Clinical Decision Support for Hypertension Management in Chronic Kidney Disease: A Randomized Clinical Trial.

Importance: Chronic kidney disease (CKD) affects 37 million adults in the United States, and for patients with CKD, hypertension is a key risk factor for adverse outcomes, such as kidney failure, cardiovascular events, and death. Objective: To evaluate a computerized clinical decision support (CDS) system for the management of uncontrolled hypertension in patients with CKD. Design, Setting, and Participants: This multiclinic, randomized clinical trial randomized primary care practitioners (PCPs) at a primary care network, including 15 hospital-based, ambulatory, and community health center-based clinics, through a stratified, matched-pair randomization approach February 2021 to February 2022. All adult patients with a visit to a PCP in the last 2 years were eligible and those with evidence of CKD and hypertension were included. Intervention: The intervention consisted of a CDS system based on behavioral economic principles and human-centered design methods that delivered tailored, evidence-based recommendations, including initiation or titration of renin-angiotensin-aldosterone system inhibitors. The patients in the control group received usual care from PCPs with the CDS system operating in silent mode. Main Outcomes and Measures: The primary outcome was the change in mean systolic blood pressure (SBP) between baseline and 180 days compared between groups. The primary analysis was a repeated measures linear mixed model, using SBP at baseline, 90 days, and 180 days in an intention-to-treat repeated measures model to account for missing data. Secondary outcomes included blood pressure (BP) control and outcomes such as percentage of patients who received an action that aligned with the CDS recommendations. Results: The study included 174 PCPs and 2026 patients (mean [SD] age, 75.3 [0.3] years; 1223 [60.4%] female; mean [SD] SBP at baseline, 154.0 [14.3] mm Hg), with 87 PCPs and 1029 patients randomized to the intervention and 87 PCPs and 997 patients randomized to usual care. Overall, 1714 patients (84.6%) were treated for hypertension at baseline. There were 1623 patients (80.1%) with an SBP measurement at 180 days. From the linear mixed model, there was a statistically significant difference in mean SBP change in the intervention group compared with the usual care group (change, -14.6 [95% CI, -13.1 to -16.0] mm Hg vs -11.7 [-10.2 to -13.1] mm Hg; P = .005). There was no difference in the percentage of patients who achieved BP control in the intervention group compared with the control group (50.4% [95% CI, 46.5% to 54.3%] vs 47.1% [95% CI, 43.3% to 51.0%]). More patients received an action aligned with the CDS recommendations in the intervention group than in the usual care group (49.9% [95% CI, 45.1% to 54.8%] vs 34.6% [95% CI, 29.8% to 39.4%]; P < .001). Conclusions and Relevance: These findings suggest that implementing this computerized CDS system could lead to improved management of uncontrolled hypertension and potentially improved clinical outcomes at the population level for patients with CKD. Trial Registration: ClinicalTrials.gov Identifier: NCT03679247.

Implementation of a Scalable Online Weight Management Programme in Clinical Settings: Protocol for the PROPS 2.0 Programme (Partnerships for Reducing Overweight and Obesity with Patient-Centered Strategies 2.0).

INTRODUCTION: There is an urgent need for scalable strategies for treating overweight and obesity in clinical settings. PROPS 2.0 (Partnerships for Reducing Overweight and Obesity with Patient-Centered Strategies 2.0) aims to adapt and implement the combined intervention from the PROPS Study at scale, in a diverse cross-section of patients and providers. METHODS AND ANALYSIS: We are implementing PROPS 2.0 across a variety of clinics at Brigham and Women's Hospital, targeting enrolment of 5000 patients. Providers can refer patients or patients can self-refer. Eligible patients must be ≥20 years old and have a body mass index (BMI) of ≥30 kg/m2 or a BMI of 25-29.9 kg/m2 plus another cardiovascular risk factor or obesity-related condition. After enrolment, patients register for the RestoreHealth online programme/app (HealthFleet Inc.) and participate for 12 months. Patients can engage with the programme and receive personalized feedback from a coach. Patient navigators help to enrol patients, enter updates in the electronic health record, and refer patients to additional resources. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework is guiding the evaluation. ETHICS AND DISSEMINATION: The Mass General Brigham Human Research Committee approved this protocol. An implementation guide will be created and disseminated, to help other sites adopt the intervention in the future. TRIAL REGISTRATION NUMBER: NCT0555925.

