Browsing by Subject "Critical illness"

Now showing 1 - 10 of 28
  • Thumbnail Image
    Item
    A research definition and framework for acute paediatric critical illness across resource-variable settings: a modified Delphi consensus
    (Elsevier, 2024) Arias, Anita V.; Lintner-Rivera, Michael; Shafi, Nadeem I.; Abbas, Qalab; Abdelhafeez, Abdelhafeez H.; Ali, Muhammad; Ammar, Halaashuor; Anwar, Ali I.; Appiah, John Adabie; Attebery, Jonah E.; Diaz Villalobos, Willmer E.; Ferreira, Daiane; González-Dambrauskas, Sebastián; Habib, Muhammad Irfan; Lee, Jan Hau; Kissoon, Niranjan; Tekleab, Atnafu M.; Molyneux, Elizabeth M.; Morrow, Brenda M.; Nadkarni, Vinay M.; Rivera, Jocelyn; Silvers, Rebecca; Steere, Mardi; Tatay, Daniel; Bhutta, Adnan T.; Kortz, Teresa B.; Agulnik, Asya; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network on behalf of the PALISI Global Health Subgroup; Pediatrics, School of Medicine
    The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness. DEFCRIT was developed following a scoping review of 29 studies and key concepts identified by an interdisciplinary, international core expert panel (n=24). A modified Delphi process was then done with a panel of multidisciplinary health-care global experts (n=109) until consensus was reached on eight essential attributes and 28 statements as the basis of DEFCRIT. Consensus was reached in two Delphi rounds with an expert retention rate of 89%. The final consensus definition for acute paediatric critical illness is: an infant, child, or adolescent with an illness, injury, or post-operative state that increases the risk for or results in acute physiological instability (abnormal physiological parameters or vital organ dysfunction or failure) or a clinical support requirement (such as frequent or continuous monitoring or time-sensitive interventions) to prevent further deterioration or death. The proposed definition and framework provide the conceptual clarity needed for a unified approach for global research across resource-variable settings. Future work will centre on validating DEFCRIT and determining high priority measures and guidelines for data collection and analysis that will promote its use in research.
  • Thumbnail Image
    Item
    Abnormal liver tests are not sufficient for diagnosis of hepatic graft‐versus‐host disease in critically ill patients
    (Wolters Kluwer, 2022) Yang, Alexander H.; Han, Mai Ai Thanda; Samala, Niharika; Rizvi, Bisharah S.; Marchalik, Rachel; Etzion, Ohad; Wright, Elizabeth C.; Patel, Ruchi; Khan, Vinshi; Kapuria, Devika; Venkat, Vikramaditya Samala; Kleiner, David E.; Koh, Christopher; Kanakry, Jennifer A.; Kanakry, Christopher G.; Pavletic, Steven; Williams, Kirsten M.; Heller, Theo; Medicine, School of Medicine
    Hepatic graft-versus-host disease (HGVHD) contributes significantly to morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Clinical findings and liver biomarkers are neither sensitive nor specific. The relationship between clinical and histologic diagnoses of HGVHD was assessed premortem and at autopsy. Medical records from patients who underwent HSCT at the National Institutes of Health (NIH) Clinical Center between 2000 and 2012 and expired with autopsy were reviewed, and laboratory tests within 45 days of death were divided into 15-day periods. Clinical diagnosis of HGVHD was based on Keystone Criteria or NIH Consensus Criteria, histologic diagnosis based on bile duct injury without significant inflammation, and exclusion of other potential etiologies. We included 37 patients, 17 of whom had a cholestatic pattern of liver injury and two had a mixed pattern. Fifteen were clinically diagnosed with HGVHD, two showed HGVHD on autopsy, and 13 had histologic evidence of other processes but no HGVHD. Biopsy or clinical diagnosis of GVHD of other organs during life did not correlate with HGVHD on autopsy. The diagnostic accuracy of the current criteria was poor (κ = -0.20). A logistic regression model accounting for dynamic changes included peak bilirubin 15 days before death, and an increase from period -30 (days 30 to 16 before death) to period -15 (15 days before death) showed an area under the receiver operating characteristic curve of 0.77. Infection was the immediate cause of death in 68% of patients. In conclusion, liver biomarkers at baseline and GVHD elsewhere are poor predictors of HGVHD on autopsy, and current clinical diagnostic criteria have unsatisfactory performance. Peak bilirubin and cholestatic injury predicted HGVHD on autopsy. A predictive model was developed accounting for changes over time. Further validation is needed.
