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Background: Cutaneous lupus erythematosus (CLE) can present later in life, but frequency and risk factors of late-onset CLE patients are not well characterized. The study determined frequency of late-onset CLE and compared the demographic and disease characteristics between early-onset and late-onset CLE in a cohort of patients with CLE. Objectives: To determine the frequency and compare clinical features of early-onset and late-onset CLE. Methods: This was a cross-sectional study of CLE patients seen in outpatient dermatology clinics at University of Texas Southwestern Medical Center (UTSW) and Parkland Health and Hospital System, Dallas, TX, from April 2009 to May 2019. The primary outcome was the age of CLE onset, stratified by early-onset (<50 years) and late-onset CLE (≥50 years). Predictor variables significantly associated with CLE onset groups were identified by univariate and multivariable logistic regression analyses. Results: Of the 291 CLE patients studied, 79% were early-onset, and 21% were late-onset. Multivariable logistic regression analyses identified that Caucasian race (odds ratio (OR): 2.23, 95% Confidence Interval (CI): 1.19–4.19, p = 0.013), having a CLE subtype other than chronic (OR: 2.18, 95% CI: 1.02–4.65, p = 0.044), and drug-induced cases (OR: 4.65, 95% CI: 1.18–18.24, p = 0.028) were significantly associated with late-onset CLE. Early-onset CLE patients were more likely to have oral ulcers (OR: 3.58, 95% CI: 1.46–8.78, p = 0.005) and renal disorders (OR: 4.02, 95% CI: 1.10–14.71, p = 0.036). Limitations: This was a single center study. Age of onset was self-reported and late-onset CLE cohort has a small sample size. Conclusions: Our diverse cohort of CLE patients had about one out of five patients with CLE experiencing disease onset after 50 years old. These patients have distinct demographic and clinical presentations compared to early-onset CLE patients. Providers should remain mindful of CLE in older patients with photosensitive rashes and mild systemic symptoms. [ABSTRACT FROM AUTHOR]

Objective: Few concussion studies have investigated the psychological domain of concussions. Of the 22 postconcussion symptoms assessed on the Graded Symptom Checklist of the SCAT-5, five do not overlap with core symptoms of anxiety and depression. 43% of patients report at least one psychiatric symptom, the median is four after injury. Previous studies focus on total scores and not individual items; furthermore, few consider resilience as part of psychological factors that impact recovery. This research aims to describe general and specific characteristics of psychological functioning in males/females ages 12-18 after concussion to help guide treatment. We compared total scores for each measure between males/females and looked at the differences between the genders for individual items in each measure. Participants and Methods: Participants were evaluated at an outpatient concussion clinic participating in the North Texas Concussion Registry (ConTex; N=1238, 53% female, mean age=15.4 years, SD=1.16 years). The Generalized Anxiety Disorder 7-item Scale (GAD-7, the Patient Health Questionnaire-8 (PHQ-8), the Brief Resilience Scale (BRS), and the Pittsburgh Sleep Quality Index (PSQI) were used to determine levels of anxiety, depression, resilience, and sleep quality. Results: Utilizing Mann-Whitney U tests (median, interquartile range) to examine group distributions for the GAD-7, PHQ-8, and BRS, females had significantly higher scores than males for the GAD (p<0.001; Female: 4, 1-9 v. Male: 2, 0-5) and PHQ (p<0.001; Female: 5, 210 v. Male: 3, 1-7). For the BRS, total scores for females were significantly lower than males (p<0.001; Female: 3.67, 3-4 v. Male: 3.83, 3.214.33). The PSQI media score was significantly different between males and females: item 2, p=.016 and item 4 p=.007 using an exact sampling distribution for U. Pearson Chi square tests were used to examine sex differences for each item of the psychological measures. Items 1-7 within the GAD-7 were significant between sexes (i.e. male or female). The seven items assess (1) Feelings of nervousness, (2) Inability to stop/control worry, (3) Worrying too much about different things, (4) Trouble relaxing, (5) Inability to sit still due to restlessness, (6) Irritability, and (7) Feeling afraid. Items 2-8 within the PHQ were significant between sexes. The items assess (2) Feeling down/depressed/hopeless, (3) Trouble falling/staying asleep, (4) Feeling tired/no energy, (5) Appetite changes, (6) Lowered/poor self-esteem, (7) Concentration issues, and (8) Feeling slowed down or unable to be still. There was a statistically significant difference between genders and Items 2 and 4 within the BRS were significant between sexes. The items assess (2) Difficulty surviving hard times and (4) Difficulty snapping back from something bad. Conclusions: Like other studies, this study found females have higher levels of negative affect (i.e., depressive and anxious symptoms). Females displayed lower resilience and reported poorer sleep. By analyzing psychiatric measures, treatment protocols can be tailored to address specific problems, and mental health difficulties can be mitigated by teaching specific coping techniques. These results suggest clinicians should consistently be providing education on depression, anxiety, sleep, and resilience, particularly to female patients, who appear at greater risk for psychological distress. [ABSTRACT FROM AUTHOR]

Background: Changes in Gc‐globulin (Gc) and in alpha‐foetoprotein (AFP) have been shown to be related to outcome in patients with acute liver failure (ALF). Gc is a serum protein that complexes with intravascular actin released during cellular necrosis. AFP, also made by hepatocytes, is associated with hepatocellular growth and regeneration. Previously, low absolute levels or decreases over time in either AFP or Gc portended to be a poor outcome. Methods: In a retrospective analysis of the double‐blind trial of intravenous N‐acetylcysteine (NAC) for ALF not because of acetaminophen, sera on days 1 and 3 or days 2 and 4 following admission were available to measure AFP in 70 patients and Gc in 66 patients. Mann‐Whitney U tests were performed on the admission values, the absolute change and the fractional change of AFP and Gc to compare TFS (transplant‐free survival) and non‐TFS (death or transplantation). Logistic regression and receiver operating characteristic (ROC) analyses were performed to evaluate the markers in comparison and in addition to King's College Criteria (KCC). Results: Transplant‐free survival patients were characterized by increases in AFP, whereas non‐TFS had significantly different (negative) absolute and fractional changes (P < .01). The addition of declining AFP levels to KCC improved the area under the curve in predicting non‐TFS (AUC >70%). Gc globulin values did not differ between TFS and non‐TFS in the 2‐day intervals studied (P> .2). Conclusion: In this comparison of two prognostic markers in patients with non‐acetaminophen‐induced ALF, rising AFP but not rising Gc levels was associated with TFS. Trial Registration: ClinicalTrials.gov number NCT00004467. [ABSTRACT FROM AUTHOR]

With mobile health technologies serving as an alternative means of providing healthcare, evaluating patients' abilities to navigate digital infrastructures is becoming increasingly relevant. The goal of this study is to investigate smartphone use patterns among individuals with history of moderate-to-severe traumatic brain injury (TBI). An anonymous survey was delivered via e-mail or text message to eligible participants who had a history of moderate-to-severe TBI and were prospectively followed at one of the eight participating Traumatic Brain Injury Model Systems centers for at least 1-year post-injury. The survey captured demographic data and included a questionnaire to evaluate smartphone use (calling, texting, web browsing, etc.). A total of 2665 eligible individuals were contacted to complete the survey, 472 of which responded. 441 of them reported smartphone use. Individuals ages 45 and older were significantly less likely to use their phones for functions other than calling and texting when compared to individuals ages 18–44 (p < 0.05). Most individuals with moderate-to-severe TBI in this cohort demonstrated intentional smartphone use, suggesting that mobile health technologies may be feasible as a cost-effective healthcare alternative. However, doing so will require additional interventions to provide further technological education especially in older individuals with TBI. [ABSTRACT FROM AUTHOR]

Background: There are limited data on the efficacy of adjuvant therapy in ampullary cancer. The aim of this study was to determine whether adjuvant therapy was associated with improved survival for patients with ampullary cancer.Methods: From the National Cancer Database, we identified ampullary cancer patients who underwent resection between 2004 and 2013. We performed 1:1 propensity score matching, comparing patients who had postoperative observation to patients who received adjuvant chemotherapy (ACT) or adjuvant chemoradiotherapy (ACRT).Results: We identified 4190 patients who fit our inclusion criteria; 63% had postoperative observation, 21% received ACT, and 16% underwent ACRT. In the matched cohorts, the use of ACT was associated with improved overall survival (HR = 0.82, 95% CI = 0.71 to 0.95). The median overall survival was 47.2 months for the ACT group and 35.5 months for the observation group. In a separate matched analysis, ACRT was also associated with improved survival (HR = 0.84, 95% CI = 0.72 to 0.98) as compared to observation. The median overall survival was 38.1 months for the ACRT group and 31.0 months for the observation group. The benefit was more pronounced in high-risk patients, such as ones with higher T and N categories.Conclusions: In this retrospective study, the use of adjuvant therapy in ampullary cancer was associated with significantly improved overall survival. The benefit of adjuvant therapy for this disease should be confirmed in a more rigorous fashion via randomized controlled trials. [ABSTRACT FROM AUTHOR]

Objective: Persisting concussion symptoms may adversely affect return to work and functioning in daily activities. This study compared adults who were initially evaluated < 30 days versus those evaluated ≥ 30 days following a concussion at a specialty concussion clinic to determine if delayed initial evaluation is associated with persisting symptoms during recovery. Method: Participants (N = 205) 18 years of age and older who sustained a concussion and presented to a North Texas Concussion Registry (ConTex) clinic were evaluated at two time points: initial clinical visit and three-month follow-up. Participants provided medical history, injury related information, and completed the Sport Concussion Assessment Tool-5 Symptom Evaluation, Generalized Anxiety Disorder 7-item scale (GAD-7), and Patient Health Questionnaire (PHQ-8). Participants were divided into two groups: early and delayed evaluation (±30 days post injury). Results: Number and severity of concussion symptoms were similar between both groups at their initial clinical visit. However, linear regression models showed that a delayed clinical evaluation was associated with a greater number and severity of concussion symptoms along with greater aggravation of symptoms from physical and cognitive activity at three-month follow-up. Conclusions: Individuals who sought care at specialty concussion clinics regardless of previous care 30 or more days following their injury reported more serious persisting concussion symptoms at three month follow-up than those who sought care sooner. Education to improve adults' recognition of concussions when they occur and obtaining earlier clinical evaluation may represent important opportunities in promoting better recovery and reducing persisting concussion symptoms. This study found that a delayed presentation to a specialty concussion clinic (30 or more days post-injury) regardless of previous evaluation was associated with poorer recovery outcomes in adults compared to those with an earlier presentation. Time from injury to a formal clinical evaluation of a concussion should be considered at initial evaluation by all providers and incorporated into prognosis and treatment planning. Concussion educational programs should be developed specifically for adults to promote recognition of concussions and importance of seeking prompt evaluation by specialized providers for this injury. [ABSTRACT FROM AUTHOR]