Associations between neighborhood socioeconomic deprivation, IFNγ, and high-density lipoprotein particle size: Data from the Washington, D.C. cardiovascular health and needs assessment.

INTRODUCTION: Neighborhood socioeconomic deprivation is associated with increased cardiovascular risk factors, including inflammation. Inflammation plays an important role in modifying the cardioprotective function of high-density lipoprotein (HDL). Moreover, recent studies suggest that very high HDL is associated with adverse cardiovascular disease (CVD) outcomes. Thus, we sought to explore the relationships between neighborhood socioeconomic deprivation as a marker of chronic stress, inflammation, proprotein convertase subtilisin/kexin type 9 (PCSK9) (a core component of the HDL proteome), HDL characterisitcs, and biological aging as a predictor of CVD and all-cause mortality. METHODS: Sixty African American subjects were recruited to the NIH Clinical Center as part of a community-based participatory research-designed observational study. Neighborhood deprivation index (NDI), a marker of neighborhood socioeconomic deprivation, was measured using US Census data. HDL characteristics (cholesterol, particle number, size, subspecies) were determined from NMR lipoprotein profiling, and plasma cytokines (IL-1ß, IL-6, IL-8, TNFα, IFNγ) were measured using an ELISA-based multiplex technique. Epigenetic clock biomarkers of aging were measured using DNA methylation data obtained from participants' buffy coat samples. We used linear regression modeling adjusted for atherosclerotic cardiovascular disease (ASCVD) risk score, body mass index (BMI), and lipid-lowering medication use to investigate relationships of interest. RESULTS: NDI directly associated with large HDL particle count (H7P) and IFNγ and trended toward significance with HDL-C and PCSK9. IFNγ and PCSK9 then directly associated with H7P. H7P also directly associated with higher DNA methylation phenotypic age (PhenoAge). CONCLUSION: We highlight associations between neighborhood socioeconomic deprivation, IFNγ, PCSK9, HDL subspecies, and epigenetic biomarkers of aging. Taken together, our findings suggest indirect pathways linking neighborhood deprivation-related stress and inflammation to HDL and immune epigenetic changes. Moreover, these results add to recent work showing the pathogenicity of high HDL levels and underscore the need to understand how chronic stress-related inflammation and lipoprotein subspecies relate to CVD risk across diverse populations.

Associations among maternal characteristics, labour interventions, delivery mode and maternal antenatal complications in a NSW large rural town, and comparison to NSW state data.

OBJECTIVE: To determine associations between maternal characteristics, labour interventions, delivery mode and maternal antenatal complications in a NSW rural hospital, and compare these to state data. METHODS: Data (maternal characteristics, labour type, delivery mode and maternal antenatal complications) pertaining to women who had delivered a singleton birth at Griffith Base hospital were analysed. DESIGN: Retrospective data analysis of Griffith Base Hospital 'eMaternity' database SETTING: Single large rural town in NSW. PARTICIPANTS: Women who delivered a singleton birth between July 2018 and June 2019 inclusive at Griffith Base Hospital. MAIN OUTCOME MEASURES: 1. Comparison of maternal characteristics of age, BMI, gravida, parity and gestation data between labour type (spontaneous, augmented, induced and planned caesarean section) and delivery modes (vaginal, instrumental vaginal and caesarean section). 2. Associations between labour type, augmentation or induction method, delivery mode and maternal antenatal complications. 3. Multiple regression analysis for influence of age, BMI, parity and labour type on emergency caesarean section outcome. 4. Comparison of maternal, labour and delivery data with NSW state data. RESULTS: Among 457 women, there were higher rates of obesity and spontaneous labour, lower rates of planned caesarean section and augmented labour, and similar rates of induction of labour and emergency caesarean section, compared with NSW. Emergency caesarean section was significantly associated with older age (ß = 0.163), and labour augmentation (ß = 0.114) and induction (ß = 0.169). Labour augmentation with synthetic oxytocin, and induction with balloon catheter, were associated with the highest rates of emergency caesarean section. CONCLUSION: This large rural town had fewer labour and delivery medical interventions compared with NSW overall. Augmentation and induction of labour contribute to increasing caesarean section rates: directly via associations with emergency caesarean section, and indirectly because previous caesarean section was the most common reason for elective caesarean section.

Intrinsic fluctuations in sustained attention and distractor processing.

