Pharmacologic Treatments for Acute Respiratory Distress Syndrome and Acute Lung Injury

Background: Multiple pharmacologic treatments have been studied for patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Our objective was to systematically evaluate this literature to determine the effects of these interventions on important clinical outcomes. Methods: We searched OVID versions of CENTRAL (The Cochrane Library Issue 3, 2003), MEDLINE (1966-week 2, January 2004), EMBASE (1980-week 4, 2004), CINAHL (1982-week 2, January 2004), and HEALTHSTAR (1995-December 2003); proceedings from four conferences (1994–2003); and bibliographies of review articles and included studies. We included randomized controlled trials (RCTs) of pharmacologic treatments compared with no therapy or placebo for established ARDS and ALI in adults admitted to an intensive care unit, with measurement of early mortality, late mortality, duration of ventilation, ventilator-free days, non-pulmonary organ dysfunction, or adverse events. We excluded trials in other populations incorporating subgroup analyses of patients with ARDS and ALI and studies of nitric oxide, partial liquid ventilation, and fluid and nutritional interventions. Two reviewers independently screened studies and abstracted data from studies included in the analysis. Data were pooled using random effects models where appropriate. Results: We retrieved 75 potentially relevant articles and abstracts, of which 33 trials randomizing 3272 patients met our selection criteria. Meta-analysis showed no effect on early mortality for alprostadil ([prostaglandin E₁] seven studies; 693 patients; relative risk [RR] 0.95; 95% confidence interval [CI], 0.77, 1.17), acetylcysteine (five studies; 235 patients; RR 0.89; 95% CI, 0.65, 1.21), early high-dose corticosteroids (two studies; 180 patients; RR 1.12; 95% CI, 0.72, 1.74), or surfactant therapy (nine studies; 1418 patients; RR 0.93; 95% CI, 0.77, 1.12). Most trials of alprostadil, early high-dose corticosteroids, and surfactant therapy showed more adverse events in the active therapy arm. Single small RCTs demonstrated lower hospital mortality (24 patients, RR 0.20; 95% CI, 0.05, 0.81) with corticosteroids for late phase ARDS and lower 1-month mortality (30 patients, RR 0.67; 95% CI, 0.47, 0.95) with pentoxifylline for patients with metastatic cancer and ARDS. Individual trials of nine additional interventions failed to show beneficial effects on prespecified outcomes. Conclusions: Effective pharmacotherapy for ARDS is extremely limited. Corticosteroids for late phase ARDS and pentoxifylline for patients with metastatic cancer and ARDS reduced mortality in single small studies. However, further research is required to investigate their potential benefit in the treatment of ALI/ARDS.     

Assessing the readiness of black churches to engage in health disparities research

We assessed church readiness to engage in health disparities research using a newly developed instrument, examined the correlates of readiness, and described strategies that churches used to promote health. We pilot tested the instrument with churches in a church-academic partnership (n = 12). We determined level of readiness to engage in research and assessed correlates of readiness. We also conducted interviews with participating pastors to explore strategies they had in place to support research engagement. Churches scored fairly high in readiness (average of 4.04 out of 5). Churches with a pastor who promoted the importance of good nutrition in a sermon or had a budget for health-related activities had significantly higher readiness scores than churches without such practices. Having a tool to evaluate church readiness to engage in research will inform targeted technical assistance and research projects that will strengthen church-academic partnerships and improve capacity to address health disparities.     

R6/2 neurons with intranuclear inclusions survive for prolonged periods in the brains of chimeric mice

The R6/2 mouse possesses mutant exon 1 of human Hdh, and R6/2 mice with 150 CAG repeats show neurological abnormalities by 10 weeks and die by 15 weeks. Few brain abnormalities, however, are evident at death, other than widespread ubiquitinated neuronal intranuclear inclusions (NIIs). We constructed R6/2t+/t- <--> wildtype (WT) chimeric mice to prolong survival of R6/2 cells and determine if neuronal death and/or neuronal injury become evident with longer survival. ROSA26 mice (which bear a lacZ transgene) were used as WT to distinguish between R6/2 and WT neurons. Chimeric mice consisting partly of R6/2 cells lived longer than pure R6/2 mice (up to 10 months), with the survival proportional to the R6/2 contribution. Genotypically R6/2 cells formed NIIs in the chimeras, and these NIIs grew only slightly larger than in 12-week pure R6/2 mice, even after 10 months. Additionally, neuropil aggregates formed near R6/2 neurons in chimeric mice older than 15 weeks. Thus, R6/2 neurons could survive well beyond 15 weeks in chimeras. Moreover, little neuronal degeneration was evident in either cortex or striatum by routine histological stains. Nonetheless, striatal shrinkage and ventricular enlargement occurred, and striatal projection neuron markers characteristically reduced in Huntington's disease were diminished. Consistent with such abnormalities, cortex and striatum in chimeras showed increased astrocytic glial fibrillary acidic protein. These results suggest that while cortical and striatal neurons can survive nearly a year with nuclear and extranuclear aggregates of mutant huntingtin, such lengthy survival does reveal cortical and striatal abnormality brought on by the truncated mutant protein.     

Suicidality, aggression, and other treatment considerations among pregnant, substance-dependent women with posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) and other Axis I comorbidity among women with substance use disorders (SUDs) appear similarly prevalent and are associated with comparable negative clinical profiles and treatment outcomes. The relative contribution of comorbid PTSD vs other Axis I psychiatric disorders to clinical characteristics is largely unexamined, however, despite theory and empirical data indicating that PTSD and SUDs may have a unique relationship that confers specific risk for clinical severity and poor treatment outcome. In a sample of pregnant, opioid- and/or cocaine-dependent women entering substance abuse treatment, women with PTSD (SUD-PTSD; n = 23) were compared to those with other Axis I comorbidity (SUD-PSY; n = 45) and those without Axis I comorbidity (SUD-only; n = 37). Data were collected via face-to-face interviews and urinalysis drug assays. Although the study groups had similar substance use severity, the SUD-PTSD group was more likely to report suicidality, aggression, and psychosocial impairment than both the SUD-PSY and SUD-only groups. Findings indicate treatment considerations for substance-dependent women with PTSD are broader and more severe than those with other Axis I conditions or substance dependence alone.