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Steven Z George,1,2 Maggie E Horn2 1Duke Clinical Research Institute, Duke University, Durham, NC, USA; 2Departments of Orthopaedic Surgery and Population Health Science, Duke University, Durham, NC, USACorrespondence: Steven Z George, Duke University, 300 Morgan Street, Office 480, Durham, NC, 27707, USA, Tel +1 919-668-0825, Email steven.george@duke.eduAims and Objective: The purpose of this pilot study was to explore whether AIH produces changes in pain sensitivity or in reports of self-reported pain intensity for individuals with low back pain.Methods: In a quasi-experimental, cross-over design we compared participants (n = 9) exposed to normal room air and hypoxia using a commercially available gas blender. The treatment period consisted of 5 consecutive days of randomly assigned to AIH or room air. For the participants initially randomized to AIH there was cross-over to receive 5 more consecutive days of room air. Therefore, this design allowed for between group and within subject assessment of AIH effects. Pain sensitivity was assessed with quantitative sensory testing (QST) for posterior superior iliac spine pressure threshold, plantar thermal threshold, and peak pain ratings. Self-reported pain intensity for low back pain was assessed via the Brief Pain Inventory.Results: There were no between group differences for AIH and room air in pain sensitivity or self-reported pain intensity. In the within subject analyses larger effect sizes favoring AIH were detected for plantar measures of pain sensitivity but not for self-reported pain intensity.Conclusion: This study, while presenting null findings, describes an initial step in determining whether AIH can be used to increase pain relief. Based on this pilot study we offer guidance for future research including study design, AIH dosage, participant selection, and using AIH in combination with non-pharmacologic treatments.Keywords: hypoxia, hypoalgesia, low back pain, pain sensitivity

Maggie E Horn,1 Steven Z George,2 Cai Li,3 Sheng Luo,4 Trevor A Lentz2 1Duke University, Department of Orthopaedic Surgery, Durham, NC, 27701, USA; 2Duke University, Department of Orthopaedic Surgery and Duke Clinical Research Institute, Durham, NC, 27701, USA; 3Yale University, Department of Biostatistics, New Haven, CT, USA; 4Duke University, Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USACorrespondence: Maggie E HornDuke University, Department of Orthopaedic Surgery, Box 100402, Durham, NC, 27701, USATel +1 9196841365Email maggie.horn@duke.eduRationale: Risk assessment tools can improve clinical decision-making for individuals with musculoskeletal pain, but do not currently exist for predicting reduction of pain intensity as an outcome from physical therapy.Aims and Objective: The objective of this study was to develop a tool that predicts failure to achieve a 50% pain intensity reduction by 1) determining the appropriate statistical model to inform the tool and 2) select the model that considers the tradeoff between clinical feasibility and statistical accuracy.Methods: This was a retrospective, secondary data analysis of the Optimal Screening for Prediction of Referral and Outcome (OSPRO) cohort. Two hundred and seventy-nine individuals seeking physical therapy for neck, shoulder, back, or knee pain who completed 12-month follow-up were included. Two modeling approaches were taken: a longitudinal model included demographics, presence of previous episodes of pain, and regions of pain in addition to baseline and change in OSPRO Yellow Flag scores to 12 months; two comparison models included the same predictors but assessed only baseline and early change (4 weeks) scores. The primary outcome was failure to achieve a 50% reduction in pain intensity score at 12 months. We compared the area under the curve (AUC) to assess the performance of each candidate model and to determine which to inform the Personalized Pain Prediction (P3) risk assessment tool.Results: The baseline only and early change models demonstrated lower accuracy (AUC=0.68 and 0.71, respectively) than the longitudinal model (0.79) but were within an acceptable predictive range. Therefore, both baseline and early change models were used to inform the P3 risk assessment tool.Conclusion: The P3 tool provides physical therapists with a data-driven approach to identify patients who may be at risk for not achieving improvements in pain intensity following physical therapy.Keywords: persistent pain, risk assessment tool, musculoskeletal pain, risk prediction, psychological factors

Charles W Gay,1 Meryl J Alappattu,1 Rogelio A Coronado,1 Maggie E Horn,1 Mark D Bishop21Rehabilitation Science Doctoral Program, College of Public Health and Health Professions, 2Department of Physical Therapy, University of Florida, Gainesville, FLBackground: Muscle-biased therapies (MBT) are commonly used to treat pain, yet several reviews suggest evidence for the clinical effectiveness of these therapies is lacking. Inadequate treatment parameters have been suggested to account for inconsistent effects across studies. Pain sensitivity may serve as an intermediate physiologic endpoint helping to establish optimal MBT treatment parameters. The purpose of this review was to summarize the current literature investigating the short-term effect of a single dose of MBT on pain sensitivity in both healthy and clinical populations, with particular attention to specific MBT parameters of intensity and duration.Methods: A systematic search for articles meeting our prespecified criteria was conducted using Cumulative Index to Nursing and Allied Health Literature (CINAHL) and MEDLINE from the inception of each database until July 2012, in accordance with guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analysis. Relevant characteristics from studies included type, intensity, and duration of MBT and whether short-term changes in pain sensitivity and clinical pain were noted with MBT application. Study results were pooled using a random-effects model to estimate the overall effect size of a single dose of MBT on pain sensitivity as well as the effect of MBT, dependent on comparison group and population type.Results: Reports from 24 randomized controlled trials (23 articles) were included, representing 36 MBT treatment arms and 29 comparative groups, where 10 groups received active agents, 11 received sham/inert treatments, and eight received no treatment. MBT demonstrated a favorable and consistent ability to modulate pain sensitivity. Short-term modulation of pain sensitivity was associated with short-term beneficial effects on clinical pain. Intensity of MBT, but not duration, was linked with change in pain sensitivity. A meta-analysis was conducted on 17 studies that assessed the effect of MBT on pressure pain thresholds. The results suggest that MBT had a favorable effect on pressure pain thresholds when compared with no-treatment and sham/inert groups, and effects comparable with those of other active treatments.Conclusion: The evidence supports the use of pain sensitivity measures by future research to help elucidate optimal therapeutic parameters for MBT as an intermediate physiologic marker.Keywords: muscle-biased therapy, pain sensitivity, pressure pain threshold

Background: Increasing deformity of the lower extremities, as measured by the hip-knee-ankle angle (HKAA), is associated with poor patient outcomes after total hip and knee arthroplasty (THA, TKA). Automated calculation of HKAA is imperative to reduce the burden on orthopaedic surgeons. We proposed a detection-based deep learning (DL) model to calculate HKAA in THA and TKA patients and assessed the agreement between DL-derived HKAAs and manual measurement., Methods: We retrospectively identified 1,379 long-leg radiographs (LLRs) from patients scheduled for THA or TKA within an academic medical center. There were 1,221 LLRs used to develop the model (randomly split into 70% training, 20% validation, and 10% held-out test sets); 158 LLRs were considered "difficult," as the femoral head was difficult to distinguish from surrounding tissue. There were 2 raters who annotated the HKAA of both lower extremities, and inter-rater reliability was calculated to compare the DL-derived HKAAs with manual measurement within the test set., Results: The DL model achieved a mean average precision of 0.985 on the test set. The average HKAA of the operative leg was 173.05 ± 4.54°; the nonoperative leg was 175.55 ± 3.56°. The inter-rater reliability between manual and DL-derived HKAA measurements on the operative leg and nonoperative leg indicated excellent reliability (intraclass correlation (2,k) = 0.987 [0.96, 0.99], intraclass correlation (2, k) = 0.987 [0.98, 0.99, respectively]). The standard error of measurement for the DL-derived HKAA for the operative and nonoperative legs was 0.515° and 0.403°, respectively., Conclusions: A detection-based DL algorithm can calculate the HKAA in LLRs and is comparable to that calculated by manual measurement. The algorithm can detect the bilateral femoral head, knee, and ankle joints with high precision, even in patients where the femoral head is difficult to visualize., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Translation of knee osteoarthritis (KOA) clinical practice guidelines (CPGs) to practice remains suboptimal. The primary purpose of this systematic review was to describe the use of implementation strategies to promote KOA CPG-recommended care., Methods: Medline (via PubMed), Embase, CINAHL, and Web of Science were searched from inception to February 23, 2023, and the search was subsequently updated and expanded on January 16, 2024. Implementation strategies were mapped per the Expert Recommendations for Implementing Change taxonomy. Risk of bias (RoB) was assessed using the Cochrane Effective Practice and Organisation of Care criteria. The review was registered prospectively (PROSPERO identifier: CRD42023402383)., Results: Nineteen studies were included in the final review. All (100% [n = 4]) studies that included the domains of "provide interactive assistance," "train and educate stakeholders" (89% [n = 16]), "engage consumers" (87% [n = 13]), and "support clinicians" (79% [n = 11]) showed a change to provider adherence. Studies that showed a change to disability included the domains of "train and educate stakeholders," "engage consumers," and "adapt and tailor to context." Studies that used the domains "train and educate stakeholders," "engage consumers," and "support clinicians" showed a change in pain and quality of life. Most studies had a low to moderate RoB., Conclusion: Implementation strategies have the potential to impact clinician uptake of CPGs and patient-reported outcomes. The implementation context, using an active learning strategy with a patient partner, restructuring funding models, and integrating taxonomies to tailor multifaceted strategies should be prioritized. Further experimental research is recommended to determine which implementation strategies are most effective., (© 2024 American College of Rheumatology.)

