariable logistic regression analysis identified higher National Early Warning Score, diabetes, COPD, heart failure, malignancy and current or previous smoking habits as independent variables suggesting the diagnosis of sepsis. We observed that sepsis is more prevalent in the general ward and ED than previously suggested before and that screening and effective treatment for sepsis and severe sepsis is far from being operationalized in this environment, leading to high 90 days mortality.

Effects of a differential observing response on intraverbal performance of preschool children: a preliminary investigation.

Axe (2008) speculated that some instances of intraverbal responding might be associated with limited or delayed acquisition because they require discrimination of multiple components of verbal stimuli. Past studies suggest that acquisition of responses under control of complex, multicomponent antecedent stimuli (e.g., conditional or compound stimulus control) can be facilitated with the introduction of a differential observing response (DOR; Dube & McIlvane, 1999; Gutowski, Geren, Stromer, & Mackay, 1995). The purpose of the current study was to evaluate the effects of a DOR (i.e., repeating the question) on intraverbal responding with six neurotypical preschool children. Findings included that (a) accuracy of intraverbal performance increased when the experimenter prompted a DOR; (b) 1 of 6 participants overtly emitted the DOR for a second relation in the absence of prompts, which was correlated with increased accuracy; and (c) following mastery, response accuracy was variable for 3 participants. Based on these findings, prompted DORs may offer an effective, if temporary, aid to intraverbal instruction for neurotypical preschool children.