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Introduction
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malignant hemopathies, hematologic disorders, pain
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HEMATOLOGIC DISORDERS, CREST
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Bone marrow biopsy is a routine procedure for the exploration of hematologic disorders and malignant hemopathies. Biopsy is generally performed on the anterior or posterior iliac crest, and despite local analgesia with lidocaine, the pain level still remains high [
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PMC9978987
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Methods
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PMC9978987
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Study Design
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MAY
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We conducted an open-label, prospective study between September 6, 2018, and May 18, 2020, in 5 centers in France.
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PMC9978987
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Ethical Considerations
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The trial was conducted in accordance with the Declaration of Helsinki of 1975, as revised in 2008, and the International Conference on Harmonization Good Clinical Practice guidelines for biomedical research. The “Sud-Méditerranéen I” Regional Ethics Committee approved the study on February 14, 2018 (2017-A02701-52), and the Agence Nationale de Sécurité du Médicament approved it on March 9, 2018. All patients provided written informed consent.
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PMC9978987
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Study Population and Inclusion and Exclusion Criteria
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coagulation deficit, iliac lymphoma, malignant hemopathy, thrombocytopenia
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ONCOLOGY, THROMBOCYTOPENIA
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Eligible patients were aged 18 years and older with previously documented or suspected untreated malignant hemopathy with an indication for a bone marrow biopsy. An Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2 and normal biological coagulation parameters were required. Clinical examination and bone pelvic imaging were performed before inclusion to exclude iliac lymphoma localization. The exclusion criteria were pregnancy, congenital or acquired coagulation deficit, thrombocytopenia less than 50,000/mm
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PMC9978987
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Randomization
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hemopathy, pain
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Randomization was planned by minimization upon inclusion of patients in the study and programmed using ENNOV clinical data management software (ENNOV; Paris, France). Patients were randomly assigned 1:1 to a pain prevention program using MEOPA or VR. Treatment allocation was stratified by center, age, sex, and hemopathy. In case of intolerance in the VR arm, a change to MEOPA was permitted.
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PMC9978987
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Primary and Secondary End Points
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anxiety, pain
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SECONDARY
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The primary endpoint was a pain reduction of 1.5 points on the VAS for patients included in the VR group in comparison with the MEOPA group. The secondary objectives were the number of lidocaine vials used; duration of exposure to MEOPA (not evaluated in the VR arm); tolerance of the VR session; anxiety level before and after the biopsy; sense of presence for the VR arm; level of residual pain and memory of pain after 1 month of follow-up; and assessment of patient, nurse, and physician satisfaction.
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PMC9978987
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Bone Marrow Procedure
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pain
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All patients were lying face down with their hands positioned under the head (based on the French Society of Hematology guidelines) [In the MEOPA group, administration was started at the same time as the local anesthesia. In the VR group, a 5-minute demonstration session was proposed on the day of randomization to assess tolerance before the biopsy, and the program was started 5 minutes before anesthesia with a maximum duration of 40 minutes. In cases of intolerable pain during the procedure, salvage treatment with a second local injection of lidocaine and/or paracetamol (1 g) or alprazolam (0.25 mg) was proposed.
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PMC9978987
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Description of VR Programs
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Papillon
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Bliss is a type 1 medical device with European accreditation (EN 50581: 2012; manufacturer: Effet Papillon Company, Laval, France). It is a 3-dimensional interactive VR application. The program runs on a smartphone and a GearVR head-mounted display. We proposed 4 imaginary VR environments with a median duration of 15 minutes to 40 minutes: Nohara (dream-like walk on the country side), Kaitei (seabed exploration), Uchuu (space walk), and Mori (dream-like walk in the forest; Nohara environment.Kaetei environment.Uchuu environment.Mori environment.
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PMC9978987
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Data Recorded the Day of the Biopsy
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Anxiety, pain
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BLOOD
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Blood pressure was measured before the biopsy and 15 minutes after the biopsy. Anxiety was assessed using 2 questionnaires: a local fear of pain questionnaire before the biopsy (presence of fear, intensity of fear by VAS, and causes of fear) and the adapted Spielberger State-Trait Anxiety Inventory (STAI) form Y before and 15 minutes after the biopsy [
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PMC9978987
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Data Recorded 1 Month After the Biopsy
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pain
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The level of residual pain and the memory of pain were assessed by the investigators 1 month after the biopsy (responses: yes or no; if yes, the intensity level was assessed using a VAS).
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PMC9978987
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Statistical Analysis
|
pain
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The primary end point was to measure the intensity of pain in each group using the VAS and to demonstrate a 1.5-point reduction in pain in the VR group. We enrolled 120 patients to validate this hypothesis with an SD of 2.5, power of 90%, and type I error rate of 5%. We included 6 more patients, considering that 5% could not be evaluated using 2-tailed tests. Intention-to-treat analysis included patients for whom pain assessment was available.Variables are presented in tables; the Student All statistical analyses were conducted using SAS 9.3 software (SAS Institute Inc) with a significance of 5%.
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PMC9978987
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Results
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PMC9978987
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Sample
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anxiety, pain
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MAY, RECRUITMENT
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A total of 126 patients were enrolled between September 6, 2018, and May 18, 2020, in 5 centers in France: Le Mans (n=80), Strasbourg (n=32), Bordeaux (n=8), Saint-Mandé (n=5), and Angers (n=1). Trial recruitment stopped after inclusion of the target population. We excluded 3 patients before randomization (2 patients did not meet the inclusion criteria, and 1 patient withdrew consent), and 5 patients were excluded after randomization from the final analysis (intensity of pain not documented: 4 patients in the VR group and 1 patient in the MEOPA group). An additional 3 patients did not complete the VR session in the VR group: 1 patient refused VR after the short demonstration and then also refused MEOPA, 1 patient was intolerant, and 1 patient experienced unbearable anxiety. The 2 latter patients both received MEOPA during the biopsy. They were excluded from the per-protocol analysis but included in the intention-to-treat analysis (CONSORT diagram. MEOPA: mixture of nitrous oxide/oxygen; VR: virtual reality.
