Search

BACKGROUND: The cyclooxygenase-2 specific inhibitor valdecoxib has not been approved in the United States for treatment of acute pain. HYPOTHESIS: Valdecoxib 20 mg twice daily or once daily (both with a 40-mg loading dose) is not clinically inferior to tramadol for treating the signs and symptoms of acute ankle pain. STUDY DESIGN: Randomized, controlled clinical trial; Level of evidence, 1. METHODS: Patients (N = 829) with acute first- or second-degree ankle sprain received 7 days' treatment with valdecoxib 20 mg either twice daily or once daily (both with 40-mg loading dose), tramadol 50 mg 4 times daily, or placebo. The primary end point was Patient's Assessment of Ankle Pain visual analog scale on day 4; a test of noninferiority compared valdecoxib with tramadol. RESULTS: On day 4, both valdecoxib doses were significantly better versus placebo and were comparable with tramadol in relieving ankle pain. On day 7, valdecoxib, but not tramadol, significantly reduced pain versus placebo. On days 4 and 7, more patients resumed normal walking with valdecoxib (45%-47% and 73%-79%, respectively) than with placebo (35% and 64%, respectively) or tramadol (38% and 67%, respectively). In contrast to valdecoxib, the number of withdrawals due to adverse events was significantly higher in the tramadol group (12.2% vs 3.4%; P = .0005). CONCLUSIONS: Valdecoxib was comparable with tramadol and was significantly better than placebo in treating acute ankle sprain, and it enabled more patients to resume normal walking on days 4 and 7. Both valdecoxib and tramadol were well tolerated. [ABSTRACT FROM AUTHOR]

Abstract Background Long distance running causes acute muscle damage resulting in inflammation and decreased force production. Endurance athletes use NSAIDs during competition to prevent or reduce pain, which carries the risk of adverse effects. Tart cherries, rich in antioxidant and anti-inflammatory properties, may have a protective effect to reduce muscle damage and pain during strenuous exercise. This study aimed to assess the effects of tart cherry juice as compared to a placebo cherry drink on pain among runners in a long distance relay race. Methods The design was a randomized, double blind, placebo controlled trial. Fifty-four healthy runners (36 male, 18 female; 35.8 ± 9.6 yrs) ran an average of 26.3 ± 2.5 km over a 24 hour period. Participants ingested 355 mL bottles of tart cherry juice or placebo cherry drink twice daily for 7 days prior to the event and on the day of the race. Participants assessed level of pain on a standard 100 mm Visual Analog Scale (VAS) at baseline, before the race, and after the race. Results While both groups reported increased pain after the race, the cherry juice group reported a significantly smaller increase in pain (12 ± 18 mm) compared to the placebo group (37 ± 20 mm) (p < .001). Participants in the cherry juice group were more willing to use the drink in the future (p < 0.001) and reported higher satisfaction with the pain reduction they attributed to the drink (p < 0.001). Conclusions Ingesting tart cherry juice for 7 days prior to and during a strenuous running event can minimize post-run muscle pain.

Background: Fire seasons are longer, with more and larger wildfires, placing increased demands and risks on those fighting wildland fires. There are multiple agencies involved with fighting wildland fires and unique worksite conditions make meeting these workers' needs a challenge., Objective: The aim of the study is to develop and establish the effectiveness of a web-based safety and health program for those fighting wildland fires., Methods: This mixed methods project had 3 phases. The initial qualitative phase assessed the needs of 150 diverse firefighters through interviews and focus groups across 11 US sites to establish and prioritize program content. Interview transcripts were read for thematic content with iterative readings used to identify, code, and rank health and safety issues. The second phase used that information to build a comprehensive Total Worker Health program for those fighting wildfires. The program content was based on the qualitative interview data and consisted of 6 core and 8 elective 30-minute, web-based modules primarily done individually on a smartphone or computer. The final, third phase evaluated the program with a quantitative prospective proof-of-concept, usability, and effectiveness trial among wildland firefighter participants. Effectiveness was assessed with paired 2-tailed t tests for pre- and post-Likert agreement scale survey items, adjusted for multiple comparisons. In addition to assessing mean and SD at baseline and postsurvey, observed effect sizes were calculated (Cohen d). Usability and reaction to the program among firefighters who responded to postsurvey were also assessed., Results: The qualitative themes and subthemes were used to inform the program's content. For the effectiveness trial, 131 firefighters completed the presurvey, and 50 (38.2%) completed the postsurvey. The majority of the participants were White (n=123, 93.9%), male (n=117, 89.3%), with an average age of 41 (SD 12.9) years. Significant increases in knowledge and desired health and safety behaviors were found for both cancer (P<.001) and cardiovascular risk (P=.01), nutrition behaviors (P=.01), hydration or overheating (P=.001), binge drinking (P=.002), and getting medical checkups (P=.001). More than 80% (n=40) of postsurvey respondents agreed or strongly agreed that the program was easy to use and would recommend it to others., Conclusions: An innovative web-based safety and health promotion program for those fighting wildland fires was feasible, scalable, and usable. It improved the health and safety of those fighting wildland fires., Trial Registration: ClinicalTrials.gov NCT05753358; https://classic.clinicaltrials.gov/ct2/show/NCT05753358., (©Kerry Kuehl, Diane Elliot, Carol DeFrancesco, Wendy McGinnis, Susanna Ek, Bharti Garg. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 25.10.2023.)

