Good Risk or Bad Risk: Development of a Holistic Assessment of Risk Perception

The goal of the current project was to create a measurement tool that could be used to assess all aspects of risk perception with one measure. There is a wide variety of risk-perception measures currently available; however, the vast majority of these measures assess a very specific risky activity, and many only assess a person’s perception of the possible negative consequences from the risk. There are notable exceptions, such as measures that assess risk in various domains (e.g., DOSPERT scale; Weber et al., 2002) and assess perception of possible benefits (e.g., Fromme et al., 1997). There has also been research into the various dimensions or facets of risk perception, such as whether a person believes that they have more control in one activity over another (e.g., Benthin et al., 1993; Fischhoff et al.,1978; Hampson et al., 2001). Grounded in Balance Theory (Janis & Mann, 1977), the current project utilized knowledge from these previous studies to create the Holistic Assessment of Risk Perception (HARP Scale) that assesses possible negative consequences, possible positive benefits, and the various facets of risk perception across risk domains. This project involved a series of studies that collectively used thematic analyses of interview data to identify the various facets involved in risk perception (e.g., controllability of situation, past experience) while ensuring that the identified facets were not conflated with cognitive biases or risk-taking behaviour, and then used the identified facets to create a scale and perform a psychometric evaluation to determine the reliability and validity of the new scale. Specifically, Study 1 was performed in two parts. Study 1-A assessed the extent of possible confounds using participant scores on various measures, such as measures of cognitive bias and risk propensity. The participants from Study 1-A were then used as the sampling frame for Study 1-B, which recruited participants in order to form four groups that were relatively equal in gender and other possible confounds. Participants in these four groups were then interviewed for the purpose of identifying risk-perception facets (e.g., controllability of the situation) that were common across the four groups. In Study 2 the scale items were refined, and an unsuccessful attempt was made to use quantitative data to verify the weighting of the facets that had been identified in Study 1-B. The final scale was brought forward for psychometric evaluation in Study 3, which provided evidence in support of the convergent validity, discriminant validity, concurrent validity, and internal reliability of the new HARP Scale. In sum, the current project has provided a relatively parsimonious measurement tool that enables research into various risk domains, acknowledges both potential consequences and benefits, assesses facets that contribute to risk perception, and does not conflate cognitive bias or risk-taking behaviour with risk perception. The resulting HARP Scale is able to assess whether people perceive an activity as a good risk, or a bad risk

Health Literacy and Medication Adherence Among Patients Treated in a Free Health Clinic: A Pilot Study

Background: A patient’s health literacy is not routinely assessed during visits with a health care provider. Since low health literacy is a risk factor for poor health outcomes, assessing health literacy should be considered as part of the standard medical workup. Objectives: To evaluate the health literacy levels and medication adherence of patients treated by pharmacists in both the general medicine and the chronic care clinics at an urban free health clinic. Methods: Eligible patients from the free health clinic completed the Rapid Estimate of Adult Literacy in Medicine (REALM), a health literacy measurement tool, during their clinic visit in 2011. Medication adherence was self-reported by the patients. Results: A total of 100 patients participated (mean age = 48). The majority of participants were female (56%) and white (55%). Most (64%) of the patients scored at a high school reading level according to REALM. Only 21% of participants read at a seventh- to eighth-grade level. Overall medication adherence rate was 73%. Forgetting to take medication was the most popular reason given for nonadherence. Conclusion: Disease state and adherence were significantly related in patients with HIV/AIDS and hypertension. Patient’s ethnicity was significantly associated with literacy levels (P < .05). Although patients’ literacy levels were not significantly associated with self-reported adherence in this population, availability of a patient’s baseline health literacy level as a part of the medical record may help clinicians to individualize their interaction based on the patient’s health literacy level in order to achieve better health outcomes, including improved medication adherence, especially for underserved populations

Criteria for reducing unnecessary testing for herpes simplex virus, varicella-zoster virus, cytomegalovirus, and enterovirus in cerebrospinal fluid samples from adults

Excessive utilization of laboratory diagnostic testing leads to increased health care costs. We evaluated criteria to reduce unnecessary nucleic acid amplification testing (NAAT) for viral pathogens in cerebrospinal fluid (CSF) samples from adults. This is a single-center split retrospective observational study with a screening cohort from 2008 to 2012 and a validation cohort from 2013. Adults with available results for herpes simplex virus 1/2 (HSV-1/2), varicella-zoster virus (VZV), cytomegalovirus (CMV), or enterovirus (EV) NAAT with CSF samples between 2008 and 2013 were included (n = 10,917). During this study, 1.3% (n = 140) of viral NAAT studies yielded positive results. The acceptance criteria of >10 nucleated cells/μl in the CSF of immunocompetent subjects would have reduced HSV-1/2, VZV, CMV, and EV testing by 63%, 50%, 44%, and 51%, respectively, from 2008 to 2012. When these criteria were applied to the 2013 validation data set, 54% of HSV-1/2, 57% of VZV, 35% of CMV, and 56% of EV tests would have been cancelled. No clinically significant positive tests would have been cancelled in 2013 with this approach. The introduction of a computerized order entry set was associated with increased test requests, suggesting that computerized order sets may contribute to unnecessary testing. Acceptance criteria of >10 nucleated cells/μl in the CSF of immunocompetent adults for viral CSF NAAT assays would increase clinical specificity and preserve sensitivity, resulting in significant cost savings. Implementation of these acceptance criteria led to a 46% reduction in testing during a limited follow-up period

Patterns of impact resulting from a 'sit less, move more' web-based program in sedentary office employees.