  • Thumbnail Image
    Item
    Association between Change in the peripheral biomarkers of inflammation, astrocyte activation, and neuroprotection at one week of critical illness and hospital mortality in patients with delirium: A prospective cohort study
    (Public Library of Science, 2023-09-01) Khan, Sikandar H.; Perkins, Anthony J.; Eltarras, Ahmed M.; Chi, Rosalyn; Athar, Ammar A.; Wang, Sophia; Campbell, Noll L.; Gao, Sujuan; Boustani, Malaz A.; Khan, Babar A.; Medicine, School of Medicine
    Objective: In critically ill adults with delirium, biomarkers of systemic inflammation, astrocyte activation, neuroprotection, and systemic inflammation measured at one week of critical illness may be associated with mortality. Design: Prospective observational study. Setting: Intensive care unit (ICU). Patients: 178 ICU patients with delirium, alive and remaining in ICU at one week. Interventions: None. Measurements and main results: Blood samples collected for a pair of previously published, negative, clinical trials were utilized. Samples were collected at study enrollment/ICU admission (Day 1 sample) and one week later (Day 8 sample), and analyzed for interleukins (IL)-6, 8, 10, Insulin-like Growth Factor (IGF), S100 Binding Protein (S100B), Tumor Necrosis Factor Alpha (TNF-A) and C-Reactive Protein (CRP). Delirium, delirium severity, and coma were assessed twice daily using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), CAM-ICU-7, and Richmond Agitation-Sedation Scale (RASS), respectively. Mortality was assessed until discharge using the electronic medical record. Logistic regression models adjusting for age, sex, severity of illness, comorbidities, sepsis, and randomization status, were used to assess the relationship among biomarkers and mortality. Higher IL-10 quartiles at day 8 were associated with increased odds of hospital mortality (IL-10: OR 2.00 95%CI: 1.1-3.65, p = 0.023). There was a significant interaction between day 1 and day 8 biomarker quartiles only for IL-6. Patients with IL-6 values in the first three quartiles on admission to the ICU that transitioned to higher IL-6 quartiles at day 8 had increased probability of hospital mortality. Conclusion: In this hypothesis-generating study, higher IL-6 and IL-10 quartiles at one week, and increase in IL-6 from day 1 to day 8 were associated with increased hospital mortality. Studies with larger sample sizes are needed to confirm the mechanisms for these observations.
  • Thumbnail Image
    Item
    Biomarkers of Delirium Duration and Delirium Severity: A Reply
    (Wolters Kluwer, 2021) Khan, Sikandar H.; Perkins, Anthony J.; Gao, Sujuan; Khan, Babar A.; Medicine, School of Medicine
  • Thumbnail Image
    Item
    BNT162b2 Protection against the Omicron Variant in Children and Adolescents
    (Massachusetts Medical Society, 2022) Price, Ashley M.; Olson, Samantha M.; Newhams, Margaret M.; Halasa, Natasha B.; Boom, Julie A.; Sahni, Leila C.; Pannaraj, Pia S.; Irby, Katherine; Bline, Katherine E.; Maddux, Aline B.; Nofziger, Ryan A.; Cameron, Melissa A.; Walker, Tracie C.; Schwartz, Stephanie P.; Mack, Elizabeth H.; Smallcomb, Laura; Schuster, Jennifer E.; Hobbs, Charlotte V.; Kamidani, Satoshi; Tarquinio, Keiko M.; Bradford, Tamara T.; Levy, Emily R.; Chiotos, Kathleen; Bhumbra, Samina S.; Cvijanovich, Natalie Z.; Heidemann, Sabrina M.; Cullimore, Melissa L.; Gertz, Shira J.; Coates, Bria M.; Staat, Mary A.; Zinter, Matt S.; Kong, Michele; Chatani, Brandon M.; Hume, Janet R.; Typpo, Katri V.; Maamari, Mia; Flori, Heidi R.; Tenforde, Mark W.; Zambrano, Laura D.; Campbell, Angela P.; Patel, Manish M.; Randolph, Adrienne G.; Overcoming Covid-19 Investigators; Pediatrics, School of Medicine
