Identification of the Human Skeletal Stem Cell.

Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation toward cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion in response to acute skeletal injury. In addition, hSSC-derived stroma can maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis. VIDEO ABSTRACT.

Inaccurately Reported Statin Use Affects the Assessing of Lipid Profile Measures and Their Association with Coronary Artery Disease Risk.

BACKGROUND: Lipid profiling is central for coronary artery disease (CAD) risk assessment. Nonadherence or unreported use of lipid-lowering drugs, particularly statins, can significantly complicate the association between lipid profile measures and CAD clinical outcomes. By combining medication history evaluation with statin analysis in plasma, we determined the effects of inaccurately reported statin use on lipid profile measures and their association with CAD risk. METHODS: We compared medication history of statin use with statin concentration measurements, by liquid chromatography-tandem mass spectrometry, in 690 participants undergoing coronary angiography (63 ± 11 years of age). Nominal logistic regression was employed to model CAD diagnosis with statin measurements, phenotypic, and lipid profile characteristics. RESULTS: Medication history of statin use was confirmed by statin assay for 81% of the patients. Surprisingly, statins were detected in 46% of patients without statin use records. Nonreported statin use was disproportionately higher among older participants. Stratifying samples by statin history resulted in underestimated LDL-lipid measures. Apolipoprotein B concentrations had a significant inverse CAD association, which became nonsignificant upon re-stratification using the statin assay data. CONCLUSIONS: Our study uncovered prominent discrepancies between medication records and actual statin use measured by mass spectrometry. We showed that inaccurate statin use assessments may lead to overestimation and underestimation of LDL levels in statin user and nonuser categories, exaggerating the reverse epidemiology association between LDL levels and CAD diagnosis. Combining medication history and quantitative statin assay data can significantly improve the design, analysis, and interpretation of clinical and epidemiological studies.

A return-on-investment approach for prioritization of rigorous taxonomic research needed to inform responses to the biodiversity crisis.

Global biodiversity loss is a profound consequence of human activity. Disturbingly, biodiversity loss is greater than realized because of the unknown number of undocumented species. Conservation fundamentally relies on taxonomic recognition of species, but only a fraction of biodiversity is described. Here, we provide a new quantitative approach for prioritizing rigorous taxonomic research for conservation. We implement this approach in a highly diverse vertebrate group-Australian lizards and snakes. Of 870 species assessed, we identified 282 (32.4%) with taxonomic uncertainty, of which 17.6% likely comprise undescribed species of conservation concern. We identify 24 species in need of immediate taxonomic attention to facilitate conservation. Using a broadly applicable return-on-investment framework, we demonstrate the importance of prioritizing the fundamental work of identifying species before they are lost.

Comparison of Reptilian Genomes Reveals Deletions Associated with the Natural Loss of γδ T Cells in Squamates.

T lymphocytes or T cells are key components of the vertebrate response to pathogens and cancer. There are two T cell classes based on their TCRs, αß T cells and γδ T cells, and each plays a critical role in immune responses. The squamate reptiles may be unique among the vertebrate lineages by lacking an entire class of T cells, the γδ T cells. In this study, we investigated the basis of the loss of the γδ T cells in squamates. The genome and transcriptome of a sleepy lizard, the skink Tiliqua rugosa, were compared with those of tuatara, Sphenodon punctatus, the last living member of the Rhynchocephalian reptiles. We demonstrate that the lack of TCRγ and TCRδ transcripts in the skink are due to large deletions in the T. rugosa genome. We also show that tuataras are on a growing list of species, including sharks, frogs, birds, alligators, and platypus, that can use an atypical TCRδ that appears to be a chimera of a TCR chain with an Ab-like Ag-binding domain. Tuatara represents the nearest living relative to squamates that retain γδ T cells. The loss of γδTCR in the skink is due to genomic deletions that appear to be conserved in other squamates. The genes encoding the αßTCR chains in the skink do not appear to have increased in complexity to compensate for the loss of γδ T cells.

Unresolved haemosporidia of the Australian skink, Egernia stokesii.

