Inhibit progression of coronary artery calcification with vitamin K in hemodialysis patients (the iPACK-HD study): a randomized, placebo-controlled multi-center, pilot trial.

BACKGROUND: Vitamin K activates matrix Gla protein (MGP), a key inhibitor of vascular calcification. There is a high prevalence of sub-clinical vitamin K deficiency in patients with end-stage kidney disease. METHODS: A parallel randomized placebo-controlled pilot trial was designed to determine whether 10 mg of phylloquinone thrice weekly versus placebo modifies coronary artery calcification progression over 12 months in patients requiring hemodialysis with a coronary artery calcium score (CAC) ≥30 Agatston Units (ClinicalTrials.gov identifier NCT01528800). The primary outcome was feasibility (recruitment rate, compliance with study medication, study completion and adherence overall to study protocol). CAC score was used to assess calcification at baseline and 12 months. Secondary objectives were to explore the impact of phylloquinone on vitamin K-related biomarkers (phylloquinone, dephospho-uncarboxylated MGP and the Gla-osteocalcin to Glu-osteocalcin ratio) and events of clinical interest. RESULTS: A total of 86 patients with a CAC score ≥30 Agatston Units were randomized to either 10 mg of phylloquinone or a matching placebo three times per week. In all, 69 participants (80%) completed the trial. Recruitment rate (4.4 participants/month) and medication compliance (96%) met pre-defined feasibility criteria of ≥4.17 and ≥90%, respectively. Patients randomized to phylloquinone for 12 months had significantly reduced levels of dephospho-uncarboxylated MGP (86% reduction) and increased levels of phylloquinone and Gla-osteocalcin to Glu-osteocalcin ratio compared with placebo. There was no difference in the absolute or relative progression of coronary artery calcification between groups. CONCLUSION: We demonstrated that phylloquinone treatment improves vitamin K status and that a fully powered randomized trial may be feasible.

Traits that distinguish dominant species across aridity gradients differ from those that respond to soil moisture.

Many plant traits respond to changes in water availability and might be useful for understanding ecosystem properties such as net primary production (NPP). This is especially evident in grasslands where NPP is water-limited and primarily determined by the traits of dominant species. We measured root and shoot morphology, leaf hydraulic traits, and NPP of four dominant North American prairie grasses in response to four levels of soil moisture in a greenhouse experiment. We expected that traits of species from drier regions would be more responsive to reduced water availability and that this would make these species more resistant to low soil moisture than species from wetter regions. All four species grew taller, produced more biomass, and increased total root length in wetter treatments. Each species reduced its leaf turgor loss point (TLP) in drier conditions, but only two species (one xeric, one mesic) maintained leaf water potential above TLP. We identified a suite of traits that clearly distinguished species from one another, but, surprisingly, these traits were relatively unresponsive to reduced soil moisture. Specifically, more xeric species produced thinner roots with higher specific root length and had a lower root mass fraction. This suggest that root traits are critical for distinguishing species from one another but might not respond strongly to changing water availability, though this warrants further investigation in the field. Overall, we found that NPP of these dominant grass species responded similarly to varying levels of soil moisture despite differences in species morphology, physiology, and habitat of origin.

Non-asbestiform elongate mineral particles and mesothelioma risk: Human and experimental evidence.

The presentations in this session of the Monticello II conference were aimed at summarizing what is known about asbestiform and non-asbestiform elongate mineral particles (EMPs) and mesothelioma risks based on evidence from experimental and epidemiology studies. Dr. Case discussed case reports of mesothelioma over the last several decades. Dr. Taioli indicated that the epidemiology evidence concerning non-asbestiform EMPs is weak or lacking, and that progress would be limited unless mesothelioma registries are established. One exception discussed is that of taconite miners, who are exposed to grunerite. Drs. Mandel and Odo noted that studies of taconite miners in Minnesota have revealed an excess rate of mesothelioma, but the role of non-asbestiform EMPs in this excess incidence of mesothelioma is unclear. Dr. Becich discussed the National Mesothelioma Virtual Bank (NMVB), a virtual mesothelioma patient registry that includes mesothelioma patients' lifetime work histories, exposure histories, biospecimens, proteogenomic information, and imaging data that can be used in epidemiology research on mesothelioma. Dr. Bernstein indicated that there is a strong consensus that long, highly durable respirable asbestiform EMPs have the potential to cause mesothelioma, but there is continued debate concerning the biodurability required, and the dimensions (both length and diameter), the shape, and the dose associated with mesothelioma risk. Finally, Dr. Nel discussed how experimental studies of High Aspect Ratio Engineered Nanomaterials have clarified dimensional and durability features that impact disease risk, the impact of inflammation and oxidative stress on the epigenetic regulation of tumor suppressor genes, and the generation of immune suppressive effects in the mesothelioma tumor microenvironment. The session ended with a discussion of future research needs.

