Notch signalling drives synovial fibroblast identity and arthritis pathology.

The synovium is a mesenchymal tissue composed mainly of fibroblasts, with a lining and sublining that surround the joints. In rheumatoid arthritis the synovial tissue undergoes marked hyperplasia, becomes inflamed and invasive, and destroys the joint1,2. It has recently been shown that a subset of fibroblasts in the sublining undergoes a major expansion in rheumatoid arthritis that is linked to disease activity3-5; however, the molecular mechanism by which these fibroblasts differentiate and expand is unknown. Here we identify a critical role for NOTCH3 signalling in the differentiation of perivascular and sublining fibroblasts that express CD90 (encoded by THY1). Using single-cell RNA sequencing and synovial tissue organoids, we found that NOTCH3 signalling drives both transcriptional and spatial gradients-emanating from vascular endothelial cells outwards-in fibroblasts. In active rheumatoid arthritis, NOTCH3 and Notch target genes are markedly upregulated in synovial fibroblasts. In mice, the genetic deletion of Notch3 or the blockade of NOTCH3 signalling attenuates inflammation and prevents joint damage in inflammatory arthritis. Our results indicate that synovial fibroblasts exhibit a positional identity that is regulated by endothelium-derived Notch signalling, and that this stromal crosstalk pathway underlies inflammation and pathology in inflammatory arthritis.

Patterns of Infectious Disease Associated With Injection Drug Use in Massachusetts.

BACKGROUND: Since 2014, multiple outbreaks of human immunodeficiency virus (HIV) among people who inject drugs have occurred across the United States along with hepatitis C virus (HCV), skin and soft tissue infections (SSTIs), and infective endocarditis (IE), creating a converging public health crisis. METHODS: We analyzed the temporal patterns of infectious disease and overdose using a hierarchical Bayesian distributed lag logistic regression model examining the probability that a given geographic area experienced at least 1 HIV case in a given month as a function of the counts/rates of overdose, HCV, SSTI, and IE and associated medical procedures at different lagged time periods. RESULTS: Current-month HIV is associated with increasing HCV cases, abscess incision and drainage, and SSTI cases, in distinct temporal patterns. For example, 1 additional HCV case occurring 5 and 7 months previously is associated with a 4% increase in the odds of observing at least 1 current-month HIV case in a given locale (odds ratios, 1.04 [90% credible interval {CrI}: 1.01-1.10] and 1.04 [90% CrI: 1.00-1.09]). No such associations were observed for echocardiograms, IE, or overdose. CONCLUSIONS: Lagged associations in other infections preceding rises in current-month HIV counts cannot be described as predictive of HIV outbreaks but may point toward newly discovered epidemics of injection drug use and associated clinical sequalae, prompting clinicians to screen patients more carefully for substance use disorder and associated infections.

Trusted residents and housing assistance to decrease violence exposure in New Haven (TRUE HAVEN): a strengths-based and community-driven stepped-wedge intervention to reduce gun violence.

BACKGROUND: We describe the rationale and study design for "TRUsted rEsidents and Housing Assistance to decrease Violence Exposure in New Haven (TRUE HAVEN)," a prospective type 1 hybrid effectiveness/implementation study of a multi-level intervention using a stepped wedge design. TRUE HAVEN aims to lower rates of community gun violence by fostering the stability, wealth, and well-being of individuals and families directly impacted by incarceration through the provision of stable housing and by breaking the cycle of trauma. DESIGN: TRUE HAVEN is an ongoing, multi-level intervention with three primary components: financial education paired with housing support (individual level), trauma-informed counseling (neighborhood level), and policy changes to address structural racism (city/state level). Six neighborhoods with among the highest rates of gun violence in New Haven, Connecticut, will receive the individual and neighborhood level intervention components sequentially beginning at staggered 6-month steps. Residents of these neighborhoods will be eligible to participate in the housing stability and financial education component if they were recently incarcerated or are family members of currently incarcerated people; participants will receive intense financial education and follow-up for six months and be eligible for special down payment and rental assistance programs. In addition, trusted community members and organization leaders within each target neighborhood will participate in trauma-informed care training sessions to then be able to recognize when their peers are suffering from trauma symptoms, to support these affected peers, and to destigmatize accessing professional mental health services and connect them to these services when needed. Finally, a multi-stakeholder coalition will be convened to address policies that act as barriers to housing stability or accessing mental healthcare. Interventions will be delivered through existing partnerships with community-based organizations and networks. The primary outcome is neighborhood rate of incident gun violence. To inform future implementation and optimize the intervention package as the study progresses, we will use the Learn As You Go approach to optimize and assess the effectiveness of the intervention package on the primary study outcome. DISCUSSION: Results from this protocol will yield novel evidence for whether and how addressing structural racism citywide leads to a reduction in gun violence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05723614. Registration date: February 01, 2023. Please refer to https://clinicaltrials.gov/ct2/show/NCT05723614 for public and scientific inquiries.

