Patient and Public Involvement (PPI) in aphasia research requires researchers to include people with aphasia as research partners from the beginning of the study. Yet the quality of reporting on the level and type of involvement is poorly documented in the absence of a framework to guide PPI in aphasia research. This study aimed to extract the items and statements relevant for the development of the People with Aphasia and Other Layperson Involvement (PAOLI) framework for designing and implementing PPI in aphasia research, in collaboration with people with aphasia.The method recommended by the EQUATOR network was followed. This involved: (1) evidence from a scoping review, (2) a thematic analysis of the in-depth interviews, of people with stroke and aphasia, on the topics to be included in the pilot draft, (3) a two round Delphi survey for item/statement selection and (4) an experts’ consensus meeting. The research team involved two PPI partners with chronic stroke-induced aphasia. The research process involved co-design and was informed by the Dialogue model.Twenty-three panellists, from 13 countries, voted in round one with 87% (20/23) responding in round two. The final PAOLI framework includes the following 17 items (with 66 descriptive statements): establish collaborations, recruit patients, gain informed consent, organize induction meetings, train patient partners, create communication links, engage communication partners, conceptualize topics, establish research priorities, reach consensus, work with co-design methods, develop proposals, assist with dissemination of results, promote implementation of the outcomes, support patient partners and promote self-evaluation, monitor progress and assess impact of the patient involvement. These items were considered by the panellists as the most relevant for the involvement of people with aphasia as research partners.The PAOLI is the first international consensus framework for guiding patient involvement in aphasia research. Researchers are encouraged to adopt the framework to improve the quality of their research by promoting the meaningful involvement of people with aphasia within the research team from the start. Aphasia is a communication disorder which results in challenges with everyday interactions and impacts quality of life. Qualitative research involving people with aphasia often investigates quality of life. Until very recently people with aphasia were either excluded from such research teams or occasionally included as consultants but without their contribution documented or reported by the research team. The current work builds on evidence that has identified the absence of a standardized approach for designing and implementing the active involvement of people with aphasia in aphasia research teams. This approach was informed by patient participation involvement principles and the Dialogue model that involves engaging with patients/clients about such issues. This prompted the creation of the People with Aphasia and Other Layperson Involvement (PAOLI) framework, in close collaboration with people with aphasia. The research team involved two patient partners with chronic aphasia after stroke.To decide on the content to be included in the PAOLI framework a two-round international voting (Delphi survey), with 23 panellists from 13 different countries, and a meeting to finalize the framework were completed. The PAOLI includes 17 items (with 66 descriptive statements) on how to: establish collaborations, recruit patients, gain informed consent, organize induction meetings, train patient partners, create communication links, engage communication partners, conceptualize topics, establish research priorities, reach consensus, work with co-design methods, develop proposals, assist with dissemination of results, promote implementation of the outcomes, support patient partners and promote self-evaluation, monitor progress and assess impact of the patient involvement. These items were considered by the panellists as the most important for the involvement of people with aphasia as partners in research teams.The PAOLI is the first international framework for guiding patient involvement in aphasia research. Researchers are encouraged to use the PAOLI framework to improve the quality of their research by supporting the meaningful involvement of people with aphasia within their research team. Aphasia is an acquired communication disorder caused by damage to the language areas of the brain mainly resulting from a stroke . ApproxiNevertheless, until very recently people with aphasia (PWA) and their significant others (the public) were excluded as research partners from teams carrying out the research , 6; espePatient and Public Involvement (PPI) is the required need for the direct and active involvement of PWA (and the public) within the research team, from the onset of the research process. This approach ensures the democratic representation of PWA in research teams, that the research is ethically responsible and relevant, and that wasting valuable resources is minimized . FundingPatient and public involvement involves various participatory approaches and includes a range of different activities throughout the research procedure . In 1969As there is no ‘one size fits all’ approach to conducting PPI research with PWA we initiated this project by conducting a review to explore whether PWA were involved as research partners in the creation of patient reported outcome measures (PROMS) exploring quality of life with aphasia. These PROMs are questionnaires that collect data to report and monitor patients’ subjective assessments of their symptoms, functional status, and quality of life . Twenty The EQUATOR  network  has deveIt was important for this project that the insights of PWA are “voiced” to help the team identify important dimensions that may be overlooked by researchers, leading to more comprehensive and valid outcomes. The involvement of PWA during the codesign stage can provide valuable input on the acceptability and feasibility of the research questions. PWA can assess whether the language, wording, or response options of the materials are clear, easy to understand, and are culturally appropriate. The input from PWA can help identify potential barriers to research completion, or limitations in certain areas of the research process, enabling researchers to refine and improve their outcomes to maximize the usability and acceptability of the research outcome/end-product. Therefore, aphasia, and the corresponding communication difficulties, make it ideal to develop a methodological PPI framework like the PAOLI.Restrictions that make their involvement challenging, (2) the levels and manner of Involvement, (3) the Support required for meaningful contribution, and (4) the Impact of their input on the research outcome. These four areas served as the key topics during the PAOLI codesign phase ).For the development of the PAOLI, the EQUATOR  network’s recommended method for developing a methodological framework  was follDialogue Model [To begin the PAOLI development process, the ue Model , a multiue Model  and the ue Model , was selExploration phase involved contacting patient organizations, such as the Association Internationale Aphasie, the Stroke Alliance for Europe, the World Stroke Organization, to inform potential stakeholders about the PAOLI project, recruit panellists, form the PAOLI consortium and establish the research team. Specifically, prior to commencing the PAOLI study, and to accommodate the needs of PWA for active involvement and promote their autonomy [The autonomy , we applautonomy . This inautonomy .The research team consisted of 7 individuals: the leading investigator, 2 PPI partners and 4 communication partners. The first author (MC), a senior speech and language therapist practising in aphasia rehabilitation, with previous PPI experience in aphasia researchConsultation phase involved 8 semi-structured interviews with people with chronic stroke, four with aphasia and four without. These interviews were subject to a thematic analysis from which the key topics to be included in the pilot draft of the PAOLI were identified. [. The RT consulted several published guidelines and frameworks [the patient and service user engagement (PSUE) framework  on how tthe European Alliance of Associations for Rheumatology (EULAR) recommendations  to deterthe research processes from the Enhancing the Quality of User Involvement in care Planning (EQUIP) study , 39 to gthe Guidance for Reporting Involvement of Patients and the Public (GRIPP2) checklist  on selecThe ntified.  The Consntified.  was compameworks , 35 to bFour phases: Foundation, Development, Translational and Ongoing Processes.Phase I: Foundation, on establishing collaborations, recruiting patients, gaining informed consent, organizing induction meetings, training patient partners, creating communication links and engaging communication partners.33 statements in Phase II: Development, on conceptualizing topics, establishing research priorities, reaching consensus, working with co-design methods, and developing research proposals.34 statements in Phase III: Translational, on data analysis, assisting with the dissemination of the results and promoting the implementation of the outcomes.18 statements in Phase IV: Ongoing Processes, on supporting patient partners and promoting self-evaluation, monitoring progress, and assessing the impact of the patient involvement.14 statements in 18 items  which inAll this information combined, resulted in the conceptual development of the PAOLI leading to the adoption of 18 items and 99 statements and the creation of the first pilot draft. For this study items are defined as the minimum set of information that compose and define a set of statements ; whereasAfter organizing the conceptual constructs, the research team formulated the 99 statements using a 5-point Likert Scale by asking, “How important is it to…” (1 = not important to 4 = very important 5 = extremely important) using an accessible format selected by AK as appropriate for PWA.After the first draft was created, two rounds of cognitive interviewing and a pilot test to explore how patient partners with aphasia understood the statements were completed. The cognitive interview study aimed to improve the validity and acceptability of the questionnaire and followed the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology . This meSince the first two pilot tests were face-to-face, a third pilot was completed to test the method online. During the final pilot, DT a person presenting with stroke-induced expressive aphasia completed the questionnaire online. DT recommended that instructions in the email be simplified regarding