2020 Sep - Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19

 JAMA 2020. doi:10.1001/jama.2020.17022

Conclusions and Relevance : Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

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2020 Jan -The PEPTIC Randomized Clinical Trial


Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation

The PEPTIC Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Alberta Health Services Critical Care Strategic Clinical Network, and the Irish Critical Care Trials Group


Question  What is the comparative effect on in-hospital mortality of using proton pump inhibitors (PPIs) vs histamine-2 receptor blockers (H2RBs) for stress ulcer prophylaxis among adults requiring invasive mechanical ventilation in the intensive care unit (ICU)?

Findings  In this cluster crossover randomized clinical trial, 26 982 patients requiring invasive mechanical ventilation within 24 hours of ICU admission were randomized by site at 50 ICUs in 5 countries to a PPI strategy or an H2RB strategy for stress ulcer prophylaxis. In-hospital mortality was 18.3% for patients treated at sites randomized to PPI use vs 17.5% for those treated at sites randomized to H2RB use, a difference that did not reach statistical significance (P = .054). Among patients treated at sites randomized to PPIs, 4.1% received H2RBs; among patients treated at sites randomized to H2RBs, 20.1% received PPIs.

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2016 May - Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury: The ELAIN Randomized Clinical Trial

Zarbock A, Kellum JA, Schmidt C, Van Aken H, Wempe C, Pavenstädt H, Boanta A, Gerß J, Meersch M.; JAMA. 2016 May 24-31;315(20):2190-9.

IMPORTANCE: Optimal timing of initiation of renal replacement therapy (RRT) for severe acute kidney injury (AKI) but without life-threatening indications is still unknown.

OBJECTIVE: To determine whether early initiation of RRT in patients who are critically ill with AKI reduces 90-day all-cause mortality.

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2016 Apr - Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients: A Randomized Clinical Trial

Hernández G, Vaquero C, González P, Subira C, Frutos-Vivar F, Rialp G, Laborda C, Colinas L, Cuena R, Fernández R.; JAMA. 2016 Apr 5;315(13):1354-61.

IMPORTANCE: Studies of mechanically ventilated critically ill patients that combine populations that are at high and low risk for reintubation suggest that conditioned high-flow nasal cannula oxygen therapy after extubation improves oxygenation compared with conventional oxygen therapy. However, conclusive data about reintubation are lacking.

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2016 Feb - Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC.; JAMA. 2016 Feb 23;315(8):762-74.

IMPORTANCE: The Third International Consensus Definitions Task Force defined sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection." The performance of clinical criteria for this sepsis definition is unknown.

OBJECTIVE: To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis.

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2016 Feb - Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, Angus DC, Rubenfeld GD, Singer M; Sepsis Definitions Task Force.; JAMA. 2016 Feb 23;315(8):775-87.

IMPORTANCE: Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition.

OBJECTIVE: To develop a new definition and clinical criteria for identifying septic shock in adults.

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2016 Feb - The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC.; JAMA. 2016 Feb 23;315(8):801-10.

ImportanceDefinitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.

Objective:  To evaluate and, as needed, update definitions for sepsis and septic shock.

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2015 Nov - Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis

Badhiwala JH, Nassiri F, Alhazzani W, Selim MH, Farrokhyar F, Spears J, Kulkarni AV, Singh S, Alqahtani A, Rochwerg B, Alshahrani M, Murty NK, Alhazzani A, Yarascavitch B, Reddy K, Zaidat OO, Almenawer SA.;JAMA. 2015 Nov 3;314(17):1832-43.

IMPORTANCE: Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of endovascular intervention among subgroups needs better definition.

OBJECTIVE: To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke.

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2015 Feb - Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial

Torres A, Sibila O, Ferrer M, Polverino E, Menendez R, Mensa J, Gabarrús A, Sellarés J, Restrepo MI, Anzueto A, Niederman MS, Agustí C.; JAMA. 2015 Feb 17;313(7):677-86.

IMPORTANCE: In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial.

OBJECTIVE: To assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response.

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2015 Feb - Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial

Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, del Junco DJ, Brasel KJ, Bulger EM, Callcut RA, Cohen MJ, Cotton BA, Fabian TC, Inaba K, Kerby JD, Muskat P, O'Keeffe T, Rizoli S, Robinson BR, Scalea TM, Schreiber MA, Stein DM, Weinberg JA, Callum JL, Hess JR, Matijevic N, Miller CN, Pittet JF, Hoyt DB, Pearson GD, Leroux B, van Belle G; PROPPR Study Group.; JAMA. 2015 Feb 3;313(5):471-82.

IMPORTANCE: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials.

OBJECTIVE: To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio.

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2015 Jan - Diagnosis and treatment of Clostridium difficile in adults: a systematic review

Bagdasarian N, Rao K, Malani PN. JAMA. 2015 Jan 27;313(4):398-408.

IMPORTANCE: Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased.

OBJECTIVE: To review current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age ≥ 18 years).

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2014 Aug - High-Protein Enteral Nutrition Enriched With Immune-Modulating Nutrients vs Standard High-Protein Enteral Nutrition and Nosocomial Infections in the ICU

van Zanten AR, Sztark F, Kaisers UX, Zielmann S, Felbinger TW, Sablotzki AR, De Waele JJ, Timsit JF, Honing ML, Keh D, Vincent JL, Zazzo JF, Fijn HB, Petit L, Preiser JC, van Horssen PJ, Hofman Z. ;JAMA. 2014 Aug 6;312(5):514-24.

IMPORTANCE: Enteral administration of immune-modulating nutrients (eg, glutamine, omega-3 fatty acids, selenium, and antioxidants) has been suggested to reduce infections and improve recovery from critical illness. However, controversy exists on the use of immune-modulating enteral nutrition, reflected by lack of consensus in guidelines.

