17 research outputs found

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    Eight Weeks of Lifestyle Change: What are the Effects of the Healthy Lifestyle Community Programme (Cohort 1) on Cortisol Awakening Response (CAR) and Perceived Stress?

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    Background: Stress and cortisol dysregulation are linked to NCDs. Moreover, stress favours unhealthy lifestyle patterns, which increase the risk for NCDs. The role of the Cortisol Awakening Response (CAR) and the effect of lifestyle interventions on the same remain unclear. Methods: The impact of the intensive 8-week phase of the Healthy Lifestyle Community Programme (HLCP, cohort 1) on parameters of the CAR, ie cortisol values 0 (sample [S]1), 30), 45 and 60 minutes post-awakening, average peak, S1-peak delta and area under the increase curve (AUCI), and perceived stress levels (PSL) was evaluated in a non-randomized, controlled trial. Covariates of the CAR (eg sleep measures) and irregularities in sampling were assessed. The intervention focussed on stress management, a healthy diet, regular exercise, and social support. Participants were recruited from the general population. Multiple linear regression analyses were conducted. Results: 97 participants (age: 56±10 years; 71% female), with 68 in the intervention group (IG; age: 55±8, 77% female) and 29 participants in the control group (CG; age: 59±12, 59% female), were included in the analysis. The baseline characteristics of both groups were comparable, except participants of IG were younger. On average, the PSL at baseline was low in both groups (IG: 9.7 ±5.4 points; CG: 8.5 ±6.9 points; p=.165), but 22% (n =15) in the IG and 20% (n =6) in the CG reported a high PSL. Most participants reported irregularities in CAR sampling, eg interruption of sleep (IG: 80% CG: 81%). After 8 weeks, most CAR parameters and the PSL decreased in the IG and CG, resulting in no differences of change between the groups. In the IG only, a decrease of PSL was linked to an increase of CAR parameters, eg AUCI (correlation coefficient =−0.307; p =.017). Conclusion: The HLCP may potentially reduce PSL and change the CAR, but results cannot be clearly attributed to the programme. Methodological challenges and multiple confounders, limit suitability of the CAR in the context of lifestyle interventions. Other measures (eg hair-cortisol) may give further insights. Trial registration: German Clinical Trials Register (DRKS); DRKS00018821; www.drks.d

    Objective activity tracking in spine surgery: a prospective feasibility study with a low-cost consumer grade wearable accelerometer

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    Patient-reported outcome measures (PROMs) are commonly used to estimate disability of patients with spinal degenerative disease. Emerging technological advances present an opportunity to provide objective measurements of activity. In a prospective, observational study we utilized a low-cost consumer grade wearable accelerometer (LCA) to determine patient activity (steps per day) preoperatively (baseline) and up to one year (Y1) after cervical and lumbar spine surgery. We studied 30 patients (46.7% male; mean age 57 years; 70% Caucasian) with a baseline activity level of 5624 steps per day. The activity level decreased by 71% in the 1st^{st} postoperative week (p < 0.001) and remained 37% lower in the 2nd^{nd} (p < 0.001) and 23% lower in the 4th^{th} week (p = 0.015). At no time point until Y1 did patients increase their activity level, compared to baseline. Activity was greater in patients with cervical, as compared to patients with lumbar spine disease. Age, sex, ethnic group, anesthesia risk score and fusion were variables associated with activity. There was no correlation between activity and PROMs, but a strong correlation with depression. Determining activity using LCAs provides real-time and longitudinal information about patient mobility and return of function. Recovery took place over the first eight postoperative weeks, with subtle improvement afterwards

    Association between Physician Industry Payments and Cost of Anterior Cervical Discectomy and Fusion in Medicare Beneficiaries

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    BACKGROUND Neurosurgical spine specialists receive considerable amounts of industry support which may impact the cost of care. The aim of this study was to evaluate the association between industry payments received by spine surgeons and the total hospital and operating room (OR) costs of an anterior cervical discectomy and fusion (ACDF) procedure among Medicare beneficiaries. METHODS All ACDF cases were identified among the Medicare Carrier Files, from January 1, 2013, to December 31, 2014, and matched to the Medicare Inpatient Baseline File. The total hospital and OR charges were obtained for these cases. Charges were converted to cost using year-specific cost-to-charge ratios. Surgeons were identified among Open Payments database, which is used to quantify industry support. Analyses was performed to examine the association between industry payments received and ACDF costs. RESULTS Matching resulting in the inclusion of 2,209 ACDF claims from 2013-2014. In 2013 and 2014, the mean total cost for an ACDF was 21,798and21,798 and 21,008, respectively; mean OR cost was 5,878and5,878 and 6,064, respectively. Mann-Whitney U test demonstrated no significant differences in the mean total or OR cost for an ACDF based on quartile of general industry payment received (p=0.21 and p=0.54), and linear regression found no association between industry general payments, research support, or investments on the total hospital cost (p=0.41, p=0.13, and p=0.25), or OR cost for an ACDF (p=0.35, p=0.24, and p=0.40). CONCLUSIONS This study suggests that spine surgeons performing ACDF surgeries may receive industry support without impacting the cost of care

