title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Methods | PMC10504071 | |||
Study design | CRB-401 ( | PMC10504071 | ||
Patients | DISEASE | Patients with RRMM who were ≥18 years of age and had ECOG PS 0-1 were eligible for the study. Patients were required to have measurable disease (serum M-protein ≥0.5 g dl | PMC10504071 | |
Treatment | PMBCs obtained from leukapheresis were stimulated with αCD3 and αCD28 antibodies, transduced with the anti-BCMA CAR-containing lentiviral vector and expanded over 10 d as previously described | PMC10504071 | ||
Assessments | MULTIPLE MYELOMA | The IMWG Uniform Response Criteria for Multiple Myeloma were used to assess response and progression | PMC10504071 | |
Translational | Cellular kinetics (PB and bone marrow) and sBCMA were evaluated as previously described | PMC10504071 | ||
PBMC and product characterization | PBMC used for ide-cel manufacturing and DP characteristics were evaluated from cryopreserved samples produced during the ide-cel clinical manufacturing process. PBMC or DP samples were thawed, washed and stained with cocktails of fluorescently labeled antibodies targeting T cell differentiation, exhaustion and senescen... | PMC10504071 | ||
Statistical analysis | The sample size planned for this study was based on clinical considerations and a standard dose-escalation design, as previously describedAnalyses were performed with SAS software, version 9.4. | PMC10504071 | ||
Reporting summary | Further information on research design is available in the | PMC10504071 | ||
Online content | Any methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at 10.1038/s41591-023-02496-0. | PMC10504071 | ||
Supplementary information | The online version contains supplementary material available at 10.1038/s41591-023-02496-0. | PMC10504071 | ||
Acknowledgements | Media | The study was supported by Celgene, Bristol Myers Squibb, and 2Seventy Bio (previously bluebird bio). The authors thank the study patients and their families and the clinical study teams. Writing and editorial assistance were provided by P.J. Simon of MediTech Media and A.L. Loeb and R. Beck Jr of SciMentum, both of wh... | PMC10504071 | |
Author contributions | Y.L., N.S.R., M.V.M., O.F., N.M., J.F., T.B.C., K.H. conceived, designed or planned the study. Y.L., N.S.R., J.G.B., D.S.S., S.J., D.M., M.L., J.R., M.V.M., M.M., F.P., A.Y., N.C.M., J.N.K. acquired the data. A.Y., Z.Y., T.B.C., N.M., K.H., J.F. analyzed the data. Y.L., D.S.S., A.Y., O.F., T.B.C., N.M., A.C., Z.Y., K.H... | PMC10504071 | ||
Peer review | PMC10504071 | |||
Data availability | De-identified and anonymized data will be made available within a secured portal to qualified researchers who submit an in-scope proposal approved by the Independent Review Committee. Proposals will be reviewed to ensure that there is adequate scientific rationale and methodology, a robust statistical analysis plan and... | PMC10504071 | ||
Competing interests | NSR, Cancer | ONCOLOGY, CANCER, MYELOMA, EMD | Y.L. received institutional grants and consulting fees from Bristol Myers Squibb, Kite-Gilead and Janssen; institutional grants only from 2Seventy Bio, Merck and Takeda; institutional consulting fees only from Novartis, CellMedica and Legend Biotech; and participated in a data safety monitoring or advisory board for Pf... | PMC10504071 |
References | PMC10504071 | |||
Abstract | PMC10154863 | |||
Introduction | breast cancer | SECONDARY, BREAST CANCER | Understanding participants' concerns and information needs regarding broadened consent is crucial to ensure transparency and participant autonomy. Our study qualitatively examined these issues in women participating in the Personalized RISk‐based MAmmascreening study (PRISMA). The original PRISMA informed consent was p... | PMC10154863 |
Methods | Focus groups (FGs) were performed following a semistructured discussion guide. Two independent researchers analysed the data thematically using an inductive approach. | PMC10154863 | ||
Findings | breast cancer | BREAST CANCER | Twenty‐three asymptomatic women and 13 women diagnosed with breast cancer were randomly divided into six FGs. Four superordinate themes were identified: (1) Normalization, (2) Attitude towards the pharmaceutical industry, (3) Privacy and (4) Knowledge. Our participants viewed data sharing as an important conduit for ad... | PMC10154863 |
Conclusion | Our participants expressed clear information needs and a strong desire to be actively engaged in future data sharing decisions. Given that many researchers collaborate with commercial parties, building public confidence in these institutions would be beneficial. Illustrative examples addressing privacy concerns and cla... | PMC10154863 | ||
Patient and Public Contribution | breast cancer | BREAST CANCER | Women were recruited from the general breast cancer screening population. Their perceptions and information needs, as reported in this study, will not only inform broadened consent for PRISMA but ideally guide other consent templates and decisions regarding consent processes.
