Sweat parameters such as volume and chloride concentration may offer invaluable clinical insights for people with CF (PwCF). Pilocarpine-induced sweat collection for chloridometry measurement is the gold-standard for sweat chloride, but this technique is cumbersome and not suitable for remote settings. We have previously reported the utility of a skin-interfaced microfluidic device (CF Patch) in conjunction with a smartphone image processing platform that enables real-time measurement of sweating rates and sodium chloride loss in laboratory and remote settings. Here we conducted clinical studies characterizing the accuracy of the CF Patch compared to pilocarpine-induced sweat measurements using chloridometry and tested the feasibility of exercise-induced sweat chloride measurements in PwCF. The CF Patch demonstrated strong correlations compared to sweat chloride measured by chloridometry across clinic and remote settings and detected greater day-to-day sweat chloride variability in PwCF on CFTR modulators than healthy volunteers. These findings demonstrate that the CF Patch is suitable as a remote management device capable of measuring chloride concentrations and offers the potential of monitoring the efficacy of CF medication regimens.

Objectives To explore pre-doctoral faculty perceptions toward implementation of value-based care (VBC) in didactic and clinical teaching. Methods This project was a collaborative effort between CareQuest and the University of North Carolina at Chapel Hill, Adams School of Dentistry introducing VBC to pre-doctoral dental faculty as part of a new curriculum. Following a faculty development session on VBC in June 2021, faculty and subject matter experts were invited to participate in qualitative interviews. Subject matter experts were interviewed to establish a baseline for VBC knowledge and understanding. Interviews were recorded and transcribed verbatim. Analysis was conducted by two analysts using ATLAS.ti and a thematic analysis approach. Results Six faculty and two subject matter experts participated in interviews. Although dental faculty demonstrated some understanding of VBC, they recognized that more training is required to build in-depth knowledge and implementation strategies for teaching dental students. Faculty discussed value-based concepts such as prevention-focused teaching, person-centered care, and disease management over invasive restoration of teeth, and how VBC is bringing about a paradigm shift in dentistry that needs to be reflected in dental education. They acknowledged a disconnect between VBC in didactic teaching versus clinical instruction. Those interviewed believed it would take time to shift faculty mindset and readiness to teach VBC, and continued efforts are needed at the leadership and faculty level for acceptance and implementation. Conclusions Although dental faculty recognize that VBC can bring a shift in dental practice, more training and guidance to implement it in didactic and clinical teaching is needed.

Objective Patients with meniscal tears reporting meniscal symptoms such as catching or locking have traditionally undergone arthroscopy. The present study was undertaken to investigate whether patients with meniscal tears who report meniscal symptoms have greater improvement with arthroscopic partial meniscectomy (APM) than physical therapy (PT). Methods We used data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial, which randomized participants with knee osteoarthritis (OA) and meniscal tear to APM or PT. The frequency of each meniscal symptom (clicking, catching, popping, intermittent locking, giving way, swelling) was measured at baseline and 6 months. We used linear regression models to determine whether the difference in improvement in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score at 6 months between patients treated with APM versus PT was modified by the presence of each meniscal symptom. We also determined the percentage of participants with resolution of meniscal symptoms by treatment group. Results We included 287 participants. The presence (versus absence) of any of the meniscal symptoms did not modify the improvement in KOOS pain score between APM versus PT by >0.5 SD (all P interaction >0.05). APM led to greater resolution of intermittent locking and clicking than PT (locking 70% versus 46%, clicking 41% versus 25%). No difference in resolution of the other meniscal symptoms was observed. Conclusion Meniscal symptoms were not associated with improved pain relief. Although symptoms of clicking and intermittent locking had a greater reduction in the APM group, the presence of meniscal symptoms in isolation should not inform clinical decisions surrounding APM versus PT in patients with meniscal tear and knee OA.