Resolving the Dust Bowl paradox of grassland responses to extreme drought.

During the 1930s Dust Bowl drought in the central United States, species with the C3 photosynthetic pathway expanded throughout C4-dominated grasslands. This widespread increase in C3 grasses during a decade of low rainfall and high temperatures is inconsistent with well-known traits of C3 vs. C4 pathways. Indeed, water use efficiency is generally lower, and photosynthesis is more sensitive to high temperatures in C3 than C4 species, consistent with the predominant distribution of C3 grasslands in cooler environments and at higher latitudes globally. We experimentally imposed extreme drought for 4 y in mixed C3/C4 grasslands in Kansas and Wyoming and, similar to Dust Bowl observations, also documented three- to fivefold increases in C3/C4 biomass ratios. To explain these paradoxical responses, we first analyzed long-term climate records to show that under nominal conditions in the central United States, C4 grasses dominate where precipitation and air temperature are strongly related (warmest months are wettest months). In contrast, C3 grasses flourish where precipitation inputs are less strongly coupled to warm temperatures. We then show that during extreme drought years, precipitation-temperature relationships weaken, and the proportion of precipitation falling during cooler months increases. This shift in precipitation seasonality provides a mechanism for C3 grasses to respond positively to multiyear drought, resolving the Dust Bowl paradox. Grasslands are globally important biomes and increasingly vulnerable to direct effects of climate extremes. Our findings highlight how extreme drought can indirectly alter precipitation seasonality and shift ecosystem phenology, affecting function in ways not predictable from key traits of C3 and C4 species.

Legacy effects of a multi-year extreme drought on belowground bud banks in rhizomatous vs bunchgrass-dominated grasslands.

Belowground bud banks play a crucial role in plant population regeneration, community dynamics, and functional responses of ecosystems to environmental change and disturbance. In mesic grasslands, belowground bud banks are largely resistant to short-term drought. However, the sensitivity of belowground bud banks to long-term extreme drought in semi-arid grasslands is less understood. We investigated the legacy effects of a four-year experimental drought (i.e., 66% reduction in growing season precipitation) on belowground bud density, aboveground shoot density, and the meristem limitation index (MLI; the ratio of bud to shoot density) in two semi-arid grasslands that differ in dominant grass species growth forms (i.e., rhizomatous vs. bunchgrasses). Measurements were made during the first recovery year following drought; thus, we report the legacy effects of drought on belowground bud banks. At the community level, drought reduced belowground bud density and aboveground shoot density with no change in MLI. However, drought had no significant influences on belowground buds, aboveground shoots and MLI of the dominant plant growth form in each community. The legacy effects of drought were largely dependent on plant community type and growth form. Specifically, bunchgrasses and bunchgrass-dominated communities were characterized by greater meristem limitation than rhizomatous grasses, likely due to their cluster/phalanx clonal growth. Overall, our study suggests bud banks may indeed be sensitive to long-term drought, although this depends on plant growth forms and community characteristics.

Digital Health Interventions for Depression and Anxiety Among People With Chronic Conditions: Scoping Review.