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PMC9978987
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Biopsy Procedure
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≥140/90 mm Hg, Hypertension
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HYPERTENSION
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Bone marrow biopsy was performed for all patients, and the median blood pressure was 141/79 mm Hg before and after biopsy for all patients, without a significant difference between the groups. Hypertension (≥140/90 mm Hg) was documented in 59.4% (63/118) of patients before biopsy (34/60, 63% in the MEOPA group, 29/58, 56% in the VR group;
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PMC9978987
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Tolerance of the VR Session and Feeling Immersed
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anxiety
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ADVERSE EVENTS, ADVERSE EVENT
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Patients enrolled in the VR group received a short demonstration of VR (5 minutes) to assess their tolerance. During the VR demonstration, most (57/59, 97%) of them watched the entire session, while 2 patients stopped the session: The first patient felt intolerance during the demonstration, and the second patient finally refused VR after completing the demonstration session without an adverse event (Table S2 in For patients who completed the VR program during the biopsy, no adverse events occurred, and only 1 patient experienced a high level of anxiety and switched to MEOPA. Regarding sense of presence, 84% (47/56) of patients felt immersed during the VR session, 73% (41/56) felt elsewhere, and 66% (37/56) felt like they were in a dream (Table S3 in
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PMC9978987
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Discussion
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ascites, fatigue, anxiety, Pain, pain, depression
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ASCITES
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REVEH is the first randomized study to compare VR with standard MEOPA in preventing pain during bone marrow biopsy. The intensity of pain did not significantly differ between VR and MEOPA: 3.0 versus 3.5 (The main technical difficulty was related to the handling of the phone (connection and start of the VR program); a new generation of head-mounted displays has recently emerged with full smartphone integration to facilitate set-up and reduce start-up time (not investigated in this study). Only bone marrow biopsy was evaluated; the impact of VR in the same context should be evaluated for other procedures (eg, lumbar puncture, ascites puncture, pleural puncture, catheter placement). We do not know if the patients had already been exposed to VR during their leisure time (movies, video games; data not available). Patient choice of the scenario was not recorded in this study, so programs were not compared with each other. Patients also could not compare them from one procedure to another (only 1 biopsy per patient). Pain and anxiety are very subjective symptoms that vary from patient to patient and are influenced by the self-experience. Physiological markers (clinical, biological parameters, neuroimaging markers) to objectively assess pain and anxiety have been published: blood pressure and heart rate variations, pupil reflexes, stress hormonal changes, electro-encephalography, magnetic resonance imaging, and positron emission tomography to assess brain activity [Even if the primary outcome of the study has not been achieved, the VR-based relaxation method was well tolerated, and the satisfaction of patients and physicians was very high in the VR group. In the future, the patient will put the helmet on himself or herself and choose his or her own program; in contrast to the use of analgesics or sedatives, no medical monitoring is indicated during and after the procedure, and driving is allowed. The length of time that the patient must be present will be shorter, with a probable socioeconomic impact, which will have to be evaluated.Several meta-analyses were published between 2019 and 2020 that evaluated the impact of VR on fatigue, anxiety, depression, and care-induced pain [
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PMC9978987
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Conclusion
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opioid dependence, fatigue, anxiety, Pain, cancer, FM, ALS, pain, depression
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CHRONIC PAIN, EVENTS, CANCER
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Pain intensity did not significantly differ between VR and MEOPA arms during bone marrow biopsy in this study. The VR-based distraction method was safe and appreciated by patients and caregivers. Digital therapeutics could be an alternative treatment in case of contraindication or intolerance to MEOPA and could be integrated into the oncology support care panel.Further studies should focus on demonstrating the efficacy of a VR program (content, type, interactions, number of sessions, program duration) in pain prevention and other symptoms (fatigue, depression, anxiety, cognitive functions) for each indication, compared with conventional drugs with a noninferiority outcome, if possible, and based on feasible objective parameters. The impact of VR will also have to be studied for patients hospitalized for a long period of time and at home for outpatients. For chronic pain, VR should be evaluated in terms of scheduling, efficacy, and tolerability to reduce opioid dependence in cancer patients [The authors would like to thank the patients and their families for their participation and Melanie Peron, Etienne Lepoutre, and Magali Balavoine for their intellectual input and advice. This investigation was supported by a grant from the French Lymphome Espoir Association and the Fundings of Hoffman-Roche lab and the Elsan group.The study was supported by Hoffmann-La Roche, the Elsan group, and the France Lymphome Espoir Association.Authors' Contributions: KLD, ALS, and SB designed the study. ALS assembled, analyzed, and interpreted the data. KLD wrote the first draft of the manuscript. All authors were involved in the preparation and revisions of the manuscript and approved the final version of the manuscript for submission.Conflicts of Interest: KLD reports receiving consulting fees from Incyte, Abbvie, and Janssen-Cilag and research support from Roche. FM reports receiving consulting fees from Pfizer, Amgen, Incyte, and Roche. SB is president and part owner of In Virtuo, a company that distributes virtual environments.Bone marrow events.VR tolerance (n=59).Feeling of immersion (n=56).Fear of pain.CONSORT-eHEALTH checklist V 1.6.1.
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PMC9978987
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Abbreviations
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Anxiety
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ONCOLOGY
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Eastern Cooperative Oncology Groupmixture of nitrous oxide/oxygenPreferred Reporting Items for Systematic Reviews and Meta-AnalysesSpielberger State-Trait Anxiety Inventoryvisual analog scalevirtual reality
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PMC9978987
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Data Availability
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All data from the study are freely available upon request to the corresponding author.
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PMC9978987
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Subject terms
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We report the findings from a randomized, parallel study designed to evaluate nicotine pharmacokinetics (PK) following 10 min of ad libitum use of electronic nicotine delivery system (ENDS) in four flavor variants. Subjects were randomized an investigational product (IP) and blood samples were collected for PK assessments during a test session. Primary endpoints were baseline-adjusted values of maximum plasma nicotine concentration (C
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PMC10235118
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Introduction
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lung cancer, premature death
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HEART DISEASE, CHRONIC BRONCHITIS, LUNG CANCER, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, DISEASES
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Cigarette smoking is a leading cause of preventable premature death, and significantly increases the risk of developing lung cancer, heart disease, chronic bronchitis, chronic obstructive pulmonary disease and other serious diseases and adverse health conditionsThis publication is part of a three-part series describing the clinical assessment of Vuse Solo (cig-a-like ENDS). Vuse Solo has a rechargeable battery and has separate nicotine containing cartridges. The clinical studies included in this publication series describe the nicotine pharmacokinetics (PK) of Vuse Solo across four e-liquid flavors; an assessment of the abuse liability of Vuse Solo as compared to combustible cigarettes (CC) and a nicotine replacement therapy productWe report findings from a clinical study that was performed as part of a regulatory submission to the FDA CTP to assess the nicotine PK parameters of Vuse Solo flavor variants after a single ad libitum use in solus and dual users of cigarette and ENDS. The study data was reviewed by the FDA and granted a marketing order for Original (tobacco) flavor Vuse Solo ENDS cartridges and the Vuse Solo power unit as they deemed the product was appropriate for the protection of public health
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PMC10235118
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Results
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PMC10235118
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Study population
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A total of 148 subjects were enrolled and randomized; all subjects were randomized to one of four Vuse Solo investigational products (IPs) and 122 (82.4%) subjects completed all scheduled PK assessments. A total of 26 randomized subjects (17.6%) withdrew or early termed from the study for reasons unrelated to study products. Of these 122 study completers, four subjects were excluded from the final PK analysis due to CThe demographic and baseline characteristics of the subjects are summarized in Supplementary Table
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PMC10235118
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Adverse events
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oropharyngeal pain
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ADVERSE EVENTS, GASTROESOPHAGEAL REFLUX, OCULAR HYPEREMIA
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Nine of 148 (6%) subjects experienced nine adverse events during the study. Gastroesophageal reflux (one subject) and oropharyngeal pain (one subject) were each considered by the principal investigator (PI) to be possibly related and related to IP, respectively. All other adverse events were judged by the PI not to be related to IP. All adverse events were of mild intensity except for moderate ocular hyperemia in one subject, which was deemed unrelated to product use and led to subject withdrawal from the study by the PI. No serious adverse events were reported.
