Publications by authors named "Christopher King"

508 Publications

Antifibrotic Therapies and Progressive Fibrosing Interstitial Lung Disease (PF-ILD): Building on INBUILD.

J Clin Med 2021 May 25;10(11). Epub 2021 May 25.

Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, VA 22042, USA.

Progressive fibrosing interstitial lung disease (PF-ILD) describes a phenotypic subset of interstitial lung diseases characterized by progressive, intractable lung fibrosis. PF-ILD is separate from, but has radiographic, histopathologic, and clinical similarities to idiopathic pulmonary fibrosis. Two antifibrotic medications, nintedanib and pirfenidone, have been approved for use in patients with idiopathic pulmonary fibrosis. Recently completed randomized controlled trials have demonstrated the clinical efficacy of antifibrotic therapy in patients with PF-ILD. The validation of efficacy of antifibrotic therapy in PF-ILD has changed the treatment landscape for all of the fibrotic lung diseases, providing a new treatment pathway and opening the door for combined antifibrotic and immunosuppressant drug therapy to address both the fibrotic and inflammatory components of ILD characterized by mixed pathophysiologic pathways.
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http://dx.doi.org/10.3390/jcm10112285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197477PMC
May 2021

Guided Relaxation-Based Virtual Reality for Acute Postoperative Pain and Anxiety: A Pilot Study in a Pediatric Population.

J Med Internet Res 2021 May 4. Epub 2021 May 4.

Cincinnati Childrens Hospital Medical Center, 3333 Burnet AvenueMLC 2001, Cincinnati, US.

Background: Distraction-based therapies, such as virtual reality (VR), have been used to reduce pain during acutely painful procedures. However, distraction alone cannot produce the prolonged pain reduction required to manage sustained postoperative pain. Integration of VR with other pain reducing therapies, like guided relaxation, may enhance its clinical impact.

Objective: The goal of this pilot study was to assess the association of a single guided relaxation-based VR (VR-GR) session with a reduction in postoperative pain and anxiety in children. We also explored whether pain catastrophizing and anxiety sensitivity influenced this association.

Methods: A total of 51 children and adolescents (7-21 years) with postoperative pain followed by the Acute Pain Service at Cincinnati Children's Hospital were recruited over an 8-month period to undergo a single VR-GR session. Prior to VR, patients completed pain catastrophizing (PCS-C) and anxiety sensitivity (CASI) questionnaires. The primary outcome was change in pain intensity following VR-GR (immediately, 15, and 30 minutes). Secondary outcomes included changes in pain unpleasantness and anxiety.

Results: VR-GR decreased pain intensity immediately (p < 0.001) and 30 minutes (p = 0.04) after the VR session, but not at 15 minutes (p = 0.16) post-session. Reductions in pain unpleasantness were observed during all time intervals (p < 0.001 at all intervals). Anxiety was reduced immediately (p = 0.02) but not at 15- (p = 0.08) or 30- (p = 0.30) minutes following VR-GR. Patients with higher CASI reported greater reductions in pain intensity (p = 0.04) and unpleasantness (p = 0.01) following VR-GR. Pain catastrophizing was not associated with changes in pain and anxiety.

Conclusions: A single, short VR-GR session showed transient reductions in pain intensity, pain unpleasantness, and anxiety in children and adolescents with acute postoperative pain. These results encourage a future randomized clinical trial assessing efficacy of VR-GR.

Clinicaltrial: Clinical Trials ID: NCT04556747.
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http://dx.doi.org/10.2196/26328DOI Listing
May 2021

Supplementing the Subinternship: Effect of E-learning Modules on Subintern Knowledge and Confidence.

Am J Med 2021 May 19. Epub 2021 May 19.

Assistant Professor of Medicine and Pediatrics, Division of Hospital Medicine, Associate Director, Core Clerkship in Pediatrics, Director, Advanced Clerkship in Internal Medicine at Johns Hopkins Hospital, Johns Hopkins University School of Medicine.

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http://dx.doi.org/10.1016/j.amjmed.2021.04.012DOI Listing
May 2021

The Role of Surgical Lung Biopsy in the Diagnosis of Fibrotic Interstitial Lung Disease: Perspective from the Pulmonary Fibrosis Foundation.

Ann Am Thorac Soc 2021 May 18. Epub 2021 May 18.

University of California, San Francisco, Department of Medicine, San Francisco, California, United States.

Diagnosis of interstitial lung disease (ILD) requires a multidisciplinary diagnosis (MDD) approach that includes clinicians, radiologists, and pathologists. Surgical lung biopsy (SLB) is currently the recommended standard in obtaining pathological specimens for patients with ILD requiring a tissue diagnosis. The increased diagnostic confidence and accuracy provided by microscopic pathology assessment of SLB specimens must be balanced with the associated risks in ILD patients. This document was developed by the Surgical Lung Biopsy Working Group of the Pulmonary Fibrosis Foundation, composed of a multidisciplinary group of ILD physicians including pulmonologists, radiologists, pathologists, and thoracic surgeons. In this document, we present an up-to-date literature review of the indications, contraindications, risks, and alternatives to SLB in the diagnosis of fibrotic ILD, outline an integrated approach to the decision-making around SLB in the diagnosis of fibrotic ILD, and provide practical information to maximize the yield and safety of SLB.
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http://dx.doi.org/10.1513/AnnalsATS.202009-1179FRDOI Listing
May 2021

Incidence and prognostic significance of pleural effusions in pulmonary arterial hypertension.

Pulm Circ 2021 Apr-Jun;11(2):20458940211012366. Epub 2021 Apr 28.

Advanced Lung Disease and Transplant Center, Inova Fairfax Hospital, Falls Church, VA, USA.

It has been suggested pleural effusions may develop in right heart failure in the absence of left heart disease. The incidence and prognostic significance of pleural effusions in pulmonary arterial hypertension is uncertain. Patients with pulmonary arterial hypertension followed at our tertiary care center were reviewed. Survival was examined based on the subsequent development of a pleural effusion. A total of 191 patients with pulmonary arterial hypertension met the inclusion criteria. The prevalence of pleural effusions on initial assessment was 7.3%. Among patients without a pleural effusion on initial imaging and at least one follow-up computerized tomography ( = 142), pleural effusion developed in 27.5% ( = 39) of patients. No alternative etiology of the effusion was identified in 19 (48.7%) cases and effusions deemed related to pulmonary arterial hypertension occurred at an incident rate of 38.6 cases per 1000 person-years. Of these, 14 (73.7%) were bilateral, 3 (15.8%) were right-sided, and 2 (10.5%) were left-sided. Effusion size was trace or small in 18 patients (94.7%). Development of a new pleural effusion was associated with attenuated survival in unadjusted survival analysis (HR: 3.80; 95% CI: 1.55-9.31), multivariate analysis (HR: 5.13; 95% CI: 1.86-14.16), and after the multivariate model was adjusted for concomitant pericardial effusion (HR: 4.86; 95% CI: 1.51-15.71). Negative impact on survival remained unchanged when effusions more likely related to an alternative cause were removed from analysis. In conclusion, pleural effusions can complicate pulmonary arterial hypertension in the absence of left heart disease. These effusions are frequently small in size, bilateral in location, and their presence is associated with decreased survival. Attenuated survival appears independent of the risk associated with a new pericardial effusion.
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http://dx.doi.org/10.1177/20458940211012366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108083PMC
April 2021

Reduced BNT162b2 mRNA vaccine response in SARS-CoV-2-naive nursing home residents.

