Estimated Urinary Flow Rate and Contrast-Associated Acute Kidney Injury Risk: The PRESERVE (Prevention of Serious Adverse Events Following Angiography) Trial.
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SUBMITTER: Bullen AL
PROVIDER: S-EPMC8178467 | biostudies-literature | 2021 May-Jun
REPOSITORIES: biostudies-literature
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Estimated Urinary Flow Rate and Contrast-Associated Acute Kidney Injury Risk: The PRESERVE (Prevention of Serious Adverse Events Following Angiography) Trial.
Bullen Alexander L AL Cashion Winn W Webster Luke L Palevsky Paul M PM Weisbord Steven D SD Ix Joachim H JH
Kidney medicine 20210227 3
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Project description:Contrast-induced AKI (CI-AKI) is a common condition associated with serious, adverse outcomes. CI-AKI may be preventable because its risk factors are well characterized and the timing of renal insult is commonly known in advance. Intravenous (IV) fluids and N-acetylcysteine (NAC) are two of the most widely studied preventive measures for CI-AKI. Despite a multitude of clinical trials and meta-analyses, the most effective type of IV fluid (sodium bicarbonate versus sodium chloride) and the benefit of NAC remain unclear. Careful review of published trials of these interventions reveals design limitations that contributed to their inconclusive findings. Such design limitations include the enrollment of small numbers of patients, increasing the risk for type I and type II statistical errors; the use of surrogate primary endpoints defined by small increments in serum creatinine, which are associated with, but not necessarily causally related to serious, adverse, patient-centered outcomes; and the inclusion of low-risk patients with intact baseline kidney function, yielding low event rates and reduced generalizability to a higher-risk population. The Prevention of Serious Adverse Events following Angiography (PRESERVE) trial is a randomized, double-blind, multicenter trial that will enroll 8680 high-risk patients undergoing coronary or noncoronary angiography to compare the effectiveness of IV isotonic sodium bicarbonate versus IV isotonic sodium chloride and oral NAC versus oral placebo for the prevention of serious, adverse outcomes associated with CI-AKI. This article discusses key methodological issues of past trials investigating IV fluids and NAC and how they informed the design of the PRESERVE trial.
| S-EPMC3805082 | biostudies-literature
Project description:Rationale & objectiveRecent studies in patients with chronic kidney disease (CKD) indicate that most cases of contrast-associated acute kidney injury (CA-AKI) are mild and are not associated with elevation in kidney injury biomarkers. We used highly sensitive kidney cell cycle arrest and cardiac biomarkers to assess the risk of CA-AKI and major adverse kidney events in patients with CKD undergoing angiography.Study designA retrospective study.Setting & participantsA subset of 922 participants from the Prevention of Serious Adverse Events following Angiography trial.PredictorsPre- and postangiography urinary tissue inhibitor of matrix metalloproteinase [TIMP]-2 and insulin growth factor binding protein [IGFBP]-7 were measured in 742 subjects, and plasma β natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP), and serum troponin (Tn) in 854 participants using samples obtained 1-2 hours before and 2-4 hours after angiography.OutcomesCA-AKI and major adverse kidney events.Analytical approachWe fitted logistic regression to examine association and area under the receiver operating characteristic curves for risk prediction.ResultsThere were no differences in postangiography urinary [TIMP-2]•[IGFBP7], plasma BNP, serum Tn, and hs-CRP concentrations among patients with and without CA-AKI and major adverse kidney events. However, higher pre- and postangiography median plasma BNP (pre: 200.0 vs 71.5, pg/mL, P = 0.05; post: 165.0 vs 81 pg/mL, P = 0.02); serum Tn (pre: 0.03 vs 0.01, ng/mL, P < 0.001; post, 0.04 vs 0.02, ng/mL, P = 0.01); and hs-CRP (pre: 9.55 vs 3.40 mg/L, P = 0.01; post: 9.90 vs 3.20 mg/L, P = 0.002) concentrations were associated with major adverse kidney events, although their discriminatory capacity was only modest (area under the receiver operating characteristic curves <0.7).LimitationsMost participants were men.ConclusionsMost mild CA-AKI cases are not associated with urinary cell cycle arrest biomarker elevation. Significant elevation in preangiography cardiac biomarkers may reflect patients with more significant cardiovascular disease that may predispose to poor long-term outcomes independent of CA-AKI status.