Background: The decision to treat shoulder osteoarthritis (OA) definitively with shoulder arthroplasty (SA) is multifactorial, considering objective findings, subjective information, and patient goals. The first goal of this study was to determine if Patient Reported Outcome Measurement Information System (PROMIS) measures correlated with patients with shoulder OA who underwent SA within 1 year. The second goal of this study was to determine if score cut-offs in PROMIS domains could further discriminate which shoulder OA patients underwent SA within 1 year., Methods: This retrospective case-control study examined patients with a diagnosis of shoulder OA who consulted an orthopedic provider from November 1, 2020 to May 23, 2022, and recorded PROMIS measures in the domains of Physical Function, Depression, and/or Pain Interference. A surgical group was defined as patients who underwent SA within 1 year of the most recent PROMIS measures and the nonsurgical patients were defined as the control group. Mean PROMIS scores were compared between the surgical and control groups. Separate logistic regression models controlling for age, race, ethnicity, and comorbidity count were performed for each PROMIS domain as a 1) continuous variable, and then as 2) binary variable defined by PROMIS score cut-off points to determine which scores correlated with undergoing SA to further characterize the potential clinical utility of PROMIS score cut-offs in relating to undergoing SA., Results: The surgical group of 478 patients was older (68.2 vs. 63.8 years), more often of White race (82.6% vs. 70.9%), and less often of Hispanic Ethnicity (1.5% vs. 2.9%) than the control group of 3343 patients. Using optimal cut-offs in PROMIS scores, Pain Interference ≥63 (odds ratio [OR] = 2.97 (2.41-3.64), P < .001), Physical Function ≤39 (OR = 1.81 (95% confidence interval, 1.48-2.22), P < .001), and depression ≥49 (OR = 1.82 (95% confidence interval, 1.50-2.22), P < .001) were all found to correlate with undergoing SA within 1 year in multivariable logistic regressions., Conclusion: The results of this study demonstrate that cut-off scores for PROMIS measures differentiated patients undergoing SA within 1 year. These cut-off scores may have clinical utility in aiding in decision-making regarding surgical candidates for SA. Further research is needed to validate these cut-off scores and determine how they relate to patient outcomes after SA., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Weight loss is commonly recommended before total knee arthroplasty (TKA) despite inconsistent evidence for better outcomes. This study sought to examine the impacts of preoperative weight loss on patient-reported and adverse outcomes among TKA patients supervised by a medical weight management clinic., Methods: This study retrospectively analyzed patients who underwent medical weight management supervision within 18 months before TKA comparing patients who did and did not have clinically relevant weight loss. Preoperative body mass indices, demographics, Patient-Reported Outcomes Measurement Information System physical function and pain interference scores, pain intensity scores, and adverse outcomes were extracted. Multivariable linear regressions were performed to determine if preoperative weight loss correlated with patient-reported outcomes after controlling for confounders., Results: There were 90 patients, 75.6% women, who had a mean age of 65 years (range, 42-82) and were analyzed. There were 51 (56.7%) patients who underwent clinically relevant weight loss with a mean weight loss of 10.4% and experienced no difference in adverse outcomes. Preoperative weight loss predicted significantly improved 3-month postoperative physical function (β = 15.2 [13.0-17.3], P < .001), but not pain interference (β = -18.9 [-57.1-19.4], P = .215) or pain intensity (β = -1.8 [-4.9-1.2], P = .222) scores., Conclusion: We found that medically supervised preoperative weight loss predicted improvement in physical function 3 months after TKA. This weight loss caused no major adverse effects. Further research is needed to understand the causal relationships between preoperative weight loss, medical supervision, and outcome after TKA and to elucidate potential longer-term benefits in a larger sample., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: High body mass index (BMI) is associated with adverse outcomes after total knee arthroplasty (TKA). Thus, many patients are advised to lose weight before TKA. This study examined how weight loss before TKA is associated with adverse outcomes depending on patients' initial BMI., Methods: This was a retrospective study of 2,110 primary TKAs at a single academic center. Data on preoperative BMIs, demographics, comorbidities, and incidences of revision or prosthetic joint infection (PJI) were obtained. Multivariable logistic regressions segmented by patients' initial (1-year preoperative) BMI classifications were performed to determine if a > 5% BMI decrease from 1 year or 6 months preoperatively predicted PJI and revision controlling for patient age, race, sex, and Elixhauser comorbidity index., Results: Preoperative weight loss did not predict adverse outcomes for patients who had Obesity Class II or III. 6-month weight loss had greater odds of adverse outcomes than 1-year weight loss and most significantly predicted the occurrence of 1-year PJI (adjusted odds ratio: 6.55, P < .001) for patients who had Obesity Class 1 or lower., Conclusion: This study does not show a statistically significant effect to patients who had Obesity Class II and III losing weight preoperatively with respect to PJI or revision. For patients who have Obesity Class I or lower pursuing TKA, future research should consider potential risks associated with weight loss. Further study is needed to determine if weight loss can be implemented as a safe and effective risk reduction strategy for specific BMI classes of TKA patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To determine associations between post-emergency department (ED) management pathways and downstream opioid prescriptions in patients seeking care for incident neck and/or back pain., Patients and Methods: We identified patients seeking first-time ED care for neck and/or back pain from January 1, 2013, through November 6, 2017. We reported demographic characteristics and opioid prescriptions across management pathways using descriptive statistics and assessed the relative risk of any opioid prescription 12 months post-ED visit among 5 different post-ED management pathways using Poisson regression adjusted for patient demographic characteristics., Results: Within 12 months after the index ED visit, 58.0% (n=10,949) were prescribed an opioid, with most patients prescribed an opioid within the first week (average daily morphine milligram equivalents of 6.8 mg (SD 9.6 mg). The morphine milligram equivalents decreased to 0.7 mg (SD 8.2 mg) by week 4 and remained consistently less than 1 mg between week 4 and 12 months. Compared with the ED to primary care provider pathway, the relative risk of opioid prescription between 7 days and 12 months after the index ED visit was similar for the ED to physical therapy pathway, higher for both the ED to hospital admission or repeat ED visit pathway (30% increase; relative risk (RR), 1.3; 95% CI, 1.17-1.44) and the ED to specialist pathway (19% increase; RR, 1.19; 95% CI, 1.07-1.33), and lower in the ED with no follow-up visits pathway (41% decrease; RR, 0.59; 95% CI, 0.54-0.65)., Conclusion: In general, more conservative care was associated with lower opioid prescription rates, and escalated care was associated with higher opioid prescription rates., Competing Interests: The authors report no competing interests., (© 2023 The Authors.)

Background: Understanding which patient-reported outcome measures are being collected and utilized in clinical practice and research for patients with neck pain will help to inform recommendations for a core set of measures that provide value to patients and clinicians during diagnosis, clinical decision-making, goal setting and evaluation of responsiveness to treatment. Therefore, the aim of this study was to conduct a review of systematic reviews using a qualitative synthesis on the use of patient-reported outcome measures (PROMs) for patients presenting with neck pain to physical therapy., Methods: An electronic search of systematic reviews and guideline publications was performed using MEDLINE (OVID), Embase (Elsevier), CINAHL Complete (EBSCOhost), and Web of Science (Clarivate) databases to identify reviews that evaluated physical therapy interventions or interventions commonly performed by a physical therapist for individuals with neck pain and included at least one patient-reported outcome measure. The frequency and variability in which the outcome measures were reported among the studies in the review and the constructs for which they measured were evaluated. The evaluation of a core set of outcome measures was assessed. Risk of bias and quality assessment was performed using A Measurement Tool to Assess systematic Reviews 2., Results: Of the initial 7,003 articles, a total of 37 studies were included in the final review. Thirty-one PROMs were represented within the 37 reviews with eleven patient-reported outcome measures in three or more reviews. The eleven PROMs assessed the constructs of disability, pain intensity, psychosocial factors and quality of life. The greatest variability was found amongst individual measures assessing psychosocial factors. Assessment of psychosocial factors was the least represented construct in the included studies. Overall, the most frequently utilized patient reported outcome measures were the Neck Disability Index, Visual Analog Scale, and Numeric Pain Rating Scale. The most frequently used measures evaluating the constructs of disability, pain intensity, quality of life and psychosocial functioning included the Neck Disability Index, Visual Analog Scale, Short-Form-36 health survey and Fear Avoidance Belief Questionnaire respectively. Overall risk of bias and quality assessment confidence levels ranged from critically low (2 studies), low (12 studies), moderate (8 studies), and high (15 studies)., Conclusion: This study identified a core set of patient-reported outcome measures that represented the constructs of disability, pain intensity and quality of life. This review recommends the collection and use of the Neck Disability Index and the Numeric Pain Rating Scale or Visual Analog Scale. Recommendation for a QoL measure needs to be considered in the context of available resources and administrative burden. Further research is needed to confidently recommend a QoL and psychosocial measure for patients presenting with neck pain. Other measures that were not included in this review but should be further evaluated for patients with neck pain are the Patient Reported Outcomes Measurement Information System (PROMIS) Physical function, PROMIS Pain Interference and the Optimal Screening for Prediction of Referral and Outcome Yellow Flag (OSPRO-YF) tool., (© 2023. International Society for Quality of Life Research (ISOQOL).)

