397 research outputs found

    Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design.

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    ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024

    Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design.

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    IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options. REGISTRATION: NCT05172024

    Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

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    IMPORTANCE: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. OBJECTIVE: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: PASC and 44 participant-reported symptoms (with severity thresholds). RESULTS: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. CONCLUSIONS AND RELEVANCE: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC

    Improvements in Outcomes and Cost after Adult Spinal Deformity Corrective Surgery between 2008 and 2019.

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    STUDY DESIGN: Retrospective cohort. OBJECTIVE: To assess whether patient outcomes and cost effectiveness of adult spinal deformity (ASD) surgery have improved over the past decade. BACKGROUND: Surgery for ASD is an effective intervention, but one that is also associated with large initial healthcare expenditures. Changes in the cost profile for ASD surgery over the last decade has not been evaluated previously. METHODS: ASD patients who received surgery between 2008-19 were included. ANCOVA was used to marginal means for outcome measures (complication rates, reoperations, HRQLs, total cost, utility gained, QALYs, cost efficiency [cost per QALY]) by year of initial surgery. Cost was calculated using the PearlDiver database and represented national averages of Medicare reimbursement for services within a 30-day window including length of stay and death differentiated by complication/comorbidity, revision, and surgical approach. Internal cost data was based on individual patient DRG codes, limiting revisions to those within 2Y of the initial surgery. Cost per QALY over the course of 2008-2019 were then calculated. RESULTS: There were 1236 patients included. There was an overall decrease in rates of any complication (0.78 vs. 0.61), any reoperation (0.25 vs. 0.10), and minor complication (0.54 vs. 0.37) between 2009 and 2018 (all P CONCLUSION: Between 2008 and 2019, rates of complications have decreased concurrently with improvements in patient reported outcomes, resulting in improved cost effectiveness according to national Medicare average and individual patient cost data. The value of ASD surgery has improved substantially over the course of the last decade

    Chemical Tomography in a Fresh Wildland Fire Plume: A Large Eddy Simulation (LES) Study

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    Wildland fires involve complicated processes that are challenging to represent in chemical transport models. Recent airborne measurements reveal remarkable chemical tomography in fresh wildland fire plumes, which remain yet to be fully explored using models. Here, we present a high-resolution large eddy simulation model coupled to chemistry to study the chemical evolution in fresh wildland fire plume. The model is configured for a large fire heavily sampled during the Fire Influence on Regional to Global Environments and Air Quality field campaign, and a variety of airborne measurements are used to evaluate the chemical heterogeneity revealed by the model. We show that the model captures the observed cross-transect variations of a number of compounds quite well, including ozone (O3), nitrous acid (HONO), and peroxyacetyl nitrate. The combined observational and modeling results suggest that the top and edges of fresh plume drive the photochemistry, while dark chemistry is also present but in the lower part of the plume. The model spatial resolution is shown to be very important as it may shift the chemical regime, leading to biases in O3 and NOx chemistry. Based on findings in this work, we speculate that the impact of small fires on air quality may be largely underestimated in models with coarse spatial resolutions

    Increasing Cost Efficiency in Adult Spinal Deformity Surgery: Identifying Predictors of Lower Total Costs.

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    STUDY DESIGN: Retrospective study of a prospective multicenter database. OBJECTIVE: The purpose of this study was to identify predictors of lower total surgery costs at 3 years for Adult Spinal Deformity (ASD) patients. SUMMARY OF BACKGROUND DATA: ASD surgery involves complex deformity correction. METHODS: Inclusion criteria: surgical ASD (scoliosis≥20°, SVA≥5 cm, PT≥25°, or thoracic kyphosis ≥60°) patients \u3e18 years. Total costs for surgery were calculated using the PearlDiver database. Cost per quality adjusted life year was assessed. A Conditional Variable Importance Table used non-replacement sampling set of 20,000 Conditional Inference trees to identify top factors associated with lower cost surgery for low (LSVA), moderate (MSVA), and high (HSVA) SRS Schwab SVA grades. RESULTS: 316/322 ASD patients met inclusion criteria. At 3Y follow up, the potential cost of ASD surgery ranged from 57,606.88to57,606.88 to 116,312.54. The average costs of surgery at 3 years was found to be 72,947.87,withnosignificantdifferenceincostsbetweendeformitygroups(p3˘e0.05).Therewere152LSVApatients,53MSVApatients,and111HSVApatients.Forallpatients,thetoppredictorsoflowercostswerefrailtyscores1.5,baseline(BL)ODI3˘c503˘e(allp3˘c0.05).ForLSVApatients,nohistoryofosteoporosis,SRSActivityscores3˘e1.5,ageCONCLUSIONS:ASDsurgeryhasthepotentialforimprovedcostefficiency,ascostsrangedfrom72,947.87, with no significant difference in costs between deformity groups (p \u3e 0.05). There were 152 LSVA patients, 53 MSVA patients, and 111 HSVA patients. For all patients, the top predictors of lower costs were frailty scores1.5, baseline (BL) ODI \u3c50 \u3e(all p \u3c 0.05). For LSVA patients, no history of osteoporosis, SRS Activity scores \u3e1.5, age CONCLUSIONS: ASD surgery has the potential for improved cost efficiency, as costs ranged from 57,606.88 to $116,312.54. Predictors of lower costs included higher baseline SRS activity, decreased frailty, and not having depression. Additionally, predictors of lower costs were identified for different baseline deformity profiles, allowing for the optimization of cost efficiency for all patients.Level of Evidence: 3

