Associations between Verbal Learning Slope and Neuroimaging Markers across the Cognitive Aging Spectrum.

A symptom of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is a flat learning profile. Learning slope calculation methods vary, and the optimal method for capturing neuroanatomical changes associated with MCI and early AD pathology is unclear. This study cross-sectionally compared four different learning slope measures from the Rey Auditory Verbal Learning Test (simple slope, regression-based slope, two-slope method, peak slope) to structural neuroimaging markers of early AD neurodegeneration (hippocampal volume, cortical thickness in parahippocampal gyrus, precuneus, and lateral prefrontal cortex) across the cognitive aging spectrum [normal control (NC); (n=198; age=76±5), MCI (n=370; age=75±7), and AD (n=171; age=76±7)] in ADNI. Within diagnostic group, general linear models related slope methods individually to neuroimaging variables, adjusting for age, sex, education, and APOE4 status. Among MCI, better learning performance on simple slope, regression-based slope, and late slope (Trial 2-5) from the two-slope method related to larger parahippocampal thickness (all p-values<.01) and hippocampal volume (p<.01). Better regression-based slope (p<.01) and late slope (p<.01) were related to larger ventrolateral prefrontal cortex in MCI. No significant associations emerged between any slope and neuroimaging variables for NC (p-values ≥.05) or AD (p-values ≥.02). Better learning performances related to larger medial temporal lobe (i.e., hippocampal volume, parahippocampal gyrus thickness) and ventrolateral prefrontal cortex in MCI only. Regression-based and late slope were most highly correlated with neuroimaging markers and explained more variance above and beyond other common memory indices, such as total learning. Simple slope may offer an acceptable alternative given its ease of calculation.

Longitudinal differences in aerobic capacity between children with sickle cell anemia and matched controls.

BACKGROUND: The purpose of this study was to compare longitudinal trajectories of maximal aerobic capacity in children with sickle cell anemia (SCA) and matched healthy controls, and explore whether these trajectories were associated with selected physiologic variables. PROCEDURE: Children with SCA (n = 33) and healthy controls (n = 30) matched at baseline for race, sex, Tanner stage, height, and weight completed three consecutive annual fitness assessments (VO2peak ). Data were compared between the groups at each time point and within groups over time. Change in VO2peak between the two groups over time was assessed using a linear mixed model with age, sex, fat-free mass (FFM), Tanner stage, and hemoglobin (Hgb) concentration as covariates. RESULTS: At baseline, children with SCA had significantly lower Hgb concentration (8.9 vs. 13.7 g/dL, P < 0.001) and relative VO2peak (24.2 vs. 27.9 ml/kg/min, P = 0.006) than healthy controls. Over time, children with SCA had smaller increases than healthy controls in VO2peak (-0.1 and +4.9 ml/kg/min, P < 0.001), Tanner stage at year 2 (15% and 66% Tanner 4, P < 0.001), and FFM (+4.0 and +6.8 kg, P = 0.02). Changes in Hgb concentration did not differ between groups (+0.03 and +0.09 g/dL, P = 1.0). After adjusting for age, sex, Tanner stage, FFM, and Hgb concentration the differences in change in VO2peak over time remained significant (P < 0.001). CONCLUSION: Children with SCA demonstrate lower relative VO2peak compared to healthy children and the difference increases over time. The difference in VO2peak trajectories between the two groups during puberty remains significant after adjusting for age, sex, FFM, Tanner stage, and Hgb concentration.

Evaluation of post-contrast myocardial t1 in duchenne muscular dystrophy using cardiac magnetic resonance imaging.

