A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity.

BACKGROUND: Meta-analyses of N-acetylcysteine (NAC) for preventing contrast-induced nephrotoxicity (CIN) have led to disparate conclusions. Here we examine and attempt to resolve the heterogeneity evident among these trials. METHODS: Two reviewers independently extracted and graded the data. Limiting studies to randomized, controlled trials with adequate outcome data yielded 22 reports with 2746 patients. RESULTS: Significant heterogeneity was detected among these trials (I2 = 37%; p = 0.04). Meta-regression analysis failed to identify significant sources of heterogeneity. A modified L'Abbé plot that substituted groupwise changes in serum creatinine for nephrotoxicity rates, followed by model-based, unsupervised clustering resolved trials into two distinct, significantly different (p < 0.0001) and homogeneous populations (I2 = 0 and p > 0.5, for both). Cluster 1 studies (n = 18; 2445 patients) showed no benefit (relative risk (RR) = 0.87; 95% confidence interval (CI) 0.68-1.12, p = 0.28), while cluster 2 studies (n = 4; 301 patients) indicated that NAC was highly beneficial (RR = 0.15; 95% CI 0.07-0.33, p < 0.0001). Benefit in cluster 2 was unexpectedly associated with NAC-induced decreases in creatinine from baseline (p = 0.07). Cluster 2 studies were relatively early, small and of lower quality compared with cluster 1 studies (p = 0.01 for the three factors combined). Dialysis use across all studies (five control, eight treatment; p = 0.42) did not suggest that NAC is beneficial. CONCLUSION: This meta-analysis does not support the efficacy of NAC to prevent CIN.

Implications of nested designs in school-based mental health services research.

Evaluating school-based mental health services for children and youth with emotional disturbance (ED) has been a challenge for researchers. One particular challenge is the study design of using the student as the statistical unit of analysis, which in certain cases may lead to a violation of the "independence of error" assumption. However, the alternative to this nested design, including fewer students and more schools, can be costly and administratively complex. This study examines data from two national studies including 314 students with ED and served in special education programs and their caregivers from 24 schools in the US to identify the extent to which nesting or design effects occur in this population. The results show that variables focusing on psychopathology are less affected by nesting but school-related variables such as academic functioning are more affected. Design effects varied by grade level, suggesting that grade should be considered when designing such evaluations.

CJDATS CO-OCCURRING DISORDERS SCREENING INSTRUMENT (CODSI) FOR MENTAL DISORDERS (MD): A Validation Study.

Three standardized screening instruments-the Global Appraisal of Individual Needs Short Screener (GSS), the Mini-International Neuropsychiatric Interview-Modified (MINI-M), and the Mental Health Screening Form (MHSF)-were compared to two shorter instruments, the 6-item Co-Occurring Disorders Screening Instrument for Mental Disorders (CODSI-MD) and the 3-item CODSI for Severe Mental Disorders (CODSI-SMD) for use with offenders in prison substance-abuse treatment programs. Results showed that the CODSI screening instruments were comparable to the longer instruments in overall accuracy and that all of the instruments performed reasonably well. The CODSI instruments showed sufficient value to justify their use in prison substance-abuse treatment programs and to warrant validation testing in other criminal justice populations and settings.

Preclinical trial of L-arginine monotherapy alone or with N-acetylcysteine in septic shock.

