Blinded Data Analysis Research Articles

Search for Weakly Interacting Massive Particles with the First Five-Tower Data from the Cryogenic Dark Matter Search at the Soudan Underground Laboratory

We report results from the Cryogenic Dark Matter Search at the Soudan Underground Laboratory (CDMS II) featuring the full complement of 30 detectors. A blind analysis of data taken between October 2006 and July 2007 sets an upper limit on the weakly interacting massive particle (WIMP) nucleon spin-independent cross section of 6.6x10;{-44} cm;{2} (4.6x10;{-44} cm;{2} when combined with previous CDMS II data) at the 90% confidence level for a WIMP mass of 60 GeV/c;{2}. This achieves the best sensitivity for dark matter WIMPs with masses above 44 GeV/c;{2}, and significantly restricts the parameter space for some favored supersymmetric models.

Ventilation Strategy Using Low Tidal Volumes, Recruitment Maneuvers, and High Positive End-Expiratory Pressure for Acute Lung Injury and Acute Respiratory Distress Syndrome

Low-tidal-volume ventilation reduces mortality in critically ill patients with acute lung injury and acute respiratory distress syndrome. Instituting additional strategies to open collapsed lung tissue may further reduce mortality. To compare an established low-tidal-volume ventilation strategy with an experimental strategy based on the original "open-lung approach," combining low tidal volume, lung recruitment maneuvers, and high positive-end-expiratory pressure. Randomized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada, Australia, and Saudi Arabia. Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250. The control strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau airway pressures not exceeding 30 cm H2O, and conventional levels of positive end-expiratory pressure (n = 508). The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau pressures not exceeding 40 cm H2O, recruitment maneuvers, and higher positive end-expiratory pressures (n = 475). All-cause hospital mortality. Eighty-five percent of the 983 study patients met criteria for acute respiratory distress syndrome at enrollment. Tidal volumes remained similar in the 2 groups, and mean positive end-expiratory pressures were 14.6 (SD, 3.4) cm H2O in the experimental group vs 9.8 (SD, 2.7) cm H2O among controls during the first 72 hours (P < .001). All-cause hospital mortality rates were 36.4% and 40.4%, respectively (relative risk [RR], 0.90; 95% confidence interval [CI], 0.77-1.05; P = .19). Barotrauma rates were 11.2% and 9.1% (RR, 1.21; 95% CI, 0.83-1.75; P = .33). The experimental group had lower rates of refractory hypoxemia (4.6% vs 10.2%; RR, 0.54; 95% CI, 0.34-0.86; P = .01), death with refractory hypoxemia (4.2% vs 8.9%; RR, 0.56; 95% CI, 0.34-0.93; P = .03), and previously defined eligible use of rescue therapies (5.1% vs 9.3%; RR, 0.61; 95% CI, 0.38-0.99; P = .045). For patients with acute lung injury and acute respiratory distress syndrome, a multifaceted protocolized ventilation strategy designed to recruit and open the lung resulted in no significant difference in all-cause hospital mortality or barotrauma compared with an established low-tidal-volume protocolized ventilation strategy. This "open-lung" strategy did appear to improve secondary end points related to hypoxemia and use of rescue therapies. clinicaltrials.gov Identifier: NCT00182195.

Lapatinib (L) with paclitaxel compared to paclitaxel as first-line treatment for patients with metastatic breast cancer: A phase III randomized, double-blind study of 580 patients

1011 Background: L is an oral tyrosine kinase inhibitor of EGFR/HER2, active as monotherapy and in combination for HER2-overexpressing advanced/metastatic breast cancer (BC). A Phase I study of L with paclitaxel (P) indicated no unexpected adverse events (AEs). PK profile indicated no relationship between peak plasma concentration of P+L and neuropathy, neutropenia, diarrhea, rash or myalgia. We report here blinded efficacy and safety data for patients (pts) with incurable Stage IIIb/IIIc/IV BC at first diagnosis or relapse, untested or negative (0/1+ IHC or FISH neg) for HER2. Unblinded data will be presented at ASCO 2007. Methods: Between Jan 2004 and Jul 2005, 580 pts from 24 countries were stratified by metastatic site and randomized 1:1 to L 1500 mg QD + 175 mg/m2 P q3w or placebo QD + 175 mg/m2 P q3w. Primary endpoint was TTP; secondary endpoints were AEs, ORR, PFS, CBR, RFS, and OS. Tumor tissue was obtained from the most recent biopsy of 451 (78%) pts and was centrally analyzed in blinded fashion for biomarker patterns. Serum samples were collected for central EGFR and HER2 ECD analysis. Results and Conclusions: 579 pts were analyzed; 87% presented with Stage IV BC. 55% received prior adjuvant chemotherapy or anti-hormonal therapy. No pts received previous trastuzumab. At the time of analysis, 561 (97%) pts progressed or otherwise withdrew. Most common AEs were alopecia (58%), neurological (55%, gr=3:8%), diarrhea (42%, gr=3:9%), nausea (32%), and rash (32%, gr=3:2%). Neutropenia and thrombocytopenia AEs related to study treatment were 18% and &lt;1%, respectively. LVEF decrease of 20% relative to baseline and below LLN was reported 15 times. 12% of AEs led to treatment withdrawal. Blinded data analysis revealed a median TTP of 25 wks and ORR of 30%. CNS relapse was reported in 11 pts (2%). Enrollment predominantly came from countries with limited HER2 testing capacity thus a subgroup of pts is expected to be HER2+ve. Blinded analyses of HER2, ER and PR are ongoing at this time and final biomarker evaluations will be presented with unblinded efficacy data. [Table: see text]

