Emergence of an early SARS-CoV-2 epidemic in the United States.

The emergence of the COVID-19 epidemic in the United States (U.S.) went largely undetected due to inadequate testing. New Orleans experienced one of the earliest and fastest accelerating outbreaks, coinciding with Mardi Gras. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large-scale events accelerate transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana had limited diversity compared to other U.S. states and that one introduction of SARS-CoV-2 led to almost all of the early transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras, and the festival dramatically accelerated transmission. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate epidemics.

Comparative analysis of real-world adherence and persistence patterns with vibegron, mirabegron, and anticholinergics in patients with overactive bladder: A retrospective claims study.

INTRODUCTION: Vibegron is a selective ß3-adrenergic receptor agonist that was approved by the US Food and Drug Administration in December 2020 for the treatment of overactive bladder in adults. This retrospective study assessed US pharmacy claims data to evaluate the real-world adherence and persistence of vibegron compared with mirabegron and with anticholinergics. MATERIALS AND METHODS: This analysis used the Optum Research Database to identify adults with ≥1 pharmacy claim for vibegron, mirabegron, or an anticholinergic from April 1, 2021, to August 31, 2022. Patients had ≥ 90 days of continuous commercial or Medicare medical and pharmacy coverage preindex and ≥ 60 days of continuous pharmacy coverage postindex. Two independent propensity-score models matched patients treated with (1) vibegron versus mirabegron and (2) vibegron versus anticholinergics on key variables such as demographics and clinical characteristics, index copay, days' supply, and time of entry into analysis (index quarter). Adherence was measured by proportion of days covered (PDC) from index to the end of follow-up and was defined as PDC ≥ 80%. Persistence was defined as days to discontinuation of index medication (first 30-day gap) or end of follow-up. RESULTS: The matched vibegron and mirabegron cohorts included 4921 and 9842 patients, respectively, and the matched vibegron and anticholinergic cohorts included 4676 and 9352 patients, respectively. Patients receiving vibegron had greater mean PDC versus patients receiving mirabegron (0.67 vs. 0.64, respectively; p < 0.001) or anticholinergics (0.67 vs. 0.58; p < 0.001). A greater percentage of patients receiving vibegron were adherent versus those receiving mirabegron (49.0% vs. 45.1%, respectively; p < 0.001) or anticholinergics (49.1% vs. 38.5%; p < 0.001). Persistence was longer with vibegron compared with both mirabegron (median [95% CI], 171 [159-182] vs. 128 [122-137] days, respectively; p < 0.001) and anticholinergics (172 [159-183] vs. 91 [91] days; p < 0.001). CONCLUSION: In this retrospective analysis of pharmacy claims data, patients receiving vibegron exhibited significantly higher adherence and demonstrated longer persistence in comparison to matched patient cohorts receiving either mirabegron or anticholinergics.

Percutaneous Transluminal Angioplasty for Infrapopliteal Chronic Limb-Threatening Ischemia: A Systematic Review and Meta-analysis of Primary Patency and Binary Restenosis Rates.

