Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases and sedentary controls in response to maximal exercise.

In healthy individuals, physical exercise improves cardiovascular health and muscle strength, alleviates fatigue and reduces the risk of chronic diseases. Although exercise is suggested as a lifestyle intervention to manage various chronic illnesses, it negatively affects people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), who suffer from exercise intolerance. We hypothesized that altered extracellular vesicle (EV) signalling in ME/CFS patients after an exercise challenge may contribute to their prolonged and exacerbated negative response to exertion (post-exertional malaise). EVs were isolated by size exclusion chromatography from the plasma of 18 female ME/CFS patients and 17 age- and BMI-matched female sedentary controls at three time points: before, 15 min, and 24 h after a maximal cardiopulmonary exercise test. EVs were characterized using nanoparticle tracking analysis and their protein cargo was quantified using Tandem Mass Tag-based (TMT) proteomics. The results show that exercise affects the EV proteome in ME/CFS patients differently than in healthy individuals and that changes in EV proteins after exercise are strongly correlated with symptom severity in ME/CFS. Differentially abundant proteins in ME/CFS patients versus controls were involved in many pathways and systems, including coagulation processes, muscle contraction (both smooth and skeletal muscle), cytoskeletal proteins, the immune system and brain signalling.

Sterile protection against P. vivax malaria by repeated blood stage infection in the Aotus monkey model.

The malaria parasite Plasmodium vivax remains a major global public health challenge, and no vaccine is approved for use in humans. Here, we assessed whether P. vivax strain-transcendent immunity can be achieved by repeated infection in Aotus monkeys. Sterile immunity was achieved after two homologous infections, whereas subsequent heterologous challenge provided only partial protection. IgG levels based on P. vivax lysate ELISA and protein microarray increased with repeated infections and correlated with the level of homologous protection. Parasite transcriptional profiles provided no evidence of major antigenic switching upon homologous or heterologous challenge. However, we observed significant sequence diversity and transcriptional differences in the P. vivax core gene repertoire between the two strains used in the study, suggesting that partial protection upon heterologous challenge is due to molecular differences between strains rather than immune evasion by antigenic switching. Our study demonstrates that sterile immunity against P. vivax can be achieved by repeated homologous blood stage infection in Aotus monkeys, thus providing a benchmark to test the efficacy of candidate blood stage P. vivax malaria vaccines.

Dysregulation of extracellular vesicle protein cargo in female ME/CFS cases and sedentary controls in response to maximal exercise.

In healthy individuals, physical exercise improves cardiovascular health and muscle strength, alleviates fatigue, and reduces risk of chronic diseases. Although exercise is suggested as a lifestyle intervention to manage various chronic illnesses, it negatively affects people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), who suffer from exercise intolerance. We hypothesized that altered extracellular vesicle (EV) signaling in ME/CFS patients after an exercise challenge may contribute to their prolonged and exacerbated negative response to exertion (post-exertional malaise). EVs were isolated by size exclusion chromatography from the plasma of 18 female ME/CFS patients and 17 age- and BMI-matched female sedentary controls at three time points: before, 15 minutes, and 24 hours after a maximal cardiopulmonary exercise test. EVs were characterized using nanoparticle tracking analysis and their protein cargo was quantified using Tandem Mass Tag-based (TMT) proteomics. The results show that exercise affects the EV proteome in ME/CFS patients differently than in healthy individuals and that changes in EV proteins after exercise are strongly correlated with symptom severity in ME/CFS. Differentially abundant proteins in ME/CFS patients vs. controls were involved in many pathways and systems, including coagulation processes, muscle contraction (both smooth and skeletal muscle), cytoskeletal proteins, the immune system, and brain signaling.

Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with unknown etiology or effective treatments. Post-exertional malaise (PEM) is a key symptom that distinguishes ME/CFS patients. Investigating changes in the urine metabolome between ME/CFS patients and healthy subjects following exertion may help us understand PEM. The aim of this pilot study was to comprehensively characterize the urine metabolomes of eight female healthy sedentary control subjects and ten female ME/CFS patients in response to a maximal cardiopulmonary exercise test (CPET). Each subject provided urine samples at baseline and 24 h post-exercise. A total of 1403 metabolites were detected via LC-MS/MS by Metabolon® including amino acids, carbohydrates, lipids, nucleotides, cofactors and vitamins, xenobiotics, and unknown compounds. Using a linear mixed effects model, pathway enrichment analysis, topology analysis, and correlations between urine and plasma metabolite levels, significant differences were discovered between controls and ME/CFS patients in many lipid (steroids, acyl carnitines and acyl glycines) and amino acid subpathways (cysteine, methionine, SAM, and taurine; leucine, isoleucine, and valine; polyamine; tryptophan; and urea cycle, arginine and proline). Our most unanticipated discovery is the lack of changes in the urine metabolome of ME/CFS patients during recovery while significant changes are induced in controls after CPET, potentially demonstrating the lack of adaptation to a severe stress in ME/CFS patients.

Survey of Anti-Pathogen Antibody Levels in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Infectious pathogens are implicated in the etiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) because of the occurrence of outbreaks of the disease. While a number of different infectious agents have been associated with the onset of ME/CFS, the identity of a specific organism has been difficult to determine in individual cases. The aim of our study is to survey ME/CFS subjects for evidence of an infectious trigger and/or evidence of immune dysregulation via serological testing of plasma samples for antibodies to 122 different pathogen antigens. Immune profiles were compared to age-, sex-, and BMI-matched controls to provide a basis for comparison. Antibody levels to individual antigens surveyed in this study do not implicate any one of the pathogens in ME/CFS, nor do they rule out common pathogens that frequently infect the US population. However, our results revealed sex-based differences in steady-state humoral immunity, both within the ME/CFS cohort and when compared to trends seen in the healthy control cohort.

Optimization of Meniscus Cell Transduction Using Lentivirus and Adeno-Associated Virus for Gene Editing and Tissue Engineering Applications.

OBJECTIVES: The utilization of viral vectors to deliver genes of interest directly to meniscus cells and promote long-term modulation of gene expression may prove useful to enhance meniscus repair and regeneration. The objective of this study was to optimize and compare the potential of lentivirus (LV) and adeno-associated virus (AAV) to deliver transgenes to meniscus cells in both intact meniscus tissue and isolated primary cells in monolayer. DESIGN: Porcine meniscus tissue explants and primary meniscus cells in monolayer were transduced with LV or self-complementary AAV2 (scAAV2) encoding green fluorescent protein (GFP). Following transduction, explants were enzymatically digested to isolate meniscus cells, and monolayer cells were trypsinized. Isolated cells were analyzed by flow cytometry to determine percent transduction. RESULTS: LV and scAAV2 showed a high transduction efficiency in monolayer meniscus cells. scAAV2 was most effective at transducing cells within intact meniscus tissue but the efficiency was less than 20%. Outer zone meniscus cells were more readily transduced by both LV and scAAV2 than the inner zone cells. Higher virus titers and higher cell density resulted in improved transduction efficiency. Polybrene was necessary for the highest transduction efficiency with LV, but it reduced scAAV2 transduction. CONCLUSIONS: Both LV and scAAV2 efficiently transduce primary meniscus cells but only scAAV2 can modestly transduce cells embedded in meniscus tissue. This work lays the foundation for viral gene transfer to be utilized to deliver bioactive transgenes or gene editing machinery, which can induce long-term and tunable expression of therapeutic proteins from tissue-engineered constructs for meniscus repair and regeneration.

Meniscus-Derived Matrix Scaffolds Promote the Integrative Repair of Meniscal Defects.

Meniscal tears have a poor healing capacity, and damage to the meniscus is associated with significant pain, disability, and progressive degenerative changes in the knee joint that lead to osteoarthritis. Therefore, strategies to promote meniscus repair and improve meniscus function are needed. The objective of this study was to generate porcine meniscus-derived matrix (MDM) scaffolds and test their effectiveness in promoting meniscus repair via migration of endogenous meniscus cells from the surrounding meniscus or exogenously seeded human bone marrow-derived mesenchymal stem cells (MSCs). Both endogenous meniscal cells and MSCs infiltrated the MDM scaffolds. In the absence of exogenous cells, the 8% MDM scaffolds promoted the integrative repair of an in vitro meniscal defect. Dehydrothermal crosslinking and concentration of the MDM influenced the biochemical content and shear strength of repair, demonstrating that the MDM can be tailored to promote tissue repair. These findings indicate that native meniscus cells can enhance meniscus healing if a scaffold is provided that promotes cellular infiltration and tissue growth. The high affinity of cells for the MDM and the ability to remodel the scaffold reveals the potential of MDM to integrate with native meniscal tissue to promote long-term repair without necessarily requiring exogenous cells.

