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How do we form mental links between related items? Forming associations between representations is a key feature of episodic memory and provides the foundation for learning and guiding behavior. Theories suggest that spatial context plays a supportive role in episodic memory, providing a scaffold on which to form associations, but this has mostly been tested in the context of autobiographical memory. We examined the memory boosting effect of spatial stimuli in memory using an associative inference paradigm combined with eye-tracking. Across two experiments, we found that memory was better for associations that included scenes, even indirectly, compared to objects and faces. Eye-tracking measures indicated that these effects may be partly mediated by greater fixations to scenes compared to objects, but did not explain the differences between scenes and faces. These results suggest that scenes facilitate associative memory and integration across memories, demonstrating evidence in support of theories of scenes as a spatial scaffold for episodic memory. A shared spatial context may promote learning and could potentially be leveraged to improve learning and memory in educational settings or for memory-impaired populations.

ObjectiveCompare the efficacy of two interventions addressing emotional and existential well-being in early life-limiting illness.MethodPrimary trial analysis (n = 135) included patients with advanced cancer, congestive heart failure, or end-stage renal disease; Arm 1 received the Outlook intervention, addressing issues of life completion and preparation, and Arm 2 received relaxation meditation (RM). Primary outcomes at five weeks (primary endpoint) and seven weeks (secondary): completion and preparation (QUAL-E); secondary outcomes: anxiety (POMS) quality of life (FACT-G) and spiritual well-being (FACIT-Sp) subscales of faith, meaning, and peace.ResultsAverage age was 62; 56% were post-high school-educated, 54% were married, 52% white, 44% female, and 70% had a cancer diagnosis. At baseline, participants demonstrated low levels of anxiety (p = 0.49) or seven weeks (15.2 vs.15.4; between-group difference −0.2 [95% CI, −1.5, 1.0], p = 0.73). There were also no significant differences in mean Life Completion by treatment arm between five weeks (26.6 Outlook vs. 26.3 RM; between-group difference 0.2 [95% CI, −1.2, 1.7], p = 0.76) or seven weeks (26.5 vs. 27.5; between-group difference −1.0 [95% CI, −2.7, 0.7], p = 0.23). Compared to RM, Outlook participants did not have significant differences over time in the secondary outcomes of overall quality of life, anxiety, depression, FACT-G subscales, and FACIT-Sp subscales.DiscussionIn early-stage life-limiting illness, Outlook did not demonstrate a significant difference in primary or secondary outcomes relative to RM. Results underscore the importance of pre-screening for distress. Qualitatively, Outlook participants were able to express suppressed emotions, place illness context, reflect on adaptations, and strengthen identity. Screening for distress and identifying specified measures of distress, beyond anxiety and depression, is essential in our ability to adequately assess the multi-dimensional mechanisms that decrease existential suffering.

A functional gradient has been proposed across the medial temporal lobes (MTL) such that the anterior MTL is thought to support processing of individual items (e.g., item memory and complex object perception), whereas the posterior MTL is thought to support item-context retrieval (e.g., source memory). Whereas functional imaging studies have provided evidence supporting this anatomical organization, results from structural analyses remain inconclusive. The current study examined the relationship between volume of MTL regions of interest (ROIs), and performance on a source memory task and a fine-grain complex object perception task, in healthy young adults (mean age = 21.5, range = 18-29). Using a semiautomated procedure, we segmented the parahippocampal and perirhinal cortices (PHC, PRC), posteromedial and anterolateral entorhinal cortices (pmERC, alERC), and posterior and anterior hippocampus (postHC, antHC) on high-resolution T2-weighted MRIs. Regional volumes were computed as proportions of intracranial volume, and as posterior-anterior volumetric ratios (PHC:PRC, pmERC:alERC, postHC:antHC). Partial-least squares regressions were applied to predict source and item memory, and perceptual discrimination accuracy, based on ROI and ratio volumes. In our ROI regressions, we found that postHC volume was positively correlated with a latent factor predicting source memory, and PRC and antHC volumes were negatively correlated to this latent factor. In our ratio regressions, we observed an effect relating the posterior-anterior distribution of gray matter across the MTL with source memory. Our results demonstrate differential associations between anterior and posterior MTL and source memory performance. Findings from this study highlight the importance of considering patterns of structure-behavior associations in the neurobiology of episodic memory.

SIGNIFICANCE Outpatient vision rehabilitation improves function in veterans with vision impairment, but the prevalence of cognitive impairment and the degree to which it may affect rehabilitation outcomes in the Veterans Affairs system are unknown. PURPOSE The purpose of this study was to determine the prevalence of cognitive impairment among veterans receiving outpatient vision rehabilitation in the Veterans Affairs system and compare the benefits of rehabilitation in veterans with and without cognitive impairment. METHODS We conducted cognitive assessments and a nested longitudinal cohort study in veterans with eye disorders at two outpatient rehabilitation sites. Cognition was assessed with the Modified Telephone Interview for Cognitive Status administered in person. Eligible veterans and their companions in the longitudinal study responded to questions about the veteran's function at baseline and 90 days later. Visual function was measured with the 48-item Low Vision Visual Function Questionnaire (LV-VFQ-48) and items from the Activity Inventory. RESULTS Of 291 veterans assessed (mean ± standard deviation age, 78.2 ± 12 years), 136 (46.7%) were cognitively intact (Modified Telephone Interview for Cognitive Status scores, ≥33), whereas 58 (19.9%) had borderline scores of 30 to 32, 82 (28.2%) had scores suggesting mild/moderate cognitive impairment (scores of 20 to 29), and 15 (5.2%) had scores suggesting severe cognitive impairment (score of

OBJECTIVE: This study describes early-phase development of a behavioral intervention to reduce weight regain following bariatric surgery. We utilized the Obesity-Related Behavioral Intervention Trials (ORBIT) model to guide intervention development and evaluation. We sought to establish recruitment, retention, and fidelity monitoring procedures; evaluate feasibility of utilizing weight from the electronic medical record (EMR) as an outcome; observe improvement in behavioral risk factors; and evaluate treatment acceptability. METHODS: The intervention comprised four weekly telephone calls addressing behavior change strategies for diet, physical activity, and nutrition supplement adherence and five biweekly calls addressing weight loss maintenance constructs. Veterans (N=33) who received bariatric surgery 9–15 months prior consented to a 16-week, pre-post study. Self-reported outcomes were obtained by telephone at baseline and 16 weeks. Clinic weights were obtained from the EMR six months pre- and post-consent. Qualitative interviews were conducted at 16 weeks to evaluate treatment acceptability. We aimed to achieve a recruitment rate of ≥ 25%, retention rate of ≥ 80%, and have ≥50% of participants regain

This cohort study assesses whether higher levels of family member–reported palliative care needs are observed among those whose critically ill loved ones meet a clinical palliative care trigger compared with those who do not meet such a trigger., Key Points Question Does clinical palliative care trigger status accurately identify individuals with the most serious unmet palliative care needs? Findings In this cohort study including 257 dyads (1 patient in an intensive care unit [ICU] and 1 family member of each patient), there was no significant difference in self-reported palliative care needs between those with and without a clinical trigger (median Needs at the End-of-Life Screening Tool scores, 21.0 vs 22.5). Clinical triggers’ 45% sensitivity and 55% specificity suggested that they were no better than chance at identifying serious needs. Meaning The findings suggest that using clinical trigger status to prompt palliative care consultation in ICU settings may be an inefficient use of this limited resource; incorporating direct measures of unmet need in care may be a promising alternative strategy., Importance Palliative care consultations in intensive care units (ICUs) are increasingly prompted by clinical characteristics associated with mortality or resource utilization. However, it is not known whether these triggers reflect actual palliative care needs. Objective To compare unmet needs by clinical palliative care trigger status (present vs absent). Design, Setting, and Participants This prospective cohort study was conducted in 6 adult medical and surgical ICUs in academic and community hospitals in North Carolina between January 2019 and September 2020. Participants were consecutive patients receiving mechanical ventilation and their family members. Exposure Presence of any of 9 common clinical palliative care triggers. Main Outcomes and Measures The primary outcome was the Needs at the End-of-Life Screening Tool (NEST) score (range, 0-130, with higher scores reflecting greater need), which was completed after 3 days of ICU care. Trigger status performance in identifying serious need (NEST score ≥30) was assessed using sensitivity, specificity, positive and negative likelihood ratios, and C statistics. Results Surveys were completed by 257 of 360 family members of patients (71.4% of the potentially eligible patient–family member dyads approached) with a median age of 54.0 years (IQR, 44-62 years); 197 family members (76.7%) were female, and 83 (32.3%) were Black. The median age of patients was 58.0 years (IQR, 46-68 years); 126 patients (49.0%) were female, and 88 (33.5%) were Black. There was no difference in median NEST score between participants with a trigger present (45%) and those with a trigger absent (55%) (21.0; IQR, 12.0-37.0 vs 22.5; IQR, 12.0-39.0; P = .52). Trigger presence was associated with poor sensitivity (45%; 95% CI, 34%-55%), specificity (55%; 95% CI, 48%-63%), positive likelihood ratio (1.0; 95% CI, 0.7-1.3), negative likelihood ratio (1.0; 95% CI, 0.8-1.2), and C statistic (0.50; 95% CI, 0.44-0.57). Conclusions and Relevance In this cohort study, clinical palliative care trigger status was not associated with palliative care needs and no better than chance at identifying the most serious needs, which raises questions about an increasingly common clinical practice. Focusing care delivery on directly measured needs may represent a more person-centered alternative.

