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Association Between Cytomegalovirus Reactivation and Clinical Outcomes in Immunocompetent Critically Ill Patients: A Systematic Review and Meta-Analysis.

ABSTRACT: The aim of our systematic review was to investigate the association between cytomegalovirus (CMV) reactivation and outcomes in immunocompetent critically ill patients.We searched electronic databases and gray literature for original studies and abstracts published between 1990 and October 2016. The review was limited to studies including critically ill immunocompetent patients. Cytomegalovirus reactivation was defined as positive polymerase chain reaction, pp65 antigenemia, or viral culture from blood or bronchoalveolar lavage. Selected patient-centered outcomes included mortality, duration of mechanical ventilation, need for renal replacement therapy (RRT), and nosocomial infections. Health resource utilization outcomes included intensive care unit and hospital lengths of stay.Twenty-two studies were included. In our primary analysis, CMV reactivation was associated with increased ICU mortality (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.87-3.47), overall mortality (OR, 2.02; 95% CI, 1.60-2.56), duration of mechanical ventilation (mean difference 6.60 days; 95% CI, 3.09-10.12), nosocomial infections (OR, 3.20; 95% CI, 2.05-4.98), need for RRT (OR, 2.37; 95% CI, 1.31-4.31), and ICU length of stay (mean difference 8.18 days; 95% CI, 6.14-10.22). In addition, numerous sensitivity analyses were performed.In this meta-analysis, CMV reactivation was associated with worse clinical outcomes and greater health resource utilization in critically ill patients. However, it remains unclear whether CMV reactivation plays a causal role or if it is a surrogate for more severe illness.

SUBMITTER: Lachance P

PROVIDER: S-EPMC5781329 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Association Between Cytomegalovirus Reactivation and Clinical Outcomes in Immunocompetent Critically Ill Patients: A Systematic Review and Meta-Analysis.

Lachance Philippe P Chen Justin J Featherstone Robin R Sligl Wendy I WI

Open forum infectious diseases 20170213 2

<h4>Background</h4>The aim of our systematic review was to investigate the association between cytomegalovirus (CMV) reactivation and outcomes in immunocompetent critically ill patients.<h4>Methods</h4>We searched electronic databases and gray literature for original studies and abstracts published between 1990 and October 2016. The review was limited to studies including critically ill immunocompetent patients. Cytomegalovirus reactivation was defined as positive polymerase chain reaction, pp65 ...[more]

PMID: 29497626

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Project description:Importance:Latent cytomegalovirus (CMV) infection is present in more than half the adult population, and a viral reactivation (ie, when the virus becomes measurable in body fluids such as blood) can occur in up to one-third of these individuals during episodes of critical illness. Objective:To determine whether antiviral therapy is safe and effective for preventing CMV reactivation in a general population of critically ill patients. Design, Setting, and Participants:A single-center, open-label, randomized, controlled clinical trial recruited 124 CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours in the intensive care unit between January 1, 2012, and January 31, 2014. The mean baseline Acute Physiology and Chronic Health Evaluation II score of all patients was 17.6. Interventions:Patients were randomized to receive anti-CMV prophylaxis with valacyclovir hydrochloride (n?=?34) or low-dose valganciclovir hydrochloride (n?=?46) for up to 28 days to suppress viral reactivation, or to a control group with no intervention (n?=?44). Main Outcomes and Measures:Time to first CMV reactivation in blood within the 28-day follow-up period following initiation of the study drug. Results:Among the 124 patients in the study (46 women and 78 men; mean [SD] age, 56.9 [16.9] years), viral reactivation in the blood occurred in 12 patients in the control group, compared with 1 patient in the valganciclovir group and 2 patients in the valacyclovir group (combined treatment groups vs control: hazard ratio, 0.14; 95% CI 0.04-0.50). Although this trial was not powered to assess clinical end points, the valacyclovir arm was halted prematurely because of higher mortality; 14 of 34 patients (41.2%) had died by 28 days, compared with 5 of 37 (13.5%) patients in the control arm at the point of the decision to halt this arm. Other safety end points showed similar outcomes between groups. Conclusions and Relevance:Antiviral prophylaxis with valacyclovir or low-dose valganciclovir suppresses CMV reactivation in patients with critical illness. However, given the higher mortality, a large-scale trial would be needed to determine the clinical efficacy and safety of CMV suppression. Trial Registration:clinicaltrials.gov Identifier: NCT01503918.