Clin Infect Dis 2021 May 16. Epub 2021 May 16.

Case Western Reserve University School of Medicine, Cleveland, OH, USA.

After BNT162b2 mRNA vaccination, antibody levels to spike, receptor binding domain (RBD) and virus neutralization were examined in 149 nursing home (NH) residents and 110 health care worker controls. SARS-CoV-2-naive NH residents median post-2nd vaccine dose antibody neutralization titers are ¼ that of SARS-CoV-2-naive healthcare workers.
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http://dx.doi.org/10.1093/cid/ciab447DOI Listing
May 2021

Triple-Drug Treatment Is Effective for Lymphatic Filariasis Microfilaria Clearance in Samoa.

Trop Med Infect Dis 2021 Apr 1;6(2). Epub 2021 Apr 1.

School of Public Health, The University of Queensland, Brisbane, QLD 4006, Australia.

Following the first triple-drug mass drug administration (MDA) for lymphatic filariasis in Samoa in 2018, unexpected persistence of microfilaria (Mf) positivity in 18 (15%) of 121 antigen-positive persons was observed in a nationwide household survey 1-2 months later. Of the 18 Mf positive persons, 14 reported taking the MDA, raising concerns about MDA efficacy. In 2019, 5-6 months after the 2018 survey, a monitored treatment study was done to evaluate directly observed weight-based treatment in these Mf positive individuals. Mf presence and density were assessed before and 7 days after treatment, using 1 mL membrane filtered venous blood, and 60 uL thick blood films on slides prepared from venous or fingerprick blood. All 14 participants were still Mf positive on filters from venous blood pre-treatment samples, but two were negative by slide made from the same samples. Mf were cleared completely by day 7 in 12 of 13 participants followed up, and by day 30 in the remaining participant. Filtered blood using EDTA samples (to reduce clumping of Mf) is preferred over slides alone for improving the likelihood of detecting Mf and estimating their density. The triple-drug MDA strategy was effective at clearing Mf when given and taken at the correct dose.
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http://dx.doi.org/10.3390/tropicalmed6020044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167748PMC
April 2021

Impact of the new definition for pulmonary hypertension in patients with lung disease: an analysis of the United Network for Organ Sharing database.

Pulm Circ 2021 Apr-Jun;11(2):2045894021999960. Epub 2021 Mar 30.

University of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig University Giessen, Giessen, Germany.

The implications of the recent change in the definition of pulmonary hypertension on epidemiology and outcomes are not known. We sought to determine the percentage of patients with the two most common lung diseases that would be reclassified regarding the presence/absence of pulmonary hypertension with the revised definition. A query of the United Network for Organ Sharing database was performed. The percentage of patients meeting the current and previous definition of pulmonary hypertension was described. Outcomes of patients stratified by the current and previous definitions were compared. There were 15,563 patients with right heart catheterization data analyzed. Pulmonary hypertension was more prevalent in both chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis under the new definition at 52.4% versus 82.4%, and 47.6% versus 73.6%, respectively. "Pre-capillary" pulmonary hypertension by the new definition was lower at 28.1% for chronic obstructive pulmonary disease and 36.8% for idiopathic pulmonary fibrosis. Of the patients with pulmonary hypertension by the old definition, 23.9% of chronic obstructive pulmonary disease patients and 18.7% of idiopathic pulmonary fibrosis patients were not classified as pulmonary hypertension by the new definition. Conversely, 15.9% of chronic obstructive pulmonary disease patients and 15.1% of idiopathic pulmonary fibrosis patients who did not meet diagnostic criteria for pulmonary hypertension by the old definition did have pulmonary hypertension by the new definition. Patients in both disease categories had shorter transplant-free waitlist survival in the presence of pulmonary hypertension by both the new and old definitions. There was a trend toward the new definition of pre-capillary pulmonary hypertension better discerning outcomes compared to the old definition of pulmonary hypertension in idiopathic pulmonary fibrosis patients. Most patients with advanced lung disease who are listed for lung transplantation have pulmonary hypertension, but fewer have pre-capillary pulmonary hypertension than pulmonary hypertension by the old definition. Both the old and new definition of precapillary pulmonary hypertension appear to discern outcomes among the two groups of lung disease analyzed, with some evidence to suggest that the new definition performs slightly better in the idiopathic pulmonary fibrosis population.
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http://dx.doi.org/10.1177/2045894021999960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020109PMC
March 2021

Does 1-minute walk test predict results of 6-minute walk test in patients with idiopathic pulmonary fibrosis?

Sarcoidosis Vasc Diffuse Lung Dis 2021 31;38(1):e2021005. Epub 2021 Mar 31.

Inova Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, VA, USA.

Background: The six-minute walk test (6MWT) is a readily available tool used to evaluate functional capacity in patients with idiopathic pulmonary fibrosis (IPF). However, it is often logistically challenging to perform in the context of a busy clinical practice. We sought to investigate if the 1MWT distance (1MWD) predicts the 6MWT distance (6MWD), and if an abbreviated walk could accurately predict outcomes in IPF patients.

Methods: Baseline demographics and pulmonary function testing of IPF patients evaluated at a tertiary referral center between 2010 and 2017 were collected. 6MWT variables at baseline as well as 1 and 6 minutes were collected. Time to death, lung transplantation, or most recent follow-up was ascertained.

Results: There were 177 patients, the majority of whom (80%) were male. The mean age was 67 ± 9 years and mean FVC was 64 ± 18% predicted. Forty eight (27%) patients used oxygen supplementation during the 6MWT. The median 6MWD was 366 meters (IQR: 268-471) while the median 1MWD was 65 meters (IQR: 46-81). Stratified by the median, 89 patients were "High Walkers" based on the 6MWD ≥ 366m (HW) and 88 patients were "Low Walkers" (LW). HW had a higher FVC% (70 ± 15 vs 57 ± 18, p= 0.001), higher DLCO% (45 ± 12 vs 34 ± 14, p= 0.001) and higher 1MWD (83 ± 28 vs 47 ± 16, m p= 0.001). Median transplant-free survival was better in HW vs LW (27 ± 16 vs 22 ± 18 months, log rank p= 0.018). There was a strong correlation between the 1MWD and the 6MWD (r= 0.91, Spearman's correlation, p < 0.0001). Also, the transplant-free survival curves stratified by 1MWD were very similar to the curves for 6MWD, showing a lower survival in the LW cohort (log rank p= 0.009).