accessing, completing, and submitting the questionnaire. These issues were addressed before the initiation of the Delphi study. See screenshot in Appendix 3 of the accessible online version of the Delphi survey.Supported the anonymity of the panellists and the confidentiality of their responses;Brought together a geographically dispersed international panel of experts;Encouraged honest opinion;Allowed a structured/organized group communication process;Facilitated endorsement of the computer-based survey by the PPI partners (AK and JRS) as simple to use;Was a method free from group pressure, especially for patient partners .The Delphi technique is widely used to achieve reliable consensus from a group of subject experts on a particular issue . For thiPPI and aphasia experts in academia, scientific publications, and training;“Experts by experience” who were PWA and stroke survivors without aphasia ;Aphasia rehabilitation clinicians;Stroke and aphasia advocates;Stroke policy makers;The author of previous PPI guidelines/frameworks/recommendations; and aResearch funding agent.The “Recommendations for the Conducting and Reporting of Delphi Studies” (CREDES)  was follThe authors  identified experts in the field of PPI, stroke and aphasia research and rehabilitation through a nomination process. People with stroke and aphasia were also nominated and recruited by MC, AK and JRS in Europe through a snowball effect. Individuals were considered eligible to be invited to participate in the expert panel if they had relevant clinical and or/academic backgrounds and experiences concerning PPI in stroke and aphasia research and/or rehabilitation and could contribute to the topic of the study.The criteria for the patient partners were as follows: (1) to be a stroke survivor, (2) to be in the chronic stage of stroke (> 6 months post-stroke), (3) to be able to speak, understand, read, and write in English post-stroke, (4) to be socially active as confirmed from case history, (5) to have at least one academic qualification (Bachelor), and (6) to have had previous research experience, either as a student or as a researcher. Furthermore, for PWA evidence from case history interview of mild-moderate chronic aphasia was a criterion. The Aphasia Severity Rating Scale (ASRS), of the Boston Diagnostic Aphasia Examination (BDAE)  was usedThe panel consisted of 23 panellists deemed sufficient for the survey . GeograpPatient partners were enlisted from the Cyprus Stroke Association, the French Association S’ Adapter- AVC et Aphasie, the Portugal AVC Stroke Association, the Norwegian Stroke Association, Aphasie Suisse and the Stroke Association UK. Nine people with chronic stroke, five with chronic aphasia and four without, met the inclusion criteria. Patient partners were aged between 27 and 70 years old, with a range of education of 15–22 years. All patient partners had completed a research project during their studies or work commitments prior to the stroke. Specifically, PWA 3 was the primary investigator in several projects throughout his academic career and two SSwoA (1 and 4) are now the primary investigators in studies in their perspective fields. The remaining patient partners were familiar with the research process because of prior experience from the completion of thesis work while studying. The demographic characteristics of the PWA and the SSwoA are reported in Table A consensus level of 80% was selected as this percentage marks a clear majority opinion  and was In round one, panellists received an electronic invitation, with an attached link and simplified instructions. While rating all statements in each section, panellists were also asked to comment on each statement, if they wished, in the space provided. Each panellist was allowed 4 weeks to respond to the survey questionnaire . After rIn round two each panellist was asked to review the statements summarized based on the information provided in round one and to rate them again using the Likert scale. As a result of round two, there was a high level of agreement for most statements and consensus was achieved. Again, after round two, MC send out a summary report to the panel with the revised set of statements.The statistical measures used for analysis were measures of central tendency (medians and mode), widely applied in Delphi studies  for the n = 56) reaching consensus > 80%, 40 statements ‘nearing’ consensus > 70% and 4 statements discarded < 69%. During round two, 20/23 (85%) of the panellists re-voted on the 40 statements that neared consensus from round one, with 10 statements meeting the consensus criterion (> 80%). From the 18 initial items only 1 item, ‘Data analysis’, was discarded as it did not receive adequate votes from the panelists. The quality of this Delphi survey was increased by the quick turnaround (4 weeks) between the two rounds [During round one, 23/23 (100%) of the panellists responded to the initial questionnaire with statements . See Table Integration phase the aim was to discuss the results of the Delphi survey with the panellists in an expert’s consensus meeting [During the  meeting . This waData analysis and Interpretation’ was voted on in any of the two rounds. The group discussed this issue at length and agreed that data analysis should not be included in the PAOLI framework as it was considered a complex task for PWA. Also, AK and JRS and the patient partner with stroke, expressed their views on PPI and gave feedback on their experience of this procedure. The PPI academic experts and patient advocates shared their views on the challenges of PPI in aphasia research. The n = 66 statements were confirmed within the experts’ consensus meeting. See the experts’ meeting outcomes in Appendix 6.The experts meeting (n = 12 panellists) involved the co-author PPI partners AK and JRS, a patient partner with stroke and no aphasia, three aphasia academic experts, an aphasia researcher, an aphasia rehabilitation clinician, a stroke advocate from the World Stroke Organization, a policy maker from Stroke Alliance for Europe, the author of the EULAR PPI recommendations and MC serving as the facilitator of the meeting. Before the experts meeting, each panellist received a report that included all statements and ratings from the two rounds. The meeting was held via the Zoom-online conferencing platform, for 90 min and gave the panellists the opportunity to further discuss the importance of the statements and the structure of the framework. MC presented the trajectory of the development of the PAOLI framework with the results from each round. The experts discussed the topics and statements that did not reach consensus, e.g., the fact that no statement from the section ‘For this Delphi study two iterations and one experts’ meeting (March 2020- Dec 2020) were sufficient to collect the information needed to reach consensus . See theThe final draft of the framework was examined in collaboration with AK and JRS. Specifically, JRS made edits to some of the statements for clarity with PWA. The draft framework was then sent to AK who reviewed it and agreed on the final version. AK proposed the substitution of the word ‘layperson’ with ‘non-professional persons’ in the statements’ description. See Appendix 8 for examples of the edited statements.The final draft of the PAOLI framework.Foundation involves items and statements related to the creation of a support system, for PWA, to function independently within the research team. Such items include the onset of collaborations for patient-partner recruitment, the groundwork for the induction of PWA to the project, and the delivery of adapted PPI research training sessions accustomed to the specific communication needs of PWA. The Foundation phase illustrates the importance of establishing functional communication by proposing the use of various communication means and the liaison with communication partners to prompt positive encounters and collaborations with the other members of the research team and to function autonomously and equally. The Foundation is the most extensive phase of the PAOLI framework with particular attention to the groundwork that needs to be considered by the researchers prior to the initiation of their study to involve PWA as equal partners in the research process.The Development phase, items and statements highlight the importance of the meaningful involvement of PWA in the conceptualization and the identification of the topics most important to them using codesign methodology. Themes and topics should be mutually important to patient partners and the researchers to maintain shared motivation. This practice will enhance the energetic engagement of the patient partners during the co-design and co-production [Under the oduction . This wiTranslational phase the dissemination of the research findings is a key topic by adding the importance of the contribution of national aphasia associations and communication support groups [The content of this phase is classified based on the implementation, dissemination, and sustainability of the findings. This includes the creation of case studies for PWA to report their experiences during their involvement in the study and to suggest potential improvements in the participatory project . During t groups . This phhttps://mulberrysymbols.org/) opposed to black and white line drawing infographics from the noun project website (https://thenounproject.com/).This ongoing phase includes items and statements on the provision of constant support of PWA to self-evaluate their involvement in each stage of the study . This inProgramming, an ongoing phase that was instigated from Phase 1, aims to sustain the engagement of the stakeholders. This included short informative meetings with the invited stakeholders on the purpose and commitments of the PAOLI project, online interviews with patient partners, aphasia and stroke advocates and policy makers, continuous updates of all panellists via email and with controlled feedback reports [, MC drafted the manuscript with AK and JRS as co-authors and presented the preliminary data of the study at the European Life After Stroke Forum of the Stroke Alliance for Europe (March 2023). reports . Also, dIn this study the authors developed, with international consensus, the PAOLI framework, with the active involvement of PWA as PPI partners at all stages of the project. The PAOLI must be considered as a practical, PPI conceptual framework to be implemented in aphasia participatory studies. The PAOLI framework motivates to empower both researchers and PWA to build interactive, democratic, and “balanced” research teams. PAOLI includes 4 main phases, 17 items and 66 descriptive statements on how to, step by step, report on the ways of involving patient partners