Recently, the use of Yttrium-90 transarterial radioembolization in non-surgical hepatocellular carcinoma was suggested but the evidence supporting its use is unclear.
We searched Medline, Embase, Web ...of Science and Cochrane CENTRAL from inception up to April 14, 2020 for randomized controlled trials comparing Y90-TARE to standard of care in non-surgical HCC patients. Our primary outcome was overall survival (OS). Our secondary outcomes were progression-free survival, time to progression, disease control rate, grade ≥3 adverse events and rates of gastro-intestinal ulcers. Hazard ratios (HR) and risk ratios (RR) with random-effects model were used for our analyses. The risk of bias of the included studies was assessed using Cochrane's RoB 2 tool.
Of 1,604 citations identified, eight studies (1,439 patients) were included in our analysis. No improvement in overall survival were noted when Yttrium-90 transarterial radioembolization was compared to standard treatments (HR 0.99 95% CI 0.81-1.21, 6 studies, I2 = 77.6%). However, Yttrium-90 transarterial radioembolization was associated with fewer grade ≥3 adverse events (RR 0.64 95% CI 0.45-0.92, 7 studies, I2 = 66%). No difference was observed on other secondary outcomes.
In non-surgical HCC patients, Yttrium-90 transarterial radioembolization was not associated with significant effect on survival, progression-free survival, time to progression, disease control rate and the incidence of gastro-intestinal ulcers but was however associated with significantly lower rates of grade ≥3 adverse events. Further randomized controlled trials are warranted to better delineate optimal treatment.
Incomplete reporting of study methods and results has become a focal point for failures in the reproducibility and translation of findings from preclinical research. Here we demonstrate that ...incomplete reporting of preclinical research is not limited to a few elements of research design, but rather is a broader problem that extends to the reporting of the methods and results. We evaluated 47 preclinical research studies from a systematic review of acute lung injury that use mesenchymal stem cells (MSCs) as a treatment. We operationalized the ARRIVE (Animal Research: Reporting of In Vivo Experiments) reporting guidelines for pre-clinical studies into 109 discrete reporting sub-items and extracted 5,123 data elements. Overall, studies reported less than half (47%) of all sub-items (median 51 items; range 37-64). Across all studies, the Methods Section reported less than half (45%) and the Results Section reported less than a third (29%). There was no association between journal impact factor and completeness of reporting, which suggests that incomplete reporting of preclinical research occurs across all journals regardless of their perceived prestige. Incomplete reporting of methods and results will impede attempts to replicate research findings and maximize the value of preclinical studies.
Fresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive ...materials in blood components during prolonged storage.
In this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality.
Between March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (±SD) of 6.1±4.9 days in the fresh-blood group as compared with 22.0±8.4 days in the standard-blood group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and 430 patients (35.3%) in the standard-blood group had died (absolute risk difference, 1.7 percentage points; 95% confidence interval CI, -2.1 to 5.5). In the survival analysis, the hazard ratio for death in the fresh-blood group, as compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38). There were no significant between-group differences in any of the secondary outcomes (major illnesses; duration of respiratory, hemodynamic, or renal support; length of stay in the hospital; and transfusion reactions) or in the subgroup analyses.
Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718.).
Hydroxyethyl starch is commonly used for volume resuscitation yet has been associated with serious adverse events, including acute kidney injury and death. Clinical trials of hydroxyethyl starch are ...conflicting. Moreover, multiple trials from one investigator have been retracted because of scientific misconduct.
To evaluate the association of hydroxyethyl starch use with mortality and acute kidney injury.
Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, Global Health, HealthStar, Scopus, Web of Science, the International Clinical Trials Registry Platform (inception to October 2012), reference lists of relevant articles, and gray literature.
Two reviewers independently identified randomized controlled trials comparing hydroxyethyl starch with other resuscitation fluids in critically ill patients receiving acute volume resuscitation.
Two reviewers independently extracted trial-level data including population characteristics, interventions, outcomes, and funding sources. Risk of bias was assessed using the risk of bias tool; the strength of evidence was adjudicated using the GRADE methodology.