| PMC10154863 |
INTRODUCTION | breast cancer | BREAST CANCER | Informed consent refers to the autonomous permission granted for an activity with the underlying premise that the individual fully comprehends what that activity entails.Disconcertingly, there is no globally accepted consensus on the definition of broad consent. Following guidance from the World Medical Association's 2... | PMC10154863 |
METHODS | PMC10154863 | |||
Design | Focus groups (FGs) were performed following a semistructured discussion guide to explore PRISMA participants' perceptions of expanding the boundaries of their previous consent. Per the Regional Ethics Committee CMO Arnhem‐Nijmegen Ethics Committee (the Netherlands), this study fell outside the remit of the Dutch Medica... | PMC10154863 | ||
Setting | Cancer, breast cancer | CANCER, BREAST CANCER | PRISMA is an observational prospective cohort study which was carried out in the Netherlands between 2014 and 2019. Since participants were recruited from the Dutch breast cancer screening programme, in line with screening eligibility criteria, all participants were asymptomatic females aged between 50 and 75 years. Fo... | PMC10154863 |
Original PRISMA consent protocol | breast cancer | BREAST CANCER | Participants in the PRISMA study were asked to consent to use their data and biomaterial for research into early detection, prognosis and treatment of breast cancer. They were further asked to consent to use their data and any residual biomaterial for ancillary studies into breast cancer; this included the possibility ... | PMC10154863 |
PRISMA Biobank | Biomaterials are stored at the Radboud Biobank, a hospital‐integrated central biobanking facility located within the Radboud University Medical Center (Radboudumc), Nijmegen, the Netherlands. | PMC10154863 | ||
Participants | breast cancer | BREAST CANCER | Women were randomly selected from the PRISMA database using a digital random number calculator, stratified across asymptomatic participants and incident breast cancer cases. This stratification aimed to explore whether breast cancer status affects women's opinions of data sharing. Inclusion criteria included:
Consented... | PMC10154863 |
Procedures | Due to the Covid‐19 pandemic and subsequent government regulations, the FGs were performed digitally. We used Zoom,The discussion guide, available in Supporting Information: FGs were recorded and transcribed verbatim. FGs were organised until data saturation was achieved, that is, until no new themes were raised. Parti... | PMC10154863 | ||
Data analysis | Data were thematically analyzed by two independent researchers (L. R., M. d. J.) using an inductive approach.Final thematic map of perspectives on broadened consent: Themes and subthemes. | PMC10154863 | ||
FAIR data statement | The authors are highly committed to FAIR data to ensure that data are Findable, Accessible, Interoperable and Reusable. | PMC10154863 | ||
FINDINGS | breast cancer | BREAST CANCER | Twenty‐three asymptomatic women (response: 5.8%) and 13 women who had been diagnosed with breast cancer (response: 13.0%) participated in our study. We organized six FGs ranging in size from four to seven women; on average, there were six women per group. The average age of participants was 62 years (SD: 7; range: 52–7... | PMC10154863 |
Theme 1: Normalisation | Participants perceived data sharing as | PMC10154863 | ||
Theme 2: Attitude towards the pharmaceutical industry | EVENTS | Attitude towards the pharmaceutical industry was a major theme in the FGs and it was evident that topical events, namely the COVID‐19 pandemic, influenced this discussion. Participants expressed a great | PMC10154863 | |
Theme 3: Privacy | Concerns about privacy were raised frequently. In general, participants agreed that data sharing is acceptable as long as their data are de‐identified and the key to their identifiable information is kept at the university, for example, ‘If anonymity can be guaranteed, I'll allow data sharing’ and ‘I assume that the li... | PMC10154863 | ||
Theme 4: Knowledge | Choosing whether or not to be informed about future findings, particularly from genetic research, was critical for participants. Some felt that it is their | PMC10154863 | ||
Procedural preferences and information needs | RISk‐based, death, ’ | Participants drew on both their professional and personal experiences when stating their procedural preferences and information needs. Although broadly posed, this question elicited quite specific responses. One participant who worked in the area of knowledge transfer, for example, mentioned the availability of a ‘soci... | PMC10154863 | |