Background: Correction professionals are a highly stressed workforce with heightened risks for depression, suicide, obesity, cardiovascular disease, and injury. These professionals, largely hidden from view, have received little study concerning means to improve their safety, health, and well-being. In other settings, mindfulness has resulted in lowered stress, along with other benefits. We hypothesized that a program that promoted mindfulness combined with more typical health and safety components could uniquely benefit corrections professionals., Objective: This project will assess a novel scalable, self-administered program to enhance the mindfulness, safety, and health of a vulnerable worker group., Methods: In partnership with the Oregon Department of Corrections, we are conducting a prospective quasi-experimental trial of a safety, health, and mindfulness program among 100 corrections professionals from 2 institutions. Survey and physiologic data will be collected at enrollment, upon weekly program completion (3 months), and at 9 months after enrollment. Primary outcome behaviors promoted by the program are being mindful, healthier eating, more physical activity, and greater restorative sleep. Secondary downstream benefits are anticipated in stress level, mood, positive feelings about the organization, vascular health, and cellular aging, along with job performance, injuries, and economic costs. Participants will meet in-person or in a Zoom-type meeting as 3- to 5-member coworker groups during their usual work hours for 30-minute sessions once a week for 12 weeks. The program uses self-guided web-based learning modules that include brief mindfulness practice, and it is accessible by smartphone, tablet, or laptop. Daily mindfulness practice is encouraged between sessions, which is facilitated by the study website and group format. The modules' structure emphasizes prerequisite knowledge, peer support, skill practice, self-monitoring, and enhancing self-efficacy for change. The program continues through self-directed use of the Headspace app following the 12 weekly sessions., Results: Participants are being enrolled, and the intervention is ready to launch., Conclusions: Although mindfulness training has gained traction for worker well-being, its usual format requires a skilled trainer, an initial retreat, and weekly 2-hour meetings for several weeks. The content is limited to mindfulness without safety or health promotion aspects. The need for skilled trainers and time commitment limits the scalability of the usual mindfulness interventions. The planned program is an innovative combination of technology, e-learning, and a group format to add mindfulness to a safety and health curriculum. If acceptable and effective, the format would facilitate its widespread use., Trial Registration: ClinicalTrials.gov NCT05608889; https://classic.clinicaltrials.gov/ct2/show/NCT05608889., International Registered Report Identifier (irrid): PRR1-10.2196/45535., (©Diane Elliot, Kerry Kuehl, Carol DeFrancesco, Wendy McGinnis, Susanna Ek, Allee Van Horne, Katherine Ginsberg Kempany. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 22.09.2023.)

Eastern equine encephalitis virus (EEEV) is mosquito-borne virus that produces fatal encephalitis in humans. We recently conducted a first of its kind study to investigate EEEV clinical disease course following aerosol challenge in a cynomolgus macaque model utilizing the state-of-the-art telemetry to measure critical physiological parameters. Here, we report the results of a comprehensive pathology study of NHP tissues collected at euthanasia to gain insights into EEEV pathogenesis. Viral RNA and proteins as well as microscopic lesions were absent in the visceral organs. In contrast, viral RNA and proteins were readily detected throughout the brain including autonomic nervous system (ANS) control centers and spinal cord. However, despite presence of viral RNA and proteins, majority of the brain and spinal cord tissues exhibited minimal or no microscopic lesions. The virus tropism was restricted primarily to neurons, and virus particles (~61-68 nm) were present within axons of neurons and throughout the extracellular spaces. However, active virus replication was absent or minimal in majority of the brain and was limited to regions proximal to the olfactory tract. These data suggest that EEEV initially replicates in/near the olfactory bulb following aerosol challenge and is rapidly transported to distal regions of the brain by exploiting the neuronal axonal transport system to facilitate neuron-to-neuron spread. Once within the brain, the virus gains access to the ANS control centers likely leading to disruption and/or dysregulation of critical physiological parameters to produce severe disease. Moreover, the absence of microscopic lesions strongly suggests that the underlying mechanism of EEEV pathogenesis is due to neuronal dysfunction rather than neuronal death. This study is the first comprehensive investigation into EEEV pathology in a NHP model and will provide significant insights into the evaluation of countermeasure., Competing Interests: The authors have declared that no competing interests exist.