Conclusion: The 1MWD obtained during the first minute of a 6MWD shows a strong correlation to total 6MWD and retains its ability to predict transplant-free survival. 1MWT may serve as a practical substitute for the more cumbersome 6MWT. Our findings require further validation prospectively in larger cohorts of IPF patients.
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http://dx.doi.org/10.36141/svdld.v38i1.9258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050623PMC
March 2021

Measuring and Quantifying Collateral Information in Psychiatry: Development and Preliminary Validation of the McLean Collateral Information and Clinical Actionability Scale.

JMIR Ment Health 2021 Apr 14;8(4):e25050. Epub 2021 Apr 14.

Division of Geriatric Psychiatry, McLean Hospital, Belmont, MA, United States.

Background: The review of collateral information is an essential component of patient care. Although this is standard practice, minimal research has been done to quantify collateral information collection and to understand how collateral information translates to clinical decision making. To address this, we developed and piloted a novel measure (the McLean Collateral Information and Clinical Actionability Scale [M-CICAS]) to evaluate the types and number of collateral sources viewed and the resulting actions made in a psychiatric setting.

Objective: This study aims to test the feasibility of the M-CICAS, validate this measure against clinician notes via medical records, and evaluate whether reviewing a higher volume of collateral sources is associated with more clinical actions taken.

Methods: For the M-CICAS, we developed a three-part instrument, focusing on measuring collateral sources reviewed, clinical actions taken, and shared decision making between the clinician and patient. To determine feasibility and preliminary validity, we piloted this measure among clinicians providing psychotherapy at McLean Hospital. These clinicians (n=7) completed the M-CICAS after individual clinical sessions with 89 distinct patient encounters. Scales were completed by clinicians only once for each patient during routine follow-up visits. After clinicians completed these scales, researchers conducted chart reviews by completing the M-CICAS using only the clinician's corresponding note from that session. For the analyses, we generated summary scores for the number of collateral sources and clinical actions for each encounter. We examined Pearson correlation coefficients to assess interrater reliability between clinicians and chart reviewers, and simple univariate regression modeling followed by multilevel mixed effects regression modeling to test the relationship between collateral information accessed and clinical actions taken.

Results: The study staff had high interrater reliability on the M-CICAS for the sources reviewed (r=0.98; P<.001) and actions taken (r=0.97; P<.001). Clinician and study staff ratings were moderately correlated and statistically significant on the M-CICAS summary scores for the sources viewed (r=0.24, P=.02 and r=0.25, P=.02, respectively). Univariate regression modeling with a two-tailed test demonstrated a significant association between collateral sources and clinical actions taken when clinicians completed the M-CICAS (β=.27; t=2.47; P=.02). The multilevel fixed slopes random intercepts model confirmed a significant association even when accounting for clinician differences (β=.23; t=2.13; P=.04).

Conclusions: This pilot study established the feasibility and preliminary validity of the M-CICAS in assessing collateral sources and clinical decision making in psychiatry. This study also indicated that reviewing more collateral sources may lead to an increased number of clinical actions following a session.
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http://dx.doi.org/10.2196/25050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082386PMC
April 2021

Development and Validation of a Clinical Diagnostic Scoring System for the Diagnosis of IPF.

Ann Am Thorac Soc 2021 Apr 12. Epub 2021 Apr 12.

Inova Fairfax Hospital, 23146, Advanced Lung Disease Program, Falls Church, Virginia, United States.

Rationale: Interpreting the radiological data in conjunction with an objective clinical score could help to harmonize IPF diagnostic and improve accuracy.

Objectives: We sought to establish and validate a multivariable objective scoring model based on clinical parameters, by stratifying the risk for patients to be diagnosed as IPF versus other forms of interstitial lung disease (ILD).

Methods: A clinical score was derived from review of patients evaluated at the Inova Fairfax ILD program and validated in three distinct cohorts. Based on known IPF clinical characteristics, a multivariable model was created and assessed by receiver operator curve (ROC) characteristics.

Results: There were 844 ILD patients diagnosed as either IPF (n=347, 41%) or non-IPF ILD (n=497, 59%). Based on calculated odds ratios, a score was assigned to each of the following clinical parameters: age, sex, smoking history, ethnicity, ILD family history, exposures, presence of CTD signs or symptoms, and Velcro crackles. The final Fairfax IPF clinical score (FICS) ranged from 1 to 25. The clinical diagnostic score system was accurate in predicting IPF, as measured by the area under the curve (AUC 0.88) in the derivation cohort with similar AUCs of 0.91, 0.81 and 0.71 in the respective validation cohorts.

Conclusion: The FICS appears to be an accurate tool for estimating the pretest probability of IPF in patients with ILD. How the FICS performs in conjunction with the various HRCT patterns remains to be determined. This model could ultimately be useful for increasing the degree of confidence in the final diagnosis and help to obviate the need for lung biopsy in cases of non-UIP patterns on HRCT.
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http://dx.doi.org/10.1513/AnnalsATS.202011-1430OCDOI Listing
April 2021

Reduced BNT162b2 mRNA vaccine response in SARS-CoV-2-naive nursing home residents.

medRxiv 2021 Mar 22. Epub 2021 Mar 22.

Case Western Reserve University School of Medicine, Cleveland, OH.

The SARS-CoV-2 pandemic impact on nursing home (NH) residents prompted their prioritization for early vaccination. To fill the data gap for vaccine immunogenicity in NH residents, we examined antibody levels after BNT162b2 mRNA vaccine to spike, receptor binding domain (RBD) and for virus neutralization in 149 NH residents and 111 health care worker controls. SARS-CoV-2-naive NH residents mount antibody responses with nearly 4-fold lower median neutralization titers and half the anti-spike level compared to SARS-CoV-2-naive healthcare workers. By contrast, SARS-CoV-2-recovered vaccinated NH residents had neutralization, anti-spike and anti-RBD titers similar to SARS-CoV-2-recovered vaccinated healthcare workers. NH residents' blunted antibody responses have important implications regarding the quality and durability of protection afforded by neoantigen vaccines. We urgently need better longitudinal evidence on vaccine effectiveness specific to NH resident populations to inform best practices for NH infection control measures, outbreak prevention and potential indication for a vaccine boost.
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http://dx.doi.org/10.1101/2021.03.19.21253920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010759PMC
March 2021

Use of Machine Learning to Develop and Evaluate Models Using Preoperative and Intraoperative Data to Identify Risks of Postoperative Complications.

