Management of the peri-intubation period in patients with pulmonary arterial hypertension and respiratory failure.

PURPOSE OF REVIEW: The endotracheal intubation of patients with pulmonary arterial hypertension (PAH) in respiratory distress is a highly morbid procedure that can precipitate hemodynamic collapse. Here we review our strategy for confronting this difficult clinical situation. RECENT FINDINGS: There are no clinical trials that explore best practices in the management of patients with PAH and respiratory failure. Here we provide a practical approach to respiratory support, inopressor and pulmonary vasodilator selection, hemodynamic considerations, point-of-care ultrasound monitoring, and endotracheal intubation in patients with PAH in respiratory failure.

Operative treatment of acromial and scapular spine fracture nonunions complicating reverse total shoulder arthroplasty.

BACKGROUND: Fractures of the acromion and spine can have a major impact on the outcome of reverse shoulder arthroplasty (RSA) with respect to pain, motion, and function. Reports on internal fixation for these fractures are isolated to small series or case reports with variable outcomes. The purpose of this study was to report on the outcome of open reduction and internal fixation (ORIF) of acromion or spine fractures encountered before or after RSA and describes our evolution of fixation techniques. METHODS: Between 2011 and 2023, 22 fractures or nonunions of the acromion or spine of the scapula underwent ORIF at a single institution and were followed for a minimum of 1 year. In 16 shoulders, fractures occurred after RSA, whereas 5 shoulders underwent ORIF prior to RSA. One shoulder had undergone prior failed ORIF elsewhere and revision ORIF was performed at our institution. There were 10 males and 12 females with a mean age of 67 (SD = 15.1) years. Fixation strategies included single (n = 11) and double plate fixation (n = 11). Kruskal-Wallis one-way analyses of variance were used to analyze continuous variables and Chi-square tests employed for categorical variables. RESULTS: Of the 5 fractures treated with ORIF pre-RSA, 1 shoulder suffered an additional fracture medial to the hardware and 1 required additional bone grafting for incomplete union at the time of RSA. These 5 shoulders all underwent RSA uneventfully, but 1 fracture experienced late displacement of the scapular spine nonunion, leading to plate removal. Of the 16 post-RSA ORIF shoulders, radiographic union was confirmed in 14 and substantial residual inferior angulation identified in 3. New fractures occurred after ORIF in 5 shoulders. For patients who underwent ORIF after RSA, pain scores improved from a mean of 8 to 1.9 points, with more modest elevation gains (58.2°-91.3° pre and postoperatively, respectively). CONCLUSIONS: ORIF of acromion and scapular spine fractures or nonunions in the setting of RSA have the potential to lead to union. When these fractures and nonunions are encountered prior to RSA, ORIF allows for uneventful RSA implantation, but secondary displacement may occur. ORIF seems to lead to improvements in pain, but more modest improvements in motion and function. Our fixation strategy has evolved to (1) dual plating, (2) spanning the whole length of the spine with 1 of the plates, (3) use of hook features under the acromion or os trigonum if possible, and (4) liberal use of bone graft.

Polyanionic Receptors for Carboxylates in Water.

Receptors for carboxylate anions have many possible biomedical applications, including mimicry of the vancomycin group of antibiotics.  However, binding carboxylates in water, the biological solvent, is highly challenging due to the hydrophilicity of these polar anions.  Here we report, for the first time, the recognition of simple carboxylates such as acetate and formate in water by synthetic receptors with charge-neutral binding sites.  The receptors are solubilised by polyanionic side-chains which, remarkably, do not preclude anion binding.  The tricyclic structures feature two identical binding sites linked by polyaromatic bridges, capable of folding into closed, twisted conformations.  This folding is hypothesised to preorganise the structures for anion recognition, mimicking the process which generates many protein binding sites.  The architecture is suitable for elaboration into enclosed structures with potential for selective recognition of biologically relevant carboxylates.

Inhaled Pulmonary Vasodilator Utilization and Cost Following Initiation of a Protocol in a Quaternary Academic Heart Center Intensive Care Unit.