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Project description:Technological advances allow continuous vital sign monitoring at the general ward, but traditional vital signs alone may not predict serious adverse events (SAE). This study investigated continuous heart rate variability (HRV) monitoring's predictive value for SAEs in acute medical and major surgical patients. Data was collected from four prospective observational studies and two randomized controlled trials using a single-lead ECG. The primary outcome was any SAE, secondary outcomes included all-cause mortality and specific non-fatal SAE groups, all within 30 days. Subgroup analyses of medical and surgical patients were performed. The primary analysis compared the last 24 h preceding an SAE with the last 24 h of measurements in patients without an SAE. The area under a receiver operating characteristics curve (AUROC) quantified predictive performance, interpretated as low prognostic ability (0.5-0.7), moderate prognostic ability (0.7-0.9), or high prognostic ability (> 0.9). Of 1402 assessed patients, 923 were analysed, with 297 (32%) experiencing at least one SAE. The best performing threshold had an AUROC of 0.67 (95% confidence interval (CI) 0.63-0.71) for predicting cardiovascular SAEs. In the surgical subgroup, the best performing threshold had an AUROC of 0.70 (95% CI 0.60-0.81) for neurologic SAE prediction. In the medical subgroup, thresholds for all-cause mortality, cardiovascular, infectious, and neurologic SAEs had moderate prognostic ability, and the best performing threshold had an AUROC of 0.85 (95% CI 0.76-0.95) for predicting neurologic SAEs. Predicting SAEs based on the accumulated time below thresholds for individual continuously measured HRV parameters demonstrated overall low prognostic ability in high-risk hospitalized patients. Certain HRV thresholds had moderate prognostic ability for prediction of specific SAEs in the medical subgroup.
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Project description:BackgroundCystic fibrosis (CF) is an autosomal recessive disease characterized by chronic sinopulmonary symptoms and chronic gastrointestinal symptoms that begins in infancy. Children with CF are increasingly being included in clinical trials. In order to fully evaluate the impact of new therapies in future clinical trials, an understanding of baseline adverse event (AE) rates in children with CF is needed. To address this, we determined the rates of common AEs in pediatric patients with CF who participated in two clinical trials.MethodsWe reviewed AEs for placebo recipients in the AZ0004 study and inhaled tobramycin recipients in the Early Pseudomonas Infection Control (EPIC) clinical trial. AEs were categorized based on Medical Dictionary for Regulatory Activities (MedDRA) coding classifications and pooled into common, batched AE descriptors. AE rates were estimated from negative binomial models according to age groups, severity of lung disease, and season.ResultsA total of 433 children had 8,266 total AEs reported, or 18.1 (95% CI 17.0, 19.2) AEs per person per year. Respiratory AEs were the most commonly reported AEs, with a rate of 7.6 events per person-year. The total SAE rate was 0.33 per person per-year. Cough was the most commonly reported respiratory AE, with 61% of subjects reporting at least one episode of cough within 4 months. The rate ratio of any AE was higher in Spring, Fall, and Winter, compared with Summer.ConclusionsAEs occur commonly in pediatric CF clinical trial participants. Season of enrollment could affect AE rates.
| S-EPMC8448791 | biostudies-literature
Project description:The genetic basis of congenital heart disease is yet to be defined, and the interactions between the malformed heart and biomechanical cardiac performance remain poorly understood. Functional optical imaging enables detailed biomechanical phenotyping of cardiac dysfunction in small animal models, which in turn enables specific gene-phenotype relationship. We have developed a new microangiography technique based on flow imaging using endogenous hemoglobin contrast enabling in vivo assessment and biomechanical phenotyping of Xenopus tropicalis embryonic heart. We demonstrated that hemoglobin contrast angiography can be used to quantify physiological response to treatment with well-established cardioactive drugs.
