Instructions For Use Research Articles

Five-Year Outcomes of Endovascular Aortic Repair With the TREO Abdominal Endograft.

Newer generation abdominal endografts, including Treo (Terumo Aortic, Sunrise, Florida), have shown optimal safety and effectiveness in treating abdominal aortic aneurysms (AAAs), even with hostile anatomy over the short- and mid-term. The durability of such results, however, is still a controversial issue, due to the paucity of long-term data. Our aim is to show the long-term outcomes of endovascular aortic repair of both standard and hostile AAAs with the Treo endograft on a cohort of patients treated between 2016 and 2017. We analyzed the postoperative follow-up of 37 consecutive patients who have undergone endovascular aortic repair (EVAR) with the Treo Endograft between 2016 and 2017, whose baseline clinical conditions, operative data, and short-term outcomes had been published in 2018. All patients were followed up by computed tomography angiography (CTA) at 6 and 12 months and 5 years postoperatively. Primary endpoints were aortic-related mortality, type I-III endoleak (EL), and reintervention rate. Secondary endpoints were the rates of type II ELs and aneurysm sac regression. Of 37 patients, 27 had at least one criterion of anatomic hostility and 11 were performed outside the device-specific instructions for use (IFU). In the perioperative period, we observed 100% technical success, with no perioperative mortality. Over a mean follow-up of 5.5 years (66 months), 3 patients (8.1%) were lost to follow-up and 3 (8.1%) died of non-aortic causes (overall survival: 91.9%). One type IA EL of an AAA with a hostile neck (but within the IFU) and a type III EL of an AAA with standard anatomy were observed and treated by endovascular relining (overall reintervention rate: 5.5%). Four type II ELs were associated with aneurysm sac stability over time and are still under surveillance. Mean aneurysm shrinkage was 11.25±8.30 mm. The optimal results of the Treo Endograft in terms of complication and reintervention rates reported over the mid-term by the current literature (ITA-ENDOBOOT registry) are maintained on the long term, both in case of hostile and friendly aortic anatomy, with a satisfactory shrinkage rate of the aneurysm sac. The innovative characteristics of Treo and its short-term results are well-known and reported. The present case series contributes to the scientific validation of a new-generation abdominal aortic endograft over the long-term, focusing especially on its performance in treating AAAs with hostile anatomy. Its 5-years outcomes confirm the optimal results already reported over the short- and mid-term.

Assessing Endovascular Aneurysm Repair Suitability According to Graft-Specific Instructions for Use in Patients With a Ruptured Abdominal Aortic Aneurysm

The purpose of the study is to ascertain endovascular aneurysm repair (EVAR) suitability in relation to stent-graft-specific instructions for use (IFU) in patients with a ruptured abdominal aortic aneurysm (RAAA). Using the preoperative computed tomography angiography (CTA), the aortic morphology of patients undergoing surgical repair of a RAAA in 2 Dutch hospitals between January 2014 and December 2019 was retrospectively assessed. Three-dimensional and central luminal line reconstructions were used. Anatomical suitability was defined according to the IFU of the stent graft system used. Of 128 included patients, 112 (88%) were men and the mean age was 74.1 (SD=7.6) years. Anatomy within IFU for EVAR was present in 31 patients (24%). Overall, 94 patients (73%) were treated with open surgical repair (OSR) and 34 patients (27%) were treated with EVAR. Anatomy within IFU was present in 15 OSR patients (16%) and 16 EVAR patients (47%). In patients with anatomy outside of IFU, 90% (87/97) had unsuitable neck anatomy and 64% (62/97) had insufficient neck length. An unsuitable distal iliac landing zone was observed in 35 patients. Perioperative mortality was 27% (34/128), with no difference between OSR and EVAR (25/94 vs 9/34; p=0.989). Most RAAA patients in this series did not have aortic anatomy within IFU for EVAR, mainly due to insufficient neck length. However, whether anatomy outside of IFU equates to unsuitability for EVAR in an emergency setting remains a matter of debate and warrants further research. The treatment of a ruptured abdominal aortic aneurysm can consist of endovascular repair or open repair. Retrospective anatomical assessment shows that most patients do not have anatomy inside the instructions for use for endovascular aneurysm repair, mainly due to insufficient neck length. Whether anatomy outside the instructions for use equates unsuitability for endovascular aneurysm repair remains a matter of debate.

