Impact of Mitral Regurgitation Severity and Cause on Effort Tolerance-Integrated Stress Myocardial Perfusion Imaging and Echocardiographic Assessment of Patients With Known or Suspected Coronary Artery Disease Undergoing Exercise Treadmill Testing.

Background Mitral regurgitation ( MR ) has the potential to impede exercise capacity; it is uncertain whether this is because of regurgitation itself or the underlying cause of valvular insufficiency. Methods and Results The population comprised 3267 patients who underwent exercise treadmill myocardial perfusion imaging and transthoracic echocardiography within 6±8 days. MR was present in 28%, including 176 patients (5%) with moderate or greater MR . Left ventricular systolic function significantly decreased and chamber size increased in relation to MR , paralleling increments in stress and rest myocardial perfusion deficits (all P<0.001). Exercise tolerance (metabolic equivalents of task) decreased stepwise in relation to graded MR severity ( P<0.05). Workload was significantly lower with mild versus no MR (mean±SD, 9.8±3.0 versus 10.1±3.0; P=0.02); magnitude of workload reduction significantly increased among patients with advanced versus those with mild MR (mean±SD, 8.6±3.0 versus 9.8±3.0; P<0.001). MR -associated exercise impairment was accompanied by lower heart rate and blood pressure augmentation and greater dyspnea (all P<0.05). Both functional and nonfunctional MR subgroups demonstrated significantly decreased effort tolerance in relation to MR severity ( P≤0.01); impairment was greater with functional MR ( P=0.04) corresponding to more advanced left ventricular dysfunction and dilation (both P<0.001). Functional MR predicted reduced metabolic equivalent of task-based effort (B=-0.39 [95% CI, -0.62 to -0.17]; P=0.001) independent of MR severity. Among the overall cohort, advanced (moderate or greater) MR was associated with reduced effort tolerance (B=-1.36 [95% CI, -1.80 to -0.93]; P<0.001) and remained significant ( P=0.01) after controlling for age, clinical indexes, stress perfusion defects, and left ventricular dysfunction. Conclusions MR impairs exercise tolerance independent of left ventricular ischemia, dysfunction, and clinical indexes. Magnitude of exercise impairment parallels severity of MR .

Lab-on-a-Film disposable for genotyping multidrug-resistant Mycobacterium tuberculosis from sputum extracts.

We describe a Lab-on-a-Film disposable that detects multidrug-resistant tuberculosis (MDR-TB) from sputum extracts. The Lab-on-a-Film disposable consists of 203 gel elements that include DNA sequences (probes) for 37 mutations, deletions, or insertion elements across 5 genes (including an internal control). These gel elements are printed on a flexible film, which costs approximately 500 times less than microarray glass. The film with printed gel elements is then laminated to additional rollable materials (films) to form a microfluidic flow cell. We combined multiplex amplification and hybridization steps in a single microfluidic chamber, without buffer exchanges or other manipulations up to and throughout hybridization. This flow cell also incorporates post hybridization wash steps while retaining an entirely closed-amplicon system, thus minimizing the potential for sample or amplicon cross-contamination. We report analytical sensitivity of 32 cfu mL-1 across all MDR-TB markers and detection of MDR-TB positive clinical specimens using an automated TruTip workstation for extraction and the Lab-on-a-Film disposable for amplification and detection of the extracts.

Automated TruTip nucleic acid extraction and purification from raw sputum.

Automated nucleic acid extraction from primary (raw) sputum continues to be a significant technical challenge for molecular diagnostics. In this work, we developed a prototype open-architecture, automated nucleic acid workstation that includes a mechanical homogenization and lysis function integrated with heating and TruTip purification; optimized an extraction protocol for raw sputum; and evaluated system performance on primary clinical specimens. Eight samples could be processed within 70 min. The system efficiently homogenized primary sputa and doubled nucleic acid recovery relative to an automated protocol that did not incorporate sample homogenization. Nucleic acid recovery was at least five times higher from raw sputum as compared to that of matched sediments regardless of smear or culture grade, and the automated workstation reproducibly recovered PCR-detectable DNA to at least 80 CFU mL-1 raw sputum. M. tuberculosis DNA was recovered and detected from 122/123 (99.2%) and 124/124 (100%) primary sputum and sediment extracts, respectively. There was no detectable cross-contamination across 53 automated system runs and amplification or fluorescent inhibitors (if present) were not detectable. The open fluidic architecture of the prototype automated workstation yields purified sputum DNA that can be used for any molecular diagnostic test. The ability to transfer TruTip protocols between personalized, on-demand pipetting tools and the fully automated workstation also affords public health agencies an opportunity to standardize sputum nucleic acid sample preparation procedures, reagents, and quality control across multiple levels of the health care system.

A bench-top automated workstation for nucleic acid isolation from clinical sample types.

Systems that automate extraction of nucleic acid from cells or viruses in complex clinical matrices have tremendous value even in the absence of an integrated downstream detector. We describe our bench-top automated workstation that integrates our previously-reported extraction method - TruTip - with our newly-developed mechanical lysis method. This is the first report of this method for homogenizing viscous and heterogeneous samples and lysing difficult-to-disrupt cells using "MagVor": a rotating magnet that rotates a miniature stir disk amidst glass beads confined inside of a disposable tube. Using this system, we demonstrate automated nucleic acid extraction from methicillin-resistant Staphylococcus aureus (MRSA) in nasopharyngeal aspirate (NPA), influenza A in nasopharyngeal swabs (NPS), human genomic DNA from whole blood, and Mycobacterium tuberculosis in NPA. The automated workstation yields nucleic acid with comparable extraction efficiency to manual protocols, which include commercially-available Qiagen spin column kits, across each of these sample types. This work expands the scope of applications beyond previous reports of TruTip to include difficult-to-disrupt cell types and automates the process, including a method for removal of organics, inside a compact bench-top workstation.