Background: Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF patients is challenging. Procalcitonin (PCT) has proven to be a useful marker in detecting bacterial infection. We sought to determine whether PCT discriminated between presence and absence of infection in patients with ALF. Method: Retrospective analysis of data and samples of 115 ALF patients from the United States Acute Liver Failure Study Group randomly selected from 1863 patients were classified for disease severity and ALF etiology. Twenty uninfected chronic liver disease (CLD) subjects served as controls. Results: Procalcitonin concentrations in most samples were elevated, with median values for all ALF groups near or above a 2.0 ng/mL cut-off that generally indicates severe sepsis. While PCT concentrations increased somewhat with apparent liver injury severity, there were no differences in PCT levels between the pre-defined severity groups–non-SIRS and SIRS groups with no documented infections and Severe Sepsis and Septic Shock groups with documented infections, (p = 0.169). PCT values from CLD patients differed from all ALF groups (median CLD PCT value 0.104 ng/mL, (p ≤0.001)). Subjects with acetaminophen (APAP) toxicity, many without evidence of infection, demonstrated median PCT >2.0 ng/mL, regardless of SIRS features, while some culture positive subjects had PCT values <2.0 ng/mL. Summary/Conclusions: While PCT appears to be a robust assay for detecting bacterial infection in the general population, there was poor discrimination between ALF patients with or without bacterial infection presumably because of the massive inflammation observed. Severe hepatocyte necrosis with inflammation results in elevated PCT levels, rendering this biomarker unreliable in the ALF setting. [ABSTRACT FROM AUTHOR]

Introduction: A recent metabolomic screen of sera from patients with Systemic Lupus Erythematosus (SLE) found reduction of antioxidants and substrates for energy generation. These metabolic alterations may underlie one of the most common features of SLE - fatigue. The metabolomic studies also noted reduced omega-3 fatty acids, which are powerful anti- oxidants. This deficiency may be causally related to oxidative stress, inflammation, disease activity, and fatigue in SLE. Supplementation of omega-3 fatty acids using fish oil in SLE has been shown to reduce oxidative stress in other studies. The objective of this study is to evaluate the effect of fish oil supplementation on clinical measures of fatigue, quality of life, and disease activity as part of a randomized clinical trial. Methods: Fifty SLE patients recruited in outpatient clinics were randomized 1:1 to fish oil supplementation or olive oil placebo, and blinded to their treatment group. At baseline and after 6 months of treatment, RAND Short Form-36 (RAND SF-36), Fatigue Severity Scale (FSS), SLE Disease Activity Index (SLEDAI), and Physician Global Assessment (PGA) were completed; serum was also collected for soluble mediator analysis. Results: Thirty-two patients completed the study. PGA improved significantly in the fish oil group compared with the placebo group (p = 0.015). The RAND SF-36 Energy/fatigue and Emotional well-being scores demonstrated improvement trends (p = 0.092 and 0.070). No clear difference was seen in FSS and SLEDAI (p = 0.350 and p = 0.417). Erythrocyte sedimentation rate and serum IL-12 were reduced (p = 0.008 and p = 0.058); while serum IL-13 was increased by fish oil supplementation (p = 0.033). Conclusions: In this randomized, placebo-controlled 6-month trial, SLE patients randomized to fish oil supplementation demonstrated improvement in their PGA, RAND SF-36, and some circulating inflammatory markers. Trial registration: ClinicalTrials.gov Identifier: NCT02021513 (registered 13 [ABSTRACT FROM AUTHOR]

Introduction: A recent metabolomic screen of sera from patients with Systemic Lupus Erythematosus (SLE) found reduction of antioxidants and substrates for energy generation. These metabolic alterations may underlie one of the most common features of SLE - fatigue. The metabolomic studies also noted reduced omega-3 fatty acids, which are powerful anti- oxidants. This deficiency may be causally related to oxidative stress, inflammation, disease activity, and fatigue in SLE. Supplementation of omega-3 fatty acids using fish oil in SLE has been shown to reduce oxidative stress in other studies. The objective of this study is to evaluate the effect of fish oil supplementation on clinical measures of fatigue, quality of life, and disease activity as part of a randomized clinical trial. Methods: Fifty SLE patients recruited in outpatient clinics were randomized 1:1 to fish oil supplementation or olive oil placebo, and blinded to their treatment group. At baseline and after 6 months of treatment, RAND Short Form-36 (RAND SF-36), Fatigue Severity Scale (FSS), SLE Disease Activity Index (SLEDAI), and Physician Global Assessment (PGA) were completed; serum was also collected for soluble mediator analysis. Results: Thirty-two patients completed the study. PGA improved significantly in the fish oil group compared with the placebo group (p = 0.015). The RAND SF-36 Energy/fatigue and Emotional well-being scores demonstrated improvement trends (p = 0.092 and 0.070). No clear difference was seen in FSS and SLEDAI (p = 0.350 and p = 0.417). Erythrocyte sedimentation rate and serum IL-12 were reduced (p = 0.008 and p = 0.058); while serum IL-13 was increased by fish oil supplementation (p = 0.033). Conclusions: In this randomized, placebo-controlled 6-month trial, SLE patients randomized to fish oil supplementation demonstrated improvement in their PGA, RAND SF-36, and some circulating inflammatory markers. [ABSTRACT FROM AUTHOR]

Objective: The Montreal Cognitive Assessment (MoCA) is a cognitive screening instrument growing in popularity, but few studies have conducted psychometric item analyses or attempted to develop abbreviated forms. We sought to derive and validate a short-form MoCA (SF-MoCA) and compare its classification accuracy to the standard MoCA and Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI), Alzheimer disease (AD), and normal aging.Methods: 408 subjects (MCIn = 169, ADn = 87, and normaln = 152) were randomly divided into derivation and validation samples. Item analysis in the derivation sample identified most sensitive MoCA items. Receiver Operating Characteristic (ROC) analyses were used to develop cut-off scores and evaluate the classification accuracy of the SF-MoCA, standard MoCA, and MMSE. Net Reclassification Improvement (NRI) analyses and comparison of ROC curves were used to compare classification accuracy of the three measures.Results: Serial subtraction (Cramer’sV = .408), delayed recall (Cramer’sV = .702), and orientation items (Cramer’sV = .832) were included in the SF-MoCA based on largest effect sizes in item analyses. Results revealed 72.6% classification accuracy of the SF-MoCA, compared with 71.9% for the standard MoCA and 67.4% for the MMSE. Results of NRI analyses and ROC curve comparisons revealed that classification accuracy of the SF-MoCA was comparable to the standard version and generally superior to the MMSE.Conclusions: Findings suggest the SF-MoCA could be an effective brief tool in detecting cognitive impairment. [ABSTRACT FROM PUBLISHER]

Alzheimer disease (AD) characteristically begins with episodic memory impairment followed by other cognitive deficits; however, the course of illness varies, with substantial differences in therateof cognitive decline. For research and clinical purposes it would be useful to distinguish between persons who will progress slowly from persons who will progress at an average or faster rate. Our objective was to use neurocognitive performance features and disease-specific and health information to determine a predictive model for the rate of cognitive decline in participants with mild AD. We reviewed the records of a series of 96 consecutive participants with mild AD from 1995 to 2011 who had been administered selected neurocognitive tests and clinical measures. Based on Clinical Dementia Rating (CDR) of functional and cognitive decline over 2 years, participants were classified as Faster (n= 45) or Slower (n= 51) Progressors. Stepwise logistic regression analyses using neurocognitive performance features, disease-specific, health, and demographic variables were performed. Neuropsychological scores that distinguished Faster from Slower Progressors included Trail Making Test - A, Digit Symbol, and California Verbal Learning Test (CVLT) Total Learned and Primacy Recall. No disease-specific, health, or demographic variable predicted rate of progression; however, history of heart disease showed a trend. Among the neuropsychological variables, Trail Making Test - A best distinguished Faster from Slower Progressors, with an overall accuracy of 68%. In an omnibus model including neuropsychological, disease-specific, health, and demographic variables, only Trail Making Test - A distinguished between groups. Several neuropsychological performance features were associated with the rate of cognitive decline in mild AD, with baseline Trail Making Test - A performance best separating those who declined at an average or faster rate from those who showed slower progression. [ABSTRACT FROM AUTHOR]

We conducted an open-trial proof of concept study to determine the safety, acceptability, and feasibility of Mindful Self-Care for Caregivers (MSCC) for parents of children with Autism Spectrum Disorders (ASD) (N = 13). The intervention was offered as a co-located care model in a pediatric specialty center where the participants' children received care. Results demonstrated that the intervention was: highly acceptable to all stakeholders (i.e., participants, the group facilitator, and center administration) and could be conducted safely by a masters-level practitioner with minimal resources. Further, secondary measures support a hypothesized interventional model of MSCC, demonstrating gains in mindfulness skills and sense of competency in the parenting role reduced perceived stress and depression in parents of children with ASD. [ABSTRACT FROM AUTHOR]