Suppression of acute bone marrow edema (osteitis) in the sacroiliac joints with long-term use of non-steroidal anti-inflammatory drugs in patients with axial spondyloarthritis

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is a concern for both doctors and patients. However, in axial spondyloarthritis (axSpA), NSAIDs are used not only as a symptomatic therapy, but also to prevent the progression of the disease. Therefore, in active axSpA, NSAIDs are recommended to be administered for a much longer period of time than it is indicated in the instructions for use of the drug. The article presents two clinical cases of long-term use of etoricoxib in active axSpA. In both cases, clinical efficacy and resolution of active osteitis in the sacroiliac joints, good tolerability of treatment were noted.

Epidemiology and patients' self-reported knowledge of implantable medical devices: Results of a cross-sectional survey in Hungary.

Implantable medical devices (IMDs) are medical instruments embedded inside the body. Well-informed and empowered patients living with IMDs are key players of improving IMD-related patient safety and health outcomes. However, little is known about IMD patients' epidemiology, characteristics, and current awareness levels. Our primary aim was to investigate the point and lifetime prevalence of patients living with IMDs. Patients' IMD-related knowledge and determinants of IMDs' impact on their life were also explored. An online cross-sectional survey was conducted. Respondents' IMD history, whether they received instructions for use and IMD's overall impact on life were recorded by self-reports. Patients' knowledge about living with IMDs was assessed on visual analogue scales (VAS, 0-10). Shared decision-making was analyzed by the 9-item Shared Decision Making Questionnaire (SDM-Q-9). Descriptive statistics and subgroup comparisons between IMD wearers were performed for statistical differences. Significant determinants of IMD's overall impact on life were examined in linear regression analysis. In the total sample (N = 1400, mean age 58.1 ±11.1; female 53.7%), nearly one third of respondents were living with IMD (30.9%; 433/1400). Among them, the most frequent IMDs were tooth implants (30.9%) and intraocular lens (26.8%). Mean knowledge VAS scores were similar (range: 5.5 ±3.8-6.5 ±3.2) but differences by IMD types were observed. Patients who received instructions for use or reported better impact on life indicated higher self-reported knowledge. Regression confirmed that patients' knowledge was significant predictor of IMD's impact on life, but this effect was overwritten by the SDM-Q-9. This first comprehensive epidemiological study on IMDs provides basic data for public health strategy planning alongside the implementation of MDR. Improved self-perceived outcomes were associated with higher knowledge hence education of patients receiving IMD deserves consideration. We suggest to investigate further the role of shared decision-making on IMD's overall impact on patients' life in future prospective studies.

'Post-Close' Femoral Arterial Haemostasis at Endovascular Aneurysm Repair using a Dedicated Large-Bore Vascular Closure Device: A Prospective Real-World Audit.

Percutaneous access for endovascular aneurysm repair (EVAR) is commonplace, with its attendant benefits. The combination of continued reduction in device profile and evolution of vascular closure device (VCD) design drives successful and safe percutaneous EVAR. A new such VCD is the MANTA Large-Bore Closure Device designed in two iterations for closure of arterial defects from 10 to 25F. We present a prospective audit of 131 large-bore femoral closures using an 'all-comers' approach to device selection. One hundred and thirty-one large-bore femoral arterial defects were analysed. Both 14F and 18F MANTA VCDs were deployed in this series as per instructions for use. Primary objectives were technical success, particularly successful deployment, and haemostasis achieved. Failures were denoted as failure to deploy; failure to achieve haemostasis was denoted as active bleeding, haematoma, or pseudoaneurysm formation requiring intervention. Later complications assessed were vessel occlusion/thrombosis or stenosis. Seventy-six patients (65 males and 11 females, age 75.2 ± 8.7years) underwent a range of procedures including EVAR (n = 66), TEVAR (n = 2), and reinterventions (n = 8) requiring large-bore percutaneous femoral arterial access in 131 groins. Of these, the 14F MANTA VCD was used in 61 closures (defects ranging from 12 to 18F) and the 18F in 70 closures (defects ranging from 16 to 24F). Deployments achieved successful haemostasis in 120 (91.6%), and failures occurred in 11(8.4%) groins. This study indicates that a post-close approach using the novel MANTA Large-Bore Closure Device can be undertaken successfully to close a range of large-bore femoral arterial defects at EVAR/TEVAR with an acceptable rate ofcomplications.

