Study design considerations for the Standardized Treatment of Pulmonary Exacerbations 2 (STOP2): A trial to compare intravenous antibiotic treatment durations in CF

BACKGROUND: Pulmonary exacerbations (PEx) in cystic fibrosis (CF) are common and contribute to morbidity and mortality. Duration of IV antibiotic therapy to treat PEx varies widely in the US, and there are few data to guide treatment decisions. METHODS: We combined a survey of CF stakeholders with retrospective analyses of a recent observational study of CF PEx to design a multicenter, randomized, prospective study comparing the efficacy and safety of different durations of IV antibiotics for PEx to meet the needs of people with CF and their caregivers. RESULTS: IV antibiotic duration was cited as the most important PEx research question by responding CF physicians and top concern among surveyed CF patients/caregivers. During PEx, forced expiratory volume in 1s (FEV1% predicted) and symptom responses at 7-10days of IV antibiotics identified two distinct groups: early robust responders (ERR) who subsequently experienced greater FEV1 improvements compared to non-ERR (NERR). In addition to greater FEV1 and symptom responses, only 14% of ERR patients were treated with IV antibiotics for >15days, compared with 45% of NERR patients. CONCLUSIONS: A divergent trial design that evaluates subjects' interim improvement in FEV1 and symptoms to tailor randomization to IV treatment duration (10 vs. 14days for ERR, 14 vs. 21days for NERR) may alleviate physician and patient concerns about excess or inadequate treatment. Such a study has the potential to provide evidence necessary to standardize IV antibiotic duration in CF PEx care -a first step to conducting PEx research of other treatment features

Control of a Glove-Based Grasp Assist Device

A grasp assist system includes a glove and sleeve. The glove includes a digit, i.e., a finger or thumb, and a force sensor. The sensor measures a grasping force applied to an object by an operator wearing the glove. The glove contains a tendon connected at a first end to the digit. The sleeve has an actuator assembly connected to a second end of the tendon and a controller in communication with the sensor. The controller includes a configuration module having selectable operating modes and a processor that calculates a tensile force to apply to the tendon for each of the selectable operating modes to assist the grasping force in a manner that differs for each of the operating modes. A method includes measuring the grasping force, selecting the mode, calculating the tensile force, and applying the tensile force to the tendon using the actuator assembly

Photonics

Contains reports on seven research projects.Air Force Rome Air Development Center (in collaboration with C.C. Leiby, Jr.)U.S. Air Force-Rome Air Development Center (Contract F19628-80-C-0077)National Science Foundation (Grant PHY79-09739)Joint Services Electronics Program (Contract DAAG29-80-C-0104)U.S. Air Force Geophysics Laboratory (Contract F19628-79-C-0082

Quantum Electronics

Contains reports on eleven research projects.Air Force Rome Air Development Center (in collaboration with C.C. Leiby Jr)U.S. Air Force - Rome Air Development Center (Contract F19628-80-C-0077)National Science Foundation (Grant PHY79-09739)Joint Services Electronics Program (Contract DAAG29-80-C-0104)Air Force Geophysics Laboratory (Contract F 19628-79-C-0082)National Science Foundation (Grant DAR80-08752)National Science Foundation (Grant ECS79-19475)National Science Foundation (Grant ECS80-17705)National Science Foundation (Grant ENG79-09980

3,4-Diaminopyridine Base Effectively Treats the Weakness of Lambert-Eaton Myasthenia

Introduction: 3,4-diaminopyridine has been used to treat Lambert Eaton myasthenia (LEM) for thirty years despite the lack of conclusive evidence of efficacy. Methods: We conducted a randomized double-blind placebo-controlled withdrawal study in LEM patients who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for ≥ 3 months. The primary efficacy endpoint was >30% deterioration in Triple Timed Up-and-Go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self-assessment of LEM–related weakness (W-SAS). Results: 32 participants were randomized to continuous 3,4-DAP or placebo. None of the 14 receiving continuous 3,4-DAP had >30% deterioration in 3TUG time vs 72% of the 18 who tapered to placebo (p<0.0001). W-SAS similarly demonstrated an advantage for continuous treatment over placebo (p<0.0001). Need for rescue and adverse events were more common in the placebo group. Discussion: This trial provides significant evidence of efficacy of 3,4-DAP in the maintenance of strength in LEM

