scholarly journals Biological and Clinical Factors contributing to the Metabolic Heterogeneity of Hospitalized Patients with and without COVID-19

Author(s):  
Angelo D'Alessandro ◽  
Imo Akpan ◽  
Tiffany Thomas ◽  
Julie Reisz ◽  
Francesca Cendali ◽  
...  

Abstract The Corona Virus Disease 2019 (COVID-19) pandemic represents an ongoing worldwide challenge. Exploratory studies evaluating the impact of COVID-19 infection on the plasma metabolome have been performed, often with small numbers of patients, and with or without relevant control data; however, determining the impact of biological and clinical variables remains critical to understanding potential markers of disease severity and progression. The present large study, including relevant controls, sought to understand independent and overlapping metabolic features of samples from acutely ill patients (n = 831), testing positive (n = 543) or negative (n = 288) for COVID-19. High-throughput metabolomics analyses were complemented with antigen and enzymatic activity assays on 831 plasma samples from acutely ill patients while in the emergency department, at admission, and during hospitalization. We then performed additional lipidomics analyses of the 60 subjects with the lowest and highest body mass index, either COVID-19 positive or negative. Omics data were correlated to detailed data on patient characteristics and clinical laboratory assays measuring coagulation, hematology and chemistry analytes. Significant changes in arginine/proline/citrulline, tryptophan/indole/kynurenine, fatty acid and acyl-carnitine metabolism emerged as highly relevant markers of disease severity, progression and prognosis as a function of biological and clinical variables in these patients. Further, machine learning models were trained by entering all metabolomics and clinical data from half of the COVID-19 patient cohort and then tested on the other half yielding ~ 78% prediction accuracy. Finally, the extensive amount of information accumulated in this large, prospective, observational study provides a foundation for follow-up mechanistic studies and data sharing opportunities, which will advance our understanding of the characteristics of the plasma metabolism in COVID-19 and other acute critical illnesses.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 620-620 ◽  
Author(s):  
Janine Marie Davies ◽  
Eugene Batuyong ◽  
Sasha M. Lupichuk ◽  
Robert Hilsden ◽  
Misha Eliasziw ◽  
...  

620 Background: The 2005 ASCO guidelines recommend surveillance testing and frequencies following surgical +/− adjuvant therapy for stage II/III CRC. In Canada, many patients are discharged from their oncologist to their primary care physician (PCP) for ongoing surveillance. However, adherence to surveillance recommendations is low. This cohort study evaluated adherence to surveillance 1 year after treatment of stage II/III CRC prior to and following implementation of a DL. Methods: Cohort 1 (C1) patients were retrospectively identified from the Alberta Cancer Registry following adjuvant therapy (as applicable) at a tertiary cancer centre (07/2006 - 09/2007). Cohort 2 (C2) patients were prospectively identified from the Registry and clinic records following adjuvant therapy (as applicable), as those discharged from the centre (10/2007 - 4/2009); DL was sent to the patient and PCP recommending surveillance tests and dates. Clinical, laboratory, diagnostic imaging, and endoscopy data was collated. Adherence at 1 year follow-up was compared between cohorts using Kaplan-Meier time-to-event analyses. Results: C1 (n=218) was larger than C2 (n=114) despite the longer accrual time for C2. There were no differences between cohorts by age, sex, primary site of disease, stage, or adjuvant oxaliplatin use. During year 1 of follow-up, 11.8% and 11.4% recurred (local or metastatic) and 6.5% and 2.7% died (p=0.1) in C1 and C2 respectively. Comparing C1 with C2, 14.8% vs. 23.0% of patients had one CEA test within 3 months, 45.2% vs. 72.2% within 6 months, and 71.7% vs. 85.1% within 1 year (p<0.001). Only 44.0% (C1) and 68.6% (C2) had 2 CEA tests within 1 year. Only 3.9% (C1) vs. 6.6% (C2) of patients had 4 CEA tests within the year following treatment as recommended. The rate of CT imaging was 32.3% (C1) and 56.1% (C2); endoscopy was 36.7% (C1) and 42.1% (C2). Conclusions: Implementation of a DL improved compliance with surveillance at 1 year of follow-up following discharge from a tertiary cancer centre, although optimal adherence remains low. However, adherence to CT imaging nearly doubled. Evaluation of compliance at 3 years of follow-up is ongoing.


