Poorer Baseline Performance Research Articles

TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL

The aim of this retrospective study was to evaluate the efficiency and safety of total body irradiation plus cyclophosphamide (TBI/Cy) followed by autogenetic hematopoietic stem cell transplantation (auto-HSCT) in T-LBL/ALL patients that cannot receive allogeneic hematopoietic stem cell transplant (allo-HSCT). Between 2013 and 2023, 24 patients received auto-HSCT following by TBI/Cy, 26 patients underwent allo-HSCT, all patients achieved completed hematopoietic reconstitution after HSCT. The progression free survival (PFS) and overall survival (OS) had no statistically significant differences between the two groups (P = 0.791, HR 1.127, 95%CI 0.456–2.785; P = 0.456, HR 0.685, 95%CI 0.256–1.828). Although the cumulative incidence of relapse was lower for patients who received allo-HSCT than auto-HSCT (P = 0.033, HR 3.707, 95%CI 1.188–11.570, 2-year relapse 11.5% vs. 33.3%), the incidence of non-relapse mortality (NRM) was higher than that in the auto-HSCT group (P = 0.014, HR 0.000, 95%CI -1.000 - -1.000, 2-year NRM, 23.1% vs. 0%). Trough Landmark analysis, the two groups showed a statistically significant difference in 3-year PFS and 4-year OS curves (Figure S2A&B, P = 0.039, HR 0.426, 95%CI 0.163–1.117; P = 0.014, HR 0.317, 95%CI 0.113–0.887). By COX analysis, poor baseline performance status (ECOG-PS ≥ 2) and CNS involvement were risk factors for PFS and OS. In conclusion, TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL.

Remote support of an external quality assessment program in 10 laboratories in Bhutan, Uganda, and Malawi: Pathologists Overseas experience between 2009 and 2017.

This article describes Pathologists Overseas (PO) experience supporting external quality assessment (EQA) programs in 10 clinical laboratories across 3 countries between 2009 and 2017. Laboratories were enrolled in the condensed chemical pathology EQA program provided by the Royal College of Pathologists of Australasia Quality Assurance Program. Participants were given an initial 2- to 4-day in-person training, followed by 1 year of active feedback on performance via emails or phone calls by a PO volunteer. There were 2 performance metrics: percentage of reported results as a measure of compliance and percentage of acceptable reported results as a measure of accuracy. Laboratories demonstrated high compliance with result reporting, with medians of 69.9%, 71.7%, and 81.3% before, during, and after feedback, respectively. Concomitant medians for the percentage of acceptable reported results were 41.2%, 57.3%, and 53.5%, respectively. Six laboratories had low performance in terms of accuracy at baseline (<60%). Active feedback improved the percentage of acceptable reported results for these lower-performing laboratories. External quality assessment programs can be successfully adopted long term by laboratories in low-resource settings. Active feedback requires significant time and effort but could be especially beneficial for laboratories with poor baseline performance.

Progression risk stratification with six-minute walk gait speed trajectory in multiple sclerosis.

Multiple Sclerosis (MS) disease progression has notable heterogeneity among patients and over time. There is no available single method to predict the risk of progression, which represents a significant and unmet need in MS. MS and healthy control (HC) participants were recruited for a 2-year observational study. A latent-variable growth mixture model (GMM) was applied to cluster baseline 6-min walk gait speed trajectories (6MWGST). MS patients within different 6 MWGST clusters were identified and stratified. The group membership of these MS patients was compared against 2-year confirmed-disease progression (CDP). Clinical and patient-reported outcome (PRO) measures were compared between HC and MS subgroups over 2 years. 62 MS and 41 HC participants completed the 2-year study. Within the MS cohort, 90% were relapsing MS. Two distinct patterns of baseline 6 MWGST emerged, with one cluster displaying a faster gait speed and a typical "U" shape, and the other showing a slower gait speed and a "flattened" 6 MWGST curve. We stratified MS participants in each cluster as low- and high-risk progressors (LRP and HRP, respectively). When compared against 2-year CDP, our 6 MWGST approach had 71% accuracy and 60% positive predictive value. Compared to the LRP group, those MS participants stratified as HRP (15 out of 62 MS participants), were on average 3.8 years older, had longer MS disease duration and poorer baseline performance on clinical outcomes and PROs scores. Over the subsequent 2 years, only the HRP subgroup showed a significant worsened performance on 6 MW, clinical measures and PROs from baseline. Baseline 6 MWGST was useful for stratifying MS participants with high or low risks for progression over the subsequent 2 years. Findings represent the first reported single measure to predict MS disease progression with important potential applications in both clinical trials and care in MS.

