Small pipes: preliminary experience with 3-mm or smaller pipeline flow-diverting stents for aneurysm repair prior to regulatory approval.
Ontology highlight
ABSTRACT:
SUBMITTER: Martin AR
PROVIDER: S-EPMC8013041 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Few publications have dealt exclusively with the use of flow diverter stents for the treatment of para-ophthalmic aneurysms. We sought to determine the efficacy of flow diverting stents (FDSs) to treat aneurysms in this specific location.We retrospectively reviewed our database of prospectively collected information for all patients treated with flow diversion for an unruptured saccular para-ophthalmic aneurysm between September 2009 and January 2016. The aneurysm fundus size, neck size, number and type of FDS, complications, and follow-up data were recorded.We identified 74 patients that matched our inclusion criteria. Of these patients, 18 patients were male (24.3%). The average fundus size was 4.8 mm, 11 aneurysms had previous coil occlusions and 63 were treated solely with flow diversion. At an initial angiographic follow-up (mean avg. 3.2 months), 71.8% of the aneurysms were occluded, and at the last follow-up (mean avg. 31.8 months), 88.9% of aneurysms were occluded. One patient suffered permanent morbidity (1.36%) secondary to interruption of the antiplatelet medication and another died (1.36%) secondary to in-stent thrombosis that was also due to an interruption in the antiplatelet medication.Treatment of saccular para-ophthalmic aneurysms with FDS is feasible and carries a high degree of technical success with low complication rates and excellent rates of aneurysm exclusion.
| S-EPMC5545935 | biostudies-other
Project description:BACKGROUND AND PURPOSE:Computational fluid dynamics modeling is useful in the study of the hemodynamic environment of cerebral aneurysms, but patient-specific measurements of boundary conditions, such as blood flow velocity and pressure, have not been previously applied to the study of flow-diverting stents. We integrated patient-specific intravascular blood flow velocity and pressure measurements into computational models of aneurysms before and after treatment with flow-diverting stents to determine stent effects on aneurysm hemodynamics. MATERIALS AND METHODS:Blood flow velocity and pressure were measured in peri-aneurysmal locations by use of an intravascular dual-sensor pressure and Doppler velocity guidewire before and after flow-diverting stent treatment of 4 unruptured cerebral aneurysms. These measurements defined inflow and outflow boundary conditions for computational models. Intra-aneurysmal flow rates, wall shear stress, and wall shear stress gradient were calculated. RESULTS:Measurements of inflow velocity and outflow pressure were successful in all 4 patients. Computational models incorporating these measurements demonstrated significant reductions in intra-aneurysmal wall shear stress and wall shear stress gradient and a trend in reduced intra-aneurysmal blood flow. CONCLUSIONS:Integration of intravascular dual-sensor guidewire measurements of blood flow velocity and blood pressure provided patient-specific computational models of cerebral aneurysms. Aneurysm treatment with flow-diverting stents reduces blood flow and hemodynamic shear stress in the aneurysm dome.
| S-EPMC3858573 | biostudies-literature
Project description: Not available
| S-EPMC8411241 | biostudies-literature
Project description:Spontaneous aneurysm regression is a rare phenomenon. We present the interesting case of a 54-year-old woman who was admitted with a Hunt/Hess grade IV, Fisher grade III subarachnoid hemorrhage and multiple intracranial aneurysms. She was treated with coiling of the largest paraclinoid aneurysm and placement of a flow diverting pipeline embolization device that covered all internal carotid artery (ICA) aneurysms. A follow-up angiogram at 6 months showed remodeling of the ICA with complete obliteration of all treated aneurysms. A distant, untreated, right frontal M2 aneurysm regressed spontaneously, after the flow was diverted away from it with the stent. The literature is reviewed, and potential pathophysiological mechanisms leading to aneurysm regression are discussed.
