Evaluation of a Rapid Molecular Drug-Susceptibility Test for Tuberculosis.

BACKGROUND: Fluoroquinolones and second-line injectable drugs are the backbone of treatment regimens for multidrug-resistant tuberculosis, and resistance to these drugs defines extensively drug-resistant tuberculosis. We assessed the accuracy of an automated, cartridge-based molecular assay for the detection, directly from sputum specimens, of Mycobacterium tuberculosis with resistance to fluoroquinolones, aminoglycosides, and isoniazid. METHODS: We conducted a prospective diagnostic accuracy study to compare the investigational assay against phenotypic drug-susceptibility testing and DNA sequencing among adults in China and South Korea who had symptoms of tuberculosis. The Xpert MTB/RIF assay and sputum culture were performed. M. tuberculosis isolates underwent phenotypic drug-susceptibility testing and DNA sequencing of the genes katG, gyrA, gyrB, and rrs and of the eis and inhA promoter regions. RESULTS: Among the 308 participants who were culture-positive for M. tuberculosis, when phenotypic drug-susceptibility testing was used as the reference standard, the sensitivities of the investigational assay for detecting resistance were 83.3% for isoniazid (95% confidence interval [CI], 77.1 to 88.5), 88.4% for ofloxacin (95% CI, 80.2 to 94.1), 87.6% for moxifloxacin at a critical concentration of 0.5 µg per milliliter (95% CI, 79.0 to 93.7), 96.2% for moxifloxacin at a critical concentration of 2.0 µg per milliliter (95% CI, 87.0 to 99.5), 71.4% for kanamycin (95% CI, 56.7 to 83.4), and 70.7% for amikacin (95% CI, 54.5 to 83.9). The specificity of the assay for the detection of phenotypic resistance was 94.3% or greater for all drugs except moxifloxacin at a critical concentration of 2.0 µg per milliliter (specificity, 84.0% [95% CI, 78.9 to 88.3]). When DNA sequencing was used as the reference standard, the sensitivities of the investigational assay for detecting mutations associated with resistance were 98.1% for isoniazid (95% CI, 94.4 to 99.6), 95.8% for fluoroquinolones (95% CI, 89.6 to 98.8), 92.7% for kanamycin (95% CI, 80.1 to 98.5), and 96.8% for amikacin (95% CI, 83.3 to 99.9), and the specificity for all drugs was 99.6% (95% CI, 97.9 to 100) or greater. CONCLUSIONS: This investigational assay accurately detected M. tuberculosis mutations associated with resistance to isoniazid, fluoroquinolones, and aminoglycosides and holds promise as a rapid point-of-care test to guide therapeutic decisions for patients with tuberculosis. (Funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Ministry of Science and Technology of China; ClinicalTrials.gov number, NCT02251327 .).

Novel probe-based confocal laser endomicroscopy criteria and interobserver agreement for the detection of dysplasia in Barrett's esophagus.

OBJECTIVES: Probe-based confocal laser endomicroscopy (pCLE) is an imaging technique that allows real-time in vivo histological assessment of Barrett's esophagus (BE). The objectives of this study were to create and test novel pCLE criteria for dysplastic BE (phase I), and to evaluate accuracy, interobserver variability, and learning curve in dysplasia prediction (phase II) using these criteria. METHODS: In phase I, using 50 pCLE videos, a pCLE expert and gastrointestinal pathologist formulated new BE criteria by consensus. These criteria were tested and refined in an independent set of 30 pCLE videos. In phase II, a formal training session for all assessors (three each experts/trainees) was conducted. Finally, using 75 testing videos, each video was interpreted as dysplasia (high-grade dysplasia (HGD)/cancer) vs. no dysplasia and the assessors' confidence in interpretation was noted. Interobserver agreement and accuracy (95% confidence interval (CI)) were determined for BE histology prediction. RESULTS: Of multiple pCLE criteria tested (phase I), only those with ≥70% sensitivity or specificity were included in the final set: epithelial surface: saw-toothed; cells: enlarged; cells: pleomorphic; glands: not equidistant; glands: unequal in size and shape; goblet cells: not easily identified. Overall accuracy in diagnosing dysplasia was 81.5% (95% CI: 77.5-81), with no difference between experts vs. non-experts. Accuracy of prediction was significantly higher when endoscopists were "confident" about their diagnosis (98% (95-99) vs. 62% (54-70), P<0.001). Accuracy of dysplasia prediction for the first 30 videos was not different from the last 45 (93 vs. 81%, P=0.51). Overall agreement of the criteria was substantial, κ=0.61 (0.53-0.69), with no difference between experts and non-experts. CONCLUSIONS: We demonstrate the development and validation of new pCLE criteria for the prediction of HGD/cancer in BE patients. Using these criteria, this study demonstrated that overall accuracy in predicting dysplasia was high with substantial interobserver agreement. After a structured teaching session, accuracy and agreement between experienced and non-experienced observers was not different, suggesting a short learning curve.