2019 ◽  
Vol 23 (25) ◽  
pp. 1-98 ◽  
Author(s):  
Rod S Taylor ◽  
Sarah Walker ◽  
Oriana Ciani ◽  
Fiona Warren ◽  
Neil A Smart ◽  
...  

Background Current national and international guidelines on the management of heart failure (HF) recommend exercise-based cardiac rehabilitation (ExCR), but do not differentiate this recommendation according to patient subgroups. Objectives (1) To obtain definitive estimates of the impact of ExCR interventions compared with no exercise intervention (control) on mortality, hospitalisation, exercise capacity and health-related quality of life (HRQoL) in HF patients; (2) to determine the differential (subgroup) effects of ExCR in HF patients according to their age, sex, left ventricular ejection fraction, HF aetiology, New York Heart Association class and baseline exercise capacity; and (3) to assess whether or not the change in exercise capacity mediates for the impact of the ExCR on final outcomes (mortality, hospitalisation and HRQoL), and determine if this is an acceptable surrogate end point. Design This was an individual participant data (IPD) meta-analysis. Setting An international literature review. Participants HF patients in randomised controlled trials (RCTs) of ExCR. Interventions ExCR for at least 3 weeks compared with a no-exercise control, with 6 months’ follow-up. Main outcome measures All-cause and HF-specific mortality, all-cause and HF-specific hospitalisation, exercise capacity and HRQoL. Data sources IPD from eligible RCTs. Review methods RCTs from the Exercise Training Meta-Analysis of Trials for Chronic Heart Failure (ExTraMATCH/ExTraMATCH II) IPD meta-analysis and a 2014 Cochrane systematic review of ExCR (Taylor RS, Sagar VA, Davies EJ, Briscoe S, Coats AJ, Dalal H, et al. Exercise-based rehabilitation for heart failure. Cochrane Database Syst Rev 2014;4:CD003331). Results Out of the 23 eligible RCTs (4398 patients), 19 RCTs (3990 patients) contributed data to this IPD meta-analysis. There was a wide variation in exercise programme prescriptions across included studies. Compared with control, there was no statistically significant difference in pooled time-to-event estimates in favour of ExCR, although confidence intervals (CIs) were wide: all-cause mortality had a hazard ratio (HR) of 0.83 (95% CI 0.67 to 1.04); HF-related mortality had a HR of 0.84 (95% CI 0.49 to 1.46); all-cause hospitalisation had a HR of 0.90 (95% CI 0.76 to 1.06); and HF-related hospitalisation had a HR of 0.98 (95% CI 0.72 to 1.35). There was a statistically significant difference in favour of ExCR for exercise capacity and HRQoL. Compared with the control, improvements were seen in the 6-minute walk test (6MWT) (mean 21.0 m, 95% CI 1.57 to 40.4 m) and Minnesota Living with Heart Failure Questionnaire score (mean –5.94, 95% CI –1.0 to –10.9; lower scores indicate improved HRQoL) at 12 months’ follow-up. No strong evidence for differential intervention effects across patient characteristics was found for any outcomes. Moderate to good levels of correlation (R 2 trial > 50% and p > 0.50) between peak oxygen uptake (VO2peak) or the 6MWT with mortality and HRQoL were seen. The estimated surrogate threshold effect was an increase of 1.6 to 4.6 ml/kg/minute for VO2peak. Limitations There was a lack of consistency in how included RCTs defined and collected the outcomes: it was not possible to obtain IPD from all includable trials for all outcomes and patient-level data on exercise adherence was not sought. Conclusions In comparison with the no-exercise control, participation in ExCR improved the exercise and HRQoL in HF patients, but appeared to have no effect on their mortality or hospitalisation. No strong evidence was found of differential intervention effects of ExCR across patient characteristics. VO2peak and 6MWT may be suitable surrogate end points for the treatment effect of ExCR on mortality and HRQoL in HF. Future studies should aim to achieve a consensus on the definition of outcomes and promote reporting of a core set of HF data. The research team also seeks to extend current policies to encourage study authors to allow access to RCT data for the purpose of meta-analysis. Study registration This study is registered as PROSPERO CRD42014007170. Funding The National Institute for Health Research Health Technology Assessment programme.