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PMC10235118
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Discussion
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AUCAs, NRS
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We evaluated PK parameters of four flavor variants of e-liquids used in Vuse Solo ENDS which include 4.8% nicotine by weight (~ 57 mg/mL), and contain nicotine salts following an acute exposure in predominately ENDS naïve smokers. Our data showed that subjects achieved similar overall nicotine exposure (AUCAs stated above, the results and distribution of baseline adjusted CAs was the case with CSt. Helen and colleagues examined the impact of flavors (Strawberry vs. Tobacco) on nicotine uptake and topographyIn addition to PK assessments, subjects were also asked to rate OPL for the Vuse Solo flavor variants on an 11-point NRS at 13 min after initiating the ENDS use. Subjects rated the Tropical flavor highest, followed by the Original (tobacco), Fusion, and Mint flavor (Table Similarly, in a topography study to assess the effect of flavor in regular smokers, Voos et al. concluded that the flavors used in their study delivered differential amounts of nicotine, potentially associated with product use topography, and that differences in subjective effects are not solely a product of nicotine delivery and recommended additional researchIn this study, subjects were asked to familiarize themselves with ENDS products at home for one week prior to a PK test session. For at-home trial use, subjects were dispensed two cartridges of ENDS product flavor they were randomized to use during a PK test session with an option to request more had they used both prior to the end of the at-home trial period. Subjects were encouraged to use ENDS at least once a day while they continue to use their usual brand of cigarettes. All subjects returned one partially used cartridge at check-in, along with their second cartridge which no subject had begun to use. The amount of e-liquid consumed was measured by differences in cartridges weights obtained before and after a week of at home use, where ENDS naïve subjects were encouraged to use the ENDS ad libitum as often as possible. We found that subjects used approximately 10% of e-liquid by weight ranging from 0.16 (± 0.17) mg to 0.21 (± 0.25) mg across the four flavors (Table Subjects were also required to abstain from tobacco products for 12 h prior to PK test sessions to ensure their blood nicotine concentrations were close to baseline prior to the start of product use. Furthermore, we collected blood samples at intervals that allowed characterization of nicotine PK following ad libitum ENDS exposure and the nicotine concentrations of blood samples were baseline-adjusted to ensure more accurate results. Lastly, for this study, subjects were allowed a 10-min ad libitum use of the ENDSThis study had several limitations. Although we allowed participation of dual users, more than 90% of our subjects were exclusive cigarette smokersIn conclusion, the primary endpoints of this study, C
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PMC10235118
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Methods
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ICH
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This study was a single-center study (ClinicalTrials.gov identifier: NCT03234010, 31/07/ 2017) designed to evaluate plasma nicotine uptake and overall product liking with use of four flavor variants of the Vuse Solo ENDS (Vuse Solo Original, Mint, Tropical and Fusion) in tobacco consumers who were exclusive smokers or dual users of cigarettes and ENDS. The study was completed at a single clinical research site (DaVita Clinical Research, Lakewood, CO) and was reviewed and approved by Chesapeake Institutional Review Board (Columbia, MD).No formal sample size calculations were performed as the study was designed to assess nicotine uptake from flavor variants of Vuse Solo ENDS and no comparisons between flavors was intended. The study was designed to assess nicotine PK from use of flavor variants for the purpose of regulatory submission, rather than comparing a single flavor against other flavor variants. The target number of subjects to be randomized for this study was 35 subjects per flavor variants or total of 140. This allowed for approximately 15% drop out rate (5 subjects per flavor variant) with goal of obtaining 120 study completers or 30 study completers per flavor.Attempts were made to recruit 15–20% African-Americans within each IP group in an effort to balance the study sample for the reported percentage of U.S. smokers who are African AmericanThe study was conducted in accordance with the ethical standards in the Declaration of Helsinki, applicable sections of the United States Code of Federal Regulations, and ICH E6 Good Clinical Practice guidelines.
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PMC10235118
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Study product
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Each Vuse Solo ENDS consist of power unit and a cartridge. Each cartridge is a sealed unit containing 0.5 mL of e-liquid comprising 4.8% nicotine by weight (~ 57 mg/mL), and containing nicotine salts, propylene glycol, glycerin, flavorings, and water. The products were powered by a rechargeable power unit and included a heating element, microchips, and a sensor. Aerosol generation is activated by detection of a pressure differential within the ENDS product during puffing.
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PMC10235118
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Study design
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ADVERSE EVENTS
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The study was designed as a randomized, open-label, parallel-cohort study to assess nicotine uptake in human subjects following ENDS use. The study examined plasma nicotine PK parameters in Vuse Solo ENDS with four flavor variants: Original, Mint, Tropical and Fusion.Subjects were given a 1-week at-home trial period to become familiar with the assigned Vuse IPs. Subjects were encouraged to use ENDS at least once a day at-home trial period while they continue to use their usual brand of cigarettes. The product use compliance during the at-home trial period was monitored by obtaining cartridge weight before the dispensing and after subject checked in to the site for overnight confinement. Subjects were randomized to specific ENDS flavors and were provided two cartridges with instructions for use. Product use compliance was checked by weighing ENDS cartridges three times before and after use to a sensitivity of 1 × 10On Study Day 1, subjects arrived at the study site and began their check-in procedures prior to confinement. Subjects returned ENDS IP e-liquid cartridges from the at-home trial period to the site. Eligibility criteria were reconfirmed, and those who successfully completed all check-in procedures were confined to the study site for approximately 24 h. Subjects were allowed to use their assigned IP ad libitum until the start of a mandatory 12-h abstinence from tobacco and nicotine products.On the morning of Study Day 2, each subject was given their assigned ENDS IP for use during the PK assessment. Subjects were then allowed to use the assigned ENDS IP ad libitum for 10 min (± 10 s). Start and stop times were documented. ENDS IP cartridges were weighed three times before and after use to 1 × 10During the PK assessment, blood samples were collected and processed to plasma for nicotine measurements at the following time points relative to the start of IP use: − 5, − 0.5, 3, 5, 8, 10, 11, 12, 15, 20, 30, and 60 min. The − 0.5 min sample was used as the preferred baseline sample. Samples were collected and centrifuged within 60 min of collection. The plasma was transferred into 2 methanol pre-washed tubes and frozen prior to shipment on dry ice to the bioanalytical lab. All samples were transferred to Celerion Global Bioanalytical Services (Lincoln, NE) for nicotine quantitation using a validated liquid chromatography tandem mass spectrometry method.
In addition to blood sample collection, subjects were required to provide an OPL score at 13 min after start of IP use on a numeric scale of 0 to 10, with 0 corresponding to “strongly dislike,” 5 corresponding to “neither like nor dislike”, and 10 corresponding to “strongly like.” Each subject was assessed for adverse events and vital signs, and a symptom-driven physical examination was performed, if necessary, prior to discharge from the study to ensure subject’s safety. Upon the PI’s review of subjects’ status, if there were no new adverse events or physical examination findings to warrant further follow up, subjects were discharged from the study.