BACKGROUND: Chronic conditions are characterized by their long duration (≥1 year), need for ongoing medical attention, and limitations in activities of daily living. These can often co-occur with depression and anxiety as common and detrimental comorbidities among the growing population living with chronic conditions. Digital health interventions (DHIs) hold promise in overcoming barriers to accessing mental health support for these individuals; however, the design and implementation of DHIs for depression and anxiety in people with chronic conditions are yet to be explored. OBJECTIVE: This study aimed to explore what is known in the literature regarding DHIs for the prevention, detection, or treatment of depression and anxiety among people with chronic conditions. METHODS: A scoping review of the literature was conducted using the Arksey and O'Malley framework. Searches of the literature published in 5 databases between 1990 and 2019 were conducted in April 2019 and updated in March 2021. To be included, studies must have described a DHI tested with, or designed for, the prevention, detection, or treatment of depression or anxiety in people with common chronic conditions (arthritis, asthma, diabetes mellitus, heart disease, chronic obstructive pulmonary disease, cancer, stroke, and Alzheimer disease or dementia). Studies were independently screened by 2 reviewers against the inclusion and exclusion criteria. Both quantitative and qualitative data were extracted, charted, and synthesized to provide a descriptive summary of the trends and considerations for future research. RESULTS: Database searches yielded 11,422 articles across the initial and updated searches, 53 (0.46%) of which were included in this review. DHIs predominantly sought to provide treatment (44/53, 83%), followed by detection (5/53, 9%) and prevention (4/53, 8%). Most DHIs were focused on depression (36/53, 68%), guided (32/53, 60%), tailored to chronic physical conditions (19/53, 36%), and delivered through web-based platforms (20/53, 38%). Only 2 studies described the implementation of a DHI. CONCLUSIONS: As a growing research area, DHIs offer the potential to address the gap in care for depression and anxiety among people with chronic conditions; however, their implementation in standard care is scarce. Although stepped care has been identified as a promising model to implement efficacious DHIs, few studies have investigated the use of DHIs for depression and anxiety among chronic conditions using such models. In developing stepped care, we outlined DHI tailoring, guidance, and intensity as key considerations that require further research.

Is a drought a drought in grasslands? Productivity responses to different types of drought.

Drought, defined as a marked deficiency of precipitation relative to normal, occurs as periods of below-average precipitation or complete failure of precipitation inputs, and can be limited to a single season or prolonged over multiple years. Grasslands are typically quite sensitive to drought, but there can be substantial variability in the magnitude of loss of ecosystem function. We hypothesized that differences in how drought occurs may contribute to this variability. In four native Great Plains grasslands (three C4- and one C3-dominated) spanning a ~ 500-mm precipitation gradient, we imposed drought for four consecutive years by (1) reducing each rainfall event by 66% during the growing season (chronic drought) or (2) completely excluding rainfall during a shorter portion of the growing season (intense drought). The drought treatments were similar in magnitude but differed in the following characteristics: event number, event size and length of dry periods. We observed consistent drought-induced reductions (28-37%) in aboveground net primary production (ANPP) only in the C4-dominated grasslands. In general, intense drought reduced ANPP more than chronic drought, with little evidence that drought duration altered this pattern. Conversely, belowground net primary production (BNPP) was reduced by drought in all grasslands (32-64%), with BNPP reductions greater in intense vs. chronic drought treatments in the most mesic grassland. We conclude that grassland productivity responses to drought did not strongly differ between these two types of drought, but when differences existed, intense drought consistently reduced function more than chronic drought.

Pregnant patient in the emergency department: An observational investigation of predictive values of symptoms and lab measures in predicting culture confirmed urinary tract infection.

Many women in their first trimester present to the Emergency Department (ED) for evaluation. Urinalysis is a common test performed with these patients to evaluate for possible UTI. There are no clear results to determine if a patient requires antibiotic in the ED vs waiting for the culture result to start antibiotics. We prospectively studied a convenience sample of 198 women in their first trimester of pregnancy presenting to a community ED recording standard symptoms and lab analysis and then compared these results to the urine culture. We determined that no single symptom was significantly sensitive nor specific for ruling in or out UTI. Overall, the presence of Nitrites was the most significant with a specificity of 98.6%, NPV of 81.9% and PPV of 86.6%. Presence of specific historical findings, namely dysuria (88% specificity) and hematuria (93% specificity) performed well for predicting culture positive UTI but performed poorly in ruling out this condition. The diagnosis of a culture confirmed UTI in the ED cannot be reliably predicted using symptomology or labs values other than nitrates.

A cultural and gender-based approach to understanding patient adjustment to chronic heart failure.