PURPOSE: Percutaneous transluminal angioplasty (PTA) remains the mainstay of endovascular therapy for infrapopliteal chronic limb-threatening ischemia (CLTI), but outcomes have not been well characterized using high-quality data. The aim of this meta-analysis was to provide an updated benchmark for rates of primary patency and binary restenosis after PTA using prospectively collected, predominantly core-lab adjudicated randomized controlled trial (RCT) data. MATERIALS AND METHODS: MEDLINE, EMBASE, Cochrane Central, and ClinicalTrials.gov were queried for RCTs published through November 2022 using PTA as a control arm and including patients with infrapopliteal CLTI. Studies were excluded if >25% of patients had intermittent claudication, other vessels were included, or primary patency or binary restenosis were not outcomes. Outcomes were analyzed using random effects models. This analysis was publicly registered (PROSPERO ID#394543). No funding was utilized. RESULTS: Seventeen RCTs were included (1048 patients, 1279 lesions). Pooled primary patency rates using data from 6 RCTs were 68% at 6 months (95% confidence interval [CI]=45%-84%) and 66% at 12 months (95% CI=51%-79%). Pooled binary restenosis rates using data from 11 RCTs were 54% at 6 months (95% CI=33%-73%) and 60% at 9 to 12 months (95% CI=39%-78%). Significant heterogeneity was present in all outcomes (I2>50%, p<0.0001). Publication bias was not observed (Egger's p>0.1). CONCLUSIONS: This meta-analysis provides estimates for binary restenosis and primary patency following PTA utilizing prospectively collected, predominantly core-lab adjudicated data. Results demonstrate 1-year primary patency rates that are 10% to 20% higher than what has been historically used in power calculations. These new estimates will help facilitate more accurate power analysis for future RCTs. CLINICAL IMPACT: Rates of primary patency and binary restenosis after percutaneous transluminal angioplasty (PTA) have not been well-described using high-quality data, and investigators have been utilizing estimates of 40% to 50% and 45% to 65%, respectively, when performing power calculations for trials. This meta-analysis demonstrates using high-quality, prospectively collected, and predominantly core-lab adjudicated randomized controlled trial data that actual rates of primary patency are closer to 60% up to 1 year following PTA and provides the first meta-analysis estimate of binary restenosis rates up to 1 year after PTA. These estimates will help facilitate more accurate power calculations for future RCTs in this space.

Association between Hispanic or Latino ethnicity and pulmonary embolism severity, management, and in-hospital outcomes.

BACKGROUND: Hispanic and Latino patients are under-represented in existing healthcare disparities research in pulmonary embolism (PE). The goal of this study was to determine if differences in PE severity, treatment modality, or in-hospital outcomes exist for Hispanic or Latino patients with PE. METHODS: All PE cases from 2013 to 2019 at a single institution were reviewed. Clinical characteristics, imaging findings, intervention types, and in-hospital and 30-day outcomes were collected. Two cohorts were created based on patients' self-reported ethnicity. Outcomes were compared using univariate and multivariate analysis. RESULTS: A total of 1265 patients were identified with confirmed PE; 474 (37%) identified as Hispanic or Latino. Hispanic or Latino patients presented with high-risk PE significantly less often (19% vs 25%, p = 0.03). On univariate analysis, Hispanic or Latino patients had lower rates of PE-specific intervention (15% vs 19%, p = 0.03) and similar rates of inpatient mortality (6.8% vs 7.5%, p = 0.64). On ordinal regression analysis, Hispanic or Latino ethnicity was associated with lower PE severity (OR 0.69, 95% CI 0.54-0.89, p = 0.003). In subgroup analyses of intermediate and high-risk PEs, ethnicity was not a significant predictor of receipt of PE-specific intervention or in-hospital mortality. CONCLUSIONS: At this institution, Hispanic or Latino patients were less likely to present with high-risk PE but had similar rates of inpatient mortality. Future research is needed to identify if disparities in in-hospital care are driving perceived differences in PE severity and what addressable systematic factors are driving higher-than-expected in-hospital mortality for Hispanic or Latino patients.

Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder.

BACKGROUND: Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective ß3-adrenergic receptor agonist approved in the US in December 2020, demonstrated efficacy in reducing symptoms of OAB and was safe and well tolerated in the 12-week EMPOWUR trial and its 40-week, double-blind extension trial. The goal of the COMPOSUR study is to evaluate vibegron in a real-world setting to assess patient treatment satisfaction, tolerability, safety, duration of treatment, and persistence. METHODS: This is a 12-month, prospective, observational, real-world study, with an optional 12-month extension to 24 months, in the US assessing adults ≥ 18 years old starting a new course of vibegron. Patients must be previously diagnosed with OAB with or without UUI, symptomatic for ≥ 3 months before enrollment, and receive prior treatment with an anticholinergic, with mirabegron, or with a combination of an anticholinergic and mirabegron. Enrollment is performed by the investigator following exclusion and inclusion criteria guided by US product labeling, reinforcing a real-world approach. Patients complete the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q) monthly and the OAB Questionnaire short form (OAB-q-SF) and Work Productivity and Activity Impairment Questionnaire (WPAI:US) at baseline and monthly for 12 months. Patients are followed up via phone call, in-person visits, or telehealth (ie, virtual) visits. The primary endpoint is patient treatment satisfaction as determined by the OAB-SAT-q satisfaction domain score. Secondary endpoints include percent positive responses to individual OAB-SAT-q questions, additional OAB-SAT-q domain scores, and safety. Exploratory endpoints include adherence and persistence. DISCUSSION: OAB leads to a significant decrease in quality of life, as well as impairment of work activities and productivity. Persistence with OAB treatments can be challenging, often due to lack of efficacy and adverse effects. COMPOSUR is the first study to provide long-term, prospective, pragmatic treatment data for vibegron in the US and the resultant effect on quality of life among patients with OAB in a real-world clinical setting. Trial registration ClinicalTrials.gov identifier: NCT05067478; registered: October 5, 2021.