A Comparison of Instructions for Use Documents and Manufacturer Produced Administration Videos for Biological Products.

To compare Instructions for Use (IFU) and Manufacturer Produced Administration Videos (MPAV) for biological products to describe if they are highly similar or different. To identify differences between the two that may lead to medication errors and to point out possible solutions to optimize safety. We screened 139 biological products having both an IFU and a MPAV. Differences between the IFU and MPAV of each biological product were noted and categorized by importance and how likely it would cause harm to patients. Strategies were discussed based on differences observed. Of the products screened, 51 had an IFU and a MPAV available for evaluation. They were primarily made to support the use of auto-injectors (n = 25) and pre-filled syringes (n = 19). Of this group, we found that 11 had no differences between the IFU and MPAV, while the other 40 had at least one or more identifiable differences. Differences were stratified into the following sub-categories from most to least prevalent: word choice differences, supplementary information, missing information, and unaligned directions. We looked at the distribution of differences per biological product and found an average of two differences per MPAV (IQR 1-3). We suggest that when sponsors create or update MPAVs, to focus on aligning critical content between the respective IFU and MPAV. We believe that it is possible for MPAVs to potentially reduce medication errors as a non-text-based media form and that care should be taken to avoid substantial differences in critical content between the IFU and MPAV.

Isolation of Cystic Echinococcosis Causative Agents of Echinococcus equinus and Echinococcus ortleppi Species from Humans in the Central Anatolia Region of Türkiye

Cystic Echinococcosis (CE) caused by Echinococcus granulosus sensu strico is neglected in Türkiye despite being one of the common diseases due to agriculture being at the forefront, low socioeconomic status and unhygienic animal slaughter. Considering the morbidity, mortality, and difficulties in treatment, more studies and precautions are needed regarding this disease. In this study, it was aimed to genotype Echinococcus isolated from CE patients in the Central Anatolia region. DNA isolation from tissue samples taken from 60 CE patients was performed using the QIAamp DNA FFPE tissue kit. Cytochrome c oxidase subunit gene region of Echinococcus was targeted and JB3/JB4.5 primers were used for genotyping. Polymerase chain reaction (PCR) products were purified according to the instructions for use of the QIAquick PCR purification kit. PCR products were prepared using the ABI Prism BigDye Terminator V3.1 Cycle sequencing kit and the nucleotide sequences in the samples were evaluated with the ABI 3100 sequencing device. The nucleotide sequences obtained in the study were analyzed using MetaPIGA2, MRBAYES v.3.1.2, phyogenetic analysis using parsimony, Unigen programs, maximum likelihood, Bayesian and parsimony methods. It has been found that 88.4% (53/60) of Echinococcus isolates were E.granulosus s.s. in this study. It has been genotyped as 41.7% (25/60) G1, 30.0% (18/60) G3 and 16.7% (10/60) G2 genotype. It has been determined that 6.6% (4/60) of the other Echinococcus isolates were E.equinus and 5.5% (3/60) were E.ortleppi. It was observed that E.equinus and E.ortleppi were isolated from atypically located cysts and from those living in rural areas. The E.equinus and E.ortleppi species were not found in CE patients living in urban areas. CE cases are common in the Central Anatolia region due to dog and cattle breeding, and the disease agent Echinococcus species vary. Genotyping of Echinococcus species is effective in the development of CE treatment and control strategies. Study results can play an active role in the fight against CE, which has formed the basis of the "one health" approach in the world and in Türkiye in recent years.

