Evaluation of Educational YouTube Videos for Distal Radius Fracture Treatment.

Purpose: Distal radius fractures (DRFs) are one of the most common fractures in adults. Adequate patient education is crucial for adherence to treatment. YouTube is a popular, accessible resource that has become a valuable tool for obtaining health information. The current study evaluated the top 50 YouTube videos on DRF treatment for patient education. Methods: A systematic search was conducted on YouTube using three searches to obtain 150 videos. Duplicate, nonrelevant, paid, and non-English videos were removed, and the top 50 rank-ordered videos were reviewed and characterized in terms of general (views, likes, video length, and publication date), source (publisher affiliation, presenter type, and target audience), and content (media type, topic coverage, advertisements, and bias) parameters. Results: Only 56% of videos were directed toward patients versus 40% for health care providers, highlighting a gap in patient-oriented educational content on YouTube. Most (86%) videos included effective visual aids, aligning with best practices for educational videos. Surgical management was overrepresented in 64% of the videos as opposed to nonsurgical management in 34% of videos. Only 31% of patient-oriented videos discussed surgical complications. Home exercises were emphasized in 75% of the videos discussing recovery topics. Conclusions: Although YouTube has the potential to be an effective resource for disseminating health information to patients, it has several limitations for education in DRF treatment including the lack of patient-oriented educational videos, overrepresentation of surgical treatment, and lack of information on surgical complications. Nonetheless, YouTube may have an important role as a supplementary resource, especially in certain topics such as guiding postoperative recovery with home exercises. Clinical relevance: This study allows health care providers and content creators to proactively address information gaps identified in educational YouTube videos on DRF treatment. It helps characterize the role of YouTube in supporting the treatment and recovery of patients experiencing DRFs.

High-Capacity, Cooperative CO2 Capture in a Diamine-Appended Metal-Organic Framework through a Combined Chemisorptive and Physisorptive Mechanism.

Diamine-appended Mg2(dobpdc) (dobpdc4- = 4,4'-dioxidobiphenyl-3,3'-dicarboxylate) metal-organic frameworks are promising candidates for carbon capture that exhibit exceptional selectivities and high capacities for CO2. To date, CO2 uptake in these materials has been shown to occur predominantly via a chemisorption mechanism involving CO2 insertion at the amine-appended metal sites, a mechanism that limits the capacity of the material to ∼1 equiv of CO2 per diamine. Herein, we report a new framework, pip2-Mg2(dobpdc) (pip2 = 1-(2-aminoethyl)piperidine), that exhibits two-step CO2 uptake and achieves an unusually high CO2 capacity approaching 1.5 CO2 per diamine at saturation. Analysis of variable-pressure CO2 uptake in the material using solid-state nuclear magnetic resonance (NMR) spectroscopy and in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) reveals that pip2-Mg2(dobpdc) captures CO2 via an unprecedented mechanism involving the initial insertion of CO2 to form ammonium carbamate chains at half of the sites in the material, followed by tandem cooperative chemisorption and physisorption. Powder X-ray diffraction analysis, supported by van der Waals-corrected density functional theory, reveals that physisorbed CO2 occupies a pocket formed by adjacent ammonium carbamate chains and the linker. Based on breakthrough and extended cycling experiments, pip2-Mg2(dobpdc) exhibits exceptional performance for CO2 capture under conditions relevant to the separation of CO2 from landfill gas. More broadly, these results highlight new opportunities for the fundamental design of diamine-Mg2(dobpdc) materials with even higher capacities than those predicted based on CO2 chemisorption alone.

Selective Adsorption of Oxygen from Humid Air in a Metal-Organic Framework with Trigonal Pyramidal Copper(I) Sites.