One gene, multiple ecological strategies: A biofilm regulator is a capacitor for sustainable diversity.

Many bacteria cycle between sessile and motile forms in which they must sense and respond to internal and external signals to coordinate appropriate physiology. Maintaining fitness requires genetic networks that have been honed in variable environments to integrate these signals. The identity of the major regulators and how their control mechanisms evolved remain largely unknown in most organisms. During four different evolution experiments with the opportunist betaproteobacterium Burkholderia cenocepacia in a biofilm model, mutations were most frequently selected in the conserved gene rpfR RpfR uniquely integrates two major signaling systems-quorum sensing and the motile-sessile switch mediated by cyclic-di-GMP-by two domains that sense, respond to, and control the synthesis of the autoinducer cis-2-dodecenoic acid (BDSF). The BDSF response in turn regulates the activity of diguanylate cyclase and phosphodiesterase domains acting on cyclic-di-GMP. Parallel adaptive substitutions evolved in each of these domains to produce unique life history strategies by regulating cyclic-di-GMP levels, global transcriptional responses, biofilm production, and polysaccharide composition. These phenotypes translated into distinct ecology and biofilm structures that enabled mutants to coexist and produce more biomass than expected from their constituents grown alone. This study shows that when bacterial populations are selected in environments challenging the limits of their plasticity, the evolved mutations not only alter genes at the nexus of signaling networks but also reveal the scope of their regulatory functions.

Whole-Genome Sequencing Surveillance and Machine Learning of the Electronic Health Record for Enhanced Healthcare Outbreak Detection.

BACKGROUND: Most hospitals use traditional infection prevention (IP) methods for outbreak detection. We developed the Enhanced Detection System for Healthcare-Associated Transmission (EDS-HAT), which combines whole-genome sequencing (WGS) surveillance and machine learning (ML) of the electronic health record (EHR) to identify undetected outbreaks and the responsible transmission routes, respectively. METHODS: We performed WGS surveillance of healthcare-associated bacterial pathogens from November 2016 to November 2018. EHR ML was used to identify the transmission routes for WGS-detected outbreaks, which were investigated by an IP expert. Potential infections prevented were estimated and compared with traditional IP practice during the same period. RESULTS: Of 3165 isolates, there were 2752 unique patient isolates in 99 clusters involving 297 (10.8%) patient isolates identified by WGS; clusters ranged from 2-14 patients. At least 1 transmission route was detected for 65.7% of clusters. During the same time, traditional IP investigation prompted WGS for 15 suspected outbreaks involving 133 patients, for which transmission events were identified for 5 (3.8%). If EDS-HAT had been running in real time, 25-63 transmissions could have been prevented. EDS-HAT was found to be cost-saving and more effective than traditional IP practice, with overall savings of $192 408-$692 532. CONCLUSIONS: EDS-HAT detected multiple outbreaks not identified using traditional IP methods, correctly identified the transmission routes for most outbreaks, and would save the hospital substantial costs. Traditional IP practice misidentified outbreaks for which transmission did not occur. WGS surveillance combined with EHR ML has the potential to save costs and enhance patient safety.

Structural basis of DSF recognition by its receptor RpfR and its regulatory interaction with the DSF synthase RpfF.