We included 38 eligible trials comparing hydroxyethyl starch to crystalloids, albumin, or gelatin. The majority of trials were categorized as having an unclear risk or high risk of bias. For the 10,880 patients in studies contributing mortality data, the risk ratio (RR) for death among patients randomized to receive hydroxyethyl starch was 1.07 (95% CI, 1.00 to 1.14; I2, 0%; absolute risk AR, 1.20%; 95% CI, -0.26% to 2.66%). This summary effect measure included results from 7 trials performed by an investigator whose subsequent research had been retracted because of scientific misconduct. When we excluded these 7 trials that involved 590 patients, hydroxyethyl starch was found to be associated with increased mortality among 10,290 patients (RR, 1.09; 95% CI, 1.02 to 1.17; I2, 0%; AR, 1.51%; 95% CI, 0.02% to 3.00%), increased renal failure among 8725 patients (RR, 1.27; 95% CI, 1.09 to 1.47; I2, 26%; AR, 5.45%; 95% CI, 0.44% to 10.47%), and increased use of renal replacement therapy among 9258 patients (RR, 1.32; 95% CI, 1.15 to 1.50; I2, 0%; AR, 3.12%; 95% CI, 0.47% to 5.78%).
In critically ill patients requiring acute volume resuscitation, use of hydroxyethyl starch compared with other resuscitation solutions was not associated with a decrease in mortality. Moreover, after exclusion of 7 trials performed by an investigator whose research has been retracted because of scientific misconduct, hydroxyethyl starch was associated with a significant increased risk of mortality and acute kidney injury. Clinical use of hydroxyethyl starch for acute volume resuscitation is not warranted due to serious safety concerns.
Purpose
Increasingly, very old patients are admitted to Intensive Care Units (ICUs). The objective of this study was to describe 12-month outcomes of these patients and determine which ...characteristics are associated with a return to baseline physical function 1 year later.
Methods
In this prospective cohort study in 22 Canadian hospitals, we recruited 610 patients aged 80 years or older who were admitted to ICU for at least 24 h. At baseline, we completed a comprehensive geriatric assessment and followed patients to determine 12-month survival and physical function. Our primary outcome was physical recovery from critical illness at 12 months, defined as being alive with Short Form-36 physical function score of at least 10 points, and not 10 or more points below baseline. We used regression analysis to examine factors associated with physical recovery.
Results
Patients were on average 84 years old (range 80–99). Mortality was 14 % in ICU, 26 % in hospital and 44 % at 12 months after admission. Of 505 patients evaluable at 12 months, 26 % achieved physical recovery. In the multivariable model, physical recovery was significantly associated with younger age, lower APACHE II score, lower Charlson comorbidity score, lower frailty index, lower baseline physical function score, and specific admission diagnoses.
Conclusions
One-quarter of patients aged 80 years or older who are admitted to ICU survived and returned to baseline levels of physical function at 1 year. Routine assessment of baseline physical function and frailty status could aid in prognostication and informed decision-making for very old critically ill patients. (ClinicalTrials.gov number NCT01293708).
Background: Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) ...poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning.
Methods: Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method.
Results: For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin.
For LA-toxicity we suggest the use of Intralipid
®
20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence.
Conclusion: Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.
Dynamic tests of fluid responsiveness have been developed and investigated in clinical trials of goal-directed therapy. The impact of this approach on clinically relevant outcomes is unknown. We ...performed a systematic review and meta-analysis to evaluate whether fluid therapy guided by dynamic assessment of fluid responsiveness compared with standard care improves clinically relevant outcomes in adults admitted to the ICU.
Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov, and the International Clinical Trials Registry Platform from inception to December 2016, conference proceedings, and reference lists of relevant articles.
Two reviewers independently identified randomized controlled trials comparing dynamic assessment of fluid responsiveness with standard care for acute volume resuscitation in adults admitted to the ICU.
Two reviewers independently abstracted trial-level data including population characteristics, interventions, clinical outcomes, and source of funding. Our primary outcome was mortality at longest duration of follow-up. Our secondary outcomes were ICU and hospital length of stay, duration of mechanical ventilation, and frequency of renal complications. The internal validity of trials was assessed in duplicate using the Cochrane Collaboration's Risk of Bias tool.