PURPOSE: Encouraging office workers to 'sit less and move more' encompasses two public health priorities. However, there is little evidence on the effectiveness of workplace interventions for reducing sitting, even less about the longer term effects of such interventions and still less on dual-focused interventions. This study assessed the short and mid-term impacts of a workplace web-based intervention (Walk@WorkSpain, W@WS; 2010-11) on self-reported sitting time, step counts and physical risk factors (waist circumference, BMI, blood pressure) for chronic disease. METHODS: Employees at six Spanish university campuses (n=264; 42±10 years; 171 female) were randomly assigned by worksite and campus to an Intervention (used W@WS; n=129; 87 female) or a Comparison group (maintained normal behavior; n=135; 84 female). This phased, 19-week program aimed to decrease occupational sitting time through increased incidental movement and short walks. A linear mixed model assessed changes in outcome measures between the baseline, ramping (8 weeks), maintenance (11 weeks) and follow-up (two months) phases for Intervention versus Comparison groups. RESULTS: A significant 2 (group) × 2 (program phases) interaction was found for self-reported occupational sitting (F[3]=7.97, p=0.046), daily step counts (F[3]=15.68, p=0.0013) and waist circumference (F[3]=11.67, p=0.0086). The Intervention group decreased minutes of daily occupational sitting while also increasing step counts from baseline (446±126; 8,862±2,475) through ramping (+425±120; 9,345±2,435), maintenance (+422±123; 9,638±3,131) and follow-up (+414±129; 9,786±3,205). In the Comparison group, compared to baseline (404±106), sitting time remained unchanged through ramping and maintenance, but decreased at follow-up (-388±120), while step counts diminished across all phases. The Intervention group significantly reduced waist circumference by 2.1cms from baseline to follow-up while the Comparison group reduced waist circumference by 1.3cms over the same period. CONCLUSIONS: W@WS is a feasible and effective evidence-based intervention that can be successfully deployed with sedentary employees to elicit sustained changes on "sitting less and moving more"

Blood pressure–associated polymorphism controls ARHGAP42 expression via serum response factor DNA binding

We recently demonstrated that selective expression of the Rho GTPase-activating protein ARHGAP42 in smooth muscle cells (SMCs) controls blood pressure by inhibiting RhoA-dependent contractility, providing a mechanism for the blood pressure–associated locus within the ARHGAP42 gene. The goals of the current study were to identify polymorphisms that affect ARHGAP42 expression and to better assess ARHGAP42’s role in the development of hypertension. Using DNase I hypersensitivity methods and ENCODE data, we have identified a regulatory element encompassing the ARHGAP42 SNP rs604723 that exhibits strong SMC-selective, allele-specific activity. Importantly, CRISPR/Cas9–mediated deletion of this element in cultured human SMCs markedly reduced endogenous ARHGAP42 expression. DNA binding and transcription assays demonstrated that the minor T allele variation at rs604723 increased the activity of this fragment by promoting serum response transcription factor binding to a cryptic cis-element. ARHGAP42 expression was increased by cell stretch and sphingosine 1-phosphate in a RhoA-dependent manner, and deletion of ARHGAP42 enhanced the progression of hypertension in mice treated with DOCA-salt. Our analysis of a well-characterized cohort of untreated borderline hypertensive patients suggested that ARHGAP42 genotype has important implications in regard to hypertension risk. Taken together, our data add insight into the genetic mechanisms that control blood pressure and provide a potential target for individualized antihypertensive therapies

Cytochrome P450-derived epoxyeicosatrienoic acids and coronary artery disease in humans: a targeted metabolomics study

Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) exhibit potent cardiovascular protective effects in preclinical models, and promoting the effects of EETs has emerged as a potential therapeutic strategy for coronary artery disease (CAD). The relationship between circulating EET levels and CAD extent in humans, however, remains unknown. A panel of free (unesterified) plasma eicosanoid metabolites was quantified in 162 patients referred for coronary angiography, and associations with extent of CAD [no apparent CAD (N = 39), nonobstructive CAD (N = 51), and obstructive CAD (N = 72)] were evaluated. A significant relationship between free EET levels and CAD extent was observed (P = 0.003) such that the presence of obstructive CAD was associated with lower circulating EET levels. This relationship was confirmed in multiple regression analysis where CAD extent was inversely and significantly associated with EET levels (P = 0.013), and with a biomarker of EET biosynthesis (P < 0.001), independent of clinical and demographic factors. Furthermore, quantitative enrichment analysis revealed that these associations were the most pronounced compared with other eicosanoid metabolism pathways. Collectively, these findings suggest that the presence of obstructive CAD is associated with lower EET metabolite levels secondary to suppressed EET biosynthesis. Novel strategies that promote the effects of EETs may have therapeutic promise for patients with obstructive CAD

Sex- and isoform-specific mechanism of neuroprotection by transgenic expression of P450 epoxygenase in vascular endothelium

Cytochrome P450 epoxygenases (CYP) metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs), which exhibit vasodilatory, anti-inflammatory and neuroprotective actions in experimental cerebral ischemia. We evaluated the effect of endothelial-specific CYP overexpression on cerebral blood flow, inflammatory cytokine expression and tissue infarction after focal cerebral ischemia in transgenic mice

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role