JAMA Netw Open 2021 03 1;4(3):e212240. Epub 2021 Mar 1.

Institute for Informatics, Washington University in St Louis School of Medicine, St Louis, Missouri.

Importance: Postoperative complications can significantly impact perioperative care management and planning.

Objectives: To assess machine learning (ML) models for predicting postoperative complications using independent and combined preoperative and intraoperative data and their clinically meaningful model-agnostic interpretations.

Design, Setting, And Participants: This retrospective cohort study assessed 111 888 operations performed on adults at a single academic medical center from June 1, 2012, to August 31, 2016, with a mean duration of follow-up based on the length of postoperative hospital stay less than 7 days. Data analysis was performed from February 1 to September 31, 2020.

Main Outcomes And Measures: Outcomes included 5 postoperative complications: acute kidney injury (AKI), delirium, deep vein thrombosis (DVT), pulmonary embolism (PE), and pneumonia. Patient and clinical characteristics available preoperatively, intraoperatively, and a combination of both were used as inputs for 5 candidate ML models: logistic regression, support vector machine, random forest, gradient boosting tree (GBT), and deep neural network (DNN). Model performance was compared using the area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using Shapley Additive Explanations by transforming model features into clinical variables and representing them as patient-specific visualizations.

Results: A total of 111 888 patients (mean [SD] age, 54.4 [16.8] years; 56 915 [50.9%] female; 82 533 [73.8%] White) were included in this study. The best-performing model for each complication combined the preoperative and intraoperative data with the following AUROCs: pneumonia (GBT), 0.905 (95% CI, 0.903-0.907); AKI (GBT), 0.848 (95% CI, 0.846-0.851); DVT (GBT), 0.881 (95% CI, 0.878-0.884); PE (DNN), 0.831 (95% CI, 0.824-0.839); and delirium (GBT), 0.762 (95% CI, 0.759-0.765). Performance of models that used only preoperative data or only intraoperative data was marginally lower than that of models that used combined data. When adding variables with missing data as input, AUROCs increased from 0.588 to 0.905 for pneumonia, 0.579 to 0.848 for AKI, 0.574 to 0.881 for DVT, 0.5 to 0.831 for PE, and 0.6 to 0.762 for delirium. The Shapley Additive Explanations analysis generated model-agnostic interpretation that illustrated significant clinical contributors associated with risks of postoperative complications.

Conclusions And Relevance: The ML models for predicting postoperative complications with model-agnostic interpretation offer opportunities for integrating risk predictions for clinical decision support. Such real-time clinical decision support can mitigate patient risks and help in anticipatory management for perioperative contingency planning.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.2240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010590PMC
March 2021

Improvements in Sleep Correlate With Improvements in Clinical Outcomes Among Adolescents Undergoing Intensive Interdisciplinary Pain Treatment.

Clin J Pain 2021 Jun;37(6):443-453

Divisions of Behavioral Medicine and Clinical Psychology.

Objectives: Intensive interdisciplinary pain treatment (IIPT) programs have been shown to restore function, improve coping, and reduce pain in adolescents with chronic pain. Yet, little is known about patients' sleep during IIPT and whether or not improvements in pain treatment outcomes are associated with changes in sleep pre-to-post IIPT treatment. The objectives of the current study were to describe sleep among adolescents entering IIPT and examine associations between sleep parameters and IIPT treatment effects.

Materials And Methods: Self-reported sleep measures and clinical outcomes (eg, functional disability, coping, average pain), were collected from 44 adolescents (mean age=14.57, 68.2% female) at admission and discharge from an inpatient IIPT program. Wrist-worn actigraphy data and sleep diaries from participants' first week and last week in the program were analyzed to characterize sleep parameters.

Results: Participants self-reported poor sleep/wake patterns, high levels of insomnia symptoms, and subclinical problems with daytime sleepiness upon admission into IIPT, although actigraphic indices of sleep from the first week of IIPT admission were only just under clinical guidelines for healthy adolescent sleep. Better self-reported sleep quality assessed via aggregated sleep diaries from the first week was associated with improvement in average pain and disability over the course of the program. Furthermore, improvements in insomnia symptoms and daytime sleepiness throughout the program were positively correlated with concurrent improvements in functional disability and coping.

Discussion: Taken together, results suggest that sleep may be associated with IIPT treatment effects and pave the way for future research to continue examining these relationships.
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http://dx.doi.org/10.1097/AJP.0000000000000936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102426PMC
June 2021

Extracorporeal life support for cardiogenic shock during pregnancy and postpartum: a single center experience.

Perfusion 2021 Mar 26:2676591211004369. Epub 2021 Mar 26.

INOVA Cardiac and Thoracic Surgery, INOVA Fairfax Hospital, Falls Church, VA, USA.

Background: The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for cardiogenic shock in pregnant and postpartum patients remains limited by concerns of bleeding, hemolysis, and fetal risks. This case series examines the underlying characteristics and management strategies for this high-risk population.

Methods: All pregnant and post-partum patients who underwent VA ECMO in the cardiovascular intensive care unit between January 1, 2016 and November 1, 2019, were included in this retrospective study. Management of maternal and fetal O delivery, left ventricular (LV) unloading, anticoagulation, and ECMO circuit characteristics were evaluated.

Results: Five patients required veno-arterial ECMO for restoration of systemic perfusion. Three patients developed peripartum cardiomyopathy, one septic cardiomyopathy, and one acute right ventricular (RV) failure. The median age was 30.6 years, with median gestational age in pregnant patients of 31 weeks. Maternal and fetal survival to discharge was 80%. Bleeding was the primary complication, with two patients requiring blood transfusions; one requiring interventional radiology (IR) embolization and the other requiring surgical intervention to control bleeding. One patient was successfully delivered on VA ECMO. No fetal complications were directly attributed to VA ECMO.

Conclusions: VA ECMO can be employed successfully in obstetric patients with cardiogenic shock with appropriate patient selection. Further research is needed to determine if VA ECMO provides a survival advantage over traditional management strategies in this vulnerable population.
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http://dx.doi.org/10.1177/02676591211004369DOI Listing
March 2021

Naturally acquired blocking human monoclonal antibodies to Plasmodium vivax reticulocyte binding protein 2b.

Nat Commun 2021 03 9;12(1):1538. Epub 2021 Mar 9.

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.

