Why Do Patients Choose Skilled Nursing Facilities After Total Hip and Knee Arthroplasty?

BACKGROUND: Current research indicates that total joint arthroplasty patients who are discharged to skilled nursing facilities (SNFs) have higher complication rates as compared to home. Many factors like age, sex, race, Medicare status, and past medical history have been shown to influence discharge destination. The present study sought to gather patient-indicated reasons for SNF discharge and identify potentially modifiable factors influencing the decision. METHODS: Primary total joint arthroplasty patients were asked to complete surveys at their presurgical and 2-week postsurgical follow-up appointments. The surveys included home access and social support questions as well as patient-reported outcome measures: Patient-Reported Outcomes Measurement and Information System, Risk Assessment and Prediction Tool, Knee injury and Osteoarthritis Outcome Score for Joint Replacement, or Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement. RESULTS: Of 765 patients who met inclusion criteria, 3.9% were discharged to an SNF and these were more frequently post-THA, women, older, Black, and persons living alone. Regression analyses indicated that lower Risk Assessment and Prediction Tool score, higher age, no caregiver presence, and Black race were significantly associated with SNF discharge. Patients discharged to an SNF most commonly reported social concerns rather than medical or home access concerns as the main factor for SNF discharge. CONCLUSIONS: While age and sex are nonmodifiable factors, the availability of a caregiver and social support represents an important modifiable factor in regard to discharge destination. Dedicated attention during the preoperative planning period may help augment social support and avoid unnecessary discharges to SNFs.

Do 'Surgeon Champions' and High-Volume Surgeons Have Lower Rates of Periprosthetic Femur Fracture? Perspective From a State-Wide Quality Improvement Registry.

BACKGROUND: Recently, a state-wide registry identified fracture as a major cause of total hip arthroplasty revision. There were 52.8% of revisions occurring within 6 months (fracture leading cause). Registry sites have a 'surgeon champion' who acts as liaison and advocate. This study evaluated the effect of surgeon volume and role of 'surgeon champion' on fracture rates. METHODS: There were 95,948 cases from 2012 to 2019 queried with peri-implant femoral fractures identified (within 6 months). Funnel plots were generated to compare individual surgeon-specific fracture rates. Surgeons who had a fracture rate below the confidence interval were labeled 'green' (lower than mean), within were 'yellow' (no difference), and above were 'red' (significantly higher). RESULTS: For all surgeons, 19.6% were red, 72.1% yellow, and 8.3% green. There were 17.2% 'surgeon champions' and 6.2% 'nonchampions' that were green (P = .01), while 20.7 and 19.3% were red (P = .82). There was a significant association between volume and performance (P < .01). No surgeons in the lower two quartiles (<84; 84 to 180 cases), while 4 and 29% of higher-volume surgeons (181 to 404; >404 cases) were green. There was no statistical difference in red status by volume (P = .53). CONCLUSION: 'Surgeon champions' and high-volume surgeons were more likely to be high performers but not less likely to be low performers. Active involvement in quality improvement and/or high volume was associated with better outcomes but did not impart complication immunity. 'Green' surgeons should mentor colleagues to help reduce fractures by re-evaluating modifiable factors. Analyzing outcomes to promote quality and decrease complications is paramount.

Non-bonding energy directed designing of HDAC2 inhibitors through molecular dynamics simulation.

Designing an inhibitor having strong affinity in the active site pocket is the cherished goal of structure based drug designing. To achieve this, it is considerably important to predict which structural scaffold is better suited for change to increase affinity. We have explored five HDAC2 co-crystals having PDB ligand code-SHH (vorinostat), LLX, 20Y, IWX (BRD4884) and 6EZ (BRD7232). For analyzing protein-ligand interaction at an atomistic level, we have employed the NAMD molecular dynamics (MD) package. The obtained 100 ns long MD trajectories were subjected to quantitative estimations of non-bonding energies (NBEs) for inferring their interactions with the whole protein or its composite active site (CAS). In addition, relative ΔGbind was calculated to rank the inhibitors. These inhibitors' NBEs reveal that the phenyl moieties are the major structural scaffold where modifications should be attempted. We designed new compounds (NCs) via introducing hydroxyl groups at 4,5 position of the phenyl moiety of 6EZ, called NC1. Improvement in NC1 further encouraged us for CAP modification by isochromane and isoindoline moieties in place of oxabicyclooctane in NC1, resulting in NC2 and NC3. We also explored trifluoromethyl oxadiazole in 6EZ (NC4 and NC5) and SHH (NC6 and NC7). This moiety acts as a ZBG in NC4 while acting as a part of the foot-pocket in the rest. NC2 and NC6 have highest favorable NBEs among all studied ligands due increased favorable electrostatic contribution. We expect these NBEs data will provide atomistic level insights and benefit in designing new and improved HDAC2 inhibitors. Communicated by Ramaswamy H. Sarma.