The Association of Sacro-Femoro-Pubic Angle and Postoperative Dislocation Following Total Hip Arthroplasty.

BACKGROUND: Spino-pelvic orientation may affect dislocation risk following total hip arthroplasty (THA). It can be measured on lateral lumbo-pelvic radiographs. The sacro-femoro-pubic (SFP) angle, measured on an antero-posterior (AP) pelvis radiograph, is a reliable proxy for pelvic tilt, a measurement of spino-pelvic orientation measured on a lateral lumbo-pelvic radiograph. The purpose of this study was to investigate the relationship between SFP angle and dislocation following THA. METHODS: An Institutional Review Board-approved retrospective case-control study was conducted at a single academic center. We matched 71 dislocators (cases) to 71 nondislocators (controls) following THA performed by 1 of 10 surgeons between September 2001 and December 2010. Two authors (readers) independently calculated SFP angle from single preoperative AP pelvis radiographs. Readers were blinded to cases and controls. Conditional logistic regressions were used to identify factors differentiating cases and controls. RESULTS: The data did not show a clinically relevant or statistically significant difference in SFP angles after adjusting for gender, American Society of Anesthesiologists classification, prosthetic head size, age at time of THA, measurement laterality, and surgeon. CONCLUSION: We did not find an association between preoperative SFP angle and dislocation following THA in our cohort. Based on our data, SFP angle as measured on a single AP pelvis radiograph should not be used to assess dislocation risk prior to THA.

Adventures in COVID-19 Policy Modeling: Education Edition.

PURPOSE OF REVIEW: To introduce readers to policy modeling, a multidisciplinary field of quantitative analysis, primarily used to help guide decision-making. This review focuses on the choices facing educational administrators, from K-12 to universities in the USA, as they confronted the COVID-19 pandemic. We survey three key model-based approaches to mitigation of SARS-CoV-2 spread in schools and on university campuses. RECENT FINDINGS: Frequent testing, coupled with strict attention to behavioral interventions to prevent further transmission can avoid large outbreaks on college campuses. K-12 administrators can greatly reduce the risks of severe outbreaks of COVID-19 in schools through various mitigation measures including classroom infection control, scheduling and cohorting strategies, staff and teacher vaccination, and asymptomatic screening. Safer re-opening of college and university campuses as well as in-person instruction for K-12 students is possible, under many though not all epidemic scenarios if rigorous disease control and screening programs are in place.

The Evolution of Implant Design Decreases the Incidence of Lateral Release in Primary Total Knee Arthroplasty.

BACKGROUND: Appropriate balancing of the patellofemoral joint (PFJ) using a lateral release can help to prevent patellar instability in total knee arthroplasty (TKA). Contemporary total knee implant designs are characterized by enhanced trochlear geometry more similar to native knee anatomy to minimize instability and reduce utilization of a lateral release. METHODS: We retrospectively reviewed consecutive TKA cases from a single senior surgeon's practice with 3 successive total knee designs: the Press-Fit Condylar (PFC), the Sigma, and the ATTUNE (DePuy, Warsaw, IN). We evaluated the use of lateral release with each implant type to determine if design changes have improved patellar stability, reducing the need for lateral release. We used multivariate analysis to determine the association between implant type and lateral release, adjusting for age, sex, preoperative alignment, and bearing type. RESULTS: We evaluated 1991 records of primary TKAs performed from 1980-2015. As compared with the ATTUNE, the adjusted odds of lateral release were greater for patients receiving PFC implants (Odds ratio [OR] 6.35, 95% confidence interval [CI] 3.85,10.49) and Sigma implants (OR 2.02, 95% CI 1.26, 3.23). In addition, fixed bearing implants were associated with greater adjusted odds of lateral release (OR 1.80, 95% CI 1.24, 2.62). CONCLUSION: We found that older knee implants were associated with higher use of lateral release, with successive designs the need for lateral release to balance the PFJ decreased. Continued design improvements to match the native knee anatomy may further improve the stability of the PFJ in future designs.