BACKGROUND: Persons identifying as Black, Chinese, or South Asian make up the largest minority groups in Canada. Individuals with chronic heart failure (CHF) from these groups experience a greater rate of re-hospitalization and poorer quality of life. Although experts agree that culture can shape the experience of CHF, little is known about how patients from these minority populations define a good quality of life with CHF and what barriers they experience when carrying out self-care behaviours. The aim of this qualitative study was to examine cultural and gender-based influences on quality of life in patients with CHF. METHODS: Purposive sampling included 30 patients (67% male), 18 to 75 years of age, who self-identified as Black (n = 8), Chinese (n = 9), or South Asian (n = 6). Caucasians (n = 7) were included as a comparison group. Semi-structured interviews (see the online appendix), lasting approximately 60 min, were conducted, which focused on personal understanding of CHF and living with the disease, including impact on lifestyle and quality of life. An inductive qualitative approach with thematic content analysis was used to develop key insights into individual experience of CHF, as well as cultural and gender-based influences on self-care and quality of life. Descriptive statistics were generated from questionnaire responses. RESULTS: Five key themes emerged from the narrative analysis of participant interviews: (i) CHF as an emergent reality, (ii) quality of life and disruption of lifecourse milestones, (iii) the challenge to accept CHF and re-evaluation of quality of life; (iv) impact on social activities essential to quality of life, and (v) life with CHF as a commitment to culturally tailored self-care. Participants described the unique impact of CHF on their quality of life, including life trajectory milestones such as dating, parenting, and retirement planning, as well as the importance of accepting their diagnosis, and the reframing goals for living well with heart failure. Positive and negative impacts on social relationships were noted, including sexual intimacy and interactions with spouses, other family members, and co-workers. CONCLUSIONS: Study findings highlight important lifespan, cultural, and gender considerations that can inform the improvement of patient care and quality of life for patients and their families.

Extending the osmometer method for assessing drought tolerance in herbaceous species.

Community-scale surveys of plant drought tolerance are essential for understanding semi-arid ecosystems and community responses to climate change. Thus, there is a need for an accurate and rapid methodology for assessing drought tolerance strategies across plant functional types. The osmometer method for predicting leaf osmotic potential at full turgor (πo), a key metric of leaf-level drought tolerance, has resulted in a 50-fold increase in the measurement speed of this trait; however, the applicability of this method has only been tested in woody species and crops. Here, we assess the osmometer method for use in herbaceous grassland species and test whether πo is an appropriate plant trait for understanding drought strategies of herbaceous species as well as species distributions along climate gradients. Our model for predicting leaf turgor loss point (πTLP) from πo (πTLP = 0.80πo-0.845) is nearly identical to the model previously presented for woody species. Additionally, πo was highly correlated with πTLP for graminoid species (πtlp = 0.944πo-0.611; r2 = 0.96), a plant functional group previously flagged for having the potential to cause erroneous measurements when using an osmometer. We report that πo, measured with an osmometer, is well correlated with other traits linked to drought tolerance (namely, leaf dry matter content and leaf vulnerability to hydraulic failure) as well as climate extremes linked to water availability. The validation of the osmometer method in an herb-dominated ecosystem paves the way for rapid community-scale surveys of drought tolerance across plant functional groups, which could improve trait-based predictions of ecosystem responses to climate change.

A reality check for climate change experiments: Do they reflect the real world?

Experiments are widely used in ecology, particularly for assessing global change impacts on ecosystem function. However, results from experiments often are inconsistent with observations made under natural conditions, suggesting the need for rigorous comparisons of experimental and observational studies. We conducted such a "reality check" for a grassland ecosystem by compiling results from nine independently conducted climate change experiments. Each experiment manipulated growing season precipitation (GSP) and measured responses in aboveground net primary production (ANPP). We compared results from experiments with long-term (33-yr) annual precipitation and ANPP records to ask if collectively (n = 44 experiment-years) experiments yielded estimates of ANPP, rain-use efficiency (RUE, grams per square meter ANPP per mm precipitation), and the relationship between GSP and ANPP comparable to observations. We found that mean ANPP and RUE from experiments did not deviate from observations. Experiments and observational data also yielded similar functional relationships between ANPP and GSP, but only within the range of historically observed GSP. Fewer experiments imposed extreme levels of GSP (outside the observed 33-yr record), but when these were included, they altered the GSP-ANPP relationship. This result underscores the need for more experiments imposing extreme precipitation levels to resolve how forecast changes in climate regimes will affect ecosystem function in the future.