with aphasia in the research project. It encourages the active and meaningful involvement of PWA via codesign approaches, by providing constant support for self-reflection, and assessing the impact of their contribution to the project’s outcome and the aphasia community at large. These items were considered by the PAOLI consortium as the most important for the involvement of PWA as research partners.The PAOLI framework represents an exciting new frontier for the creation of novel PPI studies to identify aphasia rehabilitation needs and outcomes in both clinical and community settings. Placing the patient at the center of healthcare decisions has the potential to transform traditional approaches to both aphasia care and research. However, the collection and interpretation of patient generated data are not without challenges; the aphasia community will be required to invest in the work needed to ensure that the integration of the data collected following the PAOLI framework, lives up to its promise of improving the lives of PWA. PAOLI aims to empower both researchers and PWA to engage with mutual respect, and experience positive research relationships . The PAOEncourages patient-centered priorities: By involving PWA as partners, research teams can ensure that the research questions, outcomes, and interventions are aligned with the needs and priorities of PWA. This patient-centered approach improves the relevance and applicability of research findings, leading to better health outcomes for patients.Equalizes the power in relationships: PWA can provide valuable input during the codesign and implementation of the research. This prompts researchers to respond to the individual needs of the patient partners and share common goals.Engages in broad dissemination: Patient partners with aphasia can assist in disseminating the results of the study by sharing the outcomes with their communities. Additionally, the insights and experiences of PWA within the team can enhance retention efforts by identifying strategies to improve patient partner engagement and reduce attrition rates.Elevates research impact: PWA can contribute to the development of the research protocol, to tailored materials, ensuring that they are accessible and inclusive to people with communication difficulties. PWA can also help identify potential barriers or ethical considerations that researchers might overlook, leading to more robust and ethical research practices.Embodies best practice statements: PWA as partners can play a crucial role in translating research findings into practice. They can help researchers communicate study results in an accessible manner, ensuring that the information is understandable, relevant, and actioned. The involvement of PWA in knowledge translation can bridge the gap between research and implementation, facilitating the uptake of evidence-based practices in clinical settings and empowering PWA to make informed decisions about their healthcare.Endorses recommendations of funding bodies and ethical review boards: Including PWA in research teams promotes ethical research practices and shared decision-making. PWA can contribute to the development of research ethics guidelines, advocate for patient rights and welfare, and ensure that research aligns with patients' values and preferences. Their involvement will help to promote a more equitable and collaborative research environment and endorse research funder demands.According to the 6Es mission statement, implementing the PAOLI framework in aphasia PPI studies is crucial because it:The PAOLI framework supports that the involvement of aphasia PPI contributors be authentic, address local needs and aim to improve overall population health and wellbeing . The advThe PAOLI and the GRIPP2 aim to promote and advance the quality, transparency, and consistency of the international PPI evidence base, and to ensure best PPI practice. Jointly, GRIPP2 and the PAOLI involved PPI partners from the beginning during the conceptualization, recruitment, content selection, consensus meeting participation, validation, and finalization. Nevertheless, the GRIPP2 aims for researchers to design general PPI studies and use it as a quality assurance measure in the documentation of patient involvement while writing the scientific publication. GRIPP2 includes 34 generic items like “Describe the methods used by which patients and the public were involved” “Report the aim of the study” “Report on how PPI is used at different stages of the study” etc. In contrast, the PAOLI framework, has 17 items as an end-user targeted recommendation, aiming to help researchers support the active involvement of patients with acquired communication challenges in the research team. The main results of our study are the large number of statements (66) which were collected by our PPI approach during the PAOLI co-development phase e.g., “Identify the topics most important to PWA” and “Make the purpose of the study understandable for all partners”. These statements were codesigned to be tailored to the meaningful involvement of people with aphasia and are considered to assist both researchers and research partners in navigating a truly participatory project successfully.The PAOLI, serves as an end-user targeted framework, aiming to help researchers support the active involvement of patients with communication challenges and acquired disabilities in the research team. PAOLI also endorses the constant support of PWA for self-evaluation. The consortium deems necessary that researchers receive constant feedback from the patient partners to avoid dropouts, inactivity, and tokenism. Additionally, although the GRIPP2 provides key items on PPI data analysis and the economic assessment of PPI; the PAOLI does not include any of these items, as they were considered by the consortium as irrelevant to the aim of this framework and the needs of the targeted population. Finally, PAOLI directs the guidance of end-users on how to generate research topics that are mutually inclusive of PWA; an area which was previously acknowledged as vague in studies including PWA.PAOLI represents the first international evidence-based, consensus informed framework for designing and implementing PPI in aphasia research. It encompasses the issues and complexities of involving patients with persistent communication challenges and/or other disabilities within research teams. The PAOLI framework provides key PPI concepts for aphasia research that authors of future papers should incorporate, to enhance the transparency of the evidence of patient involvement. Aphasia researchers can use the PAOLI framework in advance to plan and support patient and other layperson involvement in research studies. The authors propose that researchers use the PAOLI framework to measure the impact of PPI at different stages of the research process. PAOLI provides practical guidance and actions how to transition from intention to operationalizing meaningful involvement and aims to promote aphasia advocacy and dissemination via stroke/aphasia networks. It is recommended that research studies are carried out with or by PWA through their involvement from the beginning of the research process, and in as many stages as possible. The PAOLI framework recognizes the importance of engaging those who use the healthcare system and are affected by aphasia in research to ensure that their perspectives, experiences, and needs are considered and prioritized during and after their rehabilitation. Patient and public involvement in studies on aphasia play a crucial role in shaping healthcare systems and policies, and the PAOLI framework aims to promote more relevant and responsive research through the active involvement of members with aphasia in research teams.This Delphi survey for the development of the PAOLI framework included the consistent and active involvement of two partners with chronic aphasia (AK and JRS) throughout the project timeline. JRS was involved with the recruitment of additional people with aphasia and stroke whereas AK was involved in the preparation of invitation letters, the consent forms, and the design of the of the questionnaire in accessible format. Also, AK was involved in collating the evidence and identifying topics and statements for the PAOLI framework. People with aphasia advised on the comprehensiveness, comprehensibility, and relevance of the included statements during the cognitive interviews. The communication partners (SLT students and family members) assisted PWA with the procedure for informed consent, the technical aspects of completing the cognitive interviews, and with the online Delphi questionnaires for improving the response rate in each Delphi round. Co-authors AK and JRS and a patient partner with stroke, took part in the experts meeting. Also, JRS and AK completed the validation stage of the PAOLI framework and contributed to the lay section of this paper, during the write-up phase.The implementation of the Dialogue Model throughout the study promoted equal partnership between stakeholders and enabled patient partners to have an independent role in decision‐making for the co-development process of the PAOLI framework . NeverthA limitation of this study is that co-authors PPI partners did not have extensive experience with PPI projects; AK was involved in the thematic analysis  and in tA further limitation was the lack of funding to proceed with a more extensive, and probable face-to-face, international expert’s consensus meeting. Further obstacles throughout the process were initially a difficulty to identify global guidelines for determining consensus, sample size, and sampling techniques for the Delphi survey. The format of the “aphasia-friendly” resources in this study does not align with the published guidelines , 42. NevImplementation phase [For the completion of the on phase  it is reon phase . Also, tThe PAOLI framework represents the first international evidence-based, consensus informed guide, for designing and implementing patient and public (meaningful) involvement in aphasia research. It encompasses the issues and complexities of involving patients with persistent communication impairments within research teams. The PAOLI framework aspires to improve the transparency and consistency of the international PPI aphasia inclusive research. To facilitate more effective synthesis of PPI teams, the aphasia researchers need to set up a robust support system, develop patient-relevant research questions and codesign methods adjusted to the unique needs of people with aphasia. The PAOLI framework will contribute to the advancement of understanding, knowledge, and action around meaningful involvement for exploring the impact of PPI on future aphasia research.