OBJECTIVES: To examine the use of inhaled nitric oxide (iNO) and inhaled epoprostenol (iPGI2) before and after implementation of an iPGI2-preferential protocol and the associated cost differences after rollout. DESIGN: A single-center, retrospective analysis. SETTING: A quaternary university hospital. PARTICIPANTS: All patients admitted to the Heart Center Intensive Care Unit (HCICU) who required inhaled pulmonary vasodilator use between December 2017 and November 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The HCICU comprised 84% of hospital-wide iNO utilization and 59% of hospital-wide iPGI2 use across the entire study period. There was no significant difference in postsurgical HCICU admission rates across the study period. There was a significant decrease in iNO mean monthly use from 578 ± 230 to 69 ± 71 hours, and a significant concurrent increase in iPGI2 from 756 ± 443 to 1,210 ± 547 hours after the implementation of a protocol. There were no changes in the average length of ICU stay between the 2 time periods. The protocol implementation led to a projected annual savings of roughly $1,180,000. CONCLUSIONS: These findings showed that multidisciplinary protocol development and implementation can have a substantial impact on medication utilization and lead to significant reductions in cost.

Acute versus delayed radial head arthroplasty for the treatment of radial head fractures.

BACKGROUND: Radial head arthroplasty (RHA) is an important tool in the acute treatment of comminuted radial head and neck fractures. RHA is also performed in a delayed manner after failed open reduction and internal fixation, for fracture malunion or nonunion, and other chronic post-traumatic elbow disorders where restoration of the lateral column of the elbow is considered necessary. The relative efficacy and longevity of acute vs. delayed RHA is unknown. We sought to compare clinical, radiographic, and patient-reported outcomes between these groups. METHODS: We identified patients ≥18 years old who underwent an RHA between 2000 and 2018 and then extracted 135 total elbows with a mean follow-up of 2.3 years that sustained isolated radial head fractures (30%), terrible triad injuries (66%), or Essex-Lopresti injuries (4%). The acute cohort (RHA: <12 weeks) contained 101 elbows that underwent surgery at a mean of 0.6 weeks (range, 0 days to 7 weeks, 96% <2 weeks) from injury, whereas the delayed cohort (RHA: 12 weeks to 2 years) contained 34 elbows that underwent surgery at a mean of 36 weeks (range, 14-82 weeks) from injury. Patients in the acute group had a higher percentage of terrible triad injuries (75% vs. 40%, P < .001) and Mason 3 fractures (98% vs. 45%, P < .001). RESULTS: At the final follow-up, 13 of 101 patients in the acute cohort (13%) and 7 of 34 patients in the delayed cohort (21%) required implant revision or resection. A total of 25 patients (25%) in the acute cohort and 12 patients (35%) in the delayed cohort required a reoperation. Kaplan-Meier 2-year survival estimates free of implant resection or revision (90% acute, 86% delayed) and reoperation (76% acute, 70% delayed) were similar between groups. In patients with 5-year follow-up, there was an increased rate of revision or resection in the delayed group (30% vs. 13%). Two-year survival estimates free of radiographic loosening were 80% in the acute cohort vs. 57% in the delayed cohort (P = .04). Mayo Elbow Performance Score at 2 years demonstrated mean scores of 83 and 79 in the acute and delayed groups, respectively, with 71% of the acute cohort and 64% of the delayed cohort achieving good or excellent scores. CONCLUSIONS: Our results demonstrated that although 2-year Kaplan-Meier survival free of revision or resection estimates and reoperation rates was equivalent between the groups, the delayed group experienced worse Mayo Elbow Performance Score outcomes, a higher revision or resection rate at 5 years, and an increased rate of radiographic loosening.

Does proximal versus distal injury location of the medial ulnar collateral ligament of the elbow differentially impact elbow stability? An ultrasound-guided and robot-assisted biomechanical study.