High or enriched-purity O2 is used in numerous industries and is predominantly produced from the cryogenic distillation of air, an extremely capital- and energy-intensive process. There is significant interest in the development of new approaches for O2-selective air separations, including the use of metal-organic frameworks featuring coordinatively unsaturated metal sites that can selectively bind O2 over N2 via electron transfer. However, most of these materials exhibit appreciable and/or reversible O2 uptake only at low temperatures, and their open metal sites are also potential strong binding sites for the water present in air. Here, we study the framework CuI-MFU-4l (CuxZn5-xCl4-x(btdd)3; H2btdd = bis(1H-1,2,3-triazolo[4,5-b],[4',5'-i])dibenzo[1,4]dioxin), which binds O2 reversibly at ambient temperature. We develop an optimized synthesis for the material to access a high density of trigonal pyramidal CuI sites, and we show that this material reversibly captures O2 from air at 25 °C, even in the presence of water. When exposed to air up to 100% relative humidity, CuI-MFU-4l retains a constant O2 capacity over the course of repeated cycling under dynamic breakthrough conditions. While this material simultaneously adsorbs N2, differences in O2 and N2 desorption kinetics allow for the isolation of high-purity O2 (>99%) under relatively mild regeneration conditions. Spectroscopic, magnetic, and computational analyses reveal that O2 binds to the copper(I) sites to form copper(II)-superoxide moieties that exhibit temperature-dependent side-on and end-on binding modes. Overall, these results suggest that CuI-MFU-4l is a promising material for the separation of O2 from ambient air, even without dehumidification.

Anteromedial coronoid fractures: technical description of an extensile surgical approach and outcomes from a small series using this technique.

Background: Varus posteromedial rotatory instability is a difficult clinical problem to diagnose and treat. Fixation of the anteromedial coronoid fracture is often necessary to achieve elbow stability. We describe an extensile surgical approach to the anteromedial coronoid. Methods: A retrospective review was performed of all patients at our institution who had anteromedial coronoid fracture fixed with this approach between 2012 and 2020. Results: Six patients were identified. They all achieved a stable elbow. Four of 6 developed heterotopic ossification and 2/6 required further surgery for this. Only 1 patient had a transient ulnar sensory loss. Conclusion: We describe an approach to the coronoid that allows great visualization of the joint and access to large coronoid fractures. The approach is extensile and does not require extensive dissection or work around the ulnar nerve. Access to fracture and for fixation can be improved by release of the common flexor pronator origin and the medial collateral ligament.

Morphology of Proximal Ulna Bare Area: A Guide for Olecranon Osteotomy.

PURPOSE: Olecranon osteotomy is commonly used to obtain access to the distal humerus for fracture fixation. The goal of this study was to accurately describe the anatomy of the bare area to minimize articular cartilage damage while performing olecranon osteotomies. METHODS: Twenty cadaveric ulnae were denuded to expose the bare area. Laser surface mapping was used to create 3-dimensional models, and the nonarticular portions of the ulnae were digitally measured. RESULTS: The morphology of the bare area from all aspects of the proximal ulna was defined. The central bare area was consistent in its location, 4.9 ± 1.5 mm distal to the deepest portion of the trochlear notch and 23.2 ± 2.3 mm distal to the olecranon tip. The maximum chevron osteotomy apical angle to stay within the bare area averaged 110° ± 11.8°. However, there was little tolerance for error without the risk of violating the articular cartilage. With transverse osteotomy, averaging 18° ± 10.6° in the coronal plane, there is less risk of damaging the articular cartilage. CONCLUSIONS: Transverse osteotomy perpendicular to the posterior surface of the ulna aiming at the visible bare area on the medial and lateral sides of the greater sigmoid notch may reduce the chances of violating the nonvisible articular cartilage of the proximal ulna. Based on the findings of this study, if chevron osteotomy is used, a shallow apex distal angle of more than 110° is recommended. CLINICAL RELEVANCE: This study provides intraoperative landmarks to guide surgeons performing olecranon osteotomies to stay within the bare area.

Highly Selective N-Alkylation of Pyrazoles: Crystal Structure Evidence for Attractive Interactions.

