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4.
BMC Med ; 19(1): 46, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33618741

RESUMEN

BACKGROUND: Following the initial identification of the 2019 coronavirus disease (covid-19), the subsequent months saw substantial increases in published biomedical research. Concerns have been raised in both scientific and lay press around the quality of some of this research. We assessed clinical research from major clinical journals, comparing methodological and reporting quality of covid-19 papers published in the first wave (here defined as December 2019 to May 2020 inclusive) of the viral pandemic with non-covid papers published at the same time. METHODS: We reviewed research publications (print and online) from The BMJ, Journal of the American Medical Association (JAMA), The Lancet, and New England Journal of Medicine, from first publication of a covid-19 research paper (February 2020) to May 2020 inclusive. Paired reviewers were randomly allocated to extract data on methodological quality (risk of bias) and reporting quality (adherence to reporting guidance) from each paper using validated assessment tools. A random 10% of papers were assessed by a third, independent rater. Overall methodological quality for each paper was rated high, low or unclear. Reporting quality was described as percentage of total items reported. RESULTS: From 168 research papers, 165 were eligible, including 54 (33%) papers with a covid-19 focus. For methodological quality, 18 (33%) covid-19 papers and 83 (73%) non-covid papers were rated as low risk of bias, OR 6.32 (95%CI 2.85 to 14.00). The difference in quality was maintained after adjusting for publication date, results, funding, study design, journal and raters (OR 6.09 (95%CI 2.09 to 17.72)). For reporting quality, adherence to reporting guidelines was poorer for covid-19 papers, mean percentage of total items reported 72% (95%CI:66 to 77) for covid-19 papers and 84% (95%CI:81 to 87) for non-covid. CONCLUSIONS: Across various measures, we have demonstrated that covid-19 research from the first wave of the pandemic was potentially of lower quality than contemporaneous non-covid research. While some differences may be an inevitable consequence of conducting research during a viral pandemic, poor reporting should not be accepted.


Asunto(s)
/epidemiología , Publicaciones Periódicas como Asunto/normas , Calidad de la Atención de Salud/normas , Investigación Biomédica , Humanos , Proyectos de Investigación/normas , Informe de Investigación
5.
BMJ ; 372: n48, 2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33531350

RESUMEN

OBJECTIVE: To identify redundant clinical trials evaluating statin treatment in patients with coronary artery disease from mainland China, and to estimate the number of extra major adverse cardiac events (MACEs) experienced by participants not treated with statins in those trials. DESIGN: Cross sectional study. SETTING: 2577 randomized clinical trials comparing statin treatment with placebo or no treatment in patients with coronary artery disease from mainland China, searched from bibliographic databases to December 2019. PARTICIPANTS: 250 810 patients with any type of coronary artery disease who were enrolled in the 2577 randomized clinical trials. MAIN OUTCOME MEASURES: Redundant clinical trials were defined as randomized clinical trials that initiated or continued recruiting after 2008 (ie, one year after statin treatment was strongly recommended by clinical practice guidelines). The primary outcome is the number of extra MACEs that were attributable to the deprivation of statins among patients in the control groups of redundant clinical trials-that is, the number of extra MACEs that could have been prevented if patients were given statins. Cumulative meta-analyses were also conducted to establish the time points when statins were shown to have a statistically significant effect on coronary artery disease. RESULTS: 2045 redundant clinical trials were identified published between 2008 and 2019, comprising 101 486 patients in the control groups not treated with statins for 24 638 person years. 3470 (95% confidence interval 3230 to 3619) extra MACEs were reported, including 559 (95% confidence interval 506 to 612) deaths, 973 (95% confidence interval 897 to 1052) patients with new or recurrent myocardial infarction, 161 (132 to 190) patients with stroke, 83 (58 to 105) patients requiring revascularization, 398 (352 to 448) patients with heart failure, 1197 (1110 to 1282) patients with recurrent or deteriorated angina pectoris, and 99 (95% confidence interval 69 to 129) unspecified MACEs. CONCLUSIONS: Of more than 2000 redundant clinical trials on statins in patients with coronary artery disease identified from mainland China, an extra 3000 MACEs, including nearly 600 deaths, were experienced by participants not treated with statins in these trials. The scale of redundancy necessitates urgent reform to protect patients.