The objective of the study was to perform a retrospective pilot study to evaluate the potential of myocardial T1 in assessment of Duchenne muscular dystrophy (DMD) cardiomyopathy. Early identification of DMD cardiac disease, particularly myocardial fibrosis, would allow earlier therapy, potentially improving outcomes. Shortened myocardial T1 measured by cardiac MRI (CMR) is a measure of cardiac fibrosis that may be detected before late gadolinium enhancement (LGE). We hypothesized that the post-contrast T1 obtained from the Look-Locker sequences (T1LL), an easily obtainable surrogate of myocardial T1, would be abnormally shortened in DMD compared with controls. T1LL measurement was performed on 21 DMD subjects and 11 controls; to account for individual variations in gadolinium distribution, myocardial T1LL was divided by blood pool T1LL, deriving T1LL ratios. DMD subjects had shorter mean T1LL ratio than controls (1.42 vs 1.72, p < 0.001). Subset analyses in DMD subjects with normal LVEF and without LGE also demonstrated significantly shorter T1LL ratio (-0.28, p < 0.001 and -0.25, p = 0.028). Post-contrast T1LL ratio is abnormally shortened in DMD compared with controls, even in DMD patients with otherwise normal CMRs. The application of more aggressive therapy for those with shorter T1LL may favorably alter morbidity and improve mortality associated with DMD cardiomyopathy. These data suggest that further prospective evaluation of myocardial T1 will be of benefit to patients with DMD.

Fetuses of Mothers with Thyroid Disease May Be at Higher Risk of Developing Supraventricular Tachycardia.

OBJECTIVE: Fetal tachyarrhythmias complicate 0.5% of pregnancies, with high morbidity and mortality. We hypothesized that maternal factors may predispose to fetal supraventricular tachycardia (SVT). STUDY DESIGN: We reviewed medical records of all 124 mothers who presented to the Vanderbilt Fetal Cardiology Clinic from 2004 to 2010 for fetal arrhythmias, excluding heart block. Maternal factors were compared between 28 fetuses with SVT and a control group of 112 fetuses screened for noncardiac conditions. The proportions were analyzed using chi-square or Fisher exact test for categorical variables and Wilcoxon rank sum test for continuous variables. RESULTS: Of maternal factors, thyroid disease was statistically significant compared with controls. Among mothers whose fetuses had SVT, 21% had thyroid disease (83% hypothyroidism) compared with 3% of controls (p < 0.001). CONCLUSION: In this cohort, the maternal thyroid disease was more common in fetuses with SVT compared with controls (odds ratio = 9.8, 95% confidence interval 2.3-42.3), suggesting closer screening for fetal arrhythmias and SVT in mothers with thyroid disease. Also, routine screening of thyroid functions and thyroid autoantibodies may be warranted in mothers of fetuses with SVT.

Clinical predictors of autoimmune and severe atopic disease in pediatric heart transplant recipients.

Autoimmune and allergic diseases cause morbidity and diminished quality of life in pediatric organ transplant recipients. We hypothesize that younger age at transplantation and immunosuppression regimen play a role in the development of immune-mediated disease following heart transplant. A single institution retrospective review identified all patients undergoing heart transplant at ≤18 yr of age from 1987 to 2010 who survived ≥1 yr. Using medical record and database review, patients were evaluated for development of autoimmune or severe allergic disease. Of 129 patients who met criteria, seven patients (5.4%) with autoimmune or severe atopic disease were identified. Immune-mediated diseases included inflammatory bowel disease (n = 3), eosinophilic esophagitis/colitis (n = 4), and chronic bullous disease of childhood (n = 1). Patients <1 yr of age at transplant were at greater risk of developing autoimmune disease than patients 1-18 yr at transplant (OR = 9.3, 95% CI 1.1-79.2, p = 0.02). All affected patients underwent thymectomy at <1 yr of age (7/71 vs. 0/58, p = 0.02). In our experience, heart transplantation in infancy is associated with the development of immune-mediated gastrointestinal and dermatologic diseases. Further study is needed to determine risk factors for the development of immune-mediated disease to identify best practices to decrease incidence.

Outcomes following infliximab therapy for pediatric patients hospitalized with refractory colitis-predominant IBD.