Colorectal cancer screening, perceived discrimination, and low-income and trust in doctors: a survey of minority patients.

BACKGROUND: Completion of colorectal cancer (CRC) screening testing is lower among low-income and minority groups than the population as a whole. Given the multiple cancer screening health disparities known to exist within the U.S., this study investigated the relationship between perceived discrimination, trust in most doctors, and completion of Fecal Occult Blood Testing (FOBT) among a low-income, minority primary care population in an urban setting. METHODS: We recruited a convenience sample of adults over age 40 (n = 282) from a federally qualified community health center (70% African American). Participants completed a survey which included measures of trust in most doctors, perceived discrimination, demographics and report of cancer screening. RESULTS: Participants reported high levels of trust in most doctors, regardless of sex, race, education or income. High trust was associated with low perceived discrimination (p < 0.01). The trend was for older participants to express more trust (p = 0.09) and less perceived discrimination (p < 0.01). Neither trust nor discrimination was associated with race or education. Trust was higher among participants over 50 who were up-to-date on FOBT screening vs. those who were not (31 vs. 29 (median), p < 0.05 by T-test). Among those over 50, up-to-date FOBT screening was nearly associated with high trust (p < 0.06; 95% CI 0.99, 1.28) and low perceived discrimination (p < 0.01; 95% CI 0.76, 0.96). Nevertheless, in multivariate-modeling, age and income explained FOBT completion better than race, trust and discrimination. CONCLUSION: Perceived discrimination was related to income, but not race, suggesting that discrimination is not unique to minorities, but common to those in poverty. Since trust in most doctors trended toward being related to age, FOBT screening could be negatively influenced by low trust and perceived discrimination in health care settings. A failure to address these issues in middle-aged, low income individuals could exacerbate future disparities in CRC screening.

Discussing weight with obese primary care patients: physician and patient perceptions.

OBJECTIVE: To evaluate patient-provider agreement on whether weight and related behaviors were discussed during routine visits. DESIGN: Post-visit survey assessments of patients and providers. PARTICIPANTS: Obese patients make up the majority of all patients seen in primary care (PC). The patients and physicians were recruited at the time of PC visits. MEASUREMENTS AND MAIN RESULTS: Percent patient-physician agreement and patient, provider and practice characteristics associated with agreement. Patients (456) and physicians (30) agreed about whether or not they discussed weight, physical activity (PA), and diet for 61% of office visits. There was disagreement on one of the items (weight, PA, or diet) for 23% of office visits, and for 2 or more of the items for 16% of the visits. Agreement was relatively greater for discussing weight than for discussing diet or physical activity. Physicians reported discussing weight issues more often than did patients. Overall patient-physician agreement was 0.51-0.59 (weighted Kappa statistic). In a multivariate analyses of factors associated with patient-physician agreement, health insurance (odds ratio [OR]=3.67, p value = 0.002), physician description of patient weight status (OR = 2.27, p value = 0.002), patient report of how weight relates to health (OR = 1.70, p value = 0.04), and female patient gender (OR = 1.62, p = value = 0.02) were significantly related to agreement. CONCLUSIONS: Patients and providers disagreed about whether or not weight issues were discussed in a large number of primary care encounters in this study. Physicians may be able to improve care for their obese patients by focusing discussions on specific details of diet and physical activity behaviors, and by clarifying that patients perceive weight-related information has been shared.

Does pharmacist-led medication review help to reduce hospital admissions and deaths in older people? A systematic review and meta-analysis.