Investigation of HDAC8-ligands' intermolecular forces through molecular dynamics simulations: profiling of non-bonding energies to design potential compounds as new anti-cancer agents.

Histone deacetylases are zinc-dependent isoform enzymes and play important role in cellular homeostasis. Among these, HDAC8 is a potential anticancer drug target. To design new inhibitors using protein-ligand energy profiles, an all atom molecular dynamics (MD) simulations were carried out on nine HDAC8-ligand co-crystals (PDBs: 1T64, 1T69, 1T67, 3F07, 1W22, 1VKG, 5FCW, 3SFF and 3SFH). TSN, SHH, B3N, AGE, NHB, CRI, 5YA, 0DI and 1DI are ligands of PDBs, respectively. For these HDAC8-ligands, relative Gibbs binding free energy (ΔGbind) from MM/PBSA method and non-bonding energies (NBE) are in agreement with each other (r2=0.678). Therefore, the NBEs are used to analyze ligands' sub-structures, namely zinc-binding, linker and CAP groups. For linker/CAP regions, this identified carbonyl, amide, and sulfonamide moieties as desirable and alkyl/aryl moieties as electrostatically unfavourable. Using this information, systematically new compounds were designed and subjected to MD simulations. This resulted in seven compounds (NC-I to NC-VII) with encouraging energy profiles (NBE: -76.25 to -127.09 kcal/mol; ΔGbind: -17.21 to -57.42 kcal/mol) in comparison to that of the HDAC8 ligands (NBE: -46.25 to -106.29 kcal/mol; ΔGbind: -14.74 to -49.52 kcal/mol). From these, NC-VI showed best energy profile (NBE = -126.15 kcal/mol; ΔGbind = -57.42 kcal/mol) suggesting its binding affinity and thermodynamic stability. In addition to this, NC-II and NC-III have shown promising NBE and ΔGbind profiles. These may serve as lead molecules for exploration against HDAC8 in cancer therapy. This has provided a basis for designing new compounds with improved NBE and ΔGbind profiles by modifying the unfavourable or not so favourable regions of ligands. [Formula: see text] Communicated by Ramaswamy H. Sarma.

IBX-mediated oxidative addition of isocyanides to cyclic secondary amines: total syntheses of alangiobussine and alangiobussinine.

The present study describes a robust and general method for the synthesis of C(1)-carboxamides through IBX-mediated oxidative addition of isocyanides to tryptolines and 1,2,3,4-tetrahydroisoquinolines. In this transformation, IBX plays a dual role of an oxidant and Lewis acid to activate imine facilitating isocyanide addition. Detailed mechanistic investigations were performed by isotopic labeling and real-time NMR experiments. The method was utilized for the gram scale syntheses of two alkaloids alangiobussine and alangiobussinine in 63% and 45% overall yield, respectively.

The Flint Lock: A Novel Technique in Total Knee Arthroplasty Closure.

Conventional interrupted sutures are traditionally used in extensor mechanism closure during total knee arthroplasty (TKA). In recent years, barbed suture has been introduced with the proposed benefits of decreased closure time and a watertight seal that is superior to interrupted sutures. Complication rates using barbed sutures and conventional interrupted sutures are similar. We propose a novel closure technique known as the Flint Lock, which is a double continuous interlocking stitch. The Flint Lock provides a quick and efficient closure to the extensor mechanism in TKA. In addition, similar to barbed suture, the Flint Lock should provide a superior watertight seal. It utilizes relatively inexpensive and readily available materials.

Identification of novel ß-lactams and pyrrolidinone derivatives as selective Histamine-3 receptor (H3R) modulators as possible anti-obesity agents.