The diffusible signal factors (DSFs) are a family of quorum-sensing autoinducers (AIs) produced and detected by numerous gram-negative bacteria. The DSF family AIs are fatty acids, differing in their acyl chain length, branching, and substitution but having in common a cis-2 double bond that is required for their activity. In both human and plant pathogens, DSFs regulate diverse phenotypes, including virulence factor expression, antibiotic resistance, and biofilm dispersal. Despite their widespread relevance to both human health and agriculture, the molecular basis of DSF recognition by their cellular receptors remained a mystery. Here, we report the first structure-function studies of the DSF receptor regulation of pathogenicity factor R (RpfR). We present the X-ray crystal structure of the RpfR DSF-binding domain in complex with the Burkholderia DSF (BDSF), which to our knowledge is the first structure of a DSF receptor in complex with its AI. To begin to understand the mechanistic role of the BDSF-RpfR contacts observed in the biologically important complex, we have also determined the X-ray crystal structure of the RpfR DSF-binding domain in complex with the inactive, saturated isomer of BDSF, dodecanoic acid (C12:0). In addition to these ligand-receptor complex structures, we report the discovery of a previously overlooked RpfR domain and show that it binds to and negatively regulates the DSF synthase regulation of pathogenicity factor F (RpfF). We have named this RpfR region the RpfF interaction (FI) domain, and we have determined its X-ray crystal structure alone and in complex with RpfF. These X-ray crystal structures, together with extensive complementary in vivo and in vitro functional studies, reveal the molecular basis of DSF recognition and the importance of the cis-2 double bond to DSF function. Finally, we show that throughout cellular growth, the production of BDSF by RpfF is post-translationally controlled by the RpfR N-terminal FI domain, affecting the cellular concentration of the bacterial second messenger bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP). Thus, in addition to describing the molecular basis for the binding and specificity of a DSF for its receptor, we describe a receptor-synthase interaction regulating bacterial quorum-sensing signaling and second messenger signal transduction.

Hidden resources in the Escherichia coli genome restore PLP synthesis and robust growth after deletion of the essential gene pdxB.

PdxB (erythronate 4-phosphate dehydrogenase) is expected to be required for synthesis of the essential cofactor pyridoxal 5'-phosphate (PLP) in Escherichia coli Surprisingly, incubation of the ∆pdxB strain in medium containing glucose as a sole carbon source for 10 d resulted in visible turbidity, suggesting that PLP is being produced by some alternative pathway. Continued evolution of parallel lineages for 110 to 150 generations produced several strains that grow robustly in glucose. We identified a 4-step bypass pathway patched together from promiscuous enzymes that restores PLP synthesis in strain JK1. None of the mutations in JK1 occurs in a gene encoding an enzyme in the new pathway. Two mutations indirectly enhance the ability of SerA (3-phosphoglycerate dehydrogenase) to perform a new function in the bypass pathway. Another disrupts a gene encoding a PLP phosphatase, thus preserving PLP levels. These results demonstrate that a functional pathway can be patched together from promiscuous enzymes in the proteome, even without mutations in the genes encoding those enzymes.

The Overdose Crisis and Using Alone: Perspectives of People Who Use Drugs in Rural and Semi-Urban Areas of British Columbia.

Background: A significant rise in the rate of overdose deaths in British Columbia (BC), driven by fentanyl contamination of the illicit drug supply, led to the declaration of a public health emergency in 2016. Those at greatest risk of death are people who use alone. This community-based participatory action research study based in the Fraser East region of BC study aimed to overview underlying factors that contribute to unwitnessed overdoses in semi-urban and rural settings. Methods: This descriptive study used a community-based participatory action research model with peer research associates (PRAs) involved at various research stages. In total, 22 interviews were conducted with participants aged 19 and over who used illicit drugs in the Fraser East since the start of the public health emergency in 2016. A collaborative data analysis approach was taken for data interpretation, and content analysis was performed to explore themes surrounding using alone. Results: Among people who use drugs (PWUD), using alone was found to be influenced by (a) the availability of drugs and personal funds, (b) personal safety, (c) stigma and shame, (d) protecting privacy, (e) mental health conditions and addiction, and (f) the lack of engagement with harm reduction services. At times, using alone was due to unforeseen, episode-specific situations. Conclusion: A multi-dimentional and context-specific approach is needed in overdose prevention and response for people who use drugs alone. There is need for enhanced approaches that address or include support services for families to reduce stigma and isolation of those at risk of an overdose.