ИСПОЛЬЗОВАНИЕ ГУМАНИЗИРОВАННЫХ МОНОКЛОНАЛЬНЫХ АНТИТЕЛ OFF-LABEL В ПЕДИАТРИЧЕСКОЙ ПРАКТИКЕ

In recent years, the use of off-label drugs (the use of drugs for indications not approved by state regulatory bodies, and also not mentioned in the instructions for use) has become widespread in the pediatric population. For a long time, clinical trials in the pediatric population were considered difficult to conduct due to ethical issues, leading to frequent off-label drug use. Off-label drug use remains an important public health problem, especially in children with rare diseases or diseases not responding to standard treatment. The purpose of the review is to analyze foreign literature sources on the use of biological preparations outside the instructions. The use of drugs outside the instructions (off-label) is a topical issue in the clinical practice of doctors of various specialties, and this is especially in demand in pediatric practice. This is due to the fact that a registered drug may have a successful experience in adults, but at the same time not have official approval for use in children. The need to use drugs outside the instructions for use, as a rule, occurs in patients with severe, chronic, life-threatening pathology. Further studies analyzing their efficacy, safety, and cost-benefit ratio are needed to expand the use of biological therapy in the pediatric population.

Clinical Issues - April 2023.

Flying insects in the OR Keywords: fly, pest control, infestation, surgical wound classification, sterile field. Reprocessing and reusing single-use devices Keywords: US Food and Drug Administration (FDA), reprocessing, manufacturer, single-use devices (SUDs), adverse event. Using instrument-marking tape Keywords: instrument tape, sterile processing, manufacturer's instructions for use (IFU), inspection, unintentionally retained surgical item. Epinephrine in orthopedic irrigation Keywords: epinephrine, irrigation, vasoconstrictor, arthroscopic procedures, visual field.

Requirements for human pluripotent stem cell derived small extracellular vesicles

AbstractSmall extracellular vesicles derived from human pluripotent stem cells (hPSC‐sEVs) have shown great application potential in regenerative medicine. To standardise its research and clinical application, the first set of guidelines on hPSC‐sEVs in China ‘Requirements for human pluripotent stem cell derived small extracellular vesicles’ was released by the Chinese Research Hospital Association on 28 December 2021 and came into effect on 1 January 2022. It was jointly drafted and agreed upon by the experts from the Chinese Society of Extracellular Vesicles. This standard specifies the technical requirements, test methods and regulations, packaging, instructions for use, labelling, storage, transportation, and waste handling for hPSC‐sEVs, which apply to the production and quality control of hPSC‐sEVs. We hope that the publication of these guidelines will make it one step closer to international standardisation of hPSC‐sEVs for research and application.

Trust Factors in the Social Figuration of Online Drug Trafficking: A Qualitative Content Analysis on a Darknet Market

The rise in illicit drug trafficking on darknet markets (DNMs) was boosted by those restrictions imposed due to the COVID-19 pandemic. This study aims to put this trend into context by exploring the characteristics of vendors’ services and reputations and understand how products are advertised and what customers tend to value. Qualitative content analysis was conducted on a sample ( n = 100) randomly selected from 6,357 product descriptions and a sample ( n = 500) randomly selected from 34,619 reviews. Both samples are from products found in the drug category of the darknet market Dark0de Reborn. On the supply side, vendors tended to provide basic information on the drugs, a mention of their high quality, the speed and stealth of delivery, their availability for responding to messages, the effects of the drugs, and sometimes even instructions for use. Regarding the demand side, customers usually praised the quality of the product, mentioned the speed and stealth-secure packaging of delivery as essentials, and expressed only a small number of issues. These results support the applicability of Norbert Elias’ social figuration theory in which the interdependencies of the actors are fueled by trust. This theoretical frame sheds light on the social value of the community of DNMs. Furthermore, the findings formulate a robust hypothesis for future research about the previously undervalued role of delivery providers.