Predictors of Patient-Reported Outcomes of Total Joint Arthroplasty in a Developing Country.

BACKGROUND: In response to the growing burden of joint disease, developing countries are starting to create their own total joint arthroplasty (TJA) programs. To date, there has been limited research on predictors of TJA outcomes in a developing country. This investigation uses patient-reported outcome measures collected by a medical mission to assess predictors of TJA outcomes in the Dominican Republic. METHODS: Baseline and postoperative information from 156 of the mission's recipients of hip and knee TJA was used. Demographics were abstracted from clinical notes, and self-reported pain and functional status were assessed using Western Ontario and McMaster University Osteoarthritis Index and Short-Form 36 measures. Bivariate analysis identified variables to include in multivariable regression models of factors associated with function and pain outcomes and improvement in these domains 1 or 2 years postoperatively. RESULTS: The cohort had a mean age of 61.3 years, 82% were female, 79% had total knee arthroplasty, and 42% of the procedures were bilateral. In multivariate analyses, at P < .05, male sex, better preoperative function, and use of bilateral procedure were associated with better functional outcome. Male sex and worse preoperative pain were associated with better pain outcome. Worse preoperative pain and function, as well as bilateral surgery were associated with greater improvement in function. Additionally, a greater number of bothersome joints was associated with greater pain reduction. CONCLUSION: Our findings of better follow-up pain scores among patients with worse pain preoperatively and better functional improvement among those undergoing bilateral replacements contrast with study results from developed countries. The explanations for these observations merit further study.

Cruciate-retaining TKA is an option in patients with prior patellectomy.

BACKGROUND: The recommendation for using posterior-stabilized (PS) implants in patellectomy patients undergoing total knee arthroplasty (TKA) is based on older case series with heterogeneous patient populations. The use of cruciate-retaining implants in these patients has not been evaluated with more contemporary implant designs. QUESTIONS/PURPOSES: The purpose of this study was to evaluate the survivorship and functional outcomes (Knee Society score, presence of an extensor lag, and range of motion) of cruciate-retaining (CR) TKA in patients with prior patellectomy. METHODS: Between 1986 and 2012, we performed 27 CR TKAs in 25 patients after patellectomy. Of those, 23 CR TKAs in 21 patients were available for followup at a minimum of 2 years (mean, 11.2 years; range, 2.3-25.1 years). In this retrospective study, we queried a prospectively maintained database to assess functional outcomes and survivorship. RESULTS: Aseptic loosening-free survival was 100% at 5 and 10 years, and survival with revision for any reason as the outcome was 96% at 5 years (95% confidence interval [CI], 87.7%-100%) and 84% at 10 years (95% CI, 69.5%-100%). One patient was revised for aseptic loosening at 10.2 years postoperatively. Mean Knee Society scores improved from 36±13 preoperatively to 92±9.6 at followup. Extensor lag was present in seven patients preoperatively and only three at followup. Average knee flexion at followup was 112°±12.5°. CONCLUSIONS: In this study we found good long-term survivorship and functional outcomes with a CR implant design in patients following patellectomy. Earlier studies have favored PS over CR implants for patients with patellectomies. We believe this series suggests that CR TKA is indeed an option in patients with patellectomy. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Can therapy dogs improve pain and satisfaction after total joint arthroplasty? A randomized controlled trial.

