Changes in Anticholinergic Burden in Parkinson's Disease After Deep Brain Stimulation.

OBJECTIVE: This study aimed to evaluate the effect of deep brain stimulation (DBS) on anticholinergic burden in Parkinson's disease (PD) and the association of anticholinergic burden with cognition. MATERIALS AND METHODS: A retrospective chart review in patients with PD who underwent bilateral subthalamic nucleus (STN) or globus pallidus internus (GPi) DBS from 2010 to 2020 reviewed medications with anticholinergic burden at baseline, six months, and one year (N = 216) after surgery. The cumulative anticholinergic burden at each visit was calculated using the Anticholinergic Risk Scale (ARS). RESULTS: ARS scores were significantly lower for patients six months and one year after surgery than at baseline (z = 6.58, p < 0.0001; z = 6.99, p < 0.0001). Change in ARS scores at both six months and one year were driven by down-titration of PD medications (z = 9.35, p < 0.0001; z = 8.61, p < 0.0001), rather than changes in pain, psychiatric, or urinary medications with anticholinergic effects. There was no significant difference in change in ARS scores at one year between targets (t = 0.41, p = 0.68). In addition, there was no significant association between anticholinergic burden and cognitive performance. CONCLUSION: GPi and STN DBS are associated with decreased anticholinergic burden due to PD medications in the first year after surgery.

Opal Actigraphy (Activity and Sleep) Measures Compared to ActiGraph: A Validation Study.

Physical activity and sleep monitoring in daily life provide vital information to track health status and physical fitness. The aim of this study was to establish concurrent validity for the new Opal Actigraphy solution in relation to the widely used ActiGraph GT9X for measuring physical activity from accelerometry epic counts (sedentary to vigorous levels) and sleep periods in daily life. Twenty participants (age 56 + 22 years) wore two wearable devices on each wrist for 7 days and nights, recording 3-D accelerations at 30 Hz. Bland-Altman plots and intraclass correlation coefficients (ICCs) assessed validity (agreement) and test-retest reliability between ActiGraph and Opal Actigraphy sleep durations and activity levels, as well as between the two different versions of the ActiGraph. ICCs showed excellent reliability for physical activity measures and moderate-to-excellent reliability for sleep measures between Opal versus Actigraph GT9X and between GT3X versus GT9X. Bland-Altman plots and mean absolute percentage error (MAPE) also show a comparable performance (within 10%) between Opal and ActiGraph and between the two ActiGraph monitors across activity and sleep measures. In conclusion, physical activity and sleep measures using Opal Actigraphy demonstrate performance comparable to that of ActiGraph, supporting concurrent validation. Opal Actigraphy can be used to quantify activity and monitor sleep patterns in research and clinical studies.

Assessment of balance in people with mild traumatic brain injury using a balance systems model approach.

PURPOSE: Measuring persistent imbalance after mTBI is challenging and may include subjective symptom-reporting as well as clinical scales. Clinical assessments for quantifying balance following mTBI have focused on sensory orientation. It is theorized that balance control goes beyond sensory orientation and also includes subdomains of anticipatory postural adjustments, reactive postural control, and dynamic gait. The Mini Balance Evaluation Systems Test (Mini-BESTest) is a validated balance test that measures balance according to these subdomains for a more comprehensive assessment. The purpose of this study was to compare Mini-BESTest total and subdomain scores after subacute mTBI with healthy controls. METHODS: Symptomatic mTBI (n = 90, 20 % male, age=36.0 ± 12.0, 46.3.4 ± 22.1 days since injury) and healthy control (n = 45, 20 % male, age=35.4 ± 12.5) participants completed the Mini-BESTest for balance. Mini-BESTest between-group differences were evaluated using Wilcoxon rank-sum tests. RESULTS: The mTBI group (Median[minimum,maximum]) had a significantly worse Mini-BESTest total score than the healthy controls (24[18,28] vs 27[23-28], p < 0.001). The mTBI group performed significantly worse in 3 of the 4 subdomains compared to the healthy controls: reactive postural control: 5[2-6] vs 6[3-6], p = 0.003; sensory orientation: 6[5,6] vs 6[6], p = 0.005; dynamic gait: 8[5-10] vs 9[8-10], p < 0.001. There was no significance difference between groups in the anticipatory postural adjustments domain (5[3-6] vs 5[3-6], p = 0.12). CONCLUSIONS: The Mini-BESTest identified deficits in people with subacute mTBI in the total score and 3 out of 4 subdomains, suggesting it may be helpful to use in the clinic to identify balance subdomain deficits in the subacute mTBI population. In combination with self-reported assessments, the mini-BESTest may identify balance domain deficits in the subacute mTBI population and help guide treatment for this population.