Intravascular Ultrasound Versus Computed Tomography Angiography in Sizing and Operative Management of Endovascular Aortic Aneurysm Repair

Objectives: An abdominal aortic aneurysm (AAA) is a potentially life-threatening condition, the management of which has dramatically evolved over the past 2 decades with an increasing tendency toward endovascular repair (EVAR) rather than open surgical repair. Classically, contrast-enhanced multislice computed tomography (CT) angiography (CTA) is performed preoperatively for procedure sizing and EVAR planning. This entails voluminous contrast injection with risk of allergic reaction, nephropathy, and radiation exposure. Intra-vascular ultrasound (IVUS) has been increasingly used to guide EVAR procedures intraoperatively. The aim of this study is to investigate the accuracy of IVUS in sizing AAAs, device selection, and EVAR planning compared to the gold standard CTA. Design: This is a prospective observational study enrolling 10 patients who underwent standard infrarenal EVAR procedures performed for unruptured infrarenal AAAs over the course of 1 year. All patients had a preoperative CTA done upon which aneurysm sizing and device planning were performed, and the measurements obtained were compared to those obtained from intraoperative IVUS. Methods: All participating patients had unruptured infrarenal AAA, had no renal impairment, and had anatomical suitability for EVAR according to the instructions for use (IFU) of the device manufacturer. Primary endpoint was comparing anatomical measurements recorded by IVUS with those obtained from the preoperative CTA. Results: Mean age was 65.6 (±6.19), all patients were males and hypertensives and 4 (40%) had a positive family history for AAA. On comparing mean measurements taken by CTA and IVUS, there was no statistically significant differences with exception of maximal aortic diameter and aortic diameter at site of bifurcation (both p-values <.001). There were no statistically significant differences in length measurements between the 2 imaging modalities. Computed tomography angiography was more associated with neck thrombus detection, and IVUS was more associated with calcification detection. Conclusion: Although CT angiography is still the gold standard imaging modality for AAA, IVUS use is very beneficial in EVAR sizing and planning, in addition to intra-operative guidance of the procedure, saving the patient significant time, contrast administration, and radiation exposure, especially in patients with renal impairment and contrast allergy. Clinical Impact A preoperative CT angiogram is the gold standard required investigation for planning and sizing EVARs, with subsequent contrast injection entailing a risk of contrast induced nephropathy and allergic reactions. IVUS has been used as an adjuvant technique to guide EVAR stent graft deployment. However, our study concluded that it can also be reliably used in sizing and planning of the EVAR stent graft along with complementary non contrast imaging, especially in patients with high risk for contrast induced nephropathy and contrast allergy.

Adverse Outcomes in Topical Lidocaine Exposure: A Pediatric Case Series From the United States National Poison Data System.

To examine the clinical outcomes of topical lidocaine exposures in pediatric patients reported to the National Poison Data System (NPDS). We performed a retrospective review of the NPDS in pediatric patients with topical lidocaine toxicity from 2000 to 2020. Specific data analyzed were age, exposure chronicity, medical outcome, clinical effects, treatments, and disposition. Narrative case records were requested from poison centers. Of 37 cases identified, mean age was 5 years with age distribution of 1- to 0 days (n = 8), 1 to 24 months (n = 11), and 2-18 years (n = 18). Exposure chronicity was acute in 33 (89.2%) or chronic in 4 (10.8%). Moderate effects were seen in 25 (67.6%), major effects in 10 (27%), and 2 deaths (5.4%). The most common clinical effects included cyanosis (29.7%), seizures (18.9%), central nervous systems (CNS) depression (13.5%), drowsiness/lethargy (13.5%), and tachycardia (10.8%). The most common treatments were dilution/irrigation (35.1%), intravenous (IV) fluids (29.7%), oxygen (29.7%), methylene blue (27%), benzodiazepines (13.5%), and intubation (10.8%). Non-intensive care unit (ICU) disposition occurred for 23 patients (62.2%) and ICU admission for 14 (37.8%). Case details were requested for 37 cases, 16 cases (43.2%) were provided. Of the 2 deaths, 1 had significant cardiac history. The most common use of topical lidocaine was at home prior to a dermatologic procedure (37.5%). Topical lidocaine can induce serious outcomes resulting in ICU level care or death; however, moderate/major effects were well tolerated without comorbidities. Most patients discharged home. Given frequent use of topical, especially in outpatient settings, greater vigilance should be taken with prescriptions, instructions for use, and anticipatory guidance.

