Protective conditioning for acute graft-versus-host disease.

BACKGROUND: Conditioning with total lymphoid irradiation plus antithymocyte serum protects mice against acute graft-versus-host disease (GVHD) after hematopoietic-cell transplantation. We tested this strategy in humans. METHODS: Thirty-seven patients with lymphoid malignant diseases or acute leukemia underwent an experimental conditioning regimen with 10 doses of total lymphoid irradiation (80 cGy each) plus antithymocyte globulin, followed by an infusion of HLA-matched peripheral-blood mononuclear cells from related or unrelated donors who received granulocyte colony-stimulating factor. RESULTS: Of the 37 transplant recipients, only 2 had acute GVHD after hematopoietic-cell transplantation. Potent antitumor effects in patients with lymphoid malignant diseases were shown by the change from partial to complete remission. In the transplant recipients who underwent conditioning with total lymphoid irradiation and antithymocyte globulin, the fraction of donor CD4+ T cells that produced interleukin-4 after in vitro stimulation increased by a factor of five, and the proliferative response to alloantigens in vitro was reduced, as compared with normal control subjects and control subjects who underwent conditioning with a single dose of total-body irradiation (200 cGy). CONCLUSIONS: A regimen of total lymphoid irradiation plus antithymocyte globulin decreases the incidence of acute GVHD and allows graft antitumor activity in patients with lymphoid malignant diseases or acute leukemia treated with hematopoietic-cell transplantation.

A comparison of speculum and nonspeculum collection of cervicovaginal specimens for fetal fibronectin testing.

OBJECTIVE: Current recommendations include the use of a vaginal speculum for fetal fibronectin specimen collection. This article evaluates the equivalency of nonspeculum methods for collecting fetal fibronectin specimens. STUDY DESIGN: Two separate prospective studies of patients more than 22 weeks' gestation were performed at 2 institutions with similar hypotheses and methods. Two sequential specimens were collected on each patient: 1 with speculum and 1 with the nonspeculum method. The order of collection was reversed or randomized in both studies. Two alternative nonspeculum collection methods are described. RESULTS: The 2 study sample sizes were 169 and 31. Comparison of the fetal fibronectin test results between the speculum and nonspeculum methods demonstrated greater than 95% agreement with an intraclass Kappa coefficient greater than 0.85 in both studies. The order of collection did not result in significantly different fetal fibronectin averages. CONCLUSION: These studies demonstrate that there is excellent agreement between fetal fibronectin results obtained by speculum and nonspeculum collection methods.

Multicenter Trial of Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer: Survival and Toxicity Endpoints.

PURPOSE: The radiobiology of prostate cancer may favor the extreme hypofractionation inherent in stereotactic body radiation therapy (SBRT); however, data from a large multicenter study are lacking. We therefore examined the hypothesis that dose-escalated SBRT can be safely administered across multiple institutions, with favorable 5-year disease-free survival (DFS) rates compared with historical controls. METHODS AND MATERIALS: Twenty-one centers enrolled 309 patients with prostate adenocarcinoma: 172 with low-risk (LR) and 137 with intermediate-risk (IR) disease. All were treated with a non-coplanar robotic SBRT platform using real-time tracking of implanted fiducials. The prostate was prescribed 40 Gy in 5 fractions of 8 Gy. We assessed toxicities using Common Terminology Criteria for Adverse Events (CTCAE) version 3 and biochemical failure using the "nadir + 2" definition. The study population yielded 90% power to identify excessive (>10%) rates of grade ≥3 genitourinary (GU) or gastrointestinal toxicities and, in the LR group, 80% power to show superiority in DFS over a 93% historical comparison rate. RESULTS: At a median follow-up of 61 months, 2 LR patients (1.2%) and 2 IR patients (1.5%) experienced grade 3 GU toxicities, far below the 10% toxicity rate deemed excessive (upper limits of 95% confidence interval, 3.5% and 4.3%, respectively). No grade 4 or 5 toxicities occurred. All grade 3 toxicities were GU, occurring 11 to 51 months after treatment. For the entire group, the actuarial 5-year overall survival rate was 95.6% and the DFS rate was 97.1%. The 5-year DFS rate was 97.3% for LR patients (superior to the 93% DFS rate for historical controls; P = .0008; lower limit of 95% confidence interval, 94.6%) and 97.1% for IR patients. CONCLUSIONS: Dose-escalated prostate SBRT was administered with minimal toxicity in this multi-institutional study. Relapse rates compared favorably with historical controls. SBRT is a suitable option for LR and IR prostate cancer.

