Effects of Intensive Versus Standard Ambulatory Blood Pressure Control on Cerebrovascular Outcomes in Older People (INFINITY).

BACKGROUND: Subcortical microvascular disease represented by brain white matter hyperintensity on magnetic resonance imaging is associated with functional decline in older people with hypertension. The effects of 2 levels of 24-hour average systolic blood pressure (BP) on mobility, white matter disease progression, and cognitive function over 3 years were studied. METHODS: This trial was a prospective, randomized, blinded end-points study in patients ≥75 years of age with systolic hypertension and magnetic resonance imaging evidence of white matter hyperintensity lesions. Patients were randomized to a 24-hour mean systolic BP of ≤130 mm Hg (intensive treatment) versus ≤145 mm Hg (standard treatment) with antihypertensive therapies. Primary study outcomes were changes in mobility (gait speed) and accrual of white matter hyperintensity volume after 3 years. Changes in cognitive function (executive processing) and adverse events were also evaluated. RESULTS: In 199 randomized patients, the mean age of the cohort was 80.5 years, and 54% were women; the average 24-hour systolic BP was 149 mm Hg. Goal BPs were achieved after a median treatment period of 3 to 4 months; at that time, the mean 24-hour systolic BP was 127.7 mm Hg in the intensive treatment group and 144.0 mm Hg in the standard treatment group for an average difference of 16.3 mm Hg. Changes in gait speed were not different between treatment groups (0.40±2.0 versus 0.42±2.7 s in the intensive treatment and standard treatment groups, respectively; P=0.91), whereas changes from baseline in white matter hyperintensity volumes were smaller (0.29%) in the intensive treatment group compared with the standard treatment group (0.48%; P=0.03). Cognitive outcomes also were not different between the treatment groups. Major adverse cardiovascular events were higher in the standard treatment group compared with the intensive treatment group (17 versus 4 patients; P=0.01). Falls, with or without injury, and syncope were comparable in the treatment groups. CONCLUSIONS: Intensive lowering of ambulatory BP reduction in older patients with hypertension did not result in differences in mobility outcomes but was associated with a reduction in accrual of subcortical white matter disease. Over periods >3 years, a reduction in the accumulation of white matter disease may be a factor in conserving function. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01650402.

Relationships among clinic, home, and ambulatory blood pressures with small vessel disease of the brain and functional status in older people with hypertension.

BACKGROUND: Subcortical small vessel disease, represented as white matter hyperintensity (WMH) on magnetic resonance images (MRI) is associated with functional decline in older people with hypertension. We evaluated the relationships of clinic and out-of-office blood pressures (BP) with WMH and functional status in older persons. METHODS: Using cross-sectional data from 199 older study participants enrolled in the INFINITY trial, we analyzed the clinic, 24-hour ambulatory, and home BPs and their relationships with WMH burden and mobility and cognitive outcomes. RESULTS: Volume of WMH was associated with clinic and 24-hour ambulatory systolic BP but not home systolic BP. The mobility measure, supine-to-sit time, had a significant association with 24-hour systolic BP and pulse pressure but not with diastolic BP or values obtained by home BP. Cognitive measures of processing speed (Trails Making Test Part A and the Stroop Word Test) were significantly associated with 24-hour systolic BP, but not clinic and home BPs. CONCLUSION: These data demonstrate that ambulatory BP measurements in older people are more strongly associated with WMH and certain measures of functional status compared to home BP measurements. Hence, home BP may not be a useful substitute for ambulatory BP for assessing subcortical small vessel disease and its consequences. Further longitudinal analyses comparing clinic and various types of out-of-office BP measures with small vessel brain disease are needed. Clinicaltrials.gov identifier: NCT01650402.

INtensive versus standard ambulatory blood pressure lowering to prevent functional DeclINe in the ElderlY (INFINITY).