| S-EPMC3881542 | biostudies-literature
Project description:ImportanceSome ophthalmologists may be reluctant to prescribe oral carbonic anhydrase inhibitors, given the potential for life-threatening systemic adverse reactions.ObjectiveTo conduct a population-based analysis of the safety of oral or topical carbonic anhydrase inhibitors in clinical care.Design, setting, and participantsThis matched longitudinal cohort study took place in Ontario, Canada. Consecutive patients older than 65 years who were prescribed an oral or topical carbonic anhydrase inhibitor in Ontario, Canada, between January 1, 1995, and January 1, 2020, were identified. Patients were matched 1-to-1 based on age, sex, and diabetes status. Time zero was defined as the date of the first identified prescription for the medication, and the primary analysis focused on the first 120 days of follow-up.Main outcomes and measuresThe primary end point was a severe complicated adverse event of either Stevens-Johnson syndrome, toxic epidermal necrolysis, or aplastic anemia.ResultsOverall, 128 942 matched patients initiated an oral or topical carbonic anhydrase inhibitor during the 25-year study period. The mean (SD) age was 75 (6.6) years, 71 958 (55.8%) were women, and 25 058 (19.4%) had a diagnosis of diabetes. The oral and topical carbonic anhydrase inhibitor groups had similar baseline demographics. Patients prescribed an oral carbonic anhydrase inhibitor had an absolute risk of a severe complicated adverse event of 2.90 per 1000 patients, whereas patients prescribed a topical carbonic anhydrase inhibitor had an absolute risk of 2.08 per 1000 patients. This difference was equivalent to a risk ratio of 1.40, with a number needed to harm of 1 in 1220 patients (95% CI, 1.12-1.74; P = .003). This generally low risk was replicated in multivariable regression controlling for confounding factors. Additional risk factors for a severe complicated adverse event included patients with more comorbidities and those with more frequent clinic contacts.Conclusions and relevanceThe risk of a serious adverse reaction following prescription of an oral or topical carbonic anhydrase inhibitor was low and similar between agents. Given the low risk of severe adverse reactions, this population-level analysis supports reconsidering the reluctance toward prescribing an oral carbonic anhydrase inhibitor.
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Project description:BackgroundElective total knee arthroplasty (TKA) is a common surgery which has evolved rapidly. However, there are no recent large systematic reviews of serious adverse event (SAE) rate and 30-day readmission rate (30-dRR) or an indication of whether surgical methods have improved.MethodsTo obtain a pooled estimate of SAE rate and 30-dRR following TKA, we searched Medline, Web of Science, Cochrane Library, and Google Scholar databases. Data were extracted by two authors following PRISMA guidelines. Eligibility criteria were defined prior to a comprehensive search. Studies were eligible if they were published in 2007 or later, described sequelae of TKA with patient N > 1000, and the SAE or 30-dRR rate could be calculated. SAEs included return to operating room, death or coma, venous thromboembolism (VTE), deep infection or sepsis, myocardial infarction, heart failure or cardiac arrest, stroke or cerebrovascular accident, or pneumonia.ResultsOf 248 references reviewed, 28 are included, involving 10,153,503 patients; this includes 9,483,387 patients with primary TKA (pTKA), and 670,116 patients with revision TKA (rTKA). For pTKA, the SAE rate was 5.7% (95% CI 4.4-7.2%, I2 = 100%), and the 30-dRR was 4.8% (95% CI 4.3-5.4%, I2 = 100%). For rTKA, the SAE rate was 8.5% (95% CI 8.3-8.7%, I2 = 77%), while the 30-dRR was 7.2% (95% CI 6.4-8.0%, I2 = 81%). Odds of 30-dRR following pTKA were about half that of rTKA (OR 0.57, 95% CI 0.53-0.62%, p < 0.001, I2 = 45%). Of patients who received pTKA, the commonest SAEs were VTE (1.22%; 95% CI 0.83-1.70%) and genitourinary complications including renal insufficiency or renal failure (1.22%; 95% CI 0.83-1.67%). There has been significant improvement in SAE rate and 30-dRR since 2010 (χ2 test < 0.001).ConclusionsTKA procedures have a relatively low complication rate, and there has been a significant improvement in SAE rate and 30-dRR over the past decade.