DESAIN WEBSITE PEMBELAJARAN MATERI LIMIT FUNGSI ALJABAR

The current learning process requires teachers to provide opportunities for students to actively acquire their knowledge, thus requiring the support of interesting and innovative teaching materials that can deliver students to the learning information they want to learn, one of which is a learning website. In fact, mathematics teachers at SMA Negeri 2 Huruna still have difficulties in preparing teaching materials according to the needs and characteristics of their students due to limited time and abilities of teachers, so teachers still use teaching materials obtained from the internet in learning. This study aims to produce a product in the form of a learning website material for algebraic limit functions to help teachers facilitate student learning. The development model used in this study is the Borg and Gall development model, in this article it is only presented up to the design stage, namely by designing a learning website for material limits of algebraic functions based on the results of analysis at the research and data collection stages. The learning website was developed using Microsoft FrontPage software and provides several menus, namely: 1) Home, providing instructions for use and a brief description of the website; 2) KD and concept maps; 3) Material, containing learning videos, e-modules, as well as applications for processing learning outcomes; 4) Summary, presenting a summary/core of learning material; and 5) Design team, containing a brief profile of the learning website designer team.

Total Iodine Contrast-free Strategy for the Endovascular Management of Abdominal Aortic Aneurysms in Chronic Kidney Disease Patients: A Pilot Study

To retrospectively evaluate the feasibility and effectiveness of the endovascular treatment of patients with abdominal aortic aneurysm and chronic kidney disease (CKD) without the need for using iodinated contrast media throughout the diagnostic, therapeutic, and follow-up pathway. A retrospective review of prospectively collected data concerning 251 consecutive patients presenting an abdominal aortic or aorto-iliac aneurysm who underwent endovascular aneurysm repair (EVAR) from January 2019 to November 2022 at our academic institution was performed in order to identify patients with feasible anatomy with respect to manufacturer's instructions for use and with CKD. Patients whose preoperative workout included duplex ultrasound and plain computed tomography for preprocedural planning were extracted from a dedicated EVAR database. EVAR was performed with the use of carbon dioxide (CO2) as the contrast media of choice, whereas follow-up examinations consisted of either duplex ultrasound, plain computed tomography, or contrast-enhanced ultrasound. Primary endpoints were technical success, perioperative mortality, and early renal function variations. Secondary endpoints were all-type endoleaks and reinterventions, midterm aneurysm-related and kidney-related mortality. Forty-five patients had CKD and were treated electively (45/251, 17.9%). Of them, 17 patients were managed with a total iodinated contrast media-free strategy and constituted the object of the present study (17/45, 37.8%; 17/251, 6.8%). In 7 cases, an adjunctive planned procedure was performed (7/17, 41.2%). No intraoperative bail-out procedures were needed. This extracted cohort of patients presented similar mean preoperative and postoperative (at discharge) glomerular filtration rate values, 28.14 (SD 13.09; median 28.06, interquartile range (IQR) 20.25) ml/min/1.73m2 and 29.33 (SD 14.61; median 27.35, IQR 22) ml/min/1.73m2, respectively (P=0.210). Mean follow-up was 16.4months (SD 11.89; median 18, IQR 23). During follow-up, no graft-related complications occurred in terms of either thrombosis, type I or III endoleaks, aneurysm rupture, or conversion. The mean glomerular filtration rate at follow-up was 30.39ml/min/1.73m2 (SD 14.45; median 30.75, IQR 21.93), with no significant worsening in comparison with preoperative and postoperative values (P=0.327 and P=0.856 respectively). No aneurysm- or kidney-related deaths occurred during follow-up. Our initial experience shows that total iodine contrast-free abdominal aortic aneurysm endovascular management in patients with CKD may be feasible and safe. Such an approach seems to guarantee the preservation of residual kidney function without increasing the risks of aneurysm-related complications in the early and midterm postoperative periods, and it could be considered even in the case of complex endovascular procedures.