Aerobic exercise in type 1 diabetes (T1D) causes rapid increase in glucose utilization due to muscle work during exercise, followed by increased insulin sensitivity after exercise. Better understanding of these changes is necessary for models of exercise in T1D. Twenty-six individuals with T1D underwent three sessions at three insulin rates (100%, 150%, 300% of basal). After 3-h run-in, participants performed 45 min aerobic exercise (moderate or intense). We determined area under the curve for endogenous glucose production (AUC EGP ) and rate of glucose disappearance (AUC Rd ) over 45 min from exercise start. A novel application of linear regression of R d across the three insulin sessions allowed separation of insulin-mediated from non-insulin-mediated glucose uptake before, during, and after exercise. AUC Rd increased 12.45 mmol/L (CI = 10.33-14.58, P < 0.001) and 13.13 mmol/L (CI = 11.01-15.26, P < 0.001) whereas AUC EGP increased 1.66 mmol/L (CI = 1.01-2.31, P < 0.001) and 3.46 mmol/L (CI = 2.81-4.11, P < 0.001) above baseline during moderate and intense exercise, respectively. AUC EGP increased during intense exercise by 2.14 mmol/L (CI = 0.91-3.37, P < 0.001) compared with moderate exercise. There was significant effect of insulin infusion rate on AUC Rd equal to 0.06 mmol/L per % above basal rate (CI = 0.05-0.07, P < 0.001). Insulin-mediated glucose uptake rose during exercise and persisted hours afterward, whereas non-insulin-mediated effect was limited to the exercise period. To our knowledge, this method of isolating dynamic insulin- and non-insulin-mediated uptake has not been previously employed during exercise. These results will be useful in informing glucoregulatory models of T1D. The study has been registered at www.clinicaltrials.gov as NCT03090451. NEW & NOTEWORTHY Separating insulin and non-insulin glucose uptake dynamically during exercise in type 1 diabetes has not been done before. We use a multistep process, including a previously described linear regression method, over three insulin infusion sessions, to perform this separation and can graph these components before, during, and after exercise for the first time.

Objective: The aim of this study was to present safety, health and well-being profiles of workers within five occupations: call center work ( N = 139), corrections ( N = 85), construction ( N = 348), homecare ( N = 149), and parks and recreation ( N = 178). Methods: Baseline data from the Data Repository of Oregon's Healthy Workforce Center were used. Measures were compared with clinical healthcare guidelines and national norms. Results: The prevalence of health and safety risks for adults was as follows: overweight (83.2%), high blood pressure (16.4%), injury causing lost work (9.9%), and reported pain (47.0%). Young workers were least likely to report adequate sleep (46.6%). Construction workers reported the highest rate of smoking (20.7%). All of the adult workers reported significantly lower general health than the general population. Conclusion: The number of workers experiencing poor safety, health and well-being outcomes suggest the need for improved working conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hanson, Rameshbabu, Bodner, Hammer, Rohlman, Olson, Wipfli, Kuehl, Perrin, Alley, Schue, Thompson and Parish.)

Purpose: We determined if a high-intensity aerobic exercise program would be safe, improve expected fitness and clinical outcomes, and alter exploratory phosphorous magnetic resonance spectroscopy (P MRS) outcomes in persons with multiple sclerosis (PwMS)., Methods: This open-label prospective pilot study compared two cohorts of ambulatory PwMS matched for age, sex and V˙O2max. Cohorts underwent 8 wk of high-intensity aerobic exercise (MS-Ex, n = 10) or guided stretching (MS-Ctr, n = 7). Aerobic exercise consisted of four 30-min sessions per week while maintaining ≥70% maximal HR. Changes in cardiorespiratory fitness, clinical outcomes, and P MRS of tibialis anterior (TA) muscle and brain were compared. Cross-sectional P MRS comparisons were made between all MS participants and a separate matched healthy control population., Results: The MS-Ex cohort achieved target increases in V˙O2max (mean, +12.7%; P = <0.001, between-group improvement, P = 0.03). One participant was withdrawn for exercise-induced syncope. The MS-Ex cohort had within-group improvements in fat mass (-5.8%; P = 0.04), lean muscle mass (+2.6%; P = 0.02), Symbol Digit Modalities Test (+15.1%; P = 0.04), and cognitive subscore of the Modified Fatigue Impact Scale (-26%; P = 0.03), whereas only the physical subscore of the Modified Fatigue Impact Scale improved in MS-Ctr (-16.1%; P = 0.007). P MRS revealed significant within-group increases in MS-Ex participants in TA rate constant of phosphocreatine (PCr) recovery (+31.5%; P = 0.03) and adenosine triphosphate/PCr (+3.2%; P = 0.01), and near significant between-group increases in TA PCr recovery rate constant (P = 0.05) but no significant changes in brain P MRS after exercise. Cross-sectional differences existed between MS and healthy control brain PCr/inorganic phosphate (4.61 ± 0.44, 3.93 ± 0.19; P = 0.0019)., Conclusions: High-intensity aerobic exercise in PwMS improved expected cardiorespiratory and clinical outcomes but provoked one serious adverse event. The P MRS may serve to explore underlying mechanisms by which aerobic exercise exerts cerebral benefits.