Asunto(s)
Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , China , Enfermedad de la Arteria Coronaria/mortalidad , Estudios Transversales , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Proyectos de Investigación/normas , Revisiones Sistemáticas como Asunto
6.
J Perinat Med ; 49(3): 255-261, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33554570

RESUMEN

OBJECTIVES: Fever is the single most frequently reported manifestation of COVID-19 and is a critical element of screening persons for COVID-19. The meaning of "fever" varies depending on the cutoff temperature used, the type of thermometer, the time of the day, the site of measurements, and the person's gender and race. The absence of a universally accepted definition for fever has been especially problematic during the current COVID-19 pandemic. METHODS: This investigation determined the extent to which fever is defined in COVID-19 publications, with special attention to those associated with pregnancy. RESULTS: Of 53 publications identified in which "fever" is reported as a manifestation of COVID-19 illness, none described the method used to measure patient's temperatures. Only 10 (19%) publications specified the minimum temperature used to define a fever with values that varied from a 37.3 °C (99.1 °F) to 38.1 °C (100.6 °F). CONCLUSIONS: There is a disturbing lack of precision in defining fever in COVID-19 publications. Given the many factors influencing temperature measurements in humans, there can never be a single, universally accepted temperature cut-off defining a fever. This clinical reality should not prevent precision in reporting fever. To achieve the precision and improve scientific and clinical communication, when fever is reported in clinical investigations, at a minimum the cut-off temperature used in determining the presence of fever, the anatomical site at which temperatures are taken, and the instrument used to measure temperatures should each be described. In the absence of such information, what is meant by the term "fever" is uncertain.


Asunto(s)
/métodos , Exactitud de los Datos , Fiebre/diagnóstico , Publicaciones Periódicas como Asunto , Proyectos de Investigación/normas , Termometría/normas , /complicaciones , /normas , Femenino , Fiebre/virología , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Estándares de Referencia , Proyectos de Investigación/estadística & datos numéricos , Termómetros , Termometría/instrumentación , Termometría/métodos
7.
Medicine (Baltimore) ; 100(4): e24389, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33530234

RESUMEN

BACKGROUND: To evaluate the methodological quality of systematic reviews (SRs) or meta-analysis of trastuzumab-based therapy for breast cancer. METHODS: We searched the PubMed, EMBASE, Web of science, Cochrane library, international prospective register of systematic reviews, Chinese BioMedical Literature Database, Wan Fang, China National Knowledge Infrastructure and VIP database for SRs or meta-analysis. The methodological quality of included literatures was appraised by risk of bias in systematic review (ROBIS) tool. RESULTS: Twenty three eligible systematic reviews or meta-analysis were included. Only 2 systematic reviews provided protocol. The most frequently searched databases were PubMed, MEDLINE, EMBASE, and the Cochrane. The two-reviewers model described in the screening for eligible original articles, data extraction, and methodological quality evaluation had 30%, 61%, and 26%, respectively. In methodological quality assessment, 52% SRs or meta-analysis used the Jadad scoring or Cochrane reviewer' handbook. Research question were well matched to all SRs or meta-analysis in phase 1 and 35% of them evaluated "high" risk bias in study eligibility criteria. The "high" risk of bias in all non-Cochrane SRs or meta-analyses, which involve methods used to identify and/or select studies. And more than half SRs or meta-analysis had a high risk of bias in data collection and study appraisal. More than two-third of SRs or meta-analysis were accomplished with high risk of bias in the synthesis and findings. CONCLUSIONS: The study indicated poor methodological and reporting quality of SRs/meta-analysis assessing trastuzumab-based therapy for breast cancer. Registration or publishing the protocol and the reporting followed the PRISMA checklist are recommended in future research.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto/normas , Trastuzumab/uso terapéutico , Sesgo , Femenino , Humanos , Proyectos de Investigación/normas
8.
Nat Commun ; 12(1): 1107, 2021 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-33597541

RESUMEN

One of the primary tools that researchers use to predict risk is the case-control study. We identify a flaw, temporal bias, that is specific to and uniquely associated with these studies that occurs when the study period is not representative of the data that clinicians have during the diagnostic process. Temporal bias acts to undermine the validity of predictions by over-emphasizing features close to the outcome of interest. We examine the impact of temporal bias across the medical literature, and highlight examples of exaggerated effect sizes, false-negative predictions, and replication failure. Given the ubiquity and practical advantages of case-control studies, we discuss strategies for estimating the influence of and preventing temporal bias where it exists.