BACKGROUND: The use of animals to augment traditional medical therapies was reported as early as the 9th century but to our knowledge has not been studied in an orthopaedic patient population. The purpose of this study was to evaluate the role of animal-assisted therapy using therapy dogs in the postoperative recovery of patients after THA and TKA. QUESTIONS/PURPOSES: We asked: (1) Do therapy dogs have an effect on patients' perception of pain after total joint arthroplasty as measured by the VAS? (3) Do therapy dogs have an effect on patients' satisfaction with their hospital stay after total joint arthroplasty as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS)? METHODS: A randomized controlled trial of 72 patients undergoing primary unilateral THA or TKA was conducted. Patients were randomized to a 15-minute visitation with a therapy dog before physical therapy or standard postoperative physical therapy regimens. Both groups had similar demographic characteristics. Reduction in pain was assessed using the VAS after each physical therapy session, beginning on postoperative Day 1 and continuing for three consecutive sessions. To ascertain patient satisfaction, the proportion of patients selecting top-category ratings in each subsection of the HCAHPS was compared. RESULTS: Patients in the treatment group had lower VAS scores after each physical therapy session with a final VAS score difference of 2.4 units (animal-assisted therapy VAS, 1.7; SD, 0.97 [95% CI, 1.4-2.0] versus control VAS, 4.1; SD, 0.97 [95% CI, 3.8-4.4], p<0.001) after the third physical therapy session. Patients in the treatment group had a higher proportion of top-box HCAHPS scores in the following fields: nursing communication (33 of 36, 92% [95% CI, 78%-98%] versus 69%, 25 of 36 [95% CI, 52%-84%], p=0.035; risk ratio, 1.3 [95% CI of risk ratio, 1.0-1.7]; risk difference, 23% [95% CI of risk difference, 5%-40%]), pain management (34 of 36, 94% [95% CI, 81%-99%], versus 26 of 36, 72% [95% CI, 55%-86%], p=0.024; risk ratio, 1.3 [95% CI of risk ratio, 1.1-1.6]; risk difference, 18% [95% CI of risk difference, 5%-39%]). The overall hospital rating also was greater in the treatment group (0-10 scale) (9.6; SD, 0.7 [95% CI, 9.3-9.8] versus 8.6, SD, 0.9 [95% CI, 8.3-8.9], p<0.001). CONCLUSIONS: The use of therapy dogs has a positive effect on patients' pain level and satisfaction with hospital stay after total joint replacement. Surgeons are encouraged to inquire about the status of volunteer-based animal-assisted therapy programs in their hospital as this may provide a means to improve the immediate postoperative recovery for a select group of patients having total joint arthroplasty. LEVEL OF EVIDENCE: Level II, randomized controlled study. See Instructions for Authors for a complete description of levels of evidence.

Effect of smoking and soft tissue release on risk of revision after total knee arthroplasty: a case- control study.

BACKGROUND: Increasing utilization of primary total knee arthroplasty (TKA) is projected to expand demand for revision TKA. Revision TKAs are procedurally complex and incur high costs on our financially constrained healthcare system. The purpose of this study was to use a case-control design to identify factors predisposing to revision TKA, particularly demographic, clinical and perioperative technical factors. METHODS: We conducted a case control study to investigate patient, surgical and perioperative factors associated with greater risk of revision TKA. We included patients who received TKA at a tertiary center between 1996 and 2009. Cases (patients that had primary and revision TKA) were matched to controls (patients with primary TKA that was not revised) in a 1:2 ratio and risk of revision examined using conditional logistic regression. RESULTS: We identified 146 cases and 290 controls. Patient factors independently associated with revision included male sex (OR 1.73; 95% CI 1.06-2.81) and smoking (OR 2.87; 1.33-6.19). Older age was associated with decreased risk (OR 0.83 per 5-year increment; 95% CI 0.75-0.92). Lateral release was the only technical factor associated with revision (OR 1.92; 1.07-3.43). CONCLUSIONS: In this case control study younger patient age, male gender, soft tissue release and active smoking status were associated with increased revision risk. Although we do not know whether the risk of smoking arises from short- or long-term exposure, smoking cessation prior to TKA should be considered as an intervention for decreasing revision risk.

Participation in physical activity in patients 1-4 years post total joint replacement in the Dominican Republic.