Background: to combat the COVID-19 pandemic, adherence to COVID-19 recommendations and vaccination against COVID-19 have been important. Among people who use drugs (PWUD), little is known regarding compliance towards COVID-19 recommendations, COVID-19 testing, or attitudes towards COVID-19 vaccination. We aimed to examine these issues in a sample of PWUD. Methods: a cross-sectional study was conducted between January and March 2021. Through users’ organizations and different low-threshold services for substance users, we recruited former drug users and professionals to include participants and perform the interviews. Participants completed an interviewer-administered questionnaire. Any person above 16 years of age who used substances were recruited. Results: 477 Norwegian PWUD participated in the study. The mean age was 43.8 (SD 12.8) years and 77% were males. Thirty-four percent had injected drugs the past four weeks. Alcohol (41%) and cannabis (41%) were the most common drugs used the past four weeks, followed by tranquilizers (37%), central stimulants (35%) and opioids (30%). The majority (90%) had washed their hands frequently, used alcohol sanitizer during the past two weeks, had used face masks, kept one-meter distance to other people and stayed at home if feeling unwell. Fifty-four percent had been COVID-19 tested. More than half the sample (58%) had positive attitudes to COVID-19 vaccination, while 26% were fairly or very unlikely to accept vaccination. Those older (OR = 0.96, 95% CI 0.94; 0.98) and using face masks (OR = 0.49, 95% CI 0.30; 0.79) were more likely to have positive attitudes towards vaccination, while those reporting low life-satisfaction (OR = 3.86, 95% CI 1.43; 10.40), using opioids (OR = 2.97, 95% CI 1.43; 6.18) or almost never staying at home when feeling unwell (OR = 2.76, 95% 1.39; 5.45) expressed more negative attitudes towards vaccination. Conclusion: there was generally a high compliance towards COVID-19 recommendations, but one quarter of the sample was sceptical towards COVID-19 vaccination. This indicates a need for targeted and tailored information and well-designed vaccination roll-out programs to reach all PWUD.

Vagus nerve stimulation (VNS) improves cognition in humans and rodents, but the effects of a single session of VNS on performance and plasticity are not well understood.Behavioral performance and hippocampal (HC) electrophysiology/neurotrophin expression were measured in healthy adult rats after VNS paired training to investigate changes in cognition and synaptic plasticity.Platinum/iridium electrodes were surgically implanted around the left cervical branch of the VN of anesthetized male Sprague-Dawley rats (N = 47). VNS (100 μs biphasic pulses, 30 Hz, 0.8 mA) paired Novel Object Recognition (NOR)/Passive Avoidance Task (PAT) were assessed 24 h after training and post-mortem tissue was collected 48 h after VNS (N = 28). Electrophysiology recordings were collected using a microelectrode array system to assess functional effects on HC slices 90 min after VNS (N = 19). Sham received the same treatment without VNS and experimenters were blinded.Stimulated rats exhibited improved performance in NOR (p 0.05, n = 12) and PAT (p 0.05, n = 14). VNS enhanced long-term potentiation (p 0.05, n = 7-12), and spontaneous spike amplitude (p 0.05, n = 7-12) and frequency (p 0.05, n = 7-12) in the CA1. Immunohistochemical analysis found increased brain-derived neurotrophic factor expression in the CA1 (p 0.05, n = 8-9) and CA2 (p 0.01, n = 7-8).These findings suggest that our VNS parameters promote synaptic plasticity and target the CA1, which may mediate the positive cognitive effects of VNS. This study significantly contributes to a better understanding of VNS mediated HC synaptic plasticity, which may improve clinical utilization of VNS for cognitive enhancement.

Evidence is accumulating to suggest that viral infections and consequent viral-mediated neuroinflammation may contribute to the etiology of idiopathic Parkinson's disease. Moreover, viruses have been shown to influence α-synuclein oligomerization as well as the autophagic clearance of abnormal intra-cellular proteins aggregations, both of which are key neuropathological events in Parkinson's disease pathogenesis. To further investigate the interaction between viral-mediated neuroinflammation and α-synuclein aggregation in the context of Parkinson's disease, this study sought to determine the impact of viral neuroinflammatory priming on α-synuclein aggregate-induced neuroinflammation and neurotoxicity in the rat nigrostriatal pathway. To do so, male Sprague-Dawley rats were intra-nigrally injected with a synthetic mimetic of viral dsRNA (poly I:C) followed two weeks later by a peptidomimetic small molecule which accelerates α-synuclein fibril formation (FN075). The impact of the viral priming on α-synuclein aggregation-induced neuroinflammation, neurodegeneration and motor dysfunction was assessed. We found that prior administration of the viral mimetic poly I:C significantly exacerbated or precipitated the α-synuclein aggregate induced neuropathological and behavioral effects. Specifically, sequential exposure to the two challenges caused a significant increase in nigral microgliosis (p 0.001) and astrocytosis (p 0.01); precipitated a significant degeneration of the nigrostriatal cell bodies (p 0.05); and precipitated a significant impairment in forelimb kinesis (p 0.01) and sensorimotor integration (p 0.01). The enhanced sensitivity of the nigrostriatal neurons to pathological α-synuclein aggregation after viral neuroinflammatory priming further suggests that viral infections may contribute to the etiology and pathogenesis of Parkinson's disease.

Introduction Sex- and gender-specific science is essential to inform patient-centered, evidence-based care. Developing such evidence requires adequate inclusion of both women and men in trials. We sought to describe study participation of women and men in Department of Veterans Affairs Health Services Research and Development trials. Methods We identified recent health services research trials from one Health Services Research and Development Center of Innovation and compared the participation of women and men from trial recruitment to study completion. We also calculated the participation to prevalence ratio (PPR) by sex for each trial. Results We included eight trials that started recruitment between 2011 and 2014. Only one study purposefully attempted to boost the recruitment of women. Overall, the PPR for women ranged from 0.2 to 4.5, with seven studies having a PPR of greater than 1, indicating that women participated in these trials at proportions greater than their prevalence in the disease population within the Department of Veterans Affairs. The PPR for men ranged from 0.8 to 1.1. Retention was best with those studies that used administrative data for final outcomes assessment. No studies provided results stratified by sex or conducted analyses to explore treatment effect by sex. Conclusions At a single site, women participated in Health Services Research and Development trials at similar or greater rates to men without cross-study efforts to enrich the recruitment or retention of women. Adding strategic recruitment approaches could further boost the proportion of women in Department of Veterans Affairs trials and enable adequately powered sex-based analyses.

BACKGROUND: Health coaching is an effective behavior change strategy. Understanding if there is a differential impact of health coaching on patients with low health literacy has not been well investigated. OBJECTIVE: To determine whether a telephone coaching intervention would result in similar improvements in enrollment in prevention programs and patient activation among Veterans with low versus high health literacy (specifically, reading literacy and numeracy). DESIGN: Secondary analysis of a randomized controlled trial. PARTICIPANTS: Four hundred seventeen Veterans with at least one modifiable risk factor: current smoker, BMI ≥ 30, or

Background While social distancing policies protect older adults with advanced chronic kidney disease (CKD) from exposure to COVID-19, reduced social interaction may also have unintended consequences. Methods To identify subgroups of patients at risk for unintended health consequences of social distancing, we conducted a cross-sectional analysis of data from a national cohort study of older veterans with advanced CKD (n = 223). Characteristics included activities of daily living (ADLs), instrumental ADLs (IADLs), cognition score, depression score, social support, financial stress, symptom burden, and number of chronic conditions. Unintended consequences of social distancing included restricted Life Space mobility, low willingness for video telehealth, reduced in-person contact with caregivers, and food insecurity. We identified subgroups of patients at risk of unintended consequences using model-based recursive partitioning (MoB). Results Participants had a mean age of 77.9 years, 64.6% were white, and 96.9% were male. Overall, 22.4% of participants had restricted Life Space, 33.9% reported low willingness for video telehealth, 19.0% reported reduced caregiver contact, and 3.2% reported food insecurity. For Life Space restriction, 4 subgroups partitioned (ie, split) by IADL difficulty, cognition score, and ADL difficulty were identified. The highest rate of restricted Life Space was 54.7% in the subgroup of participants with >3 IADL difficulties. For low willingness for telehealth and reduced caregiver contact, separate models identified 2 subgroups split by cognition score and depression score, respectively. Conclusions Measures of function, cognition, and depressive symptoms may identify older adults with advanced CKD who are at higher risk for unintended health consequences of social distancing.