Alcohol use and comorbid anxiety, traumatic stress, and hopelessness among Hispanics.

Little is known about the comorbidity of alcohol use, anxiety, hopelessness, and trauma among Mexican Americans, especially those living in impoverished and often isolated communities or neighborhoods (colonias in Spanish) along the U.S.-Mexico border that may be particularly vulnerable due to stressful living conditions. The current study utilized a community participatory model to investigate the relationships of alcohol use, acculturation, anxiety, hopelessness, and trauma in 100 Mexican origin colonia residents. Significant comorbidity was expected and that anxiety, hopelessness, and post-traumatic symptoms were hypothesized to be associated with the severity of the alcohol use disorders of participants. Participants who met DSM-IV criteria for alcohol dependence reported significantly more symptoms of anxiety and post-traumatic stress, and symptoms of anxiety were significantly associated with alcohol use disorders. This study provides evidence of the need for further investigation of stress, trauma, anxiety, hopelessness, and alcohol abuse in Mexican American residents and to inform future prevention and treatment efforts to improve both the physical and mental health of this population.

Response of Native American clients to three treatment methods for alcohol dependence.

OBJECTIVE: It is well-documented that American Indians suffer disproportionately high rates of alcohol use disorders as well as correspondingly high rates of alcohol based mortality, health, and social problems. Despite these health disparities, anecdotal evidence continues to guide alcohol treatment approaches in Indian Country, in part due to a dearth of clinical trials with Native Americans. Project MATCH, a multisite clinical trial, included 25 Native Americans (1.4% of the total sample) who were randomized to three psychosocial treatments. Based on cultural compatibility, our a priori hypothesis was that Native Americans in Motivational Enhancement Therapy (MET) would fare better than those assigned either to Cognitive Behavioral Therapy (CBT) or to Twelve-step Facilitation (TSF). METHOD: Of 25 Native Americans in Project MATCH, 23 (92%) were interviewed at all six assessment points. Four ANOCOVA's were computed to investigate possible differential treatment response. RESULTS: Despite a small sample, Native Americans assigned to MET reported significantly less drinking intensity relative to those assigned to CBT or TSF, with the highest proportion of abstinent days and lowest drinking intensity at both proximal and distal follow-ups. CONCLUSIONS: These findings suggest a differentially better response to MET than to TSF or to CBT among Native Americans with alcohol dependence. Although this is, to date, the largest randomized trial of treatments for alcohol dependence in Native Americans, the findings require replication.

Posttraumatic stress disorder, alcohol, and tribes: obstacles to research.

Based on research and clinical experiences on and off Indian reservations in California, Arizona, and New Mexico, the author shares his perspective on systemic obstacles to psychological research in Indian Country. Using those obstacles as a springboard, he maps the emergent epistemological differences between western and native approaches to gathering knowledge and engendering change. The resulting discussion suggests different ways in which research can be conceptualized with Indian tribes.

Motivation and neuropsychological test performance following mild head injury.

Effect of motivation on neuropsychological test performance in mild head injury was assessed. Motivation was measured using the Portland Digit RecognitionTest. Three groups were compared: (a) mildhead injury, financial incentives, good motivation; (b) mild head injury, financial incentives, poor motivation; (c) moderate/severe head injury, good motivation. The neuropsychological battery included measures of sensory function, motor function, attention, intelligence, abstract reasoning, and memory. Mild head injury well motivated patients performed significantly better than the other two groups on some tests. Mild head injury poorly motivated individuals and moderate-severe head injury patients were indistinguishable on many tests. Consistent with previous reports, tactile sensory (finger recognition and Fingertip Number Writing Perception) and recognition memory (Rey Auditory Verbal Learning) tasks were identified as clinically useful measures of poor motivation. On these measures mild head injury well motivated examinees performed no better than moderate-severe patients, with both groups superior to mild head injury poorly motivated examinees. Sensitivity and specificity data are reported. Our measures of tactile sensation and verbal recognition memory were more affected by motivation than by the severity of head injury.

Pain Assessment for the Dementing Elderly (PADE): reliability and validity of a new measure.

OBJECTIVES: To establish the reliability and validity of a measure to assess pain in individuals with advanced dementia. DESIGN: Sixty-five residents of long-term care facilities were assessed using a new rating tool, the Pain Assessment for the Dementing Elderly (PADE), in two separate studies: (1) Residents were assessed simultaneously by two different raters, at Time 1 and 2, to establish interrater reliability, stability, and internal consistency. (2) Validity was established by assessing the correlation between an agitation scale and the PADE; by comparing groups with pain as a significant clinical factor (as assessed by an independent rater) versus not a significant factor, and by assessing individuals receiving versus not receiving psychoactive medications. SETTING: Four different long-term care facilities, three skilled nursing facilities, and a locked dementia assisted-living facility. PARTICIPANTS: Twenty-five residents of long-term care facilities with advanced levels of dementia in Study 1, and 40 residents with similar level of dementia in Study 2; 42% of the total sample were rated as having significant painful conditions. MEASUREMENTS: For Study 1, the PADE was administered; for Study 2, the PADE and the Cohen-Mansfield Agitation Inventory (CMAI) were administered. RESULTS: Reliability coefficients were adequate (interrater = 0.54-0.95; stability = 0.70-0.98; and internal consistency = 0.24-0.88). Validity coefficients were likewise encouraging, with the PADE demonstrating the expected relationship with a measure of agitation. The PADE also differentiated between groups that were independently judged to suffer clinically problematic pain versus those who were not. CONCLUSION: The PADE is a reliable and valid tool to assess pain in dementing elderly residents of long-term care facilities.