Reductions in mobility and cognitive function linked to accrual of brain microvascular disease related white matter hyperintensities (WMHs) on magnetic resonance imaging can occur in older hypertensive patients in as little as 2 years. We have designed a trial evaluating 2 levels of ambulatory blood pressure (ABP) control in individuals with normal or mildly impaired mobility and cognition who have detectable cerebrovascular disease (>0.5% WMH fraction of intracranial volume) on functional outcomes. The study is a prospective randomized, open-label trial with blinded end points, in patients ages ≥75 years with elevated 24-hour systolic blood pressure (BP) (145 mm Hg in the untreated state) who do not have unstable cardiovascular disease, heart failure, or stroke. The primary and key secondary outcomes in the trial are change from baseline in mobility and cognitive function and damage to brain white matter as demonstrated by accrual of WMH volume and changes in diffusion tensor imaging. Approximately 300 patients will be enrolled, and 200 randomized to 1 of 2 levels of ABP control (intensive to achieve a goal 24-hour systolic BP of ≤130 mm Hg or standard to achieve a goal 24-hour systolic BP of ≤145 mm Hg) for a total of 36 months using similar antihypertensive regimens. The analytical approach provides 85% power to show a clinically meaningful effect in differences in mobility accompanied by quantitative differences in WMH between treatment groups. The INFINITY trial is the first to guide antihypertensive therapy using ABP monitoring rather than clinic BP to reduce cerebrovascular disease.

Late-life onset bipolar disorder presenting as a case of pseudo-dementia: a case discussion and review of literature.

Depression and comorbid cognitive impairment in the elderly can be difficult to distinguish from dementia. Adding to the complex differential is that depression may be part of a bipolar illness rather than a unipolar mood disorder. A diligent workup and close monitoring of patients can inform appropriate treatment and can make the difference between recovery and persistence of symptoms. The present case will illustrate how a comprehensive workup utilizing extensive data gathering, laboratory workup, use of neuropsychological testing, neuroimaging, and timely treatment can lead to successful clinical outcomes that can be sustained for many years.

Average daily blood pressure, not office blood pressure, is associated with progression of cerebrovascular disease and cognitive decline in older people.

BACKGROUND: High blood pressure (BP) is a risk factor for cerebrovascular disease, including stroke. Little is known about the importance of BP on the progression of microvascular disease of the brain, which has been associated with functional decline in mobility and cognition in older people. METHODS AND RESULTS: This was a prospective cohort of subjects 75 to 89 years of age to determine relations among vascular risk factors, white matter hyperintensity volume, and functional status. Ninety-nine subjects were enrolled through the use of a balanced 3×3 matrix stratified by age and mobility performance, and 72 subjects completed all sets of baseline and follow-up studies at 2 years. Subjects were excluded if there were medications or systemic or neurological diseases that could compromise mobility. Ambulatory and clinic BP monitoring, magnetic resonance imaging, gait studies, and neuropsychological testing were performed at baseline and after 24 months. Brain classification into normal white matter and T2-hyperintense white matter hyperintensity volume was performed with semiautomated segmentation. Quantitative measures of mobility and cognitive function were obtained longitudinally. Increased ambulatory systolic BP, but not clinic systolic BP, from baseline to 24 month follow-up was associated with increased white matter hyperintensity volume over that same period, as well as measures of executive function/processing speed. Similar associations were observed for 24-hour BP, awake BP, and sleep BP but not for the surge between the sleep and awake time at the 24-month time point. CONCLUSIONS: These data demonstrate for the first time the importance of 24-hour systolic BP in the progression of brain white matter hyperintensity volume burden associated with impairment of cognitive function in older people. The 24-hour systolic BP may be a potential target for intervention in the elderly to reduce vascular disease of the brain and impairment of function.

Biological markers of cognition in prodromal Huntington's disease: a review.