We set out to determine the effects of pharmacist-led medication review in older people by means of a systematic review and meta-analysis covering 11 electronic databases. Randomized controlled trials in any setting, concerning older people (mean age > 60 years), were considered, aimed at optimizing drug regimens and improving patient outcomes. Our primary outcome was emergency hospital admission (all cause). Secondary outcomes were mortality and numbers of drugs prescribed. We also recorded data on drug knowledge, adherence and adverse drug reactions. We retrieved 32 studies which fitted the inclusion criteria. Meta-analysis of 17 trials revealed no significant effect on all-cause admission, relative risk (RR) of 0.99 [95% confidence interval (CI) 0.87, 1.14, P = 0.92], with moderate heterogeneity (I(2) = 49.5, P = 0.01). Meta-analysis of mortality data from 22 trials found no significant benefit, with a RR of mortality of 0.96 (95% CI 0.82, 1.13, P = 0.62), with no heterogeneity (I(2) = 0%). Pharmacist-led medication review may slightly decrease numbers of drugs prescribed (weighted mean difference = -0.48, 95% CI -0.89, -0.07), but significant heterogeneity was found (I(2) = 85.9%, P < 0.001). Results for additional outcomes could not be pooled, but suggested that interventions could improve knowledge and adherence. Pharmacist-led medication review interventions do not have any effect on reducing mortality or hospital admission in older people, and can not be assumed to provide substantial clinical benefit. Such interventions may improve drug knowledge and adherence, but there are insufficient data to know whether quality of life is improved.

The impact of socioeconomic status on perceived barriers to colorectal cancer testing.

PURPOSE: Colorectal cancer (CRC) screening is effective, but only one-half of age-eligible adults adhere to national guidelines. Lower socioeconomic status (SES) groups are less likely to be screened. METHODS: Baseline data from a prospective study were, used to examine the associations among CRC screening screening barriers, and SES. A convenience sample of adults (N = 291) aged 40 years and older was recruited from a federally qualified health center. Questionnaires were administered orally and included demographics, health, health behavior, and screening barriers. RESULTS: In logistic regression, having health insurance was associated with greater odds of screening Bivariate analyses detected few differences in fecal occult blood test (FOBT) barriers, but several endoscopy barriers were more common among the lowest SES groups. For example, fear of injury from endoscopy was more likely among low-income and uninsured participants. DISCUSSION: The impact of SES on cancer screening is complex, but low-SES participants more often reported certain barriers than their higher-SES counterparts. This was more evident for endoscopy than for FOBT. Programs targeted at low-SES patients may need to focus on barriers that are not fully addressed in traditional promotion efforts.

Comparison of body perceptions between obese primary care patients and physicians: implications for practice.

OBJECTIVE: To compare the body image and weight perceptions of primary care patients and their physicians as a first step toward identifying a potential tool to aid physician-patient communication. METHODS: Patients with a body mass index (BMI)> or =30 (n=456, 66% female) completed body image and weight status measures after office visits; physicians (n=29) rated the body figures and weight status of these same patients after office visits. RESULTS: Controlling for BMI, female patients and their physicians showed little or no difference in body figure selection or weight status classification, whereas male patients were significantly less likely than their physicians to self-identify with larger body figures (z=3.74, p<0.01) and to classify themselves as obese or very obese (z=4.83, p<0.0001). CONCLUSION: Findings reveal that physicians and female patients have generally concordant views of the patient's body size and weight status, whereas male patients perceive themselves to be smaller than do their physicians. The discrepancy between male patient and physician views is especially evident at increasingly larger body figure/weight status categories. PRACTICE IMPLICATIONS: When counseling male patients on weight loss, it could be helpful to assess body image and use this information to raise patient awareness of their size and to facilitate communication about weight.

How Using Generative Learning Strategies Improved Medical Student Self-Competency in End-of-Life Care.

