The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study.

OBJECTIVE: Investigate the efficacy of nabilone capsules (NAB) in reducing the frequency and intensity of nightmares in subjects with PTSD. PATIENTS AND METHODS: Canadian male military personnel with PTSD, who despite standard treatment continued to experience trauma-related nightmares, received double-blind treatment with 0.5mg NAB or placebo (PBO), and then titrated to the effective dose (nightmare suppression) or reaching a maximum of 3.0mg. Subjects were followed for 7 weeks and then, following a 2-week washout period, were titrated with the other study treatment and followed for an additional 7 weeks. The modified intent-to-treat (mITT) population, which included all treated subjects that met inclusion/exclusion criteria, was analyzed. RESULTS: Ten subjects were included in the mITT population. The mean reduction in nightmares as measured by the CAPS Recurring and Distressing Dream scores were -3.6 ± 2.4 and -1.0 ± 2.1 in the NAB and PBO groups, respectively (p=0.03). Mean global improvement as measured by the Clinical Global Impression of Change (CGI-C) was 1.9 ± 1.1 (i.e. much improved) and 3.2 ± 1.2 (i.e. minimally improved) in the NAB and PBO groups, respectively (p=0.05) Five out of 10 (50%) were much improved on NAB versus 1 out of 9 (11%) on PBO. Results for the General Well Being Questionnaire (WBQ) were 20.8 ± 22 and -0.4 ± 20.6 in the NAB and PBO groups, respectively (p=0.04). The proportion of subjects who experienced a treatment-related occurrence of adverse events was 50% in the NBO group and 60% in the PBO group. No event was severe nor resulted in a drop-out. This study is registered with Health Canada. CONCLUSION: In this small sample NAB provided significant relief for military personnel with PTSD, indicating that it shows promise as a clinically-relevant treatment for patients with nightmares and a history of non-response to traditional therapies. These findings need to be replicated in a larger cohort. There is a need for further exploration of the effect of nabilone on other symptoms of PTSD such as re-experiencing, hyper vigilance and insomnia.

Virologic suppression measured by a cytomegalovirus (CMV) DNA test calibrated to the World Health Organization international standard is predictive of CMV disease resolution in transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) load measurement is used to assess the efficacy of treatment of CMV disease, but lacks standardization. Using the World Health Organization (WHO) international standard for reporting, we correlated viral load with CMV disease resolution. METHODS: CMV load was quantified in plasma using a test calibrated to the WHO standard. Three predictive rules were predefined to determine association between CMV DNAemia and outcome: (1) pretreatment CMV DNA of <18,200 (4.3 log(10)) IU/mL; (2) viral load declines of 1.0, 1.5, 2.0, and 2.5 log(10) IU/mL from baseline to days 7, 14, and 21 of treatment, respectively; and (3) viral suppression <137 (2.1 log(10)) IU/mL at days 7, 14, and 21. Analysis was performed using Cox proportional hazard models. RESULTS: Of 267 patients, 251 had CMV disease resolution by day 49 of treatment. Patients with pretreatment CMV DNA of <18,200 (4.3 log(10)) IU/mL had faster time to disease resolution (adjusted hazard ratio [AHR], 1.56; P = .001). Patients with CMV load suppression (<137 IU/mL [<2.1 log(10)]) at days 7, 14, and 21 had faster times to clinical disease resolution (AHRs, 1.61, 1.73, and 1.64, and P = .005, <.001, and <.001, respectively). Relative CMV load reductions from baseline were not significantly associated with faster resolution of CMV disease. CONCLUSIONS: Patients with pretreatment CMV DNA of <18,200 (4.3 log(10)) IU/mL are 1.5 times more likely to have CMV disease resolution. CMV suppression (<137 [2.1 log(10)] IU/mL), as measured by a test calibrated to the WHO Standard, is predictive of clinical response to antiviral treatment. CLINICAL TRIALS REGISTRATION: NCT00431353.

Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery.

BACKGROUND: Perioperative myocardial ischemia occurs in 20-40% of patients at risk for cardiac morbidity and is associated with a ninefold increase in risk of cardiac morbidity. METHODS: In a prospective, double-blinded, clinical trial, we studied 190 patients with or at risk for coronary artery disease in two study groups with a 2:1 ratio (clonidine, n = 125 vs. placebo, n = 65) to test the hypothesis that prophylactic clonidine reduces the incidence of perioperative myocardial ischemia and postoperative death in patients undergoing noncardiac surgery. Clonidine (0.2 mg orally as well as a patch) or placebo (tablet and patch) was administered the night before surgery, and clonidine (0.2 mg orally) or placebo (tablet) was administered on the morning of surgery. The patch or placebo remained on the patient for 4 days and was then removed. RESULTS: The incidence of perioperative myocardial ischemia was significantly reduced with clonidine (intraoperative and postoperative, 18 of 125, 14% vs. placebo, 20 of 65, 31%; P = 0.01). Prophylactic clonidine administration had minimal hemodynamic effects. Clonidine reduced the incidence of postoperative mortality for up to 2 yr (clonidine, 19 of 125 [15%] vs. placebo, 19 of 65 [29%]; relative risk = 0.43 [confidence interval, 0.21-0.89]; P = 0.035). CONCLUSIONS: Perioperative administration of clonidine for 4 days to patients at risk for coronary artery disease significantly reduces the incidence of perioperative myocardial ischemia and postoperative death.