10.2196/24357 ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. e24357
Author(s):  
Claudia Marques ◽  
Adriana Maria Kakehasi ◽  
Ana Paula Monteiro Gomides ◽  
Eduardo Dos Santos Paiva ◽  
Edgard Torres dos Reis Neto ◽  
...  

Background Patients with immune-mediated rheumatic diseases (IMRD) are at increased risk of infections, including significant morbidity and high mortality. Considering the potential for unfavorable outcomes of SARS-CoV-2 infection in patients with IMRD, several questions were raised regarding the impact of COVID-19 at the start of the pandemic. Objective This paper presents the protocol of a study that aims to prospectively evaluate patients with IMRD and a confirmed COVID-19 diagnosis (using criteria provided by the Brazilian Ministry of Health). Methods The study comprised a prospective, observational cohort (patients with IMRD and COVID-19) and a comparison group (patients with only IMRD), with a follow-up time of 6 months to evaluate differences in health outcomes. The primary outcomes will be changes in IMRD disease activity after SARS-CoV-2 infection at 4 time points: (1) at baseline, (2) within 4-6 weeks after infection, (3) at 3 months after the second assessment (±15 days), and (4) at 6 months (±15 days). The secondary outcomes will be the progression rate to moderate or severe forms of COVID-19, need for intensive care unit admission and mechanical ventilation, death, and therapeutic changes related to IMRD. Two outcomes—pulmonary and thromboembolic events in patients with both IMRD and SARS-CoV-2 infection—are of particular interest and will be monitored with close attention (clinical, laboratory, and function tests as well as imaging). Results Recruitment opened in May 2020, with 1300 participants recruited from 43 sites as of November 2020. Patient recruitment will conclude by the end of December 2020, with follow-up occurring until April 2021. Data analysis is scheduled to start after all inclusion data have been collected, with an aim to publish a peer-reviewed paper in December 2020. Conclusions We believe this study will provide clinically relevant data on the general impact of COVID-19 on patients with IMRD. Trial Registration Brazilian Registry of Clinical Trials RBR-33YTQC; http://www.ensaiosclinicos.gov.br/rg/RBR-33ytqc/ International Registered Report Identifier (IRRID) DERR1-10.2196/24357


2019 ◽  
Vol 6 ◽  
pp. 205435811986194
Author(s):  
Farah Ladak ◽  
Pietro Ravani ◽  
Matthew J. Oliver ◽  
Fareed Kamar ◽  
Alix Clarke ◽  
...  

Background: Clinical practice guidelines recommend arteriovenous fistulas as the preferred form of vascular access for hemodialysis. However, some studies have suggested that older age is associated with poorer fistula outcomes. Objective: We assessed the impact of age on the outcomes of fistula creation and access-related procedures. Design: This was a prospective cohort study using data collected as part of the Dialysis Measurement Analysis and Reporting (DMAR) system. Setting: Participating Canadian dialysis programs, including Southern Alberta Renal Program, Manitoba Renal Program, Sunnybrook Health Sciences Centre (Toronto, Ontario), London Health Sciences Centre (London, Ontario), and The Ottawa Hospital (Ottawa, Ontario). Patients: Incident hemodialysis patients aged 18 years and older who started dialysis between January 1, 2004, and May 31, 2012. Measurements: The primary outcome was the proportion of all first fistula attempts that resulted in catheter-free fistula use, defined as independent use of a fistula for hemodialysis (ie, no catheter in place). Secondary outcomes included the time to catheter-free fistula use among patients with a fistula creation attempt, total number of days of catheter-free fistula use, and the proportion of a patient’s hemodialysis career spent with an independently functioning fistula (ie, catheter-free fistula use). Methods: We compared patient characteristics by age group, using t tests or Wilcoxon rank sum tests, and chi-square or Fisher exact tests, as appropriate. Logistic and fractional logistic regression were used to estimate the odds of achieving catheter-free fistula use by age group and the proportion of dialysis time spent catheter-free, respectively. Results: A total of 1091 patients met our inclusion criteria (567 age ≥ 65; 524 age < 65). Only 57% of first fistula attempts resulted in catheter-free fistula use irrespective of age (adjusted odds ratio [OR]≥65vs<65: 1.01; P = .93). The median time from hemodialysis start to catheter-free use of the first fistula did not differ by age when grouped into fistulas attempted pre- and post-dialysis initiation. The adjusted rates of access-related procedures were comparable (incidence rate ratio [IRR]≥65vs<65: 0.95; P = .32). The median percentage of follow-up time spent catheter-free was similar and low in patients who attempted fistulas (<65 years: 19% vs ≥65 years: 21%; P = .85). Limitations: The relatively short follow-up time may have underestimated the benefits of fistula creation and the observational study design precludes inferences about causality. Conclusions: In our study, older patients who underwent a fistula attempt were just as likely as younger patients to achieve catheter-free fistula use, within a similar time frame, and while requiring a similar number of access procedures. However, the minority of dialysis time was spent catheter-free.


