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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: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: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:ImportancePhysicians often rely on surrogate decision-makers (SDMs) to make important decisions on behalf of critically ill patients during times of incapacity. It is uncertain whether targeted interventions to improve surrogate decision-making in the intensive care unit (ICU) reduce nonbeneficial treatment and improve SDM comprehension, satisfaction, and psychological morbidity.ObjectiveTo perform a systematic review and meta-analysis of randomized clinical trials (RCTs) to determine the association of such interventions with patient- and family-centered outcomes and resource use.Data sourcesA search was conducted of MEDLINE, Embase, and other relevant databases for potentially relevant studies from inception through May 30, 2018.Study selectionRandomized clinical trials studying interventions that were targeted at SDMs or family members of critically ill adults in the ICU were included. Key search terms included surrogate or substitute decision-maker, critically ill, randomized controlled trials, and their respective related terms.Data extraction and synthesisThis study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Two independent, blinded reviewers independently screened citations and extracted data. Random effects models with inverse variance weighting were used to pool outcomes data when possible and otherwise present findings qualitatively.Main outcomes and measuresOutcomes of interest were divided into 3 categories: (1) patient-related clinical outcomes (mortality, length of stay [LOS], duration of life-sustaining therapies), (2) SDM and family-related outcomes (comprehension, major change in goals of care, incident psychological comorbidities [posttraumatic stress disorder, anxiety, depression], and satisfaction with care), and (3) use of resources (cost of care and health care resource use).ResultsOf 3735 studies screened, 13 RCTs were included, comprising a total of 10 453 patients. Interventions were categorized as health care professional led (n = 6), ethics consultation (n = 3), palliative care consultation (n = 2), and media (n = 1 pamphlet and 1 video). No association with mortality was observed (risk ratio, 1.03; 95% CI, 0.98-1.08; P = .22). Intensive care unit LOS was significantly shorter among patients who died (mean difference, -2.11 days; 95% CI, -4.16 to -0.07; P = .04), but not in the overall population (mean difference, -0.79 days; 95% CI, -2.33 to 0.76 days; P = .32). There was no consistent difference in SDM-related outcomes, including satisfaction with care or perceived quality of care (n = 6 studies) and incident psychological comorbidities (depression: ratio of means, -0.11; 95% CI, -0.29 to 0.08; P = .26; anxiety: ratio of means, -0.08; 95% CI, -0.25 to 0.08; P = .31; or posttraumatic stress disorder: ratio of means: -0.04; 95% CI, -0.21 to 0.13; P = .65). Among 6 trials reporting effects on health care resource use, only 1 nurse-led intervention observed a significant reduction in costs ($75 850 control vs $51 060 intervention; P = .04).Conclusions and relevanceSystematic interventions aimed at improving surrogate decision-making for critically ill adults may reduce ICU LOS among patients who die in the ICU, without influencing overall mortality. Better understanding of the complex processes related to surrogate decision-making is needed.

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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