Background: Life expectancy (LE) following Alzheimer's disease (AD) is highly variable. The literature to date is limited by smaller sample sizes and clinical diagnoses.Objective: No study to date has evaluated predictors of AD LE in a retrospective large autopsy-confirmed sample, which was the primary objective of this study.Methods: Participants (≥50 years old) clinically and neuropathologically diagnosed with AD were evaluated using National Alzheimer's Coordinating Center (N = 1,401) data. Analyses focused on 21 demographic, medical, neuropsychiatric, neurological, functional, and global cognitive predictors of LE at AD dementia diagnosis. These 21 predictors were evaluated in univariate analyses. Variables found to be significant were then entered into a forward multiple regression. LE was defined as months between AD diagnosis and death.Results: Fourteen predictors were significant in univariate analyses and entered into the regression. Seven predictors explained 27% of LE variance in 764 total participants. Mini-Mental State Examination (MMSE) score was the strongest predictor of LE, followed by sex, age, race/ethnicity, neuropsychiatric symptoms, abnormal neurological exam results, and functional impairment ratings. Post-hoc analyses revealed correlations of LE were strongest with MMSE ≤12.Conclusion: Global cognitive functioning was the strongest predictor of LE following diagnosis, and AD patients with severe impairment had the shortest LE. AD patients who are older, male, white, and have more motor symptoms, functional impairment, and neuropsychiatric symptoms were also more likely have shorter LE. While this model cannot provide individual prognoses, additional studies may focus on these variables to enhance predictions of LE in patients with AD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Individuals with moderate to severe traumatic brain injury (msTBI) have reported a lack of motivation, lack of time, and fatigue as perceived barriers to exercise. OBJECTIVE: To evaluate the effects of an exercise program on self-reported health-related symptoms and quality of life in persons 45-years and older with msTBI. METHODS: Post-hoc analysis of a prospective community-based 12-week exercise program of 20 adults, age 45–80 years, with msTBI. Ten were in aerobic exercise training (AET) program and 10 in a stretching and toning (SAT) program. The AET group was instructed to exercise based on their estimated maximal heart rate (HR) for 150 minutes weekly. The SAT group was to stretch for the same target time without significantly increasing HR or level of exertion. Outcome measures were Traumatic Brain Injury Quality of Life (TBI-QOL) for global, cognitive, emotional, and social health, Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. RESULTS: AET was associated with improved self-reported cognitive health and sleep compared to SAT. Moderate to large, positive effect sizes were also observed in the AET group in the QOL categories of global, emotional, and social health, and depressive symptoms. CONCLUSIONS: This study offers preliminary evidence that AET may improve health-related QOL, especially for cognition and sleep, in middle-aged and older adults with msTBI. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To identify clinical and demographic characteristics associated with prolapse recurrence by 12 months after native tissue transvaginal repair. METHODS: This was a planned secondary analysis of a randomized trial including postmenopausal participants with stage 2 or greater apical or anterior vaginal prolapse scheduled for surgical repair at three U.S. sites. Participants underwent vaginal hysterectomy (if uterus was present) and standardized uterosacral or sacrospinous ligament suspension at the surgeon's discretion. The intervention was perioperative (5 weeks or more preoperatively and 12 months postoperatively) vaginal estrogen compared with placebo cream. The primary outcome was time to failure by 12 months after surgery, defined by objective prolapse of the anterior or posterior walls beyond the hymen or the apex descending more than one-third of the vaginal length, symptomatic vaginal bulge, or retreatment. For this analysis, participants were grouped according to failure compared with success, and multiple factors were compared, including age, time since menopause, race and ethnicity, parity, body mass index (BMI), baseline genital hiatus measurement, prolapse stage and point of maximal prolapse, surgery type (uterosac-ral or sacrospinous ligament suspension), and concomitant procedures. Factors were assessed for association with the hazard of surgical failure using Cox proportional hazards models, adjusted for site and treatment group. Factors with PC.50 from this analysis were considered for inclusion in the final multivariable model; site and treatment group were kept in this model. RESULTS: One hundred eighty-six participants underwent surgery;183 provided complete data. There were 30 failures (16.4%) and 153 successes (83.4%) at 12 months. On bivariate analysis, failure was associated with decreasing age, shorter duration since menopause, Latina ethnicity, and greater baseline genital hiatus. In the final multivariable model, which included age, BMI, and point of maximal prolapse, only age remained significantly associated with surgical failure (adjusted hazard ratio [per year] 0.92, 95% CI, 0.860.98, P=.016). CONCLUSION: Among postmenopausal women, younger age was associated with increased frequency of prolapse recurrence by 12 months after native tissue repair. [ABSTRACT FROM AUTHOR]

Background: Cutaneous lupus erythematosus (CLE) is an autoimmune photosensitive skin condition. The impact of income on quality of life has been incompletely characterized in CLE. Objectives: We aimed to assess how annual income affects quality of life among CLE patients. Methods: In this cross-sectional study of 238 patients with CLE, relationships between predictor variables including annual income and each SKINDEX-29 + 3 subdomain were identified using univariate and multivariable analyses. In addition, answers to individual SKINDEX-29 + 3 questions were compared across income groups. Clinical factors in patients making less than <10,000 USD (N = 85) with worse SKINDEX-29 + 3 scores were also identified by univariate and multivariable analyses. Results: Patients making <10,000 USD annually experienced worse quality of life across multiple SKINDEX-29 + 3 subdomains (p < 0.05). These patients specifically experienced poorer quality of life relating to social isolation and self-consciousness. (p < 0.001). Among those making <10,000 USD, predictors for worse quality of life included females, smokers, and those with higher skin disease activity were identified (p < 0.05). Limitations: This is a single center study. Income was also self-reported and could not be verified. Conclusions: Lower income is related to poorer quality of life in patients with CLE. Specifically, patients experience limitations regarding social isolation and self-consciousness. [ABSTRACT FROM AUTHOR]

Background Treatment options for nontuberculous mycobacteria (NTM) infections are limited by the pathogen's intrinsic resistance profile and toxicities. Tedizolid and linezolid display in vitro activity against NTM species. However, safety data and treatment outcomes are limited in the solid organ transplant (SOT) population. Methods This was a single-center retrospective cohort study of adult SOT recipients receiving linezolid or tedizolid for an NTM infection from January 1, 2010, to August 31, 2019. The primary outcome compared the hematologic safety profiles of tedizolid vs linezolid. We also described nonhematological adverse drug events (ADEs) and therapy discontinuation rates. In an exploratory analysis, we assessed symptomatic microbiologic and clinical outcomes in those receiving tedizolid or linezolid for at least 4 weeks. Results Twenty-four patients were included (15 tedizolid, 9 linezolid). No differences were identified comparing the effects of tedizolid vs linezolid on platelet counts, absolute neutrophil counts (ANCs), and hemoglobin over 7 weeks using mixed-effects analysis of variance models. ANC was significantly decreased in both groups after 7 weeks of therapy (P =.04). Approximately 20% of patients in each arm discontinued therapy due to an ADE. Seven of 12 (58%) and 2 of 3 (67%) patients were cured or clinically cured with tedizolid- and linezolid-containing regimens, respectively. Conclusions This study suggests no significant safety benefit of tedizolid over linezolid for the treatment of NTM infections in SOT recipients. Tedizolid or linezolid-containing regimens demonstrated a potential benefit in symptomatic and microbiologic improvement. Larger cohorts are needed to further delineate the comparative role of linezolid and tedizolid for the treatment of NTM infections in SOT recipients. [ABSTRACT FROM AUTHOR]

Alarming rates of burnout in surgical training pose a concern due to its deleterious effects on both patients and providers. Datum remains lacking on rates of burnout in surgical residents based on race and ethnicity. This study aims to document the frequency of burnout in surgical residents of racially underrepresented backgrounds and elucidate contributing factors. A 35-question anonymized survey was distributed to general surgery residents from 23 programs between August 2018 and May 2019. This survey was designed from the validated Maslach Burnout Inventory, and included additional questions assessing participant demographics, educational, and social backgrounds. Responses were analyzed utilizing chi-square tests and Wilcoxon rank sum tests. There was also a free response portion of the survey which was evaluated using thematic analysis. We received 243 responses from 23 general surgery programs yielding a 9% (23/246) program response rate and 26% (243/935) response rate by surgical residents. One hundred and eighty-five participants (76%) identified as nonunderrepresented in medicine and 58 (24%) of participants identified as underrepresented in medicine. Fifty-three percent were male and 47% female. Overall, sixty-six percent of all surgical residents (n = 161) endorsed burnout with racially underrepresented residents reporting higher rates of burnout at 76% compared to 63% in their nonunderrepresented counterparts (P = 0.07). Although the generalizability of these results is limited, higher rates of reported burnout in racially underrepresented trainees noted in our study illuminates the need for continual dialogue on potential influencing factors and mitigation strategies. • Burnout is an increasing phenomenon with potential deleterious effects on both patients and providers. • Data is lacking on rates of burnout in surgical trainees who are underrepresented in medicine (UIM). • UIM residents had higher rates of burnout than non-UIM residents. • Imposter syndrome and staff interaction were the most common contributing factors. • There's a need for continual dialogue on mitigating burnout in UIM surgical trainees. [ABSTRACT FROM AUTHOR]

Objective To establish a cut score for the Montreal Cognitive Assessment (MoCA) that distinguishes mild cognitive impairment (MCI) from normal cognition (NC) in a community-based African American (AA) sample. Methods A total of 135 AA participants, from a larger aging study, diagnosed MCI (n = 90) or NC (n = 45) via consensus diagnosis using clinical history, Clinical Dementia Rating score, and comprehensive neuropsychological testing. Logistic regression models utilized sex, education, age, and MoCA score to predict MCI versus NC. Receiver operating characteristic (ROC) curve analysis determined a cut score to distinguish MCI from NC based on optimal sensitivity, specificity, diagnostic accuracy, and greatest perpendicular distance above the identity line. ROC results were compared with previously published MoCA cut scores. Results The MCI group was slightly older (M MCI = 64.76[5.87], M NC = 62.33[6.76]; p =.033) and less educated (M MCI = 13.07[2.37], M NC = 14.36[2.51]; p =.004) and had lower MoCA scores (M MCI=21.26[3.85], M NC = 25.47[2.13]; p <.001) than the NC group. Demographics were non-significant in regression models. The area under the curve (AUC) was significant (MoCA =.83, p <.01) and an optimal cut score of <24 maximized sensitivity (72%), specificity (84%), and provided 76% diagnostic accuracy. In comparison, the traditional cut score of <26 had higher sensitivity (84%), similar accuracy (76%), but much lower specificity (58%). Conclusions This study provides a MoCA cut score to help differentiate persons with MCI from NC in a community-dwelling AA sample. A cut score of <24 reduces the likelihood of misclassifying normal AA individuals as impaired than the traditional cut score. This study underscores the importance of culturally appropriate norms to optimize the utility of commonly used cognitive screening measures. [ABSTRACT FROM AUTHOR]