DISCUSSION | cancer, confusion, fatigue, breast cancer | CANCER, MINOR, LENS, BREAST CANCER | In our study, participants could reflect on their previous project‐specific consent when discussing under what conditions they would be willing to broaden their consent. Since this was not solely a hypothetical exercise, it was evident that their receptiveness to broadened consent was largely rooted in their underlying... | PMC10154863 |
CONCLUSION | Our participants expressed very clear information needs and a strong desire to be actively engaged in future data sharing decisions. Given that many researchers collaborate with commercial parties and/or pharmaceutical companies, building public confidence in these institutions may be of benefit. Illustrative examples ... | PMC10154863 | ||
AUTHOR CONTRIBUTIONS | PMC10154863 | |||
CONFLICT OF INTEREST STATEMENT | The authors declare no conflict of interest. | PMC10154863 | ||
Supporting information | Supplementary information.Click here for additional data file.Supplementary information.Click here for additional data file. | PMC10154863 | ||
ACKNOWLEDGEMENTS | Cancer | CANCER | The authors want to acknowledge the considerable contribution and time investment of all the participating women, without whom this research would not have been possible. This study was funded by the Dutch Cancer Society (KWF) under Grant 12522. The funder had no role in the study design; in the collection, analysis an... | PMC10154863 |
DATA AVAILABILITY STATEMENT | Supporting Information: | PMC10154863 | ||
REFERENCES | PMC10154863 | |||
1. Introduction | First-Episode Psychosis, AQ-27, insidious, psychosis, mental disorders | SECONDARY | Background: Mental-health-related stigma prevents active help seeking and therefore early therapeutic approaches and the recovery of functionality. National and international agencies recommend the implementation of prevention and mental health promotion programs that support the elimination of stigma in the classroom,... | PMC10671828 |
2. Material and Methods | PMC10671828 | |||
2.1. Design | SECONDARY | This was a quasi-experimental (pre and post-test) clustered pilot study carried out in a secondary school located in Spain. For this reason, the TREND checklist (Transparent Reporting of Evaluations with Nonrandomized Designs) was used [ | PMC10671828 | |
2.2. Participants and Recruitment | SECONDARY, RECRUITMENT | The sample was composed of teachers and counsellors of a secondary school located in Spain. It was selected out of a simple random sampling between the secondary schools to which we had access that belong to the department in Spain. The software programme ExcelThis type of population was chosen since they are considere... | PMC10671828 | |
2.3. Inclusion and Exclusion Criteria | SECONDARY | Inclusion criteria: To work as a teacher and/or counsellor at the moment of the programme presentation, to have Spanish as mother tongue, to develop the teaching activity full-time, to voluntarily participate, and to be public, semi-private, and private secondary schools.Exclusion criteria: Not having signed the inform... | PMC10671828 | |
2.4. Assessment Instruments | PMC10671828 | |||
2.4.1. Stigma | psychosis, AQ-27, Anger | DISORDER | The tool used for the assessment of stigma was the Attribution Questionnaire (AQ-27) (created by Weiner and collaborators) “(1988)” in its Spanish version, which is composed of 27 items (AQ-27-E). The evaluation was carried out by Muñoz and collaborators “(2015)”, obtaining a reliability of 0.855 (Cronbach’s alpha) for... | PMC10671828 |
2.4.2. Satisfaction Survey | The satisfaction survey adapted from Feixas and Vilaplana [ | PMC10671828 | ||
2.5. Intervention | schizoaffective disorder, psychosis | DISORDERS | A training workshop on psychosis and general mental health was carried out in order to raise the awareness of the teaching staff and counselling department. It was a psychoeducational-type intervention that was fundamentally inspired by the content of other guides, recommendations, and renowned entities in the field of... | PMC10671828 |
2.6. Data Analysis | All the statistical analyses were performed with IBM SPSS Statistics version 23. The level of significance was established with a Univariate analysis. The baseline sociodemographic and clinical features of the group were described using measures of central tendency for quantitative variables, and total frequency table ... | PMC10671828 | ||
3. Results | PMC10671828 | |||
3.1. Characteristics of Patients | A total of 22 participants (18% men and 82% women) were recruited for this study and completed the pre- and post-intervention questionnaires. The sample profile was mostly women aged 47.96 ± 10.12 years, with undergraduate studies and a professional experience of 18.64 ± 10.34 years. The rest of the demographic charact... | PMC10671828 | ||
