NUR 590 Evidence-Based Practice Project Proposal Presentation

Grand Canyon University NUR 590 Evidence-Based Practice Project Proposal Presentation– Step-By-Step Guide

This guide will demonstrate how to complete the Grand Canyon University NUR 590 Evidence-Based Practice Project Proposal Presentation  assignment based on general principles of academic writing. Here, we will show you the A, B, Cs of completing an academic paper, irrespective of the instructions. After guiding you through what to do, the guide will leave one or two sample essays at the end to highlight the various sections discussed below.

How to Research and Prepare for NUR 590 Evidence-Based Practice Project Proposal Presentation     

Whether one passes or fails an academic assignment such as the Grand Canyon University NUR 550 Benchmark – Evidence-Based Practice Project: Literature Review depends on the preparation done beforehand. The first thing to do once you receive an assignment is to quickly skim through the requirements. Once that is done, start going through the instructions one by one to clearly understand what the instructor wants. The most important thing here is to understand the required format—whether it is APA, MLA, Chicago, etc.

After understanding the requirements of the paper, the next phase is to gather relevant materials. The first place to start the research process is the weekly resources. Go through the resources provided in the instructions to determine which ones fit the assignment. After reviewing the provided resources, use the university library to search for additional resources. After gathering sufficient and necessary resources, you are now ready to start drafting your paper.

How to Write the Introduction for NUR 590 Evidence-Based Practice Project Proposal Presentation     

The introduction for the Grand Canyon University NUR 590 Evidence-Based Practice Project Proposal Presentation  is where you tell the instructor what your paper will encompass. In three to four statements, highlight the important points that will form the basis of your paper. Here, you can include statistics to show the importance of the topic you will be discussing. At the end of the introduction, write a clear purpose statement outlining what exactly will be contained in the paper. This statement will start with “The purpose of this paper…” and then proceed to outline the various sections of the instructions.

How to Write the Body for NUR 590 Evidence-Based Practice Project Proposal Presentation     

After the introduction, move into the main part of the NUR 590 Evidence-Based Practice Project Proposal Presentation assignment, which is the body. Given that the paper you will be writing is not experimental, the way you organize the headings and subheadings of your paper is critically important. In some cases, you might have to use more subheadings to properly organize the assignment. The organization will depend on the rubric provided. Carefully examine the rubric, as it will contain all the detailed requirements of the assignment. Sometimes, the rubric will have information that the normal instructions lack.

Another important factor to consider at this point is how to do citations. In-text citations are fundamental as they support the arguments and points you make in the paper. At this point, the resources gathered at the beginning will come in handy. Integrating the ideas of the authors with your own will ensure that you produce a comprehensive paper. Also, follow the given citation format. In most cases, APA 7 is the preferred format for nursing assignments.

How to Write the Conclusion for NUR 590 Evidence-Based Practice Project Proposal Presentation     

After completing the main sections, write the conclusion of your paper. The conclusion is a summary of the main points you made in your paper. However, you need to rewrite the points and not simply copy and paste them. By restating the points from each subheading, you will provide a nuanced overview of the assignment to the reader.

How to Format the References List for NUR 590 Evidence-Based Practice Project Proposal Presentation     

The very last part of your paper involves listing the sources used in your paper. These sources should be listed in alphabetical order and double-spaced. Additionally, use a hanging indent for each source that appears in this list. Lastly, only the sources cited within the body of the paper should appear here.

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Sample Answer for NUR 590 Evidence-Based Practice Project Proposal Presentation

Introduction

Covid-19 pandemic impacted peoples’ lives negatively, it led to millions of deaths, harmed people’s health and negatively impacted people financially. As such, the Covid-19 vaccines were made in record time in a bid to control the pandemic and bring life back to normal (Santos et al.,2021). Even though the vaccines have played a big role in reducing the impacts of the pandemic, there is still a need to ensure that people take the vaccine to prevent further infections. As such, it is important to use strategies that can be used to improve people’s willingness to take the vaccine. Therefore, the purpose of this project is to use health education to increase the willingness to those at risk of Covid-19 virus to take the vaccine.

PICOT statement: Among the general population and individuals at risk of covid-19, will the use of health education about covid-19 vaccination plans, as compared to no intervention, lead to a 50% increased willingness to take covid-19 vaccine within six months?