STUDY OBJECTIVES: The objectives of this study were to examine the proportion of study participants screening positive for insomnia disorder and/or sleep apnea in veterans engaged in routine health care and known to be at risk for cardiovascular disease and to compare these proportions with those previously documented in medical records. METHODS: This was a cross-sectional analysis of baseline data from a randomized clinical intervention trial for patients at risk of cardiovascular disease and a review of study participants’ medical records. Participants were veterans ≥ 40 years of age, enrolled in Veterans Affairs primary care, and diagnosed with hypertension and/or hypercholesterolemia. Self-report outcomes were the proportion of patients screening positive for an insomnia disorder and sleep apnea, self-reporting a sleep apnea diagnosis, and endorsing undertreated sleep apnea. Medical record outcomes were the proportion of patients diagnosed with insomnia and sleep apnea. RESULTS: Participants (n = 420) were veterans (84.8% male) with a mean age of 61.1 years. More than half of the sample (52.1%) screened positive for sleep apnea without prior self-reported diagnosis. More than one-third of the sample (39%) screened positive for an insomnia disorder. Medical records revealed considerably lower rates, with 3.8% diagnosed with insomnia, 20.5% diagnosed with sleep apnea, and about 1% diagnosed with both conditions. CONCLUSIONS: Undiagnosed and undertreated sleep disorders are common among veterans at risk for cardiovascular disease. Most of the sample (82%) screened positive for, or met, study criteria for sleep apnea or an insomnia disorder. Limitations include the use of self-reported sleep apnea treatment adherence, an insomnia disorder diagnosis based on questionnaire score, and a sample comprised primarily of male veterans. Routine sleep disorders screening in veterans at risk for cardiovascular disease could help to identify those at even greater risk because of the adverse effects of undiagnosed or undertreated sleep disorders. CLINICAL TRIAL REGISTRATION: Registry; ClinicalTrials.gov; Name: Cardiovascular Intervention Improvement Telemedicine Study; URL: https://clinicaltrials.gov/ct2/show/NCT01142908; Identifier: NCT01142908. CITATION: Ulmer CS, McCant F, Stechuchak KM, Olsen M, Bosworth HB. Prevalence of insomnia disorder and sleep apnea in a sample of veterans at risk for cardiovascular disease. J Clin Sleep Med. 2021;17(7):1441–1446.

PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. CONCLUSION: Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging.We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database.Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation.Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

Introduction The technologies used to treat the millions who receive care in intensive care unit (ICUs) each year have steadily advanced. However, the quality of ICU-based communication has remained suboptimal, particularly concerning for Black patients and their family members. Therefore we developed a mobile app intervention for ICU clinicians and family members called ICUconnect that assists with delivering need-based care. Objective To describe the methods and early experiences of a clustered randomized clinical trial (RCT) being conducted to compare ICUconnect vs. usual care. Methods and analysis The goal of this two-arm, parallel group clustered RCT is to determine the clinical impact of the ICUconnect intervention in improving outcomes overall and for each racial subgroup on reducing racial disparities in core palliative care outcomes over a 3-month follow up period. ICU attending physicians are randomized to either ICUconnect or usual care, with outcomes obtained from family members of ICU patients. The primary outcome is change in unmet palliative care needs measured by the NEST instrument between baseline and 3 days post-randomization. Secondary outcomes include goal concordance of care and interpersonal processes of care at 3 days post-randomization; length of stay; as well as symptoms of depression, anxiety, and post-traumatic stress disorder at 3 months post-randomization. We will use hierarchical linear models to compare outcomes between the ICUconnect and usual care arms within all participants and assess for differential intervention effects in Blacks and Whites by adding a patient-race interaction term. We hypothesize that both compared to usual care as well as among Blacks compared to Whites, ICUconnect will reduce unmet palliative care needs, psychological distress and healthcare resource utilization while improving goal concordance and interpersonal processes of care. In this manuscript, we also describe steps taken to adapt the ICUconnect intervention to the COVID-19 pandemic healthcare setting. Enrollment status A total of 36 (90%) of 40 ICU physicians have been randomized and 83 (52%) of 160 patient-family dyads have been enrolled to date. Enrollment will continue until the end of 2021.

Importance Bariatric surgical procedures have been associated with increased risk of unhealthy alcohol use, but no previous research has evaluated the long-term alcohol-related risks after laparoscopic sleeve gastrectomy (LSG), currently the most used bariatric procedure. No US-based study has compared long-term alcohol-related outcomes between patients who have undergone Roux-en-Y gastric bypass (RYGB) and those who have not. Objective To evaluate the changes over time in alcohol use and unhealthy alcohol use from 2 years before to 8 years after a bariatric surgical procedure among individuals with or without preoperative unhealthy alcohol use. Design, Setting, and Participants This retrospective cohort study analyzed electronic health record (EHR) data on military veterans who underwent a bariatric surgical procedure at any of the bariatric centers in the US Department of Veterans Affairs (VA) health system between October 1, 2008, and September 30, 2016. Surgical patients without unhealthy alcohol use at baseline were matched using sequential stratification to nonsurgical control patients without unhealthy alcohol use at baseline, and surgical patients with unhealthy alcohol use at baseline were matched to nonsurgical patients with unhealthy alcohol use at baseline. Data were analyzed in February 2020. Interventions LSG (n = 1684) and RYGB (n = 924). Main Outcomes and Measures Mean alcohol use, unhealthy alcohol use, and no alcohol use were estimated using scores from the validated 3-item Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), which had been documented in the VA EHR. Alcohol outcomes were estimated with mixed-effects models. Results A total of 2608 surgical patients were included in the final cohort (1964 male [75.3%] and 644 female [24.7%] veterans. Mean (SD) age of surgical patients was 53.0 (9.9) years and 53.6 (9.9) years for the matched nonsurgical patients. Among patients without baseline unhealthy alcohol use, 1539 patients who underwent an LSG were matched to 14 555 nonsurgical control patients and 854 patients who underwent an RYGB were matched to 8038 nonsurgical control patients. In patients without baseline unhealthy alcohol use, the mean AUDIT-C scores and the probability of unhealthy alcohol use both increased significantly 3 to 8 years after an LSG or an RYGB, compared with control patients. Eight years after an LSG, the probability of unhealthy alcohol use was higher in surgical vs control patients (7.9% [95% CI, 6.4-9.5] vs 4.5% [95% CI, 4.1-4.9]; difference, 3.4% [95% CI, 1.8-5.0])). Similarly, 8 years after an RYGB, the probability of unhealthy alcohol use was higher in surgical vs control patients (9.2% [95% CI, 8.0-10.3] vs 4.4% [95% CI, 4.1-4.6]; difference, 4.8% [95% CI, 3.6-5.9]). The probability of no alcohol use also decreased significantly 5 to 8 years after both procedures for surgical vs control patients. Among patients with unhealthy alcohol use at baseline, prevalence of unhealthy alcohol use was higher for patients who underwent an RYGB than matched controls. Conclusions and Relevance In this multi-site cohort study of predominantly male patients, among those who did not have unhealthy alcohol use in the 2 years before bariatric surgery, the probability of developing unhealthy alcohol use increased significantly 3-8 years after bariatric procedures compared with matched controls during follow-up.