The Australian skink Egernia stokesii had been recognised as a host of two species of Plasmodium, Plasmodium mackerrasae and P. circularis; nevertheless, molecular data are available for only a single haemosporidian species of this host. Its sequences are labelled as "Plasmodium sp." or "Plasmodium mackerrasae", but morphological characteristics of this isolate are unavailable. Phylogenetic analyses of these sequences placed them into the clade of the genus Haemocystidium. In this study, blood samples of six E. stokesii were analysed by both, molecular and microscopic methods to clarify the haemosporidia of this lizard. Application of these approaches offered discordant results. Whereas sequence analysis clustered our isolates with lizard species of Haemocystidium, morphology of blood stages is more akin to Plasmodium than Haemocystidium. However, limited sampling, indistinguishable nuclei/merozoites and risk of possible hidden presence of mixed infection prevent reliable species identification of detected parasites or their description as new species of Haemocystidium.

Proximal Humerus Fractures: How to Achieve Best Outcomes.

The treatment of proximal humerus fractures remains controversial. Although treatment modalities may vary, the goal of obtaining the best outcomes for patients remains the same. Most proximal humerus fractures can be treated nonsurgically but should still be managed actively. Deciding on surgical management requires a good understanding of indications and options. Indications for open reduction and internal fixation include younger or active patients with displaced two-, three-, and four-part fractures as well as fracture-dislocations with head-split patterns. Obtaining ideal outcomes requires anatomic reduction with restoration of the medial calcar as well as optimal position of implants to favor biomechanical stability. Reverse total shoulder arthroplasty is indicated for patients with severe and displaced fractures in older or low-demand patients. Obtaining the best functional outcomes depends on implant position, tuberosity healing, and early surgical intervention. Regardless of the treatment modality, these fractures can be challenging, and proper patient rehabilitation must be implemented. Future research will focus on patient selection and improving surgical techniques to maximize outcomes.

Limb position affects intraoperative assessment of condylar width.

PURPOSE: We sought to define how changes in position and rotation of fluoroscopic imaging may affect the assessment of condylar widening intraoperatively. METHODS: Thirty-three patients with tibial plateau fractures were prospectively identified and included in this study. Fluoroscopic images of the uninjured tibial plateau were obtained in (1) full extension and (2) slight flexion on foam ramp. Beginning with a plateau view, additional views of the tibial plateau were then obtained by rotating the fluoroscope around the knee in 5 degree increments up to 15 degrees in both internal and external rotation. Measurements of distal femoral condylar width (DFW), distal femoral articular width (FAW), proximal tibial articular width (TAW) and lateral plateau width (LPW) were performed. RESULTS: LPW was decreased in flexion compared to extension at all degrees of rotation (p = 0.04-0.00001). There was a trend toward increasing LPW with increasing degrees of internal rotation which reached significance at 15˚ of internal rotation when the knee was flexed. On ANOVA, there was a significant difference of LPW with increasing degree of internal rotation when the knee was in flexion (p = 0.008), but not in extension. There were no differences in DFW, FAW, TAW and DFW/TAW at any point though LPW was decreased in flexion at all degrees of rotation. The FAW/TAW ratio was increased in flexion at all degrees of rotation. DISCUSSION: The knee in flexion will underestimate the measurement of condylar width compared to the knee in full extension, by ~ 2 mm. Rotation of the knee, in comparison, did not have a significant effect on condylar width assessment. LEVEL OF EVIDENCE: Diagnostic II.

Incisional negative pressure wound therapy may not protect against post-operative surgical site complications in bicondylar tibial plateau fractures.

PURPOSE: To determine if incisional negative pressure wound therapy is protective against post-operative surgical site complications following definitive fixation of bicondylar tibial plateau fractures. METHODS: A retrospective analysis of patients diagnosed with an acute bicondylar tibial plateau fracture (AO/OTA 41-C) undergoing ORIF from 2010 to 2020 was performed. Patients received either a standard sterile dressing (SD) or incisional negative pressure wound therapy (iNPWT). Primary outcomes included surgical site infection, osteomyelitis, and wound dehiscence. Secondary outcomes included non-union and return to the operating room. Multivariate logistic regression analyses were performed. RESULTS: 180 patients were included and 22% received iNPWT (n = 40) and 78% received standard dressings (n = 140). iNPWT was more common in active smokers (24.7% vs. 19.3%, p = 0.002) and the SD group was more likely to be lost to follow up (3.6% vs. 0%, p = 0.025). iNPWT was not protective against infection or surgical site complications, and in fact, was associated with higher odds of post-operative infection (OR: 8.96, p = 0.005) and surgical site complications (OR:4.874, p = 0.009) overall. Alcohol abuse (OR: 19, p = 0.005), tobacco use (OR: 4.67, p = 0.009), and time to definitive surgery (OR = 1.21, p = 0.033) were all independent risk factors for post-operative infection. CONCLUSION: In this series of operatively treated bicondylar tibial plateau fractures, iNPWT did not protect against post-operative surgical site complications compared to conventional dressings. Tobacco use, alcohol abuse, and time to definitive surgery, were independent risk factors for post-operative infection. Further studies are needed to determine if iNPWT offers a protective benefit in exclusively high-risk patients with relevant medical and social history.

