The Opioid Analgesic Reduction Study (OARS) Pilot: A Double-Blind Randomized Multicenter Trial.

BACKGROUND: With addiction rates and opioid deaths increasing, health care providers are obligated to help stem the opioid crisis. As limited studies examine the comparative effectiveness of fixed-dose combination nonopioid analgesia to opioid-containing analgesia, a comparative effectiveness study was planned and refined by conducting a pilot study. METHODS: The Opioid Analgesic Reduction Study (OARS) pilot, a stratified, randomized, multisite, double-blind clinical trial, was designed to test technology and procedures to be used in the full OARS trial. Participants engaged in the full protocol, enabling the collection of OARS outcome data. Eligible participants reporting to 1 of 5 sites for partial or full bony impacted mandibular third molar extraction were stratified by biologic sex and randomized to 1 of 2 treatment groups, OPIOID or NONOPIOID. OPIOID participants were provided 20 doses of hydrocodone 5 mg/acetaminophen 300 mg. NONOPIOID participants were provided 20 doses of ibuprofen 400 mg/acetaminophen 500 mg. OARS outcomes data, including pain experience, adverse effects, sleep quality, pain interference, overall satisfaction, and remaining opioid tablets available for diversion, were collected via surveys, electronic medication bottles, eDiary, and activity/sleep monitor. RESULTS: Fifty-three participants were randomized with 50 completing the OARS pilot protocol. Across all outcome pain domains, in all but 1 time period, NONOPIOID was better in managing pain than OPIOID (P < 0.05 level). Other outcomes suggest less pain interference, less adverse events, better sleep quality, better overall satisfaction, and fewer opioid-containing tablets available for diversion. DISCUSSION: Results suggest patients requiring impacted mandibular third molar extraction would benefit from fixed-dose combination nonopioid analgesia. KNOWLEDGE TRANSFER STATEMENT: Study results suggest fixed-dose nonopioid combination ibuprofen 400 mg/acetaminophen 500 mg is superior to opioid-containing analgesic (hydrocodone 5 mg/acetaminophen 500 mg). This knowledge should inform surgeons and patients in the selection of postsurgical analgesia.

Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial.

The phase 3, randomized Frontline Investigation of Revlimid and Dexamethasone Versus Standard Thalidomide (FIRST) trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response. Patients randomized 1:1:1 to Rd continuous, Rd18 or MPT were divided into subgroups based on best response: complete response (CR; n=290), ⩾very good partial response (VGPR; n=679), ⩾partial response (PR; n=1 225) or ⩽stable disease (n=299). Over 13% of patients receiving Rd continuous who achieved ⩾VGPR as best response did so beyond 18 months of treatment. Rd continuous reduced the risk of progression or death by 67%, 51% and 35% vs MPT in patients with CR, ⩾VGPR and ⩾PR, respectively. Similarly, Rd continuous reduced the risk of progression or death by 61%, 54% and 38% vs Rd18 in patients with CR, ⩾VGPR and ⩾PR, respectively. In patients with CR, ⩾VGPR or ⩾PR, 4-year survival rates in the Rd continuous arm (81.1%, 73.1% or 64.6%, respectively) were higher vs MPT (70.8%, 59.8% or 57.2%, respectively) and similar vs Rd18 (76.5%, 67.7% and 62.5%, respectively). Rd continuous improved efficacy outcomes in all responding patients, including those with CR, compared with fixed duration treatment.

Treatment outcomes for older patients with relapsed/refractory aggressive lymphoma receiving salvage chemotherapy and autologous stem cell transplantation are similar to younger patients: a subgroup analysis from the phase III CCTG LY.12 trial.