Deciphering the mechanisms underlying age-related memory declines remains an important goal in cognitive neuroscience. Recently, we observed that visual sampling behavior predicted activity within the hippocampus, a region critical for memory. In younger adults, increases in the number of gaze fixations were associated with increases in hippocampal activity (Liu et al., 2017). This finding suggests a close coupling between the oculomotor and memory system. However, the extent to which this coupling is altered with aging has not been investigated. In this study, we gave older adults the same face processing task used in Liu et al. (2017) and compared their visual exploration behavior and neural activation in the hippocampus and the fusiform face area (FFA) to those of younger adults. Compared to younger adults, older adults showed an increase in visual exploration as indexed by the number of gaze fixations. However, the relationship between visual exploration and neural responses in the hippocampus and FFA was weaker than that of younger adults. Older adults also showed weaker responses to novel faces and a smaller repetition suppression effect in the hippocampus and FFA compared to younger adults. All together, this study provides novel evidence that the capacity to bind visually sampled information, in real-time, into coherent representations along the ventral visual stream and the medial temporal lobe declines with aging.

BACKGROUND: A large proportion of deaths and chronic illnesses can be attributed to three modifiable risk factors: tobacco use, overweight/obesity, and physical inactivity. OBJECTIVE: To test whether telephone-based health coaching after completion of a comprehensive health risk assessment (HRA) increases patient activation and enrollment in a prevention program compared to HRA completion alone. DESIGN: Two-arm randomized trial at three sites. SETTING: Primary care clinics at Veterans Affairs facilities. PARTICIPANTS: Four hundred seventeen veterans with at least one modifiable risk factor (BMI ≥ 30

Striking individual differences exist in the human capacity to recollect past events, yet, little is known about the neural correlates of such individual differences. Studies investigating hippocampal volume in relation to individual differences in laboratory measures of episodic memory in young adults suggest that whole hippocampal volume is unrelated (or even negatively associated) with episodic memory. However, anatomical and functional specialization across hippocampal subregions suggests that individual differences in episodic memory may be linked to particular hippocampal subregions, as opposed to whole hippocampal volume. Given that the DG/CA2/3 circuitry is thought to be especially critical for supporting episodic memory in humans, we predicted that the volume of this region would be associated with individual variability in episodic memory. This prediction was supported using high-resolution MRI of the hippocampal subfields and measures of real-world (autobiographical) episodic memory. In addition to the association with DG/CA2/3 , we further observed a relationship between episodic autobiographical memory and subiculum volume, whereas no association was observed with CA1 or with whole hippocampal volume. These findings provide insight into the possible neural substrates that mediate individual differences in real-world episodic remembering in humans.

Identification of patient characteristics that are associated with behavioral weight loss success among bariatric surgery candidates could inform selection of optimal bariatric surgery candidates. We examined the associations between psychosocial characteristics and weight loss in a group of Veterans with severe obesity who participated in a behavioral weight loss intervention. The MAINTAIN trial involved a 16-week weight loss program followed by randomization among participants losing at least 4 kg to a maintenance intervention or usual care. This secondary analysis was performed on Veterans who participated in the 16-week weight loss program and met NIH criteria for bariatric surgery (body mass index [BMI] 35.0–39.9 with at least 1 obesity-related comorbidity or BMI ≥ 40). Unadjusted and adjusted associations between baseline patient characteristics and weight loss during the 16-week induction phase were evaluated with linear regression. Missing weight measurements were multiply imputed, and results combined across ten imputations. Among the 206 patients who met inclusion criteria, mean initial BMI was 40.8 kg/m2 (SD 6.0), and mean age was 59.2 years (SD 9.4). Approximately 20% of participants were female, 51.5% were Black, and 44.7% were White. Estimated mean 16-week weight loss was 5.16 kg (SD 4.31). In adjusted analyses, greater social support and older age were associated with greater weight loss (p

This study aimed to examine the early impact of the Program of Comprehensive Assistance for Family Caregivers (PCAFC) on Veteran health care utilization and costs. A pre-post cohort design including a nonequivalent control group was used to understand how Veterans’ use of Veteran Affairs health care and total health care costs changed in 6-month intervals up to 3 years after PCAFC enrollment. The control group was an inverse probability of treatment weighted sample of Veterans whose caregivers applied for, but were not accepted into, PCAFC. Veterans in PCAFC had similar acute care utilization postenrollment when compared with those in the control group, but significantly greater primary, specialty, and mental health outpatient care use at least 30, and up to 36, months postenrollment. Estimated total health care costs for PCAFC Veterans were $1,500 to $3,400 higher per 6-month interval than for control group Veterans. PCAFC may have increased Veterans’ access to care.

We tested an uncertainty self-management telephone intervention (SMI) with patients awaiting liver transplant and their caregivers.Participants were recruited from four transplant centers and completed questionnaires at baseline, 10, and 12 weeks from baseline (generally two and four weeks after intervention delivery, respectively). Dyads were randomized to either SMI (n=56) or liver disease education (LDE; n=59), both of which involved six weekly telephone sessions. SMI participants were taught coping skills and uncertainty management strategies while LDE participants learned about liver function and how to stay healthy. Outcomes included illness uncertainty, uncertainty management, depression, anxiety, self-efficacy, and quality of life. General linear models were used to test for group differences.No differences were found between the SMI and LDE groups for study outcomes.This trial offers insight regarding design for future interventions that may allow greater flexibility in length of delivery beyond our study's 12-week timeframe.Our study was designed for the time constraints of today's clinical practice setting. This trial is a beginning point to address the unmet needs of these patients and their caregivers as they wait for transplants that could save their lives.

BACKGROUND: Short-term health care costs following completion of health risk assessments and coaching programs in the VA have not been assessed. OBJECTIVE: To compare VA health care expenditures among veterans who participated in a behavioral intervention trial that randomized patients to complete a HRA followed by health coaching (HRA + coaching) or to complete the HRA without coaching (HRA-alone). DESIGN: Four-hundred seventeen veterans at three Veterans Affairs (VA) Medical Centers or Clinics were randomized to HRA + coaching or HRA-alone. Veterans randomized to HRA-alone (n = 209) were encouraged to discuss HRA results with their primary care team, while veterans randomized to HRA + coaching (n = 208) received two brief telephone-delivered health coaching calls. PARTICIPANTS: We included 411 veterans with available cost data. MAIN MEASURES: Total VA health expenditures 6 months following trial enrollment were estimated using a generalized linear model with a gamma distribution and log link function. In exploratory analysis, model-based recursive partitioning was used to determine whether the intervention effect on short-term costs differed among any patient subgroups. KEY RESULTS: Most participants were male (85%); mean age was 56, and mean body mass index was 34. From the generalized linear model, 6-month estimated mean total VA expenditures were similar ($8665 for HRA + coaching vs $9900 for HRA-alone, p = 0.25). In exploratory subgroup analysis, among unemployed veterans with good sleep and fair or poor perceived health, mean observed expenditures in the HRA + coaching group were higher than in the HRA-alone group ($12,814 vs $7971). Among unemployed veterans with good sleep and good general health, mean observed expenditures in the HRA + coaching group were lower than in the HRA-alone group ($5082 vs $11,612). CONCLUSIONS: Compared to completing and receiving HRA results, working with health coaches to set actionable health behavior change goals following HRA completion did not reduce short-term health expenditures. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01828567

Importance Bariatric surgery has been associated with improvements in health in patients with severe obesity; however, it is unclear whether these health benefits translate into lower health care expenditures. Objective To examine 10-year health care expenditures in a large, multisite retrospective cohort study of veterans with severe obesity who did and did not undergo bariatric surgery. Design, Setting, and Participants A total of 9954 veterans with severe obesity between January 1, 2000, and September 30, 2011, were identified from veterans affairs (VA) electronic health records. Of those, 2498 veterans who underwent bariatric surgery were allocated to the surgery cohort. Sequential stratification was used to match each patient in the surgery cohort with up to 3 patients who had not undergone bariatric surgery but were of the same sex, race/ethnicity, diabetes status, and VA regional network and were closest in age, body mass index (calculated as weight in kilograms divided by height in meters squared), and comorbidities. A total of 7456 patients were identified and allocated to the nonsurgery (control) cohort. The VA health care expenditures among the surgery and nonsurgery cohorts were estimated using regression models. Data were analyzed from July to August 2018 and in April 2019. Interventions The bariatric surgical procedures (n = 2498) included in this study were Roux-en-Y gastric bypass (1842 [73.7%]), sleeve gastrectomy (381 [15.3%]), adjustable gastric banding (249 [10.0%]), and other procedures (26 [1.0%]). Main Outcomes and Measures The study measured total, outpatient, inpatient, and outpatient pharmacy expenditures from 3 years before surgery to 10 years after surgery, excluding expenditures associated with the initial bariatric surgical procedure. Results Among 9954 veterans with severe obesity, 7387 (74.2%) were men; the mean (SD) age was 52.3 (8.8) years for the surgery cohort and 52.5 (8.7) years for the nonsurgery cohort. Mean total expenditures for the surgery cohort were $5093 (95% CI, $4811-$5391) at 7 to 12 months before surgery, which increased to $7448 (95% CI, $6989-$7936) at 6 months after surgery. Postsurgical expenditures decreased to $6692 (95% CI, $6197-$7226) at 5 years after surgery, followed by a gradual increase to $8495 (95% CI, $7609-$9484) at 10 years after surgery. Total expenditures were higher in the surgery cohort than in the nonsurgery cohort during the 3 years before surgery and in the first 2 years after surgery. The expenditures of the 2 cohorts converged 5 to 10 years after surgery. Outpatient pharmacy expenditures were significantly lower among the surgery cohort in all years of follow-up ($509 lower at 3 years before surgery and $461 lower at 7 to 12 months before surgery), but these cost reductions were offset by higher inpatient and outpatient (nonpharmacy) expenditures. Conclusions and Relevance In this cohort study of 9954 predominantly older male veterans with severe obesity, total health care expenditures increased immediately after patients underwent bariatric surgery but converged with those of patients who had not undergone surgery at 10 years after surgery. This finding suggests that the value of bariatric surgery lies primarily in its associations with improvements in health and not in its potential to decrease health care costs.