Plasmodium vivax preferentially invades reticulocytes and recognition of these cells is mediated by P. vivax Reticulocyte Binding Protein 2b (PvRBP2b) binding to human Transferrin receptor 1 (TfR1) and Transferrin (Tf). Longitudinal cohort studies in Papua New Guinea, Thailand and Brazil show that PvRBP2b antibodies are correlated with protection against P. vivax infection and disease. Here, we isolate and characterize anti-PvRBP2b human monoclonal antibodies from two individuals in Cambodia with natural P. vivax infection. These antibodies bind with high affinities and map to different regions of PvRBP2b. Several human antibodies block PvRBP2b binding to reticulocytes and inhibit complex formation with human TfR1-Tf. We describe different structural mechanisms for functional inhibition, including either steric hindrance with TfR1-Tf or the reticulocyte membrane. These results show that naturally acquired human antibodies against PvRBP2b can inhibit its function which is important for P. vivax invasion.
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http://dx.doi.org/10.1038/s41467-021-21811-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943553PMC
March 2021

Individual efficacy and community impact of ivermectin, diethylcarbamazine and albendazole mass drug administration for lymphatic filariasis control in Fiji: a cluster randomised trial.

Clin Infect Dis 2021 Mar 17. Epub 2021 Mar 17.

Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.

Background: Bancroftian filariasis remains endemic in Fiji despite over 10 years of mass drug administration (MDA) using diethylcarbamazine and albendazole (DA). The addition of ivermectin to this combination (IDA) has improved efficacy of microfilarial clearance at 12 months in individually randomised trials in nocturnal transmission settings, but impact in a setting of diurnally subperiodic filarial transmission has not been evaluated.

Methods: This cluster randomised study compared the individual efficacy and community impact of IDA versus DA as MDA for lymphatic filariasis in 35 villages on two islands of Fiji. Participants were tested at enrolment for circulating filarial antigen and, if positive, for microfilariae (Mf). Weight-dosed treatment was offered according to village randomisation. Communities were visited at 12 months and retested for lymphatic filariasis. Infected individuals from Rotuma retested at 24 months.

Results: 3816 participants were enrolled and 3616 treated. At 12 months, Mf clearance was achieved in 72 of 111 participants detected with infection at baseline, with no difference in efficacy between treatment groups: DA 69.2%, 95% CI 57.2-79.1% versus IDA 62.5%, 43.6-78.2%, risk difference 11.3 %, 95% CI -10-32.7%, P = 0.30. There was no difference between treatment groups in community prevalence of Mf at 12 months or individual clearance at 24 months.

Conclusions: We found no difference between IDA and DA in individual clearance or community prevalence of lymphatic filariasis at 12 months, and no improved efficacy following a second annual round of IDA. Possible explanations for the apparent lack of benefit of IDA compared to DA include drug and parasite factors affecting clearance, and higher than expected re-infection rates.
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http://dx.doi.org/10.1093/cid/ciab202DOI Listing
March 2021

Semiannual Treatment of Albendazole Alone is Efficacious for Treatment of Lymphatic Filariasis: A Randomized Open-label Trial in Cote d'Ivoire.

Clin Infect Dis 2021 Mar 1. Epub 2021 Mar 1.

Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Background: Ivermectin (IVM) plus albendazole (ALB), or IA, is widely used in mass drug administration (MDA) programs that aim to eliminate lymphatic filariasis (LF) in Africa. However, IVM can cause severe adverse events in persons with heavy Loa loa infections that are common in Central Africa. ALB is safe in loiasis, but more information is needed on its efficacy for LF. This study compared the efficacy and safety of three years of semiannual treatment with ALB to annual IA in persons with bancroftian filariasis.

Methods: Adults with Wuchereria bancrofti microfilaremia (Mf) were randomized to receive either three annual doses of IA (N=52), six semiannual doses of ALB 400mg (N=45), or six semiannual doses of ALB 800mg (N=47). The primary outcome amicrofilaremia at 36 months.

Findings: IA was more effective for completely clearing Mf than ALB 400mg or ALB 800mg (79%, CI 67-91; vs. 48%, CI 32-66 and 57%, CI 41-73, respectively). Mean % reductions in Mf counts at 36 months relative to baseline tended to be greater after IA (98%, CI 88-100) than after ALB 400mg (88%, CI 78-98) and ALB 800mg (89%, CI 79-99) (P=0.07 and P=0.06, respectively). Adult worm nest numbers (assessed by ultrasound) were reduced in all treatment groups. Treatments were well tolerated.

Interpretation: Repeated semiannual treatment with ALB is macrofilaricidal for W. bancrofti and leads to sustained reductions in Mf counts. This is a safe and effective regimen that could be used as MDA to eliminate LF in areas ivermectin cannot be used.
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http://dx.doi.org/10.1093/cid/ciab194DOI Listing
March 2021

Leveraging Virtual Reality and Augmented Reality to Combat Chronic Pain in Youth: Position Paper From the Interdisciplinary Network on Virtual and Augmented Technologies for Pain Management.

J Med Internet Res 2021 Apr 26;23(4):e25916. Epub 2021 Apr 26.

Mighty Immersion, Inc., New York, NY, United States.

Background: Virtual reality (VR) and augmented reality (AR) interventions are emerging as promising tools in the treatment of pediatric chronic pain conditions. However, in this young field, there is little consensus to guide the process of engaging in the development and evaluation of targeted VR-based interventions.

Objective: The INOVATE-Pain (Interdisciplinary Network on Virtual and Augmented Technologies for Pain management) consortium aims to advance the field of VR for pediatric chronic pain rehabilitation by providing guidance for best practices in the design, evaluation, and dissemination of VR-based interventions targeting this population.

Methods: An interdisciplinary meeting of 16 academics, clinicians, industry partners, and philanthropy partners was held in January 2020.

Results: Reviewing the state of the field, the consortium identified important directions for research-driven innovation in VR and AR clinical care, highlighted key opportunities and challenges facing the field, and established a consensus on best methodological practices to adopt in future efforts to advance the research and practice of VR and AR in pediatric pain. The consortium also identified important next steps to undertake to continue to advance the work in this promising new area of digital health pain interventions.

Conclusions: To realize the promise of this realm of innovation, key ingredients for success include productive partnerships among industry, academic, and clinical stakeholders; a uniform set of outcome domains and measures for standardized evaluation; and widespread access to the latest opportunities, tools, and resources. The INOVATE-Pain collaborative hopes to promote the creation, rigorous yet efficient evaluation, and dissemination of innovative VR-based interventions to reduce pain and improve quality of life for children.
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http://dx.doi.org/10.2196/25916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111507PMC
April 2021

A multicenter, community-based, mixed methods assessment of the acceptability of a triple drug regimen for elimination of lymphatic filariasis.

PLoS Negl Trop Dis 2021 Mar 3;15(3):e0009002. Epub 2021 Mar 3.

Washington University, St. Louis, Missouri, United States of America.