BACKGROUND: The location (proximal vs. distal) of elbow medial ulnar collateral ligament (MUCL) tears impacts clinical outcomes of nonoperative treatment. The purposes of our study were to (1) determine whether selective releases of the MUCL could be performed under ultrasound (US) guidance without disrupting overlying soft tissues, (2) assess the difference in medial elbow stability for proximal and distal releases of the MUCL using stress US and a robotic testing device, and (3) elucidate the flexion angle that resulted in the greatest amount of medial elbow laxity after MUCL injury. METHODS: Sixteen paired, fresh-frozen elbow specimens were used. Valgus laxity was evaluated with both US and robotic-assisted measurements before and after selective MUCL releases. A percutaneous US-guided technique was used to perform proximal MUCL releases in 8 elbows and to perform distal MUCL releases in their matched pairs. The robot was used to determine the elbow flexion angle at which the maximum valgus displacement occurred for both proximally and distally released specimens. Open dissection was then performed to assess the accuracy of the percutaneous releases. RESULTS: Percutaneous US-guided releases were successfully performed in 15 of 16 specimens. The proximal release resulted in greater valgus angle displacement (11° ± 2°) than the distal release (8° ± 2°) between flexion angles of 30° and 70° (P < .0001 at 30°, P < .0001 at 40°, P = .001 at 50°, P = .005 at 60°, and P = .020 at 70°). Valgus displacement between release locations did not reach the level of statistical significance between 80° and 120° (P = .051 at 80°, P = .131 at 90°, P = .245 at 100°, P = .400 at 110°, and P = .532 at 120°). When we compared the values for the mean increase in US delta gap (stressed - supported state) from before to after MUCL release, the proximally released elbows had larger increases than the distally released elbows (5.0 mm proximal vs. 3.7 mm distal, P = .032). After MUCL release, maximum mean valgus displacement occurred at 49° of flexion. CONCLUSIONS: US-guided selective releases of the MUCL can be performed reliably without violating the overlying musculature. Valgus instability is not of greater magnitude for distal releases when compared with proximal releases. This findings suggests there must be alternative factors to explain the difference in clinical prognosis between distal and proximal tears. The observed flexion angle for maximum valgus laxity could have important implications for elbow positioning during US or fluoroscopic stress examination, as well as surgical repair or reconstruction of the MUCL.

Background complexity can mitigate poor camouflage.

Avoiding detection through camouflage is often key to survival. However, an animal's appearance is not the only factor affecting conspicuousness: background complexity also alters detectability. This has been experimentally demonstrated for both artificially patterned backgrounds in the laboratory and natural backgrounds in the wild, but only for targets that already match the background well. Do habitats of high visual complexity provide concealment to even relatively poorly camouflaged animals? Using artificial prey which differed in their degrees of background matching to tree bark, we were able to determine their survival, under bird predation, with respect to the natural complexity of the background. The latter was quantified using low-level vision metrics of feature congestion (or 'visual clutter') adapted for bird vision. Higher background orientation clutter (edges with varying orientation) reduced the detectability of all but the poorest background-matching camouflaged treatments; higher background luminance clutter (varying achromatic lightness) reduced average mortality for all treatments. Our results suggest that poorer camouflage can be mitigated by more complex backgrounds, with implications for both camouflage evolution and habitat preferences.

Metric Selection, Metric Targets, and Risk Adjustment Should be Considered in the Design of Gainsharing Models for Bundled Payment Programs in Total Joint Arthroplasty.

BACKGROUND: Under bundled payment models, gainsharing presents an important mechanism to ensure engagement and reward innovation. We hypothesized that metric selection, metric targets, and risk adjustment would impact surgeons' performance in gainsharing models. METHODS: Patients undergoing total joint arthroplasty at an urban health system from 2017 to September 2018 were included. Gainsharing metrics included the following: length of stay, % discharge-to-home, 90-day readmission rate, % of patients with episode spend under target price, and % of patients with patient-reported outcomes (PROs) collected. Four scenarios were created to evaluate how metric selection/adjustment impacted surgeons' performance designation: scenario 1 used "aspirational targets" (>60th percentile), scenario 2 used "acceptable targets" (>50th percentile), scenario 3 risk-adjusted surgeon performance prior to comparing aspirational targets, and scenario 4 included a PRO collection metric. Number of metrics achieved determined performance tier, with higher tiers getting a greater share of the gainsharing pool. RESULTS: In total, 2776 patients treated by 12 surgeons met inclusion criteria (mean length of stay 3.0 days, readmission rate 4.0%, discharge-to-home 74%, episode spend under target price 85%, PRO collection 56%). Lowering of metric targets (scenario 1 vs. 2) resulted in a 75% increase in the number of high performers and 98% of the gainsharing pool being eligible for distribution. Risk adjustment (scenario 3) caused 50% of providers to move to higher performance tiers and potential payments to increase by 28%. Adding the PRO metric did not change performance. CONCLUSION: Quality metric/target selection and risk adjustment profoundly impact surgeons' performance in gainsharing contracts. This impacts how successful these contracts can be in driving innovation and dis-incentivizing the "cherry picking" of patients. LEVEL OF EVIDENCE: Level III.