Practice pattern variability for myocardial revascularization: impact on resource use across 24 centers.

OBJECTIVE: To determine the predictors of hospital length of stay (LOS) after elective uncomplicated coronary artery bypass graft surgery. DESIGN: Retrospective analysis of the EPI-1 database, 1991-1993. SETTING: Multicenter; 24 academic, private, federal, and health maintenance institutions. PARTICIPANTS: Patients undergoing elective CABG surgery (n = 2,417). MEASUREMENTS AND MAIN RESULTS: Using a systematic sampling scheme at each site, each patient was evaluated to identify markers of chronic disease, perioperative test data, treatments, adverse outcomes, and LOS. Institutional differences in the care of patients free of complications were assessed using a multivariate model. LOS was the outcome variable selected to estimate cost. A total of 861 patients (37%) were free of any complication. The mean site LOS ranged from 5.4 to 9.0 days, with half of the 24 centers reporting a hospital LOS routinely >7.1 days. The predominant factor associated with a complication-free LOS was site per se, accounting for 32% of the variability in hospital LOS that could not be explained by any site characteristic (eg, size, geographic location, academic affiliation). Multivariable analysis identified 3 demographic predictors--age >75 years (increasing LOS by 1.3 days), admission from the emergency department (increasing LOS by 0.7 days), and uninsured or Medicaid-insured (increasing LOS by 0.4 days); 2 historical predictors--New York Heart Association class III or IV congestive heart failure (increasing LOS by 0.5 days) and history of arrhythmia (increasing LOS by 0.7 days); and 2 practice patterns--transfusion of blood products (increasing LOS by 0.3 days) and delayed extubation (increasing LOS by 0.5 days). Previous myocardial infarction, diabetes, chronic obstructive pulmonary disease, neurologic disease, and other historical factors were not associated with LOS in patients without a complication. CONCLUSION: A substantial variability in LOS after complication-free coronary artery bypass graft surgery was determined predominantly by site per se, even after adjustment for disease severity, site type or location, and surgical and anesthetic practices. The variability in LOS was likely due to practice style influences and represents an opportunity to decrease waste in the provision of a common and expensive procedure.

Isolated systolic hypertension is associated with adverse outcomes from coronary artery bypass grafting surgery.

UNLABELLED: Isolated systolic blood pressure has not been sufficiently studied in the perioperative setting and may contribute to morbidity and mortality after coronary artery bypass grafting (CABG) surgery. Our objective was to determine the prevalence of isolated systolic hypertension among patients who had CABG surgery and to assess whether isolated systolic hypertension is associated with perioperative and postoperative in-hospital morbidity or mortality. Patients who underwent CABG were selected from a prospective epidemiological study involving 2417 patients in 24 medical centers. Patients were classified as having normal preoperative blood pressure, isolated systolic hypertension (systolic blood pressure >140 mm Hg), diastolic hypertension (diastolic blood pressure >90 mm Hg), or a combination of these. Demographic risk factors (age, sex, and ethnicity), clinical risk factors (diabetes mellitus, increased cholesterol, antihypertensive medications, history of congestive heart failure, myocardial infarction, hypertension, and neurological deficits), and behavioral risk factors (smoking and heavy drinking) were controlled for statistically. Adverse outcomes included left ventricular dysfunction, cerebral vascular dysfunction or events, renal insufficiency or failure, and all-cause mortality. Isolated systolic hypertension was found in 29.6% of patients. Unadjusted isolated systolic hypertension was associated with a 40% increased risk of adverse outcomes (odds ratio, 1.4; confidence interval, 1.1-1.7). After adjusting for other potential risk factors, the increased risk of adverse outcomes with isolated systolic hypertension was 30%. We conclude that isolated systolic hypertension is associated with a 40% increase in the likelihood of cardiovascular morbidity perioperatively in CABG patients. This increase remains present regardless of antihypertensive medications, anesthetic techniques, and other perioperative cardiovascular risk factors (e.g., age older than 60 yr or history of congestive heart failure, myocardial infarction, or diabetes). IMPLICATIONS: Isolated systolic hypertension is associated with a 40% increase in the likelihood of perioperative cardiovascular morbidity in coronary artery surgery patients.