Background: Physical function and pain outcomes vary after arthroplasty. We investigated differences in postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) and pain interference (PI) scores for patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA). We aimed to identify preoperative factors that predict postoperative PROMIS scores., Methods: Patients who underwent TKA and THA from 2014-2020 were eligible. Preoperative variables including demographics, comorbidities, and pain scores were obtained from the medical record. Patients completed surveys measuring postoperative PF and PI. Descriptive statistics and separate linear regression models for each anatomical location were performed to examine factors predicting postoperative PROMIS PF and PI scores., Results: Surveys were completed by 2411 patients (19.5% response rate). Unadjusted mean PF postoperative scores were 47.2 for TKA and 48.8 for THA. Preoperative predictors of lower PF included female sex; body mass index and comorbidities for TKA and THA; and age, tobacco use, and non-White race for THA. Mean PI scores were 47.9 for THA and 49.0 for TKA. Preoperative predictors of increased PI included non-White race and increased body mass index for TKA and THA; higher preoperative pain for TKA; and female sex and increased comorbidity for THA., Conclusions: Postoperative PROMIS scores were similar for TKA and THA, with THA having slightly higher PF and lower PI scores. Regression models using preoperative variables showed similar performance for TKA compared with THA. These findings suggest areas for future development of clinical decision support tools., (© 2023 The Authors.)

The intestine is essential for nutritional uptake and as a barrier to pathogens. Inflammation of the intestine can result from chemical contaminants, dietary irritants, or disease and may lead to serious health consequences, including reduced growth rates or increased pathogen susceptibility. Traditionally, intestinal inflammation in fish has been detected through histology completed post-mortem through excision and processing of the affected tissue. However, in human clinical settings, tools have been developed to assess intestinal inflammation non-invasively. Contrast-enhanced ultrasound (CEUS) imaging is an important tool for measuring inflammation in patients because it is cost-effective and minimally invasive. Specifically, CEUS allows real-time visualization and quantification of vascular perfusion. Changes in blood flow are typical in areas of inflamed or diseased tissue, and by measuring these changes, it is possible to assess the degree of inflammation. We demonstrate that standard CEUS protocols used for small mammals can be used to quantify vascular perfusion in the intestines of rainbow trout. Our resolution was sufficient to measure a significant difference in perfusion between control and TNBS-inflamed trout intestines, with inflamed intestines showing decreased perfusion. The presence of inflammation in the TNBS-treated intestines was verified ex vivo histologically and was characterized by the thickening of intestinal folds. The minimally invasive nature of CEUS imaging presents the opportunity to evaluate intestinal health in novel ways by allowing for longitudinal observations and avoiding mortality in valuable or at-risk specimens. Recent developments of highly portable, cost-effective CEUS systems will allow broad application of this tool, from industry to research., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Steven Machtaler reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. The rest of the authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: High impact chronic pain (HICP) is not typically measured following orthopedic surgeries, but has a substantial negative impact on postoperative quality of life. This analysis determined which Patient-Reported Outcome Measurement Information System (PROMIS) measures accurately estimate HICP status following total joint arthroplasty (TJA)., Methods: This was a secondary analysis of a hip and knee TJA cohort. HICP status was determined by two items from the Graded Chronic Pain Scale-Revised. The cohort (n = 2,400) consisted of 47.5% hip (n = 1,142) and 52.5% knee TJA (n = 1,258). For total hip arthroplasty (THA), 53.7% were women (n = 615), 48.6% were 65 years or older (n = 557), 72.5% completed the survey more than 24 months after first surgery (n = 831), and 9.9% had HICP (n = 114). For total knee arthroplasty (TKA), 54.3% were women (n = 687), 59.3% were 65 years or older (n = 750), 72.3% survey completed the survey more than 24 months after first surgery (n = 915), and 11.5% had HICP (n = 145). Included PROMIS measures were pain interference, physical function, anxiety, and sleep disturbance. First, discriminant function analysis determined PROMIS measure contribution to HICP status. Then, area under the curve (AUC) calculated the accuracy of PROMIS measures to estimate HICP status. Influences of sociodemographic and surgical characteristics on AUC were explored in sensitivity analyses., Results: Results for TKA and THA were similar so they are presented collectively for the sake of brevity. Mean differences were identified for all PROMIS measures for those with HICP (All P values < 0.01). Pain interference (β = 0.934) and sleep disturbance (β = 0.154) were independently correlated with HICP status in discriminant function analyses. The AUC (95% CIs) for HICP were as follows: pain interference (.952-.973), physical function (.921-.949), sleep (.780-.838), and anxiety (.687-.757). Sensitivity analyses revealed little change in AUC and HICP cutoff scores for PROMIS pain interference and physical function., Conclusion: Two PROMIS measures commonly administered as standard of care for orthopedics, pain interference, and physical function, can be used to estimate HICP status for THA and TKA, thereby refining assessment of TJA outcomes., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Chemically-induced models of intestinal inflammation are a useful tool for the study of immune responses and inflammation. Although well established in mammals, application of these models is currently limited in teleosts. Based on a variety of factors, including genetic diversity, known toxicological sensitivity, and economic importance, we propose salmonids as a model family of fishes for studying intestinal inflammation. We present a rainbow trout model of chemically-induced intestinal inflammation using 2,4,6-trinitrobenzene sulfonic acid (TNBS), assessed through histological analysis of primary and secondary intestinal folding, enterocyte morphology, goblet cell size and frequency, tissue layer thickness, and immune cell infiltration. Twenty-four hours after treatment with one of three concentrations of TNBS, trout developed classic signs of intestinal inflammation, including notably increased thickness of primary and secondary folds, and increased immune cell infiltration as compared to controls. This study provides a simple, reproducible model of rapid TNBS-induction of moderate intestinal inflammation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Patient-Reported Outcomes Measurement Information System (PROMIS) domains for sleep disturbance, anxiety, and dyspnea have been under-reported for total joint arthroplasty (TJA). The aims of this study were to report postoperative differences for these domains based on TJA location and chronic pain state. We also investigated whether these domains were associated with physical function and pain interference outcomes., Methods: This was a retrospective, observational study of patients who underwent hip, knee, or shoulder TJA (primary and revision surgeries) at a single academic tertiary referral center. A subset of these patients completed an email-based survey for chronic pain grade (Chronic Pain Grade Scale-Revised) and sleep disturbance, anxiety, dyspnea, physical function, and pain interference (PROMIS short forms). Pre-operative and operative data were extracted from the electronic health record. Data analysis investigated PROMIS domains for differences in TJA location and chronic pain grade. Hierarchical linear regression determined associations of these domains with physical function and pain interference., Results: A total of 2638 individuals provided informed consent and completed the email survey. In the ANOVA models for sleep disturbance, anxiety, and dyspnea, there was no location by chronic pain grade interaction (p > 0.05) and no difference based on TJA location (p > 0.05). There were differences for chronic pain grade (p < 0.01). The poorest postoperative outcome score for each domain was associated with high impact chronic pain. Furthermore, sleep disturbance and dyspnea had the strongest associations with physical function and pain interference (p < 0.01)., Conclusions: Sleep disturbance, anxiety, and dyspnea did not vary based on TJA location, but were associated with postoperative chronic pain grade. Sleep disturbance and dyspnea were strongly associated with commonly reported outcomes of physical function and pain interference. These findings provide guidance for those interested in expanding TJA outcome assessment to include sleep disturbance, anxiety, and/or dyspnea., (© 2022. The Author(s).)

Background: Lumbar spinal stenosis (LSS) is a common degenerative condition that contributes to back and back-related leg pain in older adults. Most patients with symptomatic LSS initially receive non-operative care before surgical consultation. However, there is a scarcity of data regarding prognosis for patients seeking non-surgical care. The overall goal of this project is to develop and evaluate a clinically useful model to predict long-term physical function of patients initiating non-surgical care for symptomatic LSS., Methods: This is a protocol for an inception cohort study of adults 50 years and older who are initiating non-surgical care for symptomatic LSS in a secondary care setting. We plan to recruit up to 625 patients at two study sites. We exclude patients with prior lumbar spine surgeries or those who are planning on lumbar spine surgery. We also exclude patients with serious medical conditions that have back pain as a symptom or limit walking. We are using weekly, automated data pulls from the electronic health records to identify potential participants. We then contact patients by email and telephone within 21 days of a new visit to determine eligibility, obtain consent, and enroll participants. We collect data using telephone interviews, web-based surveys, and queries of electronic health records. Participants are followed for 12 months, with surveys completed at baseline, 3, 6, and 12 months. The primary outcome measure is the 8-item PROMIS Physical Function (PF) Short Form. We will identify distinct phenotypes using PROMIS PF scores at baseline and 3, 6, and 12 months using group-based trajectory modeling. We will develop and evaluate the performance of a multivariable prognostic model to predict 12-month physical function using the least absolute shrinkage and selection operator and will compare performance to other machine learning methods. Internal validation will be conducted using k-folds cross-validation., Discussion: This study will be one of the largest cohorts of individuals with symptomatic LSS initiating new episodes of non-surgical care. The successful completion of this project will produce a cross-validated prognostic model for LSS that can be used to tailor treatment approaches for patient care and clinical trials., (© 2022. The Author(s).)