Huntington's disease (HD), an autosomal-dominant genetic disorder, has historically been viewed as a degenerative movement disorder but it also includes psychiatric symptoms and progressive cognitive decline. There has been a lack of consensus in the literature about whether or not cognitive signs can be detected in carriers before clinical (motor) onset of the disease, i.e., prodromal HD. However, recently validated mathematical formulas to estimate age of clinical onset, refined over the past 5-7 years, have allowed researchers to overcome the methodological limitation of treating all prodromal carriers as a homogenous high-risk group (i.e., whether they may be 2 or 15 years from diagnosis). Here we review 23 articles on the HD prodrome, all of which related cognition to a biological marker of disease burden (i.e., genetic load, neuroimaging). All studies found at least one cognitive domain was associated with disease burden in prodromal HD participants. There was greater variability in both the detection and cognitive domain affected in those farther from onset (or those with less pathology) while most studies reliably found declines in visuomotor performance and working memory in those closer to onset. These findings indicate that cognitive signs can be reliably detected in the HD prodrome when comparing cognition to additional disease markers, however, there continues to be significant variability on cognitive findings among large and methodologically rigorous studies. This may reflect true heterogeneity in the prodromal HD phenotype which must be further explored by analyzing intra-individual variance, determining demographic risk factors associated with decline/protection, and examining if particular HD families exhibit distinct cognitive profiles. These and additional future directions are discussed.

P300 and the stroop effect in overweight minority adolescents.

AIM: The goal was to examine the relationship between a risk factor for poor cognitive control and a health outcome of growing public significance--an excess body mass--among adolescents. METHODS: To this end, 109 adolescents aged 14-20 years were recruited and assigned to 1 of 4 groups defined by the crossing of the absence versus presence of a parental history (PH) of externalizing disorders with a body mass index (BMI) percentile (BMIP) < 85 versus > or = 85. The principal measure estimating cognitive control was the P300 event-related electroencephalographic response recorded during the Stroop task. RESULTS: The analyses revealed a synergistic interaction between BMIP rank, PH and trial type: the increase in P300 latency and the decrease in response accuracy, elicited by the presence of interfering information, were markedly greater in high-BMIP subjects with a PH of externalizing disorders than in the other subject groups. Analyses of a later component, the N450, previously associated with the Stroop interference effect, revealed no effect of BMI or PH. CONCLUSIONS: We conclude that subjects with both a PH of externalizing disorders and an excess BMI constitute a unique group that is less able to resolve cognitive conflict than others. The excessive delay in P300 evoked by conflicting response demands in these subjects may be a marker of a heritable factor that increases risk for both excess body mass and substance use disorders.

Detection of carbon monoxide during routine anesthetics in infants and children.

BACKGROUND: Carbon monoxide (CO) can be produced in the anesthesia circuit when inhaled anesthetics are degraded by dried carbon dioxide absorbent and exhaled CO can potentially be rebreathed during low-flow anesthesia. Exposure to low concentrations of CO (12.5 ppm) can cause neurotoxicity in the developing brain and may lead to neurodevelopmental impairment. In this study, we aimed to quantify the amount of CO present within a circle system breathing circuit during general endotracheal anesthesia in infants and children with fresh strong metal alkali carbon dioxide absorbent and define the variables associated with the levels detected. METHODS: Fifteen infants and children (aged 4 months to 8 years) undergoing mask induction followed by general endotracheal anesthesia were evaluated in this observational study. CO was measured in real time from the inspiratory limb of the anesthesia circuit every 5 minutes for 1 hour during general anesthesia. Carboxyhemoglobin (COHb) levels were measured at the 1-hour time point and compared with baseline. RESULTS: CO was detected in all patients older than 2 years (0-18 ppm, mean 3.7 +/- 4.8 ppm) and rarely detected in patients younger than 2 years (0-2 ppm, mean 0.2 +/- 0.6 ppm). Only the relationship between CO concentration and fresh gas flow to minute ventilation ratio (FGF:(.)VE) remained significant after adjustment in longitudinal regression analysis (P < 0.001). Although not powered to determine such a relationship, CO levels were weakly associated with the use of desflurane and female sex. There was no significant association between CO concentration and anesthetic concentration. Baseline COHb levels were higher in children younger than 2 years and decreased significantly at the 1-hour time point compared with baseline and children older than 2 years. However, COHb levels increased significantly from baseline in a predictable manner consistent with CO exposure in children older than 2 years. FGF:(.)VE correlated significantly with change in COHb using simple linear regression (r = 0.62; P < 0.02). CONCLUSIONS: CO was detected routinely during general anesthesia in infants and children when FGF:(.)VE was <1. Peak CO levels measured in the anesthesia breathing circuit were in the range thought to impair the developing brain. Further study is required to identify the source of CO detected (CO produced by degradation of volatile anesthetic versus rebreathing CO from endogenous sources or both). However, these findings suggest that avoidance of low-flow anesthesia will prevent rebreathing of exhaled CO, and use of carbon dioxide absorbents that lack strong metal hydroxide could limit inspired CO if detection was attributable to degradation of volatile anesthetic.