Purpose: Burkholderia pseudomallei, the tier 1 agent of melioidosis, is a saprophytic microbe that causes endemic infections in tropical regions such as South-East Asia and Northern Australia. It is globally distributed, challenging to diagnose and treat, infectious by several routes including inhalation, and has potential for adversarial use. B. pseudomallei strain MSHR5848 produces two colony variants, smooth (S) and rough (R), which exhibit a divergent range of morphological, biochemical and metabolic phenotypes, and differ in macrophage and animal infectivity. We aimed to characterize two major phenotypic differences, analyse gene expression and study the regulatory basis of the variation., Methodology: Phenotypic expression was characterized by DNA and RNA sequencing, microscopy, and differential bacteriology. Regulatory genes were identified by cloning and bioinformatics.Results/Key findings. Whereas S produced larger quantities of extracellular DNA, R was upregulated in the production of a unique chromosome 1-encoded Siphoviridae-like bacteriophage, φMSHR5848. Exploratory transcriptional analyses revealed significant differences in variant expression of genes encoding siderophores, pili assembly, type VI secretion system cluster 4 (T6SS-4) proteins, several exopolysaccharides and secondary metabolites. A single 3 base duplication in S was the only difference that separated the variants genetically. It occurred upstream of a cluster of bacteriophage-associated genes on chromosome 2 that were upregulated in S. The first two genes were involved in regulating expression of the multiple phenotypes distinguishing S and R., Conclusion: Bacteriophage-associated proteins have a major role in the phenotypic expression of MSHR5848. The goals are to determine the regulatory basis of this phenotypic variation and its role in pathogenesis and environmental persistence of B. pseudomallei.

Background: Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Gram-negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively. Depending on the route of exposure, aerosol or transcutaneous, infection by Bp or Bm can result in an extensive range of disease - from acute to chronic, relapsing illness to fatal septicemia. Both diseases are associated with difficult diagnosis and high fatality rates. About ninety five percent of patients succumb to untreated septicemic infections and the fatality rate is 50 % even when standard antibiotic treatments are administered., Results: The goal of this study is to profile murine macrophage-mediated phenotypic and molecular responses that are characteristic to a collection of Bp, Bm, Burkholderia thailandensis (Bt) and Burkholderia oklahomensis (Bo) strains obtained from humans, animals, environment and geographically diverse locations. Burkholderia spp. (N = 21) were able to invade and replicate in macrophages, albeit to varying degrees. All Bp (N = 9) and four Bm strains were able to induce actin polymerization on the bacterial surface following infection. Several Bp and Bm strains showed reduced ability to induce multinucleated giant cell (MNGC) formation, while Bo and Bp 776 were unable to induce this phenotype. Measurement of host cytokine responses revealed a statistically significant Bm mediated IL-6 and IL-10 production compared to Bp strains. Hierarchical clustering of transcriptional data from 84 mouse cytokines, chemokines and their corresponding receptors identified 29 host genes as indicators of differential responses between the Burkholderia spp. Further validation confirmed Bm mediated Il-1b, Il-10, Tnfrsf1b and Il-36a mRNA expressions were significantly higher when compared to Bp and Bt., Conclusions: These results characterize the phenotypic and immunological differences in the host innate response to pathogenic and avirulent Burkholderia strains and provide insight into the phenotypic alterations and molecular targets underlying host-Burkholderia interactions.