Aedes mosquito species and has been considered a major public health problem in Kassala State for tens of years. This study aimed to assess the level of readiness and response toward the 2019 dengue fever outbreak in Kassala at the state and community levels.Dengue fever (DF) is a mosquito-borne viral disease transmitted by This exploratory cross-sectional study was conducted in Kassala State, Sudan, from January to March 2020. The researcher conducted interviews with the key respondents at the state level to assess the level of readiness and response and to reflect the capacity of institutions—public health authorities, health systems, and emergency response bodies.The surveillance system reported 3961 DF cases in Kassala State, representing 93.5% of the total cases in Sudan between August 2019 and January 2020. This outbreak was identified by passive surveillance, 51 samples were tested during the outbreak period, and private clinics and labs were not included in the surveillance system. According to the WHO checklist of outbreak readiness and response, Kassala's surveillance system and public health laboratory received the lowest scores.The study concludes that outbreak readiness and response could be considered below standards, mainly in the surveillance system and laboratory diagnostic facilities, due to the absence of intersectoral collaboration with a regulatory framework in terms of financial and operational participation.The online version contains supplementary material available at 10.1186/s12889-023-17020-9. Dengue fever (DF) is a neglected tropical disease that affects a large number of endemic countries and has a risk for severe manifestations, such as dengue hemorrhagic fever. The incidence of dengue has risen in the last half-century by 30-fold . Up to 4Rapid responses to dengue outbreaks are required to control the spread of the infection and to address the high number of cases. A wide range of different interventions has been employed to meet these demands . PrepareIn Sudan, mosquito-borne viruses including dengue have been considered a major public health problem, predominantly in Kassala during the last 10 years. Recently in August 2019, a dengue fever outbreak occurred in Sudan. In November 2019 the WHO reported a total of 1,197 suspected cases of dengue fever in Sudan  from 8th August through 4th November 2019, including five deaths from seven states . The repThis exploratory descriptive cross-sectional study was conducted in Kassala state, Sudan from January 2020 to June 2020. This state is characterized by the abundance of gardens and orchards and the diversity of nature. The state’s total area is 55,500 square kilometers and the estimated total population is 2,090,000 . Kassala State has 11 localities and the surveillance system covered 158 sentinel centers out of 364 of the health facilities in the state (43.4%). The Kassala locality is the center of Kassala State which consists of 6 sectors, and each sector has several neighbors.The study population is the key informant personnel who work for surveillance, health promotion, vector control, outbreak response, case management, and curative medicine at Kassala State Ministry of Health. Overall, 7 key informant personnel were interviewed from the surveillance, health promotion, vector control, outbreak response, case management, and curative medicine departments of Kassala State MoH. For in-depth information, purposeful sampling was used for the key informant personnel in the departments that were directly linked to the dengue outbreak readiness and response in Kassala MoH .All key informative personnel of the targeted departments  who were in Kassala during the dengue outbreak and participated in the outbreak readiness and response processes were included in the study. Those who did or did not participate in the outbreak readiness and response processes were excluded from the study.The interviewing data collection technique was used to collect information from the key personnel of the targeted departments at Kassala State Ministry of Health. In-depth interviews were conducted to fill out the open-ended questions and checklists developed by the WHO and related literature , 11. TheInterview contents were extensively analyzed about the main 4 dimensions affecting readiness and response . Using thematic analysis, researchers have developed codes during the close examination of the narratives. Patterns of meaning and salient themes emerged from the texts. Words that strengthened or weakened each dimension were extracted from the key informants’ interviews.With concern to Kassala State readiness, the dengue outbreak was spotted by passive surveillance, and active surveillance has not yet been set up on the routine surveillance system. Dengue fever was laid on the list (A) of notifiable diseases according to the state and federal MOH classification (a single dengue case is considered an outbreak/no surveillance thresholds). During the outbreak, case definition publications  were distributed to all health facilities of the state. Concerning laboratory readiness, there were no laboratory confirmations for all suspected dengue suspected cases, and no dengue rapid diagnostic tests were used in Kassala State during the outbreak. The FMoH supplied Kassala State with rapid diagnostic tests at the end of the outbreak. During the outbreak, all the blood samples (72 samples) were sent to the National Public Health Laboratory (Stack) in Khartoum, and they stopped receiving any more samples after 51 confirming samples out of 72 . There was no risk assessment plan prepared before the outbreak emerged, and the state MoH only utilized the same scheme used in Kassala state for the chikungunya outbreak in 2018. Otherwise, no epidemiological, entomological, laboratory or geographical alerts were used. The work of epidemiological and entomological teams was in routine surveys, their reports were only combined during the outbreak periods.The surveillance approaches that were used in the outbreak response were sentinel, community-based, and event-based surveillance. These three approaches were the main surveillance approaches normally used in Kassala State, and no syndromic surveillance or laboratory surveillance was used. Additionally, vector surveillance was not used or linked to routine surveillance. Regarding the private sector, private hospitals and polyclinics were included in the surveillance system, while private clinics and labs were not. In referring to the surveillance reports on the outbreak response, only 158 out of 362 (43.6%) health facilities reported on time to the state surveillance department as sentinel units. Until the end of the outbreak, there was no electronic system for reporting, and they conveyed the reports through active visits to health centers or by telephone calls. The analysis process of dengue case data was not conducted at the locality level, and the analysis process was conducted at the federal and state Ministry of Health.Political issues were considered one of the major challenges for the surveillance system, which led to being late in the announcement of the outbreak and delayed the outbreak response from the state directorate and the FMoH, although the surveillance department at the state was notifying for one dengue case as an outbreak. Furthermore, the fragmentation of the health system and the various outbreak activities of the departments, in addition to the lack of testing equipment for confirming the cases or having any resources for intervention procedures led to poor outbreak response.In connection with the outbreak readiness in Kassala, the health personnel were not sufficient at the beginning of the outbreak, the FMoH responded in November 2019 by sending more than 100 doctors to be trained for one month. During the outbreak, free drugs for dengue fever  were available and prescribed freely for admitted patients in governmental healthcare facilities. Additionally, insecticide-treated nets (ITNs) were distributed throughout the whole of the state after the peak of the rainy season (after the outbreak commencement) and set to every bed throughout the state health facilities.There was a contiguous plan for outbreak response after the minister of health was changed at Kassala State in the last quarter of 2019. This plan involved international nongovernmental organizations (INGOs), the central committee of Sudan doctors, and civil societies in counseling and orientation of the notification system. Additionally, the risk communication was transparent and applied with fewer restrictions.Before the INGOs took part in the outbreak intervention  in the middle of the outbreak period, all the response interventions were solely represented by the MoH. The civil societies and youth initiatives played a valuable role in the outbreak response, and they were formally involved as stakeholders in November 2019. However, governmental authorities such as those in the environmental and educational sectors did not collaborate or participate in the outbreak response with the health sector due to the lack of preestablished communication or cooperation.The significant challenges faced by the curative medicine and primary healthcare departments were considered the lack of financial resources, trained personnel, and the absence of any routine procedures and activities before the outbreak occurrence. These factors affected the quality of response in the departments of the surveillance system and vector control and led to the occurrence of dengue outbreaks in 2019 less than one year after the chikungunya outbreak in 2018. On the other hand, it was suggested to set up a protocol for case management followed by orientation sessions for the healthcare workers and establishment of rural healthcare units for the outbreak because most of the cases with complications were from rural areas.Concerning outbreak readiness, there were no specific resources for this outbreak, and most of the environmental health and vector control resources and equipment were obtained from the previous Chikungunya outbreak in 2018. Guidelines manual were available for working and supervision of the health promoters and vector control workers. The health promoter teams were trained on how to deliver educational messages to households and check their water containers, which could be considered nonchemical mosquito control measures. For chemical mosquito control, Abate 500 EC (with temephos as an active ingredient) was used as the main insecticide for vector control in this outbreak. This Abate 500 EC was checked before the outbreak for its effectiveness. On rare occasions, diesel is also used as a chemical method for vector control. The biological control was never used before in the state. Generally, there is no entomological laboratory to compare the types of virus present inside the vector and human