The use of opioids in United States has had a significant impact on both patients and society. This study aims to describe the prevalence of opioid use prior to primary total knee arthroplasty (TKA) and estimate the opioids use trend following TKA. The electronic medical records (EHR) from the Optum database (2007-2019) were used to identify TKA patients. The EHR data were available for a geographically diverse population of 5.5 million health plan members who have been successfully linked to the Optum EHR database. Preoperative and postoperative opioid use was measured by the number of opioid administration orders. Patients needed to have at least three-months baseline and one-year follow-up to be eligibly included. A total of 207,065 primary TKA were included in this study. Approximately 88.7% of the population had opioid administration three months prior to surgery. The mean number (± standard deviation (SD)) of opioid administration orders per patient had increased from 4.5±4.3 (median: 4) in 2007 to 8.8±4.8 (median: 9) in 2018. The percentage of patients who had opioids prior to surgery was 70% in 2007, 84% in 2012 and 93% in 2018. Around 10% of the cohort had opioid administration three months to six months after surgery (8% in 2007, mean: 0.58±3.01, 10% in 2018, mean: 0.73±3.06). Around 9% of the cohort had opioid administration nine months to twelve months after surgery (6% in 2007, mean: 0.44±3.35, 11% in 2018, mean: 0.73±2.80). Over 88% of TKA patients use opioids within the 3 months prior to surgery and this percentage has increased 23% during the study period. From 2007 to 2018, the mean number of opioid administration orders per patient has increased from 4.5 to 8.8 three months prior to surgery and 0.44 to 0.73 nine months to twelve months after surgery.

Superficial and mostly deep incisional infections after primary total knee arthroplasty (TKA) are associated with significant burden on hospital and the health care system. Risk of deep incisional infection is associated with multiple comorbid conditions and socio-economic factors. This study evaluated superficial infection as an independent risk factor to predict a later deep incisional infection in TKA. This retrospective cohort study used the electronic health records (EHR) from the Optum database (2007-2018) to identify TKA patients. The EHR data were available for a geographically diverse population of 5.5 million health plan members who have been successfully linked to the Optum EHR database. The main independent variable was a record for superficial infection (yes/no) within six-months post-TKA. The dependent variable was presence of a deep incisional infection (yes/no) within 12-months post-TKA. A multivariable logistic regression was developed to evaluate superficial infection as an independent predictor for a later deep incisional infection controlling for demographic and clinical factors. A total of 238,773 patients with primary TKA were identified. Mean (standard deviation, SD) age of the cohort was 66.6 (10.4) years, 62.8% were females and 88.9% patients were Caucasian. Mean Charlson Comorbidity Index (CCI) was 1.2 (1.6). Over the 12-months post-TKA, 2.5% patients developed deep incision infection and the median time to infection was 53 days. Adjusted model showed that the patients with superficial infection have statistically significantly higher odds (odds ratio, [95% Confidence Interval]- 5.0, [4.5-5.6], P<0.0001) of developing deep incisional infection as compared to those without superficial infection. Other significant factors included age, gender, race, CCI, insurance type, body mass index. This study found that superficial infection is an independent predictor of deep incisional infection in TKA; patients with superficial infection have five times higher odds of developing a deep incisional infection than those without.

Patients with bilateral knee arthritis are candidates for total knee arthroplasty and may decide between simultaneous (SIMTKA) or staged bilateral TKA (STATKA). Inconsistent outcomes have been reported for SIMTKA and STATKA. This study aims to compare the deep joint infection following SIMTKA and STATKA surgery. The electronic medical records (EHR) from the Optum database (2007-2019) were used to identify TKA patients. The EHR data were available for a geographically diverse population of 5.5 million health plan members who have been successfully linked to the Optum EHR database. Short interval STATKA was defined as having staged surgery within 2 weeks after the first unilateral TKA. The postoperative outcome assessed was deep joint infection six months after surgery. Multivariable logistic regression was developed to investigate association between surgery type and deep joint infection with age, Elixhauser comorbidity score and provider volume adjustment. A total of 6,135 SMITKA and 8,203 two-week STATKA were included in the analysis. SIMTKA were younger (mean 63±8 vs 66±10, p<0.001), with more comorbidities (Elixhauser score ≥4: 21% vs 18.6%, p<0.001), suffering more pain (back pain: 12.8% vs 6.5%, p<0.001; knee pain diagnosis: 44.6% vs 16.9%, p<0.001), and more likely to be treated in facilities with higher volume of TKA surgeries (annual volume: 120±95 vs 114±149). In the multivariable logistic regression, patients who had simultaneous TKA were more likely to suffer from deep joint infection six month after surgery compared to patients having 2-week staged TKA (aOR: 3.4, 95% CI: 2.2, 5.5, incidence: 1.14% vs 0.33%). This study demonstrates that simultaneous TKA is associated with increase risk of deep joint infection compared to 2-week staged TKA. Studies are warranted to investigate the best interval of staged TKA and to compare other surgical outcomes among SIMTKA and STATKA.