BACKGROUND: To address both the growing burden of joint disease and the gaps in medical access in developing nations, medical relief organizations have begun to launch programs to perform total joint replacement (TJR) on resident populations in developing countries. One outcome of TJR of particular interest is physical activity (PA) since it is strongly linked to general health. This study evaluates the amount of postoperative participation in PA in low-income patients who received total joint replacement in the Dominican Republic and identifies preoperative predictors of postoperative PA level. METHODS: We used the Yale Physical Activity Survey (YPAS) to assess participation in postoperative PA 1-4 years following total knee or hip replacement. We compared the amount of aerobic PA reported by postoperative TJR patients with the levels of PA recommended by the CDC and WHO. We also analyzed preoperative determinants of postoperative participation in aerobic PA in bivariate and multivariate analyses. RESULTS: 64 patients out of 170 eligible subjects (52/128 TKR and 14/42 THR) who received TJR between 2009-2012 returned for an annual follow-up visit in 2013, with a mean treatment-to-follow-up time of 2.1 years. 43.3% of respondents met CDC/WHO criteria for sufficient participation in aerobic PA. Multivariate analyses including data from 56 individuals identified that patients who were both younger than 65 and at least two years postoperative had an adjusted mean activity dimensions summary index (ADSI) 22.9 points higher than patients who were 65 or older and one year postoperative. Patients who lived with friends or family had adjusted mean ADSI 17.2 points higher than patients living alone. Patients who had the most optimistic preoperative expectations of outcome had adjusted mean ADSI scores that were 19.8 points higher than those who were less optimistic. CONCLUSION: The TJR patients in the Dominican cohort participate in less PA than recommended by the CDC/WHO. Additionally, several associations were identified that potentially affect PA in this population; specifically, participants who are older than 65, recently postoperative, less optimistic about postoperative outcomes and who live alone participate in less PA.

Accessibility of Opioid Treatment Programs Based on Conventional vs Perceived Travel Time Measures.

Importance: Transportation barriers have long been associated with poorer health outcomes; this burden is especially acute for individuals with opioid use disorder (OUD), a chronic disease often associated with low socioeconomic status. Conventional travel time analyses may not fully account for experiential components of travel, thereby understating the true travel burden and overstating treatment accessibility to opioid treatment programs (OTPs). Objective: To develop a metric of feels-like accessibility for those using public transit to access OTPs that accounts for the realistic travel burden on individuals with OUD. Design, Setting, and Participants: This cross-sectional study integrated high-resolution transit schedules and operating hours of OTPs to measure feels-like accessibility. Feels-like accessibility considers the differential outcomes of out-of-vehicle travel components and more realistically reflects individuals' transportation burden than conventional accessibility measures. Gini indices and spatial regression models were used to investigate inequities in accessibility. Geocoded data for residential addresses of 1018 overdose fatalities in Connecticut in 2019 were used as a proxy for the treatment needs of individuals with OUD. Data were analyzed between May and August 2023. Main Outcomes and Measures: Conventional and feels-like accessibility scores. Exposures: Fluctuations in public transit frequencies over the course of the day and the limited operating hours of the OTPs. Results: Of the 1018 individuals in the study, the mean (SD) age at death was 43.7 (12.6) years, 784 individuals (77%) were men, 111 (11%) were African American, and 889 (87%) were White, with other racial and ethnic categories including 18 individuals (2%). A total of 264 individuals in the sample (26%) could not access an OTP within 180 minutes. For those who could access these facilities, the average 1-way travel time was 45.6 minutes, with individuals spending approximately 70% of their trip duration on out-of-vehicle travel components. The conventional accessibility metric underestimates individuals' travel burden to OTPs as well as the inequity in accessibility compared with the feels-like accessibility metric. For example, the median (range) conventional accessibility score, defined as the number of OTPs within 120 minutes of transit travel time, was 5.0 (0.0-17.0); the median (range) feels-like accessibility score, defined as the number of OTPs within 120 minutes of transit travel time weighted to account for in- and out-of-vehicle segments, was 1.0 (0.0-10.0). There is a considerable temporal variation in travel time and accessibility depending on the departure times. Conclusions and Relevance: In this cross-sectional study of travel burdens, the calculated feels-like accessibility scores, which consider the differential outcomes of out-of-vehicle travel components (eg, walking and waiting), could better and more realistically reflect passengers' transportation burden. Policy recommendations derived from the conventional accessibility metric could be misleading, and decision-makers should use feels-like accessibility metrics that adequately capture individuals' travel burdens. In the context of access to OTPs, the findings from this study suggest that opening new OTP sites to address gaps in access due to distance to services or extending hours of operation at existing sites may ameliorate the travel burden for individuals.

Real-time fMRI links subjective experience with brain activity during focused attention.