Effective Implementation of Culturally Appropriate Tools in Addressing Overweight and Obesity in an Urban Underserved Early Childhood Population in Pediatric Primary Care.

Overweight and obese children are at an increased risk of remaining obese. The American Academy of Pediatrics recommends addressing healthy habits at well-child checks, but this poses challenges, especially in low-income populations. A clinical innovation project was designed to adapt recommendations in a busy urban clinic and consisted of motivational interviewing, culturally tailored tools, and standardizing documentation. A quasi-experimental design examined innovation outcomes. Of 137 overweight and obese children aged 24 to 66 months, providers' documentation of weight during well-child check visits improved post-innovation ( P < .01), as did development of healthy habits goals ( P < .001). Families were more likely to return for visits post-innovation ( P = .01). A logistic regression analysis showed that adding body mass index to the problem list and establishing a specific follow-up timeframe most predicted follow-up visits to assess progress ( P < .001). Comprehensive innovations consisting of motivational interviewing, implementation of culturally tailored tools, and standardized documentation can enhance engagement in an urban clinic setting.

Regulation of decellularized tissue remodeling via scaffold-mediated lentiviral delivery in anatomically-shaped osteochondral constructs.

Cartilage-derived matrix (CDM) has emerged as a promising scaffold material for tissue engineering of cartilage and bone due to its native chondroinductive capacity and its ability to support endochondral ossification. Because it consists of native tissue, CDM can undergo cellular remodeling, which can promote integration with host tissue and enables it to be degraded and replaced by neotissue over time. However, enzymatic degradation of decellularized tissues can occur unpredictably and may not allow sufficient time for mechanically competent tissue to form, especially in the harsh inflammatory environment of a diseased joint. The goal of the current study was to engineer cartilage and bone constructs with the ability to inhibit aberrant inflammatory processes caused by the cytokine interleukin-1 (IL-1), through scaffold-mediated delivery of lentiviral particles containing a doxycycline-inducible IL-1 receptor antagonist (IL-1Ra) transgene on anatomically-shaped CDM constructs. Additionally, scaffold-mediated lentiviral gene delivery was used to facilitate spatial organization of simultaneous chondrogenic and osteogenic differentiation via site-specific transduction of a single mesenchymal stem cell (MSC) population to overexpress either chondrogenic, transforming growth factor-beta 3 (TGF-ß3), or osteogenic, bone morphogenetic protein-2 (BMP-2), transgenes. Controlled induction of IL-1Ra expression protected CDM hemispheres from inflammation-mediated degradation, and supported robust bone and cartilage tissue formation even in the presence of IL-1. In the absence of inflammatory stimuli, controlled cellular remodeling was exploited as a mechanism for fusing concentric CDM hemispheres overexpressing BMP-2 and TGF-ß3 into a single bi-layered osteochondral construct. Our findings demonstrate that site-specific delivery of inducible and tunable transgenes confers spatial and temporal control over both CDM scaffold remodeling and neotissue composition. Furthermore, these constructs provide a microphysiological in vitro joint organoid model with site-specific, tunable, and inducible protein delivery systems for examining the spatiotemporal response to pro-anabolic and/or inflammatory signaling across the osteochondral interface.

Sediment exchange to mitigate pollutant exposure in urban soil.