During a mandatory fourth-year core geriatric medicine rotation at our medical school, we discovered that our medical students were struggling with end-of-life (EOL) issues both personally and professionally. We implemented curriculum changes to assist them in developing emotional awareness about death and dying, and to help develop their ability to respond personally and professionally to patients and their families during EOL experiences.In our new curriculum, a seasoned ethicist at our university conducts 2 educational sessions addressing EOL issues. Students complete self-study content before the first session, in which they have a discussion about their own experience with death and dying. Our ethicist facilitates these discussions with a small group (10-14 medical students), allowing the students to explore their own experiences, case studies, and others' experiences in EOL. Before the second session, students prepare a self-reflective narrative essay about an EOL experience. Our facilitator, by using a generative learning strategy, has a rich interaction that attempts to connect previous experiences, present training, and how the student physicians may need to adjust behaviors in order to be advocates for their patients in EOL situations in the future. Students complete a pre- and post-self-assessment in the didactic. Results show significant improvement in their perceived competence in EOL issues. In addition, the students' self-reflection essays reveal intriguing themes for future study.

Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study.

BACKGROUND: The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. METHODS: In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. FINDINGS: Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (-2·7%, -3·9 to -1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. INTERPRETATION: For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. FUNDING: Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases.

Comparison of a low carbohydrate and low fat diet for weight maintenance in overweight or obese adults enrolled in a clinical weight management program.

BACKGROUND: Recent evidence suggests that a low carbohydrate (LC) diet may be equally or more effective for short-term weight loss than a traditional low fat (LF) diet; however, less is known about how they compare for weight maintenance. The purpose of this study was to compare body weight (BW) for participants in a clinical weight management program, consuming a LC or LF weight maintenance diet for 6 months following weight loss. METHODS: Fifty-five (29 low carbohydrate diet; 26 low fat diet) overweight/obese middle-aged adults completed a 9 month weight management program that included instruction for behavior, physical activity (PA), and nutrition. For 3 months all participants consumed an identical liquid diet (2177 kJ/day) followed by 1 month of re-feeding with solid foods either low in carbohydrate or low in fat. For the remaining 5 months, participants were prescribed a meal plan low in dietary carbohydrate (~20%) or fat (~30%). BW and carbohydrate or fat grams were collected at each group meeting. Energy and macronutrient intake were assessed at baseline, 3, 6, and 9 months. RESULTS: The LC group increased BW from 89.2 +/- 14.4 kg at 3 months to 89.3 +/- 16.1 kg at 9 months (P = 0.84). The LF group decreased BW from 86.3 +/- 12.0 kg at 3 months to 86.0 +/- 14.0 kg at 9 months (P = 0.96). BW was not different between groups during weight maintenance (P = 0.87). Fifty-five percent (16/29) and 50% (13/26) of participants for the LC and LF groups, respectively, continued to decrease their body weight during weight maintenance. CONCLUSION: Following a 3 month liquid diet, the LC and LF diet groups were equally effective for BW maintenance over 6 months; however, there was significant variation in weight change within each group.

Patterns of smoking and methadone dose in drug treatment patients.

Cigarette smoking prevalence is very high, and cessation rates are very low, among people in methadone treatment. This may in part be due to interactions between methadone administration and cigarette smoking. The present study explores relationships between methadone dose timing and smoking rates. Twenty methadone patients, over a period of 19 days, used electronic cigarette packs to record their smoking patterns and called a voice mailbox daily to report their methadone dose and timing. The average proportion of daily cigarettes smoked was calculated for 2-hr blocks preceding and following methadone dose administration. For all participants, peak smoking rates occurred after methadone administration. Participants smoked a greater proportion of cigarettes in their first 2-hr block after methadone dosing (M = 0.368, SD = 0.135) than during their first 2-hr block of smoking of the day (M = 0.245, SD = 0.010; S = 85.5, p < .0001). The proportion of cigarettes smoked increased by 0.02 from more than 2 hr before methadone to the 2-hr time block before methadone, by 0.04 from the 2-hr time block before methadone to the 2-hr time block after methadone, and by 0.015 from the 2-hr time block after methadone to the next 2-hr time block. From this time block (2-4 hr after methadone), smoking decreased by 0.02 in the 4-plus hr postmethadone dose. All of these changes were statistically significant. Future research should use experimental designs to better examine whether a causal relationship exists and examine the impact of other types of opioid maintenance medications on smoking patterns.

Impact of organizational infrastructure on beta-blocker and aspirin therapy for acute myocardial infarction.