| S-EPMC4550854 | biostudies-other
Project description: Not available
| S-EPMC8411234 | biostudies-literature
Project description:BACKGROUND: At the time of approval of a new medicine, there are few long-term data on the medicine's benefit-risk balance. Clinical trials are designed to demonstrate efficacy, but have major limitations with regard to safety in terms of patient exposure and length of follow-up. This study of the number of patients who had been administered medicines at the time of medicine approval by the European Medicines Agency aimed to determine the total number of patients studied, as well as the number of patients studied long term for chronic medication use, compared with the International Conference on Harmonisation's E1 guideline recommendations. METHODS AND FINDINGS: All medicines containing new molecular entities approved between 2000 and 2010 were included in the study, including orphan medicines as a separate category. The total number of patients studied before approval was extracted (main outcome). In addition, the number of patients with long-term use (6 or 12 mo) was determined for chronic medication. 200 unique new medicines were identified: 161 standard and 39 orphan medicines. The median total number of patients studied before approval was 1,708 (interquartile range [IQR] 968-3,195) for standard medicines and 438 (IQR 132-915) for orphan medicines. On average, chronic medication was studied in a larger number of patients (median 2,338, IQR 1,462-4,135) than medication for intermediate (878, IQR 513-1,559) or short-term use (1,315, IQR 609-2,420). Safety and efficacy of chronic use was studied in fewer than 1,000 patients for at least 6 and 12 mo in 46.4% and 58.3% of new medicines, respectively. Among the 84 medicines intended for chronic use, 68 (82.1%) met the guideline recommendations for 6-mo use (at least 300 participants studied for 6 mo and at least 1,000 participants studied for any length of time), whereas 67 (79.8%) of the medicines met the criteria for 12-mo patient exposure (at least 100 participants studied for 12 mo). CONCLUSIONS: For medicines intended for chronic use, the number of patients studied before marketing is insufficient to evaluate safety and long-term efficacy. Both safety and efficacy require continued study after approval. New epidemiologic tools and legislative actions necessitate a review of the requirements for the number of patients studied prior to approval, particularly for chronic use, and adequate use of post-marketing studies. Please see later in the article for the Editors' Summary.
| S-EPMC3601954 | biostudies-literature
Project description:On November 21, 2016, the U.S. Food and Drug Administration granted regular approval to daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on two randomized, open-label trials in which daratumumab was added to these backbone therapies. The MMY3003 trial demonstrated substantial improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone. The estimated median PFS had not been reached in the daratumumab arm and was 18.4 months in the control arm (hazard ratio [HR]?=?0.37; 95% confidence interval [CI]: 0.27-0.52; p?<?.0001), representing a 63% reduction in the risk of disease progression or death. Similar results were observed in the MMY3004 trial comparing the combination of daratumumab, bortezomib, and dexamethasone with bortezomib and dexamethasone. The estimated median PFS was not reached in the daratumumab arm and was 7.2 months in the control arm (HR?=?0.39; 95% CI: 0.28-0.53; p?<?.0001), representing a 61% reduction in the risk of disease progression or death. The most frequently reported adverse reactions (greater than or equal to 20%) in MMY3003 were infusion reactions, diarrhea, nausea, fatigue, pyrexia, upper respiratory tract infection, muscle spasm, cough, and dyspnea. The most frequently reported adverse reactions (greater than or equal to 20%) in MMY3004 were infusion reactions, diarrhea, peripheral edema, upper respiratory tract infection, and peripheral sensory neuropathy. Neutropenia and thrombocytopenia have been added to the Warnings and Precautions of the drug label.Daratumumab, the first monoclonal antibody targeted against CD38, received U.S. Food and Drug Administration accelerated approval in 2015 based on data from single-agent, single-arm trials that provided response rate information. Results of the MMY3003 and MMY3004 trials established that daratumumab can be combined synergistically with some of the most highly active agents used to treat multiple myeloma, leading to daratumumab's regular approval in 2016. Daratumumab added to lenalidomide and dexamethasone, or bortezomib and dexamethasone, provides a substantial improvement in progression-free survival in previously treated patients with multiple myeloma. These combinations will likely improve the survival outlook for patients with multiple myeloma.
| S-EPMC5679834 | biostudies-literature
Project description:IntroductionWhen a new drug or biologic product enters the market, its full spectrum of side effects is not yet fully understood, as use in the real world often uncovers nuances not suggested within the relatively narrow confines of preapproval preclinical and trial work.ObjectiveWe describe a new, phenome-wide association study (PheWAS)- and evidence-based approach for detection of potential adverse drug effects.MethodsWe leveraged our established platform, which integrates human genetic data with associated phenotypes in electronic health records from 29,722 patients of European ancestry, to identify gene-phenotype associations that may represent known safety issues. We examined PheWAS data and the published literature for 16 genes, each of which encodes a protein targeted by at least one drug or biologic product.ResultsInitial data demonstrated that our novel approach (safety ascertainment using PheWAS [SA-PheWAS]) can replicate published safety information across multiple drug classes, with validated findings for 13 of 16 gene-drug class pairs.ConclusionsBy connecting and integrating in vivo and in silico data, SA-PheWAS offers an opportunity to supplement current methods for predicting or confirming safety signals associated with therapeutic agents.