Organizational Culture and Readiness

The implementation of an evidence-based practice project requires the readiness of the targeted organization in terms of its leadership and culture. Therefore, it is important to assess the readiness of the organization as well as its culture. Fortunately, there are various tools which can be used to accomplish such assessment and reflect the real picture of the organization in terms of its culture and readiness. This assessment also helps in finding out if the proposed change aligns with the organization’s vision, values and mission (Ost et al.,2020). From the assessment, the leaders are ready to support EBP initiatives to participate in improving population health in line with their mission. The organization also targets a magnet status in the future, hence  support initiatives that would bring quality to the organization. The organization also supports interprofessional teams which key to effective EBP implementation.

The organizational culture and readiness for the System-Wide Integration of the EBP survey tool was used in the assessment of the organizational culture and readiness (Patton et al.,2022). This tool have been proven to be effective in the assessment of organization culture and readiness. As such, the tool also helped in determining the organization’s ability to support and promote EBP and understand the staff and leaders readiness when it comes to the implementation of EBP. The survey results showed that up to 90% of the staff would support the EBP initiative. This implies that majority of the employees are ready for the proposed change and would positively contribute to it. In addition, up to 80% of the leaders showed an intention of supporting the EBP initiative, which is a majority. Therefore, the organization can be considered ready for the EBP project.

Problem Statement

The Covid-19 vaccines were developed in a record time to help reduce the rates of infection and help people return to normal life. Therefore, researchers made big strides and delivered the vaccines in a record time. Since the millions of people have received the vaccine which has helped in slowing the rates of infections and reinfections. However, millions of people are still skeptical of the vaccines and have failed to take the vaccine so far (Motta et al.,2021). Therefore, there is a need to use effective strategies such as health education that can be used to encourage individuals to take the vaccine.

Literature Review

A literature review was performed to explore articles which support the implementation of the proposed EBP project. Motta et al.(2021) performed a study to determine the impact of educational messages in improving individuals’ willingness to take the Covid-19 vaccine. The researchers found that the pro-vaccine health messages substantially improved the individuals’ willingness to take the vaccine. Another study was conducted by James et al. (2021). This study was conducted with the major aim of determining if the use of persuasive messages as an education strategy can impact Covid-19 vaccine uptake. The researchers noted that the use of persuasive messaging led to an increased willingness to take vaccines, influence others to do so, and become less judgmental about those who have taken the vaccine. Jensen et al. (2022) explored the use of health education delivered through video-based messages. Therefore, the purpose of this study was to determine the effectiveness of educational video-based messages in lowering hesitancy in taking the covid-19 vaccine. . The researchers found out that the messages that increased confidence in the vaccines drove the willingness to take the vaccine. The messages were also effective in increasing willingness to take the vaccine among the skeptical population.

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Piltch-Loeb et al. (2021) also conducted a study with the major aim of exploring the impact of channels for passing educational information on the Covid-19 vaccine. The researchers noted that the use of both traditional media and social media to pass vaccination education led to an increased likelihood of vaccine acceptance among the participants. Another relevant research was conducted by Li et al.(2022) with the major purpose of exploring the effect of education on Covid-19 vaccine hesitancy. The use of education significantly reduced vaccine hesitancy and improved their willingness to take the vaccine. Davis et al.(2022) conducted a study to determine if providing information contrasting the high effectiveness of covid-19 vaccine with the lower efficacy of the annual flu vaccine would increase vaccine uptake. offering such information about the safety of covid-19 vaccine improved the participants’ willingness and intentions to take the vaccine.

Argote et al. (2021) also carried out research that focused on exploring the impact of education accomplished through vaccine campaigns in improving the willingness of individuals to take vaccines. The provision of vaccine efficacy information improved the individual’s willingness to take the vaccine. The next research was conducted by Santos et al.(2021) with the major purpose of evaluating the impacts of messages targeting behavior on vaccination registration and acceptance. The educational messages were designed to target the participant’s behavior, and the researcher collected data through a survey and email. As part of the findings, the researchers found that the intervention substantially increased the number of individuals registering and willing to take the covid-19 vaccine.