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PMC10235118
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Statistical analysis
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®
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The primary PK parameters (CThe pharmacokinetic (PK) analyses were performed by Nuventra Pharma Sciences, Inc. located in Durham, NC. PK parameters were derived from the baseline-adjusted plasma nicotine concentrations-time data by noncompartmental methods using Phoenix® WinNonlin® (Version 6.3; Certara USA Inc., Princeton, NJ).
AUCs were calculated using the linear trapezoidal rule. C
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PMC10235118
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Supplementary Information
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The online version contains supplementary material available at 10.1038/s41598-023-35439-3.
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PMC10235118
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Acknowledgements
|
P.
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The authors wish to acknowledge Megan J. Whelen and Sarah Baxter-Wright for medical writing assistance, critical review, and editing of the manuscript; Gregory P. Tarleton, MD for providing medical expertise to ensure subject safety; and Jeff Coffield for maintaining the study Trial Master Files and managing other study-related documentation.
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PMC10235118
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Author contributions
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Study concept and design: K.S.H., P.D., B.A.J., E.R., P.N. Acquisition of data: E.S. Drafting of the manuscript: K.S.H., B.M.K. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: T.J. All authors have read and approved the final manuscript.
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PMC10235118
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Competing interests
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Nelson
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NELSON, SCHMIDT
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Brian M. Keyser, Kyung Soo Hong, Patricia DeLuca, Tao Jin, Bobbette A. Jones, Paul Nelson, Eckhardt Schmidt and Elaine K. Round were all full employees of RAI Services Company during the execution of the study. RAI Services Company is a wholly owned subsidiary of Reynolds American Inc., which is a wholly owned subsidiary of British American Tobacco plc. Vuse Solo is produced by RJR Vapor Co., LLC, a wholly owned subsidiary of Reynolds American Inc., which is a wholly owned subsidiary of British American Tobacco plc.
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PMC10235118
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References
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PMC10235118
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Key Points
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PMC9929699
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Question
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uveitis
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DISEASE, UVEITIS
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Is there any difference in uveitis outcomes between patients with inactive disease given recommendations for early and deferred non–messenger RNA (mRNA) COVID-19 vaccination?
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PMC9929699
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Findings
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uveitis
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DISEASE, UVEITIS
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In this open-label, randomized clinical trial involving 543 patients, recommendation for early vaccination resulted in an increased incidence of self-reported worsening of symptomatic uveitis compared with deferred vaccination, but no differences were observed in disease and visual prognosis at 3 months.
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PMC9929699
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Meaning
|
uveitis
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ADVERSE EFFECTS, DISEASE, UVEITIS
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These findings suggest that recommendation for early non-mRNA COVID-19 vaccination in patients with inactive uveitis may lead to subjective uveitis symptoms but no adverse effects on disease and visual prognosis at 3 months.This randomized clinical trial compares recommendations for early and deferred non–messenger RNA COVID-19 vaccination with respect to ocular outcomes among patients with inactive uveitis.
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PMC9929699
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Importance
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immune-mediated adverse, uveitis
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REMISSION, UVEITIS
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Improper host response to COVID-19 vaccines could trigger immune-mediated adverse events. The question remains whether COVID-19 vaccination should be postponed until complete remission in patients with uveitis, a preexisting immune-related condition.
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PMC9929699
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Objective
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uveitis
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UVEITIS
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To compare recommendations for early and deferred COVID-19 vaccination with respect to uveitis outcomes.
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PMC9929699
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Design, Setting, and Participants
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uveitis
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UVEITIS
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This open-label, randomized clinical trial at a large, specialized teaching center for uveitis care in China enrolled unvaccinated patients with inactive uveitis between August 10, 2021, and February 22, 2022, with follow-up to June 6, 2022.
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PMC9929699
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Interventions
|
uveitis
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REMISSION, UVEITIS
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Participants were randomly assigned to receive recommendation for early or deferred COVID-19 vaccination after complete remission of uveitis. Non–messenger RNA (non-mRNA) COVID-19 vaccines were available in China during the trial.
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PMC9929699
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Main Outcomes and Measures
|
uveitis
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UVEITIS
|
The primary outcome was the time to symptomatic uveitis worsening during 3 months of follow-up. Secondary outcomes included uveitis activity and best-corrected visual acuity at 3 months.
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PMC9929699
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Results
|
uveitis
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UVEITIS
|
Of the 543 participants (304 women [56.0%]; median age, 35 [IQR, 26-49] years), 262 were recommended for early vaccination and 281 for deferred vaccination. By month 3, 109 patients (41.6%) in the early group had been vaccinated compared with 14 (5.0%) in the deferred recommendation group. In the intention-to-treat population, the time to symptomatic uveitis worsening was shorter in the early group than in the deferred group (hazard ratio, 1.68 [95% CI, 1.09-2.59];
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PMC9929699
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Conclusions and Relevance
|
uveitis
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ADVERSE EFFECTS, DISEASE, UVEITIS
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In this randomized clinical trial of patients with inactive uveitis, recommendation for early non-mRNA COVID-19 vaccination resulted in a higher incidence of self-reported symptomatic uveitis worsening with possible reporting bias compared with recommendation for deferred vaccination, but no adverse effects were observed in disease and visual prognosis at 3 months. These findings would be useful to guide the individual timing choices of non-mRNA COVID-19 vaccination in this clinically vulnerable population.
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PMC9929699
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Trial Registration
|
Chinese Clinical Trial Registry:
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PMC9929699
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Introduction
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vision-threatening intraocular inflammation, death, illness, immune-related disorder, SARS-CoV-2.Uveitis
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COVID-19 vaccines remain the cornerstone of effective prevention of severe illness and death due to SARS-CoV-2.Uveitis is an immune-related disorder characterized by vision-threatening intraocular inflammation, which has a wide association with systemic inflammatory conditions.
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PMC9929699
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Methods
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PMC9929699
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Trial Design
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uveitis
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UVEITIS
|
This open-label randomized clinical trial was conducted at The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. The hospital has set up a large, specialized teaching center for uveitis care and has treated 15 373 patients with uveitis across mainland China as of 2018.
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PMC9929699
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Trial Population
|
uveitis
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UVEITIS
|
Eligible participants were 12 years or older, had not yet received COVID-19 vaccines, and were diagnosed with any form of uveitis in an inactive status.