A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of cocaine dependence.

Prior studies have demonstrated inefficacy among dopamine receptor antagonists for treating cocaine dependence. An alternative approach would be to investigate the ability of indirect inhibitors of cortico-mesolimbic dopamine release, such as the 5-HT(3) receptor antagonist ondansetron, to reduce cocaine's reinforcing effects. We hypothesized that ondansetron might be more efficacious than placebo at reducing cocaine intake and promoting abstinence in cocaine-dependent individuals. In a pilot randomized, double-blind, 10-week controlled trial, 63 treatment-seeking, cocaine-dependent men and women received ondansetron (0.25 mg, 1.0 mg, or 4.0 mg twice daily) or placebo. Up to three times per week, participants were assessed on several measures of cocaine use, including urine benzoylecgonine. Cognitive behavioral therapy was administered weekly. Ondansetron was well tolerated, causing no serious adverse events. The ondansetron 4.0 mg group had the lowest dropout rate among all treatment groups and a greater rate of improvement in percentage of participants with a cocaine-free week compared with the placebo group (p = 0.02), whereas the ondansetron 1.0 mg group had a lower rate of improvement in percentage of weekly mean non-use days than did placebo recipients (p = 0.04). These results suggest the possibility of a non-linear dose-response function, with evidence supporting efficacy for the 4.0 mg group.

Cocaine Rapid Efficacy Screening Trial (CREST): a paradigm for the controlled evaluation of candidate medications for cocaine dependence.

AIM: Development of effective medications for the treatment of cocaine dependence remains a major priority for the National Institute on Drug Abuse (NIDA) at the National Institutes of Health. The Cocaine Rapid Efficacy Screening Trial (CREST) paradigm was developed by the Division of Treatment Research and Development (DT R&D) at NIDA with the goal of enhancing pilot clinical trial validity when systematically assessing a range of medications and drug classes for potential utility in treatment of cocaine dependence. DESIGN: CREST utilizes a randomized, controlled, parallel group, blinded methodology for comparing one or more marketed medications against a standard, pharmaceutical grade placebo. The trial design is comprised of a flexible 24-week screening/baseline period followed by randomization to an 8-week treatment period. MEASURES: Standard measures of outcomes for the CREST included urinary benzoylecgonine (primary metabolite of cocaine), retention, cocaine craving, depression, clinical global impression and HIV-risk behaviors. In order to facilitate comparisons of data from the CREST studies across sites, drug classes and time, standardized procedures, measures and psychosocial counseling were used. RESULTS: A total of 19 medications were evaluated in out-patient treatment research clinics in Boston, Cincinnati, Los Angeles, New York and Philadelphia. CONCLUSIONS: Findings supported decisions to move forward three medications (cabergoline, reserpine, tiagabine) using full-scale, adequately powered, randomized placebo-controlled trial designs. Lessons learned from the CREST experience continue to shape cocaine pharmacotherapy trial design and execution.

Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence.

AIMS: The two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine dependence. DESIGN: A multi-arm, modified blinded, placebo-controlled design was used. SETTING: The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU). PARTICIPANTS: Participants met criteria for cocaine dependence during a 2-week screening period. INTERVENTION: Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study. MEASUREMENTS: Urine benzoylecgonine (BE) concentrations, self-report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period. FINDINGS: None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end-point compared to the placebo group. Significant within-group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self-reported cocaine use declined over the study period. Overall, the active medications were well tolerated. CONCLUSIONS: This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups.