Type Ic Endoleak after LifeStream Balloon-Expandable Stent Graft and Zenith Iliac Branch Device Placement

Considering the recent advancements in endovascular management of aortoiliac aneurysms, the use of an iliac branch device (IBD) to preserve pelvic blood flow and reduce complications caused by embolization of the internal iliac artery (IIA) is recommended by various guidelines. Although the outcomes reported following IBD placement are mainly positive and durable, IBD-specific complications such as a type Ic endoleak and associated reintervention may occur. Moreover, only one IBD device and one type of balloon-expandable bridging stent graft for IIA are currently available on the domestic market. Here we present two cases of type Ic endoleak following IBD placement. In both cases, IIA diameter was slightly larger than the basic instructions for use. Notably, the initial procedures were considered successful; however, type Ic endoleaks were detected on 1-month follow-up imaging. This finding emphasizes the need for a precise preoperative evaluation, intraoperative manipulation, and postoperative follow-up.

Abstract Number ‐ 96: The COGNITIVE study: Cognition and Imaging with Tigertriever

Introduction Results of systematic reviews and studies evaluating treatment effects of cerebrovascular interventions on the prevalence of post‐stroke cognitive impairment vary likely due to heterogeneity in populations, sample size, variable treatment effect, and time and methods of cognitive examination. Like thrombolytic therapy, endovascular therapy (EVT) in large vessel occlusion (LVO) stroke is strongly associated with successful reperfusion, reduced mortality, and good clinical outcomes. Nevertheless, the effect of successful reperfusion after EVT on cognitive function remains unexplored. Methods Four hundred (400) patients aged 18–75 will be enrolled in the USA and outside USA clinical centers. The primary endpoint will be the association between successful reperfusion, defined as eTICI ≥ 2b50, and cognitive benefit, defined as delta Montreal Cognitive Assessment (MoCA) from 4 days to 180 days post‐EVT or MoCA ≥ 26 at 180 days post‐EVT. Secondary endpoints will include first pass successful revascularization, reduction in hypoperfusion volumes within 24 h, functional evaluations (NIHSS, mRS), MoCA and cognitive battery evaluations, and QOLs at various timepoints, baseline to 180 days post‐EVT. The correlation between cognitive function and stroke characteristics, imaging variables, functional ability, and demographic and socio‐behavioral factors will be explored. Safety endpoints will include all‐cause mortality, symptomatic intracranial hemorrhage within 24 h, and device‐related serious adverse events. Key inclusion criteria are per instructions for use (IFU) and pre‐stroke mRS ≤1. Key exclusion criteria are per IFU, prior hemorrhage or stroke within 3 months, and pre‐existing cognitive impairment and/or dementia. Results More study details including the statistical analysis plan and study status will be discussed. Conclusions COGNITIVE is a very first multi‐center, post‐market, prospective, single‐arm EVT study to evaluate whether successful reperfusion with the Tigertriever device is associated with cognitive benefit in subjects with LVO. The study is a superiority design to evaluate whether Tigertriever treatment significantly reduces cognitive impairment.

Single-center results of the Gore Excluder Conformable Endoprosthesis with active control system in endovascular aneurysm repair.