The primary cause of dyspnea on exertion in heart failure with preserved ejection fraction (HFpEF) is presumed to be the marked rise in pulmonary capillary wedge pressure during exercise; however, this hypothesis has never been tested directly. Therefore, we evaluated invasive exercise hemodynamics and dyspnea on exertion in patients with HFpEF before and after acute nitroglycerin (NTG) treatment to lower pulmonary capillary wedge pressure. Does reducing pulmonary capillary wedge pressure during exercise with NTG improve dyspnea on exertion in HFpEF? Thirty patients with HFpEF performed two invasive 6-min constant-load cycling tests (20 W): one with placebo (PLC) and one with NTG. Ratings of perceived breathlessness (0-10 scale), pulmonary capillary wedge pressure (right side of heart catheter), and arterial blood gases (radial artery catheter) were measured. Measurements of V ˙ / Q ˙ matching, including alveolar dead space (V d alv ; Enghoff modification of the Bohr equation) and the alveolar-arterial P o 2 difference (A-aDO 2 ; alveolar gas equation), were also derived. The ventilation (V ˙ e)/CO 2 elimination (V ˙ co 2) slope was also calculated as the slope of the V ˙ e and V ˙ co 2 relationship, which reflects ventilatory efficiency. Ratings of perceived breathlessness increased (PLC: 3.43 ± 1.94 vs NTG: 4.03 ± 2.18; P =.009) despite a clear decrease in pulmonary capillary wedge pressure at 20 W (PLC: 19.7 ± 8.2 vs NTG: 15.9 ± 7.4 mm Hg; P <.001). Moreover, V d alv (PLC: 0.28 ± 0.07 vs NTG: 0.31 ± 0.08 L/breath; P =.01), A-aDO 2 (PLC: 19.6 ± 6.7 vs NTG: 21.1 ± 6.7; P =.04), and V ˙ e / V ˙ co 2 slope (PLC: 37.6 ± 5.7 vs NTG: 40.2 ± 6.5; P <.001) all increased at 20 W after a decrease in pulmonary capillary wedge pressure. These findings have important clinical implications and indicate that lowering pulmonary capillary wedge pressure does not decrease dyspnea on exertion in patients with HFpEF; rather, lowering pulmonary capillary wedge pressure exacerbates dyspnea on exertion, increases V ˙ / Q ˙ mismatch, and worsens ventilatory efficiency during exercise in these patients. This study provides compelling evidence that high pulmonary capillary wedge pressure is likely a secondary phenomenon rather than a primary cause of dyspnea on exertion in patients with HFpEF, and a new therapeutic paradigm is needed to improve symptoms of dyspnea on exertion in these patients. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does perioperative application of intravaginal estrogen cream in postmenopausal women undergoing a standardized native tissue apical vaginal prolapse repair reduce prolapse recurrence? Findings: In this randomized clinical trial that included 186 participants with symptomatic anterior/apical vaginal prolapse, there was no statistically significant difference in the composite measure of treatment failure 12 months after the operation in those using vaginal estrogen cream before and after surgery compared with placebo (adjusted hazard ratio, 1.97). Meaning: Perioperative vaginal estrogen application does not reduce prolapse recurrence rates after native tissue transvaginal repair. Importance: Surgical repairs of apical/uterovaginal prolapse are commonly performed using native tissue pelvic ligaments as the point of attachment for the vaginal cuff after a hysterectomy. Clinicians may recommend vaginal estrogen in an effort to reduce prolapse recurrence, but the effects of intravaginal estrogen on surgical prolapse management are uncertain. Objective: To compare the efficacy of perioperative vaginal estrogen vs placebo cream on prolapse recurrence following native tissue surgical prolapse repair. Design, Setting, and Participants: This randomized superiority clinical trial was conducted at 3 tertiary US clinical sites (Texas, Alabama, Rhode Island). Postmenopausal women (N = 206) with bothersome anterior and apical vaginal prolapse interested in surgical repair were enrolled in urogynecology clinics between December 2016 and February 2020. Interventions: The intervention was 1 g of conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally nightly for 2 weeks and then twice weekly to complete at least 5 weeks of application preoperatively; this continued twice weekly for 12 months postoperatively. Participants underwent a vaginal hysterectomy (if uterus present) and standardized apical fixation (either uterosacral or sacrospinous ligament fixation). Main Outcomes and Measures: The primary outcome was time to failure of prolapse repair by 12 months after surgery defined by at least 1 of the following 3 outcomes: anatomical/objective prolapse of the anterior or posterior walls beyond the hymen or the apex descending more than one-third of the vaginal length, subjective vaginal bulge symptoms, or repeated prolapse treatment. Secondary outcomes included measures of urinary and sexual function, symptoms and signs of urogenital atrophy, and adverse events. Results: Of 206 postmenopausal women, 199 were randomized and 186 underwent surgery. The mean (SD) age of participants was 65 (6.7) years. The primary outcome was not significantly different for women receiving vaginal estrogen vs placebo through 12 months: 12-month failure incidence of 19% (n = 20) for vaginal estrogen vs 9% (n = 10) for placebo (adjusted hazard ratio, 1.97 [95% CI, 0.92-4.22]), with the anatomic recurrence component being most common, rather than vaginal bulge symptoms or prolapse repeated treatment. Masked surgeon assessment of vaginal tissue quality and estrogenization was significantly better in the vaginal estrogen group at the time of the operation. In the subset of participants with at least moderately bothersome vaginal atrophy symptoms at baseline (n = 109), the vaginal atrophy score for most bothersome symptom was significantly better at 12 months with vaginal estrogen. Conclusions and Relevance: Adjunctive perioperative vaginal estrogen application did not improve surgical success rates after native tissue transvaginal prolapse repair. Trial Registration: ClinicalTrials.gov Identifier: NCT02431897 This randomized clinical superiority trial compares the efficacy of perioperative vaginal estrogen vs placebo cream on native tissue prolapse surgery outcomes. [ABSTRACT FROM AUTHOR]

Sentinel lymph node biopsy isperformedfordetectionofmicrometastasestotheregional lymph nodes with hope for improved survival, although its current role in the management of conjunctival melanoma remainscontroversial. 1 Owing to clinical and histologic overlap, the differential for AFX often includes squamous cell carcinoma (SCC), melanoma, leiomyosarcoma, and cutaneous undifferentiated pleomorphic sarcoma (UPS). Etzkorn and colleagues 5 studied patient preferences in the treatment of facial melanomas and found that patients rated local recurrence risk as the most important attribute. Patient quality of life fluctuates before and after Mohs micrographic surgery: a longitudinal assessment of the patient experience. [Extracted from the article]

Introduction: A recent metabolomic screen of sera from patients with Systemic Lupus Erythematosus (SLE) found reduction of antioxidants and substrates for energy generation. These metabolic alterations may underlie one of the most common features of SLE--fatigue. The metabolomic studies also noted reduced omega-3 fatty acids, which are powerful anti- oxidants. This deficiency may be causally related to oxidative stress, inflammation, disease activity, and fatigue in SLE. Supplementation of omega-3 fatty acids using fish oil in SLE has been shown to reduce oxidative stress in other studies. The objective of this study is to evaluate the effect of fish oil supplementation on clinical measures of fatigue, quality of life, and disease activity as part of a randomized clinical trial. Methods: Fifty SLE patients recruited in outpatient clinics were randomized 1:1 to fish oil supplementation or olive oil placebo, and blinded to their treatment group. At baseline and after 6 months of treatment, RAND Short Form-36 (RAND SF-36), Fatigue Severity Scale (FSS), SLE Disease Activity Index (SLEDAI), and Physician Global Assessment (PGA) were completed; serum was also collected for soluble mediator analysis. Results: Thirty-two patients completed the study. PGA improved significantly in the fish oil group compared with the placebo group (p = 0.015). The RAND SF-36 Energy/fatigue and Emotional well-being scores demonstrated improvement trends (p = 0.092 and 0.070). No clear difference was seen in FSS and SLEDAI (p = 0.350 and p = 0.417). Erythrocyte sedimentation rate and serum IL-12 were reduced (p = 0.008 and p = 0.058); while serum IL-13 was increased by fish oil supplementation (p = 0.033). Conclusions: In this randomized, placebo-controlled 6-month trial, SLE patients randomized to fish oil supplementation demonstrated improvement in their PGA, RAND SF-36, and some circulating inflammatory markers. Trial Registration: ClinicalTrials.gov Identifier: NCT02021513 (registered 13 December 2013). [ABSTRACT FROM AUTHOR]

This study explored the utility of the Montreal Cognitive Assessment (MoCA) in the detection of cognitive change over time in a community sample (age ranging from 58 to 77 years). The MoCA was administered twice approximately 3.5 years apart (n = 139). Participants were classified as mild cognitive impairment (MCI) or cognitively intact at follow-up based on multidisciplinary consensus. We excluded 33 participants who endorsed cognitive complaints at baseline. The MCI group (n = 53) showed a significant decrease in MoCA scores (M = −1.83, p < .001, d = 0.64). When accounting for age and education, the MCI group showed a decline of 1.7 points, while cognitively intact participants remained stable. Using Reliable Change Indices established by cognitively intact group, 42% of MCI participants demonstrated a decline in MoCA scores. Results suggest that the MoCA can detect cognitive change in MCI over a 3.5-year period and preliminarily supports the utility of the MoCA as a repeatable brief cognitive screening measure. [ABSTRACT FROM AUTHOR]