    A Risk Benefit Analysis of Increasing Surgical Invasiveness Relative to Frailty Status in Adult Spinal Deformity Surgery.

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    STUDY DESIGN: Retrospective review of a prospectively enrolled multicenter Adult Spinal Deformity (ASD) database. OBJECTIVE: Investigate invasiveness and outcomes of ASD surgery by frailty state. SUMMARY OF BACKGROUND DATA: The ASD Invasiveness Index incorporates deformity-specific components to assess correction magnitude. Intersections of invasiveness, surgical outcomes, and frailty state are understudied. METHODS: ASD patients with baseline and 3-year (3Y) data were included. Logistic regression analyzed the relationship between increasing invasiveness and major complications or reoperations and meeting minimal clinically important differences (MCID) for health-related quality of life (HRQL) measures at 3Y. Decision tree analysis assessed invasiveness risk-benefit cut-off points, above which experiencing complications or reoperations and not reaching MCID were higher. Significance was set to p \u3c 0.05. RESULTS: Overall, 195/322 patients were included. Baseline demographics: age 59.9 ± 14.4, 75% female, BMI 27.8 ± 6.2, mean Charlson Comorbidity Index: 1.7 ± 1.7. Surgical information: 61% osteotomy, 52% decompression, 11.0 ± 4.1 levels fused. There were 98 not frail (NF), 65 frail (F), and 30 severely frail (SF) patients. Relationships were found between increasing invasiveness and experiencing a major complication or reoperation for the entire cohort and by frailty group (all p \u3c 0.05). Defining a favorable outcome as no major complications or reoperation and meeting MCID in any HRQL at 3Y established an invasiveness cut-off of 63.9. Patients below this threshold were 1.8[1.38-2.35] (p \u3c 0.001) times more likely to achieve favorable outcome. For NF patients, the cut-off was 79.3 (2.11[1.39-3.20] (p \u3c 0.001), 111 for F (2.62 [1.70-4.06] (p \u3c 0.001), and 53.3 for SF (2.35[0.78-7.13] (p = 0.13). CONCLUSIONS: Increasing invasiveness is associated with increased odds of major complications and reoperations. Risk-benefit cut-offs for successful outcomes were 79.3 for NF, 111 for F, and 53.3 for SF patients. Above these, increasing invasiveness has increasing risk of major complications or reoperations and not meeting MCID at 3Y.Level of Evidence: 3

    Nighttime and daytime dark oxidation chemistry in wildfire plumes: an observation and model analysis of FIREX-AQ aircraft data