Urban soil is an ongoing source for lead (Pb) and other pollutant exposure. Sources of clean soil that are locally-available, abundant and inexpensive are needed to place a protective cover layer over degraded urban soil to eliminate direct and indirect pollutant exposures. This study evaluates a novel sediment exchange program recently established in New York City (NYC Clean Soil Bank, CSB) and found that direct exchange of surplus sediment extracted from urban construction projects satisfies these criteria. The CSB has high total yield with 4.2 × 105 t of sediment exchanged in five years. Average annual yield (8.5 × 104 t yr-1) would be sufficient to place a 15-cm (6-in.) sediment cover layer over 3.2 × 105 m2 (80 acres) of impacted urban soil or 1380 community gardens. In a case study of sediment exchange to mitigate community garden soil contamination, Pb content in sediment ranged from 2 to 5 mg kg-1. This sediment would reduce surface Pb concentrations more than 98% if it was used to encapsulate soil with Pb content exceeding USEPA residential soil standards (400 mg kg-1). The maximum observed sediment Pb content is a factor of 42 and 71 lower than median surface soil and garden soil in NYC, respectively. All costs (transportation, chemical testing, etc.) in the CSB are paid by the donor indicating that urban sediment exchange could be an ultra-low-cost source for urban soil mitigation. Urban-scale sediment exchange has advantages over existing national- or provincial-scale sediment exchanges because it can retain and upcycle local sediment resources to attain their highest and best use (e.g. lowering pollutant exposure), achieve circular urban materials metabolism, improve livability and maximize urban sustainability.

Identifying Institutional Causes of Delay to Radical Cystectomy among Patients with High Risk Bladder Cancer Treated at a Tertiary Referral Center Using Process Map Analysis.

INTRODUCTION: Treatment delay among patients with muscle invasive bladder cancer is associated with reduced survival. With limited existing literature examining institutional causes of treatment delay, we identified such causes of delay to radical cystectomy among patients with high risk bladder cancer. METHODS: We conducted a retrospective review of 176 patients with bladder cancer who underwent radical cystectomy at our tertiary referral center in 2013 to 2014. Process mapping was used to define each step in the path to cystectomy and the time interval between each step was quantified. Patients experiencing treatment delay (more than 90 days to cystectomy or chemotherapy initiation) were identified and the causes of delay examined. RESULTS: Median time from diagnosis to referral was 17 days (IQR 9-36). Following referral the urology and medical oncology evaluations occurred at a median of 5 (IQR 2-9) and 6 days (IQR 1-9), respectively. Median time from urological evaluation to transurethral resection was 14 days (IQR 8-20) and from oncology evaluation to chemotherapy initiation was 9 days (IQR 7-14). Median time to cystectomy for patients proceeding directly from urological evaluation was 28 days (IQR 20-46). Longer intervals were noted from transurethral bladder tumor resection or chemotherapy completion to cystectomy (41 and 44 days, respectively). Overall 24 patients (13.6%) experienced treatment delay. Delays in referral, awaiting preoperative medical clearance, staging studies and surgical scheduling prolonged the time to treatment. CONCLUSIONS: Several institutional factors contribute to treatment delays among patients with bladder cancer. Process mapping allowed characterization of complex paths to cystectomy and identification of causes of treatment delay.

Multidisciplinary Clinics for Colorectal Cancer Care Reduces Treatment Time.

INTRODUCTION: Management of locally advanced and metastatic colorectal cancer (CRC) requires the expertise of multiple specialists. Multidisciplinary clinics (MDCs) are a working model designed to facilitate delivery of coordinated care. The present study evaluated the effects of MDC on the time to treatment (TTT). PATIENTS AND METHODS: Patients with CRC or locally advanced anal cancer who were evaluated at a single-institution MDC from January 2014 to October 2015 were identified from an institutional registry. The clinical characteristics and timelines for various aspects of treatment were retrospectively reviewed and recorded. A control population of patients not evaluated at the MDC was matched 1:2 by disease and the number of treating specialties. The primary endpoints were the TTT from diagnosis and the TTT from the first consultation. RESULTS: A total of 105 patients were included: 35 were evaluated at the MDC and 70 were controls. The MDC patients experienced a 7.8-day shorter TTT from the first consultation (21.5 vs. 29.3 days; P = .01). The difference was greater for patients visiting 3 departments (21.3 vs. 30.6 days; P < .001). Patients requiring neoadjuvant chemoradiation accounted for most of the decreased interval compared with those requiring surgery alone as their first treatment. The proportion of patients initiating treatment within 3 weeks from the first consultation was greater for those seen in the MDC (57.1% vs. 30% for controls; P = .01). CONCLUSION: Implementation of a multidisciplinary CRC clinic yielded decreased intervals from the first consultation to treatment in our institution. Focusing efforts to increase MDC usage will improve treatment efficiency and improve patient access.