Patient- and caregiver-reported factors associated with school absenteeism in children with chronic kidney disease.

BACKGROUND: Children with chronic kidney disease (CKD) are at risk for neurocognitive deficits while simultaneously being at risk for chronic school absenteeism (≥ 18 school days per school year). Chronic school absenteeism compounds the negative impacts of CKD on academic achievement. In this study, we examined patient- and caregiver-reported factors associated with school absenteeism in children with non-dialysis- or transplant-dependent CKD in order to help identify which factors could be modifiable and ultimately improve school attendance. METHODS: We utilized a combination of chart review and questionnaires distributed in person to patients and caregivers at a pediatric nephrology clinic between November 2018 and August 2019 to gather data. We used descriptive statistics to illustrate clinical characteristics of the children included in the study, caregiver characteristics, and examined reported reasons for missing school. RESULTS: Twenty-one percent of participants (10/48) missed 18 full days of school or more, categorizing them as chronically absent. The top three reasons for missing school were doctor appointments, feeling sick, and being bullied. More specific sequelae of CKD were not highly reported as reasons for missing school. CONCLUSIONS: Chronic absenteeism is a highly reported phenomenon among children with pediatric CKD. Given that missing school for doctor appointments was a top reason for absenteeism, this data suggests alternative appointment hours and virtual appointments may reduce chronic school absenteeism in children, and by extension improve their health, behavioral, and academic outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Symptoms and Central Sensory Integration in People With Chronic mTBI: Clinical Implications.

INTRODUCTION: Balance deficits in people with chronic mild traumatic brain injury (mTBI; ≥3 months post-mTBI), thought to relate to central sensory integration deficits, are subtle and often difficult to detect. The purpose of this study was to determine the sensitivity of the instrumented modified clinical test of sensory integration for balance (mCTSIB) in identifying such balance deficits in people with symptomatic, chronic mTBI and to establish the associations between balance and mTBI symptom scores in the chronic mTBI group. METHODS: The Institutional Review Board approved these study methods. Forty-one people with chronic mTBI and balance complaints and 53 healthy controls performed the mCTSIB (eyes open/closed on firm/foam surfaces; EoFi, EcFi, EoFo, and EcFo) with a wearable sensor on their waist to quantify sway area (m2/s4). Sensory reweighting variables were calculated for the firm and foam stance conditions. A stopwatch provided the clinical outcome for the mCTSIB (time). Each participant completed the Neurobehavioral Symptom Inventory (NSI), which quantifies mTBI-related symptoms and provides a total score, as well as sub-scores on affective, cognitive, somatic, and vestibular domains. RESULTS: The mTBI group reported significantly higher symptom scores across each NSI sub-score (all Ps < .001). The mTBI group had a significantly larger sway area than the control group across all mCTSIB conditions and the mTBI group had significantly higher sensory reweighting scores compared to the control group on both the firm (P = .01) and foam (P = .04) surfaces. Within the mTBI group, the NSI vestibular score significantly related to the mCTSIB sway area EcFi (r = 0.38; P = .02), sway area EcFo (r = 0.43; P = .006), sensory reweighting firm (r = 0.33; P = .04), and sensory reweighting foam (r = 0.38; P = .02). The average sway area across the 4 mCTSIB conditions was significantly (area under the curve: 0.77; P < .001) better at differentiating groups than the mCTSIB clinical total score. The average sway area across the 4 mCTSIB conditions had a sensitivity of 73% and a specificity of 71%. The clinical mCTSIB outcome scores were not different between groups. CONCLUSION: People with chronic mTBI appear to have central sensory integration deficits detectable by instrumented measures of postural assessment. These findings suggest that central sensory integration should be targeted in rehabilitation for people with chronic mTBI.

The novel estrogen receptor modulator STX attenuates Amyloid-ß neurotoxicity in the 5XFAD mouse model of Alzheimer's disease.