Project description:Importance:After initial resuscitation, critically ill children may accumulate fluid and develop fluid overload. Accruing evidence suggests that fluid overload contributes to greater complexity of care and worse outcomes. Objective:To describe the methods to measure fluid balance, define fluid overload, and evaluate the association between fluid balance and outcomes in critically ill children. Data Sources:Systematic search of MEDLINE, EMBASE, Cochrane Library, trial registries, and selected gray literature from inception to March 2017. Study Selection:Studies of children admitted to pediatric intensive care units that described fluid balance or fluid overload and reported outcomes of interest were included. No language restrictions were applied. Data Extraction and Synthesis:All stages were conducted independently by 2 reviewers. Data extracted included study characteristics, population, fluid metrics, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale. Narrative description of fluid assessment methods and fluid overload definitions was done. When feasible, pooled analyses were performed using random-effects models. Main Outcomes and Measures:Mortality was the primary outcome. Secondary outcomes included treatment intensity, organ failure, and resource use. Results:A total of 44 studies (7507 children) were included in this systematic review and meta-analysis. Of those, 27 (61%) were retrospective cohort studies, 13 (30%) were prospective cohort studies, 3 (7%) were case-control studies, and 1 study (2%) was a secondary analysis of a randomized trial. The proportion of children with fluid overload varied by case mix and fluid overload definition (median, 33%; range, 10%-83%). Fluid overload, however defined, was associated with increased in-hospital mortality (17 studies [n = 2853]; odds ratio [OR], 4.34 [95% CI, 3.01-6.26]; I2 = 61%). Survivors had lower percentage fluid overload than nonsurvivors (22 studies [n = 2848]; mean difference, -5.62 [95% CI, -7.28 to -3.97]; I2 = 76%). After adjustment for illness severity, there was a 6% increase in odds of mortality for every 1% increase in percentage fluid overload (11 studies [n = 3200]; adjusted OR, 1.06 [95% CI, 1.03-1.10]; I2 = 66%). Fluid overload was associated with increased risk for prolonged mechanical ventilation (>48 hours) (3 studies [n = 631]; OR, 2.14 [95% CI, 1.25-3.66]; I2 = 0%) and acute kidney injury (7 studies [n = 1833]; OR, 2.36 [95% CI, 1.27-4.38]; I2 = 78%). Conclusions and Relevance:Fluid overload is common and is associated with substantial morbidity and mortality in critically ill children. Additional research should now ideally focus on interventions aimed to mitigate the potential for harm associated with fluid overload.