Four series of structurally related ß-lactams, 2,5-pyrrolidinediones, azaspirodecatrienediones (ASDT) and dihydropyrroloquinoxalinetriones (DPQT) were synthesized by utilizing post-Ugi modifications in one-pot, and their activity towards human histamine-3 receptor (H3R) was evaluated. Out of 94 compounds, screened against histamine-3 receptor (H3R), 21 compounds showed high H3R selective agonist property with EC50 values ranging from 187 nM to 0.1 nM, whereas none of the compound was found to have the affinity towards other receptors of histamine family such as histamine H1, H2, and H4 receptor. All active compounds have no assay interference activity as determined by in-silico analysis and receptor independent luciferase assay and cell cytotoxicity assay. Given the important role of H3R in hypophagia, we also evaluated the in vivo effect of the representative compound 6k on the cumulative food intake in diet induce obese C57BL6/J mice. Interestingly, we observed that single dose administration (20 mg/kg, intraperitoneal injection) of 6k significantly suppressed cumulative food intake, while no significant effect was observed at 10 mg/kg. These results suggest that ß-lactams, 2,5-pyrrolidinediones, azaspirodecatrienediones (ASDT) and dihydropyrroloquinoxalinetriones (DPQT) could be useful for the development of anti-obesity candidate drugs.

Improvement in Depression and Physical Health Following Total Joint Arthroplasty.

BACKGROUND: Depression is a common co-morbid condition seen in arthroplasty patients. Pain and depression have been understood to influence one another, which may explain why this patient group experiences higher rates of depression than the general population. Arthroplasty can relieve pain and improve function, which may thereby initiate an improvement in the patient's depressive symptoms. METHODS: This retrospective study examined physical and mental domain outcomes of Short Form-36 health-related quality of life questionnaire among 146 patients who underwent primary hip or knee arthroplasty for osteoarthritis at a single institution during 2001-2004. These patients were classified into "depressed/anxious" and "non-depressed" groups based on their pre-operative mental component summary (MCS), with MCS < 42 defining depression. MCS and the subscales from the 36-Item Short-Form Health Survey form expected to be influenced by arthroplasty, Physical Function, Pain, and Role Physical were examined at 3 months and 1 year post-operative. RESULTS: At 1 year, 66.7% of the "depressed/anxious" group reported MCS > 42, suggesting improvement of their depressive symptoms. Both groups reported similar improvements in their 36-Item Short-Form Health Survey subscale scores for Pain and Physical Function. However, the depressed group's scores were lower than the non-depressed group's at all time points. CONCLUSION: Arthroplasty significantly improved Physical Function and Pain in depressed patients, while their depressive symptoms improved. This improvement may be in response to the resolution of physical symptoms and represents an additional benefit to this elective surgery. Further studies, in larger populations, are needed to establish patient characteristics associated with non-resolution of depressive symptoms and the role of mental health interventions to optimize outcomes for hip and knee arthroplasty patients.

An Efficient Synthesis of 2-Substituted Benzimidazoles via Photocatalytic Condensation of o-Phenylenediamines and Aldehydes.

A photocatalytic method has been developed for the efficient synthesis of functionalized benzimidazoles. This protocol involves photocatalytic condensation of o-phenylenediamines with various aldehydes using the Rose Bengal as photocatalyst. The method was found to be general and was successfully employed for accessing pharmaceutically important benzimidazoles by the condensation of aromatic, heteroaromatic and aliphatic aldehydes with o-phenylenediamines, in good-to-excellent yields. Notably, the method was found to be effective for the condensation of less reactive heterocyclic aldehydes with o-phenylenediamines.

Reducing Fracture Risk Adjacent to a Plate With an Angulated Locked End Screw.

OBJECTIVES: Locking screws often are used in the treatment of osteoporotic fractures. Studies show that locking screws can increase bone stresses at the plate end, which increases the possibility of peri-implant fracture. This study evaluates whether the technique used to insert the end screw is related to the fracture tolerance adjacent to the plate. METHODS: Twelve groups of plate constructs were evaluated using a fibular diaphyseal surrogate with mechanical properties similar to osteoporotic bone. All inboard screws were nonlocked with only the end screw fixation differing among groups. The end screws were inserted either perpendicularly to the plate or at an angle of 30 degrees for 6- and 12-hole plates. For both orientations, the end screws were inserted nonlocked, locked, or by a locked overdrilling technique, resulting in 6 groups per plate length. The perpendicular nonlocked screws represented a control group. The constructs were tested to failure in 4-point bending to determine peak load, failure energy, and stiffness. RESULTS: All constructs failed by peri-implant fracture along a plane through the 2 cortical holes of the end screw. Compared with the control group, an angulated locked screw at the plate end significantly increased the peak bending moment and energy required to produce a fracture for both plate lengths (6-hole, P = 0.008, P < 0.001; 12-hole, P = 0.006, P < 0.001). CONCLUSIONS: The use of an angulated locked end screw may enhance the resistance of osteoporotic bone to peri-implant fractures caused by bending forces.