| S-EPMC7398579 | biostudies-literature
Project description:ObjectiveFlow diverting stents (FDS) are a validated device in the treatment of intracranial aneurysms, allowing for minimally invasive intervention. However, after its approval for use in the United States in 2011, post-market surveillance of adverse events is limited. This study aims to address this critical knowledge gap by analyzing the FDA Manufacturer and User Facility Device Experience (MAUDE) database for patient and device related (PR and DR) reports of adverse events and malfunctions.MethodsUsing post-market surveillance data from the MAUDE database, PR and DR reports from January 2012-December 2021 were extracted, compiled, and analyzed with R-Studio version 2021.09.2. PR and DR reports with insufficient information were excluded. Raw information was organized, and further author generated classifications were created for both PR and DR reports.ResultsA total of 2203 PR and 4017 DR events were recorded. The most frequently reported PR adverse event categories were cerebrovascular (60%), death (11%), and neurological (8%). The most frequent PR adverse event reports were death (11%), thrombosis/thrombus (9%) cerebral infarction (8%), decreased therapeutic response (7%), stroke/cerebrovascular accident (6%), intracranial hemorrhage (5%), aneurysm (4%), occlusion (4%), headache (4%), neurological deficit/dysfunction (3%). The most frequent DR reports were activation/positioning/separation problems (52%), break (9%), device operates differently than expected (4%), difficult to open or close (4%), material deformation (3%), migration or expulsion of device (3%), detachment of device or device component (2%).ConclusionsPost-market surveillance is important to guide patient counselling and identify adverse events and device problems that were not identified in initial trials. We present frequent reports of several types of cerebrovascular and neurological adverse events as well as the most common device shortcomings that should be explored by manufacturers and future studies. Although inherent limitations to the MAUDE database are present, our results highlight important PR and DR complications that can help optimize patient counseling and device development.
| S-EPMC10555618 | biostudies-literature
Project description:BACKGROUND:This study compares short-term (30 days) and intermediate term (3 years) clinical outcomes in patients with large (?31 mm) versus small aortic neck diameters (?28 and ?31 mm). METHODS:Prospectively collected data from 741 patients who underwent endovascular aortic aneurysm repair were analyzed. Some surgeons have reported the threshold for a large aortic neck for endovascular aortic aneurysm repair to be 28 mm, whereas for others it is 31 mm. Therefore, we classified aortic neck diameter into less than or equal to 28 versus greater than 28 mm; and less than or equal to 31 versus greater than 31 mm. Logistic regression and Kaplan-Meier analyses were used to compare outcomes. RESULTS:There were 688 patients who had a defined aortic neck diameter: 592 with less than or equal to 28 mm, 96 with greater than 28 mm, 655 with less than or equal to 31 mm, and 33 with greater than 31 mm. The mean follow-up was 25.2 months for less than or equal to 31 mm versus 31.8 months for greater than 31 mm. Clinical characteristics were similar in all groups, except that there were more patients outside the instructions for use in the greater than 31 mm versus less than or equal to 31 mm group (94% vs 44%; P < .0001). There was a significant increase in early type I endoleak for patients with an aortic neck diameter of greater than 31 versus less than or equal to 31 mm (9 [27%] vs 74 [11%]; P = .01); late type I endoleaks (4 [14%] vs 18 [3%]; P = .01); sac expansion (5 [17%] vs 28 [5%]; P = .01); late intervention (5 [17%] vs 23 [4%]; P = .01); and death (9 [31%] vs 48 [8%]; P < .0001). There were no differences in outcomes between the patients with greater than 28 mm aortic neck diameters and the less than or equal to 28 mm diameters. Freedom from late type I endoleak at 1, 2, and 3 years were 96%, 88%, and 88% for patients with a neck diameter of greater than 31 mm versus 97%, 97%, and 97% for a diameter less than or equal to 31 mm (P = .19). The rate of freedom from sac expansion for patients with a diameter greater than 31 mm was 88%, 81%, and 81% at 1, 2, and 3 years versus 99%, 97%, and 92% for a diameter less than or equal to 31 mm (P = .02). Freedom from late intervention for 1, 2, and 3 years for patients with a diameter greater than 31 mm were 91%, 91%, and 91% versus 99%, 97%, and 96% for those with a diameter less than or equal to 31 mm. Survival rates at 1, 2, and 3 years for a diameter greater than 31 mm were 83%, 74%, and 68% versus 96%, 92%, and 90% for a diameter less than or equal to 31 mm (P < .001). Multivariate logistic regression analysis showed that patients with a diameter greater than 31 mm had an odds ratio of 6.1 (95% confidence interval [CI], 2.2-16.8) for mortality, 4.7 (95% CI, 1.4-15.5) for sac expansion, and 4.9 (95% CI, 1.4-17.4) for late type I endoleak. CONCLUSIONS:Patients with large aortic neck diameters (>31 mm) had higher rates of early and late type I endoleak, sac expansion, late intervention, and mortality.
| S-EPMC6203596 | biostudies-literature