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PMC9929699
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Randomization, Assignment, and Follow-up
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redness, uveitis, floaters, pain
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ADVERSE EVENTS, REMISSION, UVEITIS, DECREASED VISION
|
Participants underwent simple randomization to receive the recommendation for early or deferred COVID-19 vaccination in a 1:1 ratio. Random assignment sequence was computer-generated, and individual allocations were known by telephone from a designated staff who kept the sequence and had no involvement in other parts of the trial. Patients and treating clinicians were aware of the trial assignment.Patients in the early vaccination group were recommended to receive COVID-19 vaccines as soon as possible, while patients in the deferred vaccination recommendation group were recommended to receive COVID-19 vaccines after the complete remission of uveitis. Our clinic did not provide COVID-19 vaccination service. We assessed patients’ uveitis status and only gave the recommendation to patients. Non-mRNA COVID-19 vaccines were free of charge and available in the community. During the trial, 2 inactivated SARS-CoV-2 vaccines, CoronaVac (Sinovac Biotech) and BBIBP-CorV (Sinopharm), and 1 protein subunit vaccine, ZF2001 (Anhui Zhifei Longcom Biopharmaceutical Co, Ltd), were available under emergency use authorization among people 12 years or older in China.Routine follow-up encounters occurred every month by telephone, and an in-person clinic visit was scheduled at month 3. At the telephone follow-up encounters, patients were asked about adherence to the recommendation, reasons for nonadherence, experiences of systemic adverse events, and uveitis symptoms, including the presence and duration of new-onset eye redness, eye pain, decreased vision, light sensitivity, and floaters. These queries were administered in a standardized telephone interview from the trial call center. Information on missed encounters could be completed in subsequent encounters provided that participants were brought back. In addition, all participants were repeatedly encouraged to follow the assigned vaccination recommendation during the telephone call. If the aforementioned symptoms or systemic adverse events were reported, patients would be instructed to return to the study site early or visit local hospitals for further clinical evaluation. We asked patients to provide their medical records from their local hospitals if any. Patients would receive best medical judgment and proper treatment, and intervention with trial recommendations would be terminated. At the month 3 in-person visit, patients underwent additional clinical evaluations, including slitlamp biomicroscopy, ophthalmoscopy, measurement of best-corrected visual acuity (BCVA), and other auxiliary examinations according to clinical needs.
|
PMC9929699
|
Outcomes
|
redness, uveitis, pain, haze, floaters
|
ADVERSE EVENTS, UVEITIS, DECREASED VISION, SECONDARY, DISEASES
|
The primary outcome was the time to worsening of symptomatic uveitis, defined by 1 of the following new-onset symptoms occurring in at least 1 eye and lasting for at least 2 days: eye redness, eye pain, decreased vision, light sensitivity, or floaters, as confirmed by blinded review by an adjudication committee. The adjudication committee consisted of 3 independent clinicians, and the outcome was achieved with a majority of 2. Key secondary outcomes included proportion of COVID-19 vaccination, proportion of adherence to recommendation, proportion of each worsening symptom, proportion of 2-grade increase in anterior chamber cells from baseline to month 3, proportion of 2-grade increase in vitreous haze from baseline to month 3, change in BCVA from baseline to month 3, and incidence of systemic adverse events. The original protocol also included secondary outcomes concerning clinically confirmed uveitis worsening, hospitalization, and treatment, which were determined based on in-person clinical evaluation when patients returned to the study site or visited local hospitals with symptomatic uveitis worsening. During the execution of the trial, most cases with worsening symptoms did not seek medical services and assessment at our study center, nor did they provide medical records to show their local hospital visits, possibly due to their mild diseases, self-care, remote living, or COVID-19 travel restrictions. Therefore, these secondary outcomes were not reported in terms of data unavailability.
|
PMC9929699
|
Statistical Analysis
|
REGRESSION, EVENT
|
Assuming that the cumulative incidence would be 10% in the deferred vaccination group during the month 3 follow-up and the proportion dropping out in both groups would be 15%, we estimated that an overall sample of 1314 participants would provide 80% power to detect a hazard ratio (HR) for early vaccination recommendation of 1.50 for the primary outcome compared with deferred vaccination recommendation, at a 2-sided significance level of The primary analysis was performed according to the intention-to-treat principle in all randomized participants, regardless of their adherence to the assigned recommendation. Outcome times were calculated from randomization to the encounter reporting the end point event or the last follow-up. Time-to-event data were analyzed using the Kaplan-Meier method, with trial groups compared using a log-rank test and HRs calculated using Cox proportional hazards regression. The proportional hazards assumption was met as confirmed by inspection of log-log survival plot (eFigure in Binary outcomes are presented as numbers with proportions. We calculated 95% CIs for between-group differences in proportions using the Wilson score method.
|
PMC9929699
|
|
Results
|
PMC9929699
|
|||
Patients
|
A total of 543 patients were formally assessed for eligibility and enrolled. The median age was 35 (IQR, 26-49) years; 304 patients (56.0%) were female and 239 (44.0%) were male. Two hundred sixty-two patients were recommended for early COVID-19 vaccination and 281 for deferred vaccination. The baseline characteristics were similar between 2 groups (
|
PMC9929699
|
||
Baseline Characteristics of the Intention-to-Treat Population
|
HEPATITIS B, VIRUS
|
Abbreviations: BCVA, best-corrected visual acuity; HBV, hepatitis B virus.Unless otherwise specified, data are expressed as No. (%) of patients. Percentages have been rounded and may not total 100.Includes Chinese Dong, Hani, Hui, Li, Lisu, Man, Mongolian, Miao, Tibetan, Tujia, Uygur, Yi, and Zhuang peoples.Data were missing for 4 patients in the early vaccination group.Data were missing for 2 patients in the early vaccination group and 2 patients in the deferred vaccination group.
|
PMC9929699
|
|
Randomization, Follow-up, and Analysis Populations
|
The intention-to-treat (ITT) population included 543 patients who underwent randomization. The modified ITT population excluded 32 persons who were identified as being vaccinated before randomization. The per-protocol population included the patients in the modified ITT population except 160 persons who did not adhere to assigned recommendation. The completed telephone follow-up population included the patients in the ITT population, except 37 persons who did not complete 3-month telephone call follow-up. The month 3 in-person evaluable population included the patients in the ITT population except 294 persons who did not complete month 3 in-person follow-up.
|
PMC9929699
|
||
COVID-19 Vaccine Uptake
|
By month 3, 109 patients (41.6%) of the patients assigned to early vaccination recommendation had received at least 1 dose of non-mRNA COVID-19 vaccine compared with 14 (5.0%) of those assigned to a deferred vaccination recommendation (
|
PMC9929699
|
||
Secondary Outcomes
|
uveitis
|
REMISSION, UVEITIS
|
Abbreviations: BCVA, best corrected visual acuity; LogMAR, log of the minimum angle of resolution.Unless otherwise indicated, data are expressed as No. (%) of patients.COVID-19 vaccination schedule included 2 primary doses of inactivated vaccines (CoronaVac [Sinovac Biotech] and BBIBP-CorV [Sinopharm]) or 3 doses of a protein subunit vaccine (ZF2001 [Anhui Zhifei Longcom Biopharmaceutical Co, Ltd]).In the deferred vaccination group, 4 patients had complete remission of uveitis during the study period and should have been vaccinated according to the trial recommendation.Each patient may have had 2 or more reasons.These outcomes were assessed in the month 3 in-person evaluable population (n = 249) relative to the baseline condition.Analyzed by eye with the generalized estimating equation to account for baseline values and the correlation between eyes of the same patient. Visual acuity data are expressed as LogMAR scores, with higher values indicating poorer visual acuity.