Purpose/Aim: To determine if an upper extremity functional survey may identify which patients will have eye drop administration difficulty.Materials and Methods: Participants with glaucoma treated ...

Many glaucoma eye drop users cannot successfully self-administer drops, and observing patients' drop technique can be time-consuming. We sought to examine the association of patient self-reported efficacy of eye drop technique and medication possession data as potential surrogate measures for actual drop administration success.In total, 137 adults with medically treated glaucoma were enrolled from a University eye clinic (n=54) or a Veteran Affairs (VA) eye clinic (n=83). All participants were asked, "How confident are you that you can get the medication into your eye?" Medication possession ratio (MPR), defined as the amount of eye drop available divided by the amount prescribed, was calculated for VA study site participants for 6 months. The main outcome was the correct eye drop technique, defined as the ability to get drops into the eye and to put only 1 drop into the eye at a time.Among 117 participants who were "very confident" they could administer eye drops correctly, 95 participants (81%) displayed the correct drop technique. Of those who reported being less than "very confident" (n=18), 11 participants (61%) displayed correct drop technique (the Fisher exact test, P=0.07). For the VA sample, 20 participants with MPR1.2, 20 participants with MPR=1.2 to 1.8, and 23 participants with MPR1.8 displayed correct eye drop technique (the Fisher exact test, P=0.18).Self-reported administration success and MPR are not strongly associated with successful eye drop administration. Thus, direct observation of patients' drop instillation may be the most effective means of determining patient efficacy.

IL-6 is secreted from muscles to the circulation during high-intensity and long-duration exercise, where muscle-derived IL-6 works as an energy sensor to increase release of energy substrates from liver and adipose tissues. We investigated the mechanism involved in the exercise-mediated surge in IL-6 during exercise. Using interval-based cycling in healthy young men, swimming exercise in mice, and electrical stimulation of primary human muscle cells, we explored the role of lactate production in muscular IL-6 release during exercise. First, we observed a tight correlation between lactate production and IL-6 release during both strenuous bicycling and electrically stimulated muscle cell cultures. In mice, intramuscular injection of lactate mimicked the exercise-dependent release of IL-6, and pH buffering of lactate production during exercise attenuated IL-6 secretion. Next, we used in vivo bioimaging to demonstrate that intrinsic intramuscular proteases were activated in mice during swimming, and that blockade of protease activity blunted swimming-induced IL-6 release in mice. Last, intramuscular injection of the protease hyaluronidase resulted in dramatic increases in serum IL-6 in mice, and immunohistochemical analyses showed that intramuscular lactate and hyaluronidase injections led to release of IL-6-containing intramyocellular vesicles. We identified a pool of IL-6 located within vesicles of skeletal muscle fibers, which could be readily secreted upon protease activity. This protease-dependent release of IL-6 was initiated by lactate production, linking training intensity and lactate production to IL-6 release during strenuous exercise.

There is consistent agreement regarding the positive relationship between cumulative eye movement sampling and subsequent recognition, but the role of the hippocampus in this sampling behavior is currently unknown. It is also unclear whether the eye movement repetition effect, i.e., fewer fixations to repeated, compared to novel, stimuli, depends on explicit recognition and/or an intact hippocampal system. We investigated the relationship between cumulative sampling, the eye movement repetition effect, subsequent memory, and the hippocampal system. Eye movements were monitored in a developmental amnesic case (H.C.), whose hippocampal system is compromised, and in a group of typically developing participants while they studied single faces across multiple blocks. The faces were studied from the same viewpoint or different viewpoints and were subsequently tested with the same or different viewpoint. Our previous work suggested that hippocampal representations support explicit recognition for information that changes viewpoint across repetitions (Olsen et al., 2015). Here, examination of eye movements during encoding indicated that greater cumulative sampling was associated with better memory among controls. Increased sampling, however, was not associated with better explicit memory in H.C., suggesting that increased sampling only improves memory when the hippocampal system is intact. The magnitude of the repetition effect was not correlated with cumulative sampling, nor was it related reliably to subsequent recognition. These findings indicate that eye movements collect information that can be used to strengthen memory representations that are later available for conscious remembering, whereas eye movement repetition effects reflect a processing change due to experience that does not necessarily reflect a memory representation that is available for conscious appraisal. Lastly, H.C. demonstrated a repetition effect for fixed viewpoint faces but not for variable viewpoint faces, which suggests that repetition effects are differentially supported by neocortical and hippocampal systems, depending upon the representational nature of the underlying memory trace.

Recent models of hippocampal function have emphasized its role in relational binding – the ability to form lasting representations regarding the relations among distinct elements or items which can support memory performance, even over brief delays (e.g., several seconds). The present study examined the extent to which aging is associated with changes in the recruitment of oscillatory activity within hippocampal and neocortical regions to support relational binding performance on a short delay visuospatial memory task. Structural magnetic resonance imaging and MEG were used to characterize potential age-related changes in hippocampal volume, oscillatory activity, and subsequent memory performance, and the relationships among them. Participants were required to bind the relative visuospatial positions of objects that were presented singly across time. Subsequently, the objects were re-presented simultaneously, and participants were required to indicate whether the relative spatial positions among the objects had been maintained. Older and younger adults demonstrated similar task accuracy, and older adults had preserved hippocampal volumes relative to younger adults. Age-group differences were found in pre-stimulus theta (∼5Hz) and beta (∼20Hz) oscillations, and this pre-stimulus activity was related to hippocampal volumes in younger adults. Age-group differences were also found in the recruitment of oscillatory activity from the pre-stimulus period to the task. Only younger adults showed a task-related change in theta power that was predictive of memory performance. In contrast, older adults demonstrated task-related alpha (∼10Hz) oscillatory power changes that were not observed in younger adults. These findings provide novel evidence for the role of the hippocampus and functionally connected regions in relational binding that is disrupted in aging. The present findings are discussed in the context of current models regarding the cognitive neuroscience of aging.

Introduction The primary objective of this project was to examine the effectiveness of an Internet-based smoking cessation intervention combined with a tele-health medication clinic for nicotine replacement therapy (NRT) compared to referral to clinic-based smoking cessation care. Methods A total of 413 patients were proactively recruited from the Durham VA Medical Center and followed for 12 months. Patients were randomized to receive either a referral to VA specialty smoking cessation care (control) or to the Internet intervention and tele-health medication clinic. Primary outcomes included (1) intervention reach, (2) self-reported 7-day point prevalence abstinence rates at 3 months and 12 months, and 3) relative cost-effectiveness. Results Reach of the Internet intervention and use of smoking cessation aids were significantly greater compared to the control. At 3 months-post randomization, however, there were no significant differences in quit rates: 17% (95% CI: 12%–23%) in the Internet-based intervention compared to 12% (95% CI: 8%–17%) in the control arm. Similarly, there were no differences in quit rates at 12 months (13% vs. 16%). While costs associated with the Internet arm were higher due to increased penetration and intensity of NRT use, there were no statistically significant differences in the relative cost effectiveness (e.g., life years gained, quality adjusted life years) between the two arms. Conclusions Current results suggest that using an electronic medical record to identify smokers and proactively offering smoking cessation services that are consistent with US Public Health Guidelines can significantly reduce smoking in veterans. Novel interventions that increase the reach of intensive treatment are needed to maximize quit rates in this population.

