Opioid Prescription Consumption Patterns After Total Joint Arthroplasty in Chronic Opioid Users Versus Opioid Naive Patients.

Although chronic preoperative opioid use has been linked to inferior total joint arthroplasty outcomes, little research exists on postoperative prescribing patterns for opioid-naive orthopaedic patients versus chronic opioid users. Method: The New York State Prescription Monitoring Program database, which tracks controlled prescriptions dispensed in-state over the preceding 12 months, was retrospectively queried for 386 patients who underwent primary, elective total hip or knee arthroplasty at a high-volume, urban medical center from May through December 2017. Seventy-four patients were excluded because they did not return prescription monitoring program results, leaving 312 patients. Prescribers, medications, dates prescribed and filled, and quantity dispensed were recorded 3 months preoperatively through 12 months postoperatively. We defined chronic users as ≥2 opioid prescriptions filled in 3 preoperative months and opioid-naive as <2 filled. Opioid use was compared univariately using 2-tailed Student t-tests. Results: Chronic opioid users (n = 49; 15.7%) filled an average of 13,006.64 morphine equivalent doses per patient in the 12-month postoperative period, while opioid-naive users (n = 263; 84.3%) filled an average of 854.48 morphine equivalent doses per patient (P < 0.01). Opioid use in the chronic-user group was significantly higher in each 6-week postoperative interval (P < 0.01). These trends remained significant when stratified by procedure. For opioid-naive patients, 74% of opioid prescriptions were prescribed by our orthopaedic department. For chronic users, only 21% of opioid prescriptions originated from our department. Chronic users were found to cyclically fill opioid prescriptions every 3 to 4 weeks postoperatively as far out as 12 months and were significantly more likely to fill nonopioid controlled substance prescriptions both preoperatively and postoperatively (P < 0.01). Discussion: Chronic opioid users undergoing arthroplasty filled significantly more opioid prescriptions than opioid-naive patients. Chronic users obtained prescriptions from myriad sources, only a minority of which originated from our orthopaedic department. In the current opioid epidemic, vigilance regarding opioid prescribing is critical.

Large diameter femoral heads: is bigger always better?

Dislocation remains among the most common complications of, and reasons for, revision of both primary and revision total hip replacements (THR). Hence, there is great interest in maximising stability to prevent this complication. Head size has been recognised to have a strong influence on the risk of dislocation post-operatively. As femoral head size increases, stability is augmented, secondary to an increase in impingement-free range of movement. Larger head sizes also greatly increase the 'jump distance' required for the head to dislocate in an appropriately positioned cup. Level-one studies support the use of larger diameter heads as they decrease the risk of dislocation following primary and revision THR. Highly cross-linked polyethylene has allowed us to increase femoral head size, without a marked increase in wear. However, the thin polyethylene liners necessary to accommodate larger heads may increase the risk of liner fracture and larger heads have also been implicated in causing soft-tissue impingement resulting in groin pain. Larger diameter heads also impart larger forces on the femoral trunnion, which may contribute to corrosion, metal release, and adverse local tissue reactions. Alternative large bearings including large ceramic heads and dual mobility bearings may mitigate some of these risks, and several of these devices have been used with clinical success.

What do we know about taper corrosion in total hip arthroplasty?

Mechanically assisted crevice corrosion (MACC) at metal/metal modular junctions in which at least one of the components is fabricated from cobalt-chromium alloy, has reemerged as a potential clinically significant complication in total hip arthroplasty. The clinical manifestation of MACC may include the development of an adverse local tissue reaction (ALTR), similar to what has been described in association with metal-on-metal bearing total hip and resurfacing arthroplasty. The clinical presentation of MACC-associated ALTRs may include pain and possibly late recurrent dislocations. Abnormal metal artifact reduction sequence magnetic resonance images and elevated serum metal levels (cobalt elevations out of proportion to chromium elevations) can be helpful in the diagnosis of these MACC-associated ALTRs.

Large ceramic femoral heads: what problems do they solve?

Large ceramic femoral heads offer several advantages that are potentially advantageous to patients undergoing both primary and revision total hip replacement. Many high-quality studies have demonstrated the benefit of large femoral heads in reducing post-operative instability. Ceramic femoral heads may also offer an advantage in reducing polyethylene wear that has been reported in vitro and is starting to become clinically apparent in mid-term clinical outcome studies. Additionally, the risk of taper corrosion at a ceramic femoral head-neck junction is clearly lower than when using a metal femoral head. With improvements in the material properties of both modern ceramic femoral heads and polyethylene acetabular liners that have reduced the risk of mechanical complications, large ceramic heads have gained popularity in recent years.