Postoperative malignant hyperthermia: an analysis of cases from the North American Malignant Hyperthermia Registry.

BACKGROUND: The initial presentation of malignant hyperthermia (MH) may begin in the postoperative period. However, the maximal latency period between the end of anesthesia care and the onset of postoperative MH is unknown. The authors hypothesized that this latency period is short and is not manifested by hyperthermia as the initial presenting sign. The authors sought to test this hypothesis and to describe the clinical characteristics of postoperative MH by analysis of suspected cases in the North American Malignant Hyperthermia Registry. METHODS: Of 528 possible or suspected cases of MH in the North American Malignant Hyperthermia Registry, the authors identified 64 possible reports of postoperative MH. The records were reviewed in detail by the authors, each of whom assigned a qualitative score of "likely," "not likely," "not enough information available," or "not applicable" (where MH was not the final definitive diagnosis). Postoperative MH was confirmed after a consensus meeting of the three senior authors who reviewed in detail all possible "likely" cases. RESULTS: The authors identified postoperative MH in 10 subjects. All received volatile agents and 5 also received succinylcholine. All demonstrated signs characteristic of acute MH, including generalized rigidity, hypercapnia and/or tachypnea, tachycardia, and hyperthermia. No subject demonstrated hyperthermia as the presenting sign. The latency period between the anesthesia finish time and the onset of a sign indicative of acute MH ranged from 0 to 40 min. CONCLUSIONS: Postoperative MH is uncommon, occurring in 10 of 528 suspected MH cases (1.9%) reported to the North American Malignant Hyperthermia Registry. Postoperative MH began shortly after completion of the anesthetic care. Hyperthermia was not a presenting sign of MH.

The effect of 3-year treatment with 0.25 mg/day of micronized 17beta-estradiol on cognitive function in older postmenopausal women.

OBJECTIVES: To evaluate the effect of ultra-low-dose (0.25 mg/d) micronized 17beta-estradiol on cognitive function in older postmenopausal women. DESIGN: Randomized, placebo-controlled trial conducted for 3 years. SETTING: Academic health center in greater Hartford, Connecticut. PARTICIPANTS: Fifty-seven healthy, community-dwelling, older postmenopausal women. INTERVENTION: Women received 0.25 mg/d of micronized 17beta-estradiol (estrogen therapy (ET), n=32) or placebo (n=25); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months. MEASUREMENTS: Neuropsychological measures of memory, language, mood, and executive function were collected at baseline, 3 months, and 36 months. Measures of executive function included the Controlled Oral Word Association Test, the Trail Making Test, and the Wisconsin Card Sorting Test. The Boston Naming Test was used to measure language skills. The Symbol Digit Modalities Test was used as a measure of sustained attention. Measures of memory included the Complex Figure Test, Fuld Object Memory Test, and a selected subtest from the Wechsler Memory Scale. Scores from the Geriatric Depression Scale and the Beck Anxiety Inventory were used to assess symptoms of depression. RESULTS: No differences were found between ET and placebo on any of the neurocognitive measures or depression instruments, nor were there any differences when the groups were stratified according to age. CONCLUSION: This small study, which had adequate power to detect change in some but not all domains of cognition tested, revealed that low-dose estrogen neither benefits nor harms cognitive function in older women after 3 years of treatment, but confirmation is needed from larger trials.

Anesthetic Management of Two Pediatric Patients With Concurrent Diagnoses of Mitochondrial Disease and Malignant Hyperthermia Susceptibility: A Case Report.

We report the case of 2 pediatric patients with coexisting diagnoses of malignant hyperthermia susceptibility and mitochondrial disease in 2 different surgical settings. Due to the rare occurrence of each disorder, and even more so together, we reviewed evidence-based anesthetic concerns and described our perioperative management, with the goal of aiding future practitioners in safely caring for these patients. Consent was obtained for both patients, as well as IRB approval before publication.

Cardiovascular risk factors and small vessel disease of the brain: Blood pressure, white matter lesions, and functional decline in older persons.

Several potential vascular risk factors exist for the development and accumulation of subcortical white matter disease in older people. We have reported that in older people followed for up to 4 years white matter hyperintensity (WMH) lesions on magnetic resonance imaging nearly doubled in volume and were associated with alterations in mobility and cognitive function. Herein we review the genetic, metabolic, and vascular risk factors that have been evaluated in association with the development and pathogenesis of WMH in older persons. Our research efforts have focused on systemic hypertension, particularly in the out-of-office setting as 24-hour ambulatory blood pressure (BP) has proven to be a stronger indicator of the progression of WMH in older people and the associated functional decline than doctor's office BP. Based on relations between 24-hour systolic BP levels, the accrual of WMH, and functional decline, we have designed the INFINITY trial, the first interventional study to use ambulatory BP to guide antihypertensive therapy to address this problem in the geriatric population.

Evaluation of an automated single-channel sleep staging algorithm.

BACKGROUND: We previously published the performance evaluation of an automated electroencephalography (EEG)-based single-channel sleep-wake detection algorithm called Z-ALG used by the Zmachine(®) sleep monitoring system. The objective of this paper is to evaluate the performance of a new algorithm called Z-PLUS, which further differentiates sleep as detected by Z-ALG into Light Sleep, Deep Sleep, and Rapid Eye Movement (REM) Sleep, against laboratory polysomnography (PSG) using a consensus of expert visual scorers. METHODS: Single night, in-lab PSG recordings from 99 subjects (52F/47M, 18-60 years, median age 32.7 years), including both normal sleepers and those reporting a variety of sleep complaints consistent with chronic insomnia, sleep apnea, and restless leg syndrome, as well as those taking selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor antidepressant medications, previously evaluated using Z-ALG were re-examined using Z-PLUS. EEG data collected from electrodes placed at the differential-mastoids (A1-A2) were processed by Z-ALG to determine wake and sleep, then those epochs detected as sleep were further processed by Z-PLUS to differentiate into Light Sleep, Deep Sleep, and REM. EEG data were visually scored by multiple certified polysomnographic technologists according to the Rechtschaffen and Kales criterion, and then combined using a majority-voting rule to create a PSG Consensus score file for each of the 99 subjects. Z-PLUS output was compared to the PSG Consensus score files for both epoch-by-epoch (eg, sensitivity, specificity, and kappa) and sleep stage-related statistics (eg, Latency to Deep Sleep, Latency to REM, Total Deep Sleep, and Total REM). RESULTS: Sensitivities of Z-PLUS compared to the PSG Consensus were 0.84 for Light Sleep, 0.74 for Deep Sleep, and 0.72 for REM. Similarly, positive predictive values were 0.85 for Light Sleep, 0.78 for Deep Sleep, and 0.73 for REM. Overall, kappa agreement of 0.72 is indicative of substantial agreement. CONCLUSION: This study demonstrates that Z-PLUS can automatically assess sleep stage using a single A1-A2 EEG channel when compared to the sleep stage scoring by a consensus of polysomnographic technologists. Our findings suggest that Z-PLUS may be used in conjunction with Z-ALG for single-channel EEG-based sleep staging.

The effect of short-term estradiol therapy on cognitive function in older men receiving hormonal suppression therapy for prostate cancer.

OBJECTIVES: To determine the effect of estrogen (E) alone (without the influence of testosterone (T)) on cognitive function in older men, using 17-beta micronized estradiol versus placebo in older men rendered hypogonadal (low T and E) by treatment for prostate cancer. DESIGN: Short-term double-blind, randomized, controlled trial. SETTING: An outpatient General Clinical Research Center. PARTICIPANTS: Twenty-seven community-dwelling men aged 65 and older receiving neoadjuvant or established therapy with luteinizing-hormone releasing-hormone agonists for treatment of prostate cancer enrolled in a short-term randomized, controlled trial of 17-beta micronized estradiol versus placebo on the effect on biochemical markers of bone turnover. MEASUREMENTS: Hormone levels, including E, T, and sex hormone-binding globulin; standardized neurocognitive tests, including measures of sustained attention, executive function, and memory; and questionnaires to assess subjects' perception of cognitive deficits and symptoms of depression. RESULTS: There were no significant differences between patients receiving E or placebo on 15 of 17 neurocognitive measures and no significant differences in self-reported cognitive deficits or number of depressive symptoms. CONCLUSION: Although studies have suggested that E replacement therapy may improve cognitive function, most notably memory performance in postmenopausal woman, there was no evidence in the present study that the addition of short-term E therapy was more beneficial than placebo in tests of cognitive performance in hypogonadal men.

A review of adult ADHD: a neuropsychological and neuroimaging perspective.

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder which effects an estimated 3% to 5% of children. Despite estimates that ADHD persists in 30% to 70% of adults having had the disorder in childhood, ADHD in adulthood remains controversial. This report summarizes current thinking in the diagnosis and etiology of adult ADHD. Most theories posit that ADHD is related to anomalies in frontal lobe function and dopaminergic transmission. However, there is debate as to whether ADHD is a unitary disorder with different manifestations, a syndrome, or multiple disorders. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, classifies ADHD into inattention, hyperactivity-impulsivity, and combined subtypes. Although problems with cognition are core ADHD symptoms, self-reporting has not been a reliable predictor of neuropsychological test performance. Nevertheless, we suggest that a performance-based diagnosis, including empirically derived, age-sensitive neuropsychological tests, provides the best hope of dissociating ADHD from psychiatric disorders with similar symptoms. We also describe the promise of new neuroimaging technologies, such as functional magnetic resonance imaging, in elucidating the pathophysiology of ADHD and similar psychiatric disorders.

Executive-cognitive functioning in the development of antisocial personality disorder.

The present study examined the association of cognitive-executive abilities to two risk factors for alcoholism, i.e., antisocial behaviors and a family history (FH+) of alcohol dependence. A sample of 91 right-handed, non-substance-dependent, young male adults recruited from the community were classified into three groups: (1) a control group of n=32 men with no history of DSM-III-R childhood conduct disorder (CD) or antisocial personality disorder (ASPD); (2) n=25 men who met criteria for a DSM-III-R childhood CD diagnosis, but did not meet diagnostic criteria for ASPD (i.e., CD/ASPD-); and (3) n=34 men who met DSM-III-R criteria for ASPD. They were further divided into those with and without a positive family history of alcoholism. A two-way (Antisocial Profile (3)x Family History of Alcoholism (2)) ANOVA was used to compare several neuropsychological measures of executive-cognitive functioning (ECF) ability. Verbal abstraction ability was found to be significantly lower in ASPD subjects compared with controls and CD-only subjects, inversely related to antisocial behavior severity (as measured by symptom count). CD-only and control subjects' abstraction ability were statistically indistinguishable. FH+ was associated with increased errors in planning performance on the Porteus Maze Test and diminished performance on Luria's simple alternate-tapping motor tasks. The effect was more pronounced when inhibition of prepotent motor planning was required. Results are consistent with previous work examining ECF ability in antisocial samples that find subtle differences in ECF ability compared to controls. The findings suggest that normal versus abnormal behavioral outcome for children with conduct problems may be influenced by cognitive ability profile, perhaps because of varying maturational processes.