Healthcare Costs Reduced After Incorporating the Results of the American College of Surgeons Oncology Group Z0011 Trial into Clinical Practice.

The purpose of our study was to quantitate the changes in axillary lymph node dissection (ALND), frozen section (FS), and the impact on costs after the publication of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial. We compared axillary nodal management and cost data in breast cancer patients who met Z0011 criteria and were treated with lumpectomy and sentinel lymph nodes (SLN) biopsy from 2007 to July 2013. Of 800 patients, 67 (13.5%) and 34 (12.5%) patients in the pre- and post-Z0011 era had 1-2 positive SLN. ALND decreased from 78% to 21% (p < 0.001) after publication of Z0011. The mean overall cost of SLN biopsy was $41,059 per patient, while SLN biopsy with completion ALND was $50,999 (p < 0.001). Intraoperative FS use decreased from 95% to 66% (p = 0.015). Omitting the FS decreased mean costs from $4,319 to $2,036. The application of Z0011 resulted in an overall mean cost savings of $571,653 from 2011 to July 2013. ACOSOG Z0011 significantly impacted axillary management resulting in a 20% reduction in the mean overall cost per patient by omitting ALND. In these patients, intraoperative FS analysis had poor sensitivity (56%) and doubled the cost of pathologic examination. Fewer ALND and intraoperative FS were performed after the publication of ACOSOG Z0011. Eliminating FS and ALND in patients who met Z0011 criteria, results in significant cost savings.

Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing.

Biological resurfacing of entire articular surfaces represents an important but challenging strategy for treatment of cartilage degeneration that occurs in osteoarthritis. Not only does this approach require anatomically sized and functional engineered cartilage, but the inflammatory environment within an arthritic joint may also inhibit chondrogenesis and induce degradation of native and engineered cartilage. The goal of this study was to use adult stem cells to engineer anatomically shaped, functional cartilage constructs capable of tunable and inducible expression of antiinflammatory molecules, specifically IL-1 receptor antagonist (IL-1Ra). Large (22-mm-diameter) hemispherical scaffolds were fabricated from 3D woven poly(ε-caprolactone) (PCL) fibers into two different configurations and seeded with human adipose-derived stem cells (ASCs). Doxycycline (dox)-inducible lentiviral vectors containing eGFP or IL-1Ra transgenes were immobilized to the PCL to transduce ASCs upon seeding, and constructs were cultured in chondrogenic conditions for 28 d. Constructs showed biomimetic cartilage properties and uniform tissue growth while maintaining their anatomic shape throughout culture. IL-1Ra-expressing constructs produced nearly 1 µg/mL of IL-1Ra upon controlled induction with dox. Treatment with IL-1 significantly increased matrix metalloprotease activity in the conditioned media of eGFP-expressing constructs but not in IL-1Ra-expressing constructs. Our findings show that advanced textile manufacturing combined with scaffold-mediated gene delivery can be used to tissue engineer large anatomically shaped cartilage constructs that possess controlled delivery of anticytokine therapy. Importantly, these cartilage constructs have the potential to provide mechanical functionality immediately upon implantation, as they will need to replace a majority, if not the entire joint surface to restore function.

Bone metastases and skeletal-related events from neuroendocrine tumors.

Neuroendocrine tumors (NETs) metastasize to bone; however, a multi-institution evaluation of the natural history and complications of bone metastases across multiple NET subtypes has not, to our knowledge, previously been conducted. At two tertiary academic centers, we identified patients with bone metastases from databases of patients with a diagnosis of NET between 2004 and 2008. Detection of bone metastases, occurrence of skeletal-related events (SREs), and interventions were analyzed using summary statistics and categorical methods. Time-to-event data were assessed using Kaplan-Meier estimates and log-rank tests. Between 2004 and 2008, 82 out of 691 NET patients (12%) were reported to have bone metastases. Of the 82 patients with bone metastases, 55% were men and their median age was 49. Bone metastases occurred in 25% of pheochromocytomas and paragangliomas, 20% of high-grade neuroendocrine carcinomas, 9% of carcinoid tumors, and 8% of pancreatic NETs. At time of detection of bone metastases, 60% reported symptoms, including pain; 10% developed cord compression, 9% suffered a pathological fracture, and 4% developed hypercalcemia. Occurrence of SREs did not differ significantly with regard to tumor histology. Of patients with bone metastases, 67 (82%) received at least one form of bone-directed treatment, 50% received radiation, 45% received a bisphosphonate, 18% underwent surgery, 11% received (131)I-MIBG, 5% received denosumab, and 46% were treated with more than one treatment modality. Bone metastases occur in a substantial number of patients diagnosed with NETs. Patients are often symptomatic and many develop SREs. Given the recent therapeutic advances and increasing life expectancy of patients with NETs, development of guidelines for surveillance and clinical care of bone metastases from NETs is needed.