Background: High-dose therapy and autologous stem cell transplantation (ASCT) is often considered for older patients (age >60 years) with relapsed/refractory aggressive lymphomas. Although registry data support the safety and potential efficacy of this approach, there are no prospective trials evaluating outcomes of ASCT in older patients. We evaluated the result of second-line chemotherapy and ASCT in older versus younger patients in the CCTG randomized LY.12 trial. Patients and methods: From August 2003 to November 2011, 619 patients with relapsed/refractory aggressive lymphoma were randomized to gemcitabine, dexamethasone, cisplatin (GDP) or dexamethasone, cytarabine, cisplatin (DHAP); 177 patients (28.6%) enrolled were >60.0 years of age (range, 60-74) and 442 were ≤60.0 years of age. After two to three cycles, responding patients proceeded to ASCT. Intention-to-treat analysis was used to compare response rate, transplantation rate, event-free survival (EFS) and overall survival (OS) between patients aged ≤60.0 and >60.0 years. Results: Patient characteristics were comparable between the two cohorts, except a larger proportion of older patients had high International Prognostic Index risk scores. Response to salvage therapy was 48.6% for patients aged >60.0 versus 43.0% for those aged ≤60.0 (P = 0.21). Transplantation rates were also similar: 50.3% versus 49.8% (P = 0.87) for older versus younger patients. Rates of febrile neutropenia and adverse events requiring hospitalization were comparable for older and younger patients (30.5% versus 22.9% and 37.9% versus 32.1%, respectively). With a median follow-up of 53 months, there was no difference in 4-year OS (36% and 40% for patients aged >60.0 and ≤60.0 years, P = 0.42), or 4-year EFS (20% versus 28%, P = 0.43). Mortality from salvage therapy was 8/174 (4.60%) and 5/436 (1.15%), and 100-day mortality post-ASCT was 7/88 (8.06%) and 4/219 (1.85%). Conclusion: This subgroup analysis suggests that older patients derive similar benefit from salvage therapy and ASCT to younger patients, with acceptable toxicity. ClinicalTrials.gov Identifier: NCT00078949.

Impact of nucleation on step-meandering instabilities during step-flow growth on vicinal surfaces.

Step-meandering instabilities can manifest during step-flow growth on vicinal surfaces [Bales and Zangwill, Phys. Rev. B 41, 5500 (1990); Pierre-Louis, D'Orsogna, and Einstein, Phys. Rev. Lett. 82, 3661 (1999)]. A phase diagram based on the various growth regimes of a vicinal surface allows us to study the impact of nucleation on these meanders and to predict a meandering instability caused by the nucleation and the coalescence of both islands and steps. Using an accelerated kinetic Monte Carlo method, we find that the coalescence of islands with steps produces large protrusions and deep ripples and that the resulting meandering instability is reinforced by the growth of the islands at almost the same positions from one monolayer to the other. A coarsening phenomenon occurs for the instability wavelength until mounds appear, favored by a large Ehrlich-Schwoebel barrier. Such a meandering instability could be exploited for periodic self-assembly.

Carbon nanotubes as injection electrodes for organic thin film transistors.

We have investigated the charge injection efficiency of carbon nanotube electrodes for organic semiconducting layers and compared their performance to that of traditional noble metal electrodes. Our results reveal that charge injection from a single carbon nanotube electrode is more than an order of magnitude more efficient than charge injection from metal electrodes. Moreover, organic thin film transistors that use arrays of carbon nanotube electrodes display considerable effective mobilities (0.14 cm(2)/(V.s)) and nearly ideal linear output characteristics. These results indicate that carbon nanotubes should be considered a viable alternative to metal electrodes for next-generation organic field-effect transistors.

Destabilizing and stabilizing forces to assess equilibrium during everyday activities.

Postural stability is essential to functional activities. This paper presents a new model of dynamic stability which takes into account both the equilibrium associated with the body position over the base of support (destabilizing force) and the effort the subject needs to produce to keep his/her centre of mass inside the base of support (stabilizing force). The ratio between these two forces (destabilizing over stabilizing) is calculated to provide an overall index of stability for an individual. Preliminary results from data collected during walking at preferred and maximal safe speed in four older adults (aged from 64 to 84yr) showed that both forces are lower for subjects with reduced maximal gait speed. In addition, the stabilizing force increases by 2-3 times from preferred to maximal speed, while the destabilizing force barely changes with gait speed. Overall, the model through the index of stability attributes lower dynamic stability to subjects with lower maximal gait speed. These preliminary results call for larger-scale studies to pursue the development and validation of the model and its application to different functional tasks.

Effects of long jumps, reversible aggregation, and Meyer-Neldel rule on submonolayer epitaxial growth.