    Background: Spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant, which led to increased U.S. hospitalizations for coronavirus disease 2019 (Covid-19), generated concern about immune evasion and the duration of protection from vaccines in children and adolescents. Methods: Using a case-control, test-negative design, we assessed vaccine effectiveness against laboratory-confirmed Covid-19 leading to hospitalization and against critical Covid-19 (i.e., leading to receipt of life support or to death). From July 1, 2021, to February 17, 2022, we enrolled case patients with Covid-19 and controls without Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2 messenger RNA vaccine) at least 14 days before illness among case patients and controls, according to time since vaccination for patients 12 to 18 years of age and in periods coinciding with circulation of B.1.617.2 (delta) (July 1, 2021, to December 18, 2021) and omicron (December 19, 2021, to February 17, 2022) among patients 5 to 11 and 12 to 18 years of age. Results: We enrolled 1185 case patients (1043 [88%] of whom were unvaccinated, 291 [25%] of whom received life support, and 14 of whom died) and 1627 controls. During the delta-predominant period, vaccine effectiveness against hospitalization for Covid-19 among adolescents 12 to 18 years of age was 93% (95% confidence interval [CI], 89 to 95) 2 to 22 weeks after vaccination and was 92% (95% CI, 80 to 97) at 23 to 44 weeks. Among adolescents 12 to 18 years of age (median interval since vaccination, 162 days) during the omicron-predominant period, vaccine effectiveness was 40% (95% CI, 9 to 60) against hospitalization for Covid-19, 79% (95% CI, 51 to 91) against critical Covid-19, and 20% (95% CI, -25 to 49) against noncritical Covid-19. During the omicron period, vaccine effectiveness against hospitalization among children 5 to 11 years of age was 68% (95% CI, 42 to 82; median interval since vaccination, 34 days). Conclusions: BNT162b2 vaccination reduced the risk of omicron-associated hospitalization by two thirds among children 5 to 11 years of age. Although two doses provided lower protection against omicron-associated hospitalization than against delta-associated hospitalization among adolescents 12 to 18 years of age, vaccination prevented critical illness caused by either variant.
  • Thumbnail Image
    Item
    A call for collaboration and consensus on training for endotracheal intubation in the medical intensive care unit
    (BMC, 2020-10-22) Brown, Wade; Santhosh, Lekshmi; Brady, Anna K.; Denson, Joshua L.; Niroula, Abesh; Pugh, Meredith E.; Self, Wesley H.; Joffe, Aaron M.; O’Neal Maynord, P.; Carlos, W. Graham; Medicine, School of Medicine
    Endotracheal intubation (EI) is a potentially lifesaving but high-risk procedure in critically ill patients. While the ACGME mandates that trainees in pulmonary and critical care medicine (PCCM) achieve competence in this procedure, there is wide variation in EI training across the USA. One study suggests that 40% of the US PCCM trainees feel they would not be proficient in EI upon graduation. This article presents a review of the EI training literature; the recommendations of a national group of PCCM, anesthesiology, emergency medicine, and pediatric experts; and a call for further research, collaboration, and consensus guidelines.
  • Thumbnail Image
    Item
    Delirium management in critically ill patients
    (2013) Calvo-Ayala, Enrique; Khan, Babar; Medicine, School of Medicine
    Delirium among critically ill patients is common. Presence of delirium imparts a poorer prognosis to patients, including longer ICU and hospital length of stay, increased risk of institutionalization, higher health related costs, and elevated mortality. Even with such grave consequences, the rates of delirium diagnosis are dire. The importance of early recognition through validated tools and appropriate management of this life-threatening condition cannot be over emphasized. This article provides an overview of delirium pathophysiology, diagnosis, and management with a focus on critically ill patients.