Resuscitation ◽  
2010 ◽  
Vol 81 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Paolo Calzavacca ◽  
Elisa Licari ◽  
Augustine Tee ◽  
Moritoki Egi ◽  
Andrew Downey ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2293
Author(s):  
Angelo D’Alessandro ◽  
Tiffany Thomas ◽  
Imo J. Akpan ◽  
Julie A. Reisz ◽  
Francesca I. Cendali ◽  
...  

The Corona Virus Disease 2019 (COVID-19) pandemic represents an ongoing worldwide challenge. The present large study sought to understand independent and overlapping metabolic features of samples from acutely ill patients (n = 831) that tested positive (n = 543) or negative (n = 288) for COVID-19. High-throughput metabolomics analyses were complemented with antigen and enzymatic activity assays on plasma from acutely ill patients collected while in the emergency department, at admission, or during hospitalization. Lipidomics analyses were also performed on COVID-19-positive or -negative subjects with the lowest and highest body mass index (n = 60/group). Significant changes in amino acid and fatty acid/acylcarnitine metabolism emerged as highly relevant markers of disease severity, progression, and prognosis as a function of biological and clinical variables in these patients. Further, machine learning models were trained by entering all metabolomics and clinical data from half of the COVID-19 patient cohort and then tested on the other half, yielding ~78% prediction accuracy. Finally, the extensive amount of information accumulated in this large, prospective, observational study provides a foundation for mechanistic follow-up studies and data sharing opportunities, which will advance our understanding of the characteristics of the plasma metabolism in COVID-19 and other acute critical illnesses.


2009 ◽  
Vol 101 (05) ◽  
pp. 878-885 ◽  
Author(s):  
Joel Gore ◽  
George Reed ◽  
Darleen Lessard ◽  
Luigi Pacifico ◽  
Cathy Emery ◽  
...  

SummaryBleeding is the most frequent complication of antithrombotic therapy for venous thromboembolism (VTE). However, little attention has been paid to the impact of bleeding after VTE in the community setting. The purpose of this investigation was to describe the incidence rate of bleeding after VTE, to characterize patients most at risk for bleeding, and to assess the impact of bleeding on rates of recurrent VTE and all-cause mortality. The medical records of residents of the Worcester (MA, USA) metropolitan area diagnosed with ICD-9 codes consistent with potential VTE during 1999, 2001, and 2003 were individually validated and reviewed by trained data abstracters. Clinical characteristics, acute treatment, and outcomes (including VTE recurrence rates, bleeding rates, and mortality) over follow-up (up to 3 years maximum) were evaluated. Bleeding occurred in 228 (12%) of 1,897 patients with VTE during our follow-up. Of these, 115 (58.8%) had evidence of early bleeding occurring within 30 days of VTE diagnosis. Patient characteristics associated with bleeding included impaired renal function and recent trauma. Other than a history of prior VTE, the occurrence of bleeding was the strongest predictor of recurrent VTE (hazard ratio [HR] 2.18; 95% confidence interval [CI] 1.54–3.09) and was also a predictor of total mortality (HR 1.97; 95%CI 1.57–2.47). The occur-rence of bleeding following VTE is associated with an increased risk of recurrent VTE and mortality. Future study of antithrombotic strategies for VTE should be informed by this finding. Advances that result in decreased bleeding rates may paradoxically decrease the risk of VTE recurrence.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hyun J. Kim ◽  
Laurie D. Snyder ◽  
Ayodeji Adegunsoye ◽  
Megan L. Neely ◽  
Shaun Bender ◽  
...  

