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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ABSTRACT:
SUBMITTER: Bullen AL
PROVIDER: S-EPMC8178467 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
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| S-EPMC1127542 | biostudies-literature
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.
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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: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.
| S-EPMC8011390 | biostudies-literature
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.
| S-EPMC7495966 | biostudies-literature
Project description:BackgroundContrast-associated acute kidney injury (CA-AKI) has been associated with a higher risk of cardiovascular (CV) events. We studied the risk of CV events in chronic kidney disease (CKD) patients undergoing angiography and whether biomarkers can predict such events. We also explored whether CA-AKI mediates the association of pre-angiography estimated glomerular filtration rate (eGFR) on CV events.MethodsWe analysed participants from the Prevention of Serious Adverse Events following the Angiography (PRESERVE) trial. Urinary tissue inhibitor of matrix metalloproteinase [TIMP]-2 and insulin growth factor binding protein [IGFBP]-7, plasma brain-type natriuretic peptide (BNP), high sensitivity C-reactive protein (hs-CRP), and serum cardiac troponin-I (Tn-I) were assayed before and after angiography. We assessed the composite risk of CV events by day 90.ResultsOf the 922 participants, 119 (12.9%) developed CV events, and 73 (7.9%) developed CA-AKI. Most cases of CA-AKI (90%) were stage 1. There were no differences in urinary [TIMP-2]•[IGFBP7] concentrations or the proportion of patients with CA-AKI among those with and without CV events. Higher BNP, Tn-I, and hs-CRP were associated with CV events, but their discriminatory capacity was modest (AUROC <0.7). CA-AKI did not mediate the association of the pre-angiography eGFR on CV events.ConclusionsMost episodes of CA-AKI are stage 1 AKI and are not associated with CV events. Less severe CA-AKI episodes also did not mediate the risk of pre-angiography eGFR on CV events. Our findings suggest that most CV events after contrast procedures are due to underlying CKD and CV risk factors rather than less severe CA-AKI episodes and should help enhance the utilization of clinically indicated contrast procedures among high-risk patients with CKD. Further research is required to examine whether moderate-to-severe CA-AKI episodes are associated with CV events.
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Project description:Pregnant women are increasingly considered a priority group for influenza vaccination, but the evidence in favor relies mainly on observational studies, subject to the "healthy-vaccinee bias". Propensity score methods-sometimes applied-reduce but cannot eliminate residual confounding. Meta-analyses of observational studies show relative risks far from the thresholds that would confirm the efficacy of universal vaccination for pregnant women without needing randomized controlled trials (RCTs). Critical articles have shown that in the four RCTs investigating the outcomes of this vaccination, there was a tendency towards higher offspring mortality. In the largest RCT, there was a significant excess of presumed/serious neonatal infections, and also significantly more serious adverse events. Many widely acknowledged observational results (about hormone replacing therapy, vitamin D, omega-3 fatty acids, etc.) were confuted by RCTs. Therefore the international drive to consider this vaccination a "standard of care" is not justified yet. Moreover, there is the risk of precluding further independent RCTs for "ethical considerations", so as "to not deny the benefits of influenza vaccinations to pregnant women of a control group". Instead, before promoting national campaigns for universal vaccination in pregnancy, further large, independent, and reassuring RCTs are needed, even braving challenging a current paradigm. Until then, influenza vaccination should be offered to pregnant women only once open information is available about the safety uncertainties, to allow truly informed choices, and promoting also other protective behaviors.
| S-EPMC6887964 | biostudies-literature
Project description:Severe maternal complications in pregnancy in sub-Saharan Africa contribute to high maternal mortality and morbidity. Incidence data on severe maternal complications, life-threatening conditions, maternal deaths and birth outcomes are essential for clinical audit and to inform trial design of the types and frequency of expected severe adverse events (SAEs). However, such data are very limited, especially in sub-Saharan Africa. We set up standardized, systematic clinical surveillance embedded into routine clinical care in a rural county hospital in Kenya. Pregnant women and newborns are systematically assessed and investigated. Data are reported using a standardized Maternal Admission Record that forms both the hospital's clinical record and the data collection tool. Integrating clinical surveillance with routine clinical care is feasible and should be expanded in sub-Saharan Africa, both for improving clinical practice and as a basis for intervention studies to reduce maternal and newborn mortality and morbidity where rates are highest.
| S-EPMC4817214 | biostudies-literature