Inspired by crystal structures, we designed and achieved a catalyst-free Michael reaction for the preparation of an N1-alkyl pyrazole in a high yield (>90%) with excellent regioselectivity (N1/N2 > 99.9:1). The scope of this protocol has been extended to accomplish the first general regioselective N1-alkylation of 1H-pyrazoles to give di-, tri-, and tetra-substituted pyrazoles in a single step. The resulting pyrazoles bear versatile functional groups such as bromo, ester, nitro, and nitrile, offering opportunities for late-stage functionalization. This efficient methodology will have an impact on drug discovery, as several Food and Drug Administration-approved drugs are pyrazole derivatives. A working hypothesis for the regioselectivity is proposed. X-ray crystal structures of the products that highlight the attractive interactions are discussed. This report provides a rare source for the further elucidation of the attractive interactions because the isomeric ratios and the crystal structures are directly related.

Proximal Ulna Osteotomy for Complex Fractures of the Distal Humerus: A 3-Dimensional Laser Analysis and Comparison With Olecranon Osteotomy.

PURPOSE: The current methods of distal humerus (DH) articular surface visualization only allow a limited view of the joint. This study describes an osteotomy procedure that increases the visualization of and access to the DH articular surface for fixation without compromising ligaments. METHODS: Eighteen fresh-frozen human elbows (9 matched pairs) underwent proximal ulna osteotomy (PUO) or transverse olecranon osteotomy (OO) contralaterally. The visualized articular surface of the DH was demarcated, and the surface areas of the DH, capitellum, and trochlea were measured using 3-dimensional scanning. The angular arc of the articular surface of the capitellum and trochlea was measured using a goniometer. RESULTS: The 3-dimensional scans showed that 87.6% of the total DH surface area was visualized using PUO versus 65.6% using OO. When the trochlea and capitellum surface areas were separated, 94.0% versus 75.9% of the trochlea and 74.8% versus 44.7% of the capitellum were visualized using PUO and OO, respectively. The goniometric angles demonstrated that 98.2% versus 70.9% of the trochlea and 75.1% versus 43.5% of the capitellum articular surface arc angles were visualized using PUO and OO, respectively. After PUO with further release of the flexor-pronator mass was performed, 100% of the DH articular surface was visualized. CONCLUSIONS: Proximal ulnar osteotomy improves the visualization of the DH articular surface. CLINICAL RELEVANCE: Proximal ulna osteotomy spares ligaments, avoids osteotomizing the greater sigmoid notch, involves more robust metaphyseal bone for potentially better fixation, and may permit DH arthroplasty without compromising primary ligamentous elbow stabilizers. Further clinical studies are needed to assess the utility of this type of osteotomy.

Medial elbow exposure: an anatomic comparison of 5 approaches.

PURPOSE: Several surgical approaches to the medial elbow are described; however, it remains unclear which exposure provides the optimal view of relevant medial elbow structures. The purpose of this anatomic study was to determine the visible surface area of the coronoid process, distal humerus, and radial head through 5 approaches to the medial elbow. METHODS: Eight fresh-frozen cadaveric upper extremity specimens were dissected. Five surgical approaches were performed on each specimen. The Smith muscle-splitting approach to the ulnar collateral ligament was performed first (Smith), followed by the Hotchkiss medial "Over the top" approach (Hotchkiss), the extended medial elbow approach (EMEA), the flexor carpi ulnaris splitting approach (FCU-Split), and the Taylor and Scham approach (T&S). Bony visualization was determined using laser surface scanning (Artec Space Spider; Artec 3D). The scans were segmented using commercially available digital software (Geomagic Wrap; 3D Systems Corporation), and the surface area visualized was determined. A descriptive analysis of the joint areas visible using the medial collateral ligament (MCL) as a clinical landmark was performed. RESULTS: The EMEA visualized the highest proportion of the total elbow joint from the medial side showing 13.9 ± 6.0 cm2, or 15% ± 4% of the joint. It also provided the best visualization of the coronoid (3.2 ± 1.7 cm2 of surface area, or 26% ± 9%) and distal humerus (9.9 ± 4.3 cm2, or 15% ± 4%). The Hotchkiss approach was best at visualizing the radial head (0.8 ± 0.3 cm2, or 7% ± 3%). The EMEA, Hotchkiss, and Smith approaches showed primarily the anterior bundle of the MCL, its insertion, and the regions anterior to it, whereas the FCU-Split showed the anterior bundle of the MCL and regions both anterior and posterior to it. The T&S showed primarily the areas posterior to the anterior bundle of the MCL; the anterior regions were not visible. The FCU-Split and the T&S allowed visualization of the posterior bundle of the MCL. The intraclass correlation coefficients (ICCs) for intraobserver reliability were 0.997, 0.992, and 0.974 for the test distal humerus, test coronoid, and test radial head, respectively. The ICCs for interobserver reliability were 0.915 for the test distal humerus, 0.66 for the coronoid, and 0.583 for the radial head. CONCLUSION: The EMEA provides the most visualization of the coronoid and distal humerus, whereas the Hotchkiss showed the most radial head. However, these approaches mainly visualize structures anterior to the MCL. If exposure of structures posterior to the MCL is required, the FCU-Split and T&S approaches are more appropriate.