Informal regulation by nongovernmental organizations enhances corporate compliance: Evidence from a nationwide randomized controlled trial in China

AbstractAs a key component of informal regulation, nongovernmental organization (NGO) monitoring reduces the cost of government oversight and increases the visibility of corporate performance to stakeholders, thereby promoting corporate compliance. We conduct a nationwide randomized controlled trial (RCT) to investigate the causal effect of NGO monitoring on corporate compliance as measured by the environmental information disclosure (EID) of China's highly polluting listed companies. We find that companies improve their EID after being alerted to NGO monitoring, especially private companies and companies with poor baseline performance. Both the threat of being reported to regulators and that of being reported to the market are effective ways of NGO monitoring, while companies with strong political connections show no response to regulatory threats. Our findings indicate the efficacy of informal regulations and the significance of NGOs in the promotion of corporate compliance.

Cumulative Stress Exposure and Cognitive Function Among Older Adults: The Moderating Role of a Healthy Lifestyle.

Although chronic stress is a risk factor for poor age-related cognitive health, there is limited research that has examined how cumulative stress across the lifespan affects cognitive aging. There may also be resilience factors that minimize the effects of cumulative stress on cognitive health. Engaging in a healthy lifestyle is protective against cognitive decline and may therefore interact with cumulative stress to buffer the stress-cognition relationship. The objective of the current study was to examine the moderating role of a healthy lifestyle, comprised of physical activity, social engagement, and sleep quality, in the relationship between cumulative stress exposure (CSE) and baseline and change in cognitive performance (global cognition, episodic memory, executive function) over 9 years among 1,297 older adults in the Midlife in the United States cohort (Mage = 69.0 ± 6.4, 57.8% female). CSE and healthy lifestyle behaviors were indexed using self-reported questionnaires at baseline, and cognitive function was assessed using a battery of standardized neuropsychological tests at baseline and follow-up. Controlling for age, sex, education, race, marital status, employment status, hypertension, diabetes, and depression, higher CSE was associated with poorer baseline performance and slower decline over time in global cognition and executive function, but not episodic memory. A healthy lifestyle did not significantly moderate the relationship between cumulative stress and cognitive function. Exploratory analyses showed a significant cumulative stress-cognition relationship among females only. This study lends support for a lifespan model of cognitive aging and suggests that the cognitive health consequences of stress extend beyond immediate timescales.

GDF15 and its association with cognitive performance over time in a longitudinal study of middle-aged urban adults

Serum GDF15 levels are correlated with multiple neurodegenerative diseases. Few studies have tested this marker’s association with middle-aged cognitive performance over time, and whether race affects this association is unknown. We examined associations of initial serum GDF15 concentrations with longitudinal cognitive performance, spanning domains of global mental status, visual and verbal memory, attention, fluency, and executive function in a sub-sample of adults participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 776, Agev1:30-66y, 45.6 % male, 57.0 % African American, 43.0 % below poverty). This analysis consisted of mixed-effects regression models applied to the total selected sample, while also stratifying the analyses by race in the main analyses and further stratifying by sex, age group and poverty status in an exploratory analysis. Our main findings, which passed multiple testing and covariate-adjustment, indicated that GDF15 was associated with poorer baseline performance on several cognitive tests, including animal fluency [overall sample: (Model 1: γ0 ± SE: −0.664 ± 0.208, P < 0.001; Model 2, γ0 ± SE: −0.498 ± 0.217, P < 0.05)]. Among White adults, GDF15 was linked to poorer performance on a brief test of attention (Model 1: γ0 ± SE: −0.426 ± 0.126, P < 0.001; Model 2, γ0 ± SE: −0.281 ± 0.139, P < 0.05); and Trailmaking test, part B (Model 1: γ0 ± SE: +0.129 ± 0.040, P < 0.001; Model 2, γ0 ± SE: +0.089 ± 0.041, P < 0.05), the latter being also linked to higher GDF15 among individuals living below poverty. Among women, GDF15 was associated with poor global mental status (Normalized MMSE: Model 1: γ0 ± SE: −2.617 ± 0.746, P < 0.001; Model 2: γ0 ± SE: −1.729 ± 0.709, P < 0.05). GDF15 was not associated with decline on any of the 11 cognitive test scores considered in ∼ 4 years of follow-up. In sum, we detected cross-sectional associations between GDF15 and cognition, although GDF15 did not predict rate of change in cognitive performance over time among a sample of middle-aged adults. More longitudinal studies are needed to address the clinical utility of this biomarker for early cognitive defects.