|
PMC9929699
|
Primary Outcome
|
uveitis
|
UVEITIS
|
Symptomatic uveitis worsening occurred in 51 patients (19.5%) recommended for early COVID-19 vaccination and in 34 (12.1%) recommended for deferred COVID-19 vaccination (between-group difference, 7.4% [95% CI, 1.2%-13.6%]). In the intention-to-treat analysis, the time to symptomatic uveitis worsening was shorter in the early vaccination group than in the deferred vaccination group (HR, 1.68 [95% CI, 1.09-2.59];
|
PMC9929699
|
Kaplan-Meier Estimates of the Time to Symptomatic Uveitis Worsening
|
HR indicates hazard ratio.
|
PMC9929699
|
||
Estimates of Primary Outcome Across Analysis Populations
|
HR indicates hazard ratio; ITT, intention-to-treat.
|
PMC9929699
|
||
Secondary Outcomes
|
haze, uveitis, floaters
|
UVEITIS
|
Patients in the early vaccination group more frequently reported new onset of floaters as one of the reasons for symptomatic uveitis worsening (difference, 4.2% [95% CI, 1.7%-7.5%]). The ocular conditions, including changes in anterior chamber cells, vitreous haze, and BCVA from baseline to month 3, appeared similar between the 2 groups in the month 3 in-person evaluable population (
|
PMC9929699
|
Discussion
|
uveitis, COVID-19 illness
|
SARS-COV-2 INFECTION, DISEASE, UVEITIS, ADVERSE EFFECTS, SECONDARY
|
This open-label, randomized clinical trial showed that recommendation for early non-mRNA COVID-19 vaccination to patients with inactive uveitis led to earlier self-reported symptomatic uveitis worsening than the recommendation for deferred vaccination. We found no evidence that uveitis activity and visual acuity at 3 months differed substantially according to recommendation type.This trial extends prior observations linking COVID-19 vaccination with an increased risk of newly active or worsening uveitisAs a subjective measure, the primary outcome could at least partially reflect subjective feelings about the disease condition and certain levels of quality of life. However, participants were aware of their vaccination status, and those concerned about vaccination could have an exacerbated experience of their symptoms. Our trial detected the significant effects of recommending early COVID-19 vaccination on patient’s symptoms. However, the between-group mean difference (7.4% [95% CI, 1.2%-13.6%]) in incidence of symptomatic uveitis worsening was subtle, and it would be possible to have reporting bias from people who received COVID-19 vaccines as large as that would negate the currently reported significant difference in the primary outcome. More importantly, no adverse effects were observed in disease and visual prognosis at 3 months. The inconsistency between the primary and secondary outcomes also suggested the possibility of reporting bias incurred by psychological factors related to subjective assessment of the primary outcome. These findings highlight that, in clinical practice, more psychological reassurance should be provided to patients before or after COVID-19 vaccination, especially those worried about the adverse effects of COVID-19 vaccine. The timing choices for COVID-19 vaccination in inactive uveitis may be primarily based on the individual risk of SARS-CoV-2 infection and severe COVID-19 illness as well as patient’s expectations and preferences rather than on anticipated differences in the disease and visual prognosis of uveitis.
|
PMC9929699
|
Limitations
|
inflammation, uveitis
|
INFLAMMATION, DISEASE, UVEITIS, SECONDARY
|
This study has some limitations. First, interpretation of the outcomes was limited by the open nature of the trial, especially when interpreting results for a subjective outcome in the context of COVID-19 vaccination. Moreover, all symptoms were based on self-report, and we lacked data regarding clinical evaluation to confirm disease worsening. The possibility that the greater reporting bias in patients receiving COVID-19 vaccines may lead to the slightly higher incidence rather than the vaccine increasing inflammation cannot be ruled out. Second, our sample size fell short of expectations due to the lack of eligible unvaccinated patients in China, although this sample size was powered to detect the difference in the primary outcome. Third, a number of patients were not included in the month 3 in-person evaluable population. Nevertheless, this population was only related to several secondary outcomes, in which data showed materially small between-group differences in the point estimate. Moreover, results were similar after accounting for data missing with inverse probability weighting. Fourth, we could not precisely define which uveitis worsening was caused by COVID-19 vaccination. Instead, we only examined the excess risk of symptomatic worsening in the early vaccination group compared with the deferred one, with randomization leading to the balanced background risk between the 2 groups. To mitigate the interference of other factors unrelated to vaccination, we chose a 3-month observation period for vaccine uptake and uveitis worsening because a later onset of uveitis flare was less likely to be related to COVID-19 vaccination.
|
PMC9929699
|
Conclusions
|
uveitis
|
ADVERSE EFFECTS, DISEASE, UVEITIS
|
In this randomized clinical trial of patients with inactive uveitis, recommendation for early non-mRNA COVID-19 vaccination resulted in a higher incidence of self-reported symptomatic uveitis worsening with possible reporting bias compared with recommendation for deferred vaccination, but no adverse effects were observed in disease and visual prognosis at 3 months. These findings would be useful to guide the individual timing choices of non-mRNA COVID-19 vaccination in this clinically vulnerable population.
|
PMC9929699
|
Keywords
|
prostate
|
PROSTATE
|
Radiotherapy treatment planning based only on magnetic resonance imaging (MRI) has become clinically achievable. Though computed tomography (CT) is the gold standard for radiotherapy imaging, directly providing the electron density values needed for planning calculations, MRI has superior soft tissue visualisation to guide treatment planning decisions and optimisation. MRI-only planning removes the need for the CT scan, but requires generation of a substitute/synthetic/pseudo CT (sCT) for electron density information. Shortening the MRI imaging time would improve patient comfort and reduce the likelihood of motion artefacts. A volunteer study was previously carried out to investigate and optimise faster MRI sequences for a hybrid atlas-voxel conversion to sCT for prostate treatment planning. The aim of this follow-on study was to clinically validate the performance of the new optimised sequence for sCT generation in a treated MRI-only prostate patient cohort. 10 patients undergoing MRI-only treatment were scanned on a Siemens Skyra 3T MRI as part of the MRI-only sub-study of the NINJA clinical trial (ACTRN12618001806257). Two sequences were used, the standard 3D T2-weighted SPACE sequence used for sCT conversion which has been previously validated against CT, and a modified fast SPACE sequence, selected based on the volunteer study. Both were used to generate sCT scans. These were then compared to evaluate the fast sequence conversion for anatomical and dosimetric accuracy against the clinically approved treatment plans. The average Mean Absolute Error (MAE) for the body was 14.98 ± 2.35 HU, and for bone was 40.77 ± 5.51 HU. The external volume contour comparison produced a Dice Similarity Coefficient (DSC) of at least 0.976, and an average of 0.985 ± 0.004, and the bony anatomy contour comparison a DSC of at least 0.907, and an average of 0.950 ± 0.018. The fast SPACE sCT agreed with the gold standard sCT within an isocentre dose of -0.28% ± 0.16% and an average gamma pass rate of 99.66% ± 0.41% for a 1%/1 mm gamma tolerance. In this clinical validation study, the fast sequence, which reduced the required imaging time by approximately a factor of 4, produced an sCT with similar clinical dosimetric results compared to the standard sCT, demonstrating its potential for clinical use for treatment planning. Open Access funding enabled and organized by CAUL and its Member Institutions
