ADD It Up: An Evaluation of Antibiotic Duration at Hospital Discharge at a Community Hospital.

BACKGROUND: According to the Centers for Disease Control and Prevention, patients admitted to the hospital are commonly discharged on antibiotic therapy with prolonged courses of therapy, which contributes to excessive antibiotic exposure and adverse events. The purpose of this study was to evaluate total antibiotic duration of therapy at hospital discharge at Indiana University Health Arnett, White Memorial, and Frankfort hospitals. METHODS: A multicenter, retrospective electronic health record review was conducted from 1 January to 30 June 2019. Patients were included if they were at least 18 years of age, began antibiotic therapy while admitted, and continued antibiotic therapy at hospital discharge for 1 of the following indications: skin/soft tissue infection (SSTI), urinary tract infection (UTI), community-acquired pneumonia (CAP), or acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The number of days of therapy (DOT) of each inpatient and outpatient antibiotic prescribed was collected to calculate the total DOT, which was utilized to determine the appropriateness of the duration of therapy. RESULTS: Of the 547 patients included, 233 patients (42.6%) had CAP, 120 (21.9%) had UTI, 101 (18.5%) had SSTI, and 93 (17%) had AECOPD. The median duration of antibiotic therapy across all indications was 9 days (interquartile range [IQR], 7-11). Median duration for CAP was 9 days (IQR, 7-10), AECOPD was 7 days (IQR, 5-9), UTI was 8 days (IQR, 6-10), and SSTI was 12 days (IQR, 10-14). CONCLUSIONS: Excess antimicrobial duration at hospital discharge represents an unmet need of antimicrobial stewardship programs.

Temperature-transferable coarse-graining of ionic liquids with dual graph convolutional neural networks.

Computer simulations can provide mechanistic insight into ionic liquids (ILs) and predict the properties of experimentally unrealized ion combinations. However, ILs suffer from a particularly large disparity in the time scales of atomistic and ensemble motion. Coarse-grained models are therefore used in place of costly all-atom simulations, accessing longer time scales and larger systems. Nevertheless, constructing the many-body potential of mean force that defines the structure and dynamics of a coarse-grained system can be complicated and computationally intensive. Machine learning shows great promise for the linked challenges of dimensionality reduction and learning the potential of mean force. To improve the coarse-graining of ILs, we present a neural network model trained on all-atom classical molecular dynamics simulations. The potential of mean force is expressed as two jointly trained neural network interatomic potentials that learn the coupled short-range and many-body long range molecular interactions. These interatomic potentials treat temperature as an explicit input variable to capture its influence on the potential of mean force. The model reproduces structural quantities with high fidelity, outperforms the temperature-independent baseline at capturing dynamics, generalizes to unseen temperatures, and incurs low simulation cost.

Active learning and neural network potentials accelerate molecular screening of ether-based solvate ionic liquids.

Solvate ionic liquids (SIL) have promising applications as electrolyte materials. Despite the broad design space of oligoether ligands, most reported SILs are based on simple tri- and tetraglyme. Here, we describe a computational search for complex ethers that can better stabilize SILs. Through active learning, a neural network interatomic potential is trained from density functional theory data. The learned potential fulfills two key requirements: transferability across composition space, and high speed and accuracy to find low-energy ligand-ion poses across configurational space. Candidate ether ligands for Li+, Mg2+ and Na+ SILs with higher binding affinity and electrochemical stability than the reference compounds are identified. Lastly, their properties are related to the geometry of the coordination sphere.

The Role of Crosslinked Polyethylene in Reducing Aggregated Costs of Total Hip Arthroplasty in the United States.

BACKGROUND: Widespread adoption of crosslinked polyethylene for the acetabular articular surface for total hip arthroplasty has substantially reduced revision rates and dislocation rates. We aim to provide estimates of the resulting magnitude of the annual reduction in aggregated costs of total hip arthroplasty surgery in the United States. METHODS: After we obtained, from the literature, the contrasting mid-term rates of revisions and dislocations of total hip arthroplasty using conventional polyethylene vs those using crosslinked polyethylene, specifically from only registry studies and prospective, randomized controlled studies, we multiplied these incidence figures by the cost estimates of these failures to generate approximations of the cost savings in the United States from the use of crosslinked polyethylene. RESULTS: The estimates suggest that in the United States these savings might be one billion dollars per annual cohort over a 15-year duration. CONCLUSION: The use of crosslinked polyethylene has reduced substantially the overall costs of total hip arthroplasty surgery in the United States.