Background: Overweight (OW) and obesity (OB) are endemic in the United States and affect adolescents and adults with congenital heart disease (ACHD). Defining the burden of excess weight on the cardiovascular system in ACHD is the goal of this study. Limitation of exercise capacity due to overweight or obesity might be reversible with weight loss and improve quality of life for ACHD adults., Methods: Exercise tests performed using a Bruce protocol and measurement of maximum oxygen consumption were retrospectively reviewed on 418 CHD patients. OW and OB were defined as the 85-95 or > 95 percentile respectively for age and gender or by adult criteria. Severity of CHD was assigned based on criteria published in standard guidelines., Results: 63 patients had mild, 198 moderate, and 157 severe heart disease. Each ACHD group was 32 to 34% OW or OB. Measured exercise time (ET) of CHD patients with moderate or severe heart disease was less than that of controls in each weight categories. However, OB or OW people have shorter ET than their normal weight peers with CHD. Multiple regression using ET as the dependent variable finds that female sex, relative BMI, and VE/VCO2 at peak exercise are all associated with lesser ET with high significance. Peak heart rate is associated with greater ET, with borderline significance. Severity of heart disease is not independently associated with ET., Conclusions: OW and OB are strongly associated with reduced ET in persons with congenital heart disease. Losing weight may improve exercise capacity in ACHD.

Objective(s): Congenital heart disease (CHD) and heterotaxy patients have increased postoperative and respiratory complications. We recently showed CHD-heterotaxy patients can have respiratory ciliary dysfunction (CD) similar to that associated with primary ciliary dyskinesia, including low nasal nitric oxide and abnormal ciliary motion. In this study, we investigated whether CHD-heterotaxy patients with CD may have worse postsurgical outcomes., Methods: We examined postsurgical outcome in 13 heterotaxy-CHD patients with CD (25 surgeries), compared with 14 heterotaxy-CHD patients without CD (27 surgeries). Outcome data were collected for each surgery, including respiratory complications, tracheostomy, use of inhaled β-agonists or nitric oxide, length of hospital stay, days on ventilator, and death., Results: The CD versus the no-CD CHD cohorts had similar Risk Adjustment in Congenital Heart Surgery-1 risk categories, repair track, age at surgery, and follow-up evaluation times. Respiratory complications (76% vs 37%; P = .006), need for tracheostomy (16% vs 0%; P = .047), and use of inhaled β-agonists (64% vs 11%; P = .0001) all were increased significantly in heterotaxy-CHD patients with CD. No significant differences were detected in postoperative hospital stay, days on mechanical ventilation, or surgical mortality. A trend toward increased mortality for the CD group beyond the postoperative period was observed (33% vs 0%; P = .055) in patients younger than age 10 years., Conclusions: Our findings showed that heterotaxy-CHD patients with CD may have increased risks for respiratory deficiencies. Overall, there was a trend toward increased mortality in CD patients with intermediate follow-up evaluation. Because β-agonists are known to increase ciliary beat frequency, presurgical screening for CD and perioperative treatment of CD patients with inhaled β-agonists may improve postoperative outcomes and survival., (Copyright © 2014 The American Association for Thoracic Surgery. All rights reserved.)

Objectives: The goal of this project was to quantify the prevalence of gaps in cardiology care, identify predictors of gaps, and assess barriers to care among adult congenital heart disease (adult CHD) patients., Background: Adult CHD patients risk interruptions in care that are associated with undesired outcomes., Methods: Patients (18 years of age and older) with their first presentation to an adult CHD clinic completed a survey regarding gaps in, and barriers to, care., Results: Among 12 adult CHD centers, 922 subjects (54% female) were recruited. A >3-year gap in cardiology care was identified in 42%, with 8% having gaps longer than a decade. Mean age at the first gap was 19.9 years. The majority of respondents had more than high school education and knew their heart condition. The most common reasons for gaps included feeling well, being unaware that follow-up was required, and complete absence from medical care. Disease complexity was predictive of a gap in care with 59% of mild, 42% of moderate, and 26% of severe disease subjects reporting gaps (p < 0.0001). Clinic location significantly predicted gaps (p < 0.0001), whereas sex, race, and education level did not. Common reasons for returning to care were new symptoms, referral from provider, and desire to prevent problems., Conclusions: Adult CHD patients have gaps in cardiology care; the first lapse commonly occurred at age ∼19 years, a time when transition to adult services is contemplated. Gaps were more common among subjects with mild and moderate diagnoses and at particular locations. These results provide a framework for developing strategies to decrease gaps and address barriers to care in the adult CHD population., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We report the case of a 41-year-old woman who presented with extensive papillary fibroelastomas of the heart after multiple previous surgical procedures for hypertrophic cardiomyopathy. This case is significant because of the locally aggressive nature of the cardiac papillary fibroelastoma.