Matrix-assisted nanoelectrospray mass spectrometry for soft ionization of metal(i)-protein complexes.

Metal ions play significant roles in biological processes, and investigation of metal-protein interactions provides a basis to understand the functions of metal ions in such systems. In the current study, a novel matrix-assisted nanoelectrospray ionization mass spectrometry (MANESI-MS) method was developed for investigating the interactions between metal ions (i.e., Cu+) and protein molecules (i.e., myoglobin) using Cu nanoparticles as the matrix. The results demonstrated that the present method not only was an efficient strategy for the generation of various complexes with monovalent metal ions, such as Cu+, in which no redox transitions between Cu+ and Cu2+ were observed, but also allowed a softer ionization of the generated Cu+-myoglobin complexes compared to that of myoglobin molecules with conventional nanoESI. Several parameters (i.e., the mixing mode of the myoglobin sample and Cu nanoparticle solution, size of the Cu particle, oxidation state of the Cu species, and acidity of the myoglobin solution) were found to be crucial in determining the ionization efficiency of the MANESI method. First loading a Cu nanoparticle solution into the electrospray tip followed by a myoglobin solution resulted in a favorable interaction between the generated Cu+ ions and myoglobin molecules, in which a smaller size of the Cu particle and a lower oxidation state of the metal species (Cu > Cu2O > CuO) gave a lower average charge state and hence a softer ionization of the resulting Cu+-myoglobin complexes, possibly due to the reduced denaturing effects of the Cu+ complex. The MANESI method has also been successfully used to ionize the complexes between Cu+ and other biological molecules such as cytochrome c and angiotension II, although an exception was found for lysozymes, which show an increase in the charge state. Analogous to the study with Cu, a variety of other metal nanoparticles (Ni, Fe, W, Ag, Al, Zn and Co) were explored to study their interactions with myoglobin, but only Zn and Co could produce monovalent metal ions (i.e., Zn+ and Co+) followed by a favorable interaction with myoglobin, and a soft ionization of the resulting complexes.

Correction: Metal salt assisted electrospray ionization mass spectrometry for the soft ionization of GAP polymers in negative ion mode.

Correction for 'Metal salt assisted electrospray ionization mass spectrometry for the soft ionization of GAP polymers in negative ion mode' by Theoneste Muyizere et al., Analyst, 2020, 145, 34-45.

A SANE Approach to Outcome Collection? Comparing the Performance of Single- Versus Multiple-Question Patient-Reported Outcome Measures After Total Hip Arthroplasty.