Background: Many countries will not reach elimination targets for lymphatic filariasis in 2020 using the two-drug treatment regimen (diethylcarbamazine citrate [DEC] and albendazole [DA]). A cluster-randomized, community-based safety study performed in Fiji, Haiti, India, Indonesia and Papua New Guinea tested the safety and efficacy of a new regimen of ivermectin, DEC and albendazole (IDA).

Methodology/principal Findings: To assess acceptability of IDA and DA, a mixed methods study was embedded within this community-based safety study. The study objective was to assess the acceptability of IDA versus DA. Community surveys were performed in each country with randomly selected participants (>14 years) from the safety study participant list in both DA and IDA arms. In depth interviews (IDI) and focus group discussions (FGD) assessed acceptability-related themes. In 1919 individuals, distribution of sex, microfilariae (Mf) presence and circulating filarial antigenemia (CFA), adverse events (AE) and age were similar across arms. A composite acceptability score summed the values from nine indicators (range 9-36). The median (22.5) score indicated threshold of acceptability. There was no difference in scores for IDA and DA regimens. Mean acceptability scores across both treatment arms were: Fiji 33.7 (95% CI: 33.1-34.3); Papua New Guinea 32.9 (95% CI: 31.9-33.8); Indonesia 30.6 (95% CI: 29.8-31.3); Haiti 28.6 (95% CI: 27.8-29.4); India 26.8 (95% CI: 25.6-28) (P<0.001). AE, Mf or CFA were not associated with acceptability. Qualitative research (27 FGD; 42 IDI) highlighted professionalism and appreciation for AE support. No major concerns were detected about number of tablets. Increased uptake of LF treatment by individuals who had never complied with MDA was observed.

Conclusions/significance: IDA and DA regimens for LF elimination were highly and equally acceptable in individuals participating in the community-based safety study in Fiji, Haiti, India, Indonesia, and Papua New Guinea. Country variation in acceptability was significant. Acceptability of the professionalism of the treatment delivery was highlighted.
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http://dx.doi.org/10.1371/journal.pntd.0009002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928496PMC
March 2021

Association of D-dimer and Fibrinogen With Hypercoagulability in COVID-19 Requiring Extracorporeal Membrane Oxygenation.

J Intensive Care Med 2021 Jun 1;36(6):689-695. Epub 2021 Mar 1.

Department of Advanced Lung Disease and Transplant, 23146Inova Fairfax Hospital, Falls Church, VA, USA.

Background: D-dimer concentration has been used by institutions to identify candidates for intensified anticoagulant treatment for venous thromboembolism prevention and for the mitigation of the microthrombotic complications associated with COVID-19. Thromboelastography (TEG) maximum amplitude (MA) has been validated as a marker of hypercoagulability and MA ≥68 mm has been utilized as a marker of hypercoagulability in other conditions.

Methods: The goal of this study was to evaluate the relationship between coagulation, inflammatory, and TEG parameters in patients with COVID-19 on extracorporeal membrane oxygenation (ECMO). We performed a single-center retrospective analysis of consecutive patients that received ECMO for the treatment of COVID-19. TEG, inflammatory, and coagulation markers were compared in patients with and without a thrombotic complication. Correlation tests were performed to identify the coagulation and inflammatory markers that best predict hypercoagulability as defined by an elevated TEG MA.

Results: A total of 168 TEGs were available in 24 patients. C-reactive protein and fibrinogen were significantly higher in patients that developed a thrombotic event versus those that did not ( = 0.04 and = 0.04 respectively). D-dimer was negatively correlated with TEG MA ( < 0.01), while fibrinogen was positively correlated ( < 0.01). A fibrinogen >441 mg/dL was found to have a sensitivity of 91.2% and specificity of 85.7% for the detection of MA ≥68 mm.

Conclusions: In critically ill patients with COVID-19 treated with ECMO, D-dimer concentration had an inverse relationship with degree of hypercoagulability as measured by TEG MA. D-dimer elevation may potentially reflect hemostatic perturbation in patients on ECMO or the severity of COVID-19 related sepsis rather than designate patients likely to benefit from anticoagulation. Fibrinogen concentration may represent a more useful marker of hypercoagulability in this population.
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http://dx.doi.org/10.1177/0885066621997039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145413PMC
June 2021

Ascertaining Design Requirements for Postoperative Care Transition Interventions.

Appl Clin Inform 2021 01 24;12(1):107-115. Epub 2021 Feb 24.

Department of Anesthesiology, School of Medicine, Washington University, St. Louis, Missouri, United States.

Background: Handoffs or care transitions from the operating room (OR) to intensive care unit (ICU) are fragmented and vulnerable to communication errors. Although protocols and checklists for standardization help reduce errors, such interventions suffer from limited sustainability. An unexplored aspect is the potential role of developing personalized postoperative transition interventions using artificial intelligence (AI)-generated risks.

Objectives: This study was aimed to (1) identify factors affecting sustainability of handoff standardization, (2) utilize a human-centered approach to develop design ideas and prototyping requirements for a sustainable handoff intervention, and (3) explore the potential role for AI risk assessment during handoffs.

Methods: We conducted four design workshops with 24 participants representing OR and ICU teams at a large medical academic center. Data collection phases were (1) open-ended questions, (2) closed card sorting of handoff information elements, and (3) scenario-based design ideation and prototyping for a handoff intervention. Data were analyzed using thematic analysis. Card sorts were further tallied to characterize handoff information elements as core, flexible, or unnecessary.

Results: Limited protocol awareness among clinicians and lack of an interdisciplinary electronic health record (EHR)-integrated handoff intervention prevented long-term sustainability of handoff standardization. Clinicians argued for a handoff intervention comprised of core elements (included for all patients) and flexible elements (tailored by patient condition and risks). They also identified unnecessary elements that could be omitted during handoffs. Similarities and differences in handoff intervention requirements among physicians and nurses were noted; in particular, clinicians expressed divergent views on the role of AI-generated postoperative risks.

Conclusion: Current postoperative handoff interventions focus largely on standardization of information transfer and handoff processes. Our design approach allowed us to visualize accurate models of user expectations for effective interdisciplinary communication. Insights from this study point toward EHR-integrated, "flexibly standardized" care transition interventions that can automatically generate a patient-centered summary and risk-based report.
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http://dx.doi.org/10.1055/s-0040-1721780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904383PMC
January 2021

Systemic nicotine enhances opioid self-administration and modulates the formation of opioid-associated memories partly through actions within the insular cortex.

Sci Rep 2021 Feb 8;11(1):3321. Epub 2021 Feb 8.

Program in Behavioral Neuroscience, Department of Psychology, The State University of New York University at Buffalo, 214 Park Hall, Buffalo, NY, 14260, USA.