Biofuel-powered soft electronic skin with multiplexed and wireless sensing for human-machine interfaces.

Existing electronic skin (e-skin) sensing platforms are equipped to monitor physical parameters using power from batteries or near-field communication. For e-skins to be applied in the next generation of robotics and medical devices, they must operate wirelessly and be self-powered. However, despite recent efforts to harvest energy from the human body, self-powered e-skin with the ability to perform biosensing with Bluetooth communication are limited because of lack of a continuous energy source and limited power efficiency. Here, we report a flexible and fully perspiration-powered integrated electronic skin (PPES) for multiplexed metabolic sensing in situ. The battery-free e-skin contains multimodal sensors and highly efficient lactate biofuel cells that use a unique integration of zero- to three-dimensional nanomaterials to achieve high power intensity and long-term stability. The PPES delivered a record-breaking power density of 3.5 milliwatt-centimeter-2 for biofuel cells in untreated human body fluids (human sweat) and displayed a very stable performance during a 60-hour continuous operation. It selectively monitored key metabolic analytes (e.g., urea, NH4 +, glucose, and pH) and the skin temperature during prolonged physical activities and wirelessly transmitted the data to the user interface using Bluetooth. The PPES was also able to monitor muscle contraction and work as a human-machine interface for human- prosthesis walking.

Acetabulum Cup Stability in an Early Weight-Bearing Cadaveric Model of Geriatric Posterior Wall Fractures.

BACKGROUND: Primary total hip arthroplasty (THA) has been suggested for posterior wall (PW) fractures with unfavorable features in the geriatric population. There is a paucity of studies reporting on postoperative protocols for primary THA after PW fractures. The purpose of this study was to test the biomechanical effect of immediate assisted weight-bearing on acetabulum THA cup fixation in an osteoporotic PW fracture model. METHODS: Computed tomography scans of 18 geriatric PW fractures (mean age, 77 ± 8 years) were used to generate representative PW fracture. This fracture pattern, comprising 50% of the PW and 25% of the acetabulum rim, was then created in 6 female cadaveric pelves. A multihole acetabulum THA cup was implanted with line-to-line reaming and fixed with four 5-mm screws. The pelves were cyclically loaded to up to 1.8× body weight (BW) in the intact form, after fracture creation and fracture fixation. Optical markers were used to determine acceptable cup motion of less than 150 µm. RESULTS: Five specimens withstood 3.6× BW loading after implantation and before fracture creation. At 1.8× BW load, cup motion was nonfractured: 50 ± 24 µm (range, 5-128 µm), fractured with no fixation: 37 ± 22 µm (range, 8-74 µm), or fractured with fixation: 62 ± 39 µm (range, 5-120 µm) (P = 0.0097). Cup motion was <150 µm for all groups. CONCLUSION: This study supports the practice of allowing immediate assisted weight-bearing in patients undergoing THA with PW fractures involving up to 50% of the PW and up to 25% of the acetabular rim, with or without fixation of the PW fragment.

Mapping of the Stable Articular Surface and Available Bone Corridors for Cup Fixation in Geriatric Acetabular Fractures.