Twenty minutes versus forty-five minutes morning bright light treatment on sleep onset insomnia in elderly subjects

Objective To compare the efficacy of 20 min versus 45 min light exposure for relieving psychophysiological insomnia in the elderly. Methods Prospective recruitment of subjects 60 years and older with psychophysiological insomnia. Random distribution to 20 or 45 min of daily exposure to 10,000 lux for 60 days. Sleep latency, total sleep time, fatigue and activity were measured at baseline and 3 and 6 months posttreatment. Blind analysis of data and comparison were performed using repeated-measure analysis of variance, independent samples t test and Wilcoxon rank signed test. Results At 3 months, improvement was significantly higher in the 45-min versus 20-min condition. At 6 months, variables returned toward baseline in the 20-min but not in the 45-min condition. Conclusions Twenty minutes of bright light treatment leads to a lesser treatment response than 45 min at 3-month follow-up and to a return toward baseline at 6-month follow-up that was not seen with a 45-min exposure.

Education of the trauma team: video evaluation of the compliance with universal barrier precautions in resuscitation.

To assess the effectiveness of an educational symposium designed to improve compliance with universal barrier precautions by the use of video analysis of resuscitations. Prospective single blind analysis of data. Hospital Trauma Unit, Johannesburg, South Africa. 100 severely injured patients who presented to the emergency room, divided into two study periods. An educational symposium held between the study periods, which focused on universal barrier precautions and the risk of occupational transmission of HIV. Compliance with items of universal precautions; mechanism; Injury Severity Score and Revised Trauma Score. There was a significant improvement in compliance from 48% to 74% after the symposium (p = 0.007), with specific improvement in the wearing of masks and visors. Initially there was poor compliance with universal precautions in severely injured patients, which significantly improved to 83% compliance (p = 0.0004). Video analysis of resuscitations is an effective audit and educational tool that allows analysis of compliance with protocol. The education symposium was effective in altering attitudes and behaviour towards universal barrier precautions.

The subcutaneous heparin and angioplasty restenosis prevention (SHARP) trial: Results of a multicenter randomized trial investigating the effects of high dose unfractionated heparin on angiographic restenosis and clinical outcome

We sought to determine whether 12,500 IU of unfractionated heparin given subcutaneously twice daily for 4 months after percutaneous transluminal coronary angioplasty beneficially influences the subsequent rate of angiographic restenosis and the incidence of clinical events. Heparin has been shown to exhibit powerful antiproliferative effects against smooth muscle cells in several animal models. A randomized trial with blinded data analysis was undertaken to assess the effect of unfractionated subcutaneous heparin on angiographic restenosis after coronary angioplasty. After successful angioplasty, patients were randomized to receive no heparin or 12,500 IU of heparin given subcutaneously twice daily for 4 months. Quantitative coronary angiography was performed before angioplasty, immediately after angioplasty and at follow-up ("early" [before 4 months] or electively [at 4 months]). The study group comprised 339 patients, 167 randomly assigned to receive heparin, 172 to receive no heparin. Repeat cardiac catheterization was performed in 90% of randomized patients. At early and elective restudy (mean 4.2 months), the mean +/- SD difference in minimal lumen diameter between the postangioplasty and follow-up measurement was -0.55 +/- 0.58 mm for the no heparin group and -0.43 +/- 0.59 mm for the heparin group (p = NS). Clinical events during the follow-up period did not differ significantly between groups: fatal myocardial infarction (1 patient in each group), coronary bypass grafting (5 patients in each group), repeat angioplasty (12 in the no heparin, 6 in the heparin group), angina at 4-month assessment (33% in the no heparin, 32% in the heparin group). Long-term treatment with high dose subcutaneous heparin (12,500 IU twice daily) for 4 months did not favorably influence angiographic or clinical outcome after coronary angioplasty.

Amelioration of ischemia during angioplasty of the left anterior descending coronary artery with an autoperfusion catheter

A new autoperfusion balloon angioplasty catheter with sideholes proximal and distal to the balloon—facilitating distal blood flow during inflation—was compared with standard angioplasty catheters in a prospective, randomized study with blinded data analysis. Hemodynamic and electrocardiographic markers of ischemia after 1 minute of standard or autoperfusion catheter inflations were compared with ischemia after control inflation with standard balloons. In the patient group randomized to standard balloon inflation only, ST-segment elevation after control inflation with a standard balloon catheter was 0.37 ± 0.04 mV; ST-segment elevation after final balloon inflation with a standard catheter was unchanged at 0.35 ± 0.04 mV (difference not significant). In the group randomized to the auto-perfusion catheter, control inflation with a standard catheter resulted in 0.48 ± 0.1 mV ST elevation; final inflation with the autoperfusion catheter demonstrated 0.16 ± 0.09 mV ST elevation (p < 0.005). Autoperfusion catheter inflation was continued for 2 minutes without change in electrocardiographic findings: ST segments remained at 0.08 ± 0.03 mV, unchanged from 0.07 ± 0.03 mV before angioplasty (difference not significant). Thus, while coronary angioplasty performed with standard catheters resulted in marked ST-segment elevation, in patients undergoing angioplasty with the autoperfusion catheter, ischemia was generally not seen, despite sustained balloon inflation for 2 minutes.