Arthroplasty implant registries over the past five decades: Development, current, and future impact.

Local, regional, and national registries have played an important role in the development of hip and knee arthroplasty and the treatment of patients with various maladies of these joints. Four arthroplasty registries stand out as leading forces behind the drive to popularize the use of registries and pursue the concept of evidence based medicine. The Mayo registry, started by Mark Coventry, is recognized as the oldest continuing registry for arthroplasty. The Harris Registry at Massachusetts General Hospital, along with the Mayo Registry, has greatly contributed to the advancement of arthroplasty surgery and have served an important role of identifying poorly performing implants and techniques in the United States. The Swedish Knee Arthroplasty Registry is the oldest national registry dedicated to joint arthroplasty and along with the Swedish Hip Arthroplasty Registry have established the infrastructure, analysis and reporting mechanisms, and leadership that has enabled other countries to subsequently develop national registries around the world. As more countries have adopted the concept of national registries, a new area of research is possible by pooling the resources of large registries as is now occurring with the Nordic countries. Several international organizations have been formed to promote future collaboration and develop international standards. The process of globalization of registries is a result of continued efforts over the past 50 years in improving and disseminating the knowledge gained from the early registries. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2319-2330, 2018.

To reduce routine computed tomographic angiography for thoracic aortic injury assessment in level II blunt trauma patients using three mediastinal signs on the initial chest radiograph: a preliminary report.

PURPOSE: CTA is routinely ordered on level II blunt thoraco-abdominally injured patients for assessment of injury to the thoracic aorta. The vast majority of such assessments are negative. The question being asked is, Does the accurate interpretation of the three mediastinal signs permit reliable determination of which patients need CTA for aortic assessment? The purpose of this investigation was to evaluate the role of three specifically selected mediastinal anatomic signs on the initial supine chest radiograph (CXR) of adult level II blunt thoraco-abdominally injured patients for the presence or absence of a mediastinal hematoma. The presence of a mediastinal hematoma is typically used as an indicator for computed tomographic angiography (CTA). The three mediastinal signs are the right para-tracheal stripe (RPTS), left para-spinal line (LPSL), and the left apical extra-pleural area (LAPA). MATERIALS AND METHODS: The patient triage designation (level II trauma) was made by the attending physician at the time of admission. The initial CXR image and the CTA report of the 197 adult blunt level II thoraco-abdominally injured patients obtained on the day of admission were compared. The CXR of each of the 197 patients was independently assessed by each of four observers specifically for the status of the three mediastinal signs. Each observer was blinded to the CTA report until after the status of the three mediastinal sign evaluation had been determined. Two or three of the mediastinal signs being positive were required to determine that the CXR was positive for a mediastinal hematoma. RESULTS: Two or three of the selected mediastinal signs were normal in 192 (97.5%) patients. None of these patients had either a mediastinal hematoma or a major aortic injury on CTA. In each of the remaining five (2.5%) patients, two or three of the mediastinal signs were abnormal. Each of these patients had a mediastinal hematoma and a major thoracic aortic injury on CTA. CONCLUSIONS: This preliminary study suggests that the accurate interpretation of the three specifically selected mediastinal signs on the initial supine CXR of adult level II blunt thoraco-abdominally injured patients could reduce the need for routine CTA for thoracic aortic injury assessment, and requires verification by an additional study.

Edge loading has a paradoxical effect on wear in metal-on-polyethylene total hip arthroplasties.

BACKGROUND: Edge wear is an adverse factor that can negatively impact certain THAs. In some metal-on-metal THAs, it can lead to adverse tissue reactions including aseptic lymphocytic vasculitis-associated lesions and even to pseudotumor formation. In some ceramic-on-ceramic THAs, it can lead to squeaking and/or stripe wear. Edge wear in metal-on-metal and ceramic-on-ceramic THAs can also be associated with accelerated wear across the articulation of these joints. QUESTIONS/PURPOSES: I asked: Does edge wear occur in metal-on-polyethylene (MOP) articulations? And if so, does it increase joint wear? METHODS: I examined the evidence in the literature for edge wear occurring in MOP THA and then assessed the evidence in the literature for data supporting the concept that edge wear in MOP hips could accelerate wear across the articulation over time. RESULTS: Extensive data in the literature confirm edge wear is common in MOP THA. Surprisingly, the evidence does not support that it accelerates wear across the articulation. In fact, substantial data support the concept that it does not. CONCLUSIONS: These observations suggest, in terms of edge wear accelerating overall wear, MOP articulation may have a privileged position compared to hard-on-hard THA articulations.