Synonymous mutations make dramatic contributions to fitness when growth is limited by a weak-link enzyme.

Synonymous mutations do not alter the specified amino acid but may alter the structure or function of an mRNA in ways that impact fitness. There are few examples in the literature, however, in which the effects of synonymous mutations on microbial growth rates have been measured, and even fewer for which the underlying mechanism is understood. We evolved four populations of a strain of Salmonella enterica in which a promiscuous enzyme has been recruited to replace an essential enzyme. A previously identified point mutation increases the enzyme's ability to catalyze the newly needed reaction (required for arginine biosynthesis) but decreases its ability to catalyze its native reaction (required for proline biosynthesis). The poor performance of this enzyme limits growth rate on glucose. After 260 generations, we identified two synonymous mutations in the first six codons of the gene encoding the weak-link enzyme that increase growth rate by 41 and 67%. We introduced all possible synonymous mutations into the first six codons and found substantial effects on growth rate; one doubles growth rate, and another completely abolishes growth. Computational analyses suggest that these mutations affect either the stability of a stem-loop structure that sequesters the start codon or the accessibility of the region between the Shine-Dalgarno sequence and the start codon. Thus, these mutations would be predicted to affect translational efficiency and thereby indirectly affect mRNA stability because translating ribosomes protect mRNA from degradation. Experimental data support these hypotheses. We conclude that the effects of the synonymous mutations are due to a combination of effects on mRNA stability and translation efficiency that alter levels of the weak-link enzyme. These findings suggest that synonymous mutations can have profound effects on fitness under strong selection and that their importance in evolution may be under-appreciated.

Substance use and overdose risk: documenting the perspectives of formerly incarcerated persons in the Fraser East region of BC.

BACKGROUND: The relationship between incarceration and risk of overdose has been well-documented in the literature, but few studies document the perspectives of persons at risk of overdose who were incarcerated. This sub-inquiry aimed to understand the experiences of persons with a history of substance use and incarceration in the Fraser East region of BC and how involvement with the criminal justice system affected their drug use and perceived risk of overdose. METHODS: The Fraser East Overdose Response project utilized a community-based participatory action approach that included peer researchers with lived experience in all parts of the research process. This qualitative pilot study aimed to better understand individuals at risk of an unwitnessed overdose in order to prevent deaths and identify effective local responses. A snowball sampling technique was used to recruit persons aged 19 and over who used illicit drugs over the past 3 years in the Fraser East since 2016. In total, 22 participants were interviewed. Of these, 13 participants identified a history of incarceration. Interviews were analyzed using a framework analysis approach. RESULTS: The perspectives that participants shared revealed that impacts from incarceration are influenced by policies but also highly individualized. Our inquiry found three broader themes, within which were situated differing and sometimes conflicting interpretations and experiences of systemic environments: (1) incarceration was associated with harms and was perceived to increase risk of overdose following release, (2) incarceration was perceived to have limited impact on substance use and overdose risk, and (3) incarceration was associated with a perceived reduction of substance use and overdose risk. CONCLUSIONS: Understanding the complexities of the perceptions of those with lived experience of substance use and incarceration is of importance to better inform interventions in this population. The existing knowledge base urgently requires further inquiry into the intersections between qualitative perspectives, environments and policies, and quantitative outcomes of overdose vís-a-vís correctional institution.

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.

DaxibotulinumtoxinA for Injection has a prolonged duration of response in the treatment of glabellar lines: Pooled data from two multicenter, randomized, double-blind, placebo-controlled, phase 3 studies (SAKURA 1 and SAKURA 2).