Asunto(s)
Investigación Biomédica/normas , Ensayos Clínicos como Asunto/normas , Selección de Paciente , Proyectos de Investigación/normas , Sesgo , Investigación Biomédica/métodos , Investigación Biomédica/tendencias , Estudios de Casos y Controles , Ensayos Clínicos como Asunto/métodos , Predicción , Humanos , Reproducibilidad de los Resultados
10.
Trials ; 22(1): 90, 2021 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-33494785

RESUMEN

BACKGROUND: New considerations during the ethical review processes may emerge from innovative, yet unfamiliar operational methods enabled in pragmatic randomized controlled trials (RCT), potentially making institutional review board (IRB) evaluation more complex. In this manuscript, key components of the pragmatic "Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE)" randomized trial that required a reappraisal of the IRB submission, review, and approval processes are discussed. MAIN TEXT: ADAPTABLE is a pragmatic, multicenter, open-label RCT evaluating the comparative effectiveness of two doses of aspirin widely used for secondary prevention (81 mg and 325 mg) in 15,000 patients with an established history of atherosclerotic cardiovascular disease. The electronic informed consent form is completed online by the participants at the time of enrollment, and endpoint ascertainment is conducted through queries of electronic health records. IRB challenges encountered regarding centralized IRB evaluation, electronic informed consent, patient engagement, and risk determination in ADAPTABLE are described in this manuscript. The experience of ADAPTABLE encapsulates how pragmatic protocol components intended to facilitate the study conduct have been tempered by unexpected, yet justified concerns raised by local IRBs. How the lessons learned can be applied to future similar pragmatic trials is delineated. CONCLUSION: Development of engaging communication channels between IRB and study personnel in pragmatic randomized trials as early as at the time of protocol design allows to reduce issues with IRB approval. Integrations of the lessons learned in ADAPTABLE regarding the IRB process for centralized IRBs, informed consent, patient engagement, and risk determination can be emulated and will be instrumental in future pragmatic studies.


Asunto(s)
Aspirina/administración & dosificación , Aterosclerosis/prevención & control , Comités de Ética en Investigación/normas , Proyectos de Investigación/normas , Prevención Secundaria/métodos , Adulto , Aspirina/efectos adversos , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Humanos , Consentimiento Informado/normas , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto/ética , Estudios Multicéntricos como Asunto/normas , Participación del Paciente , Ensayos Clínicos Pragmáticos como Asunto/ética , Ensayos Clínicos Pragmáticos como Asunto/normas , Ensayos Clínicos Controlados Aleatorios como Asunto/ética , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Medición de Riesgo/normas , Resultado del Tratamiento
12.
Trials ; 22(1): 102, 2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33509278

RESUMEN

BACKGROUND: A lack of consensus on the optimal outcome measures to assess the efficacy and effectiveness of interventions for the treatment of opioid use disorder (OUD) has hampered the pooling of research data for evidence synthesis and clinical guidelines. A core outcome set (COS) is a minimum set of outcome measures that are recommended for all studies of a particular condition. The National Drug Abuse Treatment Clinical Trials Network (CTN) Core Outcome Set for OUD (COS-OUD) is a development study to identify core constructs, meaningful outcomes, and their optimal measurement for all efficacy and effectiveness studies of OUD treatment and service delivery. METHODS/DESIGN: Overseen by an expert workgroup, a modified, stepwise, e-Delphi methodology will be used to gain consensus among a panel of clinical practitioners and researchers involved in the treatment of OUD, who are members of the CTN. Sequential rounds of anonymous, online questionnaires will be used to identify, rate the importance of, and refine a core outcome set. A consensus threshold will be achieved if at least 70% of the panel rate the measure as critical for inclusion in the COS-OUD. Where consensus is not reached or there are suggestions for new measures, these will be brought forward to a further round of review prior to a consensus meeting. Products from this study will be communicated via peer-reviewed scientific journals and conferences. DISCUSSION: This initiative will develop a COS for OUD intervention trials, treatment studies, and service delivery and will support the pooling of research and clinical practice data and efforts to develop measurement-based care within the OUD treatment cascade. TRIAL REGISTRATION: http://www.comet-initiative.org/Studies/Details/1579.


Asunto(s)
Consenso , Técnica Delfos , National Institute on Drug Abuse (U.S.)/normas , Trastornos Relacionados con Opioides/terapia , Proyectos de Investigación/normas , Adolescente , Adulto , Anciano , Determinación de Punto Final/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Opioides/diagnóstico , Resultado del Tratamiento , Estados Unidos , Adulto Joven
14.
Toxicol Mech Methods ; 31(1): 18-32, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33081560

RESUMEN

The need for reliable results in Toxicological Analysis is recognized and required worldwide. The analytical validation ensures that a method will provide trustworthy information about a particular sample when applied in accordance with a predefined protocol, being able to determine a specific analyte at a distinct concentration range for a well-defined purpose. The driving force for developing method validation for bioanalytical projects comes from the regulatory agencies. Thus, the approach of this work is to present theoretical and practical aspects of method validation based on the analysis objective, whether for prevention or diagnosis. Although various legislative bodies accept differing interpretations of requirements for validation, the process for applying validation criteria should be adaptable for each scientific intent or analytical purpose.