    Bridging the gap between science and society: long-term effects of the Healthy Lifestyle Community Programme (HLCP, cohort 1) on weight and the metabolic risk profile: a controlled study

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    Background: The potential of adopting a healthy lifestyle to fight non-communicable diseases (NCDs) is not fully used. We hypothesised that the Healthy Lifestyle Community Programme (HLCP, cohort 1) reduces weight and other risk markers compared with baseline and control. Methods: 24-month, non-randomised, controlled intervention trial. Intervention: intensive 8-week phase with seminars, workshops and coaching focusing on a healthy lifestyle (eg, plant-based diet, physical activity, stress management) and group support followed by a 22-month alumni phase. Weight reduction as the primary outcome and other NCD risk parameters were assessed at six time points. Participants were recruited from the general population. Multiple linear regression analyses were conducted. Results: 143 participants (58±12 years, 71% female) were enrolled (91 in the intervention (IG) and 52 in the control group (CG)). Groups’ baseline characteristics were comparable, except participants of IG were younger, more often females, overweight and reported lower energy intake (kcal/day). Weight significantly decreased in IG at all follow-ups by −1.5 ± 1.9 kg after 8 weeks to −1.9 ± 4.0 kg after 24 months and more than in CG (except after 24 months). Being male, in the IG or overweight at baseline and having a university degree predicted more weight loss. After the intervention, there were more participants in the IG with a ‘high’ adherence (+12%) to plant-based food patterns. The change of other risk parameters was most distinct after 8 weeks and in people at elevated risk. Diabetes-related risk parameters did not improve. Conclusion: The HLCP was able to reduce weight and to improve aspects of the NCD risk profile. Weight loss in the IG was moderate but maintained for 24 months. Participants of lower educational status might benefit from even more practical units. Future interventions should aim to include more participants at higher risk

    Reliability of the 6-minute walking test smartphone application

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    Objective: functional measures such as the 6-minute walking test (6WT) are increasingly applied to evaluate patients with degenerative diseases of the lumbar spine before and after (surgical) treatment. However, the traditional 6WT is cumbersome to apply, as it requires specialized in-hospital infrastructure and personnel. The authors set out to compare 6-minute walking distance (6WD) measurements obtained with a newly developed smartphone application (app) and those obtained with the gold-standard distance wheel (DW). METHODS: The authors developed a free iOS- and Android-based smartphone app that allows patients to measure the 6WD in their home environment using global positioning system (GPS) coordinates. In a laboratory setting, the authors obtained 6WD measurements over a range of smartphone models, testing environments, and walking patterns and speeds. The main outcome was the relative measurement error (rME; in percent of 6WD), with |rME| &lt; 7.5% defined as reliable. The intraclass correlation coefficient (ICC) for agreement between app- and DW-based 6WD was calculated. RESULTS: Measurements (n = 406) were reliable with all smartphone types in neighborhood, nature, and city environments (without high buildings), as well as with unspecified, straight, continuous, and stop-and-go walking patterns (ICC = 0.97, 95% CI 0.97–0.98, p &lt; 0.001). Measurements were unreliable indoors, in city areas with high buildings, and for predominantly rectangular walking courses. Walking speed had an influence on the ME, with worse accuracy (2% higher rME) for every kilometer per hour slower walking pace (95% CI 1.4%–2.5%, p &lt; 0.001). Mathematical adjustment of the app-based 6WD for velocity-dependent error mitigated the rME (p &lt; 0.011), attenuated velocity dependence (p = 0.362), and had a positive effect on accuracy (ICC = 0.98, 95% CI 0.98–0.99, p &lt; 0.001). CONCLUSIONS: The new, free, spine-specific 6WT smartphone app measures the 6WD conveniently by using GPS coordinates, empowering patients to independently determine their functional status before and after (surgical) treatment. Measurements of 6WD obtained for the target population under the recommended circumstances are highly reliable.</jats:sec

    Weighted-persistent-homology-based machine learning for RNA flexibility analysis

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    With the great significance of biomolecular flexibility in biomolecular dynamics and functional analysis, various experimental and theoretical models are developed. Experimentally, Debye-Waller factor, also known as B-factor, measures atomic mean-square displacement and is usually considered as an important measurement for flexibility. Theoretically, elastic network models, Gaussian network model, flexibility-rigidity model, and other computational models have been proposed for flexibility analysis by shedding light on the biomolecular inner topological structures. Recently, a topology-based machine learning model has been proposed. By using the features from persistent homology, this model achieves a remarkable high Pearson correlation coefficient (PCC) in protein B-factor prediction. Motivated by its success, we propose weighted-persistent-homology (WPH)-based machine learning (WPHML) models for RNA flexibility analysis. Our WPH is a newly-proposed model, which incorporate physical, chemical and biological information into topological measurements using a weight function. In particular, we use local persistent homology (LPH) to focus on the topological information of local regions. Our WPHML model is validated on a well-established RNA dataset, and numerical experiments show that our model can achieve a PCC of up to 0.5822. The comparison with the previous sequence-information-based learning models shows that a consistent improvement in performance by at least 10% is achieved in our current model
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