The Change Model

Models or frameworks for change play a critical role of guiding the process of change implementation to ensure that it is a success. They are also used to reduce the possibility of change resistance since the staff in most cases tend to oppose proposed change. Models for change act as a guide and provides steps for implementing the project, therefore, it is important to choose a suitable model. Therefore, the selected model for change is Lewin’s change model. This model has three phases including unfreezing, change and refreezing. These three phase represent distinct phases of change implementation. The change takes place when the driving forces are greater than the restraining forces (Muldoon, 2020).

Lewin’s model will be applied to guide the implementation of the proposed project (Muldoon, 2020). It is important to note that all the three phases will be used as a guide to the implementation process. Therefore, in the first stage, which is unfreezing, individuals at the organization and patients who visit will be informed of the need to increase Covid-19 vaccine uptake. This will be achieved by referring to the existing statistics. The second phase will involve educating the nurses on the health education content to teach the population to help increase the willingness to take vaccines. The final phase will entail that the culture of willingness to take vaccines is retained among people through a continuous process of health education and health promotion.

Implementation Plan

Implementation of an EBP project is one of the most crucial stages as the proposed solution is implemented in this phase to help improve the chances of the project’s success. Therefore, it is important to have an appropriate implementation plan in place. As part of the implementation plan, The setting for this project is an outpatient health facility offering care to patients with different diseases and in need of care services from the facility. As such, the potential subjects are those who come to the facility to seek patient care services and are at risk of contracting the Covid-19 virus (Dror et al.,2020). The timeline for the project has also been proposed to take six months. It is important to have a budget and resource list. Therefore, a total of $26,000 will be needed in terms of financial resources to help in a full implementation of the project.

As part of the implementation plan, quantitative design approach has been chosen. This approach will support the use of numbers to report the outcomes as opposed to qualitative, which uses narration (Jolley, 2020). The quantitative approach will also support easier data collection and analysis as quantitative data can easily be analyzed using standard statistical tools. The questionnaires will be used to understand the baseline willingness and attitude of the participants regarding taking the Covid-19 vaccine. One of the reasons for choosing the questionnaires is that they are easy to use and administer. The project will be delivered in phases, starting with needs assessment up to the implementation phase.  Various stakeholders have been identified for the project. The stakeholders include the nurse working in the outpatient unit, the nurse manager of the outpatient unit, the finance office, the nurse leader, and the nurse educator. These stakeholders are expected to accomplish their roles to ensure that the project is a success.

Evaluation Plan

Evaluation is one of the last phases of the EBP implementation process, therefore, it is also important to have an appropriate evaluation plan in place. Therefore, as part of the evaluation plan, various outcomes are expected. One of the expected outcomes is increased willingness to take any of the Covid-19 vaccines. It is also expected that the targeted population will turn up for the health education program to receive the education content (James et al.,2021). Another expected outcome is an upsurge in the intake of Covid-19 vaccines to help improve the patient’s immunity against the Covid-19 virus.  Questionnaires will be used to assess the population’s knowledge regarding the Covid-19 vaccine plans before the health education program and after the education program. The data obtained at these two points will be vital in assessing the efficacy of the health education program. Statistical tests are used as part of data analysis to help reveal any data trends. Therefore, the chosen statistical test is paired sample T-test (Ahmad et al.,2020).

Sometimes, the intervention may lead to unexpected results. Therefore, it is important to have an appropriate plan in place. As part of the strategies, the project team can re-examine the intervention applied in a project. A re-examination will enable the project team to identify areas of weakness and come up with potential improvements for better outcomes (Melnyk & Fineout-Overholt, 2022). Another strategy is to extend the project timeline to allow the project team to take various corrective measures. The project will be maintained upon achieving positive impacts and a better clinical process. The project will also be maintained if it proves to be cost-effective. The extension of the project will also be triggered in case the outcomes are inconclusive (Linsley et al.,2019). As part of the extension duration, additional data may be acquired to help in further evaluation of the project. A revision will also be done in cases where the strategies do not align with the outcomes.

References

Ahmad, W. M. A. W., Ghazali, F. M. M., & Hasan, R. (2022). Basic Statistical Analysis For Applied Sciences. Penerbit USM.