OBJECTIVES: Although randomized trials demonstrated the efficacy of infliximab for both pediatric Crohn disease and ulcerative colitis (UC), few patients in these studies exhibited colitis requiring hospitalization. The aims of this study were to determine the rate of subsequent infliximab failure and dose escalation in pediatric patients who started taking infliximab during hospitalization for colitis-predominant IBD, and to identify potential predictors of these endpoints. METHODS: This is a single-center retrospective cohort study of patients admitted from 2005 to 2010 with Crohn colitis, UC, or IBD-unspecified (IBD-U) and initiated on infliximab. RESULTS: We identified 29 patients (12 Crohn colitis, 15 UC, and 2 IBD-U; median age 14 years) with a median follow-up of 923 days. Eighteen patients (62%) required infliximab dose escalation (increased dose or decreased infusion interval). Infliximab failure occurred in 18 patients (62%) because of ineffectiveness in 12 (67%) and adverse reactions in 6 (33%). Twelve patients (41%) underwent colectomy. Subsequent need for infliximab dose escalation was associated with lower body mass index z score (P = 0.01), lower serum albumin (P = 0.03), and higher erythrocyte sedimentation rate (ESR) (P = 0.002) at baseline. ESR predicted subsequent infliximab dose escalation with an area under the curve of 0.89 (95% confidence interval [CI] 0.72-1.00) and a sensitivity and specificity at a cutoff of 38 mm/hour of 0.79 (95% CI 0.49-0.95) and 0.88 (95% CI 0.47-0.99), respectively. CONCLUSIONS: Most hospitalized pediatric patients with colitis treated with infliximab require early-dose escalation and fail the drug long term. Low body mass index and albumin and high ESR, may identify patients who would benefit from a higher infliximab starting dose.

Human rhinovirus C: Age, season, and lower respiratory illness over the past 3 decades.

BACKGROUND: Human rhinoviruses (HRVs) cause common colds, and the recently discovered HRV-C is increasingly associated with lower respiratory illness among populations such as children and asthmatic patients. OBJECTIVE: To determine how HRV-C is associated with respiratory illness and to evaluate changes in prevalence and species over 2 decades. METHODS: A prospective study of children younger than 5 years was performed at the Vanderbilt Vaccine Clinic over a 21-year period. Nasal-wash specimens from children presenting with upper or lower respiratory illness at acute care visits were tested for HRV and HRV-positives genotyped. Demographic and clinical features were compared between children with or without HRV, and with different HRV species. RESULTS: HRV was detected in 190 of 527 (36%) specimens from a population of 2009 children from 1982 through 2003. Of these, 36% were HRV-C. Age (P = .039) and month of illness (P < .001) were associated with HRV infection and HRV species. HRV-C was significantly associated with lower respiratory illness, compared with HRV-A (P = .014). HRV-A and HRV-C prevalence fluctuated throughout the 21-year period; HRV-C was more prevalent during winter (P = .058). CONCLUSIONS: HRV-C is not a new virus but has been significantly associated with childhood lower respiratory illness in this population for several decades. Temporal changes in virus prevalence occur, and season may predict virus species. Our findings have implications for diagnostic, preventive, and treatment strategies due to the variation in disease season and severity based on species of HRV infection.

The source of cognitive complaints predicts diagnostic conversion differentially among nondemented older adults.