BACKGROUND: Several patient-reported outcome measures (PROMs) exist to measure outcomes after total hip arthroplasty (THA) but can be limited by patient-perceived burden and completion rates. We analyzed whether the modified single assessment numerical evaluation (M-SANE), a one-question PROM, would perform similarly to multiple-question PROMs among patients undergoing primary THA. METHODS: Patients undergoing THA completed the Patient-Reported Outcomes Measurement Information System-10 (PROMIS-10), the Hip Disability and Osteoarthritis Outcomes Score Junior (HOOS-Jr), and M-SANE questionnaires both preoperatively and postoperatively. The M-SANE assessment asked patients to assess their hip on a scale from 0 to 10, with 10 being the best possible score. Validity of M-SANE compared with other PROMs was determined by Spearman's correlation and floor and ceiling effects. Responsiveness was analyzed using standardized response mean (SRM). RESULTS: One hundred and thirty six patients with at least 1-year follow-up were reviewed. The average M-SANE score improved from 3.3 preoperatively to 7.1 at one year postoperatively. There was moderate to strong correlation at one-year follow-up between the M-SANE and HOOS-Jr (ρ = 0.75, P < .001) and PROMIS-10 physical component summary (ρ = 0.63, P < .001). Floor and ceiling effects of the M-SANE (floor 2.0%, ceiling 21.3%) were comparable to the HOOS-Jr (floor 0.0%, ceiling 20.8%). The responsiveness of the M-SANE after THA (SRM = 1.06, 95% CI: 0.79-1.33) was comparable to HOOS-Jr (SRM = 1.33, 95% CI: 1.08-1.59) and superior to PROMIS-10 physical component summary (SRM = 0.65, 95% CI: 0.55-0.74). CONCLUSION: The M-SANE has performed similarly across multiple psychometric properties compared with more burdensome PROMs in assessing longitudinal patient-reported outcomes after THA.

Metal salt assisted electrospray ionization mass spectrometry for the soft ionization of GAP polymers in negative ion mode.

Glycidyl azide polymers (GAP) are one of the most important energetic polymers, but it is still a challenge to elucidate their structures using mass spectrometry due to their fragility upon ionization. Herein we developed a soft metal salt assisted electrospray ionization (MSAESI) to characterize directly GAP polymers using mass spectrometry. This technique combines paper spray ionization and the complexing effect of anions from metal salts with GAP in the negative ion mode to softly ionize GAP polymers prior to mass spectrometry analysis. The effects of experimental parameters (e.g., ion mode, applied voltage, and type and concentration of metal salts) have been investigated in detail. In contrast to the positive ion mode, a softer ionization was observed for GAP polymers when the negative ion mode was applied. The radius and average charge of cations and anions in metal salts were found to play crucial roles in determining the performance of the MSAESI analysis of GAP. For a given charge number, a smaller radius of cations favored the soft ionization of GAP polymers (e.g., Na+ > K+ > Rb+), whereas a larger radius of anions led to a preferred performance (e.g., F- < Cl- < Br- < I-) due to variation in dissolution ability. For anions with multiple charges, the ones with fewer charges gave a more favorable ionization to the GAP sample because of their better complexing to GAP molecules than those with more charges in the structure of anions (e.g., NO3- > SO42- > PO43-). According to the experimental observation and evidence from mass spectrometry, we proposed the plausible electrospray mechanisms of MSAESI for GAP analysis with the involvement of metal salts. Moreover, the developed protocol has been applied successfully to the analysis of various GAP samples, and works for other types of sources such as nanoelectrospray ionization.

Mapping the Diffusion of Technology in Orthopaedic Surgery: Understanding the Spread of Arthroscopic Rotator Cuff Repair in the United States.