The impact of aerobic exercise training (AET) on cerebral blood flow (CBF) regulation remains inconclusive. This study investigated the effects of one-year progressive, moderate-to-vigorous AET on CBF, central arterial stiffness, and cognitive performance in cognitively normal older adults. Seventy-three older adults were randomly assigned to AET or stretching-and-toning (SAT, active control) intervention. CBF was measured with 2D duplex ultrasonography. Central arterial stiffness, measured by carotid β-stiffness index, was assessed with the ultrasonography and applanation tonometry. Cerebrovascular resistance (CVR) was calculated as mean arterial pressure divided by CBF. A cognitive battery was administered with a focus on memory and executive function. Cardiorespiratory fitness was measured by peak oxygen consumption ( V ˙ O2peak). One-year AET increased V ˙ O2peak and CBF and decreased CVR and carotid β-stiffness index. In the AET group, improved V ˙ O2peak was correlated with increased CBF (r = 0.621, p = 0.001) and decreased CVR (r = −0.412, p = 0.037) and carotid β-stiffness index (r = −0.478, p = 0.011). Further, increased Woodcock-Johnson recall score was associated with decreased CVR (r = −0.483, p = 0.012) and carotid β-stiffness index (r = −0.498, p = 0.008) in AET group (not in SAT group). In conclusion, one-year progressive, moderate-to-vigorous aerobic exercise training increased CBF and decreased carotid arterial stiffness and CVR which were associated with improved memory function in cognitively normal older adults. [ABSTRACT FROM AUTHOR]

Purpose/Objective: This study sought to investigate the extent to which demographic and clinical characteristics predict which patients drop out of an interdisciplinary pain management program (IPP). Research Method/Design: Participants (N = 178 outpatients, 18–75 years of age) received treatment for various chronic pain conditions in an IPP (including biopsychosocial assessment, cognitive–behavioral, and physical therapies). Separate logistic regression analyses identified the demographic and clinical variables most predictive of attrition across five domains: (a) demographics, (b) number of medical and non/psychiatric diagnoses, (c) opioid use (yes versus no)/risk of misuse, (d) pain-related cognition and behavior, and (e) physical, social, and mental well-being. Significant predictors from the five domains were integrated in a final multivariable logistic regression model. Results: Among patients exposed to a 4-week IPP, 34% dropped out. In the final model, significant predictors of higher odds of attrition included younger age or being unemployed. Also, patients on opioids at preintervention had higher odds of completing the IPP than patients not on opioids at preintervention. Follow-up analyses revealed 24 of 37 completers (65%) on opioids at preintervention reduced or eliminated use over the course of the IPP. Conclusions/Implications: Because findings are limited by sample and design characteristics, they require replication yet offer novel hypotheses for identifying patients at risk of attrition. Specifically, patients with preintervention opioid use (contrasted with opioid dependence) may particularly benefit from an IPP. Patients at highest risk for early dropout can be targeted for specific engagement interventions to promote completion and effectiveness of IPP. Impact and Implications: Although research has been conducted on the topic of attrition in IPPs, the body of evidence is limited and conflicting. This study extends the work of Oosterhaven et al. (2019) by identifying additional clinical and demographic characteristics that predict attrition in adults participating in an IPP. This study confirms that younger age and unemployment status are significant predictors of IPP attrition and provides new evidence to suggest that opioid use may predict IPP completion. These findings may help clinicians reduce attrition by screening for risk factors and establish improved guidelines regarding opioid use in their specific programs (e.g., requiring complete detoxification versus partial stabilization of opioid use prior to program start). [ABSTRACT FROM AUTHOR]

Objective: To report descriptive and normative data for the Montreal Cognitive Assessment (MoCA) in a population-based African American sample. Method: The MoCA was administered to 1,419 African American participants (mean age 49.89 years, range 18-75, 64% female). After excluding those with subjective cognitive complaints (n = 301), normative data were generated by education and overlapping age ranges (n = 1,118). Pearson correlations and analysis of variance were used to examine the relationship to demographic variables, and frequency of missed items was reviewed. Results: Total MoCA scores (mean 22.3, SD 3.9) were lower than previously published normative data derived from an elderly Caucasian Canadian population with 80% falling below the suggested cutoff (<26) for impairment. Several MoCA items were missed by a large portion of the sample, including cube drawing (72%), delayed free recall (66% <4/5 words), sentence repetition (63%), and abstraction items (45%). Conclusion: This is the first study to examine normative performance on the MoCA specific to community-dwelling African Americans. Findings suggest that certain aspects of this measure and previously established cutoff scores may not be well-suited for some populations. [ABSTRACT FROM AUTHOR]

[Journal of Alzheimer's Disease, 86 (2022) 271-281, DOI 10.3233/JAD-215200] https://content.iospress.com/articles/journal-of-alzheimers-disease/jad215200 On page 275, there is an error in paragraph 2, section "Additional MMSE I post-hoc i analyses", line 9. In the original, it reads: I "Tukey's post-hoc test revealed significant differences (ps<0.001) in LE between mild (M = 35.8, SD = 26.6), moderate (M = 54.53, SD = 27.23), and severe (M = 67.14, SD = 27.49) cognitive impairment." i The correct line is: I "Tukey's post-hoc test revealed significant differences (p's<0.001) in LE between severe (M = 35.8, SD = 26.6), moderate (M = 54.53, SD = 27.23), and mild (M = 67.14,SD = 27.49) cognitive impairment.". [Extracted from the article]

Background: Exercise intolerance is a defining characteristic of heart failure with preserved ejection fraction (HFpEF). A marked rise in pulmonary capillary wedge pressure (PCWP) during exertion is pathognomonic for HFpEF and is thought to be a key cause of exercise intolerance. If true, acutely lowering PCWP should improve exercise capacity. To test this hypothesis, we evaluated peak exercise capacity with and without nitroglycerin to acutely lower PCWP during exercise in patients with HFpEF. Methods: Thirty patients with HFpEF (70+/-6 years of age; 63% female) underwent 2 bouts of upright, seated cycle exercise dosed with sublingual nitroglycerin or placebo control every 15 minutes in a single-blind, randomized, crossover design. PCWP (right heart catheterization), oxygen uptake (breath x breath gas exchange), and cardiac output (direct Fick) were assessed at rest, 20 Watts (W), and peak exercise during both placebo and nitroglycerin conditions. Results: PCWP increased from 8+/-4 to 35+/-9 mm Hg from rest to peak exercise with placebo. With nitroglycerin, there was a graded decrease in PCWP compared with placebo at rest (-1+/-2 mm Hg), 20W (-5+/-5 mm Hg), and peak exercise (-7+/-6 mm Hg; drug x exercise stage P =0.004). Nitroglycerin did not affect oxygen uptake at rest, 20W, or peak (placebo, 1.34+/-0.48 versus nitroglycerin, 1.32+/-0.46 L/min; drug x exercise P =0.984). Compared with placebo, nitroglycerin lowered stroke volume at rest (-8+/-13 mL) and 20W (-7+/-11 mL), but not peak exercise (0+/-10 mL). Conclusions: Sublingual nitroglycerin lowered PCWP during submaximal and maximal exercise. Despite reduction in PCWP, peak oxygen uptake was not changed. These results suggest that acute reductions in PCWP are insufficient to improve exercise capacity, and further argue that high PCWP during exercise is not by itself a limiting factor for exercise performance in patients with HFpEF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04068844. What Is New? * Sublingual nitroglycerin reduced exercise pulmonary capillary wedge pressure (PCWP) in patients with heart failure with preserved ejection fraction. * At a fixed 20W exercise work rate, nitroglycerin decreased PCWP by 5 mm Hg, whereas at peak exercise, PCWP decreased by 7 mm Hg. * Despite the reduction in PCWP, functional capacity (peak VO2) did not improve. What Are the Clinical Implications? * Acute reductions in PCWP are insufficient to improve exercise capacity in patients with heart failure with preserved ejection fraction. * These results suggest that high PCWP during exercise is not by itself a limiting factor for exercise performance in patients with heart failure with preserved ejection fraction. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure with preserved ejection fraction (HFpEF) exhibit many cardiopulmonary abnormalities that could result in V˙/Q˙ mismatch, manifesting as an increase in alveolar dead space (VDalveolar) during exercise. Therefore, we tested the hypothesis that VDalveolar would increase during exercise to a greater extent in patients with HFpEF compared with control participants.Research Question: Do patients with HFpEF develop VDalveolar during exercise?Study Design and Methods: Twenty-three patients with HFpEF and 12 control participants were studied. Gas exchange (ventilation [V˙E], oxygen uptake [V˙o2], and CO2 elimination [V˙co2]) and arterial blood gases were analyzed at rest, twenty watts (20W), and peak exercise. Ventilatory efficiency (evaluated as the V˙E/V˙co2 slope) also was measured from rest to 20W in patients with HFpEF. The physiologic dead space (VDphysiologic) to tidal volume (VT) ratio (VD/VT) was calculated using the Enghoff modification of the Bohr equation. VDalveolar was calculated as: (VD / VT × VT) - anatomic dead space. Data were analyzed between groups (patients with HFpEF vs control participants) across conditions (rest, 20W, and peak exercise) using a two-way repeated measures analysis of variance and relationships were analyzed using Pearson correlation coefficient.Results: VDalveolar increased from rest (0.12 ± 0.07 L/breath) to 20W (0.22 ± 0.08 L/breath) in patients with HFpEF (P < .01), whereas VDalveolar did not change from rest (0.01 ± 0.06 L/breath) to 20W (0.06 ± 0.13 L/breath) in control participants (P = .19). Thereafter, VDalveolar increased from 20W to peak exercise in patients with HFpEF (0.37 ± 0.16 L/breath; P < .01 vs 20W) and control participants (0.19 ± 0.17 L/breath; P = .03 vs 20W). VDalveolar was greater in patients with HFpEF compared with control participants at rest, 20W, and peak exercise (main effect for group, P < .01). Moreover, the increase in VDalveolar correlated with the V˙E/V˙co2 slope (r = 0.69; P < .01), which was correlated with peak V˙o2peak (r = 0.46; P < .01) in patients with HFpEF.Interpretation: These data suggest that the increase in V˙/Q˙ mismatch may be explained by increases in VDalveolar and that increases in VDalveolar worsens ventilatory efficiency, which seems to be a key contributor to exercise intolerance in patients with HFpEF. [ABSTRACT FROM AUTHOR]

