Sir: Clinicians are often reluctant to use psychomotor stimulants in patients with disinhibition from frontal lobe dysfunction because of the concern that these medications will worsen behaviors or result in psychosis. 1 We contrasted the effects of dex-troamphetamine and quetiapine, an atypical antipsychotic often used to treat agitation in dementia patients with cognitive and behavioral symptoms, in 8 patients with behavioral-variant frontotemporal dementia (FTD) in a double-blind crossover trial. We were interested in testing a stimulant for several reasons: (1) there is autopsy, cerebrospinal fluid, and imaging evidence of dopaminergic deficiencies in FTD (reviewed in Huey et al. 2); (2) there is a clinical association between FTD and basal ganglia dopaminergic dysfunction (i.e., parkinsonism) 3 ; and (3) executive dysfunction associated with psychiatric illness (e.g., attention-deficit/hyperactivity disorder) can improve with do-pamine augmentation. 4 Method. All 8 patients had behavioral symptoms. Over 1 week, medication daily dosage was gradually increased to either 20 mg of dextroamphetamine or 150 mg of quetiapine in divided doses. The patients returned home on the target dose for 3 weeks before returning to our clinic for reevaluation. At this point, the patients were tapered to half the study medication for 2 days before discontinuation and then underwent washout for 1 week, and the process was then repeated with the other medication. Medication order was randomized, and the patients, care-givers, and clinicians were blinded to the order. The individuals assigned durable power of attorney by the patients provided written consent, and all patients gave assent. The study was approved by an institutional review board and was conducted from November 2004 to August 2006. The primary measure of behavioral symptoms was the Neuropsychiat-ric Inventory (NPI), 5 and the primary cognitive measure was the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). 6 Results. All patients were able to tolerate the full dose of dextroamphetamine. One patient experienced sedation on que-tiapine treatment and was unable to tolerate the full dose. The most common adverse effect of both medications was sleep disturbance. The results for the total NPI can be seen in Figure 1. Using nonparametric methods (a 2-tailed Friedman test), there was a significant effect of treatment on the total NPI (p = .05). Post hoc Wilcoxon signed-rank tests showed that the total NPI was significantly lower than pretreatment baseline on dextro-amphetamine (p = .02), but there was no significant difference between baseline and quetiapine, nor between quetiapine and dextroamphetamine. The NPI subscales that decreased the most on dextroamphetamine were apathy (2.8 points) and disinhibi-tion (2.4 points). There was no significant overall effect of treatment on the RBANS. The order of magnitude of this effect is large compared to that observed in pharmacologic trials for behavioral symptoms of Alzheimer's disease. A summary of ava...

BACKGROUND Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear. METHODS In this study, we randomly assigned patients within 8 hours after the onset of large-vessel, anterior-circulation strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain. Randomization was stratified according to whether the patient had a favorable penumbral pattern (substantial salvageable tissue and small infarct core) or a non-penumbral pattern (large core or small or absent penumbra). We assessed outcomes using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead). RESULTS Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate differed across groups. Among all patients, mean scores on the modified Rankin scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P = 0.99). Embolectomy was not superior to standard care in patients with either a favorable penumbral pattern (mean score, 3.9 vs. 3.4; P = 0.23) or a nonpenumbral pattern (mean score, 4.0 vs. 4.4; P = 0.32). In the primary analysis of scores on the 90-day modified Rankin scale, there was no interaction between the pretreatment imaging pattern and treatment assignment (P = 0.14). CONCLUSIONS A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care. (Funded by the National Institute of Neurological Disorders and Stroke; MR RESCUE ClinicalTrials.gov number, NCT00389467.)

We investigated the range of behavioral abnormalities in patients with Alzheimer's disease (AD) compared with normal age-matched control subjects. The range of behavioral disturbances manifested and the relationship between specific abnormalities with the level of cognitive impairment have not been established. Fifty consecutive outpatients with mild (n = 17), moderate (n = 20), and severe (n = 13) AD and 40 age-matched normal controls were evaluated for behavioral abnormalities occurring in the month preceding the interview. The caregivers of the patients and the spouses of the control subjects were interviewed with the Neuropsychiatric Inventory (NPI). The frequency and severity of the following 10 behaviors were assessed: delusions, hallucinations, agitation, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, and aberrant motor behavior. Correlations among these 10 behaviors and their relationship with cognitive impairment were also investigated. Eighty-eight percent of AD patients had measurable behavioral changes. All 10 behaviors were significantly increased in the AD patients compared with normal subjects. The most common behavior was apathy, which was exhibited by 72% of patients, followed by agitation (60%), anxiety (48%), irritability (42%), dysphoria and aberrant motor behavior (both 38%), disinhibition (36%), delusions (22%), and hallucinations (10%). Agitation, dysphoria, apathy, and aberrant motor behavior were significantly correlated wit cognitive impairment.