Recent advances in brain imaging have improved the measure of neural processes related to perceptual, cognitive and affective functions, yet the relation between brain activity and subjective experience remains poorly characterized. In part, it is a challenge to obtain reliable accounts of participant's experience in such studies. Here we addressed this limitation by utilizing experienced meditators who are expert in introspection. We tested a novel method to link objective and subjective data, using real-time fMRI (rt-fMRI) to provide participants with feedback of their own brain activity during an ongoing task. We provided real-time feedback during a focused attention task from the posterior cingulate cortex, a hub of the default mode network shown to be activated during mind-wandering and deactivated during meditation. In a first experiment, both meditators and non-meditators reported significant correspondence between the feedback graph and their subjective experience of focused attention and mind-wandering. When instructed to volitionally decrease the feedback graph, meditators, but not non-meditators, showed significant deactivation of the posterior cingulate cortex. We were able to replicate these results in a separate group of meditators using a novel step-wise rt-fMRI discovery protocol in which participants were not provided with prior knowledge of the expected relationship between their experience and the feedback graph (i.e., focused attention versus mind-wandering). These findings support the feasibility of using rt-fMRI to link objective measures of brain activity with reports of ongoing subjective experience in cognitive neuroscience research, and demonstrate the generalization of expertise in introspective awareness to novel contexts.

Associations between preoperative functional status and functional outcomes of total joint replacement in the Dominican Republic.

OBJECTIVE: In developed countries, the functional status scores of patients with poor preoperative scores undergoing total joint replacement (TJR) improve more following TJR than those for patients with better preoperative scores. However, those with better preoperative scores achieve the best postoperative functional outcomes. We determined whether similar associations exist in a developing country. METHODS: Dominican patients undergoing total hip or knee replacement completed WOMAC and SF-36 surveys preoperatively and at 12-month follow-up. Patients were stratified into low-, medium- and high-scoring preoperative groups based on their preoperative WOMAC function scores. We examined the associations between the baseline functional status of these groups and two outcomes-improvement in functional status over 12 months and functional status at 12 months-using analysis of variance with multivariable linear regression. RESULTS: Patients who scored the lowest preoperatively made the greatest gains in function and pain relief following their TJRs. However, there were no significant differences in pain or function at 12-month follow-up between patients who scored low and those who scored high on preoperative WOMAC and SF-36 surveys. CONCLUSION: Patients with poor preoperative functional status had greater improvement but similar 12-month functional outcomes compared with patients who had a higher level of function before surgery. These results suggest that a policy of focusing scarce resources on patients with worse functional status in developing countries may optimize improvement following TJR without threatening functional outcome. Additional research is needed to confirm these findings in other developing countries and to understand why these associations vary between patients in the Dominican Republic and patients from developed countries.

Obesity & hypertension are determinants of poor hemodynamic control during total joint arthroplasty: a retrospective review.

BACKGROUND: Proper blood pressure control during surgical procedures such as total joint arthroplasty (TJA) is considered critical to good outcome. There is poor understanding of the pre-operative risk factors for poor intra-operative hemodynamic control. The purpose of this study is to identify risk factors for poor hemodynamic control during TJA. METHODS: We performed a retrospective cohort analysis of 118 patients receiving TJA in the Dominican Republic. We collected patient demographic and comorbidity data. We developed an a priori definition for poor hemodynamic control: 1) Mean arterial pressure (MAP) <65% of preoperative MAP or 2) MAP >135% of preoperative MAP. We performed bivariate and multivariate analyses to identify risk factors for poor hemodynamic control during TJA. RESULTS: Hypertension was relatively common in our study population (76 of 118 patients). Average preoperative mean arterial pressure was 109.0 (corresponding to an average SBP of 149 and DBP of 89). Forty-nine (41.5%) patients had intraoperative blood pressure readings consistent with poor hemodynamic control. Based on multi-variable analysis preoperative hypertension of any type (RR 2.9; 95% CI 1.3-6.3) and an increase in BMI (RR 1.2 per 5 unit increase; 95% CI 1.0-1.5) were significant risk factors for poor hemodynamic control. CONCLUSIONS: Preoperative hypertension and being overweight/obese increase the likelihood of poor blood pressure control during TJA. Hypertensive and/or obese patients warrant further attention and medical optimization prior to TJA. More work is required to elucidate the relationship between these risk factors and overall outcome.

Enhancing the quality of international orthopedic medical mission trips using the blue distinction criteria for knee and hip replacement centers.