Individuals with schizophrenia evidence impaired emotional functioning. Abnormal amygdala activity has been identified as an etiological factor underlying affective impairment in this population, but the exact nature remains unclear. The current study utilized psychophysiological interaction analyses to examine functional connectivity between the amygdala and medial prefrontal cortex (mPFC) during an emotion perception task. Participants with schizophrenia (SZ) and healthy controls (HC) viewed and rated positive, negative, and neutral images while undergoing functional neuroimaging. Results revealed a significant group difference in right amygdala-mPFC connectivity during perception of negative versus neutral images. Specifically, HC participants demonstrated positive functional coupling between the amygdala and mPFC, consistent with co-active processing of salient information. In contrast, SZ participants evidenced negative functional coupling, consistent with top-down inhibition of the amygdala by the mPFC. A significant positive correlation between connectivity strength during negative image perception and clinician-rated social functioning was also observed in SZ participants, such that weaker right amygdala-mPFC coupling during negative compared to neutral image perception was associated with poorer social functioning. Overall, results suggest that emotional dysfunction and associated deficits in functional outcome in schizophrenia may relate to abnormal interactions between the amygdala and mPFC during perception of emotional stimuli. This study adds to the growing literature on abnormal functional connections in schizophrenia and supports the functional disconnection hypothesis of schizophrenia.

Glaucoma medications reduce the risk of progressive visual field loss, but adherence to these medications is often poor. A better understanding of the appropriate metrics for quantifying glaucoma medication adherence is needed. We describe and compare different means of quantifying glaucoma medication adherence.Adults with glaucoma were enrolled in a prospective 2-site study. Participants completed a self-report instrument and received electronic medication monitors to use for ∼3 months. Pharmacy records were queried regarding requested refills over the monitoring period; medication possession ratio (MPR) was calculated.Of the 137 total participants, those who answered "Very confident" to the question, "How confident are you that you always remember to use your glaucoma medications?" and "No" to the question, "In the past 4 weeks, did you ever forget to take your medicine?" were more likely [odds ratio (OR) 2.78, 95% confidence interval (CI) 1.19-6.52] to take ≥80% of the prescribed doses according to electronic medication monitors. Mean MPR was 1.49, standard deviation (SD) 0.82, range 0.1-5.31. The proportion of participants taking greater than or equal to 80% of the prescribed doses according to the electronic monitors was 59% for participants with MPR1.2 (n = 27), 63% for participants with MPR 1.2-1.8 (n = 27), and 88% for MPR1.8 (n = 25).Asking about confidence may be a good method of screening for poor adherence for glaucoma medication. MPR may be an inadequate representation of glaucoma medication adherence.

Background Treatment decisions commonly have to be made in intensive care units (ICUs). These decisions are difficult for surrogate decision makers and often lead to decisional conflict, psychological distress, and treatments misaligned with patient preferences. Objective To determine whether a decision aid about prolonged mechanical ventilation improved prognostic concordance between surrogate decision makers and clinicians compared with a usual care control. Design Multicenter, parallel, randomized, clinical trial. (ClinicalTrials.gov: NCT01751061). Setting 13 medical and surgical ICUs at 5 hospitals. Participants Adult patients receiving prolonged mechanical ventilation and their surrogates, ICU physicians, and ICU nurses. Intervention A Web-based decision aid provided personalized prognostic estimates, explained treatment options, and interactively clarified patient values to inform a family meeting. The control group received information according to usual care practices followed by a family meeting. Measurements The primary outcome was improved concordance on 1-year survival estimates, measured with the clinician-surrogate concordance scale (range, 0 to 100 percentage points; higher scores indicate more discordance). Secondary and additional outcomes assessed the experiences of surrogates (psychological distress, decisional conflict, and quality of communication) and patients (length of stay and 6-month mortality). Outcomes assessors were blinded to group allocation. Results The study enrolled 277 patients, 416 surrogates, and 427 clinicians. Concordance improvement did not differ between intervention and control groups (mean difference in score change from baseline, -1.7 percentage points [95% CI, -8.3 to 4.8 percentage points]; P = 0.60). Surrogates' postintervention estimates of patients' 1-year prognoses did not differ between intervention and control groups (median, 86.0% [interquartile range {IQR}, 50.0%] vs. 92.5% [IQR, 47.0%]; P = 0.23) and were substantially more optimistic than results of a validated prediction model (median, 56.0% [IQR, 43.0%]) and physician estimates (median, 50.0% [IQR, 55.5%]). Eighty-two intervention surrogates (43%) favored a treatment option that was more aggressive than their report of patient preferences. Although intervention surrogates had greater reduction in decisional conflict than control surrogates (mean difference in change from baseline, 0.4 points [CI, 0.0 to 0.7 points]; P = 0.041), other surrogate and patient outcomes did not differ. Limitation Contamination among clinicians could have biased results toward the null hypothesis. Conclusion A decision aid about prolonged mechanical ventilation did not improve prognostic concordance between clinicians and surrogates, reduce psychological distress among surrogates, or alter clinical outcomes. Decision support in acute care settings may require greater individualized attention for both the cognitive and affective challenges of decision making. Primary funding source National Institutes of Health.

Context Patients with colorectal cancer have increased risk of metabolic diseases including diabetes. Exercise training may counteract metabolic dysregulation, but the impact of exercise training on glycemic control, including postprandial glycemia, has never been explored in patients with colorectal cancer. Objective To examine the effects of home-based interval walking on aerobic and metabolic fitness and quality of life in patients with colorectal cancer. Design Randomized controlled trial. Setting Clinical research center. Participants Thirty-nine sedentary ( Intervention Home-based interval walking 150 min/wk or usual care for 12 weeks. Main Outcome Measures Changes from baseline to week 12 in maximum oxygen uptake (VO2peak) by cardiopulmonary exercise test, glycemic control by oral glucose tolerance test (OGTT), body composition by dual-energy x-ray absorptiometry scan, blood biochemistry, and quality of life. Results Compared with control, interval walking had no effect on VO2peak [mean between-group difference: −0.32 mL O2 · kg−1 · min−1 (−2.09 to 1.45); P = 0.721] but significantly improved postprandial glycemic control with lower glucose OGTT area under the curve [−126 mM · min (−219 to −33); P = 0.009], 2-hour glucose concentration [−1.1 mM (−2.2 to 0.0); P = 0.056], and improved Matsuda index [1.94 (0.34; 3.54); P = 0.01]. Also, interval walking counteracted an increase in fat mass in the control group [−1.47 kg (−2.74 to −0.19); P = 0.025]. Conclusion A home-based interval-walking program led to substantial improvements in postprandial glycemic control and counteracted fat gain in posttreatment patients with colorectal cancer, possibly providing an effective strategy for prevention of secondary metabolic diseases.

Objective This study aims to describe geographic variation in veterans' prevalence of obesity, participation in Veterans Health Administration's behavioral weight management program (MOVE!), and receipt of bariatric surgery in fiscal year (FY) 2016. Methods In this retrospective cohort study of veterans with obesity who received Veterans Health Administration care in FY2016, electronic health record data were obtained on weight, height, outpatient visits to the MOVE! program, and bariatric surgeries. For each Veterans Integrated Service Network (VISN) region, the prevalence rate of veterans with obesity (BMI ≥ 30 kg/m2 ), MOVE! participation rates, and bariatric surgery rates are presented. Results The prevalence of obesity in veterans ranged from 30.5% to 40.5% across VISNs in FY2016. MOVE! participation among veterans with obesity was low (2.8%-6.9%) across all VISNs, but veterans with class II and III obesity (BMI ≥ 35) had higher MOVE! participation rates (4.3%-10.8%) than veterans with class I obesity. There was 20-fold variation across VISNs in receipt of bariatric surgery among veterans with BMI ≥ 35, ranging from 0.01% to 0.2%. Among veterans with BMI ≥ 35 participating in MOVE!, there was 46-fold variation in bariatric surgery provision, ranging from 0.07% to 3.27%. Conclusions Despite veterans' high prevalence of obesity, behavioral and surgical weight management participation is low and varies across regions.