The GORE EXCLUDER Conformable Endoprosthesis with active control (CEXC) was developed to treat challenging aortic neck anatomy. This study investigated the clinical results and changes in endograft (ap)position during follow-up. Patients treated with the CEXC between 2018 and 2022 were included in this prospective single-center study. Computed tomography angiography (CTA) follow-up was grouped into three categories: 0 to 6 (FU1), 7 to 18 (FU2), and 19 to 30 (FU3) months. Clinical end points were endograft-associated complications and reinterventions. CTA analysis included the shortest apposition length (SAL) between the endograft fabric and the first slice where circumferential apposition was lost, shortest fabric distance (SFD) between both renal arteries and the endograft fabric, and maximum infrarenal and suprarenal aortic curvature. FU2 and FU3 were compared with FU1 to establish changes. Included were 46 patients, of whom 36 (78%) had at least one hostile neck feature and 13 (28%) were treated outside instructions for use. Technical success was 100%. Median CTA follow-up was 10 months (2-20 months); 39 patients had a CTA available at FU1, 22 at FU2, and 12 at FU3. At FU1, the median SAL was 21.4 mm (13.2-27.4 mm), which did not significantly change during follow-up. No type I endoleaks, and one type III endoleak at an IBD occurred during follow-up. Two cases of endograft migration (SFD increase >10 mm) were seen during follow-up (one treated outside the instructions for use). Maximum infrarenal and suprarenal aortic curvature did not significantly change during follow-up. The use of the CEXC in challenging aortic necks enables stable apposition without significant changes in aortic morphology at short-term follow-up.

Medical Device Regulations and custom-made device documentation: A further ten frequently asked questions and their answers.

During the 1990s, three Directives were enacted that aimed to harmonise the regulation of medical devices within the European Union (EU). Custom-made devices (CMDs) were subject to Council Directive 93/42/EEC of 14 June 1993 concerning medical devices (Medical Device Directive [MDD]), which was given effect in the UK by the Medical Devices Regulations 2002 (UK MDR 2002). Regulation (EU) 2017/745 (Medical Device Regulation [EU MDR]) replaced the MDD and was transposed into the Medical Devices (Amendment etc.) (EU Exit) Regulations 2019 in the UK. The UK left the EU on 31 January 2020 and entered an 11-month implementation period (IP), during which any new EU legislation that was enacted also took effect in the UK. The EU MDR was scheduled to be fully implemented on 26 May 2020 (during the IP) but this was deferred for one year, until 26 May 2021 (after the IP had concluded), as a result of the coronavirus disease 2019 (COVID-19) pandemic. Consequently, the EU MDR was removed from the UK statute book by a further amendment to the UK MDR 2002, the Medical Devices (Amendment etc.) (EU Exit) Regulations 2020. Since 1 January 2021, CMDs manufactured in Great Britain can conform to either the UK MDR 2002 (as amended) or the EU MDR (until 30 June 2023) while devices manufactured in Northern Ireland are subject to the EU MDR alone. CMDs must be supplied with a statement, a label and, depending on the risk class, instructions for use; this paper answers ten questions regarding this documentation following these legislative changes.

US FDA Postmarketing Requirements and Commitments: A Systematic Assessment of Clinical Pharmacology Studies and Their Impact on US FDA Prescribing Information.

Many of the conditions for the safe and effective use of new molecular entities (NMEs) are understood at the time of initial drug approval. However, some remaining knowledge gaps can be addressed after drug approval through postmarketing requirements (PMRs) or commitments (PMCs) established by the US Food and Drug Administration (FDA). Our objective was to conduct an assessment of clinical pharmacology-related PMRs and PMCs established at the time of approval and evaluate the impact of fulfilled PMRs and PMCs on prescription information (PI). This analysis included clinical pharmacology-related PMRs and PMCs established for NMEs approved between 2009 and 2020. Of the 1171 PMRs and PMCs, over one-third were clinical pharmacology-related. Of these, 46% were to evaluate drug interactions, 16% were to evaluate drug dosing in patients with hepatic impairment, and 10% were related to dose. The majority (57%) of PMRs and PMCs were fulfilled at the time of analysis, with a median time to fulfillment of approximately 2.3years. The majority (94%) of the fulfilled PMRs and PMCs, either with or without a PI revision, resulted in new or modified instructions for use or supported existing instructions for use. This is the first time that clinical pharmacology-related PMRs and PMCs have been catalogued and analyzed to understand their impact on PI. An understanding of the knowledge gaps that exist at the time of drug approval could inform the most effective and efficient methods for evidence generation prior to and after new drug approval.