We demonstrate, using kinetic Monte Carlo simulations of submonolayer epitaxial growth, that long jumps and reversible aggregation have a major impact on the evolution of island morphologies. Long jumps are responsible for a supra-Arrhenius behavior of the effective diffusion coefficient as the attachment and detachment kinetics give rise to a bimodal island size distribution that depends on temperature and long jump extent limits. As the islands density increases with temperature, the average size of stable islands reaches a maximum before decreasing. We have also observed that the diffusion coefficient cannot be used alone to predict the evolution of island sizes and morphologies, the relative rate of each process having a major importance. Our theoretical developments are of direct relevance for materials systems such as Au, Pd, Ag, Cu, Ni, H/Si , H/W(110), Co/Ru , and Co/Ru(S), that are known for exhibiting a compensation effect that cannot be contained within experimental uncertainties.

Electroluminescence from single-wall carbon nanotube network transistors.

The electroluminescence (EL) properties from single-wall carbon nanotube network field-effect transistors (NNFETs) and small bundle carbon nanotube field effect transistors (CNFETs) are studied using spectroscopy and imaging in the near-infrared (NIR). At room temperature, NNFETs produce broad (approximately 180 meV) and structured NIR spectra, while they are narrower (approximately 80 meV) for CNFETs. EL emission from NNFETs is located in the vicinity of the minority carrier injecting contact (drain) and the spectrum of the emission is red shifted with respect to the corresponding absorption spectrum. A phenomenological model based on a Fermi-Dirac distribution of carriers in the nanotube network reproduces the spectral features observed. This work supports bipolar (electron-hole) current recombination as the main mechanism of emission and highlights the drastic influence of carrier distribution on the optoelectronic properties of carbon nanotube films.

Self-organization of InAs/InP quantum dot multilayers: pseudophase diagram describing the transition from aligned to antialigned structures.

Based on experimental observations for the InAs/InP(001) system and atomistic strain calculations using Keating's valence force field method, we propose a pseudophase diagram describing the regimes of 3D self-organization in quantum dot (QD) multilayers. The combined experimental and theoretical analyses--varying the spacer thickness (H), QD height (h), base (b), and lateral spacing (D)--indicate that the vertically aligned to antialigned transition occurs for a critical value of H/D which increases weakly with b/D, while varying h has virtually no effect on the transition point.

A chair with a platform setup to measure the forces under each thigh when sitting, rising from a chair and sitting down.

This paper describes the design, technical characteristics and first results of an adjustable instrumented chair with a sitting surface that records the forces under each thigh. The seat includes a force platform assembly suitable for measuring the magnitude, position and direction of the force applied to each thigh while sitting or rising from the chair. The natural frequency of the chair fixed to the floor was found to be 14.0 +/- 2 Hz with an estimated damping of xi = 0.20. Static tests showed that the maximal errors were 2% of the full-scale output (726 N vertically, 164 N horizontally) for both vertical and horizontal forces. The root mean square error of the center of pressure location was estimated as 5 mm. Preliminary data on the net joint moment at the hips of one healthy subject computed with and without consideration for the forces under the thighs revealed significant amplitude differences. In conclusion, the results indicate that the characteristics of the instrumented chair are acceptable and the chair can be used to assess the biomechanics of sitting and sit-to-stand and stand-to-sit tasks in various subject populations.

Mechanism of the far-infrared absorption of carbon-nanotube films.

The far-infrared conductivity of single-wall carbon-nanotube ensembles is dominated by a broad absorption peak around 4 THz whose origin is still debated. We observe an overall depletion of this peak when the nanotubes are excited by a short visible laser pulse. This finding excludes optical absorption due to a particle-plasmon resonance and instead shows that interband transitions in tubes with an energy gap of approximately 10 meV dominate the far-infrared conductivity. A simple model based on an ensemble of two-level systems naturally explains the weak temperature dependence of the far-infrared conductivity by the tube-to-tube variation of the chemical potential.

Evaluation of a hybrid system for three-dimensional measurement of trunk posture in motion.