OBJECTIVE: L-arginine supplementation in sepsis is controversial. Septic shock has been alternatively viewed as an L-arginine-deficient state or as a syndrome caused by excess nitric oxide, an end-product of L-arginine metabolism. DESIGN: Randomized, placebo-controlled, and double-blinded (investigators, veterinarians, and pharmacists). SETTING: Laboratory. SUBJECTS: Purpose-bred, 1- to 2-yr-old, 10- to 12-kg beagles. INTERVENTIONS: The effects of parenteral L-arginine alone or in combination with N-acetylcysteine were compared with vehicle alone in a well-characterized canine model of Escherichia coli peritonitis. Two doses were studied that delivered approximately 1.5-fold (10 mg x kg(-1) x hr(-1)) and 15-fold (100 mg x kg(-1) x hr(-1)) the L-arginine dose typically administered with standard total parenteral nutrition. Animals in the low- and high-dose L-arginine arms were further randomized to receive vehicle alone or N-acetylcysteine (20 mg x kg(-1) x hr(-1)) as an antioxidant to prevent peroxynitrite formation. MEASUREMENTS AND MAIN RESULTS: The main measurements were hemodynamics, plasma arginine and ornithine, serum nitrate/nitrite, laboratory studies for organ injury, and survival. Both doses of L-arginine similarly increased mortality (p = .02), and worsened shock (p = .001 for reduced mean arterial pressure). These effects were associated with significant increases in plasma arginine (p = .0013) and ornithine (p = .0021). In addition, serum nitrate/nitrite (p = .02), liver enzymes (p = .08), and blood urea nitrogen/creatinine ratios (p = .001) rose, whereas arterial pH (p = .001) and bicarbonate levels (p = .001) fell. N-acetylcysteine did not significantly decrease any of the harmful effects of L-arginine. Thus, parenteral L-arginine monotherapy was markedly harmful in animals with septic shock. CONCLUSIONS: These findings suggest that supplemental parenteral L-arginine, at doses above standard dietary practices, should be avoided in critically ill patients with septic shock.

Outcomes for women with co-occurring disorders and trauma: program-level effects.

Program-level effects at 6 months are reported from meta-analysis of a nine-site quasi-experimental study of comprehensive, integrated, trauma-informed, and consumer-involved services for women who have mental health problems, substance use disorders, and who have experienced interpersonal violence. The average weighted effect size is significant for the treatment condition for improved post-traumatic symptoms (p < 0.02), drug use problem severity (p < 0.02), and nearly significant for mental health symptoms (p < 0.06). There is significant heterogeneity in effect sizes across sites. Program-level variables were examined in an effort to explain this heterogeneity. The findings indicate that sites which provided significantly more integrated counseling produced more favorable results in mental health symptoms (p < 0.01) and both alcohol (p < 0.001) and drug use problem severity (p < 0.001). The same trend is observable for reductions in post-traumatic stress symptoms, although the difference does not attain statistical significance.

Supporting caregivers of frail older adults in an HMO setting.

The long-term effectiveness of a structured health education program (HEP) for spouses and frail older adults was evaluated in a staff model health maintenance organization (HMO). HEP is a multicomponent group program that includes emotion-focused and problem-focused coping strategies, education, and support. For caregivers, HEP was more effective than usual care (UC) in reducing depression, increasing knowledge of community services and how to access them, and changing caregivers' feelings of competence and the way they respond to the caregiving situation. For care recipients, HEP was more effective than UC in preventing increases in somatic symptoms and symptoms of anxiety/insomnia. ((c) 2004 APA, all rights reserved)

Outcomes from a therapeutic community for homeless addicted mothers and their children.

A women's therapeutic community (TC) designed to prevent homelessness was evaluated using a quasi-experimental process. Propensity analysis selected comparable experimental (E) and comparison (C) participants. Significant improvements were found for the E group at the domain level, both in "psychological" dysfunction on symptoms (e.g., depression), and in "health," including ratings of health and adherence to medication regimens. No significant difference was found at the domain level for "parenting" or "housing stabilization," but specific outcomes did differ. For example, a greater number of children resided with the E group mothers who also assumed financial responsibility for more of their children.

Predictors of health and human services use by persons with dementia and their family caregivers.

The aim of this study was to identify predictors of the use of health and human services by community residing persons with dementia and their family caregivers. Telephone interviews were conducted with a sample of 608 primary caregivers of community residing persons with dementia who were randomly selected from a state-wide dementia registry. The Anderson Behavioral Model of Health Care Use was used as the analytic framework. Hierarchical ordinary least squares regression models were developed to analyze predictors of health and human services use. Predisposing, enabling, and need variables explained 40.9% of the variance in service use, 29.8% of the variance in health service use, and 38.1% of the variance in the use of human services. Enabling variables explained more variance in the use of health and human services than did need or predisposing variables. In contrast to the health services utilization literature that points to the importance of need variables, the results of this study lend support to findings in the caregiving literature that indicate that enabling variables are at least as important as need variables in predicting the use of community services by family caregivers of persons with dementia.