Drought timing, not previous drought exposure, determines sensitivity of two shortgrass species to water stress.

Climate change will alter global precipitation patterns, making it increasingly important that we understand how ecosystems will be impacted by more frequent and severe droughts. Yet most drought studies examine a single, within-season drought, and we know relatively little about the impacts of multiple droughts that occur within a single growing season. This distinction is important because many plant species are able to acclimate physiologically, such that the effects of multiple droughts on ecosystem function deviate significantly from the effects of cumulative, independent droughts. Unfortunately, we know relatively little about the ability of dominant species to acclimate to drought in drought-sensitive ecosystems like semi-arid grasslands. Here, we tested for physiological acclimation to multiple drought events in two dominant shortgrass steppe species: Bouteloua gracilis (C4) and Elymus elymoides (C3). Neither species exhibited physiological acclimation to drought; leaf water potential, stomatal conductance, and photosynthesis rates were all similarly affected by a single, late period drought and a second, late period drought. Biomass was lowest in plants exposed to two droughts, but this is likely due to the cumulative effects of both an early and late period drought. Our results suggest that late period droughts do exert weaker effects on biomass production of two dominant shortgrass species, but that the weaker effects are due to ontogenetic changes in plant physiology as opposed to physiological acclimation against multiple droughts. As a consequence, current ecosystem models that incorporate grass phenology and seasonal physiology should provide accurate predictions of primary production under future climates.

Psychobehavioral Profiles to Assist Tailoring of Interventions for Patients With Hypertension: Latent Profile Analysis.

BACKGROUND: Practice guidelines advocate combining pharmacotherapy with lifestyle counseling for patients with hypertension. To allow for appropriate tailoring of interventions to meet individual patient needs, a comprehensive understanding of baseline patient characteristics is essential. However, few studies have empirically assessed behavioral profiles of hypertensive patients in Web-based lifestyle counseling programs. OBJECTIVE: The objectives of this study were to (1) specify baseline psychobehavioral profiles of patients with hypertension who were enrolled in a Web-based lifestyle counseling trial, and (2) examine mean differences among the identified profile groups in demographics, psychological distress, self-reported self-care behaviors, physiological outcomes, and program engagement to determine prognostic implications. METHODS: Participants (N=264; mean age 57.5 years; 154/264, 58.3% female; 193/264, 73.1% white) were recruited into a longitudinal, double-blind, randomized controlled trial, designed to evaluate an online lifestyle intervention for hypertensive patients. A series of latent profile analyses identified psychobehavioral profiles, indicated by baseline measures of mood, motivation, and health behaviors. Mean differences between profile groups were then explored. RESULTS: A 2-class solution provided the best model fit (the Bayesian information criterion (BIC) is 10,133.11; sample-size adjusted BIC is 10,006.54; Lo-Mendell-Rubin likelihood ratio test is 65.56, P=.001). The 2 profile groups were (1) adaptive adjustment, marked by low distress, high motivation, and somewhat satisfactory engagement in health behaviors and (2) affectively distressed, marked by clinically significant distress. At baseline, on average, affectively distressed patients had lower income, higher body mass index, and endorsed higher stress compared with their adaptive adjustment counterparts. At 12-months post intervention, treatment effects were sustained for systolic blood pressure and Framingham risk index in the adaptive adjustment group, and those in the adaptive adjustment group were 2.4 times more likely to complete the 12-month intervention study, compared with their affectively distressed counterparts. CONCLUSIONS: Interventions for patients who are adaptively adjusted may differ in focus from those designed for the affectively distressed patients. As such, this study underscores the importance of identifying psychobehavioral profiles, as they allow for evidence-based tailoring of lifestyle counseling programs for patients with hypertension. TRIAL REGISTRATION: ClinicalTrials.gov NCT01541540; https://clinicaltrials.gov/ct2/show/NCT01541540 (Archived by WebCite at http://www.webcitation.org/6yzZYZcWF).

Nonpublication Rates and Characteristics of Registered Randomized Clinical Trials in Digital Health: Cross-Sectional Analysis.