BACKGROUND: DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin type A in clinical development. Phase 2 data have shown it offers a more prolonged duration of response than onabotulinumtoxinA. OBJECTIVE: To further evaluate the efficacy, duration of response, and safety of 40 U DAXI compared with placebo in the treatment of glabellar lines. METHODS: Two identical, multicenter, randomized, double-blind, placebo-controlled, phase 3 studies were performed (NCT03014622 and NCT03014635 on www.clinicaltrials.gov). Participants with moderate or severe glabellar lines were randomly assigned (2:1) to receive 40 U DAXI or placebo into the corrugator/procerus muscles. Glabellar line severity was assessed by investigators and participants for up to 36 weeks (≥24 weeks). RESULTS: Among 609 participants enrolled (405 DAXI, 204 placebo), 92% completed. DAXI was significantly more effective than placebo in reducing glabellar line severity and maintained none or mild glabellar line severity for a median of 24.0 weeks. It was also generally well tolerated-treatment-related adverse effects were most commonly headache (6.4% vs 2.0%) and injection site pain (3.7% vs 3.9%). LIMITATIONS: The study population was predominantly female and white and received only a single treatment. CONCLUSIONS: DAXI offers a prolonged duration of response for glabellar line reduction and is well tolerated.

The Cost of Poor Mental Health in Total Joint Arthroplasty.

BACKGROUND: The purpose of this analysis was to evaluate (1) the impact of depression on resource utilization and financial outcomes in bundled total joint arthroplasty (TJA) and (2) whether similar effects are seen using baseline patient-reported outcome scores. METHODS: All elective bundled TJA cases from 2017 to 2018 at an academic system in the New York City area were included. We analyzed variables associated with cost differences seen between patients with and without depression, and between patients with low (<40th percentile) and high baseline (>60th percentile) Veterans RAND 12-Item Health Survey mental component scores (MCSs). We also analyzed whether depression or low MCS could predict worse financial outcomes. RESULTS: Our population included 825 patients, 418 with patient-reported outcome scores data. Depression was associated with higher rates of skilled nursing facility (SNF) discharge (42.7% vs 36.5%, P = .04), SNF payments ($16,200 vs $12,100, P = .0002), and average total episode costs ($31,000 vs $27,000, P = .04). Depression predicted bundle cost to be greater than target price (OR 1.82, 95% CI: 1.04-.16; P = .04) and SNF payment greater than 75th percentile (OR: 1.91; 95% CI: 1.00-3.65; P < .05). Similar effects were not seen using MCS. CONCLUSION: This is the first study to determine that depression predicts bundle cost greater than target price and SNF payment greater than 75th percentile. Our results emphasize the importance of accurate preoperative assessment of mental health in optimization of care, focusing on attenuating the increased SNF payments associated with depression. As similar effects were not seen using MCS, future studies should analyze the use of validated screening tools for depression, such as the PHQ-9, for more accurate assessments of patient mental health in TJA.

What Are the Uses and Limitations of Time-driven Activity-based Costing in Total Joint Replacement?