Wednesday, April 29April 14, 2020Free AccessTreatment Strategies in anti-myelin oligodendrocyte glycoprotein (MOG) associated Demyelinating Disease in a Pediatric Cohort (933)Anita Fletcher, John Wright, and Michael SweeneyAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.933 Letters to the Editor

Background: Increasingly, drug and device clinical trials are tracking activity levels and other quality of life indices as endpoints for therapeutic efficacy. Trials have traditionally required intermittent subject visits to the clinic that are artificial, activity-intensive, and infrequent, making trend and event detection between visits difficult. Thus, there is an unmet need for wearable sensors that produce clinical quality and medical grade physiological data from subjects in the home. The current study was designed to validate the BioStamp nPoint® system (MC10 Inc., Lexington, MA, USA), a new technology designed to meet this need. Objective: To evaluate the accuracy, performance, and ease of use of an end-to-end system called the BioStamp nPoint. The system consists of an investigator portal for design of trials and data review, conformal, low-profile, wearable biosensors that adhere to the skin, a companion technology for wireless data transfer to a proprietary cloud, and algorithms for analyzing physiological, biometric, and contextual data for clinical research. Methods: A prospective, nonrandomized clinical trial was conducted on 30 healthy adult volunteers over the course of two continuous days and nights. Supervised and unsupervised study activities enabled performance validation in clinical and remote (simulated “at home”) environments. System outputs for heart rate (HR), heart rate variability (HRV) (including root mean square of successive differences [RMSSD] and low frequency/high frequency ratio), activity classification during prescribed activities (lying, sitting, standing, walking, stationary biking, and sleep), step count during walking, posture characterization, and sleep metrics including onset/wake times, sleep duration, and respiration rate (RR) during sleep were evaluated. Outputs were compared to FDA-cleared comparator devices for HR, HRV, and RR and to ground truth investigator observations for activity and posture classifications, step count, and sleep events. Results: Thirty participants (77% male, 23% female; mean age 35.9 ± 10.1 years; mean BMI 28.1 ± 3.6) were enrolled in the study. The BioStamp nPoint system accurately measured HR and HRV (correlations: HR = 0.957, HRV RMSSD = 0.965, HRV ratio = 0.861) when compared to ActiheartTM. The system accurately monitored RR (mean absolute error [MAE] = 1.3 breaths/min) during sleep when compared to a Capnostream35TM end-tidal CO2 monitor. When compared with investigator observations, the system correctly classified activities and posture (agreement = 98.7 and 92.9%, respectively), step count (MAE = 14.7, < 3% of actual steps during a 6-min walk), and sleep events (MAE: sleep onset = 6.8 min, wake = 11.5 min, sleep duration = 13.7 min) with high accuracy. Participants indicated “good” to “excellent” usability (average System Usability Scale score of 81.3) and preferred the BioStamp nPoint system over both the Actiheart (86%) and Capnostream (97%) devices. Conclusions: The present study validated the BioStamp nPoint system’s performance and ease of use compared to FDA-cleared comparator devices in both the clinic and remote (home) environments.

BackgroundKnee osteoarthritis (OA) is among the most common and disabling persistent pain conditions, with increasing prevalence in the developed world, and affects women to a greater degree than men. In the USA, the growth of knee OA has been paralleled by an increase in rates of total knee arthroplasty (TKA), a surgical treatment option for late-stage knee OA. While TKA outcomes are generally good, postoperative trajectories of pain vary widely, with some patients reporting a complete absence of pain, but with a significant minority reporting worsening pain. Biopsychosocial factors, including anxiety and depression, are known to contribute importantly to the experience of joint pain, with women reporting a higher degree of negative affective symptoms.MethodsThis study investigated sex differences in TKA outcomes in age-matched groups of men and women at two academic medical centers. Pain and physical function were assessed in 100 patients (50 men and 50 women) during the perioperative period (preoperative visit6weeks postsurgical). The association of preoperative negative affect (anxiety and depression scores) to postoperative pain and function was evaluated, with specific attention to sex differences in this relationship.ResultsOverall, women reported more baseline pain-related physical dysfunction (although not higher baseline pain scores), as well as higher acute postoperative pain scores during the 2weeks following TKA than their male counterparts. By 6weeks postoperatively, sex differences in reported pain were no longer evident. Interestingly, although women reported higher preoperative levels of emotional distress than men, preoperative anxiety and depression scores were better predictors of severe postoperative pain among men than women, throughout the postoperative test period.ConclusionsThis study underlines the importance of considering sex and psychosocial factors, as well as their interaction, in understanding postsurgical pain trajectories.