Background: Physical therapy for neck and low back pain is highly variable despite the availability of clinical practice guidelines (CPG). This review aimed to determine the impact of CPG implementation on patient-level outcomes for spinal pain. Implementation strategies were also examined to determine prevalence and potential impact., Methods: Multiple databases were searched through April 2021 for studies assessing CPG implementation in physical therapy for neck and low back pain. Articles were screened for eligibility. The Modified Downs and Black checklist was utilized to determine study quality. Due to the heterogeneity between studies, a meta-analysis was not performed., Results: Twenty-one studies were included in this review. Implementation strategies were significantly varied between studies. Outcomes pertaining to healthcare utilization, pain, and physical functioning were assessed in relation to the implementation of CPGs. Multiple implementation strategies were identified, with Managing Quality as the most frequently utilized key implementation process. Findings indicate CPG implementation decreased healthcare utilization, but inconsistent results were found with physical functioning and pain outcomes., Conclusions: CPG implementation appears to have a beneficial effect on healthcare utilization outcomes, but may not impact pain and physical functioning outcomes. Effective CPG implementation strategies remain unknown, though utilizing implementation framework may improve outcomes. More research is needed to determine the most effective implementation strategies and effects on pain and physical function outcomes., (© 2022. The Author(s).)

Background: The Patient-Reported Outcome Measurement Information System (PROMIS) can be used to monitor patients in population-health-based programs. However, it is unknown which measures are most appropriate to differentiate patients who will undergo hip or knee total joint arthroplasty (TJA) in a cohort of patients with osteoarthritis., Methods: A retrospective cohort of new patients consulting for treatment from November 17, 2017 to April 20, 2020 (cases: hip: n = 157, knee: n = 112; randomly selected nonsurgical controls: hip: n = 314, knee: n = 224) was extracted from the electronic health record. We recorded demographics, comorbidity, and PROMIS scores for 8 domains (physical function, pain interference, pain intensity, anxiety, depression, sleep disturbance, ability to participate in social roles and activities, and fatigue). We performed descriptive statistics to characterize the cohorts and baseline PROMIS scores and conducted logistic regression models to determine which PROMIS domains differentiated patients undergoing hip and knee TJA., Results: In univariate comparisons of PROMIS domains, the hip and knee surgical cohorts differed from controls in physical function (P < .01), pain interference (P < .01), and ability to participate in social roles and activities (P < .02). In logistic regression models informed by univariate analyses, PROMIS physical function was the only PROMIS measure to differentiate undergoing surgery in both hip and knee cohorts (P < .01)., Conclusion: PROMIS physical function can differentiate TJA cases from nonsurgical controls in both hip and knee patients. These findings have implications for considering which PROMIS measures to administer in patients with hip and knee osteoarthritis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hip, knee, and shoulder arthroplasty are among the most frequently performed orthopaedic procedures in the United States. High impact and bothersome chronic pain rates following total joint arthroplasty (TJA) are unknown; as are factors that predict these chronic pain outcomes. This retrospective observational study included individuals that had a TJA from January 2014 to January 2020 (n = 2,638). Pre-operative and clinical encounter information was extracted from the electronic health record and chronic pain state was determined by email survey. Predictor variables included TJA location, number of surgeries, comorbidities, tobacco use, BMI, and pre-operative pain intensity. Primary outcomes were high impact and bothersome chronic pain. Rates of high impact pain (95% CI) were comparable for knee (9.8-13.3%), hip (8.3-11.8%) and shoulder (7.6-16.3%). Increased risk of high impact pain included non-white race, two or more comorbidities, age less than 65 years, pre-operative pain scores 5/10 or higher, knee arthroplasty, and post-operative survey completion 24 months or less. Rates of bothersome chronic pain (95% CI) were also comparable for knee (24.9-29.9%) and hip (21.3-26.3%) arthroplasty; but higher for shoulder (26.9-39.6%). Increased risk of bothersome chronic pain included non-white race, shoulder arthroplasty, knee arthroplasty, current or past tobacco use, and being female. PERSPECTIVE: In this cohort more than 1/3rd of individuals reported high impact or bothersome chronic pain following TJA. Non-white race and knee arthroplasty were the only two variables associated with both chronic pain outcomes., (Copyright © 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Characterise the health status of patients newly consulting an orthopaedic specialist across eight clinical subspecialties., Design: Retrospective cohort., Setting: 18 orthopaedic clinics, including 8 subspecialties (14 ambulatory and 4 hospital based) within an academic health system., Participants: 14 910 patients consulting an orthopaedic specialist for a new patient consultation who completed baseline Patient-Reported Outcomes Measurement Information System (PROMIS) measures associated with their appointment from 17 November 2017 to 13 May 2019. Patients were aged 55.72±5.8 years old, and 61.3% were female and 79.3% were Caucasian and 13.4% were black or African American. Patients who did not complete PROMIS measures or cancelled their appointment were excluded from the study., Primary Outcome: PROMIS domains of physical function, pain interference, pain intensity, depression, anxiety, fatigue, sleep disturbance and the ability to participate in social roles., Results: Mean PROMIS scores for physical function were (38.1±9.2), pain interference (58.9±8.1), pain intensity (4.6±2.5), depression (47.9±8.9), anxiety (49.9±9.5), fatigue (50.5±10.3), sleep disturbance (51.1±9.8) and ability to participate in social roles (49.1±10.3) for the entire cohort. Across the clinical subspecialties, neurosurgery, spine and trauma patients were most profoundly affected across almost all domains and patients consulting with a hand specialist reported the least limitations or symptoms across domains. There was a moderate, negative correlation between pain interference and physical functioning (r=-0.59) and low correlations between pain interference with anxiety (r=0.36), depression (r=0.39) as well as physical function and anxiety (r=-0.32) and depression(r=-0.30) and sleep (r=-0.31)., Conclusions: We directly compared clinically meaningful PROMIS domains across eight orthopaedic subspecialties, which would not have been possible with legacy measures alone. These results support PROMIS's utility as a common metric to assess and compare patient health status across multiple orthopaedic subspecialties., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Organisms are exposed to a wealth of chemical information during their development. Some of these chemical cues indicate present or future dangers, such as the presence of predators that feed on either the developing embryos or their nearby parents. Organisms may use this information to modify their morphology or life-history, including hatching timing, or may retain information about risk until it gains relevance. Previous research has shown predation-induced alterations in hatching among embryonic minnows that were exposed to mechanical-injury-released alarm cues from conspecific embryos. Here, we test whether minnows likewise hatch early in response to alarm cues from injured adult conspecifics. We know that embryonic minnows can detect adult alarm cues and use them to facilitate learned recognition of predators; however, it is unknown whether these adult alarm cues will also induce a change in hatching time. Early hatching may allow animals to rapidly disperse away from potential predators, but late hatching may allow animals to grow and develop structures that allow them to effectively escape when they do hatch. Here, we found here that unlike embryonic fathead minnows (Pimephales promelas) exposed to embryonic cues, embryonic minnows exposed to adult alarm cues do not exhibit early hatching. The ability of embryos to recognize adult alarm cues as a future threat, but not a current one, demonstrates sophisticated ontogenetic specificity in the hatching response of embryonic minnows., Competing Interests: The authors have declared that no competing interests exist.

Aims: Patient-reported outcome measures have become an important part of routine care. The aim of this study was to determine if Patient-Reported Outcomes Measurement Information System (PROMIS) measures can be used to create patient subgroups for individuals seeking orthopaedic care., Methods: This was a cross-sectional study of patients from Duke University Department of Orthopaedic Surgery clinics (14 ambulatory and four hospital-based). There were two separate cohorts recruited by convenience sampling (i.e. patients were included in the analysis only if they completed PROMIS measures during a new patient visit). Cohort #1 (n = 12,141; December 2017 to December 2018,) included PROMIS short forms for eight domains (Physical Function, Pain Interference, Pain Intensity, Depression, Anxiety, Sleep Quality, Participation in Social Roles, and Fatigue) and Cohort #2 (n = 4,638; January 2019 to August 2019) included PROMIS Computer Adaptive Testing instruments for four domains (Physical Function, Pain Interference, Depression, and Sleep Quality). Cluster analysis (K-means method) empirically derived subgroups and subgroup differences in clinical and sociodemographic factors were identified with one-way analysis of variance., Results: Cluster analysis yielded four subgroups with similar clinical characteristics in Cohort #1 and #2. The subgroups were: 1) Normal Function: within normal limits in Physical Function, Pain Interference, Depression, and Sleep Quality; 2) Mild Impairment: mild deficits in Physical Function, Pain Interference, and Sleep Quality but with Depression within normal limits; 3) Impaired Function, Not Distressed: moderate deficits in Physical Function and Pain Interference, but within normal limits for Depression and Sleep Quality; and 4) Impaired Function, Distressed: moderate (Physical Function, Pain Interference, and Sleep Quality) and mild (Depression) deficits., Conclusion: These findings suggest orthopaedic patient subgroups differing in physical function, pain, and psychosocial distress can be created from as few as four different PROMIS measures. Longitudinal research is necessary to determine whether these subgroups have prognostic validity. Cite this article: Bone Jt Open  2021;2(7):493-502.

