Background: Tibial shaft fractures are the most common long-bone injury, with a reported annual incidence of more than 75 000 in the United States. This study aimed to determine whether patients with ...tibial fractures managed with intramedullary nails experience a lower rate of reoperation if treated at higher-volume hospitals, or by higher-volume or more experienced surgeons. Methods: The Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures (SPRINT) was a multicentre randomized clinical trial comparing reamed and nonreamed intramedullary nailing on rates of reoperation to promote fracture union, treat infection or preserve the limb in patients with open and closed fractures of the tibial shaft. Using data from SPRINT, we quantified centre and surgeon volumes into quintiles. We performed analyses adjusted for type of fracture (open v. closed), type of injury (isolated v. multitrauma), gender and age for the primary outcome of reoperation using multivariable logistic regression. Results: There were no significant differences in the odds of reoperation between high-and low-volume centres (p = 0.9). Overall, surgeon volume significantly affected the odds of reoperation (p = 0.03). The odds of reoperation among patients treated by moderate-volume surgeons were 50% less than those among patients treated by very-low-volume surgeons (odds ratio OR 0.50, 95% confidence interval CI 0.28-0.88), and the odds of reoperation among patients treated by high-volume surgeons were 47% less than those among patients treated by very-low-volume surgeons (OR 0.53, 95% CI 0.30-0.93). Conclusion: There appears to be no significant additional patient benefit in treatment by a higher-volume centre for intramedullary fixation of tibial shaft fractures. Additional research on the effects of surgical and clinical site volume in tibial shaft fracture management is needed to confirm this finding. The odds of reoperation were higher in patients treated by very-low-volume surgeons; this finding may be used to optimize the results of tibial shaft fracture management. Clinical trial registration: ClinicalTrials.gov, NCT00038129 Contexte: La fracture de la diaphyse tibiale est la plus commune des fractures des os longs, avec une incidence annuelle declaree de plus 75 000 cas aux Etats-Unis. Cette etude visait a determiner si les patients traites par enclouage intra-medullaire pour une fracture du tibia sont moins souvent reoperes quand l'intervention est effectuee dans des etablissements qui traitent de plus forts volumes de cas ou par des chirurgiens operant un plus fort volume de cas ou plus experimentes. Methodes: L'etude SPRINT (Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures) est un essai clinique multicentrique randomise qui a compare l'effet de l'enclouage alese c. non alese sur le taux des reinterventions visant a promouvoir la consolidation osseuse de la fracture, a traiter une infection ou a preserver le membre chez des patients victimes de fractures fermees ou ouvertes de la diaphyse tibiale. A partir des donnees de l'etude SPRINT, nous avons classe les etablissements et les chirurgiens en quintiles selon les volumes de cas traites. Nous avons effectue des analyses ajustees en fonction du type de fracture (ouverte c. fermee), du type de blessure (isolee c. polytraumatisme), du sexe et de l'age, pour etablir le taux de reintervention (parametre principal), en utilisant la regression logistique multivariee. Resultats: On n'a note aucune difference significative quant au risque de reinter-vention entre les centres qui traitaient des volumes eleves c. bas (p = 0,9). Dans l'ensemble le volume d'operations des chirurgiens a significativement influe sur le risque de reintervention (p = 0,03). Le risque de reintervention chez les patients traites par des chirurgiens dont le volume d'interventions etait moyen etait de 50 % de moins que chez les patients traites par des chirurgiens dont le volume etait tres bas (risque relatif RR 0,50, intervalle de confiance IC a 95 % 0,28-0,88) et le risque de reinter-vention chez les patients traites par des chirurgiens dont le volume etait tres eleve etait de 47 % de moins que chez les patients traites par des chirurgiens dont le volume etait tres bas (RR 0,53, IC a 95 % 0,30-0,93). Conclusion: Il ne semble y avoir aucun bienfait additionnel significatif au fait d'etre opere dans un centre ou le volume d'interventions pour enclouage intra-medullaire des fractures de la diaphyse tibiale est eleve. Il faudra approfondir la recherche sur les effets du volume chirurgical et de l'experience clinique des etablissements pour confirmer cette observation. Le risque de reintervention a ete plus eleve chez les patients traites par des chirurgiens dont le volume d'interventions etait tres bas; cette observation pourrait etre utilisee pour optimiser l'issue du traite-ment des fractures de la diaphyse tibiale. Enregistrement de l'essai clinique: ClinicalTrials.gov, NCT00038129.