Based on previous evidence that the non-steroidal estrogen receptor modulator STX mitigates the effects of neurotoxic Amyloid-ß (Aß) in vitro, we have evaluated its neuroprotective benefits in a mouse model of Alzheimer's disease. Cohorts of 5XFAD mice, which begin to accumulate cerebral Aß at two months of age, were treated with orally-administered STX starting at 6 months of age for two months. After behavioral testing to evaluate cognitive function, biochemical and immunohistochemical assays were used to analyze key markers of mitochondrial function and synaptic integrity. Oral STX treatment attenuated Aß-associated mitochondrial toxicity and synaptic toxicity in the brain, as previously documented in cultured neurons. STX also moderately improved spatial memory in 5XFAD mice. In addition, STX reduced markers for reactive astrocytosis and microgliosis surrounding amyloid plaques, and also unexpectedly reduced overall levels of cerebral Aß in the brain. The neuroprotective effects of STX were more robust in females than in males. These results suggest that STX may have therapeutic potential in Alzheimer's Disease.

Gastrointestinal Motility and Response to Levodopa in Parkinson's Disease: A Proof-of-Concept Study.

BACKGROUND: Simultaneous measurement of gastrointestinal transit time (GITT) and plasma levodopa concentration (PLC) is crucial to understanding the effect of dysfunctional motility on levodopa response in patients with Parkinson's disease (PwPD). OBJECTIVE: The aim is to determine if altered segmental GITT correlates with clinical response and PLC variability in PwPD. METHODS: Ten typical and 10 erratic responders ingested the SmartPill (SP) wireless motility capsule. Serial PLC and finger tapping, obtained every 30 minutes for 3 hours after SP/levodopa ingestion, evaluated the correlation between GITT, clinical response, and PLC. Glucose breath testing assessed small intestinal bacterial overgrowth (SIBO). RESULTS: GITT was not significantly different in "typical" and "erratic" responders. SIBO was positive in half of the erratic and negative in most typical responders. CONCLUSION: SP is a feasible technology for assessing GITT in PwPD. A larger study may be able to significantly differentiate/correlate GITT in different segments of the GI tract with response to levodopa. © 2022 International Parkinson and Movement Disorder Society.

α-Synuclein Seed Amplification in CSF and Brain from Patients with Different Brain Distributions of Pathological α-Synuclein in the Context of Co-Pathology and Non-LBD Diagnoses.

OBJECTIVE: The purpose of this study was to determine the sensitivity and specificity of α-synuclein seed amplification assay (αSyn-SAA) in antemortem and postmortem cerebrospinal fluid (CSF) of autopsy-confirmed patients with different distributions of pathological αSyn, co-pathologies, and clinical diagnoses. METHODS: The αSyn-SAA was used to test antemortem CSF samples from 119 subjects with a variety of clinical syndromes and standardized neuropathological examinations from Oregon Health and Science University (OHSU) and University of California San Diego (UCSD; 56 additional postmortem CSF samples available). The αSyn-SAA was also applied to frontal cortex and amygdala homogenates. Sensitivity and specificity were compared across distributions of αSyn pathology. Clinical data and co-pathologies were compared across αSyn-SAA positive and negative groups. RESULTS: Fifty-three individuals without and 66 with αSyn-pathology (neocortical [n = 38], limbic [n = 7], and amygdala-predominant [n = 21]) were included. There was a sensitivity of 97.8% and specificity of 98.1% of the αSyn-SAA to identify patients with limbic/neocortical pathology from antemortem CSF. Sensitivity to detect amygdala-predominant pathology was only 14.3%. Postmortem CSF and brain tissue αSyn-SAA analyses also showed higher assay positivity in samples from limbic/neocortical cases. INTERPRETATION: CSF αSyn-SAA reliably identifies αSyn seeds in patients with diffuse αSyn pathology in the context of co-pathology and non-Lewy body disease (LBD) diagnoses. The analysis of brain homogenates suggests that pathological αSyn in the amygdala might differ from pathological αSyn in the frontal cortex. The αSyn-SAA might facilitate the differential diagnosis of dementias with mixed pathologies. ANN NEUROL 2022;92:650-662.

Exploring Age and Sex Patterns for Rehabilitation Referrals After a Concussion: A Retrospective Analysis.