3.3. Correlations “Age”–“AQ-27 Pre-Intervention” and “Experience”–“AQ-27 Pre-Intervention” | These correlations can be seen in | PMC10671828 | ||
3.4. Correlations of “Psychosis Test”–“Age” and “Psychosis Test”–“Professional Experience” | As seen in | PMC10671828 | ||
3.5. Psychosis Test | The mean score obtained before the intervention was 4.89 out of 10. | PMC10671828 | ||
3.6. Course Rating | Points are shown in | PMC10671828 | ||
3.7. Semi-Structured Interview | Since the end of the program, counsellors reported 11 cases referred to the health system, 9 of which required assessment and follow-up by the Child and Adolescent Mental Health Unit: 5 boys and 4 girls between 13 and 16 years due to behavioural alterations and anxious symptoms. | PMC10671828 | ||
4. Discussion | substance-induced psychosis, illness, Anger | SECONDARY, SAID, DISORDERS | From what is known, this is the first study that has explored the effect of a psychoeducational programme on mental health and FEP aimed at teachers and counsellors in a secondary school in Spain. The outcomes showed that the intervention was useful for increasing knowledge on mental health and reducing the stigma asso... | PMC10671828 |
4.1. Strengths and Limitations | psychosis | Since the study was carried out voluntarily in real life in La Ribera health department, it was not possible to randomise the participants, there could not be a control group, the sample could not be randomised given the prior need of planning lessons, and the intervention content had to be adapted to the available tim... | PMC10671828 | |
4.2. Future Lines | psychosis | Given the promising data of this Mental Health Nursing psychoeducational-type intervention, its performance in other educational centres is suggested, taking into account that the sample should be more homogeneous and representative, preferably scheduled within work hours and with the possibility of obtaining further o... | PMC10671828 | |
5. Conclusions | First-Episode Psychosis, mental disorder, psychosis | SECONDARY | The impact of a nursing intervention on mental health stigma in teachers and counsellors of a secondary school was positive, given the statistically significant differences observed in the change of average scores on stigmatising attitudes of the AQ-27 scale pre- and post-intervention. The stigmatising attitude that pr... | PMC10671828 |
Author Contributions | Conceptualization, L.S.A., L.A.P. and J.V.C.-S.; methodology, L.S.A., L.A.P. and J.V.C.-S.; validation, L.S.A., L.A.P., A.R.-H. and J.J.G.C.; formal analysis, L.S.A. and J.V.C.-S.; investigation, L.S.A. and J.V.C.-S.; resources, C.M.M., E.G.P. and S.C.P.; data curation, J.V.C.-S.; writing—original draft preparation, L.... | PMC10671828 | ||
Institutional Review Board Statement | Ethical approval was granted from the Ethics Committee-Research Commission of the pertinent Health Department [PI06072022]. All participants gave written permission for their anonymized data to be used for academic purpose. | PMC10671828 | ||
Informed Consent Statement | All participants gave written permission for their anonymized data to be used for academic purpose. | PMC10671828 | ||
Data Availability Statement | Data available on request due to privacy and ethical restrictions. Data presented in this study are available upon request from the corresponding author. | PMC10671828 | ||
Conflicts of Interest | There were no conflicts of interest with any person, company and/or institution that could affect the conduct of this research. | PMC10671828 | ||
Clinical Relevance | There are adolescents who have suffered stigma from their teachers, and consequently have minimized the symptoms and have not asked for help. For this reason, we have implemented a nursing intervention, based on education and promotion of mental health with the aim of expanding knowledge and reducing stigma. In fact, t... | PMC10671828 | ||
References | Psychosis, AQ-27 | Sociodemographic data of the sample.AF: Absolute Frequency.Correlations of the AQ-27 variable pre- and post-intervention. Wilcoxon Test.* Correlations between the variables “Age” and “AQ-27 pre-intervention”.* Correlations between the variable “Professional experience” and “AQ-27 pre-intervention”.* Correlations of “Ps... | PMC10671828 | |
Keywords | PMC10699085 | |||
Trial structure | In broad terms, the SNAP trial model is designed around several ‘structural’ trial elements: silos, domains, subdomains, subgroups, covariates, regions and countries, and epochs. In a slight abuse of notation, for simplicity, we will often use | PMC10699085 | ||