BACKGROUND: The mechanism by which surgical innovation is spread in orthopaedic surgery is not well studied. The recent widespread transition from open to arthroscopic rotator cuff repair techniques provides us with the opportunity to study the spread of new technology; doing so would be important because it is unclear how novel orthopaedic techniques disseminate across time and geography, and previous studies of innovation in healthcare may not apply to the orthopaedic community. QUESTIONS/PURPOSES: (1) How much regional variation was associated with the adoption of arthroscopic rotator cuff repair in the United States Medicare population between 2006 and 2014 and how did this change over time? (2) In which regions of the United States was arthroscopic rotator cuff repair first adopted and how did it spread geographically? (3) Which regional factors were associated with the adoption of this new technology? METHODS: We divided the United States into 306 hospital referral regions based upon referral patterns observed in the Centers for Medicare & Medicaid Services MedPAR database, which records all Medicare hospital admissions; this has been done in numerous previous studies using methodology introduced by the Dartmouth Atlas. The proportion of arthroscopic rotator cuff repairs versus open rotator cuff repairs in each hospital referral region was calculated using adjusted procedural rates from the Medicare Part B Carrier File from 2006 to 2014, as it provided a nationwide sample of patients, and was used as a measure of adoption. A population-weighted, multivariable linear regression analysis was used to identify regional characteristics independently associated with adoption. RESULTS: There was substantial regional variation associated with the adoption of arthroscopy for rotator cuff repair as the percentage of rotator cuff repair completed arthroscopically in 2006 ranged widely among hospital referral regions with a high of 85.3% in Provo, UT, USA, and a low of 16.7% in Seattle, WA, USA (OR 30, 95% CI 17.6 to 52.2; p < 0.001). In 2006, regions in the top quartiles for Medicare spending (+9.1%; p = 0.008) independently had higher adoption rates than those in the bottom quartile, as did regions with a greater proportion of college-educated residents (+12.0%; p = 0.009). The Northwest region (-14.4%; p = 0.009) and the presence of an academic medical center (-5.8%; p = 0.026) independently had lower adoption than other regions and those without academic medical centers. In 2014, regions in the top quartiles for Medicare spending (+5.7%; p = 0.033) and regions with a greater proportion of college-educated residents (+9.4%; p = 0.005) independently had higher adoption rates than those in the bottom quartiles, while the Northwest (-9.6%; p = 0.009) and Midwest regions (-5.1%; p = 0.017) independently had lower adoption than other regions. CONCLUSION: The heterogeneous diffusion of arthroscopic rotator cuff repair across the United States highlights that Medicare beneficiaries across regions did not have equal access to these procedures and that these discrepancies continued to persist over time. A higher level of education and increased healthcare spending were both associated with greater adoption in a region and conversely suggest that regions with lower education and healthcare spending may pursue innovation more slowly. There was evidence that regions with academic medical centers adopted this technology more slowly and may highlight the role that private industry and physicians in nonacademic organizations play in surgical innovation. Future studies are needed to understand if this later adoption leads to inequalities in the quality and value of surgical care delivered to patients in these regions. LEVEL OF EVIDENCE: Level III, therapeutic study.

Identifying regional characteristics influencing variation in the utilization of rotator cuff repair in the United States.

BACKGROUND: There is a lack of consensus regarding indications for surgical management of rotator cuff disease, which can lead to increased regional variation. The objectives of this study were to describe the geographic variation in rates of rotator cuff repair (RCR) in the United States over time and to identify regional characteristics associated with utilization. METHODS: The United States was divided into 306 hospital referral regions. The adjusted per capita RCR rate was calculated using procedural counts derived from the Medicare Part B Carrier File from 2004-2014. Population-weighted multivariable regression was used to identify regional characteristics independently associated with utilization in 2014. RESULTS: In 2014, an 8-fold difference in rates of RCR was found between regions. Between 2010 and 2014, the overall rate of RCR grew only 3.6% and regional variation decreased. Higher regional utilization of several other orthopedic procedures (P < .02), as well as the regional supply of orthopedic surgeons (P = .002), was independently associated with significantly increased utilization. The South, Southeast, and Southwest were independently associated with significantly higher utilization (P < .001) compared with the Northeast. A higher prevalence of resident physicians, a marker of the academic presence within a region, was independently associated with decreased utilization (P < .001). CONCLUSION: Utilization of RCR has increased substantially over the past decade, but the rate of growth appears to be slowing. RCR remains a procedure with significant regional variation, and increased utilization across regions is associated with higher orthopedic surgeon supply and increased rates of other orthopedic procedures.

Acute versus delayed reverse total shoulder arthroplasty for the treatment of proximal humeral fractures in the elderly population: a systematic review and meta-analysis.