Objective: To explore patterns of postconcussion care at a level 1 trauma center. Design: Retrospective cohort study. Setting: U.S. level 1 trauma center and local satellite units. Participants: Patients of any age with a concussion diagnosis that reported to level 1 trauma center and local satellite units between 2016 and 2018 (N=2417). Intervention: Not applicable. Main Outcome Measures: Age, sex, point of entry, rehabilitation referrals, and pre-existing comorbidity diagnosis. Results: Patient age (mean [SD]) significantly differed among points of entry, from youngest to oldest: 26.0 (14.0) years in sports medicine, 29.3 (23.0) years in the emergency department, 34.6 (23.6) years at primary care providers, and 46.0 (19.7) years at specialty care departments. Sex also significantly differed among points of entry; emergency departments reported more men (55.6%), whereas the other points of entry reported more women (59.3%-65.6%). Patients were more likely to receive a referral from sports medicine (odds ratio [OR]unadjusted=75.05, P<.001), primary care providers (ORunadjusted=7.98, P<.001), and specialty care departments (ORunadjusted=7.62, P<.001) than from the emergency department. Women were more likely to receive a referral (ORunadjusted=1.92, P<.0001), regardless of point of entry. Lastly, patients with a preexisting comorbidity were more likely (ORadjusted=2.12, P<.001) to get a rehabilitation referral than patients without a comorbidity. Conclusions: Point of entry, age, sex, and preexisting comorbidities are associated with postconcussion care rehabilitation referral patterns. Improving concussion education dissemination across all entry points of a level 1 trauma center may standardize the postconcussion rehabilitation referral patterns, potentially improving the time to recovery from a concussion.

Do sensorimotor control properties mediate sway in people with chronic balance complaints following mTBI?

BACKGROUND: Up to 40% of mild traumatic brain injuries (mTBI) can result in chronic unresolved symptoms, such as balance impairment, that persist beyond three months. Sensorimotor control, the collective coordination and regulation of both sensory and motor components of the postural control system, may underlie balance deficits in chronic mTBI. The aim of this study was to determine if the relationship between severity of impairment in chronic (> 3 months) mTBI and poorer balance performance was mediated by sensorimotor integration measures. METHODS: Data were collected from 61 healthy controls and 58 mTBI participants suffering persistent balance problems. Participants completed questionnaires (Dizziness Handicap Inventory (DHI), Neurobehavioral Symptom Inventory (NSI), and Sports Concussion Assessment Tool Symptom Questionnaire (SCAT2)) and performed instrumented postural sway assessments and a test of Central Sensory Motor Integration (CSMI). Exploratory Factor Analysis was used to reduce the variables used within the mediation models to constructs of impairment (Impairment Severity - based on questionnaires), balance (Sway Dispersion - based on instrumented postural sway measures), and sensorimotor control (Sensory Weighting, Motor Activation and Time Delay - based on parameters from CSMI tests). Mediation analyses used path analysis to estimate the direct effect (between impairment and balance) and indirect (mediating) effects (from sensorimotor control). RESULTS: Two out of three sensorimotor integration factors (Motor Activation and Time Delay) mediated the relationship between Impairment Severity and Sway Dispersion, however, there was no mediating effect of Sensory Weighting. SIGNIFICANCE: These findings have clinical implications since rehabilitation of balance commonly focuses on sensory cues. Our findings indicate the importance of Motor Activation and Time Delay, and thus a focus on strategies to improve factors related to these constructs throughout the rehabilitative process (i.e., level of muscular contractions to control joint torques; response time to stimuli/perturbations) may improve a patient's balance control.

Relationship Between Brain Volumes and Objective Balance and Gait Measures in Parkinson's Disease.