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Project description:Ruxolitinib (INCB018424) is a JAK1 and JAK2 inhibitor recently evaluated for the treatment of myelofibrosis (MF) in early- and advanced-phase clinical trials. In 2 recent communications that focused on short-term and long-term ruxolitinib treatment outcome, respectively, the drug was shown to be effective in controlling constitutional symptoms and splenomegaly but was also associated with important adverse effects, including moderate to severe thrombocytopenia and anemia. The most recent of the 2 communications focused on 51 Mayo Clinic patients who participated in the original phase 1/2 ruxolitinib clinical trial and highlighted a high treatment discontinuation rate (92% after a median time of 9.2 months), primarily for loss of treatment benefit but also because of drug-associated adverse effects. The report also discussed the occurrence of sometimes severe withdrawal symptoms during ruxolitinib treatment discontinuation. This "ruxolitinib withdrawal syndrome" was characterized by acute relapse of disease symptoms, accelerated splenomegaly, worsening of cytopenias, and occasional hemodynamic decompensation, including a septic shocklike syndrome. In the current sponsor-independent analysis, we describe the details of these events in 5 severely affected cases (11%) among 47 Mayo Clinic patients with MF in whom ruxolitinib therapy had been discontinued. Our experience calls for full disclosure of the ruxolitinib withdrawal syndrome to patients with MF before initiating ruxolitinib therapy, and treatment discontinuation must be done under close physician supervision and preferably in a tapering schedule.
| S-EPMC3228619 | biostudies-literature
Project description:BackgroundSafety data is required to be collected in all clinical trials and can be separated into two types of data, adverse events and serious adverse events. Often, these types of safety data are collected as two discrete data sets, where adverse events that also meet the criteria for seriousness should be reported in both datasets. Safety analyses are often conducted using only the adverse event dataset, which should feature all safety events reported. We investigated whether the reporting of safety in both datasets was systematically followed and explored the impact of this on safety analyses in ICON8, an ovarian cancer clinical trial.MethodsText searches of serious adverse event data identified events that could potentially match the data reported in the adverse event dataset (looking at pre-specified AE terms only). These serious adverse events were then mapped to adverse event data according to predefined criteria: (a) event term matches, (b) date of onset and date of assessment within 30 days of each other, (c) date of assessment lies between date of onset and date of resolution and (d) events confirmed to occur in the same chemotherapy cycle. A combined dataset of all unique safety events (whether originally reported in the adverse event or serious adverse event dataset) was created and safety analyses re-performed.Results51,019 adverse events were reported in ICON8, of which 42,410 were included in the mapping exercise. One thousand five hundred six serious adverse event elements were reported, of which 668 were included in the mapping exercise. Sixty-one percent of serious adverse event elements was matched to an already-reported adverse event. Supplementing these additional safety events and re-performing safety analyses increased the proportion of patients with at least one grade 3 or worse safety events in all arms from 42 to 47% in the control arm and 61 to 65% and 52 to 59% in the research arms. The difference in proportions of grade 3 or worse event in the research arms compared to the control arm changed by 18% (95% confidence interval [CI] 12 to 24%) and 12% (95% CI 6 to 18%), respectively.ConclusionsThere was low agreement in mapping serious adverse events to already reported adverse events, with nearly 40% of serious adverse events included in the mapping exercise not mapped to an already reported adverse event. Any analyses of safety data that use only adverse event datasets or do not clearly account for serious adverse event data will likely be missing important safety information. Reporting standards should make clear which datasets were used for analyses.
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