The two-stage standard in revision total hip replacement.

Two-stage exchange remains the gold standard for treatment of peri-prosthetic joint infection after total hip replacement (THR). In the first stage, all components and associated cement if present are removed, an aggressive debridement is undertaken including a complete synovectomy, and an antibiotic-loaded cement spacer is put in place. Patients are then treated with six weeks of parenteral antibiotics, followed by an 'antibiotic free period' to help ensure the infection has been eradicated. If the clinical evaluation and serum inflammatory markers suggest the infection has resolved, then the second stage can be completed, which involves removal of the cement spacer, repeat debridement, and placement of a new THR.

Liver tumors in wild flatfish: a histopathological, proteomic, and metabolomic study.

Fish play host to viral, bacterial, and parasitic diseases in addition to non-infectious conditions such as cancer. The National Marine Monitoring Programme (NMMP) provides information to the U.K. Government on the health status of marine fish stocks. An aspect of this work relates to the presence of tumors and other pathologies in the liver of the offshore sentinel flatfish species, dab (Limanda limanda). Using internationally agreed quality assurance criteria, tumors and pre-tumors are diagnosed using histopathology. The current study has expanded upon this work by integrating these traditional diagnostic approaches with ones utilizing modern technologies for analysis of proteomic and metabolomic profiles of selected lesions. We have applied SELDI and FT-ICR technologies (for proteomic and metabolomic analyses, respectively) to tumor and non-tumor samples resected from the liver of dab. This combined approach has demonstrated how these technologies are able to identify protein and metabolite profiles that are specific to liver tumors. Using histopathology to classify "analysis groups" is key to the success of such an approach since it allows for elimination of spurious samples (e.g., those containing parasite infections) that may confuse interpretation of "omic" data. As such, the pathology laboratory plays a central role in collating information relating to particular specimens and in establishing sampling groups relative to specific diagnostic questions. In this study, we present pilot data, which illustrates that proteomics and metabolomics can be used to discriminate fish liver tumors and suggest future directions for work of this type.

Precision and accuracy of a transportable dual-energy X-ray absorptiometry unit for bone mineral measurements in guinea pigs.

Dual energy X-ray absorptiometry (DXA) is a valuable tool for measuring bone mineral content (BMC) and bone mineral density (BMD) in small-animal research. The present study was devised to establish guidelines and to define sites for bone mineral measurements in guinea pigs and to evaluate the accuracy of a new transportable research DXA unit. Repeated scans were performed on 30 guinea pig hindlimbs (in situ) as well as the isolated bones from these limbs (ex situ). Nine exactly specified regions of interest (ROIs) were analyzed twice for BMC and BMD by three different observers. Additionally, the BMC of whole bones and bone segments as measured by DXA was correlated to ash weights of bone in a subset of five animals to determine the accuracy of the DXA measurements. On ex situ scans, intra-observer variability for BMD ranged from 0.09% to 2.33% and inter-observer variability from 0.23% to 5.86% depending on the site studied, with smaller ROIs exhibiting more variability. Coefficients of variance (CV) for BMC measurements were slightly higher than for BMD. However, BMC offered a better correlation between in situ and ex situ values than BMD. On in situ scans, observer variability for BMD and BMC for comparable sites was higher than the ex situ variability. The results of this study indicate that DXA provides an accurate measurement of BMC even in small specimens. The precision of BMC and BMD measurements in situ can be improved considerably by using specific, well-defined ROIs and by careful placement of the bones to be scanned in close proximity to the scanning surface.

Supramolecular organization of alpha,alpha'-disubstituted sexithiophenes.