Background: The integration of Patient Reported Outcome Measures (PROMs) into clinical care presents many challenges for health systems. PROMs provide quantitative data regarding patient-reported health status. However, the most effective model for collecting PROMs has not been established. Therefore the purpose of this study is to report the development and preliminary evaluation of the standardized collection of PROMs within a department of orthopedic surgery at a large academic health center., Methods: We utilized the Users' Guide to Integrating Patient-Reported Outcomes in Electronic Health Records by Gensheimer et al., 2018 as a framework to describe the development of PROMs collection initiative. We framed our initiative by operationalizing the three aspects of PROM collection development: Planning, Selection, and Engagement. Next, we performed a preliminary evaluation of our initiative by assessing the response rate of patients completing PROMs (no. of PROMs completed/no. of PROMs administered) across the entire department (18 clinics), ambulatory clinics only (14 clinics), and hospital-based clinics only (4 clinics). Lastly, we reported on the mean response rates for the top 5 and bottom 5 orthopaedic providers to describe the variability across providers., Results: We described the development of a fully-integrated, population health based implementation strategy leveraging the existing resources of our local EHR to maximize clinical utility of PROMs and routine collection. We collected a large volume of PROMs over a 13 month period (n = 10,951) across 18 clinical sites, 7 clinical specialties and over 100 providers. The response rates varied across the department, ranging from 29 to 42%, depending on active status for the portal to the electronic health record (MyChart). The highest single provider mean response rate was 52%, and the lowest provider rate was 13%. Rates were similar between hospital-based (26%) and ambulatory clinics (29%)., Conclusions: We found that our standardized PROMs collection initiative, informed by Gensheimer et al., achieved scope and scale, but faced challenges in achieving a high response rate commensurate with existing literature. However, most studies reported a targeted recruitment strategy within a narrow clinical population. Further research is needed to elucidate the trade-off between scalability and response rates in PROM collection initiatives.

Background: The transition to the new ICD-10 (International Classification of Diseases, Tenth Revision) coding system in the U.S. poses challenges to the ability to consistently and accurately measure trends in comorbidities and complications. We examined the prevalence of comorbidities and postoperative medical complications before and after the transition from ICD-9 to ICD-10 among patients who underwent primary total hip or knee arthroplasty (THA or TKA). We hypothesized that the transition to ICD-10 codes was associated with discontinuity and slope change in comorbidities and medical complications., Methods: The Elixhauser comorbidities and medical complications were identified using the Premier Healthcare database from fiscal year (FY)2011 to FY2018. Using multivariable segmented regression models, we examined the changes in the levels and slopes after the transition from ICD-9 to ICD-10 coding. Odds ratios (ORs) of <1 and >1 indicate decreases and increases, respectively, in levels and slopes., Results: Overall, 2,006,581 patients who underwent primary THA or TKA were identified. The mean age was 65.9 ± 10.5 years, and the median length of the hospital stay was 2 days (interquartile range [IQR], 2 to 3 days). Of the comorbidities studied, congestive heart failure, hypertension, and obesity had a statistically significant but clinically small discontinuity after the transition from ICD-9 to ICD-10 coding. Of the complications, pneumonia (OR = 0.66, 95% confidence interval [CI] = 0.48 to 0.90), acute respiratory failure (OR = 1.88, 95% CI = 1.52 to 2.33), sepsis (OR = 2.54, 95% CI = 1.45 to 4.44), and urinary tract infection (OR = 1.79, 95% CI = 1.32 to 2.42) demonstrated statistically significant discontinuity. Alcohol abuse and paralysis had an increasing prevalence before the ICD transition, followed by a decreasing prevalence after the transition. In contrast, metastatic cancer, weight loss, and acquired immunodeficiency syndrome (AIDS) showed a decreasing prevalence before the ICD transition followed by an increasing prevalence after the transition. Generally, complications showed a decreasing prevalence over time., Conclusions: The discontinuities after the transition from ICD-9 to ICD-10 coding were relatively small for most comorbidities. Medical complications generally showed a decreasing trend over the quarters studied. These findings support caution when conducting joint replacement studies that rely on ICD coding and include the ICD coding transition period., Competing Interests: Disclosure: Dr. Ellis received consulting fees from the Institute for Medical Research, Durham, North Carolina, for this work. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work (http://links.lww.com/JBJS/G357)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: The Patient-Reported Outcomes Measurement Information System Ⓡ (PROMIS Ⓡ ) is a dynamic system of psychometrically sound patient-reported outcome (PRO) measures. There has been a recent increase in the use of PROMIS measures, yet little has been written about the reporting of these measures in the field of orthopedics. The purpose of this study was to conduct a systematic review to determine the uptake of PROMIS measures across orthopedics and to identify the type of PROMIS measures and domains that are most commonly used in orthopedic research and practice., Methods: We searched PubMed, Embase, and Scopus using keywords and database-specific subject headings to capture orthopedic studies reporting PROMIS measures through November 2018. Our inclusion criteria were use of PROMIS measures as an outcome or used to describe a population of patients in an orthopedic setting in patients ≥ 18 years of age. We excluded non-quantitative studies, reviews, and case reports., Results: Our final search yielded 88 studies published from 2013 through 2018, with 57% (50 studies) published in 2018 alone. By body region, 28% (25 studies) reported PROMIS measures in the upper extremity (shoulder, elbow, hand), 36% (32 studies) reported PROMIS measures in the lower extremity (hip, knee, ankle, foot), 19% (17 studies) reported PROMIS measures in the spine, 10% (9 studies) reported PROMIS measures in trauma patients, and 6% (5 studies) reported PROMIS measures in general orthopedic patients. The majority of studies reported between one and three PROMIS domains (82%, 73 studies). The PROMIS Computerized Adaptive Test (CAT) approach was most commonly used (81%, 72 studies). The most frequently reported PROMIS domains were physical function (81%, 71 studies) and pain interference (61%, 54 studies)., Conclusion: Our review found an increase in the reporting of PROMIS measures over the recent years. Utilization of PROMIS measures in orthopedic populations is clinically appropriate and can facilitate communication of outcomes across different provider types and with reduced respondent burden., Registration: The protocol for this systematic review was designed in accordance with the PRISMA guidelines and is registered with the PROSPERO database (CRD42018088260).

Objectives: To determine the relationship between health care use and the magnitude of change in patient-reported outcomes in individuals who received treatment for subacromial pain syndrome. The secondary objective was to determine the value of care, as measured by change in pain and disability per dollar spent., Design: Secondary analysis of a randomized clinical trial that investigated the effects of nonsurgical care for subacromial pain syndrome., Methods: Two groups of treatment responders were created, based on 1-year change in Shoulder Pain and Disability Index (SPADI) score (high, 46.83 points; low, 8.21 points). Regression analysis was performed to determine the association between health care use and 1-year change in SPADI score. Baseline SPADI score was used as a covariate in the regression analysis. Value was measured by comparing health care visits and costs expended per SPADI 1-point change between responder groups., Results: Ninety-eight patients were included; 38 were classified as high responders (mean 1-year SPADI change score, 46.83 points) and 60 were classified as low responders (1-year SPADI change score, 8.21 points). Neither unadjusted medical visits (5.89; 95% confidence interval [CI]: 4.35, 7.44 versus 6.30; 95% CI: 5.14, 7.46) nor medical costs ($1404.86; 95% CI: $1109.34, $1779.09 versus $1679.26; 95% CI: $1391.54, $2026.48) were significantly different between high and low responders, respectively., Conclusion: Neither the number of visits nor the financial cost of nonsurgical shoulder- related care was associated with improvement in shoulder pain and disability at 1 year. J Orthop Sports Phys Ther 2020;50(11):642-648. doi:10.2519/jospt.2020.9440 .

