Perceived Neighborhood Safety and Psychological Distress: Exploring Protective Factors

While a growing body of literature has established a relationship between disordered neighborhoods and psychological distress, less is known about the specific mechanisms at work. Using data collected in the 2008 Arizona Health Survey (N = 4,196), hierarchal linear regression was conducted to assess both the independent effect of perception of neighborhood safety on psychological distress, as well as the mediating effects of powerlessness, social isolation and mistrust. The findings suggest that the more safe individuals feel in their neighborhood, the less psychological distress they experience (b = 1.07, SE = .17, p \u3c .001). This relationship appears to be partially mediated by feelings of powerlessness, social isolation and mistrust, indicating potential risk and protective factors

Applicability of the Theory of Planned Behavior for Predicting Alcohol Use in Spanish Early Adolescents

According to the theory of planned behavior (TPB), intentions to perform a specific behavior are the result of attitudes, norms, and perceived control, and in turn, intentions and perceived control are the main predictors of the behavior. This study aimed to test the applicability of TPB in predicting alcohol use in normative pre-adolescents. The sample was composed of 755 Spanish adolescents aged 11 to 15 (M = 12.24; SD = 0.56), 47.1% females, from 12 state secondary schools in Spain. The results of path analysis indicate that positive attitudes towards alcohol, favorable norms towards alcohol, and offer vulnerability (perceived control) are significantly positively related to intentions to use alcohol as well as negatively related to actual behavioral control (i.e., actual strategies to avoid alcohol use). In turn, intentions to use and actual control predict higher alcohol frequency and heavy drinking. Significant indirect effects of these antecedents were found on alcohol outcomes through the mediation of intentions and actual control. The findings suggest that the validity and applicability of the TPB in normative pre-adolescents depend on the severity of alcohol use and point to a need to consider negative social influence in decision making processes in early adolescenceThis research was funded by the Global Center for Applied Health Research (GCAHR; Arizona State University) and supported by the Programa de Axudas á etapa posdoutoral da Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria) and by FEDER/Ministerio de Ciencia, Innovación y Universidades—Agencia Estatal de Investigación (Grant PSI2015-65766-R)—under the Axuda para a consolidación e estruturación de unidades de investigación competitivas e outras accións de fomento nas universidades do SUG (GRC, 2018)S

Motoric Cognitive Risk Syndrome: Multicountry Prevalence and Dementia Risk

OBJECTIVES: Our objective is to report prevalence of motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints, in multiple countries, and its association with dementia risk. METHODS: Pooled MCR prevalence analysis of individual data from 26,802 adults without dementia and disability aged 60 years and older from 22 cohorts from 17 countries. We also examined risk of incident cognitive impairment (Mini-Mental State Examination decline ≥4 points) and dementia associated with MCR in 4,812 individuals without dementia with baseline Mini-Mental State Examination scores ≥25 from 4 prospective cohort studies using Cox models adjusted for potential confounders. RESULTS: At baseline, 2,808 of the 26,802 participants met MCR criteria. Pooled MCR prevalence was 9.7% (95% confidence interval [CI] 8.2%-11.2%). MCR prevalence was higher with older age but there were no sex differences. MCR predicted risk of developing incident cognitive impairment in the pooled sample (adjusted hazard ratio [aHR] 2.0, 95% CI 1.7-2.4); aHRs were 1.5 to 2.7 in the individual cohorts. MCR also predicted dementia in the pooled sample (aHR 1.9, 95% CI 1.5-2.3). The results persisted even after excluding participants with possible cognitive impairment, accounting for early dementia, and diagnostic overlap with other predementia syndromes. CONCLUSION: MCR is common in older adults, and is a strong and early risk factor for cognitive decline. This clinical approach can be easily applied to identify high-risk seniors in a wide variety of settings

The importance of examining movements within the US health care system: sequential logit modeling

Background: Utilization of specialty care may not be a discrete, isolated behavior but rather, a behavior of sequential movements within the health care system. Although patients may often visit their primary care physician and receive a referral before utilizing specialty care, prior studies have underestimated the importance of accounting for these sequential movements. Methods: The sample included 6,772 adults aged 18 years and older who participated in the 2001 Survey on Disparities in Quality of Care, sponsored by the Commonwealth Fund. A sequential logit model was used to account for movement in all stages of utilization: use of any health services (i.e., first stage), having a perceived need for specialty care (i.e., second stage), and utilization of specialty care (i.e., third stage). In the sequential logit model, all stages are nested within the previous stage. Results: Gender, race/ethnicity, education and poor health had significant explanatory effects with regard to use of any health services and having a perceived need for specialty care, however racial/ethnic, gender, and educational disparities were not present in utilization of specialty care. After controlling for use of any health services and having a perceived need for specialty care, inability to pay for specialty care via income (AOR = 1.334, CI = 1.10 to 1.62) or health insurance (unstable insurance: AOR = 0.26, CI = 0.14 to 0.48; no insurance: AOR = 0.12, CI = 0.07 to 0.20) were significant barriers to utilization of specialty care. Conclusions: Use of a sequential logit model to examine utilization of specialty care resulted in a detailed representation of utilization behaviors and patient characteristics that impact these behaviors at all stages within the health care system. After controlling for sequential movements within the health care system, the biggest barrier to utilizing specialty care is the inability to pay, while racial, gender, and educational disparities diminish to non-significance. Findings from this study represent how Americans use the health care system and more precisely reveals the disparities and inequalities in the U.S. health care system

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation