Nathaniel D. Mercaldo

The Alzheimer's Disease Centers' Uniform Data Set (UDS): the neuropsychologic test battery.

The neuropsychologic test battery from the Uniform Data Set (UDS) of the Alzheimers Disease Centers (ADC) program of the National Institute on Aging consists of brief measures of attention, processing speed, executive function, episodic memory, and language. This paper describes development of the battery and preliminary data from the initial UDS evaluation of 3268 clinically cognitively normal men and women collected over the first 24 months of utilization. The subjects represent a sample of community-dwelling, individuals who volunteer for studies of cognitive aging. Subjects were considered “clinically cognitively normal” based on clinical assessment, including the Clinical Dementia Rating scale and the Functional Assessment Questionnaire. The results demonstrate performance on tests sensitive to cognitive aging and to the early stages of Alzheimer disease in a relatively well-educated sample. Regression models investigating the impact of age, education, and sex on test scores indicate that these variables will need to be incorporated in subsequent normative studies. Future plans include: (1) determining the psychometric properties of the battery; (2) establishing normative data, including norms for different ethnic minority groups; and (3) conducting longitudinal studies on cognitively normal subjects, individuals with mild cognitive impairment, and individuals with Alzheimer disease and other forms of dementia.

Development of methodology for conducting clinical trials in frontotemporal lobar degeneration

To design clinical trials for the frontotemporal lobar degenerations (FTLD), knowledge about measurement of disease progression is needed to estimate power and enable the choice of optimal outcome measures. The aim here was to conduct a multicentre, 1 year replica of a clinical trial in patients with one of four FTLD syndromes, behavioural variant frontotemporal dementia (bvFTD), progressive nonfluent aphasia (PNFA), progressive logopenic aphasia (PLA) and semantic dementia (SMD). Patients with one of the four FTLD syndromes were recruited from five academic medical centres over a 2 year period. Standard operationalized diagnostic criteria were used. In addition to clinical inclusion and exclusion criteria, patients were required to exhibit focal frontal, temporal or insular brain atrophy or dysfunction by neuroimaging. Patients underwent neuropsychological, functional, behavioural, neurological and MR imaging assessment at baseline and approximately 12 months later. Potential outcome measures were examined for their rates of floor and ceiling values at baseline and end of study, their mean changes and variances. The neuropsychological tests were combined into two cognitive composites -- one for language functions and the other for executive functions. There were 107 patients who underwent baseline assessment and 78 who completed a follow-up assessment within 10-16 months. Two global measures, the FTLD-modified Clinical Dementia Rating (FTLD-modified CDR) and the Clinical Global Impression of Change (CGIC) demonstrated decline in the majority of patients. Several cognitive measures showed negligible floor or ceiling scores either at baseline or follow-up. Scores declined at follow-up in the majority of patients. The cognitive, executive and combined composites were shown to be sensitive to change across all FTLD syndromes. Patients improved at follow-up on the behavioural scales -- the Frontal Behavioural Inventory (22%) and the Neuropsychiatric Inventory (28%) -- suggesting that these instruments may not be ideal for clinical trial use. It was feasible to recruit FTLD patients in a simulated multi-centre trial. There are several candidate outcome measures -- including the FTLD-CDR and the cognitive composites -- that could be used in clinical trials across the spectrum of FTLD.

Polypharmacy and potentially inappropriate medication use among community-dwelling elders with dementia.

This cross-sectional study examines the association between total prescription medication use and potentially inappropriate medication use (PIRx) among community-dwelling elderly patients with and without dementia. Data (September 2005 to September 2007) were from the National Institute on Aging-funded National Alzheimers Coordinating Center Uniform Data Set. The study analyzed the Uniform Data Set initial visits of 4518 community-dwelling subjects aged 65 years and above with and without dementia (2665 and 1853, respectively). PIRx was defined using a partial list of the 2003 Beers criteria. Generalized linear mixed models were applied to estimate the association between PIRx and polypharmacy. In both groups (with and without dementia), subjects who received PIRx on average took more medications than those taking no PIRx. As the total number of medications used increased, the odds of having PIRx also increased, controlling for dementia diagnosis and other subject characteristics. Our key findings were consistent after considering 2 definitions of PIRx (with or without oral estrogens) and accounting for missing data. In summary, the total number of medications used is associated with PIRx among Alzheimers Disease Centers community-dwelling elderly patients with and without dementia, with polypharmacy increasing the risk of PIRx. Ensuring appropriate medication use in this population is clinically important because of the significant risks for institutionalization.

Risk of Burnout in Perioperative Clinicians A Survey Study and Literature Review

Background: Burnout can lead to health and psychologic problems and is apparently increasing in physicians and nurses. Previous studies have not evaluated all healthcare workers within a single work unit. This study evaluates the risk of burnout in all medical personnel in one perioperative unit. Methods: We developed an online survey that included demographics, a modified version of the Maslach Burnout Inventory–Human Services Survey, and the Social Support and Personal Coping Survey. Survey constructs (e.g., depersonalization and health) and a global score were calculated. Larger construct and global values were associated with higher risk of burnout. These were separately regressed on role, age, and sex. The global score was then regressed on each of the survey constructs. Results: Of the 145 responses, 46.2% were physicians (22.8% residents), 43.4% were nurses or nurse anesthetists, and 10.3% were other personnel. After adjusting for sex and age, residents scored higher than other physicians on the following (expected change [95% confidence interval]): global score (1.12 [0.43–1.82]), emotional exhaustion (1.54 [0.44–2.60]), and depersonalization (1.09 [0.23–1.95]). Compared with nonphysicians, residents were 1 U or more higher on these items (P < 0.05 in all cases). Residents had higher health (1.49 [0.48–2.50]) and workload (1.23 [0.07–2.40]) values compared with physicians. Better health, personal support, and work satisfaction scores were related to decreased global scores (P < 0.05). Conclusions: Physicians (particularly residents) had the largest global burnout scores, implying increased risk of burnout. Improving overall health, increasing personal support, and improving work satisfaction may decrease burnout among perioperative team members.

Obesity and Oxidative Stress Predict AKI after Cardiac Surgery

Obesity increases oxidative stress, endothelial dysfunction, and inflammation, but the effect of obesity on postoperative AKI is not known. We examined the relationship between body mass index (BMI) and AKI in 445 patients undergoing cardiac surgery and whether oxidative stress (F(2)-isoprostanes), inflammation (IL-6), or antifibrinolysis (plasminogen activator inhibitor-1 [PAI-1]) contribute to any identified relationship. Overall, 112 (25%) of the 445 patients developed AKI. Higher BMI was independently associated with increased odds of AKI (26.5% increase per 5 kg/m(2) [95% confidence interval, 4.3%-53.4%]; P=0.02). Baseline F(2)-isoprostane (P=0.04), intraoperative F(2)-isoprostane (P=0.003), and intraoperative PAI-1 (P=0.04) concentrations also independently predicted AKI. BMI no longer predicted AKI after adjustment for the effect of F(2)-isoprostanes, suggesting that obesity may affect AKI via effects on oxidative stress. In contrast, adjustment for IL-6 or PAI-1 did not substantially alter the association between BMI and AKI. Further, deconstruction of the obesity-AKI relationship into direct (i.e., independent of candidate pathways) and indirect (i.e., effect of BMI on AKI via each candidate pathway) effects indicated that F(2)-isoprostanes, but not IL-6 or PAI-1, partially mediate the relationship between obesity and AKI (P=0.001). In conclusion, obesity independently predicts AKI after cardiac surgery, and oxidative stress may partially mediate this association.

Brain and ventricular volumetric changes in frontotemporal lobar degeneration over 1 year

Background: Measurement of volumetric changes with MR might be a useful surrogate endpoint for clinical trials in frontotemporal lobar degeneration (FTLD). Because there is only limited longitudinal imaging data currently available, we measured the rate of change over 1 year of whole brain volume (WBV) and ventricular volume (VV) in patients with FTLD. Methods: Subjects with an FTLD cognitive syndrome were recruited from five centers using standard clinical diagnostic criteria for behavioral variant frontotemporal dementia (bvFTD), progressive nonfluent aphasia (PNFA), semantic dementia (SMD), and progressive logopenic aphasia. Structural brain imaging, using three-dimensional T1-weighted sequences at 1.5 teslas, and cognitive, behavioral, and functional assessments were performed at baseline and approximately 1 year later. The boundary shift integral algorithm was used to determine change in WBV and VV. Results: There were 76 patients (mean age 64 years; 41 men and 35 women) who had usable baseline and annual scans. The group-wise annualized change was −1.62% (SD 1.03, range +0.69 to −3.6) for WBV and 11.6% (SD 5.9, range −1.3 to 23.9) for VV. Rates of change were similar among bvFTD, PNFA, and SMD groups. Longitudinal changes in WBV and VV were correlated with decline on clinical global and cognitive measures. Conclusions: Multicenter, serial measurements of whole brain volume (WBV) and ventricular volume (VV) from magnetic resonance scans were feasible in patients with frontotemporal lobar degeneration (FTLD). Using WBV or VV as outcome measures would require recruiting (at 80% power) 139 or 55 subjects per group to detect a small (25%) or medium-sized (40%) effect in a randomized, placebo-controlled trial of a putative agent for FTLD.

Intraoperative risk factors for acute respiratory distress syndrome in critically ill patients.

BACKGROUND: Risk factors for the development of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) include positive fluid balance, high tidal volumes (TVs), high airway pressures, and transfusion of blood products. However, research examining intraoperative factors such as fluid resuscitation, mechanical ventilation strategies, and blood administration on the postoperative development of ARDS is lacking. METHODS: We assessed patients admitted to the ICU with postoperative hypoxemic respiratory failure requiring mechanical ventilation for the development of ARDS in the first 7 postoperative days using established clinical and radiological criteria. Data on risk factors for ARDS were obtained from the electronic anesthetic and medical records. Logistic regression was used to examine the independent association between fluid resuscitation, TV per ideal body weight, and number of blood products transfused during surgery and the postoperative development of ARDS, adjusting for important clinical covariates. RESULTS: Of the 89 patients with postoperative respiratory failure, 25 developed ARDS. Compared with those who received <10 mL/kg/h fluid resuscitation in the operating room, patients receiving >20 mL/kg/h fluid resuscitation had a 3.8 times higher adjusted odds of developing ARDS (P = 0.04), and those receiving 10 to 20 mL/kg/h had a 2.4 times higher adjusted odds of developing ARDS (P = 0.14). TV per ideal body weight and the number of blood units transfused were not associated with ARDS development in this study. CONCLUSIONS: This cohort study provides evidence to suggest a relationship between intraoperative fluid resuscitation and the development of ARDS. Larger prospective trials are required to confirm these findings.

The management of accidental dural puncture and postdural puncture headache: a North American survey ☆

STUDY OBJECTIVE To evaluate the management of accidental dural puncture (ADP) and postdural puncture headache (PDPH) among obstetric anesthesiologists practicing in North America. DESIGN Questionnaire survey of individual members of the Society for Obstetric Anesthesia and Perinatology (SOAP). SETTING University hospital. MEASUREMENTS In June 2008, a 4-part, 83-item electronic survey was distributed to all North American members of SOAP. It contained questions about respondent demographics, epidural catheter and intrathecal catheter management after ADP, PDPH management, epidural blood patch (EBP) management, and patient follow-up. MAIN RESULTS Of the 843 United States and Canadian members of SOAP who were surveyed, 160 responses were collected. Respondents reported placing an epidural 75% of the time and an intrathecal catheter 25% of the time following ADP. Common prophylactic and conservative treatment strategies included hydration, caffeine, and opioids by mouth; 76% of respondents leave an intrathecal catheter in place for 24 hours to reduce the frequency of headache. Epidural blood patches are placed by 81% of practitioners less than 24 hours after headache onset. CONCLUSIONS Protocols for ADP management are rare. There is wide variation in catheter management after dural puncture, measures used to prevent and treat a resultant headache, and EBP management.