We included 13 trials enrolling 1,652 patients. Methods used to assess fluid responsiveness included stroke volume variation (nine trials), pulse pressure variation (one trial), and stroke volume change with passive leg raise/fluid challenge (three trials). In 12 trials reporting mortality, the risk ratio for death associated with dynamic assessment of fluid responsiveness was 0.59 (95% CI, 0.42-0.83; I = 0%; n = 1,586). The absolute risk reduction in mortality associated with dynamic assessment of fluid responsiveness was -2.9% (95% CI, -5.6% to -0.2%). Dynamic assessment of fluid responsiveness was associated with reduced duration of ICU length of stay (weighted mean difference, -1.16 d 95% CI, -1.97 to -0.36; I = 74%; n = 394, six trials) and mechanical ventilation (weighted mean difference, -2.98 hr 95% CI, -5.08 to -0.89; I = 34%; n = 334, five trials). Three trials were adjudicated at unclear risk of bias; the remaining trials were at high risk of bias.
In adult patients admitted to intensive care who required acute volume resuscitation, goal-directed therapy guided by assessment of fluid responsiveness appears to be associated with reduced mortality, ICU length of stay, and duration of mechanical ventilation. High-quality clinical trials in both medical and surgical ICU populations are warranted to inform routine care.
SARS-CoV-2 infection causing the novel coronavirus disease 2019 (COVID-19) has been responsible for more than 2.8 million deaths and nearly 125 million infections worldwide as of March 2021. In March ...2020, the World Health Organization determined that the COVID-19 outbreak is a global pandemic. The urgency and magnitude of this pandemic demanded immediate action and coordination between local, regional, national, and international actors. In that mission, researchers require access to high-quality biological materials and data from SARS-CoV-2 infected and uninfected patients, covering the spectrum of disease manifestations. The "Biobanque québécoise de la COVID-19" (BQC19) is a pan-provincial initiative undertaken in Québec, Canada to enable the collection, storage and sharing of samples and data related to the COVID-19 crisis. As a disease-oriented biobank based on high-quality biosamples and clinical data of hospitalized and non-hospitalized SARS-CoV-2 PCR positive and negative individuals. The BQC19 follows a legal and ethical management framework approved by local health authorities. The biosamples include plasma, serum, peripheral blood mononuclear cells and DNA and RNA isolated from whole blood. In addition to the clinical variables, BQC19 will provide in-depth analytical data derived from the biosamples including whole genome and transcriptome sequencing, proteome and metabolome analyses, multiplex measurements of key circulating markers as well as anti-SARS-CoV-2 antibody responses. BQC19 will provide the scientific and medical communities access to data and samples to better understand, manage and ultimately limit, the impact of COVID-19. In this paper we present BQC19, describe the process according to which it is governed and organized, and address opportunities for future research collaborations. BQC19 aims to be a part of a global communal effort addressing the challenges of COVID-19.
Widely used for acute pain management, the clinical benefit from perioperative use of gabapentinoids is uncertain. The aim of this systematic review was to assess the analgesic effect and adverse ...events with the perioperative use of gabapentinoids in adult patients.
Randomized controlled trials studying the use of gabapentinoids in adult patients undergoing surgery were included. The primary outcome was the intensity of postoperative acute pain. Secondary outcomes included the intensity of postoperative subacute pain, incidence of postoperative chronic pain, cumulative opioid use, persistent opioid use, lengths of stay, and adverse events. The clinical significance of the summary estimates was assessed based on established thresholds for minimally important differences.
In total, 281 trials (N = 24,682 participants) were included in this meta-analysis. Compared with controls, gabapentinoids were associated with a lower postoperative pain intensity (100-point scale) at 6 h (mean difference, -10; 95% CI, -12 to -9), 12 h (mean difference, -9; 95% CI, -10 to -7), 24 h (mean difference, -7; 95% CI, -8 to -6), and 48 h (mean difference, -3; 95% CI, -5 to -1). This effect was not clinically significant ranging below the minimally important difference (10 points out of 100) for each time point. These results were consistent regardless of the type of drug (gabapentin or pregabalin). No effect was observed on pain intensity at 72 h, subacute and chronic pain. The use of gabapentinoids was associated with a lower risk of postoperative nausea and vomiting but with more dizziness and visual disturbance.
No clinically significant analgesic effect for the perioperative use of gabapentinoids was observed. There was also no effect on the prevention of postoperative chronic pain and a greater risk of adverse events. These results do not support the routine use of pregabalin or gabapentin for the management of postoperative pain in adult patients.
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