BACKGROUND: Although organizational change has been advocated as a critical component of quality improvement, there is little data available on the variation and effectiveness of organizational elements in the care of acute myocardial infarction (AMI). PURPOSE: This study was designed to examine the impact of organizational infrastructure on the use of aspirin and beta-blockers during and after AMI. METHODS: We assessed organizational infrastructure for AMI care in 44 hospitals in Kansas and linked these data to patient-specific process of care data collected in Kansas as part of the Cooperative Cardiovascular Project. While controlling for clustering within hospitals, we examined the relationships between hospital infrastructure and use of aspirin and beta-blocker both at admission and discharge. RESULTS: Hospitals varied widely in their inclusion of aspirin and beta-blockers in AMI pathways, protocols, and standardized order sets. Hospitals also varied in the involvement of their physicians in AMI quality improvement and in their ability to identify a physician champion for AMI care. Patients were more likely to receive aspirin on admission in hospitals that included aspirin in their emergency department order sets (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.01-2.48) and were more likely to receive beta-blockers on admission and at discharge if beta-blockers were included in an emergency department protocol or pathway (OR 2.14, 95% CI 1.25-3.77 and OR 3.5, 95% CI 1.14-14.38, respectively). Use of beta-blockers at discharge was also associated with commitment of administration to AMI care and the presence of a physician champion. CONCLUSIONS: Quality improvement efforts should include a close examination of the organization of AMI care to assure that critical elements in the care of AMI patients are not inadvertently omitted.

Weight-related perceptions among patients and physicians: how well do physicians judge patients' motivation to lose weight?

BACKGROUND: Prior studies suggest that patients and physicians have different perceptions and expectations surrounding weight; however, few studies have directly compared patients' and physicians' perspectives. OBJECTIVES: (1) To measure the extent to which obese patients and their physicians have discrepant weight-related perceptions, and (2) to explore patient and physician characteristics that may influence patient-physician discrepancy in motivation to lose weight. DESIGN AND PARTICIPANTS: Four hundred and fifty-six obese patients (302 females; mean age = 55.1 years; mean BMI = 37.9) and their 28 primary care physicians (22 males, mean age = 44.1 years) from nonmetropolitan practices completed an anonymous survey after an office visit. MEASURES: Weight-related perceptions included perceived weight status, health impact of weight, 1-year weight loss expectations, and motivation to lose weight. Correlates included patient and physician sex, age, and BMI; physicians' reported frequency, perceived patient preference, and confidence for weight counseling; and practice characteristics (e.g., years in practice). RESULTS: Physicians assigned patients to heavier descriptive weight categories and reported a worse health impact than patients perceived for themselves, whereas patients believed they could lose more weight and reported a higher motivation to lose weight than their physicians perceived for patients (P < .001). Physicians who believed patients preferred to discuss weight more often (P = .001) and who saw more patients per week (P = .04) were less likely to underestimate patient motivation. CONCLUSIONS: Patients reported more optimistic weight-related perceptions and expectations than their physicians. Further research is needed to determine how these patient-physician discrepancies may influence weight loss counseling in primary care.

Concordance of patient-physician obesity diagnosis and treatment beliefs in rural practice settings.

CONTEXT: Although clinical guidelines recommend routine screening and treatment for obesity in primary care, lack of agreement between physicians and patients about the need for obesity treatment in the primary care setting may be an unexplored factor contributing to the obesity epidemic. PURPOSE AND METHODS: To better understand this dynamic, we surveyed 439 obese patients (body mass index >or=30) at the time of clinic visits in 2003 at diverse primary care settings in rural Kansas and conducted same-day interviews with their physicians (N = 28). We used Spearman's correlation to describe and compare patient and physician responses. FINDINGS: Most patients were women (66%). Their mean age was 55.8 years, and mean body mass index was 37.7. Half (51%) reported discussing their weight on that visit date. Overall, 51% of patients wanted to discuss weight more often with their physician and 54% wanted to discuss weight sooner. Patients and physicians gave similar assessments of the patient's preference for discussing weight loss, how often weight was discussed at visits, and the patient's motivation for weight loss. Spearman's correlations on these variables were .33, .54, and .25, respectively (all P < .001). CONCLUSIONS: These patients and their physicians demonstrated a weak to moderate agreement on several variables crucial to initiating and continuing obesity care. Understanding patient and provider beliefs and preferences regarding obesity diagnosis and treatment is essential in designing obesity interventions for primary care.