The correlation between minor or unrecognized developmental deformities and the development of osteoarthritis of the hip.

The 20th century brought three major conceptual changes about osteoarthritis of the hip. The first was a dramatic change in the understanding of the etiology of many cases of osteoarthritis of the hip. The second was the establishment of the mechanism by which minor developmental abnormalities lead to arthritis. The third was, for the first time, the possibility that the rate of disease development could be retarded and even possibly prevented from progressing. To understand these conceptual changes, it is essential to define the terms used to describe osteoarthritis of the hip.

The first 50 years of total hip arthroplasty: lessons learned.

Fifty years have passed since the first total hip arthroplasty of the modern era was performed. At this, the vantage point, it is reasonable to review these five decades, inquiring behind the single dominating observation that, in its current form, this operation is one of the most successful of all surgical procedures for the management of end-stage human disease. What are the generic lessons that can be derived from the experience? Succinctly, five major observations appear valuable. They are "skunk works," "Pasteur's motto," "the totally unexpected," "research solutions," and "the role of alternatives." "Skunk works," an industrial management term, might be characterized as an innovative endeavor that is offline and off-budget resulting from the relentless pursuit of a vivid dream by creative zealots who eschew defeat. Pasteur's motto dealt with serendipity, which was crucial to total hip arthroplasty progress. The totally unexpected is represented by an entirely new manmade disease, "periprosthetic osteolysis." The research solutions are represented by the complex, sophisticated contemporary research that has unraveled periprosthetic osteolysis and suggested modes of correction. Finally, the application of "alternatives" has characterized major progress. Importantly, these, or similar generic observations, may provide insights into important progress in the future.

The etiology of osteoarthritis of the hip: an integrated mechanical concept.

UNLABELLED: The etiology of osteoarthritis of the hip has long been considered secondary (eg, to congenital or developmental deformities) or primary (presuming some underlying abnormality of articular cartilage). Recent information supports a hypothesis that so-called primary osteoarthritis is also secondary to subtle developmental abnormalities and the mechanism in these cases is femoroacetabular impingement rather than excessive contact stress. The most frequent location for femoroacetabular impingement is the anterosuperior rim area and the most critical motion is internal rotation of the hip in 90 degrees flexion. Two types of femoroacetabular impingement have been identified. Cam-type femoroacetabular impingement, more prevalent in young male patients, is caused by an offset pathomorphology between head and neck and produces an outside-in delamination of the acetabulum. Pincer-type femoroacetabular impingement, more prevalent in middle-aged women, is produced by a more linear impact between a local (retroversion of the acetabulum) or general overcoverage (coxa profunda/protrusio) of the acetabulum. The damage pattern is more restricted to the rim and the process of joint degeneration is slower. Most hips, however, show a mixed femoroacetabular impingement pattern with cam predominance. Surgical attempts to restore normal anatomy to avoid femoroacetabular impingement should be performed in the early stage before major cartilage damage is present. LEVEL OF EVIDENCE: Level V, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Minimum 6-year followup of highly cross-linked polyethylene in THA.

To reduce wear rates and particulate debris, highly cross-linked polyethylene has been in use in total hip arthroplasty for 8 years. We designed this followup study to primarily determine the total penetration rate of the femoral head and the steady-state wear rate of cross-linked polyethylene in patients undergoing primary total hip arthroplasty. We retrospectively reviewed data from 182 patients (200 hips) with a minimum 6-year followup (mean, 6.9 years; range, 6-8 years) and an average age of 60.2 years at surgery. The average Harris hip score, University of California-Los Angeles activity score, and WOMAC score were 91.1, 6.3, and 11.3, respectively. Radiographic evaluation showed no evidence of loosening or osteolytic lesions around the cup or stem. No revisions were performed for polyethylene wear or liner fracture. The average steady-state wear rate was -0.002 +/- 0.01 mm per year and -0.026 +/- 0.13 mm per year for 28-mm and 32-mm head sizes, respectively. We observed no correlation between the total wear rate and femoral head size, brand of polyethylene, age, gender, primary diagnosis, mode of fixation, surgical approach, University of California-Los Angeles activity score, Harris hip score, or WOMAC. Highly cross-linked polyethylene liners are associated with excellent midterm clinical, radiographic, and wear results in this group of patients.