Argote, P., Barham, E., Daly, S. Z., Gerez, J. E., Marshall, J., & Pocasangre, O. (2021). The shot, the message, and the messenger: COVID-19 vaccine acceptance in Latin America. NPJ Vaccines, 6(1), 118. https://doi.org/10.1038/s41541-021-00380-x

Davis, C. J., Golding, M., & McKay, R. (2022). Efficacy information influences the intention to take the COVID‐19 vaccine. British Journal of Health Psychology, 27(2), 300–319. https://doi.org/10.1111/bjhp.12546

Dror, A. A., Eisenbach, N., Taiber, S., Morozov, N. G., Mizrachi, M., Zigron, A., … & Sela, E. (2020). Vaccine hesitancy: the next challenge in the fight against COVID-19. European Journal of Epidemiology, 35, 775-779. Doi: 10.1007/s10654-020-00671-y

James, E. K., Bokemper, S. E., Gerber, A. S., Omer, S. B., & Huber, G. A. (2021). Persuasive messaging to increase COVID-19 vaccine uptake intentions. Vaccine, 39(49), 7158-7165. https://doi.org/10.1016/j.vaccine.2021.10.039

Jensen, U. T., Ayers, S., & Koskan, A. M. (2022). Video-based messages to reduce COVID-19 vaccine hesitancy and nudge vaccination intentions. PloS One, 17(4), e0265736. https://doi.org/10.1371/journal.pone.0265736

Jolley, J. (2020). Introducing Research and Evidence-Based Practice for Nursing and Healthcare Professionals. Routledge.

Li, P. C., Theis, S. R., Kelly, D., Ocampo, T., Berglund, A., Morgan, D., … & Burtson, K. (2022). Impact of an education intervention on COVID-19 vaccine hesitancy in a military base population. Military Medicine, 187(Special Issue_13), e1516-e1522. https://doi.org/10.1093/milmed/usab363

Linsley, P., Kane, R., & Barker, J. H. (2019). Evidence-based Practice for Nurses and Healthcare Professionals. SAGE.

Melnyk, B. M., & Fineout-Overholt, E. (2022). Evidence-based practice in nursing & healthcare: A guide to best practice. Lippincott Williams & Wilkins.

Motta, M., Sylvester, S., Callaghan, T., & Lunz-Trujillo, K. (2021). Encouraging COVID-19 vaccine uptake through effective health communication. Frontiers in Political Science, 3, 630133. https://doi.org/10.3389/fpos.2021.630133

Muldoon, J. (2020). Kurt Lewin: Organizational Change. The Palgrave Handbook of Management History, 615–632.

Ost, K., Blalock, C., Fagan, M., Sweeney, K. M., & Miller-Hoover, S. R. (2020). Aligning organizational culture and infrastructure to support evidence-based practice. Critical Care Nurse, 40(3), 59–63. https://doi.org/10.4037/ccn2020963

Patton, L. J., Garcia, M., Young, V., Bradfield, C., Gosdin, A., Chen, P., … & Tidwell, J. (2022). Exploring nurse beliefs and perceived readiness for system wide integration of evidence-based practice in a large pediatric health care system. Journal of Pediatric Nursing, 63, 46-51 https://doi.org/10.1016/j.pedn.2021.12.018

Piltch-Loeb, R., Savoia, E., Goldberg, B., Hughes, B., Verhey, T., Kayyem, J., … & Testa, M. (2021). Examining the effect of information channels on COVID-19 vaccine acceptance. Plos One, 16(5), e0251095. https://doi.org/10.1371/journal.pone.0251095

Santos, H. C., Goren, A., Chabris, C. F., & Meyer, M. N. (2021). Effect of targeted behavioral science messages on COVID-19 vaccination registration among employees of a large health system: A randomized trial. JAMA Network Open, 4(7), e2118702-e2118702. Doi: 10.1001/jamanetworkopen.2021.18702

Shih, H. I., Wu, C. J., Tu, Y. F., & Chi, C. Y. (2020). Fighting COVID-19: A quick review of diagnoses, therapies, and vaccines. Biomedical Journal, 43(4), 341-354. https://doi.org/10.1016/j.bj.2020.05.021

Implementing evidence-based practice (EBP) is critical for improved health outcomes in healthcare facilities. However, this process faces many barriers, hence the need for change proponents to assess organizational readiness for change. Gabutti et al. (2023) described organizational readiness for change as an organization’s capacity to implement a recommended transformation, which can be planned or sudden. Typically, EBP projects are planned change since they primarily propose an intervention to address a patient care issue. Nurses can use various tools to assess readiness depending on the organization, the scope of the proposed change, implementation time, and other factors. One of the dominant tools/instruments is the Organizational Readiness to Change Assessment (ORCA) tool. According to Kononowech et al. (2021), the ORCA tool assesses readiness by focusing on three variables: evidence supporting the proposed change, organizational context, and facilitation. Nurses can also use the Organizational Readiness for Knowledge Translation (OR4KT) tool to assess readiness. The OR4KT assesses change around six constructs, including climate for change, contextual factors, and change content (Hardy et al., 2022). Others include organizational leadership, support, and motivation.