Background: Postoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up. Methods: This study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method-based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months. Results: One hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small (r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07-1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72-1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71-2.09). Conclusions: Delirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.

Fibroblasts regulate tissue homeostasis, coordinate inflammatory responses, and mediate tissue damage. In rheumatoid arthritis (RA), synovial fibroblasts maintain chronic inflammation which leads to joint destruction. Little is known about fibroblast heterogeneity or if aberrations in fibroblast subsets relate to pathology. Here, we show functional and transcriptional differences between fibroblast subsets from human synovial tissues using bulk transcriptomics of targeted subpopulations and single-cell transcriptomics. We identify seven fibroblast subsets with distinct surface protein phenotypes, and collapse them into three subsets by integrating transcriptomic data. One fibroblast subset, characterized by the expression of proteins podoplanin, THY1 membrane glycoprotein and cadherin-11, but lacking CD34, is threefold expanded in patients with RA relative to patients with osteoarthritis. These fibroblasts localize to the perivascular zone in inflamed synovium, secrete proinflammatory cytokines, are proliferative, and have an in vitro phenotype characteristic of invasive cells. Our strategy may be used as a template to identify pathogenic stromal cellular subsets in other complex diseases.

Balance impairment is common in individuals with multiple sclerosis (MS). However, objective assessment of balance usually requires clinical expertise and/or the use of expensive and obtrusive measuring equipment. These barriers to the objective assessment of balance may be overcome with the development of a lightweight inertial sensor system. In this study, we examined the concurrent validity of a novel wireless, skin-mounted inertial sensor system (BioStamp®, MC10 Inc.) to measure postural sway in individuals with MS by comparing measurement agreement between this novel sensor and gold standard measurement tools (force plate and externally validated inertial sensor). A total of 39 individuals with MS and 15 healthy controls participated in the study. Participants with MS were divided into groups based on the amount of impairment (MSMild: EDSS 2–4, n = 19; MSSevere: EDSS ≥6, n = 20). The balance assessment consisted of two 30-s quiet standing trials in each of three conditions: eyes open/firm surface, eyes closed/firm surface, and eyes open/foam surface. For each trial, postural sway was recorded with a force plate (Bertec) and simultaneously using two accelerometers (BioStamp and Xsens) mounted on the participant’s posterior trunk at L5. Sway metrics (sway area, sway path length, root mean square amplitude, mean velocity, JERK, and total power) were derived to compare the measurement agreement among the measurement devices. Excellent agreement (intraclass correlation coefficients >0.9) between sway metrics derived from the BioStamp and the MTx sensors were observed across all conditions and groups. Good to excellent correlations (r >0.7) between devices were observed in all sway metrics and conditions. Additionally, the acceleration sway metrics were nearly as effective as the force plate sway metrics in differentiating individuals with poor balance from healthy controls. Overall, the BioStamp sensor is a valid and objective measurement tool for postural sway assessment. This novel, lightweight and portable sensor may offer unique advantages in tracking patient’s postural performance.

OBJECTIVE:The primary objective of this study was to examine the day-to-day association between physical activity and pain intensity among a sample of patients with knee osteoarthritis (KOA) and the potential moderation of this association by negative cognitive processes. METHODS:In this micro-longitudinal daily diary study, KOA patients (N = 121) completed questionnaires assessing pain (Brief Pain Inventory) and psychosocial functioning (pain catrophizing scale, WOMAC McMaster Universities Osteoarthritis Index function, Patient-Reported Outcomes Measurement Information System [PROMIS; anxiety and depression], the Godin-Shephard Leisure-Time Physical Activity questionnaire, the six-minute walking test) and were then asked to report their levels of physical activity and pain intensity once per day for a period of seven days using an electronic diary. RESULTS:Multilevel modeling analyses indicated that day-to-day increases in physical activity were associated with heightened levels of pain intensity (B = 0.13 SE = 0.03, P < 0.001). In addition, it was revealed that the association between physical activity and pain intensity was moderated by catastrophizing (B = -0.01 SE = 0.002, P < 0.05), with patients scoring higher in catastrophizing showing a relatively stronger link between day-to-day physical activity and increased knee pain. This effect was specific to catastrophizing, as depression and anxiety did not moderate the activity-pain relationship (P > 0.05). CONCLUSIONS:Our findings suggest that increases in daily physical activity are associated with concurrent increases in KOA patients' levels of knee pain, particularly among patients reporting higher levels of pain catastrophizing. These results may have clinical implications for the design and testing of interventions targeted at reducing catastrophizing and increasing physical activity among patients with chronic osteoarthritis pain.