Interaction of preoperative chemoprophylaxis and tranexamic acid use does not affect transfusion in acetabular fracture surgery.

PURPOSE: While the effects of tranexamic acid (TXA) use on transfusion rates after acetabular fracture surgery are unclear, previous evidence suggests that holding deep vein thrombosis (DVT) chemoprophylaxis may improve TXA efficacy. This study examines whether holding DVT chemoprophylaxis in patients receiving TXA affects intraoperative and postoperative transfusion rates in acetabular fracture surgery. METHODS: We reviewed electronic medical records (EMR) of 305 patients who underwent open reduction and internal fixation of acetabular fractures (AO/OTA 62) and stratified patients per the following perioperative treatment: (1) no intraoperative TXA (noTXA), (2) intraoperative TXA and no preoperative DVT prophylaxis (opTXA/noDVTP), or (3) intraoperative TXA and preoperative DVT prophylaxis (opTXA/opDVTP). The primary outcomes were need for intraoperative or postoperative transfusion. Risk factors for each primary outcome were assessed using multivariable regression. RESULTS: Intraoperative or postoperative transfusion rates did not significantly differ between opTXA/opDVTP and opTXA/noDVTP groups (46.2% vs. 36%, p = 0.463; 15.4% vs. 28%, p = 0.181). Median units transfused did not differ between groups (2 ± 1 vs. 2 ± 1, p = 0.515; 2 ± 1 vs. 2 ± 0, p = 0.099). There was no association between preoperative DVT chemoprophylaxis and TXA with intraoperative or postoperative transfusions. EBL, preoperative hematocrit, and IV fluids were associated with intraoperative transfusions; age and Charlson Comorbidity Index (CCI) were associated with postoperative transfusions. CONCLUSION: Our findings suggest holding DVT prophylaxis did not alter the effect of TXA on blood loss or need for transfusion.

The use of hinged elbow orthosis following surgical management of terrible triad injuries of the elbow.

PURPOSE: To determine outcomes following surgical management of terrible triad injuries in patients treated with and without a hinged elbow orthosis (HEO) in the post-operative setting. METHODS: This study was a retrospective review of 41 patients who underwent surgical treatment of terrible triad injuries including radial head fracture, coronoid fracture, and ulnohumeral dislocation between 2008 and 2023 with at least 10-week follow-up. RESULTS: Nineteen patients were treated post-operatively without HEO, and 22 patients were treated with HEO. There were no differences in range of motion (ROM) between patients treated with and without HEO in final flexion-extension arc (118.4° no HEO, 114.6° HEO, p = 0.59) or pronation-supination arc (147.8° no HEO, 141.4° HEO, p = 0.27). Five patients treated without HEO and one patient treated with HEO returned to the operating room for stiffness (26%, 5%, p = 0.08). QuickDASH scores were similar between groups (p = 0.69). CONCLUSIONS: This study found no difference in post-operative ROM, complications, or QuickDASH scores in patients treated post-operatively with or without HEO. Based on these results, we cannot determine whether the use of HEO adds additional stability to the elbow while initiating ROM exercises post-operatively.

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI.

BACKGROUND: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. METHODS: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. RESULTS: State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). CONCLUSIONS: Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).

A giant armoured skink from Australia expands lizard morphospace and the scope of the Pleistocene extinctions.

There are more species of lizards and snakes (squamates) alive today than any other order of land vertebrates, yet their fossil record has been poorly documented compared with other groups. Here, we describe a gigantic Pleistocene skink from Australia based on extensive material that includes much of the skull and postcranial skeleton, and spans ontogenetic stages from neonate to adult. Tiliqua frangens substantially expands the known ecomorphological diversity of squamates. At approximately 2.4 kg, it was more than double the mass of any living skink, with an exceptionally broad, deep skull, squat limbs and heavy, ornamented body armour. It probably filled the armoured herbivore niche that land tortoises (testudinids), absent from Australia, occupy on other continents. Tiliqua frangens and other giant Plio-Pleistocene skinks suggest that small-bodied groups that dominate vertebrate biodiversity might have lost their largest and often most morphologically extreme representatives in the Late Pleistocene, expanding the scope of these extinctions.