Tissue-engineered cartilage with inducible and tunable immunomodulatory properties.

The pathogenesis of osteoarthritis is mediated in part by inflammatory cytokines including interleukin-1 (IL-1), which promote degradation of articular cartilage and prevent human mesenchymal stem cell (MSC) chondrogenesis. In this study, we combined gene therapy and functional tissue engineering to develop engineered cartilage with immunomodulatory properties that allow chondrogenesis in the presence of pathologic levels of IL-1 by inducing overexpression of IL-1 receptor antagonist (IL-1Ra) in MSCs via scaffold-mediated lentiviral gene delivery. A doxycycline-inducible vector was used to transduce MSCs in monolayer or within 3D woven PCL scaffolds to enable tunable IL-1Ra production. In the presence of IL-1, IL-1Ra-expressing engineered cartilage produced cartilage-specific extracellular matrix, while resisting IL-1-induced upregulation of matrix metalloproteinases and maintaining mechanical properties similar to native articular cartilage. The ability of functional engineered cartilage to deliver tunable anti-inflammatory cytokines to the joint may enhance the long-term success of therapies for cartilage injuries or osteoarthritis.

RNA-guided gene activation by CRISPR-Cas9-based transcription factors.

Technologies for engineering synthetic transcription factors have enabled many advances in medical and scientific research. In contrast to existing methods based on engineering of DNA-binding proteins, we created a Cas9-based transactivator that is targeted to DNA sequences by guide RNA molecules. Coexpression of this transactivator and combinations of guide RNAs in human cells induced specific expression of endogenous target genes, demonstrating a simple and versatile approach for RNA-guided gene activation.

Synergistic and tunable human gene activation by combinations of synthetic transcription factors.

Mammalian genes are regulated by the cooperative and synergistic actions of many transcription factors. In this study we recapitulate this complex regulation in human cells by targeting endogenous gene promoters, including regions of closed chromatin upstream of silenced genes, with combinations of engineered transcription activator-like effectors (TALEs). These combinations of TALE transcription factors induced substantial gene activation and allowed tuning of gene expression levels that will broadly enable synthetic biology, gene therapy and biotechnology.

Shared decision making and other variables as correlates of satisfaction with health care decisions in a United States national survey.

OBJECTIVE: The purpose of this study was to examine the relationship between shared decision-making (SDM) and satisfaction with decision (SWD) within a larger survey of patient decision-making in health care consultations. METHODS: A randomly selected age-proportionate national sample of adults (aged 21-70 years) stratified on race, ethnicity, and gender (N=488) was recruited from a health research volunteer registry and completed an online survey with reference to a recent health consultation. Measures included the shared decision making-9 questionnaire (SDM-Q-9), Satisfaction With Decision (SWD) scale, sociodemographic, health, and other standardized decision-making measures. Forward selection weighted multiple regression analysis was used to model correlates of SWD. RESULTS: After controlling for sociodemographic variables, SDM-Q-9 total score was associated with SWD, adjusted R(2)=.368, p<.001. Three of nine SDM-Q-9 items accounted for significant proportions of variance in SWD. CONCLUSION: SDM was positively associated with SWD and was strongest for three areas of SDM: patients being helped in a health care consultation with understanding information, with treatment preference elicitation, and with weighing options thoroughly. PRACTICE IMPLICATIONS: By identifying variables such as SDM that are associated with SWD, health care interventions can better target modifiable factors to enhance satisfaction and other outcomes.