BACKGROUND: The optimal treatment of acetabular fractures in the senior cohort is undetermined. Total hip arthroplasty in the setting of an acetabular fracture is increasing in popularity. However, there is concern regarding the fixation of a prosthetic cup in a fractured acetabulum. The purpose of this study is to map the area of stable articular surface and bone corridors available for cup fixation in this fracture cohort. METHODS: CT scans of acetabular fractures in 131 consecutive geriatric patients older than 65 years from two level 1 academic trauma centers were analyzed. Acetabular fractures were classified using the Letournel classification, the available stable articular surface, and the bone corridors available for fixation. RESULTS: Fractures involving the anterior column were the most common fracture type seen. The dome only pattern was the most common stable articular surface pattern. The sciatic corridor was available for fixation in all fracture types, followed by the gluteal pillar corridor. Most fractures had at least two corridors (93%) available for screw fixation. CONCLUSIONS: The findings of this study may aid in the development and evaluation of fixation strategies for acetabular cups allowing geriatric acetabular fracture patients earlier weight bearing after primary hip arthroplasty.

Should the Pareto Principle Be Applied as a Cost Savings Method in Hip and Knee Arthroplasty?

BACKGROUND: Understanding the most significant contributions to the cost of completing total hip arthroplasty (THA) and total knee arthroplasty (TKA) is essential to optimize costs and meet funding standards. The objectives of this study are to determine whether cost distribution of THA and TKA follows the Pareto Principle (80/20 rule) and factors predictive of costs that could be modified. METHODS: All inpatient, primary, elective, and unilateral THA and TKA patients from April 2008 to September 2017 were retrospectively reviewed. The Pareto Principle was tested by dividing patients into top 5% cost increments and calculating patient cost category ratio. Relationship between patient-related factors and acute care costs and relationship between cost categories and length of stay (LOS) were examined using multiple regression. RESULTS: The Pareto Principle does not apply for THA or TKA patients, with the top 20% of costly patients accounting for approximately 30% of total costs. LOS is the strongest independent driver of costs. Operating room services and supplies accounted for over 50% of total costs but with low variability (coefficient of variation < 0.25). Laboratory and allied health costs had high variability (coefficient of variation > 1.5), but their contribution to total costs was low (from 0.76% to 5.68%). CONCLUSION: THA and TKA costs do not follow Pareto Principle, concluding that targeting top costly patients is not as effective as focusing on overall patient population. Efforts to decrease overall costs should focus on decreasing the LOS and improving operating room process efficiencies including human resources for supplies and instruments.

Minimally invasive plate osteosynthesis versus conventional open insertion techniques for osteosynthesis.

Osteosynthesis has evolved theoretically and practically throughout its evolution. Similar to trends in other surgical fields, surgical techniques in fracture fixation, such as minimally invasive plate osteosynthesis (MIPO), have moved from large dissections to more tissue sparing methods. These plating techniques have been developed for a variety of bones, but more universal clinical adoption will rely upon improved clinical outcomes. The current review will describe minimally invasive techniques, evaluate their rationale, and summarize evidence for their efficacy.

Double-Row Arthroscopic Rotator Cuff Repair Is More Cost-Effective Than Single-Row Repair.

BACKGROUND: The optimal technique for arthroscopic rotator cuff repair is controversial, and both single and double-row techniques are commonly used. In the current era of increasing costs, health-care delivery models are focusing on the value of care. In this study, we compared the cost-effectiveness of single-row and double-row reconstructions in patients undergoing arthroscopic rotator cuff repair. METHODS: A cost-utility analysis was performed from the perspective of a publicly funded health-care system. Health-care costs, probabilities, and utility values were derived from the published literature. Efficacy data were obtained from a previous randomized controlled trial comparing the effect of single-row (n = 48) or double-row (n = 42) reconstruction among 90 surgical patients. Unit cost data were obtained from a hospital database and the Ontario Schedule of Benefits and Fees. Results are presented as an incremental cost per quality-adjusted life year (QALY) gained. All costs are presented in 2015 Canadian dollars. A series of 1-way and probabilistic sensitivity analyses were performed. RESULTS: Double-row fixation was more costly ($2,134.41 compared with $1,654.76) but was more effective than the single-row method (4.073 compared with 4.055 QALYs). An incremental cost-effectiveness ratio (ICER) was estimated to be $26,666.75 per QALY gained for double-row relative to single-row fixation. A subgroup analysis demonstrated that patients with larger rotator cuff tears (≥3 cm) had a lower ICER, suggesting that double-row fixation may be more cost-effective for larger tears. CONCLUSIONS: Based on the willingness-to-pay threshold of $50,000 per QALY gained, double-row fixation was found to be more cost-effective than single-row. Furthermore, a double-row reconstruction was found to be more economically attractive for larger rotator cuff tears (≥3 cm). LEVEL OF EVIDENCE: Economic and Decision Analysis Level IV. See Instructions for Authors for a complete description of levels of evidence.