Sleep Disturbance in Dementia with Lewy Bodies and Alzheimer’s Disease: A Multicenter Analysis

Background/Aims: Evidence suggests that patients with dementia with Lewy bodies (DLB) may have more nocturnal sleep disturbance than patients with Alzheimer’s disease (AD). We sought to confirm such observations using a large, prospectively collected, standardized, multicenter-derived database, i.e. the National Alzheimer’s Coordinating Center Uniform Data Set. Methods: Nocturnal sleep disturbance (NSD) data, as characterized by the Neuropsychiatric Inventory Questionnaire (NPI-Q), were derived from 4,531 patients collected between September 2005 and November 2008 from 32 National Institute on Aging participating AD centers. Patient and informant characteristics were compared between those with and without NSD by dementia diagnosis (DLB and probable AD). Finally, a logistic regression model was created to quantify the association between NSD status and diagnosis while adjusting for these patient/informant characteristics, as well as center. Results: NSD was more frequent in clinically diagnosed DLB relative to clinically diagnosed AD (odds ratio = 2.93, 95% confidence interval = 2.22–3.86). These results were independent from the gender of the patient or informant, whether the informant lived with the patient, and other patient characteristics, such as dementia severity, depressive symptoms, and NPI-Q-derived measures of hallucinations, delusions, agitation and apathy. In AD, but not DLB, patients, NSD was associated with more advanced disease. Comorbidity of NSD with hallucinations, agitation and apathy was higher in DLB than in AD. There was also evidence that the percentage of DLB cases with NSD showed wide variation across centers. Conclusion: As defined by the NPI-Q, endorsement of the nocturnal behavior item by informants is more likely in patients with DLB when compared to AD, even after the adjustment of key patient/informant characteristics.

Modified Rapid Sequence Induction and Intubation: A Survey of United States Current Practice

BACKGROUND: Rapid sequence induction and intubation (RSII) is a technique commonly used to resist regurgitation of gastric contents and protect the airway. A modification of this technique is implemented in certain clinical circumstances. However, there is currently no standard definition for a modified RSII. Therefore, we surveyed clinicians at academic centers across the United States to establish a working definition of a modified RSII as well as the clinical scenarios in which it is being used. METHODS: A survey was created that queried the use and definition of modified RSII, and validated with test respondents. We then mailed the survey to all 131 anesthesia residency training programs across the United States. Logistic regression models were created to estimate the percentage of affirmative responses among respondents that performed modified RSII procedures and answered survey items in a consistent manner. Similar quantities were calculated by physician status (resident and attending). RESULTS: Four hundred ninety surveys were received from 58 institutions (44% institution response rate); 93% of respondents reported using a modified RSII, and of those 85% consistently completed the survey instrument. A majority of respondents (71%, CI: 63%–77%) reported administering oxygen before anesthesia induction, applying cricoid pressure, and attempting to ventilate the lungs via a facemask before securing the airway. Respondents noted that they would use a modified RSII procedure if the patient were either moderately or morbidly obese (each ∼59%, 53%–64%), had a history but no current symptoms of gastroesophageal reflux disease (52%, 46%–57%), had a hiatal hernia (42%, 36%–48%) or were a trauma patient who had been NPO for at least 8 h (39%, 33%–45%). Similar RSII results were obtained when repeating the analysis on the subset that did not enforce the consistency requirements. CONCLUSIONS: Based on our survey we have established three defining features of a modified RSII: (1) oxygen administration before induction; (2) the use of cricoid pressure; and (3) an attempt to ventilate the patients lungs before securing the airway. Although this definition seems intuitively obvious, no previous work has tested whether it is commonly accepted.