A medication screening trial evaluation of reserpine, gabapentin and lamotrigine pharmacotherapy of cocaine dependence.

AIMS: To conduct a preliminary evaluation of the safety and efficacy of reserpine, gabapentin or lamotrigine versus an unmatched placebo control as a treatment for cocaine dependence. DESIGN: A 10-week out-patient study using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design. SETTING: The study was conducted at the Cincinnati Medication Development Research Unit (MDRU). PARTICIPANTS: Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty participants were enrolled, with 50 participants completing the final study measures. INTERVENTION: The targeted daily doses of medication were reserpine 0.5 mg, gabapentin 1800 mg and lamotrigine 150 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis. MEASUREMENTS: Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression scale--observer and self-report of cocaine use. Safety measures included adverse events, electrocardiograms (ECGs), vital signs and laboratory tests. FINDINGS: Subjective measures of cocaine dependence indicated significant improvement for all study groups. Urine BE results indicated a significant improvement for the reserpine group (P < 0.05) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. The medications appeared to be tolerated well. CONCLUSIONS: The present findings suggest that reserpine may be worthy of further study as a cocaine dependence treatment.

A placebo-controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments.

AIMS: To conduct a preliminary evaluation of the safety and efficacy of tiagabine, sertraline or donepezil versus an unmatched placebo control as a treatment for cocaine dependence. DESIGN: A 10-week out-patient study was conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design. SETTING: This study was conducted at the Cincinnati Medication Development Research Unit (MDRU) and at an affiliated site in Dayton, Ohio. PARTICIPANTS: Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty-seven participants were enrolled with 55 completing final study measures. INTERVENTION: The targeted daily doses of medication were tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis. MEASUREMENTS: Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression Scale-Observer and self-report of cocaine use. Safety measures included adverse events, ECGs, vital signs and laboratory tests. FINDINGS: Subjective measures of cocaine dependence indicated significant improvement for all study groups. Generalized estimating equations analysis indicated that the tiagabine group showed a trend toward a significant decrease in urine BE level from baseline to weeks 5-8 (P = 0.10) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. CONCLUSIONS: The present findings suggest that tiagabine may be worthy of further study as a cocaine dependence treatment.

Retrospective analyses of pooled data from CREST I and CREST II trials for treatment of cocaine dependence.

AIM: To analyze pooled data from the Cocaine Rapid Evaluation Screening Trial (CREST). Pooling data from these small pilot trials into four major drug classes permitted data exploration for treatment and covariate effects with increased sample size. DESIGN: Small pilot trials were conducted to screen fifteen medications as prospective treatments for cocaine dependence. Studies included a flexible 2-week to 4-week screening/baseline period followed by an 8-week randomized treatment condition. Participants were randomized equally to one of up to three active medications or placebo. SETTING: Five Medications Development Research Units at the five academic centers of University of Cincinnati, New York University, University of Pennsylvania, University of California Los Angeles and Boston University. PARTICIPANTS: The pooled data set consisted of 357 total subjects. Standardized inclusion and exclusion criteria were employed in subject selection to enhance consistency of cocaine-dependent study participants across all sites (see reports on individual trials in this supplement for details). All participants provided at least two urine samples that were positive for cocaine metabolite during a two-week period prior to being randomized. INTERVENTION: All subjects in these trials, those randomized to placebo and active medications, received active treatment in the form of evidence-based cognitive behavioral therapy. MEASURES: Quantitative urine benzoylecgonine (BE), self-report of cocaine use, and total Brief Substance Craving Scale (BSCS) scores were compared between each class of medication and its matched-placebo group. FINDINGS: Regression analysis of pooled data did not identify any statistically significant differences between treatment and matched-placebo for any of the four classes. Exploration of the effects of baseline covariates indicated that gender and African American status were associated significantly with outcome. Female gender was consistently associated with poorer outcomes for medication and placebo groups, while the direction of association between African American status and outcome differed by treatment groups. Retention was also examined: dropout rates may have been somewhat higher for placebo than treatment groups during the early active-treatment period. Classification trees were used to identify characteristics of subjects who were abstinent for at least two weeks during the eight-week trial; only 4.0% of females while 17.9% of males achieved this criterion. CONCLUSIONS: Results presented here may prove useful for planning future clinical trials for therapies targeting cocaine dependence.