Incorporation of Serial 12-Lead Electrocardiogram With Machine Learning to Augment the Out-of-Hospital Diagnosis of Non-ST Elevation Acute Coronary Syndrome

Ischemic electrocardiogram (ECG) changes are subtle and transient in patients with suspected non-ST-segment elevation (NSTE)-acute coronary syndrome. However, the out-of-hospital ECG is not routinely used during subsequent evaluation at the emergency department. Therefore, we sought to compare the diagnostic performance of out-of-hospital and ED ECG and evaluate the incremental gain of artificial intelligence-augmented ECG analysis. This prospective observational cohort study recruited patients with out-of-hospital chest pain. We retrieved out-of-hospital-ECG obtained by paramedics in the field and the first ED ECG obtained by nurses during inhospital evaluation. Two independent and blinded reviewers interpreted ECG dyads in mixed order per practice recommendations. Using 179 morphological ECG features, we trained, cross-validated, and tested a random forest classifier to augment non ST-elevation acute coronary syndrome (NSTE-ACS) diagnosis. Our sample included 2,122 patients (age 59 [16]; 53% women; 44% Black, 13.5% confirmed acute coronary syndrome). The rate of diagnostic ST elevation and ST depression were 5.9% and 16.2% on out-of-hospital-ECG and 6.1% and 12.4% on ED ECG, with ∼40% of changes seen on out-of-hospital-ECG persisting and ∼60% resolving. Using expert interpretation of out-of-hospital-ECG alone gave poor baseline performance with area under the receiver operating characteristic (AUC), sensitivity, and negative predictive values of 0.69, 0.50, and 0.92. Using expert interpretation of serial ECG changes enhanced this performance (AUC 0.80, sensitivity 0.61, and specificity 0.93). Interestingly, augmenting the out-of-hospital-ECG alone with artificial intelligence algorithms boosted its performance (AUC 0.83, sensitivity 0.75, and specificity 0.95), yielding a net reclassification improvement of 29.5% against expert ECG interpretation. In this study, 60% of diagnostic ST changes resolved prior to hospital arrival, making the ED ECG suboptimal for the inhospital evaluation of NSTE-ACS. Using serial ECG changes or incorporating artificial intelligence-augmented analyses would allow correctly reclassifying one in 4 patients with suspected NSTE-ACS.

Effects of High-Definition Transcranial Direct Current Stimulation Over the Left Fusiform Face Area on Face View Discrimination Depend on the Individual Baseline Performance.

A basic human visual function is to identify objects from different viewpoints. Typically, the ability to discriminate face views based on in-depth orientation is necessary in daily life. Early neuroimaging studies have identified the involvement of the left fusiform face area (FFA) and the left superior temporal sulcus (STS) in face view discrimination. However, many studies have documented the important role of the right FFA in face processing. Thus, there remains controversy over whether one specific region or all of them are involved in discriminating face views. Thus, this research examined the influence of high-definition transcranial direct current stimulation (HD-tDCS) over the left FFA, left STS or right FFA on face view discrimination in three experiments. In experiment 1, eighteen subjects performed a face view discrimination task before and immediately, 10 min and 20 min after anodal, cathodal and sham HD-tDCS (20 min, 1.5 mA) over the left FFA in three sessions. Compared with sham stimulation, anodal and cathodal stimulation had no effects that were detected at the group level. However, the analyses at the individual level showed that the baseline performance negatively correlated with the degree of change after anodal tDCS, suggesting a dependence of the change amount on the initial performance. Specifically, tDCS decreased performance in the subjects with better baseline performance but increased performance in those with poorer baseline performance. In experiments 2 and 3, the same experimental protocol was used except that the stimulation site was the left STS or right FFA, respectively. Neither anodal nor cathodal tDCS over the left STS or right FFA influenced face view discrimination in group- or individual-level analyses. These results not only indicated the importance of the left FFA in face view discrimination but also demonstrated that individual initial performance should be taken into consideration in future research and practical applications.