Risk of progression from pre-diabetes to type 2 diabetes in a large UK adult cohort.

AIMS: People with pre-diabetes are at high risk of progressing to type 2 diabetes. This progression is not well characterised by ethnicity, deprivation and age, which we describe in a large cohort of individuals with pre-diabetes. METHODS: A retrospective cohort study with The Health Improvement Network (THIN) database was conducted. Patients aged 18 years and over and diagnosed with pre-diabetes [HbA1c 42 mmol/mol (6.0%) to 48 mmol/mol (6.5%) were included]. Cox proportional hazards regression was used to calculate adjusted hazard rate ratios (aHR) for the risk of progression from pre-diabetes to type 2 diabetes for each of the exposure categories [ethnicity, deprivation (Townsend), age and body mass index (BMI)] separately. RESULTS: Of the baseline population with pre-diabetes (n = 397,853), South Asian (aHR 1.31; 95% CI 1.26-1.37) or Mixed-Race individuals (aHR 1.22; 95% CI 1.11-1.33) had an increased risk of progression to type 2 diabetes compared with those of white European ethnicity. Likewise, deprivation (aHR 1.17; 95% CI 1.14-1.20; most vs. least deprived) was associated with an increased risk of progression. Both younger (aHR 0.63; 95% CI 0.58-0.69; 18 to <30 years) and older individuals (aHR 0.85; 95% CI 0.84-0.87; ≥65 years) had a slower risk of progression from pre-diabetes to type 2 diabetes, than middle-aged (40 to <65 years) individuals. CONCLUSIONS: South Asian or Mixed-Race individuals and people with social deprivation had an increased risk of progression from pre-diabetes to type 2 diabetes. Clinicians need to recognise the differing risk across their patient populations to implement appropriate prevention strategies.

The small HDL particle hypothesis of Alzheimer's disease.

We propose the hypothesis that small high-density lipoprotein (HDL) particles reduce the risk of Alzheimer's disease (AD) by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions. Concentrations of small HDLs in cerebrospinal fluid (CSF) and plasma were measured in 180 individuals ≥60 years of age using ion mobility methodology. Small HDL concentrations in CSF were positively associated with performance in three domains of cognitive function independent of apolipoprotein E (APOE) ε4 status, age, sex, and years of education. Moreover, there was a significant correlation between levels of small HDLs in CSF and plasma. Further studies will be aimed at determining whether specific components of small HDL exchange across the blood, brain, and CSF barriers, and developing approaches to exploit small HDLs for therapeutic purposes.

Confirmation of Statin and Fibrate Use from Small-Volume Archived Plasma Samples by High-Throughput LC-MS/MS Method.

Designing studies for lipid-metabolism-related biomarker discovery is challenging because of the high prevalence of various statin and fibrate usage for lipid-lowering therapies. When the statin and fibrate use is determined based on self-reports, patient adherence to the prescribed statin dose regimen remains unknown. A potentially more accurate way to verify a patient's medication adherence is by direct analytical measurements. Current analytical methods are prohibitive because of the limited panel of drugs per test and large sample volume requirement that is not available from archived samples. A 4-min-long method was developed for the detection of seven statins and three fibrates using 10 µL of plasma analyzed via reverse-phase liquid chromatography and tandem mass spectrometry. The method was applied to the analysis of 941 archived plasma samples collected from patients before cardiac catheterization. When statin use was self-reported, statins were detected in 78.6% of the samples. In the case of self-reported atorvastatin use, the agreement with detection was 90.2%. However, when no statin use was reported, 42.4% of the samples had detectable levels of statins, with a similar range of concentrations as the samples from the self-reported statin users. The method is highly applicable in population studies designed for biomarker discovery or diet and lifestyle intervention studies, where the accuracy of statin or fibrate use may strongly affect the statistical evaluation of the biomarker data.

Drilling the cement mantle in well-fixed periprosthetic femur fractures is not associated with arthroplasty-related complications.