The lateral portion of the entorhinal cortex is one of the first brain regions affected by tau pathology, an important biomarker for Alzheimer disease. Improving our understanding of this region's cognitive role may help identify better cognitive tests for early detection of Alzheimer disease. Based on its functional connections, we tested the idea that the human anterolateral entorhinal cortex (alERC) may play a role in integrating spatial information into object representations. We recently demonstrated that the volume of the alERC was related to processing the spatial relationships of the features within an object [Yeung, L. K., Olsen, R. K., Bild-Enkin, H. E. P., D'Angelo, M. C., Kacollja, A., McQuiggan, D. A., et al. Anterolateral entorhinal cortex volume predicted by altered intra-item configural processing. Journal of Neuroscience, 37, 5527–5538, 2017]. In this study, we investigated whether the human alERC might also play a role in processing the spatial relationships between an object and its environment using an eye-tracking task that assessed visual fixations to a critical object within a scene. Guided by rodent work, we measured both object-in-place memory, the association of an object with a given context [Wilson, D. I., Langston, R. F., Schlesiger, M. I., Wagner, M., Watanabe, S., & Ainge, J. A. Lateral entorhinal cortex is critical for novel object-context recognition. Hippocampus, 23, 352–366, 2013], and object-trace memory, the memory for the former location of objects [Tsao, A., Moser, M. B., & Moser, E. I. Traces of experience in the lateral entorhinal cortex. Current Biology, 23, 399–405, 2013]. In a group of older adults with varying stages of brain atrophy and cognitive decline, we found that the volume of the alERC and the volume of the parahippocampal cortex selectively predicted object-in-place memory, but not object-trace memory. These results provide support for the notion that the alERC may integrate spatial information into object representations.

Objective Including partners in interventions to increase physical activity (PA) could promote better adherence and longer-term effects. In preparation for a future large-scale randomized controlled trial (RCT), this randomized pilot trial tested the acceptability of a novel couple-based PA intervention for breast and prostate cancer survivors and the feasibility of conducting an RCT testing the intervention. Method Twenty cancer survivors (70% female; mean age = 63.0 years, SD = 8.9) and their partners (35% female; mean age = 62.8 years, SD = 7.7) were randomized to either the intervention or waitlist control. Couples in the intervention received four videoconference sessions including training in communication and support skills and behavior change techniques. Measures of PA and partner support for exercise were collected from survivors and partners before randomization and postintervention. Survivors also completed a physical well-being measure, and intervention participants completed a treatment acceptability measure. Results Recruitment was challenging; approximately 18% of eligible survivors and their partners agreed to participate. Ninety-two percent of randomized participants completed postintervention surveys, and 78% of dyads randomized to the intervention arm completed all 4 sessions. Mean acceptability ratings were moderate to high. Mean difference scores suggested that participants in the intervention arm tended to report greater improvements in PA, partner support, and physical well-being than those in the control arm. Conclusions These preliminary findings suggest that the couple-based PA intervention was acceptable to survivors and their partners and that a large-scale RCT is likely to be feasible with modified recruitment strategies. Recommendations for improving recruitment and conducting a larger study are presented. (PsycINFO Database Record

Behavioral weight loss interventions are often delivered in groups. Group cohesion may enhance program attendance and, thereby, weight loss. In this secondary analysis, our goals were to: (1a) assess whether group cohesion measured early in a behavioral weight loss intervention predicts program attendance and weight loss outcomes and, if so, (1b) explore whether attendance mediates the link between group cohesion and weight loss; (2) characterize the association between change in group cohesion and weight loss throughout the intervention. Veterans (n = 324) initiated a 16-week, group-based behavioral weight loss program involving biweekly in-person group visits. In linear regression models, early group cohesion was unrelated to group attendance or weight loss. Although group cohesion significantly increased during the intervention, this change was not associated with weight loss. These findings are consistent with the limited literature; however, they are inconsistent with theoretical assertions and clinical observations of the influence of group factors on outcomes.

Research using eye movement monitoring suggests that recapitulating the pattern of eye movements made during stimulus encoding at subsequent retrieval supports memory by reinstating the spatial layout of the encoded stimulus. In the present study, the authors investigated whether recapitulation of encoding fixations during a poststudy, stimulus-free delay period-an effect that has been previously linked to memory maintenance in younger adults-can support mnemonic performance in older adults. Older adults showed greater delay-period fixation reinstatement than younger adults, and this reinstatement supported age-equivalent performance on a subsequent visuospatial-memory-based change detection task, whereas in younger adults, the performance-enhancing effects of fixation reinstatement increased with task difficulty. Taken together, these results suggest that fixation reinstatement might reflect a compensatory response to increased cognitive load. The present findings provide novel evidence of compensatory fixation reinstatement in older adults and demonstrate the utility of eye movement monitoring for aging and memory research. (PsycINFO Database Record

OBJECTIVES To test a collaborative care model for interfacing sleep specialists with primary care providers to enhance patients' sleep disorders management. METHODS This study used a randomized, parallel group, clinical intervention trial design. A total of 137 adult (29 women) VA outpatients with sleep complaints were enrolled and randomly assigned to (1) an intervention (INT) consisting of a one-time consultation with a sleep specialist who provided diagnostic feedback and treatment recommendations to the patient and the patient's primary care provider; or (2) a control condition consisting of their usual primary care (UPC). Provider-focused outcomes included rates of adherence to recommended diagnostic procedures and sleep-focused interventions. Patient-focused outcomes included measures taken from sleep diaries and actigraphy; Pittsburgh Sleep Quality Index (PSQI) scores; and self-report measures of sleepiness, fatigue, mood, quality of life, and satisfaction with health care. RESULTS The proportions of provider-initiated sleep-focused interventions were significantly higher in the INT group than in the UPC group for polysomnography referrals (49% versus 6%; P < 0.001) and mental health clinic referrals (19% versus 6%; P = 0.02). At the 10-mo follow up, INT recipients showed greater estimated mean reductions in diary total wake time (-17.0 min; 95% confidence interval [CI]: -30.9, -3.1; P = 0.02) and greater increases in sleep efficiency (+3.7%; 95% CI: 0.8, 6.5; P = 0.01) than did UPC participants. A greater proportion of the INT group showed ≥ 1 standard deviation decline on the PSQI from baseline to the 10-mo follow-up (41% versus 21%; P = 0.02). Moreover, 69% of the INT group had normal (≤ 10) Epworth Sleepiness Scale scores at the 10-mo follow-up, whereas only 50% of the UPC group fell below this clinical cutoff (P = 0.03). CONCLUSIONS A one-time sleep consultation significantly increased healthcare providers' attention to sleep problems and resulted in benefits to patients' sleep/wake symptoms. CLINICAL TRIALS REGISTRATION This study is registered with clinicaltrials.gov with identifier # NCT00390572.

Objective:When caring for a loved one with a life-limiting illness, a caregiver's own physical, emotional, and spiritual suffering can be profound. While many interventions focus on physical and emotional well-being, few caregiver interventions address existential and spiritual needs and the meaning that caregivers ascribe to their role. To evaluate the feasibility and acceptability of the process and content of Caregiver Outlook, we employed a manualized chaplain-led intervention to improve well-being by exploring role-related meaning among caregivers of patients with a life-limiting illness.Method:We conducted a single-arm pre–post pilot evaluation among caregivers of patients with advanced cancer or amyotrophic lateral sclerosis (ALS). Caregivers completed three chaplain-led intervention sessions focusing on (1) a relationship review, (2) forgiveness, and (3) legacy. Outcomes administered at baseline and at 1 and 2 weeks after the intervention included quality of life, anxiety, depression, spiritual well-being, religious coping, caregiver burden, and grief.Results:The sample (N = 31) included a range of socioeconomic status groups, and the average age was approximately 60 years. A third of them worked full-time. Some 74% of our participants cared for a spouse or partner, and the other quarter of the sample cared for a parent (13%), child (10%), or other close family member (3%). At baseline, participants did not demonstrate clinical threshold levels of anxiety, depression, or other indicators of distress. Outcomes were stable over time. The qualitative results showed the ways in which Caregiver Outlook was assistive: stepping back from day-to-day tasks, the opportunity to process emotions, reflecting on support received, provoking thoughts and emotions between sessions, discussing role changes, stimulating communication with others, and the anonymity of a phone conversation. Both religious and nonreligious participants were pleased with administration of the chaplain intervention.Significance of results:The acceptability and feasibility of Caregiver Outlook were demonstrated among caregivers of patients with an advanced illness. Our pilot findings suggest minor modifications to study participant screening, interventionist guidance, and the study measures.

Telemedicine-based medication management improves hypertension control, but has been evaluated primarily in patients with low antihypertensive drug counts. Its impact on patients taking three or more antihypertensive agents is not well-established. To address this evidence gap, the authors conducted an exploratory analysis of an 18-month, 591-patient trial of telemedicine-based hypertension medication management. Using general linear models, the effect of medication management on blood pressure for patients taking two or fewer antihypertensive agents at study baseline vs those taking three or more was compared. While patients taking two or fewer antihypertensive agents had a significant reduction in systolic blood pressure with medication management, those taking three or more had no such response. The between-subgroup effect difference was statistically significant at 6 months (-6.4 mm Hg [95% confidence interval, -12.2 to -0.6]) and near significant at 18 months (-6.0 mm Hg [95% confidence interval, -12.2 to 0.2]). These findings suggest that baseline antihypertensive drug count may impact how patients respond to hypertension medication management and emphasize the need to study management strategies specifically in patients taking three or more antihypertensive medications.