Outcomes of patients with non-small cell lung cancer and poor performance status treated with immune checkpoint inhibitors in the real-world setting.

Immune-checkpoint inhibitors (ICIs) are standard treatments for metastatic non-small cell lung cancer (NSCLC). Patients with poor performance status (PS) are underrepresented in clinical trials. We evaluate the efficacy and safety of ICIs in a real-world setting. We conducted a multi-institutional retrospective study to assess clinical outcomes of NSCLC treated with ICIs. We categorized pts within two groups (PS 0-1 vs 2) and assessed clinical outcomes and safety. Two hundred and sixty nine patients were included, 44 patients (16.4%) had baseline PS 2 and 223 patients (82.9%) PS 0-1. The overall response rate (ORR) was 30.4%, median PFS was 7.26months (95% CI 5.1-9.4), and median OS was 15.18months (95% CI 9.5-20.9). Patients with a PS 2 were most likely to received ICIs in the second or later line (84.1% vs 64.6%; p = 0.01), had baseline steroids (21.4% vs 8.2%; p 0.010), lower response rate (16.7% vs 34.5%; p 0.02) and clinical benefit (35.7% vs 71%; p 0.000) compared to PS 0-1 pts. Moreover, PS ≥ 2 patients had shorter PFS, median 2.2months (95% CI 1.3-3.1) compared to 9.9months (95% CI 6.7-13.1] and shorter OS, 3.3months (95% CI 2.6-4.2) versus 24.1months (95% CI 16.1-32.1), respectively. PS was significantly associated with PFS and OS in multivariate analysis. As it was expected, immunotherapy was well tolerated with a safety profile comparable to the previous published data. Based on these retrospective results, patients with poor baseline performance status seem to have poor clinical outcomes with ICIs in the real-world setting.

Relation of Atrial Fibrillation to Cognitive Decline (from the REasons for Geographic and Racial Differences in Stroke [REGARDS] Study)

The association of atrial fibrillation (AF) with cognitive function remains unclear, especially among racially/geographically diverse populations. This analysis included 25,980 black and white adults, aged 48+, from the national REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, free from cognitive impairment and stroke at baseline. Baseline AF was identified by self-reported medical history or electrocardiogram (ECG). Cognitive testing was conducted yearly with the Six Item Screener (SIS) to define impairment and at 2-year intervals to assess decline on: animal naming and letter fluency, Montreal Cognitive Assessment (MoCA), Word List Learning (WLL) and Delayed Recall tasks (WLD). Multivariable regression models estimated the relationships between AF and baseline impairment and time to cognitive impairment. Models were adjusted sequentially for age, sex, race, geographic region, and education, then cardiovascular risk factors and finally incident stroke. AF was present in 2,168 (8.3%) participants at baseline. AF was associated with poorer baseline performance on measures of: semantic fluency (p<0.01); global cognitive performance (MoCA, p<0.01); and WLD (p<0.01). During a mean follow-up of 8.06 years, steeper declines in list learning were observed among participants with AF (p<0.03) which remained significant after adjusting for cardiovascular risk factors (p<0.04) and incident stroke (p<0.03). Effect modification by race, sex and incident stroke on AF and cognitive decline were also detected. In conclusion, AF was associated with poorer baseline cognitive performance across multiple domains and incident cognitive impairment in this bi-racial cohort. Additional adjustment for cardiovascular risk factors attenuated these relations with the exception of learning.