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    Wildfires are increasing in size across the western US, leading to increases in human smoke exposure and associated negative health impacts. The impact of biomass burning (BB) smoke, including wildfires, on regional air quality depends on emissions, transport, and chemistry, including oxidation of emitted BB volatile organic compounds (BBVOCs) by the hydroxyl radical (OH), nitrate radical (NO3), and ozone (O3). During the daytime, when light penetrates the plumes, BBVOCs are oxidized mainly by O3 and OH. In contrast, at night or in optically dense plumes, BBVOCs are oxidized mainly by O3 and NO3. This work focuses on the transition between daytime and nighttime oxidation, which has significant implications for the formation of secondary pollutants and loss of nitrogen oxides (NOx=NO+NO2) and has been understudied. We present wildfire plume observations made during FIREX-AQ (Fire Influence on Regional to Global Environments and Air Quality), a field campaign involving multiple aircraft, ground, satellite, and mobile platforms that took place in the United States in the summer of 2019 to study both wildfire and agricultural burning emissions and atmospheric chemistry. We use observations from two research aircraft, the NASA DC-8 and the NOAA Twin Otter, with a detailed chemical box model, including updated phenolic mechanisms, to analyze smoke sampled during midday, sunset, and nighttime. Aircraft observations suggest a range of NO3 production rates (0.1–1.5 ppbv h−1) in plumes transported during both midday and after dark. Modeled initial instantaneous reactivity toward BBVOCs for NO3, OH, and O3 is 80.1 %, 87.7 %, and 99.6 %, respectively. Initial NO3 reactivity is 10–104 times greater than typical values in forested or urban environments, and reactions with BBVOCs account for >97 % of NO3 loss in sunlit plumes (jNO2 up to 4×10−3s−1), while conventional photochemical NO3 loss through reaction with NO and photolysis are minor pathways. Alkenes and furans are mostly oxidized by OH and O3 (11 %–43 %, 54 %–88 % for alkenes; 18 %–55 %, 39 %–76 %, for furans, respectively), but phenolic oxidation is split between NO3, O3, and OH (26 %–52 %, 22 %–43 %, 16 %–33 %, respectively). Nitrate radical oxidation accounts for 26 %–52 % of phenolic chemical loss in sunset plumes and in an optically thick plume. Nitrocatechol yields varied between 33 % and 45 %, and NO3 chemistry in BB plumes emitted late in the day is responsible for 72 %–92 % (84 % in an optically thick midday plume) of nitrocatechol formation and controls nitrophenolic formation overall. As a result, overnight nitrophenolic formation pathways account for 56 %±2 % of NOx loss by sunrise the following day. In all but one overnight plume we modeled, there was remaining NOx (13 %–57 %) and BBVOCs (8 %–72 %) at sunrise

    Combined action observation and motor imagery: An intervention to combat the neural and behavioural deficits associated with developmental coordination disorder

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    Action observation (AO) and motor imagery (MI) have been used separately across different populations to alleviate movement impairment. Recently these two forms of covert motor simulation have been combined (combined action observation and motor imagery; AOMI), resulting in greater neurophysiological activity in the motor system, and more favourable behavioural outcomes when compared to independent AO and MI. This review aims to outline how some of the neural deficits associated with developmental coordination disorder (DCD) are evident during AO and MI, and highlight how these motor simulation techniques have been used independently to improve motor skill learning in children in this population. The growing body of evidence indicating that AOMI is superior to the independent use of either AO and MI is then synthesised and discussed in the context of children with DCD. To conclude, recommendations to optimise the delivery of AOMI for children with DCD are provided and future avenues for research are highlighted

    Classifying Complications: Assessing Adult Spinal Deformity 2-Year Surgical Outcomes.

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    STUDY DESIGN: Retrospective review of prospective database. OBJECTIVE: Complication rates for adult spinal deformity (ASD) surgery vary widely because there is no accepted system for categorization. Our objective was to identify the impact of complication occurrence, minor-major complication, and Clavien-Dindo complication classification (Cc) on clinical variables and patient-reported outcomes. METHODS: Complications in surgical ASD patients with complete baseline and 2-year data were considered intraoperatively, perioperatively (\u3c6 \u3eweeks), and postoperatively (\u3e6 weeks). Primary outcome measures were complication timing and severity according to 3 scales: complication presence (yes/no), minor-major, and Cc score. Secondary outcomes were surgical outcomes (estimated blood loss [EBL], length of stay [LOS], reoperation) and health-related quality of life (HRQL) scores. Univariate analyses determined complication presence, type, and Cc grade impact on operative variables and on HRQL scores. RESULTS: Of 167 patients, 30.5% (n = 51) had intraoperative, 48.5% (n = 81) had perioperative, and 58.7% (n = 98) had postoperative complications. Major intraoperative complications were associated with increased EBL ( CONCLUSION: The Cc Scale was most useful in predicting changes in patient outcomes; at 2 years, patients with raised perioperative Cc scores and postoperative complications saw reduced HRQL improvement. Intraoperative and perioperative complications were associated with worse short-term surgical and inpatient outcomes
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