The self-assembly of alpha,alpha'-linked sexithiophenes with chiral and achiral penta(ethylene glycol) chains attached at the alpha-positions of the terminal rings, that is, 2,2':5',2'':5'',2''':5''',2'''':5'''',2'''''-sexithiophene-5,5'''''-dicarboxylic acid-2S)-2-methyl-3,6,9,12,15-pentaoxahexadecyl ester (1) and 2,2':5',2'':5'',2''':5'''',2''''':5''''',2'''''-sexithiophene-5,5'''''-dicarboxylic acid-3,6,9,12,15-pentaoxahexadecyl ester (2), respectively is described. Analysis of the UV/vis, fluorescence, circular dichroism, and circular polarization of luminescence spectroscopic data shows that these compounds form chiral aggregates in polar solvents and in the solid state. In n-butanol aggregation occurs at temperatures below 30 degrees C, while above this threshold temperature the aggregates break up without an intermediate disordered state of aggregation, and the compounds are molecularly dissolved. The "melting temperature" of the aggregates depends on the concentration of sexithiophene, indicating that the optical changes observed are a result of intermolecular processes. Mass spectrometric measurements reveal that 1 and 2 can form mixed aggregates. Analysis of the optical spectra reveals that in these mixed aggregates, chiral 1 molecules act as "sergeants" to direct the packing of the "soldiers" 2, illustrating cooperativity within the columns. In water, the same type of chiral aggregates are formed as in n-butanol below 30 degrees C; however, these aggregates are still present, but the chirality is lost above 30 degrees C. In spin-coated films of 1 chiral aggregates are present. AFM studies show that 1 self-organizes into chiral fiberlike structures in the solid state. Furthermore both 1 and 2 display thermotropic liquid crystalline behavior between 180 and 200 degrees C.

Electrospray ionization Fourier transform mass spectrometric analysis of wine.

Positive- and negative-ion electrospray ionization Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry has been used for direct analysis of five wines (California Red, Corbiere, Zinfandel, Beaujolais, and Sauvignon Blanc), without any prior separation or purification steps. The high mass resolving power (typically m/Delta m(50%) > or = 80,000, in which Delta m(50%) is mass spectral peak full width at half-maximum peak height) and mass accuracy (< or =1 ppm) of FT-ICR mass spectrometry make it ideal for the study of complex mixtures such as wine, because the components are simultaneously resolved and identified as to elemental composition. Moreover, the high dynamic range of the instrument is advantageous for identifying trace components. The positive-ion mass spectra obtained from the wines were somewhat similar and were dominated by sucrose and (for red wines) anthocyanins. More than 30 compounds (phenolics and carbohydrates) were identified. The negative-ion mass spectra exhibited much greater variation among different wines, with several compounds peculiar to each wine. Elemental compositions could be assigned with high confidence to 76-94% of negative ions of >10% relative abundance. The present results suggest that it may be possible to fingerprint a wine on the basis of its negative-ion ESI FT-ICR mass spectrum.

Electron capture dissociation and infrared multiphoton dissociation MS/MS of an N-glycosylated tryptic peptic to yield complementary sequence information.

Glycoproteins are a functionally important class of biomolecules for which structural elucidation presents a challenge. Fragmentation of N-glycosylated peptides, employing collisionally activated dissociation, typically yields product ions that result from dissociation at glycosidic bonds, with little occurrence of dissociation at peptide backbone sites. We have applied two dissociation techniques, electron capture dissociation (ECD) and infrared multiphoton dissociation (IRMPD), in a 7-T Fourier transform ion cyclotron resonance mass spectrometer, in the investigation of an N-glycosylated peptide from an unfractionated tryptic digest of the lectin of the coral tree, Erythrina corallodendron. ECD provided c and z. ions derived from the peptide backbone, with no observed loss of sugars. Cleavage at 11 of 15 backbone amine bonds was observed. The lack of cleavage at sites located close to the glycosylated asparagine residue may result from steric blocking by the glycan. IRMPD provided abundant fragment ions, primarily through dissociation at glycosidic linkages. The monosaccharide composition and the presence of three glycan branch sites could be determined from the IRMPD fragments. The two types of spectra, obtained with the same instrument, thus provide complementary structural information about the glycopeptide. The current result extends the applicability of ECD for glycopeptide analysis to N-glycosylated peptides and to peptides containing branched, highly substituted glycans.

Specific electrochemical nitration of horse heart myoglobin.