Objective: To investigate the Optimal Screening for Prediction of Referral and Outcome Yellow Flag (OSPRO-YF) tool for longitudinal monitoring of pain associated distress with the goal of improving prediction of 50% reduction in pain intensity and disability outcomes., Design: Cohort study with 12-month follow-up after initial care episode., Setting: Ambulatory care, participants seeking care from outpatient physical therapy clinics., Participants: Participants (N=440) were seeking care for primary complaint of neck, low back, knee, or shoulder pain. This secondary analysis included 440 subjects (62.5% female; mean age, 45.1±17y) at baseline with n=279 (63.4%) providing follow-up data at 12 months., Interventions: Not applicable., Main Outcome Measures: A 50% reduction (baseline to 12-mo follow-up) in pain intensity and self-reported disability., Results: Trends for prediction accuracy were similar for all versions of the OSPRO-YF. For predicting 50% reduction in pain intensity, model fit met the statistical criterion for improvement (P<.05) with each additional time point added from baseline. Model discrimination improved statistically when the 6-month to 12-month change was added to the model (area under the curve=0.849, P=.003). For predicting 50% reduction in disability, there was no evidence of improvement in model fit or discrimination from baseline with the addition of 4-week, 6-month, or 12-month changes (P>.05)., Conclusions: These results suggested that longitudinal monitoring improved prediction accuracy for reduction in pain intensity but not for disability reduction. Differences in OSPRO-YF item sets (10 vs 17 items) or scoring methods (simple summary score vs yellow flag count) did not affect predictive accuracy for pain intensity, providing flexibility for implementing this tool in practice settings., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: It remains unclear as to what factors influence a patient's choice to seek care from a specific healthcare provider for low back and neck pain., Objective: Utilize Andersen's Behavioral Model of Health Service Utilization as a conceptual framework to identify the predisposing, enabling and need factors associated with choice of healthcare provider for back and/or neck pain., Methods: PubMed, CINAHL, EMBASE, and SCOPUS databases were searched for studies that included 1) patients seeking care for acute or chronic low back or neck pain; 2) patients at least 18 years of age; 3) reported any healthcare provider type chosen to be seen. Significant factors addressing a patient's choice of provider seen for back pain, neck pain, or both were extracted from studies and analyzed under the Behavioral Model of Health Service Utilization., Results: 20 studies were included in this review: 17 quantitative studies and 3 qualitative studies. Provider types identified were medical physicians, chiropractors, physical therapists, acupuncturists and CAM providers. Age and sex were the most commonly reported predisposing factors; financial and personal factors were the most common enabling factors; patients' duration of pain and self-reported level of functioning were the most commonly reported need factors., Conclusions: While predisposing and need factors are important, enabling factors also have an influence in choice of healthcare provider for back and/or neck pain., (Published by Elsevier Ltd.)

Purpose of Review: The purpose of this systematic review is to evaluate the current literature in patients undergoing spine surgery in the cervical, thoracic, and lumbar spine to determine the available risk assessment tools to predict the patient-centered outcomes of pain, disability, physical function, quality of life, psychological disposition, and return to work after surgery., Recent Findings: Risk assessment tools can assist surgeons and other healthcare providers in identifying the benefit-risk ratio of surgical candidates. These tools gather demographic, medical history, and other pertinent patient-reported measures to calculate a probability utilizing regression or machine learning statistical foundations. Currently, much is still unknown about the use of these tools to predict quality of life, disability, and other factors following spine surgery. A systematic review was conducted using PRISMA guidelines that identified risk assessment tools that utilized patient-reported outcome measures as part of the calculation. From 8128 identified studies, 13 articles met inclusion criteria and were accepted into this review. The range of c-index values reported in the studies was between 0.63 and 0.84, indicating fair to excellent model performance. Post-surgical patient-reported outcomes were identified in the following categories (n = total number of predictive models): return to work (n = 3), pain (n = 9), physical functioning and disability (n = 5), quality of life (QOL) (n = 6), and psychosocial disposition (n = 2). Our review has synthesized the available evidence on risk assessment tools for predicting patient-centered outcomes in patients undergoing spine surgery and described their findings and clinical utility.

Background: In Minnesota and North Dakota, a clonal strain of bla KPC-3 -producing Enterobacter cloacae complex has been reported with increasing frequency., Methods: Between July 2015 and February 2016, 13 carbapenem-resistant E. cloacae complex isolates were identified at our institution. Five bla KPC -positive isolates were identified by polymerase chain reaction and underwent pulsed-field gel electrophoresis and whole genome sequencing. Medical records of these patients were reviewed., Results: All 5 case-isolates belonged to sequence type 171 and were bla KPC-3 -positive. Three pulsed-field gel electrophoresis patterns with >90% similarity were identified in the 5 case-isolates. We identified overlaps in time and location between case patients. Plasmid types and resistance genes were nearly identical between the isolates. Whole genome sequencing showed isolates A, B, and D to be closely related with <10 core single-nucleotide polymorphisms differences. Isolates C and E were also closely related to each other, but more distantly to A, B, and D; all belonged to the clonal lineage of the major circulating E. cloacae complex strain in Minnesota and North Dakota. Despite having overlapping hospital stays, isolates for patients C and D were not identical., Conclusions: Isolates A and D were nearly identical, indicating possible transmission during hospitalization. Transmission of the other isolates may have occurred elsewhere. This report highlights the importance of using both epidemiologic and molecular data to track the spread of carbapenemase-producers., (Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.)

Background: Patients seek care from physical therapists for neck pain but it is unclear what the association of the timing of physical therapy (PT) consultation is on 1-year healthcare utilization and costs. The purpose of this study was to compare the 1-year healthcare utilization and costs between three PT timing groups: patients who consulted a physical therapist (PT) for neck pain within 14 days (early PT consultation), between 15 and 90 days (delayed PT consultation) or between 91 and 364 days (late PT consultation)., Methods: A retrospective cohort of 308 patients (69.2% female, ages 48.7[±14.5] years) were categorized into PT timing groups. Descriptive statistics were calculated for each group. In adjusted regression models, 1-year healthcare utilization of injections, imaging, opioids and costs were compared between groups., Results: Compared to early PT consultation, the odds of receiving an opioid prescription (aOR = 2.79, 95%CI: 1.35-5.79), spinal injection (aOR = 4.36, 95%CI:2.26-8.45), undergoing an MRI (aOR = 4.68, 95%CI:2.25-9.74), X-ray (aOR = 2.97, 95%CI:1.61-5.47) or CT scan (aOR = 3.36, 95%CI: 1.14-9.97) were increased in patients in the late PT consultation group. Similar increases in risk were found in the delayed group (except CT and Opioids). Compared to the early PT consultation group, mean costs were $2172 ($557, $3786) higher in the late PT contact group and $1063 (95%CI: $ 138 - $1988) higher in the delayed PT consultation group., Discussion: There was an association with the timing of physical therapy consultation on healthcare utilization and costs, where later consultation was associated with increases costs and healthcare utilization. This study examined the association of timing of physical therapy consultation on costs and healthcare utilization, but not the association of increased access to physical therapy consultation. Therefore, the findings warrant further investigation to explore the effects of increased access to physical therapy consultation on healthcare utilization and costs in a prospective study.

Excitation-inhibition balance is critical for optimal brain function, yet the mechanisms underlying the tuning of inhibition from different populations of inhibitory neurons are unclear. Here, we found evidence for two distinct pathways through which excitatory neurons cell-autonomously modulate inhibitory synapses. Synapses from parvalbumin-expressing interneurons onto hippocampal pyramidal neurons are regulated by neuronal firing, signaling through L-type calcium channels. Synapses from somatostatin-expressing interneurons are regulated by NMDA receptors, signaling through R-type calcium channels. Thus, excitatory neurons can cell-autonomously regulate their inhibition onto different subcellular compartments through their input (glutamatergic signaling) and their output (firing). Separately, while somatostatin and parvalbumin synapses onto excitatory neurons are both dependent on a common set of postsynaptic proteins, including gephyrin, collybistin, and neuroligin-2, decreasing neuroligin-3 expression selectively decreases inhibition from somatostatin interneurons, and overexpression of neuroligin-3 selectively enhances somatostatin inhibition. These results provide evidence that excitatory neurons can selectively regulate two distinct sets of inhibitory synapses., Competing Interests: The authors declare no conflict of interest.