Clinical Determinants Differentiating the Severity of SARS-CoV-2 Infection in Cancer Patients: Hospital Care or Home Recovery.

Background: Cancer patients may carry a worse prognosis with SARS-CoV-2 infection. Most of the previous studies described the outcomes of hospitalized cancer patients. We aimed to study the clinical factors differentiating patients requiring hospital care vs. home recovery, and the trajectory of their anti-cancer treatment.Methods: This study was conducted in a community cancer center in New York City. Eligible patients were those who had cancer history and were diagnosed of SARS-CoV-2 infection between March 1 and May 30, 2020, with confirmatory SARs-CoV-2 virus test or antibody test. Four groups were constructed: (A) hospitalized and survived, (B) hospitalized requiring intubation and/or deceased, (C) non-hospitalized, asymptomatic, with suspicious CT image findings, close exposure, or positive antibody test, and (D) non-hospitalized and symptomatic.Results: One hundred and six patients were included in the analysis. Thirty-five patients (33.0%) required hospitalization and 13 (12.3%) died. Thirty (28.3%) patients were asymptomatic and 41 (38.7%) were symptomatic and recovered at home. Comparing to patients who recovered at home, hospitalized patients were composed of older patients (median age 71 vs. 63 years old, p = 0.000299), more who received negative impact treatment (62.9 vs. 32.4%, p = 0.0036) that mostly represented myelosuppressive chemotherapy (45.7 vs. 23.9%, p = 0.0275), and more patients with poorer baseline performance status (PS ≥ 2 25.7 vs. 2.8%, p = 0.0007). Hypoxemia (35% in group A vs. 73.3% in group B, p = 0.0271) at presentation was significant to predict mortality in hospitalized patients. The median cumulative hospital stay for discharged patients was 16 days (range 5–60). The median duration of persistent positivity of SARS-CoV-2 RNA was 28 days (range 10–86). About 52.9% of patients who survived hospitalization and required anti-cancer treatment reinitiated therapy. Ninety-two percent of the asymptomatic patients and 51.7% of the symptomatic patients who recovered at home continued treatment on schedule and almost all reinitiated treatment after recovery.Conclusions: Cancer patients may have a more severe status of SARS-CoV-2 infection after receiving myelosuppressive chemotherapy. Avoidance should be considered in older patients with poor performance status. More than two thirds of patients exhibit minimal to moderate symptoms, and many of them can continue or restart their anti-cancer treatment upon recovery.

Cytotoxic and targeted systemic therapy in patients with advanced cutaneous squamous cell carcinoma in the head and neck.

The outcomes of patients treated with cytotoxic or targeted systemic therapy is not well defined for cutaneous squamous cell carcinoma of the head and neck (cSCCHN). Patients with cSCCHN treated with cytotoxic or targeted systemic therapy were included. Patients were divided into two groups based on the presence of distant metastasis (M1 vs. M0) at presentation. A proportional hazards model was used to assess for independent predictors of overall survival. Of 129 patients with cSCCHN, 20 (16%) were M1 and 109 (84%) were M0. Independent predictors of improved survival were M0 status, treatment of locally advanced disease with radiotherapy, and lower Eastern Cooperative Oncology Group (ECOG) score. Survival was worse in M1 patients treated with cytotoxic or targeted systemic therapy and poor baseline performance status but improved in those receiving radiotherapy. These data can serve as historical controls for future systemic therapy trials, including immunotherapy.

Value of new performance information in healthcare: evidence from Japan.

Mandatory measurement and disclosure of outcome measures are commonly used policy tools in healthcare. The effectiveness of such disclosures relies on the extent to which the new information produced by the mandatory system is internalized by the healthcare organization and influences its operations and decision-making processes. We use panel data from the Japanese National Hospital Organization to analyze performance improvements following regulation mandating standardized measurement and peer disclosure of patient satisfaction performance. Drawing on value of information theory, we document the absolute value and the benchmarking value of new information for future performance. Controlling for ceiling effects in the opportunities for improvement, we find that the new patient satisfaction measurement system introduced positive, significant, and persistent mean shifts in performance (absolute value of information) with larger improvements for poorly performing hospitals (benchmarking value of information). Our setting allows us to explore these effects in the absence of confounding factors such as incentive compensation or demand pressures. The largest positive effects occur in the initial period, and improvements diminish over time, especially for hospitals with poorer baseline performance. Our study provides empirical evidence that disclosure of patient satisfaction performance information has value to hospital decision makers.