BACKGROUND: Several organizations seek to address the growing burden of arthritis in developing countries by providing total joint replacements (TJR) to patients with advanced arthritis who otherwise would not have access to these procedures. Because these mission trips operate in resource poor environments, some of the features typically associated with high quality care may be difficult to implement. In the U.S., many hospitals that perform TJRs use the Blue Cross/Shield's Blue Distinction criteria as benchmarks of high quality care. Although these criteria were designed for use in the U.S., we applied them to Operation Walk (Op-Walk) Boston's medical mission trip to the Dominican Republic. Evaluating the program using these criteria illustrated that the program provides high quality care and, more importantly, helped the program to find areas of improvement. METHODS: We used the Blue Distinction criteria to determine if Op-Walk Boston achieves Blue Distinction. Each criterion was grouped according to the four categories included in the Blue Distinction criteria--"general and administrative", "structure", "process", or "outcomes and volume". Full points were given for criteria that the program replicates entirely and zero points were given for criteria that are not replicated entirely. Of the non-replicated criteria, Op-Walk Boston's clinical and administrative teams were asked if they compensate for failure to meet the criterion, and they were also asked to identify barriers that prevent them from meeting the criterion. RESULTS: Out of 100 possible points, the program received 71, exceeding the 60-point threshold needed to qualify as a Blue Distinction center. The program met five out of eight "required" criteria and 11 out of 19 "informational" criteria. It scored 14/27 in the "general" category, 30/36 in the "structure" category, 17/20 in the "process" category, and 10/17 in the "outcomes and volume" category. CONCLUSION: Op-Walk Boston qualified for Blue Distinction. Our analysis highlights areas of programmatic improvement and identifies targets for future quality improvement initiatives. Additionally, we note that many criteria can only be met by hospitals operating in the U.S. Future work should therefore focus on creating criteria that are applicable to TJR mission trips in the context of developing countries.

TRUsted rEsidents and Housing Assistance to decrease Violence Exposure in New Haven (TRUE HAVEN): A strengths-based and community-driven stepped-wedge intervention to reduce gun violence.

Background We describe the rationale and study design for " TRU sted r Esidents and H ousing A ssistance to decrease V iolence E xposure in N ew Haven (TRUE HAVEN)," a prospective type 1 hybrid effectiveness/implementation study of a multi-level intervention using a stepped wedge design. TRUE HAVEN aims to lower rates of community gun violence by fostering the stability, wealth, and well-being of individuals and families directly impacted by incarceration through the provision of stable housing and by breaking the cycle of trauma. Design: TRUE HAVEN is a multi-level intervention with three primary components: financial education paired with housing support (individual level), trauma-informed counseling (neighborhood level), and policy changes to address structural racism (city/state level). Six neighborhoods with among the highest rates of gun violence in New Haven, Connecticut, will receive the individual and neighborhood level intervention components sequentially beginning at staggered 6-month steps. Residents of these neighborhoods will be eligible to participate in the housing stability and financial education component if they were recently incarcerated or are family members of currently incarcerated people; participants will receive intense financial education and follow-up for six months and be eligible for special down payment and rental assistance programs. In addition, trusted community members and organization leaders within each target neighborhood will participate in trauma-informed care training sessions to then be able to recognize when their peers are suffering from trauma symptoms, to support these affected peers, and to destigmatize accessing professional mental health services and connect them to these services when needed. Finally, a multi-stakeholder coalition will be convened to address policies that act as barriers to housing stability or accessing mental healthcare. Interventions will be delivered through existing partnerships with community-based organizations and networks. The primary outcome is neighborhood rate of incident gun violence. To inform future implementation and optimize the intervention package as the study progresses, we will use the Learn As You Go approach to optimize and assess the effectiveness of the intervention package on the primary study outcome. Discussion Results from this protocol will yield novel evidence for whether and how addressing structural racism citywide leads to a reduction in gun violence. Trial registration ClinicalTrials.gov Identifier: NCT05723614. Registration date: February 01, 2023.

A broad screen for targets of immune complexes decorating arthritic joints highlights deposition of nucleosomes in rheumatoid arthritis.

Deposits of Ig and complement are abundant in affected joints of patients with rheumatoid arthritis (RA) and in animal models of RA in which antibodies are demonstrably pathogenic. To identify molecular targets of the Igs deposited in arthritic joints, which may activate local inflammation, we used a combination of mass spectrometry (MS) and protein microarrays. Immune complexes were affinity-purified from surgically removed joint tissues of 26 RA and osteoarthritis (OA) patients. Proteins complexed with IgG were identified by proteomic analysis using tandem MS. A striking diversity of components of the extracellular matrix, and some intracellular components, copurified specifically with IgG from RA and OA tissues. A smaller set of autoantigens was observed only in RA eluates. In complementary experiments, IgG fractions purified from joint immune complexes were tested on protein microarrays against a range of candidate autoantigens. These Igs bound a diverse subset of proteins and peptides from synovium and cartilage, different from that bound by normal serum Ig. One type of intracellular protein detected specifically in RA joints (histones H2A/B) was validated by immunohistology and found to be deposited on the cartilage surface of RA but not OA joints. Thus, autoantibodies to many determinants (whether deposited as "neoantigens" or normal constituents of the extracellular matrix) have the potential to contribute to arthritic inflammation.