BACKGROUND: Instrumented measures of balance and gait measure more specific balance and gait impairments than clinical rating scales. No prior studies have used objective balance/gait measures to examine associations with ventricular and brain volumes in people with Parkinson's disease (PD). OBJECTIVE: To test the hypothesis that larger ventricular and smaller cortical and subcortical volumes are associated with impaired balance and gait in people with PD. METHODS: Regional volumes from structural brain images were included from 96 PD and 50 control subjects. Wearable inertial sensors quantified gait, anticipatory postural adjustments prior to step initiation (APAs), postural responses to a manual push, and standing postural sway on a foam surface. Multiple linear regression models assessed the relationship between brain volumes and balance/gait and their interactions in PD and controls, controlling for sex, age and corrected for multiple comparisons. RESULTS: Smaller brainstem and subcortical gray matter volumes were associated with larger sway area in people with PD, but not healthy controls. In contrast, larger ventricle volume was associated with smaller APAs in healthy controls, but not in people with PD. A sub-analysis in PD showed significant interactions between freezers and non-freezers, in several subcortical areas with stride time variability, gait speed and step initiation. CONCLUSION: Our models indicate that smaller subcortical and brainstem volumes may be indicators of standing balance dysfunction in people with PD whereas enlarged ventricles may be related to step initiation difficulties in healthy aging. Also, multiple subcortical region atrophy may be associated with freezing of gait in PD.

COVID-19 vaccination willingness among people with multiple sclerosis.

BACKGROUND: Hesitancy to receive COVID-19 vaccination is a major public health concern. COVID-19 vaccine willingness and the factors contributing to willingness in adults with multiple sclerosis (MS) is unknown. We administered an online survey from 1 December 2020 to 7 January 2021 to adults with MS to estimate COVID-19 vaccine willingness among adults with MS. Bivariate analysis with chi-square testing compared categorical variables associated with vaccine willingness. RESULTS: Of 401 respondents, 70.1% were willing to receive an authorized COVID-19 vaccination if it was available to them, 22.7% were unsure, and 7.2% were unwilling. The most frequent concern for those unsure was vaccine safety. Vaccine willingness was associated with increased perceived personal risk of COVID-19 (χ2 = 45.4; p < 0.0001), prior influenza vaccine acceptance (χ2 = 97.6; p < 0.0001), higher educational level (χ2 = 50.2; p < 0.0001), and if respondents discussed or planned to discuss the COVID-19 vaccine with their neurologists (χ2 = 64.3; p < 0.0001). CONCLUSION: While COVID-19 vaccination willingness is high among people with MS, nearly 30% were either unwilling or unsure about being vaccinated. Neurologists should be aware of patient-centered factors associated with COVID-19 vaccine willingness and address COVID-19 vaccine safety concerns in discussions with their vaccine-unsure MS patients.

Prolonged Treatment with Centella asiatica Improves Memory, Reduces Amyloid-ß Pathology, and Activates NRF2-Regulated Antioxidant Response Pathway in 5xFAD Mice.

BACKGROUND: The medicinal herb Centella asiatica has been long been used for its neuroprotective and cognitive enhancing effects. We have previously shown that two weeks of treatment with a water extract of Centella asiatica (CAW) improves cognition and activates the endogenous antioxidant response pathway without altering amyloid-ß (Aß) plaque burden. OBJECTIVE: Here, we assess the effect of long-term treatment of CAW in the 5xFAD mouse model of Aß accumulation. METHODS: Four-month-old 5xFAD mice were treated with CAW in their drinking water (2 g/L) for three months at which point they underwent cognitive testing as well as analysis of Aß plaque levels and antioxidant and synaptic gene expression. In order to confirm the involvement of the antioxidant regulatory transcription factor NRF2 on the effects of CAW on synaptic plasticity, neurons isolated from 5xFAD mice were also treated with CAW and the targeted inhibitor ML385. RESULTS: Three months of treatment with CAW improved spatial and contextual memory as well as executive function in 5xFAD mice. This improvement was accompanied by increased antioxidant gene expression and a decrease in Aß plaque burden relative to untreated 5xFAD animals. In isolated neurons, treatment with ML385 blocked the effects of CAW on dendritic arborization and synaptic gene expression. CONCLUSION: These results suggest that prolonged CAW exposure could be beneficial in Alzheimer's disease and that these effects likely involve NRF2 activation. Moreover, these findings suggest that targeting NRF2 itself may be a relevant therapeutic strategy for improving synaptic plasticity and cognitive function in Alzheimer's disease.

A Report of Tamoxifen and Parkinson's Disease in a US Population and a Review of the Literature.