Quantum Electronics

Contains thirteen research projects split into three sections.U.S. Air Force - Rome Air Development Center (Contract F19628-80-C-0077)National Science Foundation (Grant PHY79-09739)Joint Services Electronics Program (Contract DAAG29-78-C-0020)Joint Services Electronics Program (Contract DAAG29-80-C-0104)U.S. Air Force Geophysics Laboratory (AFSC) (Contract F19628-79-C-0082)National Science Foundation (Grant ECS79-19475)National Science Foundation (Grant DAR80-08752)National Science Foundation (Grant ENG79-09980

Validation of the triple timed up‐and‐go test in Lambert‐Eaton myasthenia

Introduction There are no validated, practical, and quantitative measures of disease severity in Lambert‐Eaton myasthenia (LEM). Methods Data from the Effectiveness of 3,4‐Diaminopyridine in Lambert‐Eaton Myasthenic Syndrome (DAPPER) trial were analyzed to assess triple timed up‐and‐go (3TUG) reproducibility and relationships between 3TUG times and other measures of LEM severity. Results The coverage probability technique showed ≥0.90 probability for an acceptable 3TUG difference of ≤0.2, indicating that it is reproducible in LEM patients. The correlation between 3TUG times and lower extremity function scores was significant in subjects who continued and in those who were withdrawn from 3,4‐diaminopyridine free base. Worsening patient‐reported Weakness Self‐Assessment Scale and Investigator Assessment of Treatment Effect scores corresponded with prolongation of 3TUG times. Discussion The 3TUG is reproducible, demonstrates construct validity for assessment of lower extremity function in LEM patients, and correlates with changes in patient and physician assessments. These findings, along with prior reliability studies, indicate 3TUG is a valid measure of disease severity in LEM

The HETDEX Pilot Survey III: The Low Metallicities of High-Redshift Lyman Alpha Galaxies

We present Keck/NIRSPEC spectroscopic observations of three Lyman alpha emitting galaxies (LAEs) at z ~ 2.3 discovered with the HETDEX pilot survey. We detect Halpha, [OIII], and Hbeta emission from two galaxies at z = 2.29 and 2.49, designated HPS194 and HPS256, respectively, representing the first detection of multiple rest-frame optical emission lines in galaxies at high-redshift selected on the basis of their Lyman alpha emission. The redshifts of the Lyman alpha emission from these galaxies are offset redward of the systemic redshifts by Delta_v = 162 +/- 37 (photometric) +/- 42 (systematic) km/s for HPS194, and Delta_v = 36 +/- 35 +/- 18 km/s for HPS256. An interpretation for HPS194 is that a large-scale outflow may be occurring in its interstellar medium. The emission line ratios imply that neither LAE hosts an active galactic nucleus. Using the upper limits on the [NII] emission we place meaningful constraints on the gas-phase metallicities in these two LAEs of Z < 0.17 and < 0.28 Zsol (1 sigma). Measuring the stellar masses of these objects via spectral energy distribution (SED) fitting (~ 10^10 and 6 x 10^8 Msol, respectively), we study the nature of LAEs in a mass-metallicity plane. At least one of these two LAEs appears to be more metal poor than continuum-selected star-forming galaxies at the same redshift and stellar mass, implying that objects exhibiting Lyman alpha emission may be systematically less chemically enriched than the general galaxy population. We use the SEDs of these two galaxies to show that neglecting the emission lines when fitting stellar population models to the observed photometry can result in overestimates of the population age by orders of magnitude, and the stellar mass by a factor of ~ 2. This effect is particularly important at z > 7, where similarly strong emission lines may masquerade in the photometry as a 4000 A break (abridged).Comment: Replaced with the accepted (to ApJ) versio