Similar 20-year survivorship for single and bilateral total knee arthroplasty.

BACKGROUND: Long-term follow-up after total knee arthroplasty (TKA) is crucial to providing survivorship updates on available TKA implants to guide patient expectations when undergoing TKA. The purpose of this study was to compare implant survivorship between patients undergoing primary single, simultaneous bilateral, and staged bilateral TKA with 15-year minimum follow-up. METHODS: This retrospective study included 826 patients (n = 1089) who underwent primary single (n = 454), simultaneous bilateral (n = 266), or staged bilateral (n = 369) TKA using a single TKA system by a single surgeon from 1991-2005 with 15-year minimum follow-up. Demographics, clinical variables, and surgical outcomes were collected and compared using Student's t-test, chi-squared tests, or Kaplan-Meier analyses. Reoperation was defined as all surgeries performed on the knee after the index procedure; revision TKA was defined as complete implant exchange. p < 0.05 significant. RESULTS: Patients in the staged TKA cohort were younger (65.4 years = staged, 67.8 = simultaneous, 67.1 = single, p < 0.019). Women were less likely to receive simultaneous TKAs (22 %vs.29%, p < 0.001). Postoperative range of motion was similar (116.8° = simultaneous, 114.9° = staged, 114.8° = single, p = 0.11). Overall 15-year implant survival based on revision TKA was similar (97.7% = simultaneous, 97.2% = staged, 96.7% = single, p = 0.45). The estimated 15-year reoperation rate was 7.0% (95% CI, 5.5-8.7%). Reoperations were secondary to infection (35.5%), implant wear (26.3%), arthrofibrosis (18.4%), traumatic injuries (10.5%), pain (6.6%), pathologic lesion (1.3%), and avascular necrosis (1.3%). CONCLUSION: This study demonstrated a high implant survival rate of 95-97% at 20-years after primary single, staged bilateral and simultaneous bilateral TKA. Furthermore, simultaneous bilateral TKAs exhibited similar range of motion, implant survival, and rates of reoperation to staged bilateral and single TKA.

Estimating deaths averted and cost per life saved by scaling up mRNA COVID-19 vaccination in low-income and lower-middle-income countries in the COVID-19 Omicron variant era: a modelling study.

OBJECTIVES: While almost 60% of the world has received at least one dose of COVID-19 vaccine, the global distribution of vaccination has not been equitable. Only 4% of the population of low-income countries (LICs) has received a full primary vaccine series, compared with over 70% of the population of high-income nations. DESIGN: We used economic and epidemiological models, parameterised with public data on global vaccination and COVID-19 deaths, to estimate the potential benefits of scaling up vaccination programmes in LICs and lower-middle-income countries (LMICs) in 2022 in the context of global spread of the Omicron variant of SARS-CoV2. SETTING: Low-income and lower-middle-income nations. MAIN OUTCOME MEASURES: Outcomes were expressed as number of avertable deaths through vaccination, costs of scale-up and cost per death averted. We conducted sensitivity analyses over a wide range of parameter estimates to account for uncertainty around key inputs. FINDINGS: Globally, universal vaccination in LIC/LMIC with three doses of an mRNA vaccine would result in an estimated 1.5 million COVID-19 deaths averted with a total estimated cost of US$61 billion and an estimated cost-per-COVID-19 death averted of US$40 800 (sensitivity analysis range: US$7400-US$81 500). Lower estimated infection fatality ratios, higher cost-per-dose and lower vaccine effectiveness or uptake lead to higher cost-per-death averted estimates in the analysis. CONCLUSIONS: Scaling up COVID-19 global vaccination would avert millions of COVID-19 deaths and represents a reasonable investment in the context of the value of a statistical life. Given the magnitude of expected mortality facing LIC/LMIC without vaccination, this effort should be an urgent priority.