BACKGROUND: Recent literature has shown that acute reverse total shoulder arthroplasty (RTSA) yields good outcomes in the treatment of displaced proximal humeral fractures, and there have also been recent studies showing that delayed RTSA can be successfully used for sequelae of proximal humeral fractures such as nonunion and malunion. The use of meta-analysis affords the opportunity to formally compare the outcomes of acute RTSA for fracture and delayed RTSA for fracture sequelae. METHODS: We searched the MEDLINE, Embase, and Cochrane Library databases. We included all studies reporting on RTSA for the treatment of proximal humeral fracture sequelae with a comparison group of acute RTSA or with no comparison group in adults with a mean age older than 65 years and at least 2 years of follow-up. We calculated weighted mean differences for range of motion, standardized mean differences for clinical outcome scores, and relative risks for dichotomous outcomes. RESULTS: Sixteen studies met the inclusion criteria, which comprised 322 patients undergoing RTSA for fracture sequelae. Of these studies, 4 were comparative (46 patients) whereas 12 were case series (276 patients). Among studies directly comparing acute versus delayed RTSA, no differences in forward flexion (P = .72), clinical outcome scores (P = .78), or all-cause reoperation (P = .92) were found between the 2 groups. Patients undergoing delayed RTSA achieved 6° more external rotation than those undergoing acute RTSA; this difference was significant (P = .01). CONCLUSIONS: Given the risks associated with surgery in the elderly population, consideration may be given to an initial trial of nonoperative treatment in these patients, saving RTSA for those in whom nonoperative treatment fails without compromising the ultimate outcome.

Next-Generation Sequencing vs Culture-Based Methods for Diagnosing Periprosthetic Joint Infection After Total Knee Arthroplasty: A Cost-Effectiveness Analysis.

BACKGROUND: Periprosthetic joint infection (PJI) after total knee arthroplasty is challenging to diagnose. Compared with culture-based techniques, next-generation sequencing (NGS) is more sensitive for identifying organisms but is also less specific and more expensive. To date, there has been no study comparing the cost-effectiveness of these two methods to diagnose PJI after total knee arthroplasty. METHODS: A Markov, state-transition model projecting lifetime costs and quality-adjusted life years (QALYs) was constructed to determine the cost-effectiveness from a societal perspective. The primary outcome was incremental cost-effectiveness ratio, with a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses were performed to evaluate parameter assumptions. RESULTS: At our base case values, culture was not determined to be cost-effective compared to NGS, with an incremental cost-effectiveness ratio of $422,784 per QALY. One-way sensitivity analyses found NGS to be the cost-effective choice above a pretest probability of 45.5% for PJI. In addition, NGS was cost-effective if its sensitivity was greater than 70.0% and its specificity greater than 94.1%. Two-way sensitivity analyses revealed that the pretest probability and test performance parameters (sensitivity and specificity) were the largest factors for identifying whether a particular strategy was cost-effective. CONCLUSION: The results of our model suggest that the cost-effectiveness of NGS to diagnose PJI depends primarily on the pretest probability of PJI and the performance characteristics of the NGS technology. Our results are consistent with the idea that NGS should be reserved for clinical contexts with a high pretest probability of PJI. Further study is required to determine the indications and subgroups for which NGS offers clinical benefit.

A One-Question Patient-Reported Outcome Measure Is Comparable to Multiple-Question Measures in Total Knee Arthroplasty Patients.

BACKGROUND: Patient-reported outcome measures (PROMs) are important for tracking outcomes following total knee arthroplasty (TKA) but can be limited by time constraints and patient compliance. We sought to evaluate the utility of the one-question, modified single assessment numerical evaluation (M-SANE) score in TKA patients compared to legacy PROMs. METHODS: Patients undergoing TKA completed the Patient-Reported Outcomes Measurement Information System-10 (PROMIS-10), the Knee Disability and Osteoarthritis Outcomes Score Junior (KOOS Jr), and M-SANE (modified-SANE) assessments both preoperatively and postoperatively. The M-SANE score asked patients to rate their native or prosthetic knee on a scale from 0 to 10, with 10 being the best function. M-SANE validity was determined by the Spearman's correlation between the collected PROMs and the Bland-Altman plots. PROM responsiveness was assessed using the standardized response mean. RESULTS: In total, 217 patients completed PROMs preoperatively and at 1 year postoperatively. Floor and ceiling effects of the M-SANE were higher than other PROMs but still relatively low (4%-11%). There was a moderate to strong correlation at nearly all time points between the M-SANE and KOOS Jr (ρ = 0.44-0.78, P < .001). There was a weak correlation between the M-SANE and PROMIS physical component summary at the preoperative evaluation (ρ = 0.28) but a strong correlation at 1-year follow up (0.65, P < .001). The long-term responsiveness of the M-SANE to TKA (standardized response mean [SRM] = 0.98, 95% confidence interval [CI] 0.80-1.17) was comparable to both the KOOS Jr (SRM = 1.19, 95% CI 1.00-1.38) and PROMIS physical component summary (SRM = 0.82, 95% CI 0.74-0.91). Bland-Altman plots demonstrated that the M-SANE and KOOS Jr capture combined knee pain and functionality differently. CONCLUSION: The M-SANE score was comparable to validated multiple-question PROMs in TKA patients. The demonstrated validity of the M-SANE, as well as its comparable responsiveness to more lengthy PROMs, highlights its use as a one-question PROM for assessment of patient undergoing TKA.