Assessment of cardiovascular parameters, including the electrocardiogram (ECG) is required by the regulatory guidelines. In safety pharmacology studies, this is typically done using chronically ...implanted radiotelemetry devices in non-rodent species.
We compared ECG signal quality from ten male beagle dogs and 10 male cynomolgus monkeys with telemetry transmitters implanted using two surgical approaches: i) epicardial ECG lead placement via single incision, left side thoracotomy or ii) subcutaneous ECG lead placement via laparotomy. In addition, epicardial leads and semi-automated scoring were used in combination to detect changes in ECG values caused by moxifloxacin. Telemetry-instrumented male beagle dogs (n=8) and male cynomolgus monkeys (n=8) were given moxifloxacin at 10, 30, or 100mg/kg (dogs) and 10, 50, or 175mg/kg (monkeys) as a single dose by oral gavage.
ECG signals were of excellent quality with epicardial lead placement, and human activity in the room did not significantly alter signal quality. Administration of moxifloxacin was associated with prolongation of QTc interval, in both dogs and monkeys in a dose-dependant pattern. Dogs given 30mg/kg and 100mg/kg, the maximum QTcf interval prolongations were 22ms (+9%, 8h postdose) and 60ms (+24%, 15h postdose). In monkeys given 50 and 175mg/kg, the QTcb interval was significantly prolonged from 1 to 6h postdose, and QTcb interval prolongation persisted in monkeys given 175mg/kg through 19h postdose. In monkeys given 175mg/kg, the maximum QTcb interval prolongation was 43ms (+12.9%, 16 h postdose).
The present study demonstrated that placing leads directly on the epicardium drastically diminishes signal disruption due to room disturbances and subsequent animal excitement. This novel surgical model demonstrated adequate sensitivity to detect changes in ECG parameters, specifically QTc interval prolongation in both the dog and monkey.
To study the activity and incidence of knee pain after sustaining an isolated tibia fracture treated with an infrapatellar intramedullary nail at 1 year.
Retrospective review of prospective cohort.
...Multicenter Academic and Community hospitals.
Four hundred thirty-seven patients with an isolated tibia fracture completed a 12-month assessment on pain and self-reported activity.
Infrapatellar intramedullary nail.
Demographic information, comorbid conditions, injury characteristics, and surgical technique were recorded. Knee pain was defined on a 1-7 scale with 1 being "no pain" and 7 being a "very great deal of pain." Knee pain >4 was considered clinically significant. Patients reported if they were "able," "able with difficulty," or "unable" to perform the following activities: kneel, run, climb stairs, and walk prolonged. Variables were tested in multilevel multivariable regression analyses.
In knee pain, 11% of patients reported a "good deal" to a "very great deal" of pain (>4), and 52% of patients reported "no" or "very little" pain at 12 months. In activity at 12 months, 26% and 29% of patients were unable to kneel or run, respectively, and 31% and 35% of patients, respectively, stated they were able with difficulty or unable to use stairs or walk.
Clinically significant knee pain (>4/7) was present in 11% of patients 1 year after a tibia fracture. Of note, 31%-71% of patients had difficulty performing or were unable to perform routine daily activities of kneeling, running, and stair climbing, or walking prolonged distances.
Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Inadequate sample size and power in randomized trials can result in misleading findings. This study demonstrates the effect of sample size in a large clinical trial by evaluating the results of the ...Study to Prospectively evaluate Reamed Intramedullary Nails in Patients with Tibial fractures (SPRINT) trial as it progressed.
The SPRINT trial evaluated reamed versus unreamed nailing of the tibia in 1226 patients, and in open and closed fracture subgroups (N = 400 and N = 826, respectively). We analyzed the reoperation rates and relative risk comparing treatment groups at 50, 100, and then increments of 100 patients up to the final sample size. Results at various enrollments were compared with the final SPRINT findings.
In the final analysis, there was a statistically significant decreased risk of reoperation with reamed nails for closed fractures (relative risk reduction 35%). Results for the first 35 patients enrolled suggested that reamed nails increased the risk of reoperation in closed fractures by 165%. Only after 543 patients with closed fractures were enrolled did the results reflect the final advantage for reamed nails in this subgroup. Similarly, the trend toward an increased risk of reoperation for open fractures (23%) was not seen until 62 patients with open fractures were enrolled.