Characteristics of social smoking among college students.

Social smoking is a newly identified phenomenon in the young adult population that is poorly understood. We investigated differences in social smoking (smoking most commonly while partying or socializing) and other smoking within a convenience sample of college smokers (n = 351) from a large midwestern university. Results revealed that 70% of 351 current (past 30-day) smokers reported social smoking. No significant difference was found in motivation to quit between smoking groups. However, a significant difference was found between groups in confidence to quit, the number of days smoked, and the number of cigarettes smoked on those days. More social smokers than expected did not perceive themselves as smokers. Logistic regression analysis revealed that lower physical and psychological dependence and higher social support scores predicted social smoking.

Preoperative and Intraoperative Predictive Factors of Immediate Extubation After Neonatal Cardiac Surgery.

BACKGROUND: We sought to identify preoperative and intraoperative predictors of immediate extubation (IE) after open heart surgery in neonates. The effect of IE on the postoperative intensive care unit (ICU) length of stay (LOS), cost of postoperative ICU care, operating room turnover, and reintubation rates was assessed. METHODS: Patients younger than 31 days who underwent cardiac surgery with cardiopulmonary bypass (January 2010 to December 2013) at a tertiary-care children's hospital were studied. Immediate extubation was defined as successful extubation before termination of anesthetic care. Data on preoperative and intraoperative variables were compared using descriptive, bivariate, and multivariate statistics to identify the predictors of IE. Propensity scores were used to assess effects of IE on ICU LOS, the cost of ICU care, reintubation rates, and operating room turnover time. RESULTS: One hundred forty-eight procedures done at a median age of 7 days resulted in 45 IEs (30.4%). The IE rate was 22.2% with single-ventricle heart disease. Independent predictors of IE were the absence of the need for preoperative ventilatory assistance, higher gestational age, anesthesiologist, and shorter cardiopulmonary bypass. Immediate extubation was associated with shorter ICU LOS (8.3 versus 12.7 days; p < 0.0001) and lower cost of ICU care (mean postoperative ICU charges, $157,449 versus $198,197; p < 0.0001) with no significant difference in the probability of reintubation (p = 0.7). Immediate extubation was associated with longer operating room turnover time (38.4 versus 46.7 minutes; p = 0.009). CONCLUSIONS: Immediate extubation was accomplished in 30.4% of neonates undergoing open heart surgery involving cardiopulmonary bypass. Immediate extubation was associated with lesser ICU LOS, postoperative ICU costs, and minimal increase in operating room turnover time, but without an increase in reintubation rates. Low gestational age, preoperative ventilatory support requirement, and prolonged cardiopulmonary bypass time were inversely associated with the ability to accomplish IE.

A double-blind, placebo-controlled study of valproate for aggression in youth with pervasive developmental disorders.

OBJECTIVE: The aim of this study was to study valproate efficacy and safety for aggression in children and adolescents with pervasive developmental disorders (PDD). METHODS: In this prospective double-blind, placebo-controlled study, 30 subjects (20 boys, 10 girls) 6-20 years of age with PDD and significant aggression were randomized and received treatment with valproate (VPA) or placebo (PBO) for 8 weeks as outpatients. Mean VPA trough blood levels were 75.5 mcg/mL at week 4 and 77.8 mcg/mL at week 8. RESULTS: No treatment difference was observed statistically between VPA and PBO groups. The Aberrant Behavior Checklist--Community Scale (ABC-C) Irritability subscale was the primary outcome measure (p = 0.65), and CGI--Improvement (p = 0.16) and OAS (p = 0.96) were secondary outcome measures. Increased appetite and skin rash were significant side effects. Only 1 subject was dropped from the study owing to side effects, notably a spreading skin rash, which then resolved spontaneously. Two subjects receiving VPA developed increased serum ammonia levels, one with an associated parent report of slurred speech and mild cognitive slowing. Poststudy, of 16 VPA and PBO subjects receiving VPA, 10 subjects demonstrated sustained response, 4 of whom later attempted taper, with significant relapse of aggression. CONCLUSION: The present negative findings cannot be viewed as conclusive, partly owing to the large placebo response, subject heterogeneity, and size of the groups. Larger studies are needed to expand upon these findings.