Reverse oblique end screws in nonlocking plates decrease construct strength in synthetic osteoporotic bone medium.

Fracture stability can be challenging for osteoporotic individuals. The end screw of nonlocked plates is subjected to the greatest loading and is typically the site of construct failure. To enhance fixation, the end screw can be angled away from the fracture. The current study biomechanically evaluated screws angled the other direction: toward the fracture using 3.5-mm dynamic compression plates in an osteoporotic bone model. Three different plate lengths (6-, 8-, 12-hole) were tested in three-point bending with an oblique, perpendicular, or reverse oblique end screw. The peak load for loss of screw fixation for the reverse oblique end screw constructs was significantly less than the other screw orientations for all plate lengths. The 12-hole peak load, energy, and displacement magnitudes for all three screw orientations were significantly greater than all 6- and 8-hole constructs. The use of a reverse oblique end screw is inferior to both perpendicular and oblique end screws.

Rapid loss of efficacy to the antiseizure drugs lamotrigine and carbamazepine: a novel experimental model of pharmacoresistant epilepsy.

PURPOSE: Kindling is a well-established model of secondarily generalized partial seizures that is widely employed in the search for novel antiseizure drugs. During the kindling and postkindling acquisition phase, an active process of neuronal remodeling occurs. We tested the hypothesis that exposure to the voltage-gated sodium channel blockers lamotrigine (LTG) and carbamazepine (CBZ) during the period of active remodeling will lead to a diminished therapeutic effect. METHODS: Two days after the last kindling stimulation, fully kindled rats were randomized to receive either 0.5% methyl cellulose (MC), LTG (30 mg/kg), or CBZ (40 mg/kg). The effect of LTG and CBZ on behavioral seizure severity and electrographic afterdischarge duration (ADD) was recorded. One week after this treatment, rats in both groups were rechallenged with LTG 30 or CBZ 40 mg/kg and their seizure score and ADD recorded. In vitro efficacy of LTG on neuronal action potentials was also evaluated using whole cell current clamp recording in hippocampal brain slices obtained from kindled control rats, LTG-sensitive kindled rats, and LTG-resistant kindled rats. KEY FINDINGS: When acutely administered 48 h after the last kindling stimulation, LTG and CBZ blocked the expression of behavioral seizures and reduced the ADD. In contrast, a second challenge dose of LTG or CBZ administered after a 7-day "no drug, no stimulation" period did not result in reduction of either the seizure score or the ADD. Interestingly, the potassium channel opener, ezogabine, also known as retigabine (EZG; 40 mg/kg), blocked the expression of behavioral seizures at both time points evaluated (i.e., 2 days and 9 days after last stimulation). In vivo resistance to LTG was associated with a similar reduction in the ability of LTG to limit action potential firing in CA1 neurons. LTG (50 µm) significantly decreased the number of action potentials generated by a depolarizing current pulse in neurons recorded from slices obtained from kindled control and LTG-sensitive rats, but not in slices obtained from LTG-resistant rats. SIGNIFICANCE: Collectively, results obtained from both in vivo and in vitro studies demonstrate that even a single exposure to the sodium channel blockers LTG, or CBZ, during the postkindling remodeling phase leads to an altered pharmacologic response to these two ASDs, but not to EZG. The LTG- and CBZ-resistant amygdala kindled rats may serve as a useful model of therapy-resistant epilepsy.

Carbamazepine, but not valproate, displays pharmacoresistance in lamotrigine-resistant amygdala kindled rats.