Asunto(s)
Proyectos de Investigación , Pruebas de Toxicidad , Animales , Calibración , Humanos , Límite de Detección , Control de Calidad , Reproducibilidad de los Resultados , Proyectos de Investigación/normas , Medición de Riesgo , Pruebas de Toxicidad/normas
15.
PLoS One ; 15(12): e0241696, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33326445

RESUMEN

Automated quantification of behavior is increasingly prevalent in neuroscience research. Human judgments can influence machine-learning-based behavior classification at multiple steps in the process, for both supervised and unsupervised approaches. Such steps include the design of the algorithm for machine learning, the methods used for animal tracking, the choice of training images, and the benchmarking of classification outcomes. However, how these design choices contribute to the interpretation of automated behavioral classifications has not been extensively characterized. Here, we quantify the effects of experimenter choices on the outputs of automated classifiers of Drosophila social behaviors. Drosophila behaviors contain a considerable degree of variability, which was reflected in the confidence levels associated with both human and computer classifications. We found that a diversity of sex combinations and tracking features was important for robust performance of the automated classifiers. In particular, features concerning the relative position of flies contained useful information for training a machine-learning algorithm. These observations shed light on the importance of human influence on tracking algorithms, the selection of training images, and the quality of annotated sample images used to benchmark the performance of a classifier (the 'ground truth'). Evaluation of these factors is necessary for researchers to accurately interpret behavioral data quantified by a machine-learning algorithm and to further improve automated classifications.


Asunto(s)
Técnicas de Observación Conductual/métodos , Conducta de Elección , Drosophila/fisiología , Proyectos de Investigación/normas , Investigadores/psicología , Aprendizaje Automático Supervisado , Animales , Técnicas de Observación Conductual/normas , Técnicas de Observación Conductual/estadística & datos numéricos , Interpretación Estadística de Datos , Femenino , Humanos , Masculino , Variaciones Dependientes del Observador , Investigadores/normas , Factores Sexuales , Conducta Social , Grabación en Video/métodos , Grabación en Video/normas , Grabación en Video/estadística & datos numéricos
16.
Sci Data ; 7(1): 443, 2020 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-33339830

RESUMEN

Metadata that are structured using principled schemas and that use terms from ontologies are essential to making biomedical data findable and reusable for downstream analyses. The largest source of metadata that describes the experimental protocol, funding, and scientific leadership of clinical studies is ClinicalTrials.gov. We evaluated whether values in 302,091 trial records adhere to expected data types and use terms from biomedical ontologies, whether records contain fields required by government regulations, and whether structured elements could replace free-text elements. Contact information, outcome measures, and study design are frequently missing or underspecified. Important fields for search, such as condition and intervention, are not restricted to ontologies, and almost half of the conditions are not denoted by MeSH terms, as recommended. Eligibility criteria are stored as semi-structured free text. Enforcing the presence of all required elements, requiring values for certain fields to be drawn from ontologies, and creating a structured eligibility criteria element would improve the reusability of data from ClinicalTrials.gov in systematic reviews, metanalyses, and matching of eligible patients to trials.


Asunto(s)
Ensayos Clínicos como Asunto , Bases de Datos Factuales , Metadatos , Proyectos de Investigación/normas , Conjuntos de Datos como Asunto
17.
Trials ; 21(1): 1028, 2020 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-33353566