BACKGROUND: Tamoxifen, a selective estrogen receptor modulator, has been shown to variably affect Parkinson's disease (PD) risk. OBJECTIVE: The aim of this study was to review epidemiological literature and evaluate the rate of PD in women with breast cancer with tamoxifen exposure in a US population. METHODS: A literature search was conducted to identify relevant studies. We performed a retrospective cohort analysis using the Nurses' Health Study Version One to report descriptive statistics. RESULTS: Most studies suggest there may be a time-dependent effect of tamoxifen on PD risk, with the risk increasing with time from exposure. However, rates of PD in persons exposed to tamoxifen overall appear to be low. In our cohort, PD was evident in 6.2 per 1,000 of those with tamoxifen use and 3.6 per 1,000 of those without tamoxifen use. Time from breast cancer to PD diagnosis was 9.7 years among women with tamoxifen exposure and 11.7 among women without. CONCLUSIONS: Tamoxifen may be associated with an increased risk for PD. Further research is needed to elucidate the role of estrogen and selective estrogen antagonism in PD. © 2021 International Parkinson and Movement Disorder Society.

Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging.

The water extract of Centella asiatica (CAW) improves cognitive and mitochondrial function and activates the nuclear factor erythroid 2-related factor 2 (NRF2) regulated antioxidant response pathway in aged mice. Here we investigate whether NRF2 activation is required for the cognitive and mitochondrial effects of prolonged CAW exposure during aging. Five-month-old NRF2 knockout (NRF2KO) and wild-type mice were treated with CAW for 1, 7, or 13 months. Each cohort underwent cognitive testing and hippocampal mitochondrial analyses. Age-related cognitive decline was accelerated in NRF2KO mice and while CAW treatment improved cognitive performance in wild-type mice, it had no effect on NRF2KO animals. Hippocampal mitochondrial function also declined further with age in NRF2KO mice and greater hippocampal mitochondrial dysfunction was associated with poorer cognitive performance in both genotypes. Long-term CAW treatment did not affect mitochondrial endpoints in animals of either genotype. These data indicate that loss of NRF2 results in accelerated age-related cognitive decline and worsened mitochondrial deficits. NRF2 also appears to be required for the cognitive enhancing effects of CAW during aging.

Associations Between Amantadine Usage, Gait, and Cognition in PSP: A post-hoc Analysis of the Davunetide Trial.

Introduction: Amantadine anecdotally improves gait in progressive supranuclear palsy (PSP) but definitive data is lacking. We investigated associations between amantadine usage, gait, cognition, and activities of daily living in 310 subjects with PSP using data from the davunetide trial. Method: We compared baseline demographics, PSP Rating Scale (PSPRS), Repeat Battery for the Assessment of Neuropsychological Status (RBANS), and Schwab and England Activities of Daily Living (SEADL) scores between subjects taking vs. not taking amantadine using chi-square tests for categorical variables and independent sample t-tests for continuous variables. Using the general linear model (GLM), we tested whether group status predicted total PSPRS, PSPRS-gait and midline, total RBANS, RBANS-attention, and SEADL before and after the 52-weeks follow-up. Results: Subjects taking vs. not taking amantadine were similar at baseline, except subjects taking amantadine had a higher Clinical Global Impression (CGI) Score (p = 0.01). However, the CGI change score did not differ between groups at week 52 (p = 0.10). Using GLM models (controlling for covariates), we found that subjects taking vs. not taking amantadine did not significantly predict total PSPRS, PSPRS-gait and midline, total RBANS, RBANS-attention, or SEADL at baseline, week 52, or the change score between baseline and week 52. Discussion: This post-hoc analysis of the davunetide trial did not find an association between amantadine and gait or cognitive measures in PSP, but was not powered to find such a difference. Future studies should still examine amantadine for symptomatic benefit in multiple PSP subtypes.

Associations of medium and long chain omega-3 polyunsaturated fatty acids with blood pressure in Hispanic and non-Hispanic smokers and nonsmokers.