Objective. Neuropsychological measures of processing speed have long been used as sensitive indices of cognitive functioning. Most of these commonly used tests are proprietary, and there is a need for brief, freely available tools that can be used in diverse clinical and research settings. The Southwestern Assessment of Processing Speed (SWAPS) is a 60-second digit-symbol transcription task developed as a brief alternative to commercially available coding tests. Demographically-corrected normative data are presented along with reliability and sensitivity/specificity values in older adults with and without cognitive impairment. Method. SWAPS data from 915 healthy aging individuals (NC) and 858 subjects with clinical diagnoses of mild cognitive impairment (MCI; n = 430) and Alzheimer's disease clinical syndrome (ADCS; n = 428) were obtained from the Texas Alzheimer's Research and Care Consortium (TARCC). TARCC participants represent ethnically and educationally diverse community-dwelling individuals age 50+. Results. SWAPS scores showed the expected associations with age, sex, and education, and the interaction between age and education were significant predictors of SWAPS scores. Test-retest reliability in NC was good, and the SWAPS distinguished impaired and non-impaired groups with adequate to excellent sensitivity and specificity for the primary analyses, with optimal cut-off points provided. Raw score- to uncorrected normalized T-scores and demographically-corrected SWAPS T-scores using regression-based norms are presented along with scoring programs for the calculation of each. Conclusions. The SWAPS is a brief, free, easily administered test with demographically-corrected regression-based norms and promising utility for detection of cognitive impairment and efficient assessment of processing speed. [ABSTRACT FROM AUTHOR]

Background: Current evidence is inconsistent on the benefits of aerobic exercise training for preventing or attenuating age‐related cognitive decline in older adults. Objective: To investigate the effects of a 1‐year progressive, moderate‐to‐high intensity aerobic exercise intervention on cognitive function, brain volume, and cortical thickness in sedentary but otherwise healthy older adults. Methods: We randomized 73 older adults to a 1‐year aerobic exercise or stretching‐and‐toning (active control) program. The primary outcome was a cognitive composite score calculated from eight neuropsychological tests encompassing inductive reasoning, long‐term and working memory, executive function, and processing speed. Secondary outcomes were brain volume and cortical thickness assessed by MRI, and cardiorespiratory fitness measured by peak oxygen uptake (VO2). Results: One‐year aerobic exercise increased peak VO2 by ∼10% (p < 0.001) while it did not change with stretching (p = 0.241). Cognitive composite scores increased in both the aerobic and stretching groups (p < 0.001 for time effect), although no group difference was observed. Total brain volume (p < 0.001) and mean cortical thickness (p = 0.001) decreased in both groups over time, while the reduction in hippocampal volume was smaller in the stretching group compared with the aerobic group (p = 0.040 for interaction). Across all participants, improvement in peak VO2 was positively correlated with increases in cognitive composite score (r = 0.282, p = 0.042) and regional cortical thickness at the inferior parietal lobe (p = 0.016). Conclusions: One‐year aerobic exercise and stretching interventions improved cognitive performance but did not prevent age‐related brain volume loss in sedentary healthy older adults. Cardiorespiratory fitness gain was positively correlated with cognitive performance and regional cortical thickness. [ABSTRACT FROM AUTHOR]

This study examined whether history of traumatic brain injury (TBI) is associated with increased risk and earlier onset of mild cognitive impairment (MCI). Subjects with MCI (n = 3,187) and normal cognition (n = 3,244) were obtained from the National Alzheimer's Coordinating Center database. TBI was categorized based on lifetime reported TBI with loss of consciousness (LOC) without chronic deficit. Logistic regression was used to examine TBI history as a predictor of MCI, adjusted for demographics, apolipoprotein E-ɛ4 (ApoE4), a composite vascular risk score, and history of psychiatric factors. ANCOVA was used to examine whether age at MCI diagnosis and estimated age of onset differed between those with (TBI+) and without (TBI-) a history of TBI. TBI history was a significant predictor (p <  0.01) and associated with increased odds of MCI diagnosis in unadjusted (OR = 1.25; 95% CI = 1.05-1.49) and adjusted models, accounting for age, education, ApoE4, and a composite vascular score (OR = 1.32; 95% CI = 1.10-1.58). This association, however, was largely attenuated (OR = 1.14; 95% CI = 0.94-1.37; p = 0.18) after adjustment for reported history of depression. MCI was diagnosed a mean of 2.3 years earlier (p <  0.001) in the TBI+ group, and although TBI+ subjects had an estimated mean of decline 1.7 years earlier, clinician-estimated age of onset failed to differ (p = 0.13) when gender and psychiatric factors were controlled. This is the first report of a possible role for TBI as a risk factor in MCI, but its association may be related to other factors such as gender and depression and requires further investigation. [ABSTRACT FROM AUTHOR]

We investigated whether central or peripheral limitations to oxygen uptake elicit different respiratory sensations and whether dyspnea on exertion (DOE) provokes unpleasantness and negative emotions in patients with heart failure with preserved ejection fraction (HFpEF). 48 patients were categorized based on their cardiac output (Q̇c)/oxygen uptake (V̇O 2) slope and stroke volume (SV) reserve during an incremental cycling test. 15 were classified as centrally limited and 33 were classified as peripherally limited. Ratings of perceived breathlessness (RPB) and unpleasantness (RPU) were assessed (Borg 0–10 scale) during a 20 W cycling test. 15 respiratory sensations statements (1–10 scale) and 5 negative emotions statements (1−10) were subsequently rated. RPB (Central: 3.5±2.0 vs. Peripheral: 3.4±2.0, p=0.86), respiratory sensations, or negative emotions were not different between groups (p>0.05). RPB correlated (p<0.05) with RPU (r=0.925), "anxious" (r=0.610), and "afraid" (r=0.383). While DOE provokes elevated levels of negative emotions, DOE and respiratory sensations seem more related to a common mechanism rather than central and/or peripheral limitations in HFpEF. • Respiratory sensations did not differ between patient groups. • Unpleasantness and negative emotions did not differ between patients. • %body fat correlated with FVC and V̇ E , which were also correlated with RPB • V D /V T correlated with the V̇ E /V̇CO 2 slope, which was also correlated with RPB. • DOE is more related to pulmonary limitations than central/peripheral limitations. [ABSTRACT FROM AUTHOR]

Lingering concussion symptoms can negatively impact a child's well-being, yet variability in recovery is poorly understood. To aid detection of those at risk for prolonged symptom duration, we explored postconcussion mood and sleep symptoms as predictors of recovery time in adolescent athletes. We utilized analyses designed to control for potentially confounding variables, such as concussion severity indicators and premorbid psychiatric history. Participants included 393 adolescent athletes (aged 12–18 years) evaluated in outpatient concussion clinics within 2 weeks after injury. Provider-documented date of symptom resolution was obtained via medical record review. Survival analysis for recovery time was conducted in the total sample, and separately for males and females using prior medical history (psychiatric disorder, prior concussion), injury-related factors (loss of consciousness, post-traumatic amnesia [PTA], concussion symptom severity), and psychological symptoms (General Anxiety Disorder-7 Item Scale, Patient Health Questionnaire-8 Item Depression Scale, Pittsburgh Sleep Quality Index) collected at initial clinic visit. PTA, concussion symptoms, and sleep quality were associated with recovery in the total sample (HRs = 0.64–0.99, ps <.05). When analyzed by sex, only concussion symptoms were associated with recovery for females (with females reporting greater symptom severity than males), while for males PTA and greater depression symptoms were significant predictors of recovery (HRs = 0.54–0.98, ps <.05). These findings identified differences in symptom presentation between sexes, particularly for mood symptoms, and suggest that assessment of postconcussive symptoms is useful in helping to identify individuals at risk for longer recovery. Continued exploration of post-injury psychological difficulties in athletes is warranted for better concussion management. [ABSTRACT FROM AUTHOR]

Objective To examine the relationship between measures of subclinical atherosclerosis and subsequent cognitive function. Method Participants from the Dallas Heart Study (DHS), a population-based multiethnic study of cardiovascular disease pathogenesis, were re-examined 8 years later (DHS-2) with the Montreal Cognitive Assessment (MoCA); N = 1904, mean age = 42.9, range 8–65. Associations of baseline measures of subclinical atherosclerosis (coronary artery calcium, abdominal aortic plaque, and abdominal aortic wall thickness) with MoCA scores measured at follow-up were examined in the group as a whole and in relation to age and ApoE4 status. Results A significant linear trend of successively lower MoCA scores with increasing numbers of atherosclerotic indicators was observed (F(3, 1150) = 5.918, p = .001). CAC was weakly correlated with MoCA scores ( p = .047) and MoCA scores were significantly different between participants with and without CAC (M = 22.35 vs 23.69, p = 0.038). With the exception of a small association between abdominal AWT and MoCA in subjects over age 50, abdominal AWT and abdominal aortic plaque did not correlate with MoCA total score ( p ≥ .052). Cognitive scores and atherosclerosis measures were not impacted by ApoE4 status ( p ≥ .455). Conclusion In this ethnically diverse population-based sample, subclinical atherosclerosis was minimally associated with later cognitive function in middle-aged adults. [ABSTRACT FROM AUTHOR]