OBJECTIVE: The objective of this study was to compare whether different sources of cognitive complaint (i.e., subjective and informant) predict diagnostic conversion in nondemented older adults. METHODS: Participants from the National Alzheimer's Coordinating Center had a baseline diagnosis of normal cognition (NC; n = 4414; mean age, 73 ± 8 years; 69% female) or mild cognitive impairment (MCI; n = 1843; mean age, 74 ± 8 years; 52% female). Multinomial logistic regression related baseline cognitive complaint (no complaint, self only, informant only, or both self and informant) to diagnostic outcome (reversion, stable, or conversion). RESULTS: At follow-up, 14% of NC participants converted to MCI/dementia (3.5 ± 1.8 years), and 41% of MCI participants converted to dementia (3.0 ± 1.6 years). Among NC participants, self complaint only (odds ratio [OR], 2.1; 99% confidence interval (CI),1.5-2.9; P < .001), informant complaint only (OR, 2.2; 99% CI, 1.2-3.9; P < .001), and both self and informant complaint (OR, 4.2; 99% CI, 2.9-6.0; P < .001) were associated with diagnostic conversion compared with no complaint. Among participants with MCI-compared with no complaint, informant complaint only (OR, 2.2; 99% CI, 1.2-4.3, P = .002), and both self and informant complaint (OR, 2.9; 99% CI, 1.8-4.8; P < .001)-were associated with conversion. CONCLUSIONS: Cognitive complaints are related to conversion among nondemented older adults. Complaint from both (i.e. mutual complaint) sources was most predictive of diagnostic outcome, followed by informant complaint, highlighting the need for obtaining informant corroboration to enhance prognosis and distinguish underlying pathological processes from normal cognitive aging. Self complaint was related inconsistently to diagnostic outcome.

Disparities in diabetes management among medicaid recipients with intellectual and developmental disabilities (IDD): Evidence from five U.S. states.

BACKGROUND: Diabetes is one of the most common chronic conditions among adults. Little is known about the quality of diabetes care received by adults with intellectual and developmental disabilities (IDD). OBJECTIVE: To determine the extent to which the diabetes care needs are met for a population with both IDD and diabetes who are solely insured by Medicaid in five states (Iowa, Massachusetts, New York, Oregon and South Carolina). METHODS: Medicaid administrative data in 2012 were used to identify Medicaid members (excluding dual eligibles) with diabetes and IDD in five states. Four diabetes care measures were compared between members with and without IDD using bivariate analyses. For those with diabetes and IDD, a logistic regression model was fitted for each state with the following predictors: age, sex, IDD subgroup, and occurrence of a specialist visit in the current or past year. A meta-analysis was then conducted to synthesize cross-state results. RESULTS: Across the five states, 6229 (2%) of the 308,804 non-dual adult Medicaid members 18-64 years old with diabetes in 2012 also had IDD. Comparing those with IDD to their non-IDD peers on receipt of all four diabetes care measures showed differences by state, but state rates of overall adherence were very low, ranging from 16.6% to 28.5% of the population. CONCLUSIONS: Meta-analysis results identified specialist visits as a strong predictor of adults with diabetes and IDD receiving all four components of diabetes care. This important information should be considered in efforts to improve quality care for this population.

Inclusion of an informant yields strong associations between cognitive complaint and longitudinal cognitive outcomes in non-demented elders.

BACKGROUND: The relation between the source of cognitive complaint and objective cognitive performance is not well understood. OBJECTIVE: Examine self and informant cognitive complaint as predictors of objective cognitive and functional trajectory in non-demented elders. METHODS: Participants from the National Alzheimer's Coordinating Center had a baseline diagnosis of normal cognition (NC; n = 6133, 72±8 years, 68% female) or mild cognitive impairment (MCI; n = 3010, 74±8 years, 55% female). Four independent groups defined cognitive complaint: no complaint, self-only complaint, informant-only complaint, or mutual complaint (both self and informant complaint). Linear mixed model regression analyses related complaint status (referent was no complaint) to cognitive and functional trajectories, adjusting for age, sex, race, education, and follow-up period. RESULTS: Among NC participants, mutual complaint related to faster decline in global cognition (p < 0.0001), language (all p-values <0.0001), processing speed (p = 0.0002), and executive functioning (p = 0.0006). Informant-only complaint related to faster decline in global cognition (p = 0.0001) and processing speed (p = 0.0001). Self-only complaint related to greater decline in immediate (p < 0.0001) and delayed (p = 0.0005) episodic memory. In MCI, mutual complaint related to faster decline in global cognition (p < 0.0001), verbal episodic memory (all p-values <0.0001), language (all p-values <0.0001), and processing speed(all p-values <0.0006). Informant-only or self-only complaint associations with cognitive trajectory did not survive correction factor for multiple comparisons.Conclusion: Cognitive complaint appears to have clinical significance, as it is related to declines in objective cognitive performance over time. Mutual complaint was associated with the worst cognitive trajectory in both NC and MCI elders, highlighting the importance of incorporating an informant into evaluation of elders whenever feasible.