|
PMC10480277
|
Introduction
|
MR, prostate
|
PROSTATE
|
Radiotherapy treatment planning based only on magnetic resonance imaging (MRI), or MRI-only radiotherapy, has recently become clinically achievable [There are various approaches which have been utilised for sCT generation, such as bulk density correction methods, atlas methods, deep learning algorithms or a combination of these approaches. Bulk density correction requires only segmentation of the MRI, with appropriate density values applied to these segmentations for dose calculation [Within an MRI simulation session for MRI-only radiotherapy treatment planning, various MRI sequences may be captured for specific visualisation, such as fiducial marker identification, or target and organ at risk delineation purposes in addition to any particular sequence or sequences required for specific sCT generation methods. The MR imaging portion of the simulation session can take a significant amount of time [Previously, a volunteer study was conducted investigating the effects of MRI sequence time reduction on sCT generation for prostate MRI-only treatment planning and to determine a suitable sequence [
|
PMC10480277
|
Method
|
prostate
|
PROSTATE
|
Ten prostate radiotherapy patients were included in the study. These patients were recruited to the NINJA (Novel Integration of New prostate radiation therapy schedules with adjuvant Androgen deprivation) clinical trial (ACTRN12618001806257) which had local ethics approval (HREC/18/LPOOL/420), investigating stereotactic radiotherapy to the prostate comparing monotherapy against a virtual high dose rate brachytherapy boost regimen. This clinical trial also contains an MRI-only planning sub-study, demonstrating the ability to fully transition centres from CT- to MRI-based prostate radiotherapy planning, which these patients were enrolled into. Patients in this trial were prescribed either 40 Gy in 5 fractions or a stereotactic boost of 20 Gy in 2 fractions followed by a standard 36 Gy in 12 fractions, with treatment plans consisting of two VMAT arcs. The patients involved in the current study were part of the MRI-only planning sub-study, and scanned on a Siemens (Erlangen, Germany) Skyra 3T MRI with a flat radiotherapy couch and body coil mounted on coil mounts as per trial protocol. Patient age ranged from 60 to 72, and Body Mass Index (BMI) ranged from 23.1 to 32, with a mean of 27.1.The standard planning MRI sequence as used for the clinical trial was a 3D T2-weighted isotropic SPACE (Sampling Perfection with Application optimised Contrasts using different flip angle Evolution) sequence which covered the entire pelvis, with scan limits from L5/S1 to the pubic symphysis. This sequence was previously validated against CT by Dowling et al. [
MRI sequence parameters which differed between the standard and fast T2 SPACE and the average scan time for each sequence
MRI sequences were converted to sCT using a hybrid atlas-voxel method as described in Dowling et al. [
Treatment planning for these patients was completed on the S-sCT using the Pinnacle Treatment Planning System (v16.21; Philips Healthcare, Andover, MA) utilising the auto-planning module for beam optimisation. Patient treatment plans met all trial guidelines, with each treatment plan consisting of two full Volumetric Arc Therapy (VMAT) treatment beams. Each patient’s corresponding clinically approved treatment plan was copied to the F-sCT and recalculated for comparison of isocentre point dose, a 1%/1mm global gamma comparison and DVH analysis of the PTV, bladder and rectum.
|
PMC10480277
|
Results
|
The Fast sequence scan was able to be completed on all patients with no modifications required by the system. This sequence was able to be converted to sCT as per Dowling et al. [
An example of the (a) standard MRI and (b) S-sCT and the (c) fast MRI and (d) F-sCT for the same corresponding slice for one patient. The body and bone masks are also displayed on the sCT slices in (b) and (d)The mean absolute error (MAE) in HU over the ten patients for the F-sCT compared to the S-sCT with the body and bone masks from the S-sCT, in addition to tissue only, is shown in Fig.
Mean Absolute Error (MAE) of HU for the generated sCT from the fast MRI sequence compared to the sCT generated from the standard MRI sequence for all patients for the within-the-body contour, the automatic bone contour, and for tissue only
Volume percentage difference, mean Hausdorff distance and DSC results for automatic body and bone contours for the generated sCT for the fast MRI sequence compared to the standard sequence generated sCT for all patientsThe volume percentage difference, mean Hausdorff distance and DSC results for both the body and bone contour comparison can be seen in Table
Dosimetric Results for all patient plan comparisons. The isocentre point dose was compared, as well as 1%/1 mm Global Gamma analysis for the clinical plan from the S-sCT recalculated on the F-sCTTable
DVH comparison of PTV parameters and the rectum and bladder D50 for the recalculated treatment plans on the F-sCT compared to calculated on the S-sCT. This figure shows the percentage difference for each parameter for all patients
|
PMC10480277
|
||
Discussion
|
prostate
|
PROSTATE
|
This study demonstrates clinical application and validation of the results from the previous volunteer study. It provides clinical data, using a patient cohort, regarding a time-reduced MRI sequence for sCT generation for prostate MR-only treatment planning. In an MRI-only workflow, additional sequences may be required for volume definition as image contrast and resolution may be enhanced or targeted to the anatomy, or functional sequences may provide additional guidance. The time reduction and associated reduction in image quality for the sCT sequence may be appropriate if anatomical and dose differences in the generated sCT for treatment planning are considered acceptable.The potential trade-offs between reducing MR imaging time and the effects on the MR image quality and subsequent sCT generation accuracy should be considered [The clinical study results compare favourably with our previously reported volunteer study [As discussed previously in Young et al. [The current study considers a comparison of sCT with a gold standard sCT. A more appropriate comparison would be true CT, but the study utilised patient data from an MRI-only sub-study within a clinical trial, so capturing an additional CT was not possible or within the study guidelines. However, as the S-sCT approach was previously benchmarked against CT, it could be considered that this was an indirect comparison of sCT to CT. As sCT use for treatment planning and MRI-only radiotherapy becomes more common, further adjustments or improvements in sCT may need to be considered without the availability of a corresponding CT scan. In these cases similar comparisons may be appropriate in assessing suitability of a new sCT.
|
PMC10480277
|
Conclusion
|
In this clinical validation study, the fast sequence, which reduced the required imaging time by approximately a factor of 4, produced an sCT with similar clinical dosimetric results compared to the standard sCT, demonstrating its potential for clinical use for treatment planning.
|
PMC10480277
|
||
Funding
|
Cancer
|
CANCER
|
The authors received no funding for this study. The NINJA Trial receives some grant funding from Cancer Australia (GA52651). Open Access funding enabled and organized by CAUL and its Member Institutions
|
PMC10480277
|
Data availability
|
Due to the nature of this research, participants of this study did not agree for their data to be shared publicly, so supporting data is not available.
|
PMC10480277
|
||
Declarations
|
PMC10480277
|
|||
Conflicts of interest
|
Cancer
|
CANCER
|
Authors declare no conflicts of interest. Liverpool Cancer Therapy Centre has a master research agreement with Siemens, unrelated to this study.
|
PMC10480277
|
Research involving humans and animal rights
|
Patient data was acquired with local ethics committee approval, HREC/18/LPOOL/420. This clinical trial is registered with ANZCTR (ACTRN12618001806257).