Based on their focus constructs, I will use the ORCA tool to assess my organization’s readiness for change. As Kononowech et al. (2021) posited, change should be supported by strong evidence and adequate resources to allow seamless implementation. Strong evidence insinuates relevance and applicability in the current clinical practice. It is also crucial to assess how the organization helps people change their attitudes and behaviours to facilitate the proposed innovation. Generally, an organization ready for change should support employees in adjusting effectively and avoid being comfortable with the status quo. A critical evaluation of these aspects will enable me to determine both barriers and facilitators of the proposed EBP project and the likelihood of effective implementation. Besides, the ORCA tool consists of three scales, making it easier to use than the OR4KT tool.

NUR 590 Syllabus Evidence Based Practice Proposal-1 Sample Answer

NUR-590 Syllabus: Evidence-Based Practice Proposal 

Section A: Organizational Culture and Readiness 

To determine the organizational readiness for the EBP project, a readiness assessment was conducted at the organizational level using Norwegian version of the Evidence-Based Practice Attitude Scale (EBPAS) (Egeland et al., 2016). The assessment indicated that the organization is ready to implement the EBP project. However, the barrier noticed was low level of commitment from the employees towards the adoption of the EBP project. On the other hand, the facilitators observed included the on-site health care providers who were willing to promote the EBP. Moreover, the management also expressed willingness to facilitate the project by establishing sufficient system for personal and professional development (Egeland et al., 2016).  

Regarding the high scores, the assessment tool contained nineteen categories and the organizational performed well in seven categories, with the commitment by the management and providers topping the list in the high scores. On the other hand, the low scores were recorded in poor performance in six categories including lack of critical personnel such as librarian to guide employees on EBP application (Egeland et al., 2016). Moreover, the organization did not have tuition reimbursement program that could provide employees with financial incentives for advancing their education.   

Concerning incorporation of clinical inquiry, the organization will ensure that health care professionals are given adequate EBP training to enhance their confidence and inspiration for EBP. The training will be crucial in highlighting areas of weakness that need enhancement (Billsten et al., 2018). Consequently, the organization will develop policy to guide EBP implementation and assist in adopting the approved EBP solutions.  

Section B: Proposal/Problem Statement and Literature Review 

Refining PICOT into Problem Statement 

The focus of this EBP project is on cervical cancer. Cervical cancer is among the most prevalent female reproductive cancers. The PICOT developed is, in women age between 20 and 35 years, will evidence-based education on cervical cancer screening compared to lack of education lead to high screening uptake within three months? The burden of cervical cancer continues consistently among the population and it is currently the fourth leading cause of cancer-related deaths among women internationally. Kong et al. (2019) reported a significant increase of about 10.3% in the incidences of cervical cancer between the years 2000 and 2009 with approximately 570,000 new cases of cervical cancer. The study also indicated that younger women aged between 20 and 35 years are the most affected by the condition. However, Kong et al. (2019) identified delay in diagnosis as the primary cause of high mortality among patients since it lowers the survival rates. Moreover, the study reported that the higher prevalence of the cervical cancer among women aged between 20 and 35 can be attributed to the effort to preserve fertility.  

Fortunately, among all the cancers affecting reproductive organs of women, cervical cancer is the one that can be easily prevented. In most cases, screening for early detection and prevention of cervical cancer is conducted using Pap smear or Papanicolaou test, which are associated with nearly 70% reduction in cervical cancer mortality rates (Vaccarella et al., 2016). However, despite the massive devastating burden associated cervical cancer, the willingness of women to go for cervical cancer screening remains wanting. As such, this project recommended introduction of education programs on cervical cancer screening among women aged between 20 and 35 years to help in creating awareness and increase their willingness to go for screening. Education is also crucial in addressing the misconceptions that exist in the society concerning cervical cancer screening. Education will also empower women to take responsibility for their lives.  