Elucidating the Reaction Mechanisms between Triazine and Hydrogen Sulfide with pH Variation Using Mass Spectrometry.

Triazine is one of the most economical and effective scavengers for hydrogen sulfide (H2S) removal, but the reaction mechanisms between triazine and H2S with pH variation in solution are still poorly understood. Herein, we show that the reaction process can be directly probed by means of paper spray mass spectrometry, in which an aprotic solvent (e.g., acetonitrile) is more favorable to the observation of reaction intermediates than a protic solvent (e.g., methanol), because of hydrogen bond interaction. Varying the pH of the reaction leads to completely different reaction pathways. With the pH in the range of 5.58 to 7.73, the major product was thiadiazine. With a pH of 3.02-3.69, thiadiazine is converted to 2-(5-(2-hydroxyethyl)-1,3,5-thiadiazinan-3-yl)acetaldehyde, which differs from the traditional pathway of analogous reactions. However, as ammonia was added into the reaction and the pH was adjusted to the range 8.45-9.43, triazine readily undergoes hydrolysis, and the formed intermediate reacts with ammonia and formaldehyde generated in situ from triazine to produce 1-(2-hydroxyethyl)-3,5,7-triaza-1-azoniatricyclo [3.3.1.13,7]decane (HTAD). Further increasing the pH up to 10.27-11.21 leads to the decomposition of HTAD. Based on the experimental observation and evidence from high-resolution and tandem mass spectrometry, we propose the plausible reaction mechanisms between triazine and H2S, as well as the derived reaction from triazine under different pH conditions.

Double resonance ejection using novel radiofrequency phase tracking circuitry in a miniaturized planar linear ion trap mass spectrometer.

RATIONALE: Ion trap mass spectrometers are attractive due to their inherent sensitivity and specificity. Miniaturization increases trap portability for in situ mass analysis by relaxing vacuum and voltage requirements but decreases the trapping volume. To overcome signal/resolution loss from miniaturization, double resonance ejection using phase tracking circuitry was investigated. METHODS: Phase tracking circuitry was developed to induce double resonance ejection in a planar linear ion trap using the ß 2/3 hexapole resonance line. RESULTS: Double resonance was observed using phase tracking circuitry. Resolution of 0.5 m/z units and improved signal-to-noise ratio (SNR) compared with AC resonant ejection were achieved. CONCLUSIONS: The phase tracking circuitry proved effective despite deviations from a true phase locked condition. Double resonance ejection is a means to increase signal intensity in a miniaturized planar ion trap.

Optimal fabrication methods for miniature coplanar ion traps.

RATIONALE: Ion trap mass spectrometers are beneficial due to their intrinsic sensitivity and specificity. Therefore, a portable version for in situ analysis of various compounds is very attractive. Miniaturization of ion traps is paramount for the portability of such mass spectrometers. METHODS: We developed an optimized design for a planar linear ion trap mass spectrometer, consisting of two trapping plates with photolithographically patterned electrodes. Each plate is constructed using a machined glass substrate and standard microfabrication procedures. The plates are attached to a patterned circuit board via wire bonds then positioned approximately 5 mm apart. RESULTS: Trapped ions are detected by ejecting them through tapered slits, which alleviate charge buildup. Mass analysis can be performed through either boundary or resonant ion ejection. Better than unit mass resolution is demonstrated with resonant ejection. CONCLUSIONS: The optimized planar linear ion trap provides good resolution and the potential for further miniaturization. This was accomplished by vigorously testing variables associated with ion trap design including electrical connections, substrate materials, and electrode designs.