|
PMC10480277
|
||
Consent to participate
|
Informed consent was obtained from all individual participants included in the study.
|
PMC10480277
|
||
Consent to publish
|
The authors affirm that human research participants provided informed consent for publication of data.
|
PMC10480277
|
||
References
|
PMC10480277
|
|||
Key Points
|
PMC10709770
|
|||
Question
|
ATRIAL FIBRILLATION (AF), CARDIAC ARRHYTHMIA
|
Can clinician-created, video-based education improve knowledge of atrial fibrillation (AF), the most common cardiac arrhythmia?
|
PMC10709770
|
|
Findings
|
In this randomized clinical trial including 204 patients with AF, patients offered video-based education developed by treating clinicians were 23% more likely to correctly answer AF knowledge questions 3 months after their clinic visit, a statistically significant difference.
|
PMC10709770
|
||
Meaning
|
AF
|
ATRIAL FIBRILLATION (AF), DISEASES
|
These findings suggest that the clinician-created, video-based education concept could be implemented in other diseases and care settings.This randomized clinical trial assesses whether clinician-created video-based atrial fibrillation (AF) education is feasible and improves knowledge of AF among patients treated in an outpatient clinic.
|
PMC10709770
|
Importance
|
ATRIAL FIBRILLATION (AF)
|
Patient education is a critical aspect of atrial fibrillation (AF) management. However, there is limited time to provide effective patient education during routine care, and resources available online are of variable quality.
|
PMC10709770
|
|
Objective
|
To determine whether clinician-led creation of video-based AF education is feasible and improves knowledge of AF.
|
PMC10709770
|
||
Design, Setting, and Participants
|
stroke, thromboembolism, diabetes
|
TRANSIENT ISCHEMIC ATTACK, STROKE, VASCULAR DISEASE, CONGESTIVE HEART FAILURE, THROMBOEMBOLISM, HYPERTENSION, DIABETES
|
This single-center randomized clinical trial was conducted between 2020 and 2022. Outcomes were assessed prior to their clinic visit and 2 and 90 days after the visit by blinded assessors. Participants included adults with AF and congestive heart failure, hypertension, age at least 75 years (doubled), diabetes, prior stroke or transient ischemic attack or thromboembolism (doubled), vascular disease, age 65 to 74 years, and sex category scores of 1 or greater presenting for routine care at publicly funded outpatient cardiology clinics within a tertiary teaching hospital. Individuals too unwell to participate or with limited English were excluded. Data were assessed as intention to treat and analyzed from December 2022 to October 2023.
|
PMC10709770
|
Intervention
|
PATHOPHYSIOLOGY
|
Intervention participants viewed a series of 4 videos designed and narrated by clinicians that aimed to improve understanding of AF pathophysiology, clinical presentation, diagnosis, and management. After viewing the videos, participants received weekly email links to review the videos. The control group received usual care.
|
PMC10709770
|
|
Main Outcomes and Measures
|
Atrial Fibrillation
|
ATRIAL FIBRILLATION
|
The prospectively selected primary outcome was AF knowledge at 90 days, measured by the validated Jessa Atrial Fibrillation Knowledge Questionnaire (JAFKQ).
|
PMC10709770
|
Results
|
Among 657 individuals screened, 208 adults with AF were randomized (mean [SD] age, 65.0 [12.2] years; 133 [65.2%] male) and included in analysis. Participants were randomized 1-to-1, with 104 participants in the control group and 104 participants in the video intervention group. At 90 days after the baseline clinic visit, intervention participants were more likely to correctly answer JAFKQ questions than control participants (odds ratio [OR], 1.23 [95% CI, 1.01-1.49]). The difference was greater in participants who remotely accessed videos on 3 or more occasions during the study (OR, 1.46 [95% CI, 1.14-1.88]).
|
PMC10709770
|
||
Conclusions and Relevance
|
In this randomized clinical trial of patients with AF, remotely delivered, clinician-created video education improved medium-term AF knowledge beyond usual care of standard in-clinic education. The improvement demonstrated in this study provides support for the implementation of clinician-created educational resources across the care continuum. Further work is needed to assess for impact on clinical outcomes.
|
PMC10709770
|
||
Trial Registration
|
anzctr.org.au Identifier: ANZCTRN12620000729921
|
PMC10709770
|
||
Introduction
|
stroke, AF, thromboembolism
|
ATRIAL FIBRILLATION (AF), STROKE, DISEASE, CARDIAC ARRHYTHMIA, THROMBOEMBOLISM
|
Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting approximately 40 million people worldwide.Poor patient understanding of AF is a significant barrier to achieving these goals. Up to 50% of patients with new AF are unaware of their diagnosis, and more than one-third of patients are unaware of the association of AF with thromboembolism and stroke.Patients commonly search for disease information on the internet; however, such information is often inaccurate or neglects important components of management. A 2022 study by Luo et alDigitally delivered educational videos created by treating clinicians (hereafter
|
PMC10709770
|
Methods
|
This randomized clinical trial was approved by the Western Sydney Local Health District Human Research Ethics Committee. All participants provided written informed consent electronically. The full trial protocol and statistical analysis plan are available in
|
PMC10709770
|
||
Study Design
|
The Educate-AF study was a single-center, single-blind randomized clinical trial of patients with AF accessing clinical outpatient care within a tertiary teaching hospital in Sydney, Australia (
|
PMC10709770
|
||
Study Recruitment Flowchart
|
PMC10709770
|
|||
Patient Population
|
stroke, thromboembolism, diabetes
|
TRANSIENT ISCHEMIC ATTACK, STROKE, VASCULAR DISEASE, FLUTTER, CONGESTIVE HEART FAILURE, THROMBOEMBOLISM, HYPERTENSION, DIABETES
|
Eligible patients were aged 18 years and older with electrocardiography-confirmed AF or flutter of any clinical subtype (paroxysmal, persistent, and permanent); congestive heart failure, hypertension, age 75 years or older (doubled), diabetes, prior stroke or transient ischemic attack or thromboembolism (doubled), vascular disease, age 65 to 74 years, and sex category (CHA
|
PMC10709770
|
Recruitment and Consent
|
Eligible patients were recruited prior to in-person or telehealth outpatient appointments by trained research staff. Screening of all outpatient cardiology clinics was performed to identify eligible participants who were provided with study information and, if agreeable, emailed a link to facilitate participation. This directed patients directly to study consenting documents, where written informed consent was completed via eConsent within REDCap (Vanderbilt University).
|
PMC10709770
|
||
Randomization and Masking
|
RECRUITMENT, BLIND
|
Randomization occurred centrally via a sequence generated within the randomize R library of R statistical software version 3.5.1 (R Project for Statistical Computing) by S.M. Randomization was 1:1 in permuted blocks of 2 and 4 to reduce predictability and ensure balance between study groups. Study staff responsible for recruitment, follow-up outcome assessors, and individuals responsible for statistical analysis were blinded to allocation. Due to the nature of the intervention, it was not possible to blind participants.
|
PMC10709770
|
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