The purpose of this study was to compare the immediate change in temporal summation of heat pain (TSP) between spinal manipulation (SMT) and spinal mobilization (MOB) in healthy volunteers. Ninety-two volunteers (24 male; 23.8 ± 5.3 years) were randomized to receive SMT, MOB, or no treatment (REST) for 1 session. Primary outcomes were changes in TSP, measured at the hand and foot, immediately after the session. A planned subgroup analysis investigated effects across empirically derived TSP clusters. For the primary outcome there were no differences in the immediate change in TSP measured at the foot between SMT and MOB, however, both treatments were superior to the REST condition. In the subgroup analysis the response to a standard TSP protocol was best characterized by 3 clusters: 52% no change (n = 48, 52%); facilitatory response (n = 24, 26%), and inhibitory response (n = 20, 22%). There was a significant Time × Treatment group × Cluster interaction for TSP measured at the foot. The inhibitory cluster showed the greatest attenuation of TSP after SMT and MOB compared with REST. These data suggest lumbar manual therapies of different velocities produce a similar localized attenuation of TSP, compared with no treatment. Attenuation of localized pain facilitatory processes by manual therapies was greatest in pain-free individuals who show an inhibitory TSP response., Perspective: The attenuation of pain facilitatory measures may serve an important underlying role in the therapeutic response to manual therapies. Identifying patients in pain who still have an inhibitory capacity (ie, an inhibitory response subgroup) may be useful clinically in identifying the elusive "manual therapy" responder., (Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Objective: To examine patients seeking care for neck pain to determine associations between the type of provider initially consulted and 1-year health care utilization., Patients and Methods: A retrospective cohort of 1702 patients (69.25% women, average age, 45.32±14.75 years) with a new episode of neck pain who consulted a primary care provider, physical therapist (PT), chiropractor (DC), or specialist from January 1, 2012, to June 30, 2013, was analyzed. Descriptive statistics were calculated for each group, and subsequent 1-year health care utilization of imaging, opioids, surgery, and injections was compared between groups., Results: Compared with initial primary care provider consultation, patients consulting with a DC or PT had decreased odds of being prescribed opioids within 1 year from the index visit (DC: adjusted odds ratio [aOR], 0.54; 95% CI, 0.39-0.76; PT: aOR, 0.59; 95% CI, 0.44-0.78). Patients consulting with a DC additionally demonstrated decreased odds of advanced imaging (aOR, 0.43; 95% CI, 0.15-0.76) and injections (aOR, 0.34; 95% CI, 0.19-0.56). Initiating care with a specialist or PT increased the odds of advanced imaging (specialist: aOR, 2.96; 95% CI, 2.01-4.38; PT: aOR, 1.57; 95% CI, 1.01-2.46), but only initiating care with a specialist increased the odds of injections (aOR, 3.21; 95% CI, 2.31-4.47)., Conclusion: Initially consulting with a nonpharmacological provider may decrease opioid exposure (PT and DC) over the next year and also decrease advanced imaging and injections (DC only). These data provide an initial indication of how following recent practice guidelines may influence health care utilization in patients with a new episode of neck pain.

In efforts to decrease practice variation, clinical practice guidelines for neck pain have been published. The purpose of this study was to determine the effect of receiving guideline adherent physical therapy (PT) on clinical outcomes, health care utilization, and charges for health care services in patients with neck pain. A retrospective review of 298 patients with neck pain receiving PT from 2008 to 2011 was performed. Clinical outcomes, utilization, and charges were compared between patients who received guideline adherent care and nonadherent care. Patients in the adherent care group experienced a lower percentage improvement in pain score compared to nonadherent care group (p = .01), but groups did not significantly differ on percentage improvement in disability (p = .32). However, patients receiving adherent care had an average 3.6 fewer PT visits (p < .001) and less charges for PT (p < .001). Additionally, patients receiving adherent care had 7.3 fewer visits to other health care providers (p < .001), one less prescription medication (p = .02) and 43% fewer diagnostic images (p = .02) but did not differ in their charges to other health care providers (p = .68) during the calendar year of undergoing PT. Although receiving guideline adherent care demonstrated positive effects on health care utilization and financial outcomes, there appears to be a trade-off with clinical outcomes., (© The Author(s) 2015.)

Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that interact trans-synaptically with neurexins to mediate synapse development and function. NLGN2 is only at inhibitory synapses while NLGN3 is at both excitatory and inhibitory synapses. We found that NLGN3 function at inhibitory synapses in rat CA1 depends on the presence of NLGN2 and identified a domain in the extracellular region that accounted for this functional difference between NLGN2 and 3 specifically at inhibitory synapses. We further show that the presence of a cytoplasmic tail (c-tail) is indispensible, and identified two domains in the c-tail that are necessary for NLGN function at inhibitory synapses. These domains point to a gephyrin-dependent mechanism that is disrupted by an autism-associated mutation at R705 and a gephyrin-independent mechanism reliant on a putative phosphorylation site at S714. Our work highlights unique and separate roles for the extracellular and intracellular regions in specifying and carrying out NLGN function respectively., Competing Interests: The authors declare that no competing interests exist.

Background: Neck pain is one of the most common reasons for entry into the healthcare system. Recent increases in healthcare utilization and medical costs have not correlated with improvements in health. Therefore there is a need to identify management strategies for neck pain that are effective for the patient, cost efficient for the payer and provided at the optimal time during an episode of neck pain., Methods: One thousand five hundred thirty-one patients who underwent physical therapist management with a primary complaint of non-specific neck pain from January 1, 2008 to December 31, 2012 were identified from the Rehabilitation Outcomes Management System (ROMS) database at Intermountain Healthcare. Patients reporting duration of symptoms less than 4 weeks were designated as undergoing "early" management and patients with duration of symptoms greater than 4 weeks were designated as receiving "delayed" management. These groups were compared using binary logistic regression to examine odds of achieving Minimal Clinically Important Difference (MCID) on the Neck Disability Index (NDI) and Numerical Pain Rating Scale (NPRS). Separate generalized linear modeling examined the effect of timing of physical therapist management on the metrics of value and efficiency., Results: Patients who received early physical therapist management had increased odds of achieving MCID on the NDI (aOR = 2.01, 95 % CI 1.57, 2.56) and MCID on the NPRS (aOR = 1.82, 95 % CI 1.42, 2.38), when compared to patients receiving delayed management. Patients who received early management demonstrated the greatest value in decreasing disability with a 2.27 percentage point change in NDI score per 100 dollars, best value in decreasing pain with a 0.38 point change on the NPRS per 100 dollars. Finally, patients receiving early management were managed more efficiently with a 3.44 percentage point change in NDI score per visit and 0.57 point change in NPRS score per visit., Conclusions: These findings suggest that healthcare systems that provide pathways for patients to receive early physical therapist management of neck pain may realize improved patient outcomes, greater value and higher efficiency in decreasing disability and pain compared to delayed management. Further research is needed to confirm this assertion.

Sequential patterns of prefrontal activity are believed to mediate important behaviors, e.g., working memory, but it remains unclear exactly how they are generated. In accordance with previous studies of cortical circuits, we found that prefrontal microcircuits in young adult mice spontaneously generate many more stereotyped sequences of activity than expected by chance. However, the key question of whether these sequences depend on a specific functional organization within the cortical microcircuit, or emerge simply as a by-product of random interactions between neurons, remains unanswered. We observed that correlations between prefrontal neurons do follow a specific functional organization-they have a small-world topology. However, until now it has not been possible to directly link small-world topologies to specific circuit functions, e.g., sequence generation. Therefore, we developed a novel analysis to address this issue. Specifically, we constructed surrogate data sets that have identical levels of network activity at every point in time but nevertheless represent various network topologies. We call this method shuffling activity to rearrange correlations (SHARC). We found that only surrogate data sets based on the actual small-world functional organization of prefrontal microcircuits were able to reproduce the levels of sequences observed in actual data. As expected, small-world data sets contained many more sequences than surrogate data sets with randomly arranged correlations. Surprisingly, small-world data sets also outperformed data sets in which correlations were maximally clustered. Thus the small-world functional organization of cortical microcircuits, which effectively balances the random and maximally clustered regimes, is optimal for producing stereotyped sequential patterns of activity., (Copyright © 2016 the American Physiological Society.)