The voltage gated sodium channel (VGSC) blocker lamotrigine (LTG), when administered during kindling acquisition, leads to the development of resistance to LTG. The present study aimed to assess whether LTG-resistant amygdala-kindled rats display subsequent resistance to the VGSC blocker carbamazepine (CBZ) and the broad-spectrum antiepileptic drug (AED) sodium valproate (VPA). Two groups of male Sprague Dawley rats received either 0.5% methylcellulose (MC) or LTG (5mg/kg, i.p.) 1h before each amygdala kindling stimulation. Treatments were stopped once both the groups were fully kindled. Two days later, both groups were challenged with a higher dose of LTG (15mg/kg, i.p.) to verify LTG-resistance in the experimental group (i.e., LTG-pretreated rats). The efficacy of CBZ and VPA was then evaluated in both groups. A higher dose of LTG blocked fully kindled seizures in the vehicle-treated rats but not seizures in the LTG-treated group. The mean seizure score, of the control group (1.2±0.3) was significantly lower (P<.05) than that of the LTG-treated population (3.5±0.7; n=8). A lower percent of the population in the control group was observed to display a generalized stage 4-5 seizure compared to the experimental group (i.e., those that received LTG during kindling acquisition) (28.5% vs. 62%, respectively). Interestingly, CBZ (10, 20, and 40mg/kg) displayed a dose-dependent anticonvulsant effect in the vehicle-kindled group, but was less effective in LTG-treated animals. In contrast, VPA (300mg/kg) effectively blocked the behavioral seizure and decreased the afterdischarge duration (ADD) in both vehicle and LTG groups. These findings suggest that the LTG-resistant, amygdala-kindled rat may represent a novel model of pharmacoresistant epilepsy.

Bioactivity of novel transition metal complexes of N'-[(4-methoxy)thiobenzoyl]benzoic acid hydrazide.

Cu(II), Fe(III), and Mn(II) complexes of a novel ligand N'-[(4-methoxy)thiobenzoyl]benzoic acid hydrazide (H(2)mtbh) have been synthesized and characterized by elemental analyses, IR, UV-vis, NMR, mass, EPR and Mössbauer spectroscopy. The results suggest a square planar structure for [Cu(Hmtbh)Cl] and [Cu(mtbh)] whereas an octahedral structure for [Mn(Hmtbh)(2)] and [Fe(Hmtbh)(mtbh)]. Mn(II) and Fe(III) complexes were found to inhibit proliferation of HT29 cells. [Mn(Hmtbh)(2)] and [Fe(Hmtbh)(mtbh)] inhibited proliferation of HT29 cells with half maximal inhibition (IC(50)) of 8.15+/-0.87 and 68.1+/-4.8 microM, respectively, whereas H(2)mtbh showed growth inhibition with IC(50) of 90.9+/-7.8 microM and were able to inhibit NMT activity in vitro. Mn(II) and Fe(III) complexes inhibited NMT activity in a dose dependent manner with IC(50) values of 20+/-2.2 and 60+/-7.2 microM, respectively, whereas ligand (H(2)mtbh) displayed IC(50) of 3.2+/-0.5 mM.

Triethyl-ammonium N'-(benzyl-sulfanylthio-carbonyl)-2-hydroxy-benzohydrazidate.

In the title compound, C(6)H(16)N(+)·C(15)H(13)N(2)O(2)S(2) (-), the thione S atom is in a cis configuration with respect to the phenyl and benzene rings, while it adopts a trans configuration with respect to the carbonyl group. The dihedral angle between the benzene and phenyl rings is 78.81 (2)°. The mol-ecular conformation is stabilized by intra-molecular O-H⋯O and N-H⋯S hydrogen bonds, while inter-molecular N-H⋯O, N-H⋯N and weak C-H⋯O inter-actions help to stabilize the crystal structure.

Protective effect of resveratrol against pentylenetetrazole-induced seizures and its modulation by an adenosinergic system.

The effect of trans-resveratrol (resveratrol), a polyphenolic compound with potent antioxidant activity, was investigated against pentylenetetrazole (PTZ) induced seizures in rats. Resveratrol (20, 40, and 80 mg/kg i.p.) administered 20 min prior to convulsive challenge with PTZ (60 mg/kg i.p.) dose dependently reduced the percent incidence of generalized tonic-clonic convulsions. Resveratrol (40 mg/kg) also potentiated the effect of sodium valproate (150 mg/kg) and diazepam (2 mg/kg) against PTZ-induced seizures. Since adenosine, an endogenous anticonvulsant, has been demonstrated to modulate the action of various antiepileptics, experiments were also carried out to determine whether an adenosinergic mechanism is involved in the anticonvulsant action of resveratrol. When a subanticonvulsant dose of adenosine (500 mg/kg) was administered together with resveratrol, a significant reduction in the percent incidence of generalized tonic-clonic convulsions was observed. Moreover, the nonspecific adenosine receptor antagonist theophylline (50 mg/kg i.p.) significantly reversed the resveratrol-induced protection, whereas the specific adenosine A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine (1 mg/kg i.p.) could not reverse the resveratrol-induced protection. The findings of the present study suggest an antiepileptic potential of resveratrol and that an adenosinergic mechanism may play a role in its anticonvulsant activity.