Ambulatory assessment of trunk posture is important in improving our understanding of the risk of low back injury. Recently, small inertial sensors combining accelerometers, gyroscopes and magnetometers were developed and appear to be promising for measuring human movement. However, the validity of such sensors for assessing three-dimensional (3D) trunk posture in motion has not been documented. The purpose of this study was to evaluate a hybrid system (HS) composed of two inertial sensors for the 3D measurement of trunk posture. A secondary purpose was to explore the utility of adding another source of information, a potentiometer, to measure the relative rotation between both sensors in order to improve the validity of the system. The first sensor was placed over the sacrum and the second on the upper part of the thorax. Both sensors were linked by a flexible rod with a potentiometer. A complementary quaternion filter algorithm was used to estimate trunk orientation by taking advantage of the nine components of each sensor and the potentiometer. The HS's orientations were compared to those obtained from a 3D optoelectronic system. Validation of the HS was performed in three steps in which six subjects had to perform manual handling tasks in: (1) static postures; (2) dynamic motions of short duration (30s); and (3) dynamic motions of long duration (30min). The results showed that the root mean square (RMS) error of the HS was generally below 3 degrees for the flexion and lateral bending axes, and less than 6 degrees for the torsion axis, and that this error was lower for the short-duration tests compared to the long-duration one. The potentiometer proved to be an essential addition, particularly when the magnetometer signals were corrupted and only the gyroscope and accelerometer could be combined. It is concluded that the HS can be a useful tool for quantifying 3D trunk posture in motion.

Ultrafast dynamics of delocalized and localized electrons in carbon nanotubes.

We report on the dynamics of the dielectric function of single-wall carbon nanotubes in the 10-30 THz frequency range after ultrafast laser excitation. The absence of a distinct free-carrier response is attributed to the photogeneration of strongly bound excitons in the tubes with large energy gaps. We find a feature of enhanced transmission caused by the blocking of optical transitions in small-gap tubes. The rapid decay of a featureless background with pronounced dichroism is associated with the increased absorption of spatially localized charge carriers before thermalization is completed.

The analgesic efficacy of intramuscular parecoxib sodium in postoperative dental pain.

BACKGROUND: The parenteral cyclo-oxygenase, or COX, -2 selective inhibitor parecoxib sodium in a 40-milligram dose for intravenous/intramuscular, or i.v./i.m., administration is approved for postoperative pain in Europe, but not yet in the United States. However, previous trials in dental surgical patients have indicated that lower doses may be as effective. METHODS: The authors enrolled 353 patients in a single-center, double-blind, placebo-controlled, dose-ranging study to compare the efficacy and tolerability of single i.m. doses of parecoxib (1-20 mg) with ketorolac tromethamine 30 mg i.m. after dental surgery. Pain assessments occurred at baseline and through 24 hours postdose. RESULTS: A 20-mg dose of parecoxib was significantly more effective than were 1-mg to 10-mg doses and than placebo. The analgesic onset of a 20-mg dose of parecoxib was similar to that of a 30-mg dose of ketorolac. The magnitude of analgesia with a 20-mg dose of parecoxib was significantly lower than that with ketorolac, according to the mean pain intensity difference, or PID, scores from one and one-half to four hours postdose or summed PID, or SPID, -categorical scores at six hours postdose. However, there was no significant difference in mean pain relief; total pain relief, or TOTPAR; and SPID-visual analog scale, or VAS, scores six hours postdose. Mean PID scores for parecoxib 20 mg from 12 to 24 hours postdose were significantly higher than and SPID-VAS mean scores were not statistically significantly different from eight hours onward. CONCLUSIONS: Parecoxib 20 mg i.m. is an effective analgesic dose with an onset and magnitude of analgesic effect approaching that of ketorolac 30 mg i.m. after dental surgery. It also is well-tolerated. CLINICAL IMPLICATIONS: These findings support the use of parecoxib 20 mg i.m. as an initial dosing option for postoperative pain management in countries in which it is approved.

Docetaxel and Gemcitabine administered on days 1 and 8 for metastatic non-small cell lung carcinoma (NSCLC): a phase II multicenter trial.

Docetaxel and Gemcitabine are active agents in non-small cell lung carcinoma (NSCLC). They have different mechanism of action, minimal overlapping toxicity, and are easily administered on an outpatient basis. This phase II study evaluated Docetaxel administered with Gemcitabine on days 1 and 8 in a 3-week cycle, to determine its efficacy, while attempting to lower the regimen's toxicity, especially myelosuppression which can occur when Docetaxel is administered at full dose on day 1 only. Forty-three chemonaive patients, 40 evaluable, were entered in this trial between May 2001 and March 2002. Thirty-seven patients had stage IV and three patients had stage III B NSCLC, median age 58 (ages 32-78), median performance status (PS) 1 (range 0-2). They were treated with Docetaxel 36mg/m(2) and Gemcitabine 1000mg/m(2) intravenously on days 1 and 8 in a 3-week cycle. No growth factors were administered. Of 40 evaluable patients, 4 achieved partial response (10%), 25 stable disease (62.5%) and 11 progressive disease (27.5%). Median time-to-disease progression was 15 weeks. Median survival was 7.75 months. One year survival was 32.5% (13 patients). Hematologic toxicity was minimal, non-hematologic toxicity was easily treatable. Docetaxel, when given with Gemcitabine on days 1 and 8 every 3 weeks, is less myelotoxic, yet still an effective treatment for metastatic NSCLC.