Habitual use of nicotine containing products increases propensity to misuse prescription opioids and its prevalence is substantially increased in individuals currently involved in opioid-treatment programs. Nicotine enhances self-administration of many classes of drugs in rodents, though evidence for direct effects on opioids is lacking. We sought to measure the effects of nicotine pretreatment on the reinforcing efficacy of opioids in both self-administration and contextual conditioning paradigms. First, we measured the effect of systemic nicotine pretreatment on self-administration of two opioids. Additionally, we measured the degree to which systemic nicotine pretreatment impacts the formation of morphine-associated contextual memories in conditioned taste avoidance and place preference paradigms. Given the involvement of the insula in the maintenance of substance abuse, its importance in nicotine addiction, and findings that insular inactivation impairs contextual drug conditioning, we examined whether nicotine administered directly to the insula could recapitulate the effects of systemic nicotine. We demonstrate that systemic nicotine pretreatment significantly enhances opioid self-administration and alters contextual conditioning. Furthermore, intra-insula nicotine similarly altered morphine contextual conditioning by blocking the formation of taste avoidance at all three morphine doses tested (5.0, 10, and 20 mg/kg), while shifting the dose-response curve of morphine in the place preference paradigm rightward. In conclusion, these data demonstrate that nicotine facilitates opioid intake and is partly acting within the insular cortex to obfuscate aversive opiate memories while potentiating approach to morphine-associated stimuli at higher doses.
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http://dx.doi.org/10.1038/s41598-021-81955-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870813PMC
February 2021

Systemic nicotine enhances opioid self-administration and modulates the formation of opioid-associated memories partly through actions within the insular cortex.

Sci Rep 2021 Feb 8;11(1):3321. Epub 2021 Feb 8.

Program in Behavioral Neuroscience, Department of Psychology, The State University of New York University at Buffalo, 214 Park Hall, Buffalo, NY, 14260, USA.

Habitual use of nicotine containing products increases propensity to misuse prescription opioids and its prevalence is substantially increased in individuals currently involved in opioid-treatment programs. Nicotine enhances self-administration of many classes of drugs in rodents, though evidence for direct effects on opioids is lacking. We sought to measure the effects of nicotine pretreatment on the reinforcing efficacy of opioids in both self-administration and contextual conditioning paradigms. First, we measured the effect of systemic nicotine pretreatment on self-administration of two opioids. Additionally, we measured the degree to which systemic nicotine pretreatment impacts the formation of morphine-associated contextual memories in conditioned taste avoidance and place preference paradigms. Given the involvement of the insula in the maintenance of substance abuse, its importance in nicotine addiction, and findings that insular inactivation impairs contextual drug conditioning, we examined whether nicotine administered directly to the insula could recapitulate the effects of systemic nicotine. We demonstrate that systemic nicotine pretreatment significantly enhances opioid self-administration and alters contextual conditioning. Furthermore, intra-insula nicotine similarly altered morphine contextual conditioning by blocking the formation of taste avoidance at all three morphine doses tested (5.0, 10, and 20 mg/kg), while shifting the dose-response curve of morphine in the place preference paradigm rightward. In conclusion, these data demonstrate that nicotine facilitates opioid intake and is partly acting within the insular cortex to obfuscate aversive opiate memories while potentiating approach to morphine-associated stimuli at higher doses.
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http://dx.doi.org/10.1038/s41598-021-81955-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870813PMC
February 2021

Sensitivity to food and cocaine cues are independent traits in a large sample of heterogeneous stock rats.

Sci Rep 2021 Jan 26;11(1):2223. Epub 2021 Jan 26.

Behavioral Neuroscience Program, Department of Psychology, University At Buffalo, Park Hall B72, Buffalo, NY, 14260, USA.

Sensitivity to cocaine and its associated stimuli ("cues") are important factors in the development and maintenance of addiction. Rodent studies suggest that this sensitivity is related, in part, to the propensity to attribute incentive salience to food cues, which, in turn, contributes to the maintenance of cocaine self-administration, and cue-induced relapse of drug-seeking. Whereas each of these traits has established links to drug use, the relatedness between the individual traits themselves has not been well characterized in preclinical models. To this end, the propensity to attribute incentive salience to a food cue was first assessed in two distinct cohorts of 2716 outbred heterogeneous stock rats (HS; formerly N:NIH). We then determined whether each cohort was associated with performance in one of two paradigms (cocaine conditioned cue preference and cocaine contextual conditioning). These measure the unconditioned locomotor effects of cocaine, as well as conditioned approach and the locomotor response to a cocaine-paired floor or context. There was large individual variability and sex differences among all traits, but they were largely independent of one another in both males and females. These findings suggest that these traits may contribute to drug-use via independent underlying neuropsychological processes.
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http://dx.doi.org/10.1038/s41598-020-80798-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838206PMC
January 2021

A Two-Generation Education Intervention and Children's Attendance in Head Start.

Child Dev 2020 11 8;91(6):1916-1933. Epub 2020 Aug 8.

The University of Texas at Austin.

Two-generation human capital programs seek to promote the education of parents and children simultaneously. This study examines relations between family participation in CareerAdvance, which recruits parents of Head Start children into a workforce training program, and children's Head Start attendance. The sample included 293 children (on average 4 years old) and their parents. After one semester, CareerAdvance children demonstrated higher rates of attendance and lower rates of absence and chronic absence (missing 10% or more of school days) than matched comparison children. These associations were similar across a range of high- and low-risk subgroups at baseline. These findings are discussed in terms of the implications of a family systems approach for improving children's Head Start attendance.
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http://dx.doi.org/10.1111/cdev.13397DOI Listing
November 2020

Preliminary evidence for conserved transcriptional response to adversity in adults with temporomandibular disorder.

Pain Rep 2021 Jan-Feb;6(1):e874. Epub 2021 Jan 8.

Psychiatry and Biobehavioral Sciences and Medicine, University of California, Los Angeles, CA, USA.

Temporomandibular disorder (TMD) is one of the most common orofacial pain conditions. Alteration in immune functioning is one promising biological mechanism underlying pain in TMD. However, there is a gap in the understanding of molecular bases contributing to altered immune functioning in these patients.

Objectives: In the current study, we investigated whether individuals with TMD would exhibit differential activity of 3 specific transcription factors involved in inflammatory (nuclear factor-kappa B, NF-kB), antiviral (interferon-regulatory factors, IRF), and sympathetic (cAMP response element-binding protein, CREB) processes using a promoter-based bioinformatics analysis, which is characterized as the "Conserved Transcriptional Response to Adversity."