Although sustaining a moderate level of attention is critical in daily life, evidence suggests that attention is not deployed consistently, but rather fluctuates from moment to moment between optimal and suboptimal states. To better characterize these states in humans, the present study uses a gradual-onset continuous performance task with irrelevant background distractors to explore the relationship among behavioral fluctuations, brain activity, and, in particular, the processing of visual distractors. Using fMRI, we found that reaction time variability, a continuous measure of attentional instability, was positively correlated with activity in task-positive networks and negatively correlated with activity in the task-negative default mode network. We also observed greater processing of distractor images during more stable and less error prone "in the zone" epochs compared with suboptimal "out of the zone" epochs of the task. Overall, the data suggest that optimal states of attention are accomplished with more efficient and potentially less effortful recruitment of task-relevant resources, freeing remaining resources to process task irrelevant features of the environment.

Sustaining visual attention in the face of distraction: a novel gradual-onset continuous performance task.

Sustained attention is a fundamental aspect of human cognition and has been widely studied in applied and clinical contexts. Despite a growing understanding of how attention varies throughout task performance, moment-to-moment fluctuations are often difficult to assess. In order to better characterize fluctuations in sustained visual attention, in the present study we employed a novel continuous performance task (CPT), the gradual-onset CPT (gradCPT). In the gradCPT, a central face stimulus gradually transitions between individuals at a constant rate (1,200 ms), and participants are instructed to respond to each male face but not to a rare target female face. In the distractor-present version, the background distractors consist of scene images, and in the distractor-absent condition, of phase-scrambled scene images. The results confirmed that the gradCPT taxes sustained attention, as vigilance decrements were observed over the task's 12-min duration: Participants made more commission errors and showed increasingly variable response latencies (RTs) over time. Participants' attentional states also fluctuated from moment to moment, with periods of higher RT variability being associated with increased likelihood of errors and greater speed-accuracy trade-offs. In addition, task performance was related to self-reported mindfulness and the propensity for attention lapses in everyday life. The gradCPT is a useful tool for studying both low- and high-frequency fluctuations in sustained visual attention and is sensitive to individual differences in attentional ability.

In the zone or zoning out? Tracking behavioral and neural fluctuations during sustained attention.

Despite growing recognition that attention fluctuates from moment-to-moment during sustained performance, prevailing analysis strategies involve averaging data across multiple trials or time points, treating these fluctuations as noise. Here, using alternative approaches, we clarify the relationship between ongoing brain activity and performance fluctuations during sustained attention. We introduce a novel task (the gradual onset continuous performance task), along with innovative analysis procedures that probe the relationships between reaction time (RT) variability, attention lapses, and intrinsic brain activity. Our results highlight 2 attentional states-a stable, less error-prone state ("in the zone"), characterized by higher default mode network (DMN) activity but during which subjects are at risk of erring if DMN activity rises beyond intermediate levels, and a more effortful mode of processing ("out of the zone"), that is less optimal for sustained performance and relies on activity in dorsal attention network (DAN) regions. These findings motivate a new view of DMN and DAN functioning capable of integrating seemingly disparate reports of their role in goal-directed behavior. Further, they hold potential to reconcile conflicting theories of sustained attention, and represent an important step forward in linking intrinsic brain activity to behavioral phenomena.

Aberrant functional connectivity in autism: evidence from low-frequency BOLD signal fluctuations.

A number of recent studies have examined functional connectivity in individuals with Autism Spectrum Disorders (ASD), generally converging on the finding of reduced interregional coordination, or underconnectivity. Underconnectivity has been reported between many brain regions and across a range of cognitive tasks, and has been proposed to underlie behavioral and cognitive impairments associated with ASD. The current study employed functional connectivity MRI (fcMRI) to examine interregional correlations of low-frequency BOLD signal fluctuations in 10 high-functioning participants with ASD and 10 typically developing control participants. Whole-brain connectivity with three seed regions of interest (left middle frontal, left superior parietal, and left middle occipital cortex) was evaluated using fMRI datasets acquired during performance of a source recognition task. While fcMRI patterns were found to be largely similar across the two groups, including many common areas, effects for the ASD group were generally more extensive. These findings, although inconsistent with generalized underconnectivity in ASD, are compatible with a model of aberrant connectivity in which the nature of connectivity disturbance (i.e., increased or reduced) may vary by region. Taking into consideration methodological factors that might influence measured fcMRI effects, we suggest that ASD is associated with an inefficiency in optimizing network connections to achieve task performance.