Abstract Background Hospitalizations are common among patients with idiopathic pulmonary fibrosis (IPF). We investigated the impact of hospitalizations on outcomes in patients with IPF. Methods The IPF-PRO Registry is an observational US registry that enrolled patients with IPF that was diagnosed or confirmed at the enrolling center in the previous 6 months. Associations between patient characteristics and hospitalization, and between hospitalization and mortality, were analyzed using Cox regression models. Results A total of 1002 patients with IPF were enrolled into the IPF-PRO Registry. Over a median follow-up time of 23.7 months (maximum: 67.0 months), 568 patients (56.7%) had at least one hospitalization. Of these patients, 319 (56.2%) had at least one respiratory-related hospitalization and 120 (21.1%) had at least one hospitalization with ventilatory support. Younger age (HR 0.68 [95% CI 0.55, 0.84] per 5-year increase for patients < 62 years), lower BMI (0.96 [0.93, 0.98] per 1-point increase), lower FVC % predicted (0.90 [0.83, 0.97] per 10% increase), oxygen use at rest (2.85 [2.18, 3.72]) and history of pulmonary hypertension (2.02 [1.37, 2.96]) at enrollment were associated with an increased risk of respiratory-related hospitalization during follow-up. In a multivariable model, there was an eightfold increase in the risk of mortality during hospitalization or within 90 days of discharge compared with outside of this period. The risk of mortality associated with a respiratory hospitalization or a hospitalization with ventilatory support was even greater. Conclusions Data from the IPF-PRO Registry demonstrate that hospitalizations are common among patients with IPF. The risk of mortality during hospitalization or within 90 days of discharge was high, particularly among patients who were hospitalized for a respiratory cause or received ventilatory support. Trial registration ClinicalTrials.gov, NCT01915511. Registered 5 August 2013, https://clinicaltrials.gov/ct2/show/NCT01915511


2020 ◽  
Vol 59 (11) ◽  
pp. 970-977
Author(s):  
Jungwon Min ◽  
Heather M. Griffis ◽  
Melodee Mendoza ◽  
Vicky Tam ◽  
Michelle Kaplinski ◽  
...  

This study aimed to evaluate the effect of an outpatient systemic hypertension program and associated factors with attending recommended follow-up visit. All visits were tracked in the program, 2011 to 2018. We examined patient characteristics by follow-up status and changes in systolic blood pressure (SBP) and the risk of hypertension in follow-up patients using a mixed-effects regression model. Among 310 patients with first visits, 113 patients returned for a follow-up visit. Patients who did not attend a follow-up were older and less likely to have a severe chronic condition or a family history of hypertension than followed-up patients. The risk of hypertension was significantly reduced by the number of follow-up visits (odds ratio = 0.53, 95% confidence interval = 0.31-0.92). Adolescent SBP and body mass index percentiles decreased with more follow-up visits. As the risk of hypertension is significantly reduced with follow-up visits, additional effort should be made to improve the likelihood of follow-up attendance.


2019 ◽  
Vol 49 (1) ◽  
pp. 52-56 ◽  
Author(s):  
Andrew P Allen ◽  
Maria M Buckley ◽  
John F Cryan ◽  
Aoife Ní Chorcoráin ◽  
Timothy G Dinan ◽  
...  

Abstract Objectives The burden often associated with informal caregiving for patients with dementia is associated with negative effects on health, both physiologically and in terms of caregiver cognition. There is wide variation in the level of burden experienced by dementia caregivers. To better understand caregiver burden, it is thus important to understand the factors associated with level of burden. Methods In the current study, we collected carer burden and putative associated factors at baseline, 6 and 12 months. Hierarchical regression was used to assess the impact of these factors on caregiver burden. We assessed self-reported carer burden, patient behavioural and safety issues, and level of difficulty associated with providing assistance with activities of daily living (ADL). Patients’ age was also recorded, and trained nurses assessed patient cognitive performance using the quick mild cognitive impairment screen. Results At baseline, patients’ age, cognition and ADLs were associated with burden, and safety and challenging behaviour were both significantly associated with burden independent of the other factors. Change in burden was associated with change in carer-reported safety at 6-month follow-up, and with change in safety and change in carer-reported challenging behaviours at 12-month follow-up. Conclusions Safety issues and challenging behaviours are associated with carer burden, even after accounting for cognitive and functional impairment in the person with dementia. As dementia progresses, monitoring these factors may help to inform stress-management strategies for caregivers.


Sign in / Sign up

Export Citation Format

Share Document