beings in the state.Regarding the environmental health and vector control response during the outbreak, there were 7 stations in the Kassala locality plus 4 stations in rural Kassala covered weekly. The entomological indices  were reported daily during the outbreak. All localities send their reports for vector control to the state level every week. The larval control consisted of two main parts: indoor and outdoor. In the indoor part, the health promoters made home visits to clean and dry the water containers and provided educational messages to households. The outdoor part included outdoor insecticides. Adult mosquito control was represented by a fogging spray using a fogging machine. This fogging spray was used according to the number of cases, so the area with a high number of cases reported was targeted to have a fogging spray. This spray was used for a total of eight weeks throughout the outbreak period. During the outbreak, no trained staff could disseminate spatial GIS maps to help in spraying and vector control. Moreover, the response activities involved a wide number of governmental facilities (such as schools) according to the available resources by inspecting and cleaning the water containers and then conducting a fogging spray while the schools were closed at the early stage of the outbreak.The community was one of the challenges for environmental health and vector control, and some of them were unconvinced that the breeding sites of mosquitoes could be inside their homes. They heard and were aware of dengue, and some of them refused the health promoters to enter their homes. Additionally, the absence of entomological laboratories creates difficulties for the department in determining the types of viruses inside the vectors.During the outbreak in Kassala State, there was no standard approach for community engagement. The major health promotion activities focus on “house-to-house visits” and mass media programs through television episodes including an interview with healthcare promoters. The health promotion plans focused on the behavior change, especially on water container dryness. In the middle of the outbreak, the health promotion team was changed. The new team conducted a small community survey related to health promotion activity. Then they changed the main message of the health promotion campaign from the old slogan “dry the sources of mosquito breeding sites twice a week” to the new slogan “If someone at home was infected by dengue, this is because you miss drying”, the new slogan had an indirect message with emotion. Furthermore, the youth initiatives played a major role as a third partner to overcome the community resistance and build community engagement by conducting mass campaigns and participating in blood donation, providing medication for case management, and sharing knowledge and awareness throughout the community. The mass campaigns of those youth innovations were designed to be as tents located in the local markets of Kassala locality, and each tent had a catchment area to be covered at the end of the program. These tents were equipped with posters, a sound system, and trained volunteers for implementing exhibitions, roleplays, lectures, and group discussions. Any educational messages used in these tents should be reviewed and approved by the state ministry of health first. In addition to that, all the health messages were translated into the local language of the different tribes of the Kassala locality. This program continued for 20 days.In addition to the late response and poor community engagement, the obvious challenges faced by the health promotion department was community behavior. Some of the local citizens resisted the “house-to-house visit” approach and some of the households did not allow health promoters to check their underground water storage. A large number of state people showed a full reliance on the health promoters and saw them as “clerks” whose responsibility was to clean the water container. In addition, the lack of proper monitoring and evaluation processes for providing sustainable funds and resources for health promotion programs and projects can cause obstacles in the future.Based on the respondents’ feedback on the study checklist elements related to outbreak management, surveillance, health promotion, and vector control. In this outbreak, the vector control and health promotion interventions were relatively matched with the WHO model contingency plan elements. Figure Outbreak response has been recognized as a cycle containing many factors and elements such as community and partner engagement, capacity building, and providing operational connections to reach a level of structured and coordinated response. One objective of this study was to determine the readiness and responses at the state level during the dengue outbreak and provide a holistic and comprehensive concept of how surveillance, vector control, outbreak management, and health promotion plans and procedures were implemented at the time of the outbreak. The findings data gathered from the state-targeted departments and personnel were analyzed and compared to WHO documents and previous recommendations.Surveillance is a critical component of any dengue prevention and control program because it provides the information necessary for risk assessment and program guidance, including epidemic response and program evaluation. The restricted routine surveillance at the state, with the absence of active surveillance, unprepared community-based surveillance, and limited sentinel surveillance introduces the fragility of the surveillance system with the underreporting of cases that undermining the ability of surveillance to include all health facilities and home treating cases. According to the WHO global strategy for dengue prevention, the surveillance system for dengue should be a part of the national health information system, with a set of core indicators monitored at various levels of the health administration, and data quality also needs to be monitored and assessed periodically . These wGenerally, the dependence on weak fragmented passive surveillance systems provides meaningless reporting with an inaccurate number of cases, inadequate methods of notification, and weakness in the transfer of case information from the local to the central level for analysis, with a lack of local use of analysis data, which may lead to delay of response. In addition, laboratory surveillance needs to be strengthening for outbreak preparedness and response because the blood samples collected during the outbreak in Kassala were unrepresentative (1.3%) and did not demonstrate an accurate number of dengue cases or the other coinfections such as chikungunya fever and yellow fever.Regarding outbreak management and according to the previous literature. The control and response activities for a dengue outbreak generally need to be multisectoral, multidisciplinary, and multilevel, requiring environmental, political, social, and medical inputs to be coordinated. In addition, outbreak planning must achieve governance over the response, especially by involving stakeholders and providing response monitoring details . This haEffective vector control measures are critical to achieving and sustaining the reduction of morbidity attributable to dengue. The environmental health and vector control at the state showed satisfactory efforts during the outbreak in comparison with available resources, by repeating the vector/larvae control procedures, adapting the interventions to different settings, and customizing the programs to involve schools, hospitals, etc. Furthermore, there were daily entomological indices reports , and this finding was similar to some reports of a study conducted by Harrington and co-authors  that monAccording to the WHO global strategy for dengue prevention, dengue cases and dengue deaths can be reduced only through the behavioral actions of those responsible for designing and implementing dengue prevention and control programs and by the adoption of risk reduction and health protection behaviors through the populations at risk . The heaLast, the occurrence of this dengue outbreak in Kassala State after 4 months of the chikungunya outbreak with 19,902 cases  and stayThere were several limitations in this study. Generally, the lack of a previous study on the same subject made discussion of the results more difficult. In addition, the retrospective nature of the study, underreporting and poor health information system, and absence of a formula to adjust for background endemicity were considered common limitations in the study.It is recommended that the state MoH of Kassala and the FMoH of health may consider linking the various departments’ activities to outbreak readiness and response, in addition to improving intersectoral collaboration before and during the outbreak occurrence.The surveillance system should be upgraded by promoting community-based surveillance, expanding the sentinel centers, and establishing laboratory surveillance along with active surveillance to provide early warning information for timely rapid response.Routine vector control activities should be continued regularly, and the locations selected for vector surveillance should be reviewed periodically to meet the latest needs. Moreover, an entomological laboratory is needed to compare the types of viruses present inside vectors and humans.The preventive measures of health promotion and vector control should be expanded to provide a space for community participation and cooperation in all sustainable preventive measures for mosquito control.Behavioral changes should be encouraged in health promotion plans to break the transmission of the disease including appropriate and safe vector control measures.Overall, mosquito-borne diseases, such as dengue fever—can be considered endemic diseases in Kassala State. For that reason, the federal and state MOH may consider boosting their readiness plans and providing both diagnostic and curative measures to enhance the level of response to dengue fever cases. Our study revealed that most of the cases of this outbreak were reported based on clinical features and the actual number of dengue fever cases during this outbreak may be three- or fourfold larger than the reported cases due to weak surveillance systems. Therefore, this outbreak was considered one of the largest outbreaks reported in 2019 in Sudan. The outbreak readiness could be regarded as below standard, mainly in the surveillance system and laboratory diagnostic facilities. Moreover, the heterogeneous outbreak response could be considered a weakening outbreak response due to the absence of intersectoral collaboration with a regulatory framework in terms of financial and operational participation, in addition to poor community participation in operational activities.Additional file 1.