Subjective memory complaint only relates to verbal episodic memory performance in mild cognitive impairment.

BACKGROUND: A cognitive concern from the patient, informant, or clinician is required for the diagnosis of mild cognitive impairment (MCI); however, the cognitive and neuroanatomical correlates of complaint are poorly understood. OBJECTIVE: We assessed how self-complaint relates to cognitive and neuroimaging measures in older adults with MCI. METHOD: MCI participants were drawn from the Alzheimer's Disease Neuroimaging Initiative and dichotomized into two groups based on the presence of self-reported memory complaint (no complaint n = 191, 77 ± 7 years; complaint n = 206, 73 ± 8 years). Cognitive outcomes included episodic memory, executive functioning, information processing speed, and language. Imaging outcomes included regional lobar volumes (frontal, parietal, temporal, cingulate) and specific medial temporal lobe structures (hippocampal volume, entorhinal cortex thickness, parahippocampal gyrus thickness). RESULTS: Linear regressions, adjusting for age, gender, race, education, Mini-Mental State Examination score, mood, and apolipoprotein E4 status, found that cognitive complaint related to immediate (ß = -1.07, p < 0.001) and delayed episodic memory performances assessed on a serial list learning task (ß = -1.06, p = 0.001) but no other cognitive measures or neuroimaging markers. CONCLUSIONS: Self-reported memory concern was unrelated to structural neuroimaging markers of atrophy and measures of information processing speed, executive functioning, or language. In contrast, subjective memory complaint related to objective verbal episodic learning performance. Future research is warranted to better understand the relation between cognitive complaint and surrogate markers of abnormal brain aging, including Alzheimer's disease, across the cognitive aging spectrum.

Adverse vascular risk is related to cognitive decline in older adults.

BACKGROUND: Cardiovascular disease (CVD) and related risk factors are associated with Alzheimer's disease (AD). This association is less well-defined in normal cognition (NC) or prodromal AD (mild cognitive impairment, MCI). OBJECTIVE: Cross-sectionally and longitudinally relate a vascular risk index to cognitive outcomes among elders free of clinical dementia. METHODS: 3,117 MCI (74 ± 8 years, 56% female) and 6,603 NC participants (72 ± 8 years, 68% female) were drawn from the National Alzheimer's Coordinating Center. A composite measure of vascular risk was defined using the Framingham Stroke Risk Profile (FSRP) score (i.e., age, systolic blood pressure, anti-hypertensive medication, diabetes, cigarette smoking, CVD history, atrial fibrillation). Ordinary linear regressions and generalized linear mixed models related baseline FSRP to cross-sectional and longitudinal cognitive outcomes, separately for NC and MCI, adjusting for age, gender, race, education, and follow-up time (in longitudinal models). RESULTS: In NC participants, increasing FSRP was related to worse baseline global cognition, information processing speed, and sequencing abilities (p-values <0.0001) and a worse longitudinal trajectory on all cognitive measures (p-values <0.0001). In MCI, increasing FSRP correlated with worse longitudinal delayed memory (p = 0.004). In secondary models using an age-excluded FSRP score, associations persisted in NC participants for global cognition, naming, information processing speed, and sequencing abilities. CONCLUSIONS: An adverse vascular risk profile is associated with worse cognitive trajectory, especially global cognition, naming, and information processing speed, among NC elders. Future studies are needed to understand how effective management of CVD and related risk factors can modify cognitive decline to identify the ideal timeframe for primary prevention implementation.