Earlier findings on electronitration of hen egg-white lysozyme demonstrated a product which was mononitrated at Tyr23, by ion-exchange chromatography, absorbance at 430 nm, dithionite reduction, and Edman sequencing of a nitrated proteolytic peptide. However, the whole protein was not sequenced; therefore, although the enzyme remained active upon nitration, reaction at other residues could not be completely eliminated. This study has now been extended to the redox protein myoglobin. We demonstrate the novel electronitration (electrooxidation in the presence of nitrite) of a specific tyrosine residue in horse heart myoglobin and also in apomyoglobin. Production of the yellow chromophore, 3-nitrotyrosine (3-NT), was apparent in apomyoglobin from A430 but was masked in holomyoglobin by the Soret band. In both cases, the presence of 3-NT in the electronitrated samples was further indicated by the binding of antibody to 3-NT in Western blots. High-resolution electrospray ionization (ESI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry revealed a reaction product at [M + 45] (consistent with substitution of NO2 for H), indicating that the nitration reaction is the only reaction occurring which gives rise to a change in mass in the electrooxidation. Fragmentation mass spectrometry identified the nitration site as Tyr103, with no nitration at Tyr146. The procedure may be useful in preparing model nitrated proteins for the study of disease mechanisms.

The effect of screw type on the fixation of depressed fragments in tibial plateau fractures.

The ability of various screw types to stabilize depressed tibial plateau fractures was determined in a biomechanical study using a Sawbones model. Two sizes of both cancellous and cortical screws were evaluated for both supportfrom below and through the depressed fragment. As a general trend, cancellous bone screws provided a greater resistance to fragment displacement than cortical bone screws, and screws with a smaller thread diameter provided greater resistance to displacement than screws of the same thread type with a larger diameter. These results agree with the accepted standard that cancellous screws provide better fixation for tibial plateau fractures, but also are counterintuitive in that smaller screws provided greater fixation than larger screws of the same type.

Calmodulin-peptide interactions: apocalmodulin binding to the myosin light chain kinase target-site.

Noncovalent binding of the synthetic peptide RS20 to calmodulin in the presence of calcium was confirmed by electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry to form a complex with a 1:1:4 calmodulin/RS20/calcium stoichiometry. There was no evidence for formation of a calmodulin-RS20-Ca(2) species. The absence of calmodulin-RS20-Ca(2) would be consistent with models in which the two globular domains are coupled functionally. There was evidence that calmodulin, RS20-calmodulin without associated calcium, and calmodulin-RS20-Ca(4) existed together in solution, whereas calmodulin-calcium complexes were absent. It is proposed that calcium binding to form the calmodulin-RS20-Ca(4) complex occurs after an initial RS20-calmodulin binding event, and serves to secure the target within the calmodulin structure. The binding of more than one RS20 molecule to calmodulin was observed to induce unfolding of calmodulin.

Cloning and sequence analysis of kappa and gamma cynomolgus monkey immunoglobulin cDNAs.

One gamma heavy chain and 10 kappa light chain cynomolgus monkey (Macaca fascicularis) immunoglobulin cDNAs have been cloned and sequenced. Comparisons of the variable (V) regions to human antibody sequences have revealed extensive identity, exhibiting 93% at the amino acid level for the VH framework regions, and 88-99% for the V kappa frameworks. Identification of very few cynomolgus monkey-specific framework region residues suggests a role for cynomolgus monkey antibodies as donators of variable regions to chimeric monoclonal antibodies for utilisation in human therapy with human constant (C) regions. The cynomolgus monkey C kappa region exhibited 83% amino acid identity to its human counterpart, and the C gamma region was 95, 93, 95, and 95% similar to the human C gamma 1, C gamma 2, C gamma 3, and C gamma 4 regions, respectively. Evolutionary analysis of the C gamma genes, using the silent molecular clock, suggests that the divergence between cynomolgus monkey and human occurred before the time at which the ancestral gamma gene diverged into the multiple isotypes observed in humans.

Humanized monoclonal antibody CAMPATH-1H: myeloma cell expression of genomic constructs, nucleotide sequence of cDNA constructs and comparison of effector mechanisms of myeloma and Chinese hamster ovary cell-derived material.

Expression of CAMPATH-1H, a humanized MoAb directed against an abundant surface antigen on human lymphocytes, has been studied using transfected myeloma cells. As the site of chromosome integration of DNA transfected into a cell is random we investigated the feasibility and frequency of hitting a 'jackpot' site for expression after co-transfection with CAMPATH-1H heavy and light chain constructs in genomic context. A cell line generating 40 micrograms/ml of CAMPATH-1H in spent culture supernatant was achieved. The full nucleotide sequence of the CAMPATH-1H heavy and light chain cDNA clones is also shown, in addition a comparison of the effector mechanisms, antibody dependent cellular cytotoxicity and complement dependent cytotoxicity, of myeloma cell and Chinese hamster ovary (CHO) cell-derived CAMPATH-1H is reported.