Regioselective Synthesis, NMR, and Crystallographic Analysis of N1-Substituted Pyrazoles.

A systematic study of the N-substitution reactions of 3-substituted pyrazoles under basic conditions has been undertaken. Regioselective N1-alkylation, -arylation, and -heteroarylation of 3-substituted pyrazoles have been achieved using K2CO3-DMSO. The regioselectivity is justified by the DFT calculations at the B3LYP/6-31G**(d) level. A consistent steric effect on chemical shift has been observed for N-alkyl pyrazole analogues. Twenty-five X-ray crystallographic structures have been obtained to confirm the regiochemistry of the major products.

Properties of the cartilage layer from the cam-type hip impingement deformity.

Femoro-acetabular impingement (FAI) is associated with significant acetabular cartilage damage and degenerative arthritis. To understand the contact stress and thus biomechanical mechanisms that may contribute to degeneration, the material behaviour of the cartilage layer is required. The objective of this study is to determine the fibril-reinforced poroelastic properties and composition of cartilage from cam deformities and to compare to those of normal cartilage. Patients undergoing surgical treatment of a symptomatic cam FAI deformity were recruited from the clinical practice of one of the authors. Osteochondral specimens were retrieved from the deformity during surgery using a trephine. Control specimens were retrieved from the anterior femoral head bearing surface during autopsy procedures. Indentation stress-relaxation tests were performed to determine the modulus (ES), Poisson's ratio (ν) and permeability (k0) of the poroelastic component, and the strain-independent (E0) and -dependent (Eε) moduli of the fibril-reinforcement using finite element analysis and optimization. Safranin-O staining was used to quantify proteoglycan content. ES and ν were 71% and 37% lower, respectively, in Cam specimens compared to controls, and k0 was approximately triple that of Control specimens (p<0.05). No significant differences were seen in the fibrillar components, E0 and Eε. Proteoglycan content was substantially depleted in Cam specimens, and was correlated with ES, ν and k0. This study showed that cartilage from the cam deformity exhibits severe degeneration in terms of the mechanical behaviour and composition changes, and is consistent with osteoarthritis. This further supports the hypothesis that FAI is a cause of hip osteoarthritis.

Cost savings of outpatient versus standard inpatient total knee arthroplasty.

BACKGROUND: With diminishing reimbursement rates and strained public payer budgets, a high-volume inpatient procedure, such as total knee arthroplasty (TKA), is a common target for improving cost efficiencies. METHODS: This prospective case-control study compared the cost-minimization of same day discharge (SDD) versus inpatient TKA. We examined if and where cost savings can be realized and the magnitude of savings that can be achieved without compromising quality of care. Outcome variables, including detailed case costs, return to hospital rates and complications, were documented and compared between the first 20 SDD cases and 20 matched inpatient controls. RESULTS: In every case-control match, the SDD TKA was less costly than the inpatient procedure and yielded a median cost savings of approximately 30%. The savings came primarily from costs associated with the inpatient encounter, such as surgical ward, pharmacy and patient meal costs. At 1 year, there were no major complications and no return to hospital or readmission encounters for either group. CONCLUSION: Our results are consistent with previously published data on the cost savings associated with short stay or outpatient TKA. We have gone further by documenting where those savings were in a matched cohort design. Furthermore, we determined where cost savings could be realized during the patient encounter and to what degree. In carefully selected patients, outpatient TKA is a feasible alternative to traditional inpatient TKA and is significantly less costly. Furthermore, it was deemed to be safe in the perioperative period.