For health professionals, gamification is a new teaching method that has achieved an important role in recent years, with excellent results in learning and knowledge acquisition. Thus, the objective of this study was to analyze the gaming experience through different gamification resources in the classroom with physiotherapy students.A comparative study on gamification-based teaching resources was carried out during the first semester of the 2021–2022 academic year. A total of 33 physiotherapy students participated in this study. After the theoretical topics were taught, the participants were invited to participate in different gamification resources such as Kahoot!, Physiotherapy Party and Escape Room. The gaming experience with the different gamification resources was measured with the GAMEX scale.The Physiotherapy Party showed a higher score in relation to the enjoyment dimension compared to the Kahoot! and Escape Room (p = 0.004). The Escape Room presented higher scores in absorption, creative thinking, activation and dominance compared to Kahoot! and Physiotherapy Party (p < 0.005).Gamification resources promote enjoyment and creativity in the students in the classroom. The use of new teaching methods based on gamification, such as Escape Room as Physiotherapy Party should be considered as first choice in the use of gamification resources due to the benefits they bring to students.The online version contains supplementary material available at 10.1186/s12909-023-04576-8. Education for health professionals has acquired a new innovative approach in recent years –4. The sFor health professionals, gamification is a new teaching method that has achieved an important role in recent years, with excellent results in learning and knowledge acquisition . This teDifferent studies have explored the influence of game-based teaching methods on university degrees of health sciences, mainly in Nursing, as a complement to traditional teaching, in order to strengthen the skills and knowledge acquired for handling realistic situations with patients , 21. TheDuring the first semester of the 2021–2022 academic year, a quantitative study was carried out, in which different gamification resources were compared in the classroom through game-based learning in Physiotherapy Degree students. Convenience sampling was performed. A total of 33 students participated in the Physiotherapy First Aid subject, including three gamification resources, such as Kahoot !, PhysioThis study was carried out at the University of Almeria. The initial participants in the study were 40 students of the Physiotherapy Degree enrolled in the subject “First Aid from Physiotherapy”, which is an optional subject of 6 European Credit Transfer and Accumulation System (ECTS) credits, and is taught in the first semester of the 4th year of the Physiotherapy degree. This subject consists in the acquisition of practical skills and theoretical content, where students are organized in groups of 15–20 students, depending on the number of students enrolled, to develop practical content. The theoretical-practical contents of this subject introduce students to the generalities of First Aid from Physiotherapy, basic cardiopulmonary resuscitation, airway obstruction, trauma injuries, hemorrhage, skin aggression, emergency delivery, alterations of consciousness, aggression by physical or environmental agents and intoxication. (Supplementary file 1) The inclusion criteria were the following: (a) being over 18 years old, and (b) being enrolled in the elective subject of First Aid from Physiotherapy. On the other hand, the exclusion criteria were the following: (a) positive COVID-19 test, which made it impossible to participate in the classes where each of the gamification resources were developed , and (b) cancelation of enrollment in the subject during the semester , and the data was used in accordance with Organic Law 3/2018, of December 5, of Protection of Personal Data and guarantee of digital rights. The ethical principles established in the Declaration of Helsinki were also followed. Subsequently, the participants signed the informed consent.The sample consisted of 40 Physiotherapy Degree students, of which 33 students met the inclusion criteria, thus participating through the three gamification-based teaching resources. Of the total sample included in the study, 17 were women (51.5%) and 16 men (48.5%), with a mean age of 21.48 ± 1.73 years . One hundred per cent of the study participants were taking the subject “First Aid from Physiotherapy” and had not previously used gamifying resources for learning.The results obtained in the game experience scale are detailed in Table According to the obtained results, there were higher scores in the enjoyment dimension for Physiotherapy Party compared to Kahoot! and Escape Room. The highest scores regarding absorption, creative thinking, activation and dominance were obtained in Escape Room with respect to Kahoot! and Physiotherapy Party. At the same time, the lowest scores regarding the absence of negative effects were also obtained in Escape Room. There were statistically significant differences between the different gamification resources in terms of the GAMEX dimensions of enjoyment, absorption, creative thinking and dominance.As can be seen in Table The objective of this study was to analyze the gaming experience through different gamification resources in the classroom with Physiotherapy students. Once the results were analyzed, it was observed that there were statistically significant differences with respect to the GAMEX game experience scale in relation to the dimensions of enjoyment, absorption, creative thinking and dominance between the three gamifying resources used in this study in relation to Kahoot!, Physiotherapy Party and Escape Room. However, these results cannot be compared in terms of gaming experience scale, since there is no study where the GAMEX scale has been used. However, Kahoot! is widely used in several educational fields, such as nursing , 33, medFurthermore, the game experience scale in relation to the Physiotherapy Party can be compared with another study , where sIn this scenario, the fact that the different methods in the teaching-learning process using the gamification resources of this study show positive results compared to traditional methods has great weight in the literature, however, comparisons with other resources have not been investigated previously, so it is necessary to seek an explanation for the differences in the results of this study. The GAMEX scale with which Kahoot!, Physiotherapy Party and Escape Room have been analyzed, presents different dimensions in which statistically significant differences between one method and the other have been highlighted , 27. TheAs we have seen, these gamification resources present beneficial characteristics in the competency-based learning process , 35, 47,It should be noted that there are no previous studies carried out with Physiotherapy Degree students comparing different gamification resources in the classroom, such as Kahoot!, Physiotherapy Party and Escape Room. The results of this study should be considered in the context of several limitations. Firstly, the students who participated in this study were from a single Spanish university and from a single year, and the sample of students is small, since the participants were from an optional subject. Secondly, the degree of satisfaction, usefulness and effort involved in the use of the different gamification resources by teachers was not measured, which would have allowed us to obtain an even deeper understanding of their level of satisfaction with this type of gamification-based teaching resources. Further research should be carried out to measure the impact of the use of this type of resources and thus allow planning the teaching-learning process using all available tools.The main conclusion that can be drawn from this study is that, through Physiotherapy Party and Escape Room as gamification resources in the teaching process in Physiotherapy students, students present higher levels of enjoyment and creative thinking with respect to the use of Kahoot!. In addition, the absorption and dominance levels are also higher when using Escape Room compared to Kahoot!. Therefore, the results suggest that both Escape Room and Physiotherapy Party should be considered as the first choice in the use of gamification resources due to the benefits they bring to Physiotherapy Degree students.Below is the link to the electronic supplementary material.Supplementary Material 1


The win ratio was introduced into cardiovascular trials as a potentially better way of analyzing composite endpoints to account for the hierarchy of clinical significance of their components and to facilitate the inclusion of recurrent events. The basic concept of the win ratio is to define a hierarchy of clinical importance within the components of the composite outcome, form all possible pairs by comparing every subject in the treatment group with every subject in the control group, and then evaluate each pair for the occurrence of the components of the composite outcome in descending order of importance, starting at the most important and progressing down the hierarchy if the outcome does not result in a win in either pair until pairs are tied for the outcome after exhaustion of all components. Although the win ratio offers a novel method of depiction of outcomes in clinical trials, its advantages may be counterbalanced by several fallacies  and challenges in appropriate clinical interpretation . From this perspective, we discuss these and other fallacies and provide a suggested framework to overcome such limitations to enhance utility of this statistical method across the clinical trial enterprise.  