Background: Deep layer excitatory circuits in the prefrontal cortex represent the strongest locus for genetic convergence in autism, but specific abnormalities within these circuits that mediate key features of autism, such as cognitive or attentional deficits, remain unknown. Attention normally increases the sensitivity of neural populations to incoming signals by decorrelating ongoing cortical circuit activity. Here, we investigated whether mechanisms underlying this phenomenon might be disrupted within deep layer prefrontal circuits in mouse models of autism., Methods: We isolated deep layer prefrontal circuits in brain slices then used single-photon GCaMP imaging to record activity from many (50 to 100) neurons simultaneously to study patterns of spontaneous activity generated by these circuits under normal conditions and in two etiologically distinct models of autism: mice exposed to valproic acid in utero and Fmr1 knockout mice., Results: We found that modest doses of the cholinergic agonist carbachol normally decorrelate spontaneous activity generated by deep layer prefrontal networks. This effect was disrupted in both valproic acid-exposed and Fmr1 knockout mice but intact following other manipulations that did not model autism., Conclusions: Our results suggest that cholinergic modulation may contribute to attention by acting on local cortical microcircuits to decorrelate spontaneous activity. Furthermore, defects in this mechanism represent a microcircuit-level endophenotype that could link diverse genetic and developmental disruptions to attentional deficits in autism. Future studies could elucidate pathways leading from various etiologies to this circuit-level abnormality or use this abnormality itself as a target and identify novel therapeutic strategies that restore normal circuit function., (Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the effect of clinical presentations of neck pain on short-term physical therapy outcomes., Design: Retrospective analysis of pair-matched groups from a clinical cohort., Setting: Thirteen outpatient physical therapy clinics in 1 health care system., Participants: Patients (N=1069) grouped by common clinical presentations of neck pain: nonspecific neck pain (NSNP) with duration <4 weeks; NSNP with duration >4 weeks; neck pain with arm pain; neck pain with headache; and neck pain from whiplash., Intervention: Conservative interventions provided by physical therapists., Main Outcome Measures: Neck Disability Index (NDI) and numerical pain rating scale (NPRS) recorded at the initial and last visits. The main outcome of interest was achieving recovery status on the NDI. Changes in NDI and NPRS were compared between clinical presentation groups., Results: Compared with patients presenting with NSNP >4 weeks, patients with NSNP <4 weeks had increased odds of achieving recovery status on the NDI (P<.0001) and demonstrated the greatest changes in clinical outcomes of pain (P≤.0001) and disability (P≤.0001). Patients with neck pain and arm pain demonstrated an increased odds of achieving recovery status on the NDI (P=.04) compared with patients presenting with NSNP >4 weeks., Conclusions: Treating patients with NSNP within <4 weeks of onset of symptoms may lead to improved clinical outcomes from physical therapy compared with other common clinical presentations., (Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Although nearly everyone at some point in their lives experiences back pain; the amount of interference with routine activity varies significantly. The fear-avoidance (FA) model of chronic pain explains how psychological variables, such as fear, act as mediating factors influencing the relationship between clinical pain intensity and the amount of interference with daily activities. What remains less clear is how other mediating factors fit within this model. The primary objective of this report was to examine the extent to which a dynamic measure of pain sensitivity provides additional information within the context of the FA model., Method: To address our primary objective, classic mediation and moderated mediation analyses were conducted on baseline clinical, psychological and quantitative sensory measures obtained on 67 subjects with back pain (mean age, 31.4 ± 12.1 years; 70% female)., Results: There was a moderately strong relationship (r = 0.52; p < 0.01) between clinical pain intensity and interference, explaining about 27% of the variance in the outcome. Mediation analyses confirmed fear partially mediated the total effect of clinical pain intensity on interference (Δβ = 0.27; p < 0.01), and accounted for an additional 16% of the variance. In our FA model, pain sensitivity did not demonstrate additional indirect effects; however, it did moderate the strength of indirect effects of fear., Conclusion: This preliminary modelling suggests complex interactions exist between pain-related fear and pain sensitivity measures that further explain individual differences in behaviour., (© 2014 European Pain Federation - EFIC®)

Unlabelled: Spinal manipulative therapy (SMT) is effective for some individuals experiencing low back pain; however, the mechanisms are not established regarding the role of placebo. SMT is associated with changes in pain sensitivity, suggesting related altered central nervous system response or processing of afferent nociceptive input. Placebo is also associated with changes in pain sensitivity, and the efficacy of SMT for changes in pain sensitivity beyond placebo has not been adequately considered. We randomly assigned 110 participants with low back pain to receive SMT, placebo SMT, placebo SMT with the instructional set "The manual therapy technique you will receive has been shown to significantly reduce low back pain in some people," or no intervention. Participants receiving the SMT and placebo SMT received their assigned intervention 6 times over 2 weeks. Pain sensitivity was assessed prior to and immediately following the assigned intervention during the first session. Clinical outcomes were assessed at baseline and following 2 weeks of participation in the study. Immediate attenuation of suprathreshold heat response was greatest following SMT (P = .05, partial η(2) = .07). Group-dependent differences were not observed for changes in pain intensity and disability at 2 weeks. Participant satisfaction was greatest following the enhanced placebo SMT. This study was registered at www.clinicaltrials.gov under the identifier NCT01168999., Perspective: The results of this study indicate attenuation of pain sensitivity is greater in response to SMT than the expectation of receiving an SMT. These findings suggest a potential mechanism of SMT related to lessening of central sensitization and may indicate a preclinical effect beyond the expectations of receiving SMT., (Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Traumatic events generate some of the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that, in mice, successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that, whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes, which is accompanied by higher metabolic, synaptic, and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The purpose of this paper was to examine the relationship of sex and pain-related fear in pain intensity reports to thermal stimuli and whether sex differences in reported pain intensity were mediated by pain-related fear. 177 participants, 124 female (23.5 ± 4.5 years old), filled out a demographic and fear of pain questionnaire (FPQ-III). Experimental pain testing was performed using thermal stimuli applied to the lower extremity. Participants rated the intensity of pain using the numerical pain rating scale (NPRS). Independent t-tests, Sobel's test, and linear regression models were performed to examine the relationships between sex, fear of pain, and pain sensitivity. We found significant sex differences for thermal pain threshold temperatures (t = 2.04,  P = 0.04) and suprathreshold pain ratings for 49°C (t = -2.12,  P = 0.04) and 51°C (t = -2.36,  P = 0.02). FPQ-severe score mediated the effect of suprathreshold pain ratings of 49° (t = 2.00,  P = 0.05), 51° (t = 2.07,  P = 0.04), and pain threshold temperatures (t = -2.12,  P = 0.03). There are differences in the pain sensitivity between sexes, but this difference may be mediated by baseline psychosocial factors such as fear of pain.

Background. The flexion relaxation ratio (FRR) has been suggested as a measure of muscular performance in patients with low back pain (LBP). The purpose of this study was to investigate whether the FRR was responsive to acute LBP produced from a delayed onset muscle soreness (DOMS) protocol. Methods. Fifty-one pain-free volunteers performed DOMS to induce LBP. Current pain intensity, trunk flexion range of motion (ROM), and passive straight leg raise (SLR) were measured at baseline, 24 and 48 hours after DOMS. Participants were categorized into pain groups based on reported current pain intensity. Changes in FRR, trunk flexion ROM, and SLR ROM were examined using two-way repeated measures analysis of variance. Results. Pain group was not found to have a significant effect on FRR (F 1,29 = 0.054, P = 0.818), nor were there any two-way interactions for changes in FRR. The pain group had decreased trunk flexion ROM compared to the minimal pain group (F 1,38 = 7.21, P = 0.011), but no decreases in SLR ROM (F 1,38 = 3.51, P = 0.057) over time. Interpretation. There were no differences in FRR based on reported pain intensity of LBP from a DOMS protocol. The responsiveness of FRR might be limited in patients with acute onset LBP of muscular origin.

Background Context: Findings on imaging of noncontractile anatomic abnormalities and the intensity of low back pain have weak associations because of false-positive rates among asymptomatic individuals. This association might be stronger for contractile tissues., Purpose: The purpose of this study was to examine the relationship between location and reports of pain intensity in the low back and exercise-induced muscle damage to the lumbar paraspinal muscles., Study Design: Nondiagnostic observational study in a laboratory setting., Methods: Delayed onset muscle soreness was induced in the low back of healthy pain-free volunteers. Measures of pain intensity (100-mm visual analog scale [VAS]) and location (area on the pain diagram) were taken before and 48 hours after exercise. Muscle damage was quantified using mechanical pain thresholds, motor performance deficits, and transverse relaxation time (T2)-weighted magnetic resonance imaging (MRI). Changes pre- to postexercise in signal intensity on T2-weighted imaging within the erector spinae, pain intensity, pain area, mechanical pain threshold, and isometric torque were assessed using paired t tests. Bivariate correlations were conducted to assess associations among muscle damage, pain intensity, and pain drawing area., Results: Twenty participants volunteered (11 women; average age, 22.3 years; average body mass index, 23.5) for study participation. Reports of pain intensity at 48 hours ranged from 0 to 59 mm on the VAS. Muscle damage was confirmed by reductions in mechanical threshold (p=.011) and motor performance (p<.001) and by changes in T2-weighted MRI (p=.007). This study was powered to find an association of at least r=0.5 to be statistically significant. Correlations of continuous variables revealed no significant correlations between pain intensity and measures of muscle damage (ranging between -0.075 and 0.151). There was a significant association between the remaining torque deficit at 48 hours and pain area., Conclusions: The results of this study indicate that there was no association between the magnitude of muscle damage in the lumbar erector spinae and reported pain intensity in the low back. In future studies, larger cohorts may report statistically significant associations, but our data suggest that there will be low magnitude potentially indicating limited clinical relevance., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: Our primary goals were to determine whether preexisting fear of pain and pain sensitivity contributed to post-exercise pain intensity., Methods: Delayed-onset muscle pain was induced in the trunk extensors of 60 healthy volunteers using an exercise paradigm. Levels of fear of pain and experimental pain sensitivity were measured before exercise. Pain intensity in the low back was collected at 24 and 48 hours post-exercise. Participants were grouped based on pain intensity. Group membership was used as the dependent variable in separate regression models for 24 and 48 hours. Predictor variables included fear, pain sensitivity, torque lost during the exercise protocol, and demographic variables., Results: The final models predicting whether a participant reported clinically meaningful pain intensity at 24 hours only included baseline fear of pain at each level of pain intensity tested. The final model at 48 hours included average baseline pain sensitivity and the loss of muscle performance during the exercise protocol for 1 level of pain intensity tested (greater than 35 mm of 100 mm)., Discussion: Combined, these findings suggest that the initial reports of pain after injury may be more strongly influenced by fear whereas the inflammatory process and pain sensitivity may play a larger role for later pain intensity reports.