OBJECTIVE:Synovitis is a feature of knee osteoarthritis (OA) and meniscal tear and has been associated with articular cartilage damage. This study was undertaken to examine the associations of baseline effusion-synovitis and changes in effusion-synovitis with changes in cartilage damage in a cohort with OA and meniscal tear.METHODS:We analyzed data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial of surgery versus physical therapy for treatment of meniscal tear. We performed semiquantitative grading of effusion-synovitis and cartilage damage on magnetic resonance imaging, and dichotomized effusion-synovitis as none/small (minimal) and medium/large (extensive). We assessed the association of baseline effusion-synovitis and changes in effusion-synovitis with changes in cartilage damage size and depth over 18 months, using Poisson regression models. Analyses were adjusted for patient demographic characteristics, treatment, and baseline cartilage damage.RESULTS:We analyzed 221 participants. Over 18 months, effusion-synovitis was persistently minimal in 45.3% and persistently extensive in 21.3% of the patients. The remaining 33.5% of the patients had minimal synovitis on one occasion and extensive synovitis on the other. In adjusted analyses, patients with extensive effusion-synovitis at baseline had a relative risk (RR) of progression of cartilage damage depth of 1.7 (95% confidence interval [95% CI] 1.0-2.7). Compared to those with persistently minimal effusion-synovitis, those with persistently extensive effusion-synovitis had a significantly increased risk of progression of cartilage damage depth (RR 2.0 [95% CI 1.1-3.4]).CONCLUSION:Our findings indicate that the presence of extensive effusion-synovitis is associated with subsequent progression of cartilage damage over 18 months. The persistence of extensive effusion-synovitis over time is associated with the greatest risk of concurrent cartilage damage progression.

Introduction: Clinical assessment of motor symptoms in Parkinson's disease (PD) is subjective and may not reflect patient real-world experience. This two-part pilot study evaluated the accuracy of the NIMBLE wearable biosensor patch (containing an accelerometer and electromyography sensor) to record body movements in clinic and home environments versus clinical measurement of motor symptoms. Methods: Patients (Hoehn & Yahr 2-3) had motor symptom fluctuations and were on a stable levodopa dose. Part 1 investigated different sensor body locations (six patients). In Part 2, 21 patients wore four sensors (chest, and most affected side of shin, forearm and back-of-hand) during a 2-day clinic- and 1-day home-based evaluation. Patients underwent Unified Parkinson's Disease Rating Scale assessments on days 1-2, and performed pre-defined motor activities at home on day 3. An algorithm estimated motor-symptom severity (predicted scores) using patch data (in-clinic); this was compared with in-clinic motor symptom assessments (observed scores). Results: The overall correlation coefficient between in-clinic observed and sensor algorithm-predicted scores was 0.471 (p = 0.031). Predicted and observed scores were identical 45% of the time, with a predicted score within a +/- 1 range 91% of the time. Exact accuracy for each activity varied, ranging from 32% (pronation/supination) to 67% (rest-tremor-amplitude). Patients rated the patch easy-to-use and as providing valuable data for managing PD symptoms. Overall patch-adhesion success was 97.2%. The patch was safe and generally well tolerated. Conclusions: This study showed a correlation between sensor algorithm-predicted and clinician-observed motor symptom scores. Algorithm refinement using patient populations with greater symptom-severity range may potentially improve the correlation.

Peripheral nerves are often vulnerable to damage during surgeries, with risks of significant pain, loss of motor function, and reduced quality of life for the patient. Intraoperative methods for monitoring nerve activity are effective, but conventional systems rely on bench-top data acquisition tools with hard-wired connections to electrode leads that must be placed percutaneously inside target muscle tissue. These approaches are time and skill intensive and therefore costly to an extent that precludes their use in many important scenarios. Here we report a soft, skin-mounted monitoring system that measures, stores, and wirelessly transmits electrical signals and physical movement associated with muscle activity, continuously and in real-time during neurosurgical procedures on the peripheral, spinal, and cranial nerves. Surface electromyography and motion measurements can be performed non-invasively in this manner on nearly any muscle location, thereby offering many important advantages in usability and cost, with signal fidelity that matches that of the current clinical standard of care for decision making. These results could significantly improve accessibility of intraoperative monitoring across a broad range of neurosurgical procedures, with associated enhancements in patient outcomes.