Detecting the Cognitive Prodrome of Dementia in Parkinson's Disease.

More than 75% of Parkinson's disease (PD) patients will develop dementia. Previous studies on the cognitive predictors of dementia in PD had some methodological limitations and the cognitive tests identified as good predictors vary greatly. This prospective cohort study aims to identify the optimal cognitive predictors of dementia in PD using complementary statistical methods. Eighty PD patients without dementia underwent polysomnographic recording, a neurological examination, and a complete neuropsychological assessment at baseline. They were then followed for a mean of 4.3 years. Baseline group comparisons and survival analyses were used to identify optimal cognitive predictors. Moreover, patients who developed dementia were pair-matched at baseline according to age, sex, and education to healthy controls (2 : 1), and receiver operating characteristic curves were calculated for cognitive tests. At follow-up, 23 patients (29%) developed dementia. PD patients who developed dementia had poorer baseline performance and a higher proportion of clinically impaired performance on several cognitive tests. Impaired baseline performance on the Block Design subtest was the best independent predictor of dementia (HR = 8). Moreover, the Trail Making Test part B (time) and Verbal Fluency (semantic) had the best psychometric properties (area under the curve >0.90) for identifying PD patients at risk of dementia. The present study identified three cognitive tests as the most accurate to detect individuals with PD at high risk of developing dementia.

Cognitive flexibility and persistent post-surgical pain: the FLEXCAPP prospective observational study

BackgroundImpaired performance on tasks assessing executive function has been linked to chronic pain. We hypothesised that poor performance on tests assessing the ability to adjust thinking in response to changing environmental stimuli (cognitive flexibility) would be associated with persistent post-surgical pain. MethodsWe conducted a single-centre prospective observational study in two perioperative cohorts: patients undergoing total knee arthroplasty or noncardiac chest surgical procedures. The co-primary outcome measures compared preoperative performance on the Trail Making Test and the colour–word matching Stroop test between patients who developed persistent post-surgical pain and those who did not. Secondary outcome measures included the associations between these test scores and pain severity at 6 months. ResultsOf 300 participants enrolled, 198 provided 6 month follow-up data. There were no significant differences in preoperative Trail Making Test B minus A times (33 vs 34 s; P=0.59) or Stroop interference T-scores (47th vs 48th percentile; P=0.50) between patients with and without persistent post-surgical pain (primary outcome). Of those who reported persistent post-surgical pain, poorer baseline performance on the colour–word matching Stroop test was associated with higher pain scores at 6 months in both knee arthroplasty (r=–0.32; P=0.04) and chest (r=–0.44; P=0.02) surgeries (secondary outcome). ConclusionsPreoperative cognitive flexibility test performance was not predictive of overall persistent post-surgical pain incidence 6 months after surgery. However, poor performance on the colour–word matching Stroop test was independently associated with more severe persistent post-surgical pain in both cohorts. Clinical trial registrationNCT02579538.

Amyloid-β Positivity Predicts Cognitive Decline but Cognition Predicts Progression to Amyloid-β Positivity