BACKGROUND: Clinical trials are key to advancing evidence-based medical research. The medical research literature has identified the impact of publication bias in clinical trials. Selective publication for positive outcomes or nonpublication of negative results could misdirect subsequent research and result in literature reviews leaning toward positive outcomes. Digital health trials face specific challenges, including a high attrition rate, usability issues, and insufficient formative research. These challenges may contribute to nonpublication of the trial results. To our knowledge, no study has thus far reported the nonpublication rates of digital health trials. OBJECTIVE: The primary research objective was to evaluate the nonpublication rate of digital health randomized clinical trials registered in ClinicalTrials.gov. Our secondary research objective was to determine whether industry funding contributes to nonpublication of digital health trials. METHODS: To identify digital health trials, a list of 47 search terms was developed through an iterative process and applied to the "Title," "Interventions," and "Outcome Measures" fields of registered trials with completion dates between April 1, 2010, and April 1, 2013. The search was based on the full dataset exported from the ClinlicalTrials.gov database, with 265,657 trials entries downloaded on February 10, 2018, to allow publication of studies within 5 years of trial completion. We identified publications related to the results of the trials through a comprehensive approach that included an automated and manual publication-identification process. RESULTS: In total, 6717 articles matched the a priori search terms, of which 803 trials matched our latest completion date criteria. After screening, 556 trials were included in this study. We found that 150 (27%) of all included trials remained unpublished 5 years after their completion date. In bivariate analyses, we observed statistically significant differences in trial characteristics between published and unpublished trials in terms of the intervention target condition, country, trial size, trial phases, recruitment, and prospective trial registration. In multivariate analyses, differences in trial characteristics between published and unpublished trials remained statistically significant for the intervention target condition, country, trial size, trial phases, and recruitment; the odds of publication for non-US-based trials were significant, and these trials were 3.3 (95% CI 1.845-5.964) times more likely to be published than US-based trials. We observed a trend of 1.5 times higher nonpublication rates for industry-funded trials. However, the trend was not statistically significant. CONCLUSIONS: In the domain of digital health, 27% of registered clinical trials results are unpublished, which is lower than nonpublication rates in other fields. There are substantial differences in nonpublication rates between trials funded by industry and nonindustry sponsors. Further research is required to define the determinants and reasons for nonpublication and, more importantly, to articulate the impact and risk of publication bias in the field of digital health trials.

Pushing precipitation to the extremes in distributed experiments: recommendations for simulating wet and dry years.

Intensification of the global hydrological cycle, ranging from larger individual precipitation events to more extreme multiyear droughts, has the potential to cause widespread alterations in ecosystem structure and function. With evidence that the incidence of extreme precipitation years (defined statistically from historical precipitation records) is increasing, there is a clear need to identify ecosystems that are most vulnerable to these changes and understand why some ecosystems are more sensitive to extremes than others. To date, opportunistic studies of naturally occurring extreme precipitation years, combined with results from a relatively small number of experiments, have provided limited mechanistic understanding of differences in ecosystem sensitivity, suggesting that new approaches are needed. Coordinated distributed experiments (CDEs) arrayed across multiple ecosystem types and focused on water can enhance our understanding of differential ecosystem sensitivity to precipitation extremes, but there are many design challenges to overcome (e.g., cost, comparability, standardization). Here, we evaluate contemporary experimental approaches for manipulating precipitation under field conditions to inform the design of 'Drought-Net', a relatively low-cost CDE that simulates extreme precipitation years. A common method for imposing both dry and wet years is to alter each ambient precipitation event. We endorse this approach for imposing extreme precipitation years because it simultaneously alters other precipitation characteristics (i.e., event size) consistent with natural precipitation patterns. However, we do not advocate applying identical treatment levels at all sites - a common approach to standardization in CDEs. This is because precipitation variability varies >fivefold globally resulting in a wide range of ecosystem-specific thresholds for defining extreme precipitation years. For CDEs focused on precipitation extremes, treatments should be based on each site's past climatic characteristics. This approach, though not often used by ecologists, allows ecological responses to be directly compared across disparate ecosystems and climates, facilitating process-level understanding of ecosystem sensitivity to precipitation extremes.

Sequence variation in vitamin K epoxide reductase gene is associated with survival and progressive coronary calcification in chronic kidney disease.