Adherence of randomized trials within children's surgical specialties published during 2000 to 2009 to standard reporting guidelines.

BACKGROUND: Randomized clinical trials (RCTs) are uncommon in pediatric surgical specialties and the quality of reporting is unknown. Our primary purpose was to analyze published surgical RCTs involving children to measure adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. STUDY DESIGN: Published RCTs from January 1, 2000 through December 31, 2009 were reviewed. The trials were evaluated for the presence of 7 CONSORT guidelines and also graded according to the Jadad scale. RESULTS: Two hundred and twenty-eight trials were included. Five trials met all 7 CONSORT criteria (2%) and 53 had a Jadad score of ≥3 (23%). Slightly more than 50% of all trials specified primary outcomes and <25% described power calculations according to CONSORT. Adherence to CONSORT guidelines for allocation concealment, randomization description, and attrition details was even lower. There were significant differences between surgical specialties with regard to CONSORT adherence to the majority of the guidelines. Pediatric general surgery had the largest number of published RCTs. Pediatric orthopaedic surgery had the highest proportion of trials with a Jadad score ≥3 (40%). CONCLUSIONS: Adherence to CONSORT guidelines is low across the spectrum of children's surgical specialties, although significant differences do exist. Future RCTs in children's surgical specialties should specifically focus on areas of low adherence to reporting guidelines.

Role of a respiratory viral panel in the clinical management of pediatric inpatients.

BACKGROUND: Respiratory viral panels (RVPs) able to detect multiple pathogens are increasingly used in the management of pediatric inpatients. Despite this, few studies have examined whether the results of these tests are associated with clinically significant changes in medical management. METHODS: In this retrospective cohort study, we identified pediatric inpatients between August 2009 and December 2010 for whom an RVP was ordered within 24 hours of admission to a large, tertiary-care children's hospital. We used linear regression to determine whether RVP was associated with length of stay (LOS), duration of antibiotics and the number of diagnostic microbiology tests ordered, adjusting for potential confounders. RESULTS: We found that the association between results of the RVP and LOS was dependent on a patient's admission service, specifically admission to the hematology/oncology service. We also found that patients with a positive RVP had a shorter duration of intravenous antibiotic administration (P = 0.03; 42% reduction in the geometric mean), but that this was influenced by the primary admission service. We also found that positive results of the RVP were associated with decreased LOS and shorter duration of antibiotics in patients with some common respiratory diagnoses. CONCLUSIONS: This study lacked sufficient evidence to claim an association between a positive RVP and LOS in pediatric patients, adjusting for their underlying diagnosis. However, we found that a positive RVP was associated with a shorter duration of intravenous antibiotic administration in certain groups of patients and those with some common respiratory diagnoses. These findings help clarify the utility of rapid viral testing in the management of hospitalized pediatric patients.

Blood pressure and cognition among older adults: a meta-analysis.

Hypertension has adverse effects on cognition, can alter cerebral vasculature integrity, and is associated with the pathogenesis of dementia. Using meta-analysis, we correlated blood pressure to multiple cognitive domains among older adults free of clinical stroke and dementia. We identified 230 studies indexed in PubMed and PsycINFO relating blood pressure and cognition. After applying exclusion criteria, we selected n = 12 articles with n = 4,076 participants (age range 43-91 years). Meta-analysis yielded an association between blood pressure and episodic memory (r = -.18, p < .001) and between blood pressure and global cognition (r = -.07, p < .001). When limiting analyses to studies adjusting for vascular covariates (n = 8, n = 2,141), blood pressure was modestly related to global cognition (r = -.11, p < .001), attention (r = .14, p = .002), and episodic memory (r = -.20, p < .001) with a trend for language (r = -.22, p = .07). Findings underscore the need to manage blood pressure as a key prevention method in minimizing abnormal cognitive aging prior to the onset of clinical dementia.