BackgroundStage 1 of the National Institute on Aging–Alzheimer’s Association’s proposed Alzheimer’s disease continuum is defined as amyloid-β (Aβ) positive but cognitively normal. Identifying at-risk individuals before Aβ reaches pathological levels could have great benefits for early intervention. Although Aβ levels become abnormal long before severe cognitive impairments appear, increasing evidence suggests that subtle cognitive changes may begin early, potentially before Aβ surpasses the threshold for abnormality. We examined whether baseline cognitive performance would predict progression from normal to abnormal levels of Aβ. MethodsWe examined the association of baseline cognitive composites (Preclinical Alzheimer Cognitive Composite, Alzheimer’s Disease Neuroimaging Initiative (ADNI) memory factor composite) with progression to Aβ positivity in 292 nondemented, Aβ-negative ADNI participants. Additional analyses included continuous cerebrospinal fluid biomarker levels to examine the effects of subthreshold pathology. ResultsForty participants progressed to Aβ positivity during follow-up. Poorer baseline performance on both cognitive measures was significantly associated with increased odds of progression. More abnormal levels of baseline cerebrospinal fluid phosphorylated tau and subthreshold Aβ were associated with increased odds of progression to Aβ positivity. Nevertheless, baseline ADNI memory factor composite performance predicted progression even after controlling for baseline biomarker levels and APOE genotype (Preclinical Alzheimer Cognitive Composite was trend level). Survival analyses were largely consistent: controlling for baseline biomarker levels, baseline Preclinical Alzheimer Cognitive Composite still significantly predicted progression time to Aβ positivity (ADNI memory factor composite was trend level). ConclusionsThe possibility of intervening before Aβ reaches pathological levels is of obvious benefit. Low-cost, noninvasive cognitive measures can be informative for determining who is likely to progress to Aβ positivity, even after accounting for baseline subthreshold biomarker levels.

Red Cell Distribution Width Is Directly Associated with Poor Cognitive Performance among Nonanemic, Middle-Aged, Urban Adults

Background:Epidemiological evidence suggests that both anemia and elevated red cell distribution width (RDW) are associated with cognitive impairment. However, the interplay between these 2 predictors has been understudied. Objectives:We examined sex- and anemia-specific associations between RDW and cognitive performance among urban adults in the United States. Methods:Data from the Healthy Aging in Neighborhoods of Diversity Across the Life Span Study (Baltimore, MD; participants aged 30–65 y at baseline, ~59% African-American, 45% men) were used. Participants were selected based on the completion of 11 cognitive tasks at baseline (2004–2009) and follow-up (2009–2013) visits (mean time between visits: 4.64 ± 0.93 y) and availability of exposure and covariate data, yielding a sample of between 1526 and 1646 adults out of the initial 3720 adults recruited at baseline. Multiple linear mixed-effects regression models were conducted with RDW as the main exposure of interest and anemia/sex as the key effect modifiers. Results:Overall, high RDWs were linked to poorer baseline performance on the California Verbal Learning Test (CVLT) List A (per 1 unit increase in RDW %, main effect: γ01= -0.369 ± 0.114; P = 0.001) and to slower rates of decline on the CVLT Delayed Free Recall (per 1 unit increase in RDW %, RDW × time: γ11= +0.036 ± 0.013; P = 0.007). Among nonanemic participants, RDWs were consistently associated with poorer baseline performance on the Trailmaking Test, Part A (γ01= +3.11 ± 0.89; P< 0.001) and on the CVLT List A (γ01= -0.560 ± 0.158; P< 0.001). Moreover, RDWs were associated with poorer baseline performance on the Brief Test of Attention in the total population (γ01= -0.123 ± 0.039; P = 0.001) and among men (γ01= -0.221 ± 0.068; P = 0.001). We did not detect an association between hemoglobin (Hb) and baseline cognitive performance or changes over time. Conclusions:Elevated RDW had a consistent cross-sectional association with poor cognitive performance in the domains of verbal memory and attention among the nonanemic group in a sample of middle-aged, urban adults. Anemia and Hb concentrations were not associated with cognition. More longitudinal studies are needed to replicate our findings.

Factors Associated with Mortality in Patients with a Solid Malignancy Admitted to the Intensive Care Unit - A Prospective Observational Study.