  • Thumbnail Image
    Item
    Early Cumulative Fluid Balance and Outcomes in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients With Acute Respiratory Failure: A Multicenter Study
    (Frontiers Media, 2021-07-20) Sallee, Colin J.; Smith, Lincoln S.; Rowan, Courtney M.; Heckbert, Susan R.; Angelo, Joseph R.; Daniel, Megan C.; Gertz, Shira J.; Hsing, Deyin D.; Mahadeo, Kris M.; McArthur, Jennifer A.; Fitzgerald, Julie C.; Pediatrics, School of Medicine
    Objectives: To evaluate the associations between early cumulative fluid balance (CFB) and outcomes among critically ill pediatric allogeneic hematopoietic cell transplant (HCT) recipients with acute respiratory failure, and determine if these associations vary by treatment with renal replacement therapy (RRT). Methods: We performed a secondary analysis of a multicenter retrospective cohort of patients (1mo - 21yrs) post-allogeneic HCT with acute respiratory failure treated with invasive mechanical ventilation (IMV) from 2009 to 2014. Fluid intake and output were measured daily for the first week of IMV (day 0 = day of intubation). The exposure, day 3 CFB (CFB from day 0 through day 3 of IMV), was calculated using the equation [Fluid in - Fluid out] (liters)/[PICU admission weight] (kg)*100. We measured the association between day 3 CFB and PICU mortality with logistic regression, and the rate of extubation at 28 and 60 days with competing risk regression (PICU mortality = competing risk). Results: 198 patients were included in the study. Mean % CFB for the cohort was positive on day 0 of IMV, and increased further on days 1-7 of IMV. For each 1% increase in day 3 CFB, the odds of PICU mortality were 3% higher (adjusted odds ratio (aOR) 1.03, 95% CI 1.00-1.07), and the rate of extubation was 3% lower at 28 days (adjusted subdistribution hazard ratio (aSHR) 0.97, 95% CI 0.95-0.98) and 3% lower at 60 days (aSHR 0.97, 95% CI 0.95-0.98). When day 3 CFB was dichotomized, 161 (81%) had positive and 37 (19%) had negative day 3 CFB. Positive day 3 CFB was associated with higher PICU mortality (aOR 3.42, 95% CI 1.48-7.87) and a lower rate of extubation at 28 days (aSHR 0.30, 95% CI 0.18-0.48) and 60 days (aSHR 0.30, 95% 0.19-0.48). On stratified analysis, the association between positive day 3 CFB and PICU mortality was significantly stronger in those not treated with RRT (no RRT: aOR 9.11, 95% CI 2.29-36.22; RRT: aOR 1.40, 95% CI 0.42-4.74). Conclusions: Among critically ill pediatric allogeneic HCT recipients with acute respiratory failure, positive and increasing early CFB were independently associated with adverse outcomes.