Current theories state that the hippocampus is responsible for the formation of memory representations regarding relations, whereas extrahippocampal cortical regions support representations for single items. However, findings of impaired item memory in hippocampal amnesics suggest a more nuanced role for the hippocampus in item memory. The hippocampus may be necessary when the item elements need to be bound within and across episodes to form a lasting representation that can be used flexibly. The current investigation was designed to test this hypothesis in face recognition. H.C., an individual who developed with a compromised hippocampal system, and control participants incidentally studied individual faces that either varied in presentation viewpoint across study repetitions or remained in a fixed viewpoint across the study repetitions. Eye movements were recorded during encoding and participants then completed a surprise recognition memory test. H.C. demonstrated altered face viewing during encoding. Although the overall number of fixations made by H.C. was not significantly different from that of controls, the distribution of her viewing was primarily directed to the eye region. Critically, H.C. was significantly impaired in her ability to subsequently recognize faces studied from variable viewpoints, but demonstrated spared performance in recognizing faces she encoded from a fixed viewpoint, implicating a relationship between eye movement behavior in the service of a hippocampal binding function. These findings suggest that a compromised hippocampal system disrupts the ability to bind item features within and across study repetitions, ultimately disrupting recognition when it requires access to flexible relational representations.

Recent evidence suggests that sleep disturbance may play an important role in the development of cardiovascular disease (CVD). Despite the prevalence of sleep complaints among service members of recent military conflicts, few studies have examined associations between sleep and risk factors for CVD in this population. Symptom checklist items regarding distress about "trouble falling asleep" and "restless/disturbed sleep" were used as proxies for sleep onset and maintenance difficulties to examine these associations in US military service members of recent conflicts. Veterans having both sleep onset and maintenance difficulties had greater odds of being a current smoker and having psychiatric symptoms and diagnoses. Increased odds of a self-reported hypertension diagnosis and elevated systolic blood pressure were also found in certain subsets of this sample. Findings highlight the need for greater recognition of sleep difficulties as a CVD risk factor in a population known to be at increased risk for this condition.

Elevated low-density lipoprotein cholesterol (LDL-C) is a major modifiable risk factor for cardiovascular disease, a leading cause of death in the United States. Our goal was to evaluate a simple, scalable, and affordable medication packaging method for improving cholesterol medication adherence and subsequently lowering LDL-C levels.Mixed-method study.This mixed-method study involved US military veterans with LDL-C levels greater than 130 mg/dL and/or less than 80% refill adherence of cholesterol-lowering medication in the last 12 months; they were randomized to an education-only (control) group or an adherence packaging intervention group. Adherence packaging group participants' statin medication was provided in special blister packaging labeled for daily use that included written reminder prompts. Outcomes included 12-month cholesterol medication possession ratio (MPR) for medication refills; baseline, 6-, and 12-month self-reported cholesterol medication use; LDL-C and high-density lipoprotein cholesterol (HDL-C) levels; and total cholesterol changes over 12 months. Qualitative evaluation of the intervention is presented as well.We enrolled 240 individuals (120 intervention, 120 control). Overall, 54.2% of the adherence packaging intervention group was adherent per MPR over 12 months compared with 46.6% of the education-only group (difference = 7.6%; 95% confidence interval, -5% to 20%; P ≤.24). Both arms reported improvements in self-reported cholesterol adherence at 12 months, and decreases in LDL-C, HDL-C, and total cholesterol were observed, but differences in change between arms were not statistically significant. Qualitatively, patients reported high levels of satisfaction with the blister package.In a sample of US veterans, prefilled calendared blister packaging provided an inexpensive method for improving cholesterol medication adherence.

Background Comprehensive programs addressing tailored patient self-management and pharmacotherapy may reduce barriers to cardiovascular disease (CVD) risk reduction. Methods This is a 2-arm (clinical pharmacist specialist–delivered, telehealth intervention and education control) randomized controlled trial including Veterans with poorly controlled hypertension and/or hypercholesterolemia. Primary outcome was Framingham CVD risk score at 6 and 12 months, with systolic blood pressure; diastolic blood pressure; total cholesterol; low-density lipoprotein; high-density lipoprotein; body mass index; and, for those with diabetes, HbA1c as secondary outcomes. Results Among 428 Veterans, 50% were African American, 85% were men, and 33% had limited health literacy. Relative to the education control group, the clinical pharmacist specialist–delivered intervention did not show a reduction in CVD risk score at 6 months (−1.8, 95% CI −3.9 to 0.3; P = .10) or 12 months (−0.3, 95% CI −2.4 to 1.7; P = .74). No differences were seen in systolic blood pressure, diastolic blood pressure, or low-density lipoprotein at 6 or 12 months. We did observe a significant decline in total cholesterol at 6 months (−7.0, 95% CI −13.4 to −0.6; P = .03) in the intervention relative to education control group. Among patients in the intervention group, 34% received at least 5 of the 12 planned intervention calls and were considered “compliers.” A sensitivity analysis of the “complier average causal effect” of intervention compared to control showed a mean difference in CVD risk score reduction of 5.7 (95% CI −12.0 to 0.7) at 6 months and −1.7 (95% CI −7.6 to 4.8) at 12 months. Conclusions Despite increased access to pharmacist resources, we did not observe significant improvements in CVD risk for patients randomized to the intervention compared to education control over 12 months. However, the intervention may have positive impact among those who actively participate, particularly in the short term.

Background Health educators in public high schools can provide educational interventions to reduce teen unintended pregnancy and sexually transmitted infections (STIs). Characteristics of teachers and schools influence their decision to provide condom education. Studies to determine characteristics must be conducted so HIV/sex education can be improved. If schools do not participate in these studies, barriers must be identified so researchers can collect sufficient data to produce information for curriculum reform. Methods A study was conducted to identify teacher characteristics that influence their decision and intention to provide appropriate condom education. Follow-up e-mails were sent to administrators who opted out of the study to request more information about their decision to not participate. All responses were submitted via e-mail correspondence. Results Six superintendents and 6 principals provided a reason for their decision to opt out. Superintendents cited being busy with district initiatives, time constraints, and lack of interest in participating in the study as reasons they did not wish to participate. Principals cited competing requests for participation in research, participation in other surveys, and time constraints. Conclusions Securing administrative approval for human sexuality research is challenging. Administrators contend with many priorities, do not wish to overburden teachers, consider participation in voluntary research as a low priority, and may be more likely to respond to telephone requests. Administrators may not want to disclose that human sexuality or HIV education courses may not be taught by certified or qualified health educators.

Background Weight regain after successful weight loss interventions is common. Objective To establish the efficacy of a weight loss maintenance program compared with usual care in obese adults. Design 2-group, parallel, randomized trial stratified by initial weight loss (

Compared with men, women have poorer lipid control. Although potential causes of this disparity have been explored, it is unknown whether patient-centered factors such as satisfaction and confidence contribute. We evaluated (1) whether satisfaction with lipid control and confidence in ability to improve it vary by gender and (2) whether sociodemographic characteristics modify the association.We evaluated baseline survey responses from the Cardiovascular Intervention Improvement Telemedicine Study, including self-rated satisfaction with cholesterol levels and confidence in controlling cholesterol. Participants had poorly controlled hypertension and/or hypercholesterolemia.A total of 428 veterans (15% women) participated. Compared with men, women had higher low-density lipoprotein values at 141.2 versus 121.7 mg/dL, respectively (p 0.05), higher health literacy, and were less likely to have someone to help track their medications (all p 0.05). In an adjusted model, women were less satisfied with their cholesterol levels than men with estimated mean scores of 4.3 versus 5.6 on a 1-10 Likert scale (p 0.05). There was no significant difference in confidence by gender. Participants with support for tracking medications reported higher confidence levels than those without, estimated mean 7.8 versus 7.2 (p 0.05).Women veterans at high risk for cardiovascular disease were less satisfied with their lipid control than men; however, confidence in ability to improve lipid levels was similar. Veterans without someone to help to track medications were less confident, and women were less likely to have this type of social support. Lack of social support for medication tracking may be a factor in lingering gender-based disparities in hyperlipidemia.