BACKGROUND: With increasing emphasis on value-based payment models for primary total joint arthroplasty (TJA), there is greater need for orthopaedic surgeons and hospitals to better understand the actual costs and resource use of TJA. Time-driven activity-based costing (TDABC) is a methodology for accurate cost estimation, but its application in the TJA care pathway across institutions/regions has not yet been analyzed. QUESTIONS/PURPOSES: In this systematic review of studies applying TDABC to primary TJA, we investigated the following: (1) Is there variation in TDABC methodology and cost estimates across institutions? (2) Is a standard set of direct and indirect costs included across studies? (3) Is there a difference in cost estimates derived from TDABC and traditional hospital cost-accounting approaches? and (4) How are institutions using TDABC (process and outputs) with respect to the TJA care pathway? METHODS: A comprehensive search strategy was developed that included the keywords "TDABC," "time-driven activity-based cost," "THA," "TKA," "THR," "TKR," and "TJR" in the PubMed/MEDLINE, EMBASE, Web of Science, Ovid SP, Scopus, and ScienceDirect databases for articles published between 2004 and 2018 as well as extensive hand searching and citation mining. Relevant studies (n = 15) were screened to include THA or TKA as the focus of the TDABC model, full-text articles, TDABC-based cost estimates for TJA, and studies written in English (n = 8). Due to the heterogeneity of outcomes/methodology in TDABC studies involving TJA, quality assessment was based on each study's adherence to the seven steps delineated by Kaplan et al. in their original publication introducing TDABC in health care. RESULTS: There was substantial variation in TDABC methodology (especially in scope), adherence to the seven steps of TDABC, and data collection. Only five of eight studies incorporated indirect costs into their TDABC calculation, with notable differences in which direct and indirect expenses were included. TDABC-based cost estimates for TJA ranged from USD 7081 to USD 29,557, with variation driven by the TJA timeframe and whether implant costs were included in the costing calculation. TDABC was most frequently used to compare against traditional hospital accounting methods (n = 4), to increase operational efficiency (n = 4), to reduce wasted resources (n = 3), and to mitigate risk (n = 3). CONCLUSIONS: TDABC-based cost estimates are more granular and useful in practice than those calculated via traditional hospital accounting; however, there is a lack of standardized principles to guide TDABC implementation (especially for indirect costs) due to institutional and regional differences in TDABC application. Although TDABC methodology will likely continue to vary somewhat between studies, standardized principles are needed to guide the definition, estimation, and reporting of costs to enable detailed examination of study methodology and inputs by readers. LEVEL OF EVIDENCE: Level III, economic and decision analysis.

Skilled Nursing Facility Placement Process After Total Hip and Total Knee Arthroplasty: Revised Rating System and Opportunities for Intervention.

BACKGROUND: With the advent of bundled payment models, identifying high-performing skilled nursing facilities (SNFs) has become increasingly important. The goal of this study is to develop a rating system to rank SNFs within our health system and to use this system to improve the SNF discharge process at our institution. METHODS: All SNF-discharged primary total joint arthroplasty cases in 2017 at a multi-hospital academic health system were queried. Discharge patterns were assessed using heat map analysis. Regression analyses in conjunction with structured discussions with subject matter experts were used to identify measures of SNF efficiency and care quality. A revised rating system was developed and used to identify high-performing facilities within our health system. Opportunities to re-direct patients to higher performing facilities were identified. RESULTS: A revised rating system for SNFs was constructed based on risk-adjusted SNF length of stay, 30-day re-admission rate, and 30-day emergency department visit rate. As 82% of patients were discharged to SNFs in close proximity to their home, high-performing SNFs (according to the revised rating system) were identified by geographic region. Mapping of the discharge process revealed multiple opportunities where patients could be re-directed to a higher performing SNF in their area. Using conservative estimates (25% of discharges re-directed), this is expected to achieve a cost saving of $2,600,000 over a 5-year period, mainly through reductions in SNF length of stay. CONCLUSION: This study describes the development of a revised rating system for SNFs which, when implemented, is expected to achieve substantial cost savings over a 5-year period.

Preoperative Patient-Reported Outcomes and Clinical Characteristics as Predictors of 90-Day Cost/Utilization and Complications.

BACKGROUND: With the advent of mandatory bundle payments for total joint arthroplasty (TJA), assessing patients' risk for increased 90-day complications and resource utilization is crucial. This study assesses the degree to which preoperative patient-reported outcomes predict 90-day complications, episode costs, and utilization in TJA patients. METHODS: All TJA cases in 2017 at 2 high-volume hospitals were queried. Preoperative HOOS/KOOS JR (Hip Injury and Osteoarthritis Outcome Score/Knee Injury and Osteoarthritis Outcome Score) and Veterans RAND 12-item health survey (VR-12) were administered to patients preoperatively via e-collection platform. For patients enrolled in the Medicare bundle, cost data were extracted from claims. Bivariate and multivariate regression analyses were performed. RESULTS: In total, 2108 patients underwent TJA in 2017; 1182 (56%) were missing patient-reported outcome data and were excluded. The final study population included 926 patients, 199 (21%) of which had available cost data. Patients with high bundle costs tended to be older, suffer from vascular disease and anemia, and have higher Charlson scores (P < .05 for all). These patients also had lower baseline VR-12 Physical Component Summary Score (PCS; 24 vs 30, P ≤ .001) and higher rates of extended length of stay, skilled nursing facility discharge, 90-day complications, and 90-day readmission (P ≤ .04 for all). In multivariate analysis, higher baseline VR-12 PCS was protective against extended length of stay, skilled nursing facility discharge, >75th percentile bundle cost, and 90-day bundle cost exceeding target bundle price (P < .01 for all). Baseline VR-12 Mental Component Summary Score and HOOS/KOOS JR were not predictive of complications or bundle cost. CONCLUSION: Low baseline VR-12 PCS is predictive of high 90-day bundle costs. Baseline HOOS/KOOS JR scores were not predictive of utilization or cost. Neither VR-12 nor HOOS/KOOS JR was predictive of 90-day readmission or complications.