OBJECTIVE: Sequence variations in the gene(s) encoding vitamin K epoxide reductase complex subunit 1 (VKORC1), the enzyme target of warfarin, have been associated with increased cardiovascular disease in the general population. Coronary artery calcification (CAC) is a prevalent form of cardiovascular disease in chronic kidney disease. We tested the hypothesis that the VKORC1 rs8050894 CC genotype would be associated with mortality and progression of CAC ≤ 4 years. APPROACH AND RESULTS: This study is an observational, prospective study of 167 individuals with stages 3 to 5 chronic kidney disease. Survival ≤ 4 years was assessed in all participants, and CAC progression was measured in a subset of 86 patients. Participants with the CG/GG genotype of VKORC1 had higher baseline CAC scores (median score, 112 versus 299; P=0.036). Of those 86 patients who had a 4-year CAC score, those with the CG/GG genotype had an increased risk of progressive CAC (adjusted for age, diabetes mellitus, estimated glomerular filtration rate, and hypertension) compared with those with the CC genotype. Four-year mortality risk was 4 times higher for individuals with the CG/GG genotypes compared with individuals with the CC genotype (odds ratio, 3.8; 95% confidence interval, 1.2-12.5; P=0.02), adjusted for age, sex, diabetes mellitus, estimated glomerular filtration rate, baseline CAC, and hypertension. CONCLUSIONS: Patients with the CG/GG genotype of VKORC1 had a higher risk of CAC progression and a poorer survival. These data provide new perspectives on the potential extrahepatic role of VKORC1 in individuals with chronic kidney disease.

Lifesource XL-18 pedometer for measuring steps under controlled and free-living conditions.

The primary aim was to examine the criterion and construct validity and test-retest reliability of the Lifesource XL-18 pedometer (A&D Medical, Toronto, ON, Canada) for measuring steps under controlled and free-living activities. The influence of body mass index, waist size and walking speed on the criterion validity of XL-18 was also explored. Forty adults (35-74 years) performed a 6-min walk test in the controlled condition, and the criterion validity of XL-18 was assessed by comparing it to steps counted manually. Thirty-five adults participated in the free-living condition and the construct validity of XL-18 was assessed by comparing it to Yamax SW-200 (YAMAX Health & Sports, Inc., San Antonio, TX, USA). During the controlled condition, XL-18 did not significantly differ from criterion (P > 0.05) and no systematic error was found using Bland-Altman analysis. The accuracy of XL-18 decreased with slower walking speed (P = 0.001). During the free-living condition, Bland-Altman analysis revealed that XL-18 overestimated daily steps by 327 ± 118 than Yamax (P = 0.004). However, the absolute percent error (APE) (6.5 ± 0.58%) was still within an acceptable range. XL-18 did not differ statistically between pant pockets. XL-18 is suitable for measuring steps in controlled and free-living conditions. However, caution may be required when interpreting the steps recorded under slower speeds and free-living conditions.

E-counseling as an emerging preventive strategy for hypertension.

PURPOSE OF REVIEW: Lifestyle counseling that includes exercise training, diet modification, and medication adherence is critical to hypertension management. This article summarizes the efficacy of lifestyle counseling interventions in face-to-face, telehealth, and e-counseling settings. It also discusses the therapeutic potential of e-counseling as a preventive strategy for hypertension. RECENT FINDINGS: The recent proliferation of telehealth and e-counseling programs increases the reach of preventive counseling for patients with cardiovascular disorders. Blood pressure reduction following these interventions is comparable to face-to-face interventions. However, the effectiveness of e-counseling varies depending on the design features of the core protocol. An evidence-based guideline needs to be established that identifies e-counseling components which are independently associated with blood pressure reduction. As the Internet becomes more sophisticated, e-counseling is demonstrating a therapeutic advantage in comparison with other telehealth interventions. SUMMARY: Current evidence supports further development of preventive e-counseling programs for hypertension. A pressing challenge for investigators is to specify key evidence-based components of e-counseling that are essential to the core protocol. In order to achieve this goal, it will be necessary to ensure that e-counseling programs are also clinically organized, in order to guide patients through the process of initiating and sustaining therapeutic behavior change.

The effectiveness of loyalty rewards to promote the use of an Internet-based heart health program.