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We describe the first species-specific detection of bacterial pathogens in human clinical fluid samples using a microfabricated electrochemical sensor array. Each of the 16 sensors in the array consisted of three single-layer gold electrodes-working, reference, and auxiliary. Each of the working electrodes contained one representative from a library of capture probes, each specific for a clinically relevant bacterial urinary pathogen. The library included probes for Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Enterocococcus spp., and the Klebsiella-Enterobacter group. A bacterial 16S rRNA target derived from single-step bacterial lysis was hybridized both to the biotin-modified capture probe on the sensor surface and to a second, fluorescein-modified detector probe. Detection of the target-probe hybrids was achieved through binding of a horseradish peroxidase (HRP)-conjugated anti-fluorescein antibody to the detector probe. Amperometric measurement of the catalyzed HRP reaction was obtained at a fixed potential of ؊200 mV between the working and reference electrodes. Species-specific detection of as few as 2,600 uropathogenic bacteria in culture, inoculated urine, and clinical urine samples was achieved within 45 min from the beginning of sample processing. In a feasibility study of this amperometric detection system using blinded clinical urine specimens, the sensor array had 100% sensitivity for direct detection of gram-negative bacteria without nucleic acid purification or amplification. Identification was demonstrated for 98% of gram-negative bacteria for which species-specific probes were available. When combined with a microfluidics-based sample preparation module, the integrated system could serve as a point-of-care device for rapid diagnosis of urinary tract infections.Urinary tract infection (UTI) is the most common urological disease in the United States and the second most common bacterial infection of any organ system (12, 32). UTI is a major cause of patient morbidity and health care expenditure for all age groups, accounting for over 7 million office visits and more than 1 million hospital admissions per year (39). Catheterassociated UTI accounts for 40% of all nosocomial infections and more than 1 million cases per year (22,41,49). The total cost of UTI to the United States health care system in the year 2000 was approximately $3.5 billion (13,19,20). An important component of these health care costs involves the processing of urine specimens by clinical microbiology laboratories. Urine is the type of body fluid most frequently submitted to clinical microbiology laboratories for culture. A major drawback of microbiological culture systems is the time lag of approximately 2 days between specimen collection and pathogen identification. The primary cause of the delay between specimen collection and pathogen identification is the time to colony formation after the specimen is plated on solid culture media.

IMPORTANCE Electronic cigarettes (e-cigarettes) have gained unprecedented popularity, but virtually nothing is known about their cardiovascular risks. OBJECTIVE To test the hypothesis that an imbalance of cardiac autonomic tone and increased systemic oxidative stress and inflammation are detectable in otherwise healthy humans who habitually use e-cigarettes. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional case-control study of habitual e-cigarette users and nonuser control individuals from 2015 to 2016 at the University of California, Los Angeles. Otherwise healthy habitual e-cigarette users between the ages of 21 and 45 years meeting study criteria, including no current tobacco cigarette smoking and no known health problems or prescription medications, were eligible for enrollment. Healthy volunteers meeting these inclusion criteria who were not e-cigarette users were eligible to be enrolled as control individuals. A total of 42 participants meeting these criteria were enrolled in the study including 23 self-identified habitual e-cigarette users and 19 self-identified non–tobacco cigarette, non–e-cigarette user control participants. MAIN OUTCOMES AND MEASURES Heart rate variability components were analyzed for the high-frequency component (0.15–0.4 Hz), an indicator of vagal activity, the low-frequency component (0.04–0.15 Hz), a mixture of both vagal and sympathetic activity, and the ratio of the low frequency to high frequency, reflecting the cardiac sympathovagal balance. Three parameters of oxidative stress were measured in plasma: (1) low-density lipoprotein oxidizability, (2) high-density lipoprotein antioxidant/anti-inflammatory capacity, and (3) paraoxonase-1 activity. RESULTS Of the 42 participants, 35% were women, 35% were white, and the mean age was 27.6 years. The high-frequency component was significantly decreased in the e-cigarette users compared with nonuser control participants (mean [SEM], 46.5 [3.7] nu vs 57.8 [3.6] nu; P = .04). The low-frequency component (mean [SEM], 52.7 [4.0] nu vs 39.9 [3.8] nu; P = .03) and the low frequency to high frequency ratio (mean [SEM], 1.37 [0.19] vs 0.85 [0.18]; P = .05) were significantly increased in the e-cigarette users compared with nonuser control participants, consistent with sympathetic predominance. Low-density lipoprotein oxidizability, indicative of the susceptibility of apolipoprotein B–containing lipoproteins to oxidation, was significantly increased in e-cigarette users compared with nonuser control individuals (mean [SEM], 3801.0 [415.7] U vs 2413.3 [325.0] U; P = .01) consistent with increased oxidative stress, but differences in high-density antioxidant/anti-inflammatory capacity and paraoxonase-1 activity were not significant. CONCLUSIONS AND RELEVANCE In this study, habitual e-cigarette use was associated with a shift in cardiac autonomic balance toward sympathetic predominance and increased oxidative stress, both associated with increased cardiovascular risk.

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Objective To determine if specific measures of heart rate variability (HRV) are associated with the total score on a seven-item inventory for Sudden Unexplained Death in Epilepsy (SUDEP). Methods Nineteen subjects with intractable partial seizures, at least three per month, were enrolled in a randomized clinical trial of omega-3 fatty acids in epilepsy. At study entry, subjects underwent a 1-hour ECG recording for the determination of HRV. To estimate the risk of SUDEP, we assembled a seven-item inventory (The SUDEP-7 Inventory) from risk factors prospectively validated by Walczak al. [6] The SUDEP-7 score was then correlated with measures of HRV using the Pearson Correlation and other parametric and non-parametric methods. Results Subjects were highly refractory, with a mean seizure frequency of 22.8 seizures per month. Scores on the SUDEP-7 inventory ranged from 1 – 7 of a maximum possible score of 12. RMSSD, a measure of high frequency HRV was inversely correlated with the SUDEP-7 score, r = −0.64, p =0.004. Subjects with higher SUDEP-7 scores had reduced levels of HRV (RMSSD). Other time-dependent measures of HRV (SDNN, SDANN) were not significantly correlated with SUDEP risk scores. Conclusions RMSSD, a measure of HRV, which reflects the integrity of vagus nerve-mediated autonomic control of the heart, is highly associated with the total score on a new 7-item SUDEP risk inventory. Lower RMSSD values were associated with higher risk scores on a new SUDEP risk inventory. This provides new evidence that HRV (specifically RMSSD) is a marker of SUDEP risk.