Are Medicare's Nursing Home Compare Ratings Accurate Predictors of 90-Day Complications, Readmission, and Bundle Cost for Patients Undergoing Primary Total Joint Arthroplasty?

BACKGROUND: Nursing Home Compare (NHC) ratings, created and maintained by Medicare, are used by both hospitals and consumers to aid in the skilled nursing facility (SNF) selection process. To date, no studies have linked NHC ratings to actual episode-based outcomes. The purpose of this study was to evaluate whether NHC ratings are valid predictors of 90-day complications, readmission, and bundle costs for patients discharged to an SNF after primary total joint arthroplasty (TJA). METHODS: All SNF-discharged primary TJA cases in 2017 at a multihospital academic health system were queried. Demographic, psychosocial, and clinical variables were manually extracted from the health record. Medicare NHC ratings were then collected for each SNF. For patients in the Medicare bundle, postacute and total bundle cost was extracted from claims. RESULTS: Four hundred eighty-eight patients were discharged to a total of 105 unique SNFs. In multivariate analysis, overall NHC rating was not predictive of 90-day readmission/major complications, >75th percentile postacute cost, or 90-day bundle cost exceeding the target price. SNF health inspection and quality measure ratings were also not predictive of 90-day readmission/major complications or bundle performance. A higher SNF staffing rating was independently associated with a decreased odds for >75th percentile 90-day postacute spend (odds ratio, 0.58; P = .01) and a 90-day bundle cost exceeding the target price (odds ratio = 0.69; P = .02) but was similarly not predictive of 90-day readmission/complications. CONCLUSION: Results of our study suggest that Medicare's NHC tool is not a useful predictor of 90-day costs, complications, or readmissions for SNFs within our health system.

Defining and Optimizing Value in Total Joint Arthroplasty From the Patient, Payer, and Provider Perspectives.

BACKGROUND: The purpose of this study is to define value in bundled total joint arthroplasty (TJA) from the differing perspectives of the patient, payer/employer, and hospital/provider. METHODS: Demographic, psychosocial, clinical, financial, and patient-reported outcomes (PROs) data from 2017 to 2018 elective TJA cases at a multihospital academic health system were queried. Value was defined as improvement in PROs (preoperatively to 1 year postoperatively) for patients, improvement in PROs per $1000 of bundle cost for payers, and the normalized sum of improvement in PROs and hospital bundle margin for providers. Bivariate analysis was used to compare high value vs low value (>50th percentile vs <50th percentile). Multivariate analysis was performed to identify predictors. RESULTS: A total of 280 patients had PRO data, of which 71 had Medicare claims data. Diabetes (odds ratio [OR], 0.45; P = .02) predicted low value for patients; female gender (OR, 0.25), hypertension (OR, 0.17), pulmonary disease (OR, 0.12), and skilled nursing facility discharge (OR, 0.17) for payers (P ≤ .03 for all); and pulmonary disease (OR, 0.16) and skilled nursing facility discharge (OR, 0.19) for providers (P ≤ .04 for all). CONCLUSION: This is the first article to define value in TJA under a bundle payment model from multiple perspectives, providing a foundation for future studies analyzing value-based TJA.