Project description:ImportanceOxygen supplementation is a cornerstone treatment in pediatric critical care. Accumulating evidence suggests that overzealous use of oxygen, leading to hyperoxia, is associated with worse outcomes compared with patients with normoxia.ObjectivesTo evaluate the association of arterial hyperoxia with clinical outcome in critically ill children among studies using varied definitions of hyperoxia.Data sourcesA systematic search of EMBASE, MEDLINE, Cochrane Library, and ClinicalTrials.gov from inception to February 1, 2021, was conducted.Study selectionClinical trials or observational studies of children admitted to the pediatric intensive care unit that examined hyperoxia, by any definition, and described at least 1 outcome of interest. No language restrictions were applied.Data extraction and synthesisThe Meta-analysis of Observational Studies in Epidemiology guideline and Newcastle-Ottawa Scale for study quality assessment were used. The review process was performed independently by 2 reviewers. Data were pooled with a random-effects model.Main outcomes and measuresThe primary outcome was 28-day mortality; this time was converted to mortality at the longest follow-up owing to insufficient studies reporting the initial primary outcome. Secondary outcomes included length of stay, ventilator-related outcomes, extracorporeal organ support, and functional performance.ResultsIn this systematic review, 16 studies (27 555 patients) were included. All, except 1 randomized clinical pilot trial, were observational cohort studies. Study populations included were post-cardiac arrest (n = 6), traumatic brain injury (n = 1), extracorporeal membrane oxygenation (n = 2), and general critical care (n = 7). Definitions and assessment of hyperoxia differed among included studies. Partial pressure of arterial oxygen was most frequently used to define hyperoxia and mainly by categorical cutoff. In total, 11 studies (23 204 patients) were pooled for meta-analysis. Hyperoxia, by any definition, showed an odds ratio of 1.59 (95% CI, 1.00-2.51; after Hartung-Knapp adjustment, 95% CI, 1.05-2.38) for mortality with substantial between-study heterogeneity (I2 = 92%). This association was also found in less heterogeneous subsets. A signal of harm was observed at higher thresholds of arterial oxygen levels when grouped by definition of hyperoxia. Secondary outcomes were inadequate for meta-analysis.Conclusions and relevanceThese results suggest that, despite methodologic limitations of the studies, hyperoxia is associated with mortality in critically ill children. This finding identifies the further need for prospective observational studies and importance to address the clinical implications of hyperoxia in critically ill children.

Project description:The effect of statin therapy on mortality in critically ill patients is controversial, with some studies suggesting a benefit and others suggesting no benefit or even potential harm. The objective of this study was to evaluate the association between statin therapy during intensive care unit (ICU) admission and all-cause mortality in critically ill patients.This was a nested cohort study within two randomised controlled trials conducted in a tertiary care ICU. All 763 patients who participated in the two trials were included in this study. Of these, 107 patients (14%) received statins during their ICU stay. The primary endpoint was all-cause ICU and hospital mortality. Secondary endpoints included the development of sepsis and severe sepsis during the ICU stay, the ICU length of stay, the hospital length of stay, and the duration of mechanical ventilation. Multivariate logistic regression was used to adjust for clinically and statistically relevant variables.Statin therapy was associated with a reduction in hospital mortality (adjusted odds ratio [aOR] = 0.60, 95% confidence interval [CI] 0.36-0.99). Statin therapy was associated with lower hospital mortality in the following groups: patients >58 years of age (aOR = 0.58, 95% CI 0.35-0.97), those with an acute physiology and chronic health evaluation (APACHE II) score >22 (aOR = 0.54, 95% CI 0.31-0.96), diabetic patients (aOR = 0.52, 95% CI 0.30-0.90), patients on vasopressor therapy (aOR = 0.53, 95% CI 0.29-0.97), those admitted with severe sepsis (aOR = 0.22, 95% CI 0.07-0.66), patients with creatinine ? 100 ?mol/L (aOR = 0.14, 95% CI 0.04-0.51), and patients with GCS ? 9 (aOR = 0.34, 95% CI 0.17-0.71). When stratified by statin dose, the mortality reduction was mainly observed with statin equipotent doses ? 40 mg of simvastatin (aOR = 0.53, 95% CI 0.28-1.00). Mortality reduction was observed with simvastatin (aOR = 0.37, 95% CI 0.17-0.81) but not with atorvastatin (aOR = 0.80, 95% CI 0.84-1.46). Statin therapy was not associated with a difference in any of the secondary outcomes.Statin therapy during ICU stay was associated with a reduction in all-cause hospital mortality. This association was especially noted in high-risk subgroups. This potential benefit needs to be validated in a randomised, controlled trial.

Dataset Information

Association Between Cytomegalovirus Reactivation and Clinical Outcomes in Immunocompetent Critically Ill Patients: A Systematic Review and Meta-Analysis.

Publications

Association Between Cytomegalovirus Reactivation and Clinical Outcomes in Immunocompetent Critically Ill Patients: A Systematic Review and Meta-Analysis.

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