Methods: Adults with TMD (n = 19) and without (n = 17) underwent a standardized clinical examination for TMD. A blood sample was collected for genome-wide transcriptional RNA profiling. Bioinformatic analyses tested for differential prevalence of proinflammatory and antiviral transcription factor activity in core promoter sequences from all genes showing >1.2-fold differential expression in TMD vs controls.

Results: Promoter-based bioinformatic analyses of genome-wide transcriptome profiles confirmed upregulation of genes bearing response elements for proinflammatory transcription factor (NF-kB, = 0.002) and downregulation of genes with response elements for IRF ( = 0.037) in patients with TMD relative to controls. Results also indicated upregulated activity of CREB in patients with TMD ( = 0.08), consistent with increased activity of the sympathetic nervous system.

Conclusion: These results provide initial support that the regulation of immune pathways is altered in individuals with TMD. A shift of transcriptional resources to a proinflammatory state may be driven by psychosocial stress and contributes to symptoms associated with TMD.
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http://dx.doi.org/10.1097/PR9.0000000000000874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803915PMC
January 2021

Sleep among Youth with Severely Disabling Chronic Pain: Before, during, and after Inpatient Intensive Interdisciplinary Pain Treatment.

Children (Basel) 2021 Jan 12;8(1). Epub 2021 Jan 12.

Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Poor sleep is commonly reported in pediatric chronic pain. There are signals that intensive interdisciplinary pain treatments (IIPT) may inadvertently improve objective sleep, but this claim cannot be substantiated without baseline sleep data prior to IIPT. This study followed the objective sleep/wake patterns (e.g., duration, quality, timing, consistency) of pediatric patients with severely functionally disabling chronic pain before, during, and after inpatient IIPT (the Functional Independence Restoration Program-"FIRST Program"), alongside a similarly-disabled chronic pain Comparison Group. The final sample included = 10 FIRST Patients and = 9 Comparison Group patients. At baseline, the whole sample showed healthy sleep duration (~9 h), average sleep efficiency <90%, late sleep onset and offset (mean = 11:56 p.m.-8:50 a.m.), and highly inconsistent sleep schedules night to night. During IIPT, FIRST Patients maintained healthy sleep durations, moved sleep schedules 2 h earlier, and decreased timing and duration variability by >60 min while the Comparison Group maintained similar sleep to baseline. At follow up (1-2 months later), FIRST Patients' sleep schedules shifted later but were still less variable than at baseline. Results point to the malleability of sleep/wake patterns within treatment contexts with strict environmental control but suggest that these gains may be difficult for youth with chronic pain to maintain in the home environment.
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http://dx.doi.org/10.3390/children8010042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828171PMC
January 2021

Idiopathic pulmonary fibrosis patients with severe physiologic impairment: characteristics and outcomes.

Respir Res 2021 Jan 6;22(1). Epub 2021 Jan 6.

Inova Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA, 22042, USA.

Research Question: There is no widely accepted grading system for IPF disease severity, although physiologic impairment based on pulmonary function testing is frequently employed. We sought to describe clinical and functional characteristics as well as outcomes of patients with severe physiologic impairment.

Patients And Methods: IPF patients with severe physiologic impairment defined by FVC ≤ 50% and/or DLco ≤ 30% predicted evaluated in the Inova Advanced Lung Disease Program between 2011 and 2019 were included. Demographic, physiologic, functional treatment and outcome data were collated.

Results: There were 531 patients with IPF evaluated of whom 242 (46%) had severe physiologic impairment. Mean age was 72 ± 8 years; baseline FVC was 53 ± 17% and DL 28 ± 9% of predicted. The mean 6 min walks test (6MWT) distance was 304 ± 121 m with 59% of the patients requiring supplemental oxygen ([Formula: see text] group). There was a poor correlation between the 6MWT distance and both FVC% and DLco%. Patients in the 6MWT group had a better transplant-free survival than the [Formula: see text] group (p = 0.002). Patients managed before October 2014 and not receiving antifibrotic therapy had worse outcomes with reduced transplant-free survival compared with patients presenting after this date who did receive antifibrotic therapy (n = 113) (log rank p < 0.0001).

Conclusion: IPF patients often present with severe physiologic impairment which may be poorly correlated with their functional status. Assessment of IPF disease severity should not be based on physiologic impairment alone, but should also encompass functional status as well as need for supplemental oxygen. Antifibrotic therapy in patients with severe physiologic impairment is associated with improved outcomes.
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http://dx.doi.org/10.1186/s12931-020-01600-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788925PMC
January 2021

Guided relaxation-based virtual reality versus distraction-based virtual reality or passive control for postoperative pain management in children and adolescents undergoing Nuss repair of pectus excavatum: protocol for a prospective, randomised, controlled trial (FOREVR Peds trial).

BMJ Open 2020 12 30;10(12):e040295. Epub 2020 Dec 30.

Division of Behavioral Medicine and Clinical Psychology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Introduction: Virtual reality (VR) offers an innovative method to deliver non-pharmacological pain management. Distraction-based VR (VR-D) using immersive games to redirect attention has shown short-term pain reductions in various settings. To create lasting pain reduction, VR-based strategies must go beyond distraction. Guided relaxation-based VR (VR-GR) integrates pain-relieving mind-body based guided relaxation with VR, a novel therapy delivery mechanism. The primary aim of this study is to assess the impact of daily VR-GR, VR-D and 360 video (passive control) on pain intensity. We will also assess the impact of these interventions on pain unpleasantness, anxiety and opioid and benzodiazepine consumption. The secondary aim of this study will assess the impact of psychological factors (anxiety sensitivity and pain catastrophising) on pain following VR.

Methods And Analysis: This is a single centre, prospective, randomised, clinical trial. Ninety children/adolescents, aged 8-18 years, presenting for Nuss repair of pectus excavatum will be randomised to 1 of 3 study arms (VR-GR, VR-D and 360 video). Patients will use the Starlight Xperience (Google Daydream) VR suite for 10 min. Patients randomised to VR-GR (n=30) will engage in guided relaxation/mindfulness with the Aurora application. Patients randomised to VR-D (n=30) will play 1 of 3 distraction-based games, and those randomised to the 360 video (n=30) will watch the Aurora application without audio instructions or sound. Primary outcome is pain intensity. Secondary outcomes include pain unpleasantness, anxiety and opioid and benzodiazepine consumption.

Ethics And Dissemination: This study follows Standard Protocol Items: Recommendations for Interventional Trials guidelines. The protocol was approved by the Cincinnati Children's Hospital Medical Center's institutional review board. Patient recruitment began in July 2020. Written informed consent will be obtained for all participants. All information acquired will be disseminated via scientific meetings and published in peer-reviewed journals.

Trial Registration Number: NCT04351776.
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http://dx.doi.org/10.1136/bmjopen-2020-040295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780540PMC
December 2020