There are several studies that have been conducted that can support the PICOT. Naz et al., (2018) conducted a study with the aim of systematically assessing the effects id educational interventions on cervical cancer screening behavior of women. The systematic review involved searching of the Cochrane library, Web of Science, Science Direct, PubMed, Scopus and search engine of Google scholar for all interventional studies. The study produced thirty seven articles with 15,658 female participants from various parts of the world. Of the thirty seven articles, nearly three quarter delved into the behavior change interventions while nearly one fourth of the articles delved into health education models. The findings of the study revealed that various interventions and health behavior change frameworks offer an effective foundation for cervical cancer prevention. As such, health providers are advised to select educational techniques based on the individual patient situation. However, the limitation in this study is failure to include the grey literature.  

On the other hand, Abu et al., (2020) conducted a study to establish the role of health education on cervical cancer screening utilization. The study used two-pronged clustered randomized controlled trial at eight public health centers that provide cervical cancer screening services using visual inspection with acetic acid (VIA) in Addis Ababa, Ethiopia. The study found that provision of focused health education supported by print educational materials improved uptake of cervical cancer screening services. However, the limitation of this study is that it was conducted in urban setting which comprises individuals who can read and write and so, it cannot be generalized in many parts of the country especially in rural settings where most women are age and illiterate.  

Musa et al., (2017) also conducted a systematic review to understand the evidence of the effect of cervical cancer education compared to control conditions on the rates cervical cancer screening in qualified women population at risk of cervical cancer. The method used was PICO framework to develop our search strategy. The findings of the systematic review supported the application of theory-based cervical cancer educational interventions to enhance participation of women in cervical cancer screening programs, especially in communities with high illiteracy levels. The limitation of the study is failure to collect secondary outcome data on the value of tests and health insurance coverage in cervical cancer screening and how these variables influenced screening rates in women from different socio-economic status, geographical settings, and age.  

References 

Abu, S. H., Woldehanna, B. T., Nida, E. T., Tilahun, A. W., Gebremariam, M. Y., & Sisay, M. M. (2020). The role of health education on cervical cancer screening uptake at selected health centers in Addis Ababa. PloS one, 15(10), e0239580.   https://doi.org/10.1371/journal.pone.0239580 

Billsten, J., Fridell, M., Holmberg, R., & Ivarsson, A. (2018). Organizational Readiness for Change (ORC) test used in the implementation of assessment instruments and treatment methods in a Swedish National study. Journal of substance abuse treatment, 84, 9-16. https://doi.org/10.1016/j.jsat.2017.10.004 

Egeland, K. M., Ruud, T., Ogden, T., Lindstrøm, J. C., & Heiervang, K. S. (2016). Psychometric properties of the Norwegian version of the Evidence-Based Practice Attitude Scale (EBPAS): to measure implementation readiness. Health research policy and systems, 14(1), 1-10. https://doi.org/10.1186/s12961-016-0114-3 

Kong, Y., Zong, L., Yang, J., Wu, M., & Xiang, Y. (2019). Cervical cancer in women aged 25 years or younger: A retrospective study. Cancer Management and Research, 11, 2051-2058. https://doi.org/10.2147/cmar.s195098 

Musa, J., Achenbach, C. J., O’Dwyer, L. C., Evans, C. T., McHugh, M., Hou, L., & Jordan, N. (2017). Effect of cervical cancer education and provider recommendation for screening on screening rates: A systematic review and meta-analysis. PloS one, 12(9), e0183924.  https://doi.org/10.1371/journal.pone.0183924 

Naz, M. S. G., Kariman, N., Ebadi, A., Ozgoli, G., Ghasemi, V., & Fakari, F. R. (2018). Educational interventions for cervical cancer screening behavior of women: a systematic review. Asian Pacific journal of cancer prevention: APJCP, 19(4), 875. doi: 10.22034/APJCP.2018.19.4.875 

Vaccarella, S., Franceschi, S., Zaridze, D., Poljak, M., Veerus, P., Plummer, M., & Bray, F. (2016). Preventable fractions of cervical cancer via effective screening in six Baltic, central, and eastern European countries 2017–40: a population-based study. The Lancet Oncology, 17(10), 1445-1452. https://doi.org/10.1016/S1470-2045(16)30275-3