Performance evaluation of an automated single-channel sleep-wake detection algorithm.

BACKGROUND: A need exists, from both a clinical and a research standpoint, for objective sleep measurement systems that are both easy to use and can accurately assess sleep and wake. This study evaluates the output of an automated sleep-wake detection algorithm (Z-ALG) used in the Zmachine (a portable, single-channel, electroencephalographic [EEG] acquisition and analysis system) against laboratory polysomnography (PSG) using a consensus of expert visual scorers. METHODS: Overnight laboratory PSG studies from 99 subjects (52 females/47 males, 18-60 years, median age 32.7 years), including both normal sleepers and those with a variety of sleep disorders, were assessed. PSG data obtained from the differential mastoids (A1-A2) were assessed by Z-ALG, which determines sleep versus wake every 30 seconds using low-frequency, intermediate-frequency, and high-frequency and time domain EEG features. PSG data were independently scored by two to four certified PSG technologists, using standard Rechtschaffen and Kales guidelines, and these score files were combined on an epoch-by-epoch basis, using a majority voting rule, to generate a single score file per subject to compare against the Z-ALG output. Both epoch-by-epoch and standard sleep indices (eg, total sleep time, sleep efficiency, latency to persistent sleep, and wake after sleep onset) were compared between the Z-ALG output and the technologist consensus score files. RESULTS: Overall, the sensitivity and specificity for detecting sleep using the Z-ALG as compared to the technologist consensus are 95.5% and 92.5%, respectively, across all subjects, and the positive predictive value and the negative predictive value for detecting sleep are 98.0% and 84.2%, respectively. Overall κ agreement is 0.85 (approaching the level of agreement observed among sleep technologists). These results persist when the sleep disorder subgroups are analyzed separately. CONCLUSION: This study demonstrates that the Z-ALG automated sleep-wake detection algorithm, using the single A1-A2 EEG channel, has a level of accuracy that is similar to PSG technologists in the scoring of sleep and wake, thereby making it suitable for a variety of in-home monitoring applications, such as in conjunction with the Zmachine system.

Normovolemic hemodilution using hydroxyethyl starch 130/0.4 (Voluven) in a Jehovah's Witness child requiring cardiopulmonary bypass for ventricular septal defect repair.

Surgical repair of congenital heart disease during cardiopulmonary bypass is common, and performing these complicated procedures in the absence of blood transfusions is especially challenging. A case of a Jehovah's Witness child who underwent surgical repair of a ventricular septal defect utilizing a new tetrastarch for autologous normovolemic hemodilution is reported. A successful operative repair was achieved without the need for non-autologous blood transfusion.

We can predict when driving is no longer safe for people who have HD using standard neuropsychological measures.

BACKGROUND: Early cognitive dysfunction in Huntington's Disease (HD) is typically of a subcortical frontal executive type, with bradyphrenia, poor spatial and working memory, poor planning and organization, a lack of judgment, and poor mental flexibility. Although there is literature suggesting a correlation between deficits in speed of processing, working memory and executive function on driving competency, there is little direct evidence comparing these declines on tests to actual driving skills. OBJECTIVE: The current study examines the utility of specific neuropsychological measures in predicting actual driving competency in patients with HD. METHODS: Fifty-two patients at the UConn Health HD Program underwent yearly neuropsychological evaluations and were included in this study. Four scales were chosen a priori to predict driving impairment because of their reported relationship to driving ability. Within each test category, subjects who scored below the threshold suggestive of neurological impairment were found to have results within the impaired range (1.5 standard deviations below corrective normative data). A referral to the Connecticut Department of Motor Vehicles (DMV) for a driving evaluation was subsequently made on patients who were found impaired on any two of these tests. RESULTS: The authors found a strong relationship between scores on a simple battery of four neuropsychological tests and driving competency. CONCLUSIONS: This short battery may prove of pragmatic value for clinicians working with people with HD and their families.