Domains | A Domains are denoted by | PMC10699085 | ||
Subdomain | For participants within a specific silo, it is possible for the set of allocated interventions within each domain to be a subset of the full set of interventions available for that domain. We define the set of these silo-specific domain interventions by:This silo-specific set of domain interventions leads us to the def... | PMC10699085 | ||
Subgroups | A | PMC10699085 | ||
Covariates | We define Values of a particular covariate are labelled by the lower-case letter associated with that covariate indexed by covariate specific subscript | PMC10699085 | ||
Regions and countries | A We define | PMC10699085 | ||
Epochs | The concept of an | PMC10699085 | ||
Statistical modelling | The SNAP trial data will be analysed using Bayesian statistical methods, which combine probability distributions that summarise the state of knowledge independent of the observed data (a prior probability distribution) with the observed data model (through a likelihood function) to produce probability distributions tha... | PMC10699085 | ||
Models | PMC10699085 | |||
Primary endpoint model | The SNAP trial primary endpoint is binary, denoted We interpret the | PMC10699085 | ||
Prior distributions and model hierarchy | The following subsections outline the prior distribution structure for the parameters of the model using a Bernoulli distributed endpoint and logistic link function, including the primary model. The model for alternatively distributed endpoints will require an alternative prior structure, which will be described in det... | PMC10699085 | ||
Reference log-odds | The log-odds for domain-specific interventions | PMC10699085 | ||
Effects of interventions | The log-odds Where a silo has a unique subdomain (i.e. it exists only for a single silo), the log-odds ratios where the intervention is silo-specific are modelled as normally distributed such that all subgroups have the same silo-specific mean and variance: Where two or more silos share a subdomain, and the log-odds ra... | PMC10699085 | ||
Effects of domain eligibility | The log-odds ratios for domain ineligibility are assigned independent normal prior distributions such that: | PMC10699085 | ||
Effects of two-way interactions | The log-odds ratios for two-way interactions are assigned independent normal prior distributions such that: | PMC10699085 | ||
Effects of regions and countries | The log-odds ratios for regions are assigned normal distributions such that: | PMC10699085 | ||
Effects of covariates | The log-odds ratios for covariate factors are assigned independent normal prior distributions such that: | PMC10699085 | ||
Effects of epoch | Temporal trends will be accounted for by splitting the trial sample into separate cohorts defined by contiguous 26 week epochs and using first-order dynamic normal linear model within (Furthermore, an additional sensitivity analysis may be performed to evaluate all outcomes of interest using cohorts that are restricted... | PMC10699085 | ||
Exploratory analyses | Additional analyses are described in the SNAP statistical appendix and relevant domain-specific appendices that include parameters for the interactions between interventions and other covariates to enable the comparative effectiveness by covariates as a pre-planned exploratory analysis. | PMC10699085 | ||
Computational methods | The joint posterior probability distributions of the model parameters described in the preceding sections are analytically intractable, and therefore computational Bayesian methods will be used for the data analyses. We will use Markov-chain Monte Carlo (MCMC) methods implemented in stan, a probabilistic programming la... | PMC10699085 | ||
Missing data | Death | Death from | PMC10699085 | |
Concurrently randomised cohorts | By design, the way that participants are assigned to treatments in adaptive randomised trials changes over time, which can lead to treatment-outcome confounding in certain cases. For when that confounder is based on calendar time, we have included epoch modelling as one countermeasure to confounding (see the ‘As a furt... | PMC10699085 | ||
Randomisation | PMC10699085 | |||
General principles | Consented participants will be randomly allocated among interventions in subdomains for which they are eligible. Participants will be randomised to one intervention from each domain that their enrolling site is participating in, according to allocation probabilities detailed in each domain-specific appendix and stratif... | PMC10699085 |
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