Potential therapies are currently under development for two congenital muscular dystrophy (CMD) subtypes: collagen VI-related muscular dystrophy (COL6-RD) and laminin alpha 2-related dystrophy (LAMA2-RD). However, appropriate clinical outcome measures to be used in clinical trials have not been validated in CMDs. We conducted a two-year pilot study to evaluate feasibility, reliability, and validity of various outcome measures, particularly the Motor Function Measure 32, in 33 subjects with COL6-RD and LAMA2-RD. In the first year, outcome measures tested included: Motor Function Measure 32 (MFM32), forced vital capacity (FVC) percent predicted sitting, myometry, goniometry, 10-meter walk, Egen Klassification 2, and PedsQL TM Generic and Neuromuscular Cores. In the second year, we added the North Star Ambulatory Assessment (NSAA), Hammersmith Functional Motor Scale (HFMS), timed functional tests, Measure of Activity Limitations (ACTIVLIM), Quality of Upper Extremity Skills Test (QUEST), and Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue subscale. The MFM32 showed strong inter-rater (0.92) and internal consistency (0.96) reliabilities. Concurrent validity for the MFM32 was supported by large correlations (range 0.623–0.936) with the following: FVC, NSAA, HFMS, timed functional tests, ACTIVLIM, and QUEST. Significant correlations of the MFM32 were also found with select myometry measurements, mainly of the proximal extremities and domains of the PedsQL TM scales focusing on physical health and neuromuscular disease. Goniometry measurements were less reliable. The Motor Function Measure is reliable and valid in the two specific subtypes of CMD evaluated, COL6-RD and LAMA2-RD. The NSAA is useful as a complementary outcome measure in ambulatory individuals. Preliminary concurrent validity of several other clinical outcome measures was also demonstrated for these subtypes. [ABSTRACT FROM AUTHOR]

Objective: Consideration of individual differences in recovery after concussion has become a focus of concussion research. Sex and racial/ethnic identity as they may affect reporting of concussion symptoms have been studied at single time points but not over time. Our objective was to investigate the factors of self-defined sex and race/ethnicity in reporting of lingering concussion symptoms in a large sample of adolescents. Participants and Methods: Concussed, symptomatic adolescents (n=849; Female=464, Male=385) aged 13-18 years were evaluated within 30 days of injury at a North Texas Concussion Registry (ConTex) clinic. Participants were grouped by self-defined race/ethnicity into three groups: Non-Hispanic Caucasian (n=570), Hispanic Caucasian (n=157), and African American (n=122). Measures collected at the initial visit included medical history, injury related information, and the Sport Concussion Assessment Tool-5 Symptom Evaluation (SCAT-5SE). At a three-month follow-up, participants completed the SCAT-5SE. Pearson's Chi-Square analyses examined differences in categorical measures of demographics, medical history, and injury characteristics. Prior to analysis, statistical assumptions were examined, and log base 10 transformations were performed to address issues of unequal group variances and nonnormal distributions. A three-way repeated measures ANOVA (Sex x Race/Ethnicity x Time) was conducted to examine total severity scores on the SCAT-5SE. Bonferroni post-hoc tests were performed to determine specific group differences. SPSS V28 was used for analysis with p<0.05 for significance. Data reported below has been back transformed. Results: A significant interaction of Time by Race/Ethnicity was found for SCAT-5SE scores reported at initial visit and three-month follow-up (F(2, 843)=7.362, p<0.001). To understand this interaction, at initial visit, Race/Ethnicity groups reported similar levels of severity for concussion symptoms. At three month follow-up, African Americans reported the highest level of severity of lingering symptoms (M= 3.925, 95% CIs [2.938-5.158]) followed by Hispanic Caucasians(M= 2.978, 95% CIs [2.2663.845]) and Non-Hispanic Caucasians who were the lowest(M= 1.915, 95% CIs [1.6262.237]). There were significant main effects for Time, Sex, and Race/Ethnicity. Average symptom levels were higher at initial visit compared to three-month follow-up (F(1, 843)=1531.526, p<0.001). Females had higher average symptom levels compared to males (F(1, 843)=35.58, p<0.001). For Race/Ethnicity (F(2, 843)=9.236, p<0.001), Non-Hispanic Caucasians were significantly different than African Americans (p<0.001) and Hispanic Caucasians (p=0.021) in reported levels of concussion symptom severity. Conclusions: Data from a large sample of concussed adolescents supported a higher level of reported symptoms by females, but there were no significant differences in symptom reporting between sexes across racial/ethnic groups. Overall, at three-months, the African American and Hispanic Caucasians participants reported a higher level of lingering symptoms than Non-Hispanic Caucasians. In order to improve care, the difference between specific racial/ethnic groups during recovery merits exploration into the factors that may influence symptom reporting. [ABSTRACT FROM AUTHOR]

Rationale: The impact of palliative care consultation on end-of-life care has not previously been evaluated in a multi-center study.Objectives: To evaluate the impact of palliative care consultation on the incidence of cardiopulmonary resuscitation (CPR) performed and comfort care received at the end-of-life in hospitalized patients with COVID-19.Methods: We used the Society of Critical Care Medicine's COVID-19 registry to extract clinical data on patients hospitalized with COVID-19 between March 31st, 2020 to March 17th, 2021 and died during their hospitalization. The proportion of patients who received palliative care consultation was assessed in patients who did and did not receive CPR (primary outcome) and comfort care (secondary outcome). Propensity matching was used to account for potential confounding variables.Measurements and Main Results: 3,227 patients were included in the analysis. There was no significant difference in the incidence of palliative care consultation between the CPR and no-CPR groups (19.9% vs. 19.4%, p = 0.8334). Patients who received comfort care at the end-of-life were significantly more likely to have received palliative care consultation (43.3% vs. 7.7%, p < 0.0001). After propensity matching for comfort care on demographic characteristics and comorbidities, this relationship was still significant (43.2% vs. 8.5%; p < 0.0001).Conclusion: Palliative care consultation was not associated with CPR performed at the end-of-life but was associated with increased incidence of comfort care being utilized. These results suggest that utilizing palliative care consultation at the end-of-life may better align the needs and values of patients with the care they receive. [ABSTRACT FROM AUTHOR]

Aims: Left ventricular (LV) restoring forces are primed by ventricular deformation during systole and contribute to cardiac relaxation and early diastolic suction. Systolic–diastolic coupling, the relationship between systolic contraction and diastolic recoil, is a novel marker of restoring forces, but the effect of left atrial pressure (LAP) is unknown. We tested preliminary methods of systolic–diastolic coupling comparing mitral annular velocities versus excursion distances and hypothesized a recoil/contraction distance ratio would remain unaffected across varying LAP, providing a surrogate for quantifying LV restoring forces. Methods and Results: Healthy subjects (n = 61, age 52 ± 5 years) underwent manipulation of LAP with lower body negative pressure (LBNP) and rapid normal saline (NS) infusion. Pulmonary capillary wedge pressure (PCWP; pulmonary artery catheter) and tissue Doppler imaging of the mitral annulus were measured. Two models of systolic–diastolic coupling––early diastolic excursion (EDexc)/systolic contraction (Sexc) distances and e'/systolic (s') velocities were compared. Velocity (e'/s') coupling ratios varied significantly (mean e'/s', slope = 0.022, p < 0.001) in relationship with PCWP (5–20 mmHg). Excursion (EDexc/Sexc) coupling ratio did not vary in relationship with PCWP (EDexc/Sexc: slope = −0.001, p = 0.19). Conclusions: Systolic–diastolic coupling using mitral annular distance ratios to standardize early diastolic recoil to systolic contraction was not significantly impacted by LAP, in contrast to coupling ratios using velocities. The pressure invariance of annular distance coupling ratios suggests this metric quantifies the efficiency of LV restoring forces by isolating systolic contributions to early diastolic restoring forces independent from changes in LAP. [ABSTRACT FROM AUTHOR]

Motor differences are common in Autism Spectrum Disorder (ASD), but rarely evaluated against diagnostic criteria for Developmental Coordination Disorder (DCD). We aimed to determine whether motor problems in ASD represent the possible co-occurrence of DCD. We retrospectively reviewed standardized assessments and parent-reports to evaluate motor ability in 43 individuals with ASD against diagnostic criteria for DCD, and compared to 18 individuals with DCD. Over 97% of cases in the ASD group scored below the 16th percentile in motor ability, with most below the 5th percentile. Over 90% of cases in the ASD group met criteria for co-occurring DCD. Motor challenges are a clinically-significant problem in ASD; systematically assessing the prevalence of co-occurring ASD + DCD is necessary to optimize assessment and intervention. [ABSTRACT FROM AUTHOR]

Recovery and return to play are important milestones for athletes who sustain sport-related concussions (SRC). Several factors have been shown to influence resolution of post-concussion related symptoms (PCS), but resilience, a trait that reflects the ability to overcome adversity, is another factor that may influence recovery. The aim of this study was to determine the relationship of resilience with resolution of symptoms during recovery in adolescents and young adults following SRC. This prospective study is part of the North Texas Concussion Registry (ConTex). Subjects (N = 332) aged 13 to 25 years who sustained a SRC within 10 days of presenting to clinic were evaluated at two time points: initial clinical visit and three-month follow-up. Resilience was measured by the self-report Brief Resilience Survey (BRS) and PCS by the Sport Concussion Assessment Tool-5 Symptom Evaluation Post-Concussion Symptom Scale (PCSS). Recovery was determined by self-reported return to sports/physical activity and percent back to normal. Repeated measures ANCOVA and linear regression models showed that lower resilience ratings at initial visit were associated with a greater number and severity of PCSS symptoms along with higher levels of anxiety and depression symptoms during recovery from SRC. At three months, subjects with lower initial resilience ratings were less likely to report feeling back to normal and had greater aggravation of symptoms from physical and cognitive activity even when they had returned to sports/physical activity. Lower resilience was associated with greater symptoms and delayed recovery from SRC. Results suggest that resilience may be another important factor to address in recovery from SRC. Future research is needed to examine the extent to which resilience measured after SRC reflects pre-injury characteristics and to better inform the development of interventions to promote resilience during recovery. [ABSTRACT FROM AUTHOR]