Our findings highlight the risk of conducting a trial with insufficient sample size and power. Such studies are not only at risk of missing true effects but also of giving misleading results.
To determine the extent to which knowledge from clinical trial protocols is transferred to nonparticipating patients.
Retrospective review of prospectively collected data from a large clinical trial.
...Six level-1 international trauma centers.
We compared rates and timing of reoperation in a subset of patients enrolled in the Study to Prospectively evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures (SPRINT) to concurrent patients who were eligible but not enrolled. This was a retrospective review of prospectively collected trial data. The records of 6 of the original SPRINT centers were searched for non-SPRINT patients who underwent intramedullary nailing of a closed tibial fracture. The rate and timing of reoperation were compared. A P < 0.05 was considered significant.
One hundred fourteen non-SPRINT patients were compared with 328 patients enrolled in SPRINT from those same sites. There were 7 reoperations (6.1%) in non-SPRINT patients versus 18 (5.2%) in SPRINT patients odds ratio (OR) 1.19, 95% confidence interval (CI) 0.41 to 3.13; P = 0.811. There was no difference in the time to reoperation between the SPRINT and non-SPRINT patients (6.2 vs. 6.8 months, 95% CI of the difference -3.8 to 2.6; P = 0.685) or in the proportion of patients who underwent reoperation before 6 months (29% vs. 43%; OR 1.75; 95% CI 0.18 to 15.41; P = 0.647).
Patients not enrolled in SPRINT had similarly low rates of reoperation for nonunion, and the average time to reoperation for both groups was longer than 6 months. A 6-month waiting period may have allowed slow-to-heal fractures adequate time to heal, thereby reducing the rate of diagnosis of nonunion. As such, this waiting period could contribute to lower-than-expected reoperation rates for nonunion. It is possible that clinical trials may beneficially influence the care of nonenrolled patients.
A pilot-plant scale desymmetrization of the cyclic meso-epoxide 4b, using a chiral lithium amide prepared from symmetrical diamine 17, was designed and implemented to provide allylic alcohol 3b in ...high yield and greater than 99% ee. This chiral alcohol was converted to ketone 2b, a key intermediate in a new asymmetric synthesis of LY459477. Chiral diamine 17 was prepared from a readily available chiral precursor, (R)-α-methylbenzylamine, and could be recovered from the reaction mixture and reused. Studies performed to probe the mechanism of the rearrangement reaction of epoxide 4b showed that diamine 17 provided an optimal combination of selectivity and scaleability for this process.
The problem of mapping (defined as matching and scheduling) tasks and communications onto multiple machines and networks in a heterogeneous computing (HC) environment has been shown to be ...NP-complete, in general, requiring the development of heuristic techniques. Many different types of mapping heuristics have been developed in recent years. However, selecting the best heuristic to use in any given scenario remains a difficult problem. Factors making this selection difficult are discussed. Motivated by these difficulties, a new taxonomy for classifying mapping heuristics for HC environments is proposed (Purdue HC Taxonomy). The taxonomy is defined in three major parts: the models used for applications and communication requests; the models used for target hardware platforms; and the characteristics of mapping heuristics, Each part of the taxonomy is described, with examples given to help clarify the taxonomy. The benefits and uses of this taxonomy are also discussed.
The James Webb Space Telescope (JWST) is a large, infrared space telescope that has recently started its science program which will enable breakthroughs in astrophysics and planetary science. ...Notably, JWST will provide the very first observations of the earliest luminous objects in the Universe and start a new era of exoplanet atmospheric characterization. This transformative science is enabled by a 6.6 m telescope that is passively cooled with a 5-layer sunshield. The primary mirror is comprised of 18 controllable, low areal density hexagonal segments, that were aligned and phased relative to each other in orbit using innovative image-based wavefront sensing and control algorithms. This revolutionary telescope took more than two decades to develop with a widely distributed team across engineering disciplines. We present an overview of the telescope requirements, architecture, development, superb on-orbit performance, and lessons learned. JWST successfully demonstrates a segmented aperture space telescope and establishes a path to building even larger space telescopes.
PDF