CONTEXTE: Dans le contexte de budgets publics serrés et de taux de remboursement à la baisse, une intervention chirurgicale en service interne à volume élevé, comme l'arthroplastie totale du genou, est souvent ciblée pour améliorer le rapport coût­efficacité. MÉTHODES: Cette étude cas­témoins prospective a fait une analyse de minimisation des coûts de l'arthroplastie totale du genou en chirurgie d'un jour et en service interne. Nous avons examiné si et où des économies peuvent être réalisées et l'ampleur des économies pouvant être obtenues sans compromettre la qualité des soins. Les variables dépendantes, notamment les coûts détaillés des cas, le taux de retour à l'hôpital et les complications, ont été documentées, puis comparées entre les 20 premiers cas de chirurgie d'un jour et 20 cas­témoins appariés de chirurgie en service interne. RÉSULTATS: Pour chaque appariement cas­témoins, l'arthroplastie totale du genou en chirurgie d'un jour était moins coûteuse que la chirurgie en service interne et a généré des économies médianes d'environ 30 %. Les économies découlaient principalement des coûts associés à l'hospitalisation du patient tels que les coûts de l'unité de soins chirurgicaux, de la pharmacie et des repas du patient. Après 1 an, ni l'un ni l'autre des 2 groupes ne présentait de complications majeures, de retours à l'hôpital ou de réadmissions. CONCLUSION: Nos résultats concordent avec les données antérieures publiées sur les économies associées à l'arthroplastie totale du genou pratiquée en chirurgie d'un jour ou en service interne de courte durée. Nous sommes allés plus loin en documentant également où les économies se situaient dans un modèle cas­témoins. De plus, nous avons déterminé les aspects de la rencontre avec le patient où des économies pourraient être réalisées et l'ampleur de ces économies. Chez des patients soigneusement choisis, l'arthroplastie totale du genou en chirurgie d'un jour est une solution de rechange envisageable à l'arthroplastie totale du genou traditionnelle en service interne et est beaucoup moins coûteuse. De plus, elle a été jugée sécuritaire en période périopératoire.

Bruton's TK inhibitors: structural insights and evolution of clinical candidates.

Bruton's TK (BTK) is a promising biological target for therapeutic intervention of several diseases including inflammatory diseases and cancer/B cell malignancies. Numerous research groups are actively engaged in investigating the functions of BTK, and discovering potent and selective BTK inhibitors as drug candidates. Revealed by x-ray crystal structures with ligands of diverse chemical structures, the ability of BTK kinase domain to adopt various inactive conformations offers unique opportunities to identify highly potent and exquisitely selective inhibitors. Both reversible and covalent inhibitor approaches have yielded candidates demonstrating safety profiles and efficacies in multiple preclinical models of autoimmunity and oncology. Two BTK inhibitors have entered human clinical trials for oncology indications. Ibrutinib won the US FDA approval in November 2013 to become the first-in-class BTK inhibitor for treating mantle cell lymphoma. This encouraging outcome and the other on-going human studies could ultimately expand the utility of BTK inhibitors to broader autoimmune disease areas.

Discovery of isoquinolinone indole acetic acids as antagonists of chemoattractant receptor homologous molecule expressed on Th2 cells (CRTH2) for the treatment of allergic inflammatory diseases.

Previously we reported the discovery of CRA-898 (1), a diazine indole acetic acid containing CRTH2 antagonist. This compound had good in vitro and in vivo potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents. However, it showed low oral exposure in nonrodent safety species (dogs and monkeys). In the current paper, we wish to report our efforts to understand and improve the poor PK in nonrodents and development of a new isoquinolinone subseries that led to identification of a new development candidate, CRA-680 (44). This compound was efficacious in both a house dust mouse model of allergic lung inflammation (40 mg/kg qd) as well as a guinea pig allergen challenge model of lung inflammation (20 mg/kg bid).