Cocaine Rapid Efficacy Screening Trials (CREST): lessons learned.

AIMS: The Cocaine Rapid Efficacy Screening Trials (CREST) were designed by the National Institute on Drug Abuse Division of Treatment Research and Development (NIDA, DT R&D) to rapidly screen a number of medications potentially useful for the treatment of cocaine dependence. DESIGN: Each CREST trial was designed to compare several medications in a single trial against an unmatched placebo. The placebo group was included in each trial to avoid the nearly universal positive response to medications seen in open-label trials. In addition, a common set of procedures and outcome measures were employed throughout to increase comparability of results obtained from different trials and from different times. PARTICIPANTS: In all, 18 medications were screened in seven different trials, conducted in four different sites throughout the United States involving 398 cocaine-dependent patients. FINDINGS: Three medications were found to be promising enough to include in subsequent larger trials. Common statistical procedures for evaluating medications were developed to facilitate comparisons across sites and across time. A portion of the data were pooled and analyzed, which yielded some useful insights into cocaine dependence and its treatment. Finally, a review of individual trials together with the pooled analysis revealed several potential improvements for future screening trials. CONCLUSIONS: Overall, the CREST trials proved to be useful for rapidly screening medications for treatment of cocaine dependence, but several modifications in design should be made before this framework is applied further.

A comprehensive assessment of the safety of intravenous methamphetamine administration during treatment with selegiline.

Selegiline (L-deprenyl) is a selective irreversible monoamine oxidase B inhibitor shown to be effective in the treatment of Parkinson's and Alzheimer's diseases. Recent evidence suggests that selegiline may also be useful in treating specific aspects of cocaine and nicotine dependence, generating interest in this compound for the treatment of methamphetamine addiction. To investigate this, we performed a randomized, single-blind, placebo-controlled study to evaluate the safety of selegiline treatment (as compared to placebo), concurrent with intravenous methamphetamine (15 or 30 mg). Secondary study objectives included determinations of plasma levels of selegiline and its metabolites, evaluating whether selegiline administration altered the pharmacokinetics of methamphetamine or its metabolites, and evaluating whether selegiline treatment alters the subjective responses to methamphetamine. Twenty-four methamphetamine-dependent participants were randomized to treatment, and 9 of these (N = 5 selegiline, N = 4 placebo) completed the entire protocol. The principal finding from this study was that intravenous administration of moderate doses of methamphetamine was safely tolerated during treatment with selegiline. No participants had electrocardiogram changes, and there were no meaningful differences in any laboratory values either between groups at screening or as a result of the study procedures. In general, adverse events were mild or moderate, and no subjects were discontinued due to adverse events or serious adverse events. Selegiline treatment did not enhance any of the cardiovascular changes (heart rate, blood pressure) produced by methamphetamine administration. Selegiline treatment slightly increased methamphetamine associated "bad effects" but did not alter any other subjective effects. The elimination half-life of methamphetamine was approximately 12 h, and selegiline did not alter clearance of methamphetamine. The available data suggest that selegiline is likely to be safe if used as a pharmacotherapy for methamphetamine dependence.

Two-year results of a randomized controlled trial of a health promotion program in a retiree population: the Bank of America Study.