BACKGROUND: Internet-based health programs have been shown to be effective in reducing risk for cardiovascular disease. However, their rates of enrollment and engagement remain low. It is currently unclear whether rewards from established loyalty programs can serve as a conditioned stimulus to improve the use of a freely available Internet-based program. OBJECTIVE: The objectives of the study were to (1) examine enrollment rates and levels of engagement with the My Health eSupport program between a Conditioned Reward group and a Control group, and (2) investigate the influence of loyalty rewards and participant characteristics on levels of enrollment and program engagement. METHODS: The study sample (n=142,726) consisted of individuals who were offered enrollment in an Internet-based health intervention (My Health eSupport) after completing the Heart&Stroke Risk Assessment on the Heart and Stroke Foundation website. My Health eSupport programs provided encouragement and tips for lifestyle change. This is a free, self-guided, fully automated program that proactively delivers tailored email messages at 2-week intervals based on the participant's stage of motivational "readiness" and priority for lifestyle change. Participants in the Conditioned Reward group were offered a single exposure of 20 loyalty reward points from the Air Miles loyalty program for completing the Heart&Stroke Risk Assessment (10 reward points) and enrolling in the Internet-based program (10 reward points). Meanwhile, no rewards were given to the Control group participants. All data were collected between February 1, 2011 and February 10, 2012. RESULTS: In total, 51.38% (73,327/142,726) of individuals in the Conditioned Reward group and 48.62% (69,399/142,726) of individuals in the Control group completed the Heart&Stroke Risk Assessment. Subsequently, significantly more individuals from the Conditioned Reward group (52.96%, 38,835/73,327) enrolled in the My Health eSupport program than Controls (4.07%, 2826/69,399). Regression analyses indicated that individuals were 27.9 times (95% CI 26.4-29.4; P<.001) more likely to join the My Health eSupport program when presented with loyalty rewards controlling for gender, age, education, ethnicity, employment, and number of modifiable risk factors. However, ongoing engagement level was low in both groups and it was not influenced by loyalty rewards. Instead, individuals were more likely to engage with the My Health eSupport program if they were greater than 60 years of age (OR 12.56, 95% CI 5.66-27.8; P<.001), were female (OR 1.27, 95% CI 1.09-1.46; P=.002), or had one or more modifiable risk factors (OR 1.38, 95% CI 1.31-1.45; P<.001). CONCLUSIONS: Our findings suggest that a single exposure of loyalty rewards may be used to encourage individuals to enroll in an Internet-based preventative health program, but additional strategies are required to maintain engagement level. Future studies need to examine the schedules of loyalty reward reinforcement on the long-term engagement level of Internet-based health programs.

The EvalUation of goal-diRected activities to prOmote well-beIng and heAlth (EUROIA) scale: Psychometric evaluation with Confirmatory Factor Analysis.

OBJECTIVES: While state-based models of health-related quality of life (HRQL) are well-established in providing clinically relevant descriptions of HRQL status, they do not provide information on how to maintain or improve HRQL. The EvalUation of goal-diRected activities to prOmote well-beIng and heAlth (EUROIA), rooted in a novel process-based model of HRQL, measures goal-directed activities that are self-reported to promote HRQL as part of an individual's process of adapting to dynamic changes in health status. Our objectives were to condense and summarize the psychometric properties of the EUROIA by (i) defining and confirming its factor structure, (ii) evaluating its construct validity, and (iii) examining its internal consistency. METHODS: Principal component analysis was performed on the 18-item EUROIA to explore the underlying factor structure and condense the scale. Confirmatory factor analysis was conducted on the revised 14-item, 4-factor structure EUROIA instrument to evaluate the model fit. Data was obtained from adult participants with a diagnosis of chronic heart failure or advanced chronic kidney disease from 3 hospitals in Toronto, Canada. RESULTS: The revised 14-item EUROIA demonstrated 4 dimensions-Social Affiliation, fulfillment of Social Roles and Responsibilities, Self-Affirmation, and Eudaimonic Well-being-with a Cronbach's alpha of 0.83, representing good internal consistency. Our confirmatory factor analysis final model achieved good overall model fit: (χ2 / df = 1.80; Tucker-Lewis index = 0.90; comparative fit index = 0.93; standardized root-mean-square residual = 0.06; root-mean-square error of approximation = 0.06). All items exhibited a factor loading greater than λ > 0.4 and p < 0.001. CONCLUSION: The EUROIA holds clinical potential in its ability to provide informed feedback to patients on how they might maintain or modify their use of goal-directed activities to maintain and optimize perceived well-being.