PurposeSeveral studies show conflicting results regarding the prognosis and predictors of the outcome of critically ill patients with a solid malignancy. This study aims to determine the outcome of critically ill patients, admitted to a hospital, with a solid malignancy and the factors associated with the outcomes.Methods and MaterialsAll patients with a solid malignancy admitted to an intensive care unit (ICU) at a tertiary academic medical center were enrolled. Clinical data upon admission and during ICU stay were collected. Hospital, ICU, and six months outcomes were documented.ResultsThere were 252 patients with a solid malignancy during the study period. Urogenital malignancies were the most common (26.3%) followed by lung cancer (23.5%). Acute respiratory failure was the most common ICU diagnosis (51.6%) followed by sepsis in 46%. ICU mortality and hospital mortality were 21.8% and 34.3%. Six months mortality was 38.4%. Using multivariate analysis, acute kidney injury, OR 2.82, 95% CI 1.50-5.32 and P=0.001, use of mechanical ventilation, OR 2.67 95% CI 1.37 – 5.19 and P=0.004 and performance status of ≥2 with OR of 3.05, 95% CI of 1.5-6.2 and P= 0.002 were associated with hospital mortality. There were no differences in outcome between African American patients (53% of all patients) and other races.ConclusionThis study reports encouraging survival rates in patients with a solid malignancy who are admitted to ICU. Patients with a poor baseline performance status require mechanical ventilation or develop acute renal failure have worse outcomes.

T10. Interictal spike rates are correlated with verbal memory in patients with mesial temporal lobe epilepsy

Introduction In a randomized controlled trial of the RNS® System, patients with mesial temporal lobe epilepsy (MTLE) had improvements in verbal memory, with maximal benefit in those with poorer baseline memory scores. However, improvements were not correlated with changes in clinical seizures. Here ECoG data were used to retrospectively assess the relationship between memory performance and interictal spikes. Methods Neuropsychological assessments were performed during a pre-implant baseline, after a blinded period, and at 1 and 2 years post-implant (Y1, Y2). Baseline memory scores were characterized as high/low using a median split for the Rey Auditory Learning Test (RAVLT). The average interictal spike rate (avg-ISR) was calculated from ECoGs stored based on time-of-day in the 3 months prior to each assessment. Pearson correlations were calculated between avg-ISR and RAVLT scores for Y1 and Y2, as well as between the change in RAVLT score and the change in avg-ISR for Y1 and Y2 compared to the blinded period. Results MTLE patients with low baseline RAVLT scores had significant negative correlations between avg-ISR and RAVLT scores at Y1 (r = −0.59; p = 0.0007; n = 29) and Y2 (r = −0.42; 0.047; n = 23), as well as between the change in the avg-ISR and change in RAVLT at Y1 (r = −0.47; p = 0.01). Correlations were not significant between avg-ISRs and RAVLT scores for MTLE patients with high baseline scores (n = 26). Significant correlations for patients with neocortical onsets were not observed (n = 60). Conclusion There is a statistically significant negative correlation between ISR and verbal memory scores in patients with MTLE and poor baseline performance. These results suggest that reduction in ISRs could improve memory performance in MTLE patients with baseline memory deficits.

An exploratory, large-scale study of pain and quality of life outcomes in cancer patients with moderate or severe pain, and variables predicting improvement.

BackgroundThere have been few large-scale, real world studies in Spain to assess change in pain and quality of life (QOL) outcomes in cancer patients with moderate to severe pain. This study aimed to assess changes on both outcomes after 3 months of usual care and to investigate factors associated with change in QoL.Patients and methodsLarge, multi-centre, observational study in patients with lung, head and neck, colorectal or breast cancer experiencing a first episode of moderate to severe pain while attending one of the participating centres. QoL was assessed using the EuroQol-5D questionnaire and pain using the Brief Pain Inventory (BPI). Instruments were administered at baseline and after 3 months of follow up. Multivariate analyses were used to assess the impact of treatment factors, demographic and clinical variables, pain and other symptoms on QoL scores.Results1711 patients were included for analysis. After 3 months of usual care, a significant improvement was observed in pain and QoL in all four cancer groups (p<0.001). Effect sizes were medium to large on the BPI and EQ-5D Index and Visual Analogue Scale (VAS). Improvements were seen on the majority of EQ-5D dimensions in all patient groups, though breast cancer patients showed the largest gains. Poorer baseline performance status (ECOG) and the presence of anxiety/depression were associated with significantly poorer QOL outcomes. Improvements in BPI pain scores were associated with improved QoL.ConclusionIn the four cancer types studied, pain and QoL outcomes improved considerably after 3 months of usual care. Improvements in pain made a substantial contribution to QoL gains whilst the presence of anxiety and depression and poor baseline performance status significantly constrained improvement.