OBJECTIVE: To evaluate the effectiveness of a health promotion program in a retiree population in terms of health risk reduction and reduction in medical costs. DESIGN: Randomized controlled trial. SUBJECTS: Bank of America retirees (n = 4,712), divided into 33 retiree club regions, were randomized into 3 groups and followed for 24 months by patient report and claims experience. Group 1, the intervention group, received a low-cost ($30/year), individualized, serially reinforcing health promotion program including risk appraisal, recommendation letters, and self-management materials, delivered entirely through the mail. Group 2 received risk appraisals only, without feedback, for the first 12 months and subsequently the full intervention for the second 12 months. Group 3 was followed with claims data only. Participation rates of 57% at 1 year and 47% at 2 years were achieved. MAIN RESULTS: Overall health risk scores improved by 12% at 12 months compared with control (p < 0.001) and by 23% (from baseline) at 24 months (p < 0.001). Individual health habit changes were favorable for all parameters studied, and were highly statistically significant for most variables. Similar health risk reductions were seen in age groups of 55 to 65 years, 65 to 75 years, and over 75. Cost reduction differences were more than 20% by self-report (p < 0.01) and 10% by claims experience (p = 0.02) at 12 months. For the randomized controlled period of the first 12 months, reductions averaged $164 in the intervention group contrasted with an average increase of $15 in the combined control groups. CONCLUSION: Risk reduction programs directed at retiree populations can improve health risk status and can reduce costs.

Unexpectedly high prevalence of posttransplant anemia in pediatric and young adult renal transplant recipients.

BACKGROUND: Although posttransplant anemia (PTA) is recognized as a common problem in adult renal transplant recipients, few pediatric studies have been published. METHODS: In this retrospective cohort study of 162 pediatric renal transplant recipients treated at Stanford University, the authors sought to determine the prevalence, severity, and the predictive factors of PTA. Anemia was defined as a hematocrit (HCT) level greater than 2 SD below published means for age or as erythropoietin dependency to maintain a normal HCT. RESULTS: Sixty-seven percent of pediatric renal transplant recipients were anemic at the time of transplantation. The prevalence of anemia increased to 84.3% in the first month posttransplant. From 6 months to 60 months posttransplant, the prevalence of anemia remained high at 64.2% to 82.2%. Only 4 patients (2.5%) were never anemic. Iron depletion was detected in 19 of 26 and 23 of 23 anemic patients 12 and 60 months posttransplant, respectively. Serum erythropoietin levels were low relative to hematocrit levels in 38 of 56 anemic patients. Logistic regression at 3 months posttransplant showed that discharge hematocrit level (P < 0.0001), calcium (P = 0.0004), and cyclosporine dose (P = 0.0002) correlated with anemia. Creatinine clearance (P = 0.002) and white blood cell count (P = 0.004) correlated with anemia at 12 months posttransplant, but only creatinine clearance (P = 0.011) correlated with anemia 60 months posttransplant. CONCLUSION: Nearly all pediatric renal transplant recipients experience PTA. However, few children less than 2 years of age were anemic during the first year posttransplant. Antirejection therapy, bone disease, iron depletion, and creatinine clearance appear to play pivotal roles in the development of PTA in children.

Lifestyle habits and compression of morbidity.

BACKGROUND: There has been much debate regarding the degree to which healthy lifestyles can increase longevity and whether added years will be offset by increased morbidity at older ages. This study was designed to test the compression of morbidity hypothesis, proposing that healthy lifestyles can reduce and compress disability into a shorter period toward the end of life. METHODS: Functional status in 418 deceased members of an aging cohort was observed between 1986 and 1998 in relationship to lifestyle-related risk factors, including cigarette smoking, physical inactivity, and under- or overweight. Three risk groups were created based on the number of these factors at study entry. Disability scores prior to death were modeled for each risk group to compare levels and rates of change, as well as to determine if and when acceleration in functional decline occurred. RESULTS: The risk-factor-free group showed average disability scores near zero 10-12 years before death, rising slowly over time, without evidence of accelerated functional decline. In contrast, those with two or more factors maintained a greater level of disability throughout follow-up and experienced an increase in the rate of decline 1.5 years prior to death. For those at moderate risk, the rate of decline increased significantly only in the last 3 months of life. Other differences between groups provided no alternative explanations for the findings. CONCLUSIONS: These results make a compelling argument for the reduction and postponement of disability with healthier lifestyles as proposed by the compression of morbidity hypothesis.

Comparison of the NovaSom QSG, a new sleep apnea home-diagnostic system, and polysomnography.