Objective To characterize potential differences in youth concussion sustained in motor vehicle accident (MVA) versus sport-related concussion (SRC), hypothesizing that youth who sustain concussion in a MVA would endorse higher initial and persistent symptom scores compared to those with SRC, despite similar injury severity levels. Methods Participants age 12–18 who sustained a concussion (i.e. Glasgow Coma Scale = 13–15) in a MVA (n  = 35) were matched with SRC participants (n  = 35) by sex, age, and days since injury. ANCOVA comparing initial postconcussion total symptom scores between the MVA and SRC groups were performed. Chi-square analysis with injury group by recovery time was used to determine whether youth who sustained concussion from MVA were more likely to endorse symptoms persisting >30 days at 3 months postinjury, and ANCOVA compared 3-month total symptom scores. Results On average, the MVA group reported significantly higher initial postconcussion and more frequent persistent symptom scores compared to the SRC group. Conclusions This is the first known study to examine context of injury in youth concussion while matching for injury severity, age, sex, and days since injury. Findings suggest the context of injury is an important clinical variable related to initial reporting of symptoms and endorsement of symptoms lasting more than 30 days. Tailored interventions that consider the context of injury may facilitate symptom resolution. [ABSTRACT FROM AUTHOR]

Heart transplant (HT) recipients are at higher risk of varicella zoster virus (VZV) reactivation. Risk factors for VZV reactivation are currently not well defined, impeding the ability to design and implement strategies to minimize the burden of this illness in this population. Automated data extraction tools were used to retrieve data from the electronic health record (EHR) of all adult HT recipients at our center between 2010 and 2016. Information from the Organ Procurement and Transplantation Network Standard Analysis and Research Files was merged with the extracted data. Potential cases were manually reviewed and adjudicated using consensus definitions. Cumulative incidence and risk factors for VZV reactivation in HT recipients were assessed by the Kaplan‐Meier method and Cox modeling, respectively. In 203 HT recipients, the cumulative incidence of VZV reactivation at 8‐years post‐transplantation was 26.4% (95% CI: 17.8‐38.0). The median time to VZV reactivation was 2.1 years (IQR, 1.5‐4.1). Half (14/28) of the cases experienced post‐herpetic neuralgia (PHN). Post‐transplant CMV infection (HR 9.05 [95% CI: 3.76‐21.77) and post‐transplant pulse‐dose steroids (HR 3.19 [95% CI: 1.05‐9.68]) were independently associated with a higher risk of VZV reactivation in multivariable modeling. Identification of risk factors will aid in the development of targeted preventive strategies. [ABSTRACT FROM AUTHOR]

Objective Variability in recovery time following sport-related concussion (SRC) is poorly understood. We explored the utility of brief mood, anxiety, and sleep questionnaires as postinjury predictors of SRC symptom clearance in adolescents. Method At initial visit 0–2 weeks postinjury, concussed athletes aged 12–18 years self-reported injury/medical factors (prior concussion, loss of consciousness, amnesia, and concussion symptom severity) and were administered psychological symptom measures. At 3 months, medical record review determined return-to-play (RTP) date. Subjects were divided into two datasets, with the first utilized for developing cutoff scores and then validated with the second dataset. Results A total of 64% of the 141 participants had early RTP (within 21 days postinjury), and 23% had late RTP (postinjury day 30 or later). The Generalized Anxiety Disorder Screener (GAD-7, M  = 2.1, SD  = 3.1) was the only significant predictor (p  = .001), with a 1.4-fold [95% CI 1.2–1.8] increased risk for every point. No other factors in the full model discriminated recovery groups (p s > .05). Receiver operating characteristic curve analysis derived a GAD-7 cut score ≥3 (sensitivity= 56.7%, specificity = 74.2%, AUCs = 0.63–0.79, p s < .001). Conclusions Postconcussion anxiety symptoms may help identify individuals at increased risk for prolonged recovery. [ABSTRACT FROM AUTHOR]

Background: Central arterial stiffness and brain hypoperfusion are emerging risk factors of Alzheimer's disease (AD). Aerobic exercise training (AET) may improve central arterial stiffness and brain perfusion.Objective: To investigate the effects of AET on central arterial stiffness and cerebral blood flow (CBF) in patients with amnestic mild cognitive impairment (MCI), a prodromal stage of AD.Methods: This is a proof-of-concept, randomized controlled trial that assigned 70 amnestic MCI patients into a 12-month program of moderate-to-vigorous AET or stretching-and-toning (SAT) intervention. Carotid β-stiffness index and CBF were measured by color-coded duplex ultrasonography and applanation tonometry. Total CBF was measured as the sum of CBF from both the internal carotid and vertebral arteries, and divided by total brain tissue mass assessed with MRI to obtain normalized CBF (nCBF). Episodic memory and executive function were assessed using standard neuropsychological tests (CVLT-II and D-KEFS). Changes in cardiorespiratory fitness were measured by peak oxygen uptake (VO2peak).Results: Total 48 patients (29 in SAT and 19 in AET) were completed one-year training. AET improved VO2peak, decreased carotid β-stiffness index and CBF pulsatility, and increased nCBF. Changes in VO2peak were associated positively with changes in nCBF (r = 0.388, p = 0.034) and negatively with carotid β-stiffness index (r = -0.418, p = 0.007) and CBF pulsatility (r = -0.400, p = 0.014). Decreases in carotid β-stiffness were associated with increases in cerebral perfusion (r = -0.494, p = 0.003). AET effects on cognitive performance were minimal compared with SAT.Conclusion: AET reduced central arterial stiffness and increased CBF which may precede its effects on neurocognitive function in patients with MCI. [ABSTRACT FROM AUTHOR]

Background Computerized clinical decision support systems (CDSS) have shown promising effectiveness in improving outpatient antibiotic prescribing. Methods We developed an intervention in the form of EPIC (Verona, WI, USA) order sets comprised of outpatient treatment pathways for 3 pediatric bacterial acute respiratory infections (ARIs) coupled with educational sessions. Four pediatric clinics were randomized into intervention and control arms over pre- and postimplementation study periods. In the intervention clinics, education was provided in between the 2 study periods and EPIC order sets became available at the beginning of the postimplementation period. The primary end point was the percentage of first-line antibiotic prescribing, and the secondary end points included antibiotic duration and antibiotic prescription modification within 14 days. Results A total of 2690 antibiotic prescriptions were included. During the pre-implementation phase, there was no difference in first-line antibiotic prescribing (74.9% vs 77.7%; P =.211) or antibiotic duration (9.69 ± 0.96 days vs 9.63 ± 1.07 days; P >.999) between the study arms. Following implementation, the intervention clinics had a higher percentage of first-line antibiotic prescribing (83.1% vs 77.7%; P =.024) and shorter antibiotic duration (9.28 ± 1.56 days vs 9.79 ± 0.75 days; P <.001) compared with the control clinics. The percentage of modified antibiotics was small in all clinics (1.1%–1.6%) and did not differ before and after the intervention (for all statistical comparisons, P ≤.354). Conclusions A computerized CDSS involving treatment pathways in the form of order sets coupled with educational sessions was associated with a higher percentage of first-line antibiotic prescribing and shorter antibiotic duration for the outpatient treatment of pediatric bacterial ARIs. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) patients have an increased ventilatory demand. Whether their ventilatory capacity can meet this increased demand is unknown, especially in those with obesity. Body composition (DXA) and pulmonary function were measured in 20 patients with HFpEF (69 ± 6 yr;9 M/11 W). Cardiorespiratory responses, breathing mechanics, and ratings of perceived breathlessness (RPB, 0–10) were measured at rest, 20 W, and peak exercise. FVC correlated with %body fat (R2 =0.51,P = 0.0006), V̇O 2peak (%predicted,R2 =0.32, P = 0.001), and RPB (R2 =0.58,P = 0.0004). %Body fat correlated with end-expiratory lung volume at rest (R2 =0.76, P < 0.001), 20 W (R2 =0.72, P < 0.001), and peak exercise (R2 =0.74, P < 0.001). Patients were then divided into two groups: those with lower ventilatory reserve (FVC<3 L,2 M/10 W) and those with higher ventilatory reserve (FVC>3.8 L,7 M/1 W). V̇O 2peak was ∼22% less (p < 0.05) and RPB was twice as high at 20 W (p < 0.01) in patients with lower ventilatory reserve. Ventilatory reserves are limited in patients with HFpEF and obesity; indeed, the margin between ventilatory demand and capacity is so narrow that exercise capacity could be ventilatory limited in many patients. • Ventilatory reserves are limited in patients with HFpEF and obesity. • Reserves are so small that exercise capacity may be ventilatory limited. • Whether these limitations provoke dyspnea and exercise intolerance is unknown. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) has been associated with accumulation of amyloid beta (Aβ) peptides in brain, and immunotherapy targeting Aβ provides potential for AD prevention. We have used a DNA Aβ42 trimer construct for immunization of 3xTg-AD mice and found previously significant reduction of amyloid and tau pathology due to the immunotherapy. We show here that DNA Aβ42 immunized 3xTg-AD mice showed better performance in nest building activities and had a higher 24 months survival rate compared to the non-treated AD controls. The analysis of differently expressed genes in brains from 24 months old mice showed significant increases transcript levels between non-immunized AD mice and wild-type controls for genes involved in microglia and astrocyte function, cytokine and inflammatory signaling, apoptosis, the innate and adaptive immune response and are consistent with an inflammatory phenotype in AD. Most of these upregulated genes were downregulated in the DNA Aβ42 immunized 3xTg-AD mice due to the vaccine. Transcript numbers for the immediate early genes, Arc, Bdnf, Homer1, Egr1 and cfos , involved in neuronal and neurotransmission pathways which were much lower in the non-immunized 3xTg-AD mice, were restored to wild-type mouse brain levels in DNA Aβ42 immunized 3xTg-AD mice indicating positive effects of DNA Aβ42 immunotherapy on synapse stability and plasticity. The immune response after immunization is complex, but the multitude of changes after DNA Aβ42 immunization shows that this response moves beyond the amyloid hypothesis and into direction of disease prevention. Image 1 • DNA Aβ42 immunization increases life span in 3xTg-AD mouse model • DNA Aβ42 immunization downregulates transcripts of inflammatory genes in brain of 3xTg-AD mouse model • DNA Aβ42 immunization restores expression of immediate early genes in brain of 3xTg-AD mouse model to wild-type levels • This is a first report showing effects of DNA Aβ42 immunotherapy on reducing the expression of genes upregulated in AD brain. [ABSTRACT FROM AUTHOR]