Radiostereometric analysis comparison of wear of highly cross-linked polyethylene against 36- vs 28-mm femoral heads.

This study used radiostereometric analysis (RSA) to compare the femoral head penetration of 28- vs 36-mm-diameter femoral heads into highly cross-linked polyethylene in 2 groups of total hip arthroplasty patients. Thirty patients were enrolled in this RSA study using highly cross-linked polyethylene (Longevity, Zimmer Inc, Warsaw, Idaho) against either 28- or 36-mm-diameter cobalt chrome femoral heads. At 3-year follow-up, there was no significant difference in the total average femoral head penetration, including both creep and wear, using 3 methods of RSA measurement between the 2 groups. Importantly, after bedding-in, there was no further significant increase in the amount of femoral head penetration (ie, wear) with either head size between years 1 and 3. There were no radiographic signs of lysis or radiolucencies at a minimum 3-year follow-up.

Comparison of hip simulator wear of 2 different highly cross-linked ultra high molecular weight polyethylene acetabular components using both 32- and 38-mm femoral heads.

Much evidence suggests that ultra high molecular weight polyethylene (UHMWP) irradiated to 9.5 Mrad has lower wear than UHMWP given 5 Mrad. Curiously, highly cross-linked polyethylenes gain weight during hip simulator testing. We postulated that (a) UHMWP irradiated to 9.5 Mrad would wear less than UHMWP irradiated to 5 Mrad UHMWP, (b) articulation against 38-mm heads would accentuate this difference, and (c) weight gain of highly cross-linked material reflects the inadequacy of load soak controls. We compared 9.5 versus 5 Mrad polyethylene in hip simulator wear tests, with both load soak corrections and with novel "motion soak" corrections. The 9.5-Mrad material wore less than 5-Mrad material for 32- and 38-mm heads. Motion soak corrections were more accurate than load soak corrections.

Simulated normal gait wear testing of a highly cross-linked polyethylene tibial insert.

Polyethylene wear can compromise long-term performance of total knees. We investigated articular and backside wear rate of tibial inserts made from conventional vs highly cross-linked polyethylenes. The inserts were tested on a knee simulator at a frequency of 1.1 Hz using normal gait kinematics with a 7 degrees posterior slope for 7 million cycles. Gravimetrically, the combined articular and backside wear rate was 23 +/- 6 and 4.6 +/- 2 mm(3) per million cycles for the conventional and cross-linked inserts, respectively. We independently measured articular surface wear rates, which were 15 +/- 4 and 5 +/- 2 mm(3) per million cycles for conventional and cross-linked inserts, respectively. Electron beam cross-linked and subsequently melted polyethylene reduced the wear rate of polyethylene on articular and backside surfaces in a cruciate-retaining total knee design when tested on a knee simulator under simulated normal gait.

Contact stress assessment of conventional and highly crosslinked ultra high molecular weight polyethylene acetabular liners with finite element analysis and pressure sensitive film.

Stress magnitude and distribution of both conventional polyethylene versus a crosslinked polyethylene in the liner of a total hip replacement (THR) were examined using finite element analysis and pressure sensitive film. Both types of polyethylene were assessed against head sizes of 22 and 28 mm with 5-mm thick polyethylene liners and head sizes of 28, 38, and 46 mm with 3-mm thick polyethylene liners. Liners with 5-mm conventional polyethylene represented successful combinations with long track records. Our hypothesis was that although the combination of the large head and the lower modulus of the highly crosslinked polyethylene would lead to lower stresses, the stresses would be excessive if the liner was extremely thin at 3 mm. Von Mises stresses at the articulating surface of the highly crosslinked liners were lower, when compared to conventional polyethylene, in every THR size examined. Specifically, however, the 38- and 46-mm inner diameter (ID) highly crosslinked polyethylene even at the extreme of only 3-mm thick had lower stresses than the 22-mm ID conventional liner of 5-mm thickness. These data indicate that the use of a large head against highly crosslinked material even at 3-mm thickness results in lower stresses than in an existing conventional 22-mm head and 5-mm thick combination. Obviously, other considerations will influence the minimum thickness to be recommended.