OBJECTIVE: To determine if screw fixation across a cement mantle is safe and effective during plate fixation of well-fixed periprosthetic femur fractures. DESIGN: Retrospective cohort study. SETTING: Academic Level I Trauma Center. PATIENTS: Twenty-eight patients with AO/OTA 32A[B1] or 32A[C] periprosthetic femur fractures treated with open reduction and internal plate and screw fixation after cemented or uncemented hip arthroplasty. INTERVENTION: Screw placement into the cement mantle during internal fixation. OUTCOME MEASUREMENTS: Primary outcome was revision arthroplasty for aseptic loosening. Secondary outcomes included radiographic evidence of aseptic loosening, infection, nonunion, implant failure, and overall reoperation rate. RESULTS: There were 28 patients who met inclusion criteria. A total of 9 patients had screws placed in the cement mantle while the remaining 19 patients had screws placed around an uncemented stem. At a mean of 3.7-year follow-up, there were no cases of revision arthroplasty or aseptic loosening in either group. There were no significant differences in rates of infection, nonunion, implant failure, or reoperation rate between patients who had screw placement into a cement mantle vs around an uncemented stem. CONCLUSION: Drilling into the cement mantle during fixation of a periprosthetic femur fracture around a well-fixed cemented hip stem appears safe and effective. When possible, surgeons can consider bicortical screws around a cemented stem, given the biomechanical advantages over unicortical screw or cerclage fixation. Larger prospective trials confirming the safety of this technique are warranted prior to routine implementation. LEVEL OF EVIDENCE: III.

Diversity and phylogenetic relationships of haemosporidian and hemogregarine parasites in Australian lizards.

Apicomplexa is a large monophyletic phylum of unicellular, parasitic organisms. Reptiles are hosts to both haemosporidian (Haemosporida) and hemogregarine (Eucoccidiorida) apicomplexan blood parasites. Within reptiles our understanding of their diversity remains limited, with a paucity of information from Australia, despite a high diversity of squamates (snakes and lizards). We provide a preliminary assessment of haemosporidian and hemogregarine diversity occurring in lizards across northern tropical Australia, building on existing data with results from a microscopy and genetic assessment. We screened total of 233 blood slides using microscopy and detected hemogregarines in 25 geckos, 2 skinks and 1 agamid, while haemosporidians were detected in 13 geckos. DNA sequencing of 28 samples of the hemogregarine 18S rRNA (∼900 bp) nuclear gene revealed five lineages of Australian lizard hemogregarines within heteroxenous adeleids. We sequenced 10 samples of Haemosporida mtDNA (cytb & coI: ∼1313 bp) and phylogenetic analysis with 30 previously published sequences revealed that the Australian Haemosporida grouped within the Haemoproteidae but were not supported as a monophyletic clade. Our results demonstrate that there is significant undocumented evolutionary diversity in Australian lizard haemosporidian and hemogregarine parasites, with preliminary evidence of significantly higher infection rates in geckos.

Personality, spatiotemporal ecological variation and resident/explorer movement syndromes in the sleepy lizard.

Individual variation in movement is profoundly important for fitness and offers key insights into the spatial and temporal dynamics of populations and communities. Nonetheless, individual variation in fine-scale movement behaviours is rarely examined even though animal tracking devices offer the long-term, high-resolution, repeatable data in natural conditions that are ideal for studying this variation. Furthermore, of the few studies that consider individual variation in movement, even fewer also consider the internal traits and environmental factors that drive movement behaviour which are necessary for contextualising individual differences in movement patterns. In this study, we GPS tracked a free-ranging population of sleepy lizards Tiliqua rugosa, each Austral spring over 5 years to examine consistent among-individual variation in movement patterns, as well as how these differences were mediated by key internal and ecological factors. We found that individuals consistently differed in a suite of weekly movement traits, and that these traits strongly covaried among-individuals, forming movement syndromes. Lizards fell on a primary movement continuum, from 'residents' that spent extended periods of time residing within smaller core areas of their home range, to 'explorers' that moved greater distances and explored vaster areas of the environment. Importantly, we also found that these consistent differences in lizard movement were related to two ecologically important animal personality traits (boldness and aggression), their sex, key features of the environment (including food availability, and a key water resource), habitat type and seasonal variation (cool/moist vs. hot/drier) in environmental conditions. Broadly, these movement specialisations likely reflect variation in life-history tactics including foraging and mating tactics that ultimately underlie key differences in space use. Such information can be used to connect phenotypic population structure to key ecological and evolutionary processes, for example social networks and disease-transmission pathways, further highlighting the value of examining individual variation in movement behaviour.

A framework to make PROMs relevant to patients: qualitative study of communication preferences of PROMs.