  • Thumbnail Image
    Item
    Enablers and Barriers to Implementing ICU Follow-Up Clinics and Peer Support Groups Following Critical Illness: The Thrive Collaboratives
    (Wolters Kluwer, 2019-09) Haines, Kimberley J.; McPeake, Joanne; Hibbert, Elizabeth; Boehm, Leanne M.; Aparanji, Krishna; Bakhru, Rita N.; Bastin, Anthony J.; Beesley, Sarah J.; Beveridge, Lynne; Butcher, Brad W.; Drumright, Kelly; Eaton, Tammy L.; Farley, Thomas; Firshman, Penelope; Fritschle, Andrew; Holdsworth, Clare; Hope, Aluko A.; Johnson, Annie; Kenes, Michael T.; Khan, Babar A.; Kloos, Janet A.; Kross, Erin K.; Mactavish, Pamela; Meyer, Joel; Montgomery-Yates, Ashley; Quasim, Tara; Saft, Howard L.; Slack, Andrew; Stollings, Joanna; Weinhouse, Gerald; Whitten, Jessica; Netzer, Giora; Hopkins, Ramona O.; Mikkelsen, Mark E.; Iwashyna, Theodore J.; Sevin, Carla M.; Medicine, School of Medicine
    OBJECTIVES: Data are lacking regarding implementation of novel strategies such as follow-up clinics and peer support groups, to reduce the burden of postintensive care syndrome. We sought to discover enablers that helped hospital-based clinicians establish post-ICU clinics and peer support programs, and identify barriers that challenged them. DESIGN: Qualitative inquiry. The Consolidated Framework for Implementation Research was used to organize and analyze data. SETTING: Two learning collaboratives (ICU follow-up clinics and peer support groups), representing 21 sites, across three continents. SUBJECTS: Clinicians from 21 sites. MEASUREMENT AND MAIN RESULTS: Ten enablers and nine barriers to implementation of "ICU follow-up clinics" were described. A key enabler to generate support for clinics was providing insight into the human experience of survivorship, to obtain interest from hospital administrators. Significant barriers included patient and family lack of access to clinics and clinic funding. Nine enablers and five barriers to the implementation of "peer support groups" were identified. Key enablers included developing infrastructure to support successful operationalization of this complex intervention, flexibility about when peer support should be offered, belonging to the international learning collaborative. Significant barriers related to limited attendance by patients and families due to challenges in creating awareness, and uncertainty about who might be appropriate to attend and target in advertising. CONCLUSIONS: Several enablers and barriers to implementing ICU follow-up clinics and peer support groups should be taken into account and leveraged to improve ICU recovery. Among the most important enablers are motivated clinician leaders who persist to find a path forward despite obstacles.
  • Thumbnail Image
    Item
    Endothelial Activation, Acute Kidney Injury, and Cognitive Impairment in Pediatric Severe Malaria
    (Wolters Kluwer, 2020-09) Ouma, Benson J.; Ssenkusu, John M.; Shabani, Estela; Datta, Dibyadyuti; Opoka, Robert O.; Idro, Richard; Bangirana, Paul; Park, Gregory; Joloba, Moses L.; Kain, Kevin C.; John, Chandy C.; Conroy, Andrea L.; Pediatrics, School of Medicine
    Objectives: Evaluate the relationship between endothelial activation, malaria complications, and long-term cognitive outcomes in severe malaria survivors. Design: Prospectively cohort study of children with cerebral malaria, severe malarial anemia, or community children. Setting: Mulago National Referral Hospital in Kampala, Uganda. Subjects: Children 18 months to 12 years old with severe malaria (cerebral malaria, n = 253 or severe malarial anemia, n = 211) or community children (n = 206) were followed for 24 months. Interventions: None. Measurements and main results: Children underwent neurocognitive evaluation at enrollment (community children) or a week following hospital discharge (severe malaria) and 6, 12, and 24 months follow-up. Endothelial activation was assessed at admission on plasma samples (von Willebrand factor, angiopoietin-1 and angiopoietin-2, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-Selectin, and P-Selectin). False discovery rate was used to adjust for multiple comparisons. Severe malaria was associated with widespread endothelial activation compared with community children (p < 0.0001 for all markers). Acute kidney injury was independently associated with changes in von Willebrand factor, soluble intercellular adhesion molecule-1, soluble E-Selectin, P-Selectin, and angiopoietin-2 (p < 0.0001 for all). A log10 increase in angiopoietin-2 was associated with lower cognitive z scores across age groups (children < 5, β -0.42, 95% CI, -0.69 to -0.15, p = 0.002; children ≥ 5, β -0.39, 95% CI, -0.67 to -0.11, p = 0.007) independent of disease severity (coma, number of seizures, acute kidney injury) and sociodemographic factors. Angiopoietin-2 was associated with hemolysis (lactate dehydrogenase, total bilirubin) and inflammation (tumor necrosis factor-α, interleukin-10). In children with cerebral malaria who had a lumbar puncture performed, angiopoietin-2 was associated with blood-brain barrier dysfunction, and markers of neuroinflammation and injury in the cerebrospinal fluid (tumor necrosis factor-α, kynurenic acid, tau). Conclusions: These data support angiopoietin-2 as a measure of disease severity and a risk factor for long-term cognitive injury in children with severe malaria.