Epidemiology studies and clinical trials have shown that omega-3 polyunsaturated fatty acids (n-3 PUFAs) are inversely associated with blood pressure. We sought to determine the influence of cigarette smoking and Hispanic ethnicity on this association. Age- and sex-matched smokers and nonsmokers (n = 98) 19-50 years old lacking cardiovascular disease were recruited. Systolic and diastolic blood pressure (SBP, DBP), heart rate, HbA1c, lipids, BMI, and RBC fatty acids were measured. The omega-3 index (percent eicosapentaenoic and docosahexaenoic acid, EPA+DHA, in RBCs) was significantly lower in smokers (Smokers: 3.19 ± 0.86%; Nonsmokers, 3.88 ± 1.05%, p = 0.001) and Hispanics (Hispanic 3.32 ± 0.93%; Non-Hispanic, 3.82 ± 1.03%, p = 0.006). DHA exhibited a significant inverse association with BP in both smokers and nonsmokers, while alpha-linolenic acid (ALA) exhibited a significant positive association with BP only in smokers. Multiple regression analyses showed that BMI, DHA, smoking status, and smoking status*ALA interaction significantly predicted SBP (p < 0.0001, R2 = 0.44) and DBP (p < 0.0001, R2 = 0.33), while ethnicity had no effect. The observed lower BP when DHA levels are high suggests a possible protective role of DHA on BP in normotensive smokers and nonsmokers. Additionally, the observed higher BP when ALA levels are high only in smokers suggests that ALA may influence the BP-lowering effects of chronic smoking.

Intervention Mediators in a Randomized Controlled Trial to Increase Colonoscopy Uptake Among Individuals at Increased Risk of Familial Colorectal Cancer.

BACKGROUND: Understanding the pathways by which interventions achieve behavioral change is important for optimizing intervention strategies. PURPOSE: We examined mediators of behavior change in a tailored-risk communication intervention that increased guideline-based colorectal cancer screening among individuals at increased familial risk. METHODS: Participants at increased familial risk for colorectal cancer (N = 481) were randomized to one of two arms: (1) a remote, tailored-risk communication intervention (Tele-Cancer Risk Assessment and Evaluation (TeleCARE)) or (2) a mailed educational brochure intervention. RESULTS: Structural equation modeling showed that participants in TeleCARE were more likely to get a colonoscopy. The effect was partially mediated through perceived threat (ß = 0.12, p < 0.05), efficacy beliefs (ß = 0.12, p < 0.05), emotions (ß = 0.22, p < 0.001), and behavioral intentions (ß = 0.24, p < 0.001). Model fit was very good: comparative fit index = 0.95, root-mean-square error of approximation = 0.05, and standardized root-mean-square residual = 0.08. CONCLUSION: Evaluating mediating variables between an intervention (TeleCARE) and a primary outcome (colonoscopy) contributes to our understanding of underlying mechanisms that lead to health behavior change, thus leading to better informed and designed future interventions. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov , NCT01274143.

Randomized Noninferiority Trial of Telephone Delivery of BRCA1/2 Genetic Counseling Compared With In-Person Counseling: 1-Year Follow-Up.

PURPOSE: The ongoing integration of cancer genomic testing into routine clinical care has led to increased demand for cancer genetic services. To meet this demand, there is an urgent need to enhance the accessibility and reach of such services, while ensuring comparable care delivery outcomes. This randomized trial compared 1-year outcomes for telephone genetic counseling with in-person counseling among women at risk of hereditary breast and/or ovarian cancer living in geographically diverse areas. PATIENTS AND METHODS: Using population-based sampling, women at increased risk of hereditary breast and/or ovarian cancer were randomly assigned to in-person (n = 495) or telephone genetic counseling (n = 493). One-sided 97.5% CIs were used to estimate the noninferiority effects of telephone counseling on 1-year psychosocial, decision-making, and quality-of-life outcomes. Differences in test-uptake proportions for determining equivalency of a 10% prespecified margin were evaluated by 95% CIs. RESULTS: At the 1-year follow-up, telephone counseling was noninferior to in-person counseling for all psychosocial and informed decision-making outcomes: anxiety (difference [d], 0.08; upper bound 97.5% CI, 0.45), cancer-specific distress (d, 0.66; upper bound 97.5% CI, 2.28), perceived personal control (d, -0.01; lower bound 97.5% CI, -0.06), and decisional conflict (d, -0.12; upper bound 97.5% CI, 2.03). Test uptake was lower for telephone counseling (27.9%) than in-person counseling (37.3%), with the difference of 9.4% (95% CI, 2.2% to 16.8%). Uptake was appreciably higher for rural compared with urban dwellers in both counseling arms. CONCLUSION: Although telephone counseling led to lower testing uptake, our findings suggest that telephone counseling can be effectively used to increase reach and access without long-term adverse psychosocial consequences. Further work is needed to determine long-term adherence to risk management guidelines and effective strategies to boost utilization of primary and secondary preventive strategies.