PURPOSE: Patient-reported outcome measures are tools for evaluating symptoms, magnitude of limitations, baseline health status, and outcomes from the patient's perspective. Healthcare professional organizations and payers increasingly recommend PROMs for clinical care, but there lacks guidance regarding effective communication of PROMs with orthopedic surgery patients. This qualitative study aimed to identify (1) patient attitudes toward the use and communication of PROMs, and (2) what patients feel are the most relevant or important aspects of PROM results to discuss with their physicians. METHODS: Participants were recruited from a multispeciality orthopedic clinic. Three PROMs: the EuroQol-5 Dimension, the Patient-Specific Functional Scale, and the Patient-Reported Outcome Measurement Information System Physical Function Computer Adaptive Test were shown and a semi-structured interview was conducted to elicit PROMs attitudes and preferences. Interviews were transcribed and inductive-deductively coded. Coded excerpts were aggregated to (1) identify major themes and (2) analyze how themes interacted. RESULT: Three themes emerged: (1) Beliefs toward the purpose of PROMs, (2) PROMs as a reflection of self, and (3) PROMs to facilitate communication and guide healthcare decisions. These themes informed a framework outlining the patient perspective on communicating PROMs during clinical care. CONCLUSION: Patient attitudes toward the use and communication of PROMs start with the incorporation of patient beliefs, which can facilitate or act as a barrier to engagement. Patients should ideally believe that PROMs are an accurate reflection of personal health state before incorporation into care. Clinicians should endeavor to communicate the purpose of a chosen PROM in line with a patient's unique needs and what they feel is most relevant to their own care. Aspects of PROMs results which may be helpful to address include providing context for what scores mean and how they are calculated, and using scores as a way to weigh risks and benefits of treatment and tracking progress over time. Future research can focus on the effect of communication strategies on patient outcomes and engagement in care.

"My Surgical Success": Feasibility and Impact of a Single-Session Digital Behavioral Pain Medicine Intervention on Pain Intensity, Pain Catastrophizing, and Time to Opioid Cessation After Orthopedic Trauma Surgery-A Randomized Trial.

BACKGROUND: Behavioral pain treatments may improve postsurgical analgesia and recovery; however, effective and scalable options are not widely available. This study tested a digital perioperative behavioral medicine intervention in orthopedic trauma surgery patients for feasibility and efficacy for reducing pain intensity, pain catastrophizing, and opioid cessation up to 3 months after surgery. METHODS: A randomized controlled clinical trial was conducted at an orthopedic trauma surgery unit at a major academic hospital to compare a digital behavioral pain management intervention ("My Surgical Success" [MSS]) to a digital general health education (HE) intervention (HE; no pain management skills). The enrolled sample included 133 patients; 84 patients were randomized (MSS, n = 37; HE, n = 47) and completed study procedures. Most patients received their assigned intervention within 3 days of surgery (85%). The sample was predominantly male (61.5%), White (61.9%), and partnered (65.5%), with at least a bachelor's degree (69.0%). Outcomes were collected at 1-3 months after intervention through self-report e-surveys and electronic medical record review; an intention-to-treat analytic framework was applied. Feasibility was dually determined by the proportion of patients engaging in their assigned treatment and an application of an 80% threshold for patient-reported acceptability. We hypothesized that MSS would result in greater reductions in pain intensity and pain catastrophizing after surgery and earlier opioid cessation compared to the digital HE control group. RESULTS: The engagement rate with assigned interventions was 63% and exceeded commonly reported rates for fully automated Internet-based e-health interventions. Feasibility was demonstrated for the MSS engagers, with >80% reporting treatment acceptability. Overall, both groups improved in the postsurgical months across all study variables. A significant interaction effect was found for treatment group over time on pain intensity, such that the MSS group evidenced greater absolute reductions in pain intensity after surgery and up to 3 months later (treatment × time fixed effects; F [215] = 5.23; P = .024). No statistically significant between-group differences were observed for time to opioid cessation or for reductions in pain catastrophizing ( F [215] = 0.20; P = .653), although the study sample notably had subclinical baseline pain catastrophizing scores (M = 14.10; 95% confidence interval, 11.70-16.49). CONCLUSIONS: Study findings revealed that a fully automated behavioral pain management skills intervention (MSS) may be useful for motivated orthopedic trauma surgery patients and reduce postsurgical pain up to 3 months. MSS was not associated with reduced time to opioid cessation compared to the HE control intervention.