Back muscle fatigue during intermittent prone back extension exercise.

UNLABELLED: The purpose of this study was to estimate the level of muscular activation and muscle fatigue of the low back muscles during the performance of an intermittent prone back extension (PBE) exercise. Forty-one healthy students (24 males and 17 females) lying prone on a bench with the legs fixed performed two maximal voluntary contractions (MVC) in extension, a maximum of 100 repetitions of an intermittent PBE exercise immediately followed by a final MVC in extension. In addition, 12 subjects (11 males and one female) repeated the PBE exercise but with the addition of a 45-N weight on the back. The PBE exercise consisted of a task broken into four 1-s segments, while lying prone on a bench (10 degrees below horizontal): (1) raising the trunk to a horizontal position; (2) holding the trunk in the static phase (10 degrees above horizontal); (3) returning to the original position; and (4) resting on the bench. Electromyography (EMG) was used to measure the level of muscle activity (erector spinae (ES), gluteus maximus (GM), hamstrings (HA)) relative to the maximum voluntary EMG (MVE). RESULTS: Most of the subjects (34 out of 41) completed the 100 repetitions without excessive muscle fatigue according to the post-exercise MVC values. The intermittent PBE increased fatigue in the lumbar and hip extensor muscles in terms of: (1) a decrease in the MVC; (2) an increase in the level of muscle activation; and (3) a decline of the median frequency (MF). There was no gender difference in all EMG measurements. The level of muscle activation in the hip extensors (GM and HA) was associated with task failure (number of repetitions <100) for some subjects and the addition of a weight of 45 N had more impact on HA than ES. In conclusion, the PBE exercise as performed in the present study (including rest intervals), although not very strenuous for our healthy subjects, seems an adequate exercise to measure and train the aerobic capacity of the back muscles. However, to train specifically the back muscles, the exercise must be adjusted to avoid task failure due to possible hip extensor fatigue.

Estimated moments at L5/S1 level and muscular activation of back extensors for six prone back extension exercises in healthy individuals.

The purpose of this study was to identify the prone back extension (PBE) exercises that offer the most resistance to the back extensor muscles. Twenty males with no previous history of low back injury performed two repetitions of eight exercises. These consisted of two maximal isometric voluntary activations (MVA) and six different PBE exercises. The participants, while lying prone on a bench, were asked to raise either their trunk or legs to the horizontal position and hold for one second (static phase) before returning to the original position. The exercises differed according to the particular segments that were raised into extension. To assess the PBE exercises, a biomechanical model was used to estimate the level of load resistance (%MVA) relative to the maximum voluntary activation strength (MVA). In addition, electromyography (EMG) was included to measure the level of muscle activity (%MVE) relative to the maximum voluntary activation EMG (MVE) value reached during the MVA. A significant relationship of 0.86 was found between the mass of the subject and the peak reaction moment during the MVA. Peak level of load resistance averaged around 50% MVA with the exception of exercise no. 5 where the subject had to raise in extension his trunk, legs and arms (65% MVA). The erector spinae (ES) activity level reached a peak value of 61% MVE for exercise no. 5. In the exercises where only the trunk was lifted, the peak level of ES was below 47% MVE and the average activity during the static phase reached approximately 26% MVE. For healthy individuals PBE exercises can be considered low intensity exercises (< 50% MVA; except exercise no. 5) and can be used to improve the endurance of the back muscles.

Handling missing marker coordinates in 3D analysis.

The use of mathematical formulations to retrieve missing data is not usually implemented as an automated computer procedure. The purpose of this paper is to present a simple mathematical formulation that can be used to retrieve the coordinates of markers hidden during a task. A strategy based on the smoothness of the variation of distance between points is devised, which leads to an automated computer procedure for retrieving hidden skin markers or missing joint coordinates (missing 3D points). This approach has the advantage of not being restricted to the usual rigid-body assumption.