RESUMEN

BACKGROUND: Randomised controlled trials (RCTs) provide valuable information and inform the development of harm profiles of new treatments. Harms are typically assessed through the collection of adverse events (AEs). Despite AEs being routine outcomes collected in trials, analysis and reporting of AEs in journal articles are continually shown to be suboptimal. One key challenge is the large volume of AEs, which can make evaluation and communication problematic. Prominent practice is to report frequency tables of AEs by arm. Visual displays offer an effective solution to assess and communicate complex information; however, they are rarely used and there is a lack of practical guidance on what and how to visually display complex AE data. METHODS: In this article, we demonstrate the use of two plots identified to be beneficial for wide use in RCTs, since both can display multiple AEs and are suitable to display point estimates for binary, count, or time-to-event AE data: the volcano and dot plots. We compare and contrast the use of data visualisations against traditional frequency table reporting, using published AE information in two placebo-controlled trials, of remdesivir for COVID-19 and GDNF for Parkinson disease. We introduce statistical programmes for implementation in Stata. RESULTS/CASE STUDY: Visualisations of AEs in the COVID-19 trial communicated a risk profile for remdesivir which differed from the main message in the published authors' conclusion. In the Parkinson's disease trial of GDNF, the visualisation provided immediate communication of harm signals, which had otherwise been contained within lengthy descriptive text and tables. Asymmetry in the volcano plot helped flag extreme events that were less obvious from review of the frequency table and dot plot. The dot plot allowed a more comprehensive representation by means of a more detailed summary. CONCLUSIONS: Visualisations can better support investigators to assimilate large volumes of data and enable improved informal between-arm comparisons compared to tables. We endorse increased uptake for use in trial publications. Care in construction of visual displays needs to be taken as there can be potential to overemphasise treatment effects in some circumstances.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Presentación de Datos , Visualización de Datos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Factor Neurotrófico Derivado de la Línea Celular Glial/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológico , Proyectos de Investigación/normas , Adenosina Monofosfato/efectos adversos , Alanina/efectos adversos , Antiparkinsonianos/efectos adversos , Antivirales/efectos adversos , Gráficos por Computador , Exactitud de los Datos , Análisis de Datos , Monitoreo de Drogas/métodos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
19.
Medicine (Baltimore) ; 99(52): e23831, 2020 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-33350770

RESUMEN

ABSTRACT: The International Society on Thrombosis and Haemostasis (ISTH) scoring system has been used for diagnosing overt disseminated intravascular coagulation (DIC). However, the cut-off points of fibrin-related markers remain unclear. The ability of the ISTH DIC score and Multiple Organ Dysfunction (MODS) score to predict mortality in cases of exertional heat illness (EHI) was tested. In the process, 3 different D-dimer cut-off values for diagnosing overt DIC were evaluated.Data were obtained on the first day of hospitalization for 76 patients with EHI. The DIC score was calculated according to the ISTH scoring system using 3 D-dimer cut-off values.In predicting mortality, methods 1 and 2 had the same sensitivity and specificity, which were 85% and 73.2%, respectively. The sensitivity for method 3 was 70%. Furthermore, the specificity of the DIC score for method 3 was 89%, which was higher than that of the other 2 methods. The correlation coefficients of the DIC and MODS scores of these 3 methods were 0.757, 0.748, and 0.756, respectively. For the prediction of mortality, the area under the receiver operating characteristic (ROC) curve for the DIC scores of these 3 methods was 0.838, 0.842, and 0.85, respectively. Furthermore, the area under the ROC curve of the MODS score was 0.927.The DIC score had a certain predictive power of a poor outcome of EHI patients, but this was not better than the MODS score. The present data may serve as a reference in selecting the appropriate D-dimer cut-off point for the ISTH DIC score.


Asunto(s)
Coagulación Intravascular Diseminada , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Trastornos de Estrés por Calor , Puntuaciones en la Disfunción de Órganos , Adulto , China , Coagulación Intravascular Diseminada/sangre , Coagulación Intravascular Diseminada/diagnóstico , Femenino , Trastornos de Estrés por Calor/sangre , Trastornos de Estrés por Calor/diagnóstico , Trastornos de Estrés por Calor/mortalidad , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud/métodos , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Proyectos de Investigación/normas , Sensibilidad y Especificidad
20.
Rev Esp Salud Publica ; 942020 Nov 03.
Artículo en Español | MEDLINE | ID: mdl-33140740

RESUMEN

OBJECTIVE: The health crisis caused by COVID-19 required the prompt launch of research in order to generate scientific evidence pertaining to the new disease oriented to control its devastating effects and continuous spread. Therefore, it was essential to adapt the work flow of Research Ethics Committees, to prioritize and to accelerate the evaluation of projects related to this disease. METHODS: This work analyses the evaluation conducted by our Regional Ethics Committees during the initial period of the health emergency (between 13th March and 28th May 2020). RESULTS: 81 research projects were evaluated, 73 of them of regional scope (62 single-centre), 4 national and 4 international. 57 projects obtained a favourable opinion, 4 were withdrawn by the sponsors, 6 did not require ethics approval and 14 did not respond to the clarifications requested up to the date of the study's closure. CONCLUSIONS: The most important research procedures to be analysed in this context are those related to the methodology and informed consent process. It is also essential to address aspects related to the privacy of personal data, and to take into account the workload of the researchers. As an improvement proposal, we think that greater collaboration between the different research teams should be encourage to obtain more robust results.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Comités de Ética en Investigación , Neumonía Viral/epidemiología , Proyectos de Investigación/normas , Flujo de Trabajo , Betacoronavirus , Humanos , Consentimiento Informado , Pandemias , España
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