The community initiative on depression: report from a multiphase work site depression intervention.

OBJECTIVE: We sought to further understand depression, a common, disabling condition with considerable ramifications for the workplace, including higher costs, absenteeism, and reduced work performance. METHODS: A multidisciplinary health care coalition recently implemented a multiphase workplace depression initiative in Kansas City. We report results from its first phase, a 22-item, self-administered survey of depression knowledge and attitudes among employees of 13 large, local work sites. RESULTS: There were 6,399/38,945 respondents (16% response rate). Most respondents (>90%) appropriately recognized the signs and symptoms of depression. A minority (29%) would feel comfortable discussing depression with their supervisor. Sixty-two percent knew how to access company resources for depression care. CONCLUSIONS: Employees were knowledgeable about depression but were less aware of employee-assistance programs for depression care. These findings support increased attempts to raise the awareness of depression and promote of help-seeking behavior in the workplace. CLINICAL SIGNIFICANCE: Depression is a prevalent illness with risk for many deleterious outcomes if under-recognized or undertreated. Depression is a leading cause of work-related disability worldwide. Most people with depression are employed (an estimated 68%). Recognizing and initiating depression care in the workplace will facilitate depression treatment in clinical settings.

Comparison of a visual to a computer-assisted technique for detecting apoptosis.

In many studies, fluorescent dyes (ethidium bromide [EB] and acridine orange [AO]) are used to stain DNA to determine if nuclei are apoptotic. However, there are numerous visual methods for counting these stained DNA that may lead to inaccuracies Measuring apoptosis by the visual counting method may be imprecise because of the variability of individuals' perception of color. Therefore, the authors compared a visual method of counting chromatin for apoptosis with a method relying on a computer program. They began counting chromatin using the visual method, in which individuals identify the stained DNA using their own visual perception. For comparison, they used a software-based counting method (analySIS software) to determine the color (hue) of the stained DNA. Using the numeric hue values from the software eliminates the variations in human color perception. Intra and interrater reliability of the visual and computer-assisted counting methods were evaluated with Spearman's. The authors found statistical significance in the intrarater reliability (r = 1.0, P = 0.0001 for all chromatin categories) and interrater reliability (r = 0.975, P = 0.005 for both readings) when using the software program. No statistical significance was found for the visual counting method, indicating inaccuracy between and within raters. Thus, the computer-assisted counting method of identifying the damaged DNA is more accurate and precise than the individual's visual perception of color. Based on these data, apoptosis measurements using color staining with EB and AO should be determined using hue values generated by a computer program and not by a researcher's visual assessment.

Neonatal vitamin K might reduce vulnerability to alcohol dependence in Danish men.

OBJECTIVE: Levels of oxidative defenses and blood-clotting factors are normally reduced in newborns, increasing the risk of injury to developing brain structures around the time of birth. This early neonatal vulnerability corresponds to a timeframe in which the development of reward-related limbic structures is particularly active. Taking advantage of a serendipitous event in the history of treating newborns, we tested the hypothesis that vitamin K supplementation, administered to facilitate the synthesis of blood-clotting proteins within this critical timeframe, might also reduce the development of alcohol dependence later in life. METHOD: Subjects were approximately full-term male infants, selected from a large Danish birth cohort. Two thirds of the original 330 subjects in this study were high-risk sons of alcoholic fathers; 241 of the total completed the 30-year follow-up. Of subjects reported on for this article (N = 238), 44 received vitamin K supplementation at birth; 161 were considered high risk, and 66 were categorized as having lower birth weight (<6 lbs). A comprehensive series of measures was obtained on each subject before, during and shortly after birth as well as at 1 year of age. The Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, diagnosis of alcohol dependence and a measure of lifetime problem drinking served as the 30-year outcome variables. RESULTS: Vitamin K treatment, inherited risk and low birth weight each independently predicted alcohol dependence and problem drinking at age 30. Vitamin K treatment was associated with significantly lower rates of alcohol dependence and fewer symptoms of problem drinking. CONCLUSIONS: Vitamin K treatment at birth might protect against the development of alcoholism in adults by reducing early postnatal hemorrhage and oxidative brain damage.