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2014 Jul - Effect of Erythropoietin and Transfusion Threshold on Neurological Recovery After Traumatic Brain InjuryA Randomized Clinical Trial

Robertson CS, Hannay HJ, Yamal JM, Gopinath S, Goodman JC, Tilley BC; Epo Severe TBI Trial Investigators, Baldwin A, Rivera Lara L, Saucedo-Crespo H, Ahmed O, Sadasivan S, Ponce L, Cruz-Navarro J, Shahin H, Aisiku IP, Doshi P, Valadka A, Neipert L, Waguspack JM, Rubin ML, Benoit JS, Swank P.; JAMA. 2014 Jul 2;312(1):36-47.

IMPORTANCE: There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury.

OBJECTIVE: To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury.

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2014 Feb - ICU Bed Supply, Utilization, and Health Care Spending - An Example of Demand Elasticity

Gooch RA, Kahn JM.; JAMA. 2014 Feb 12;311(6):567-8.

Intensive care is a substantial financial burden on the US health care system, with spending on critical illness exceeding $80 billion per year, approximately 3% of all health care spending and nearly 1% of the gross domestic product. In contrast, the United Kingdom spends only 0.1% of its gross domestic product on critical care services, with no evidence of worse patient outcomes and similar life expectancies as in the United States...

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2013 Dec - Calcium-Channel Blocker–Clarithromycin Drug Interactions and Acute Kidney Injury

Gandhi S, Fleet JL, Bailey DG, McArthur E, Wald R, Rehman F, Garg AX.; JAMA. 2013 Dec 18;310(23):2544-53.

IMPORTANCE: Calcium-channel blockers are metabolized by the cytochrome P450 3A4 (CYP3A4; EC enzyme. Blood concentrations of these drugs may rise to harmful levels when CYP3A4 activity is inhibited. Clarithromycin is an inhibitor of CYP3A4 and azithromycin is not, which makes comparisons between these 2 macrolide antibiotics useful in assessing clinically important drug interactions.

27 Nov 2013 - Induced hypothermia in severe bacterial meningitis: a randomized clinical trial

Mourvillier B, Tubach F, van de Beek D, Garot D, Pichon N, Georges H, Lefevre LM, Bollaert PE, Boulain T, Luis D, Cariou A, Girardie P, Chelha R, Megarbane B, Delahaye A, Chalumeau-Lemoine L, Legriel S, Beuret P, Brivet F, Bruel C, Camou F, Chatellier D, Chillet P, Clair B, Constantin JM, Duguet A, Galliot R, Bayle F, Hyvernat H, Ouchenir K, Plantefeve G, Quenot JP, Richecoeur J, Schwebel C, Sirodot M, Esposito-Farèse M, Le Tulzo Y, Wolff M.; JAMA. 2013 Nov 27;310(20):2174-83

Importance:  Despite advances in care, mortality and morbidity remain high in adults with acute bacterial meningitis, particularly when due to Streptococcus pneumoniae. Induced hypothermia is beneficial in other conditions with global cerebral hypoxia.

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2013 Oct 23/30 - Effect of Statin Therapy on Mortality in Patients With Ventilator-Associated Pneumonia A Randomized Clinical Trial

Papazian L, Roch A, Charles PE, Penot-Ragon C, Perrin G, Roulier P, Goutorbe P, Lefrant JY, Wiramus S, Jung B, Perbet S, Hernu R, Nau A, Baldesi O, Allardet-Servent J, Baumstarck K, Jouve E, Moussa M, Hraiech S, Guervilly C, Forel JM; STATIN-VAP Study Group.; JAMA. 2013 Oct 23;310(16):1692-700

Importance:  Observational studies have reported that statin use may be associated with improved outcomes of various infections. Ventilator-associated pneumonia (VAP) is the most common infection in the intensive care unit (ICU) and is associated with substantial mortality.

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2013 Nov 6 - Effects of Fluid Resuscitation With Colloids vs Crystalloids on Mortality in Critically Ill Patients Presenting With Hypovolemic ShockThe CRISTAL Randomized Trial

Annane D, Siami S, Jaber S, Martin C, Elatrous S, Declère AD, Preiser JC, Outin H, Troché G, Charpentier C, Trouillet JL, Kimmoun A, Forceville X, Darmon M, Lesur O, Régnier J, Abroug F, Berger P, Clec'h C, Cousson J, Thibault L, Chevret S; CRISTAL Investigators.; JAMA. 2013 Nov 6;310(17):1809-17.

Importance:  Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear.

Objective:  To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock.

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2013 Sep 2 - A Risk Prediction Score for Kidney Failure or Mortality in Rhabdomyolysis

Gearoid M. McMahon, MB, BCh; Xiaoxi Zeng, MD; Sushrut S. Waikar, MD, MPH. JAMA Intern Med. Published online September 02, 2013. doi:10.1001/jamainternmed.2013.9774.

Importance   Rhabdomyolysis ranges in severity from asymptomatic elevations in creatine phosphokinase levels to a life-threatening disorder characterized by severe acute kidney injury requiring hemodialysis or continuous renal replacement therapy (RRT).

2013 Aug 5 - Similarity of Lateralized Rhythmic Delta Activity to Periodic Lateralized Epileptiform Discharges in Critically Ill Patients

Nicolas Gaspard, MD, PhD; Louis Manganas, MD, PhD; Nishi Rampal, MD; Ognen A. C. Petroff, MD; Lawrence J. Hirsch, MD. JAMA Neurol. 2013;():-. doi:10.1001/jamaneurol.2013.3475. Published online August 5, 2013

The increasing use of continuous electroencephalography (EEG) monitoring in the intensive care unit has led to recognition of new EEG patterns that are of unclear or unknown significance.

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