BACKGROUND: Obstructive sleep apnea (OSA) is a serious, common, and underdiagnosed disorder that challenges health care resources. While polysomnography (PSG) represents the standard diagnostic test for OSA, portable devices provide an alternative diagnostic tool when issues of cost, time, geographic availability, or other constraints pose impediments to in-lab testing. This study compares the NovaSom QSG, a new sleep apnea home diagnostic system, to PSG both in the laboratory and in the home. METHODS: Fifty-one consecutive adults referred to the sleep lab for suspicion of OSA underwent one night of in-lab, simultaneous recording of PSG and NovaSom QSG in addition to using the NovaSom QSG at home for three nights. Two separate comparisons were made using the apnea-hypopnea index (AHI): in-lab PSG to in-lab NovaSom QSG and in-lab PSG to home NovaSom QSG. RESULTS: Using a clinical cut-off of AHI=15, the sensitivity and specificity of the in-lab NovaSom QSG vs. PSG were 95% and 91%, respectively. For home NovaSom QSG vs. in-lab PSG, the sensitivity was 91% and specificity was 83%. The intra-class correlation coefficient for the agreement between three separate nights of NovaSom QSG home data was 0.88. CONCLUSIONS: In a patient population suspected of having OSA, the NovaSom QSG demonstrated acceptable sensitivity and specificity both in the lab and self-administered in the home, when compared to PSG.

Quantitative air-trapping analysis in children with mild cystic fibrosis lung disease.

The purpose of this study was to compare quantitative computed tomography air trapping (AT) and pulmonary function measurements between subjects with mild cystic fibrosis lung disease (MCF; forced expiratory volume in 1 sec (FEV1) > 70% predicted) and normal age-matched controls. Quantitative AT measurements at different levels of expiration were evaluated. Ten subjects from the MCF group and 10 normal subjects underwent inspiratory and expiratory spirometer-triggered chest high-resolution computed tomography (HRCT) and pulmonary function tests. Six matched CT images were obtained at full inflation and at a lung volume near residual volume (nRV). Quantitative measurements of AT were determined by evaluating expiratory CT lung density and by the percent of segmented lung which demonstrated AT on expiratory scans. Percent AT was evaluated for all lung slices combined (global AT), and also by regional assessment. Additional comparisons of lung density and percent air trapping were made in 10 CF subjects with three matched axial HRCT images at lung volumes corresponding to full inflation, near functional residual capacity (nFRC), and nRV. All measurements of expiratory lung density in CF subjects were significantly lower and % AT significantly higher than normal controls. Significant correlations for all subjects were observed between % global AT and RV/TLC as well as forced expiratory flow between 25-75% of forced vital capacity (FEF(25-75)) % predicted. Pulmonary density measurements and % AT better discriminated differences between groups than PFTs. Measurements made on expiratory scans near FRC showed significantly higher values for AT than those made near RV.

Positive surgical margin and perioperative complication rates of primary surgical treatments for prostate cancer: a systematic review and meta-analysis comparing retropubic, laparoscopic, and robotic prostatectomy.

CONTEXT: Radical prostatectomy (RP) approaches have rarely been compared adequately with regard to margin and perioperative complication rates. OBJECTIVE: Review the literature from 2002 to 2010 and compare margin and perioperative complication rates for open retropubic RP (ORP), laparoscopic RP (LRP), and robot-assisted LRP (RALP). EVIDENCE ACQUISITION: Summary data were abstracted from 400 original research articles representing 167,184 ORP, 57,303 LRP, and 62,389 RALP patients (total: 286,876). Articles were found through PubMed and Scopus searches and met a priori inclusion criteria (eg, surgery after 1990, reporting margin rates and/or perioperative complications, study size>25 cases). The primary outcomes were positive surgical margin (PSM) rates, as well as total intra- and perioperative complication rates. Secondary outcomes included blood loss, transfusions, conversions, length of hospital stay, and rates for specific individual complications. Weighted averages were compared for each outcome using propensity adjustment. EVIDENCE SYNTHESIS: After propensity adjustment, the LRP group had higher positive surgical margin rates than the RALP group but similar rates to the ORP group. LRP and RALP showed significantly lower blood loss and transfusions, and a shorter length of hospital stay than the ORP group. Total perioperative complication rates were higher for ORP and LRP than for RALP. Total intraoperative complication rates were low for all modalities but lowest for RALP. Rates for readmission, reoperation, nerve, ureteral, and rectal injury, deep vein thrombosis, pneumonia, hematoma, lymphocele, anastomotic leak, fistula, and wound infection showed significant differences between groups, generally favoring RALP. The lack of randomized controlled trials, use of margin status as an indicator of oncologic control, and inability to perform cost comparisons are limitations of this study. CONCLUSIONS: This meta-analysis demonstrates that RALP is at least equivalent to ORP or LRP in terms of margin rates and suggests that RALP provides certain advantages, especially regarding decreased adverse events.

Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES).

STUDY OBJECTIVE: To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA). DESIGN, SETTING, AND PARTICIPANTS: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures. INTERVENTION: Active or sham CPAP MEASUREMENTS: THREE NEUROCOGNITIVE VARIABLES, EACH REPRESENTING A NEUROCOGNITIVE DOMAIN: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F]) RESULTS: The primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test. CONCLUSIONS: CPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship. CLINICAL TRIAL INFORMATION: Registered at clinicaltrials.gov. Identifier: NCT00051363. CITATION: Kushida CA; Nichols DA; Holmes TH; Quan SF; Walsh JK; Gottlieb DJ; Simon RD; Guilleminault C; White DP; Goodwin JL; Schweitzer PK; Leary EB; Hyde PR; Hirshkowitz M; Green S; McEvoy LK; Chan C; Gevins A; Kay GG; Bloch DA; Crabtree T; Demen WC. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). SLEEP 2012;35(12):1593-1602.

Plasma disc decompression compared with fluoroscopy-guided transforaminal epidural steroid injections for symptomatic contained lumbar disc herniation: a prospective, randomized, controlled trial.

OBJECT: Patients with radiculopathy, with or without back pain, often do not respond to conservative care and may be considered for epidural steroid injection therapy or a disc decompression procedure. Plasma disc decompression (PDD) using the Coblation SpineWand device is a percutaneous, minimally invasive interventional procedure. The purpose of this study was to evaluate clinical outcomes with PDD as compared with standard care using fluoroscopy-guided transforaminal epidural steroid injection (TFESI) over the course of 2 years. METHODS: This was a multicenter randomized controlled clinical study. Ninety patients (18-66 years old) who had sciatica (visual analog scale score > or = 50) associated with a single-level lumbar contained disc herniation were enrolled. In all cases, their condition was refractory to initial conservative care and 1 epidural steroid injection had failed. Participants were randomly assigned to receive either PDD (46 patients) or TFESI (44 patients, up to 2 injections). RESULTS: The patients in the PDD Group had significantly greater reduction in leg pain scores and significantly improved Oswestry Disability Index and 36-Item Short Form Health Survey ([SF-36], physical function, bodily pain, social function, and physical components summary) scores than those in the TFESI Group. During the 2-year follow-up, 25 (56%) of the patients in the PDD Group and 11 (28%) of those in the TFESI Group remained free from having a secondary procedure following the study procedure (log-rank p = 0.02). A significantly higher percentage of patients in the PDD Group showed minimum clinically important change in scores for leg and back pain and SF-36 scores that exceeded literature-based minimum clinically important changes. Procedure-related adverse events, including injection site pain, increased leg or back pain, weakness, and lightheadedness, were observed in 5 patients in the PDD Group (7 events) and 7 in the TFESI Group (14 events). CONCLUSIONS: In study patients who had radicular pain associated with a contained lumbar disc herniation, those patients treated with PDD had significantly reduced pain and better quality of life scores than those treated using repeated TFESI. In addition, significantly more PDD patients than TFESI patients avoided having to undergo a secondary procedure during the 2-year study follow-up.