A HR of 0.75 denotes a 25% decrease in the event rate in the treatment group compared to the control group. By contrast, a WR of 1.25, which ignores pairs that are tied, simply denotes that, among the smaller subgroup of those able to be segregated into discrete wins or losses, the proportional win rate is 25% greater for a treatment under assessment. This strategy does not allow for an accurate calculation of the number needed to treat or harm, unlike what can be accomplished from examining the absolute risk reduction between groups using traditional statistical methods. In the ATTR-ACT , which examined the efficacy of tafamidis on the composite of all-cause mortality or cardiovascular-related hospitalizations in a population of individuals with transthyretin amyloid cardiomyopathy, the WR for the primary composite endpoint was 1.70, whereas the Cox model-based analyses suggested that the range of benefit was in the range of a 20% to 30% risk reduction.Historically, a small number of clinically meaningful composite endpoints have been used in the cardiovascular literature. There is familiarity with these endpoints, their advantages, and limitations and, importantly, there is scope for performing at least informal comparisons across trials that examine the same composite. By contrast, there is considerable variability in the composition of novel hierarchical endpoints analyzed with the WR. It is important to realize that, although hierarchically ordered, each endpoint component of the WR is weighted the same. Therefore, a significant WR could be entirely driven by its least clinically meaningful endpoint component. As an example, in the PARAGLIDE-HF (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF) trial, which compared sacubitril-valsartan with valsartan in patients with a left ventricular ejection fraction of >40% after a recent worsening heart failure (HF) event, a prespecified secondary outcome was a hierarchical composite outcome of, in descending order of significance, cardiovascular death, HF hospitalizations, urgent HF visits, and time averaged change in N-terminal pro B-type natriuretic peptide.An attractive feature of the WR is that it provides increased flexibility in the composition of the endpoint in allowing the use of different types of variables, including patient-reported outcomes in combination with traditional events. This factor has been touted as an advantage of providing aggregate meaningfulness, which on its surface is rational.A prerequisite for the calculation of the WR is the formation of treatment and control group subject pairs. This can be done in several ways. The most used approach is the unmatched pairs approach. Here, all participants in the treatment group are compared with all participants in the control group . The drawback of this approach is that a baseline imbalance in risk within an analyzed pair may bias the outcome . To address this issue, a matched pairs approach has been proposed with the goal of forming pairs based on shared baseline risk.,Perhaps one of the greatest issues with the WR is the fact that, in calculating the WR, when a tie occurs (neither a win nor a loss), it is largely placed aside and ignored. Cardiovascular trials that enroll many patients are typified by a greater frequency of ties that, when ignored, result in an overestimation of the treatment effect in a WR calculation. The WR is most accurate in estimating an overall effect when there are few or no ties . One proposed solution for this is to calculate a win odds (WO). In the WO, one-half of all ties are added to the wins for the treatment arm and control arms, respectively.The demonstration that an intervention has achieved its intended effects is an important legal and ethical standard that must be achieved before an intervention is introduced into general clinical practice. The statistical method by which this efficacy is established must undergo the highest level of scrutiny. We have described 5 fallacies of using the WR that highlight the complexity within this seemingly simple analytical method. As use of the WR becomes more common in cardiovascular trials, to complement the FDA’s recent guidance on the analysis of composite endpoints, we believe that the time has come to convene key stakeholders to outline consensus guidance on how (and when) the WR should be used in the analysis and interpretation of cardiovascular trials. We offer several suggestions for the optimal use and clinical interpretation of the WR within cardiovascular trials. A clinician should not stop interpretation at the WR statistic outcome alone. They must seek to understand the overall treatment effect (by accounting for ties and dropouts) and to have sufficient information from the analyses to ascertain a number needed to treat or harm. Thus, an assessment of aggregate clinical benefit is necessary to translate information from trials that demonstrate wins using the WR to not only appreciate the magnitude of effect, but temporal relationships of outcomes, their durability, and finally the overall value (or cost effectiveness). Similarly, what drives the overall win must be clearly depicted and whether a placebo effect may exist .Figure 2We also offer some important solutions to overcome the inherent challenges described in the various fallacies of using the WR or when to avoid its use. First, we recommend the traditional frequentist statistical methods approach over the simplistic WR in select scenarios. For instance, if the treatment effect is likely to be limited to nonfatal outcomes and a minimal treatment effect on mortality is anticipated, enrolling a population with an otherwise high mortality rate (from competing risk) could result in a significant loss of statistical power for the WR . If significant dropout is anticipated , the introduction of bias with censoring before study completion creates a greater risk in WR assessment. By contrast, the proportional hazards model includes a well-established method for dealing with such participants or use of a Fine-Gray competing risk model analysis should be used.In summary, although the WR offers a novel method of depiction of outcomes in clinical trials, its advantages may be counterbalanced by several potential fallacies in its conduct and clinical interpretation for which we have provided a framework to overcome such limitations and enhance the value of such utility across the clinical trial enterprise.Dr Mehra has received travel support and consulting fees, paid to Brigham and Women’s Hospital, from Abbott; fees for serving on a steering committee from Medtronic and Janssen (Johnson & Johnson); fees for serving on a data and safety monitoring board from Mesoblast; consulting fees from Natera, Paragonix, Moderna, the Baim Institute of Clinical Research, and Broadview Ventures; and fees for serving as a scientific board member from NuPulseCV, Leviticus, Transmedics and FineHeart. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.


Individual Shantala Infant Massage is an intervention that is offered by several Dutch Preventive Child Healthcare (PCH) organizations as optional preventive support, in addition to basic care as offered to all children. It targets vulnerable families and aims to enhance sensitive parenting and to reduce (effects of) parental stress. The intervention is carried out by a certified nurse. It consists of three structured home visits. Parents learn to massage their infant and receive parenting support. This study aims to investigate the effectiveness and the process of the intervention. The main hypothesis is that Individual Shantala Infant Massage leads to increased parental sensitive responsiveness, lower perceived and physiological parental stress, and improved child growth and development in the intervention group, compared to a control group where this intervention is not offered by PCH. Secondary research questions address effects on parenting confidence and parental concerns regarding the infant, the influence of background characteristics and the intervention process.The study is a quasi-experimental non-randomized trial. The aim is to include 150 infant-parent dyads in both the intervention and the control group. This takes into account possible attrition and missing data as 105 dyads with complete data per group are sufficient for analysis. All participants complete questionnaires at T0 , T1 , and T2 (follow-up at five months). At T2, a hair tuft is cut from the parents’ head to measure hair cortisol levels. Data on infant growth and development is obtained from PCH files. In the intervention group, additional data is collected to evaluate the intervention process: parents complete an evaluation questionnaire at T1, nurses keep semi-structured logbooks of intervention sessions and interviews are conducted with parents and professionals.Study results can contribute to the evidence base of infant massage as applied in Dutch PCH, and can inform parents, PCH practitioners, policy makers and researchers both inside and outside the Netherlands on feasibility and effectiveness of the infant massage intervention as applied in this format and setting.ISRCTN registry: ISRCTN16929184. Date (retrospectively) registered: 29/03/2022. The basis for many opportunities and inequalities in child development and health lies in the first 1000 days of life, from conception until a child is 2 years old. This is an important phase for the physical, cognitive and socio-emotional development of children . ParentaThe Netherlands has a solid Preventive Child Healthcare (PCH) system to promote health, prevent diseases, and enable early identification of problems in the physical, psychological, social and cognitive domains in children. Basic preventive care is provided to all children aged 0–18 years, including periodic health check-ups, vaccinations, screening, and advice e.g., on safety, lifestyle, and parenting. All PCH services are provided free of charge and they have an outreach of up to 95% . In addiA promising accessible and preventive intervention targeting parenting and stress in vulnerable parents is “The ultimate goal of the intervention is to foster a secure attachment relationship between parent and child by 1) increasing parental sensitive responsiveness, 2) increasing parenting confidence, and 3) reducing (effects of) stress, by improving stress coping and reducing experienced parenting stress of the parent, reducing stress and fussiness in the infant and reducing physiological stress in both the parent and the infant. The goals of the intervention are presented in Fig. Effects of infant massage have been studied before, on a wide range of outcomes. In premature infants, infant massage has been associated with shorter hospital stays, better infant growth and health, as well as reduced parent anxiety, depression and stress , 23). PoInfant massage is also supposed to promote positive parent–child interaction, because the parent learns to recognize signals better, reacts sensitively and makes eye contact e.g. . OxytociDespite these promising results, the evidence base is still limited. In some studies there is a high risk of bias , 25. MorResearch on infant massage programs to promote the parent–child relationship also showed that effects can depend on content as well as the target population , 35. BasSeveral of the elements that have been identified as important for effectiveness in infant massage interventions to improve the parent-infant interaction , 35 are Individual Shantala Infant Massage is offered to parents with moderate problems, who experience stress in child-raising, caring for the baby or parenting, or have an increased risk of these forms of stress or problems interacting with the baby. The embedding in PCH services facilitates initial contact with the target group. As 95% of parents of young children are in regular contact with PCH , professThe feasibility and promise of the intervention is supported by process evaluations of a PCH organization that provides this intervention as preventive support , . PCH professionals consider infant massage a feasible intervention that is highly appreciated as a tool for helping vulnerable families and their infants. Participating parents indicated that they learned the infant massage techniques but that they also learned to better recognize the signals of their infant, felt more supported in dealing with their infant, that the contact with their infant had improved and that their infant cried less.Taken together, the intervention Individual Shantala Infant Massage could be a promising answer to the demand for easily accessible interventions to support vulnerable families during infancy.Although the intervention is theoretically well-founded and evaluations from participating parents and professionals are promising, no controlled impact study has yet been conducted to study the effects of this intervention. Therefore, the aim of this quasi-experimental study is to investigate the effectiveness as well as the process of the Individual Shantala Infant Massage intervention as carried out in PCH.parental stress, both perceived stress as well as physiological stressparental sensitive responsivenesschild development and growthWhat are the effects of Individual Shantala Infant Massage carried out in PCH on:Our primary research question is:We hypothesize that the intervention Individual Shantala Infant Massage will lead to an increase in parental sensitive responsiveness, lower reported and physiological stress of the parent and improved child growth and development in the intervention group, compared to a control group where the intervention is not part of the PCH care offer.2.parenting confidence crying, feeding and sleeping behaviour of the infantWhat are effects of Individual Shantala Infant massage on:3.Which subgroups may profit the most / least from the intervention?We hypothesize that the intervention will lead to increased parenting confidence and a decrease of parental concerns . Research question 3 is explorative.Secondary research questions are:4.How do intermediate  and end users (parents) evaluate the intervention, including preconditions for further implementation?Finally, our last secondary research question is focused on the evaluation of the intervention process:The study has a quasi-experimental design. It is a non-randomized trial, carried out in the setting of PCH. A comparison is made between an intervention group and a control group: the intervention group consists of parent-infant dyads who receive the intervention Shantala Infant Massage as part of the care offered by their PCH organization. The control group consists of parent-infant dyads whose PCH organization does not offer this intervention as part of their standard care. Participant recruitment started in August 2021 and will end mid-2023. Data collection will continue until the end of 2023.Prior to acceptance, the relevance and quality of the grant application were peer-reviewed by a team of  experts of the grant provider ZonMw. The Research Ethics Committee of the Radboud University Medical Centre in Nijmegen, The Netherlands (CMO region Arnhem-Nijmegen) judged this study not to be subject to the Medical Research Involving Human Subjects Act , file number 2021–8221. The internal independent review board of TNO reviewed and approved the study’s compliance with laws and regulations concerning privacy sensitive data, reference number 2021–054. The study is conducted in accordance with guidelines and regulations of the Declaration of Helsinki. Prior to participation, all participants will receive information about the study and will provide informed consent. The study is registered in the ISRCTN registry, reference number ISRCTN16929184 . Any subd = 0.50) was included as the basis for the power and sample size calculation. Based on an ANOVA analysis between two groups of equal size with a Cohen’s d effect size of 0.50, 84 participants per research arm are required for a power of 0.9. However, because it is not possible to randomly assign participants or clusters, it is necessary to correct for possible differences between the groups e.g. by adding covariates or applying propensity score weighting [As effect sizes as found in previous research were heterogenous (see Introduction), a medium effect size  in the city of Rotterdam and PCH Kennemerland (In Dutch: Jeugdgezondheidszorg Kennemerland) in Haarlem and surrounding  areas. Parent–child dyads are eligible for participation in the study when they are about to engage in the Individual Shantala Infant Massage intervention, the infant is younger than 16 weeks and the parent is able to understand the study information and to complete the questionnaires in Dutch or English, with assistance if necessary. The parent taking part in the infant massage, is invited to participate in the study.Participants of the control group are recruited via the PCH organization in Amsterdam, which is part of the GGD Amsterdam. Recruitment is focused on 7 PCH locations within three specific areas of the Amsterdam region with relatively high rates of vulnerability in multiple domains. Inclusion criteria for parent–child dyads regarding the age of the infant and language understanding are similar as for the intervention group. The parent who spends most time with the infant is invited to participate in the study.For both the intervention and control group, suitable participants are notified of the study by PCH professionals. Contact information of interested parents is forwarded to the researchers with permission of the parents. Parents receive additional information on the research in a simple and accessible format. Participant information is provided in a written format, as well as in videos on a project website. To avoid desirable answers in the intervention group and to make participation more appealing for the control group, there is no emphasis on the effects of infant massage in the participant information. Instead, the focus of the study is described more generally, namely, the study is described as being about the wellbeing of infants and parents in the first 6 months and the support provided by PCH organizations during this period, including infant massage. Furthermore, parents are informed about the collection, storage, use and reuse of the data , privacy regulations and rights under GDPR and contact information of the research team in case of complaints or questions.The parents are given time (a couple of days) to consider participation. Parents’  consent form precedes the pre-test questionnaire. In case the informed consent form and the questionnaire are not yet completed after some time, the researchers contact the parents via e-mail and/or phone to check if everything was clear and as a reminder. For the intervention group, it is important that the first questionnaire is completed before the start of the intervention. All parents who provide informed consent and complete the first questionnaire are enrolled in the study. After their study participation is completed, participants receive a gift voucher of 15 euros as a thank-you.Parents in the intervention group all receive Individual Shantala Infant Massage. This preventive intervention is aimed at parents with a risk of low sensitive parenting behaviour and/or  a risk of attachment issues. Examples of signals thereof taken into account by PCH at the parent level are: depressive symptoms, single, very young, unrealistic views about parenting, adverse childhood experiences, mental challenges, difficulties with parenting, pregnancy or delivery. Examples of signals in the parent–child interaction are: struggles to cope with infant crying, difficulties to adapt to the infant’s temperament, inadequate touching behaviour or little affective body contact, little to no emotional support , lack of talking to the infant, not taking the infant into account and a lack of structure. When PCH professionals (nurses or physicians) notice these signals during PCH contact moments through observation and based on the conversation with the parent, the parent can be offered enrolment in the intervention. The intervention is offered as part of selective preventive PCH services, in addition to regular care as usual (see below).A detailed description of the Individual Shantala Infant Massage intervention is provided on the website of the Dutch registry of health interventions . The intAfter intervention completion, the parent is allowed to contact the nurse with questions if necessary. Participation in the intervention is registered in the PCH child file, so (other) PCH professionals can ask about it during subsequent contact moments. If it appears that follow-up action and/or additional care is required for the family, necessary steps will be undertaken.All parents, both in the intervention and in the control group, receive the regular basic preventive care from their PCH organization including periodic health check-ups, the monitoring of growth and development, advice e.g. on safety, lifestyle and parenting, and possible referral to other services. Additionally, the intervention group receives the Individual Shantala Infant Massage intervention as part of selective preventive care provided by their PCH organization.The study consists of three measurement moments: a pre-test , a post-test  or approximately four weeks after T0 (control group), and follow-up . Table Parents complete questionnaires at T0, T1, and T2. All questionnaires are administered digitally via a secure website by default, but participants can receive a paper version upon request. At T2, a tuft of hair is cut from the parents’ head for the assessment of hair cortisol levels. The hair is cut during the 5-month contact moment at the PCH organization or at home by a member of the research team, depending on the PCH organization. Data on infant growth and development from birth up to six months that are collected by PCH as part of standard care, will be obtained from the PCH files.In the intervention group, additional data is collected for the purpose of process evaluation. Between T0 and T1, the nurses carrying out the intervention keep semi-structured logbooks of the intervention sessions. At T1, parents complete an extra evaluation questionnaire. Finally, interviews are conducted with a number of parents and professionals.Perceived stress. Perceived parental stress is measured using two self-report questionnaires: the Perceived Stress Scale  and the, the MoIn the MRQ  seven coThe MIBS  aims to The Cry Perception Scale  measuresData on infant growth (weight and length) and development  will be calculated for weight and length for every measurement moment. This number indicates the difference with respect to the gender and age-specific average, expressed in standard deviations, enabling comparisons over time and between groups.The Van Wiechen Scheme is the Dutch equivalent of the Bayley scales and is used to measure development in children in a systematic way . It consParenting confidence is assessed with the Karitane Parenting Confidence Scale . The KPParental concerns regarding crying, nutrition and sleep behavior of the infant are assessed using three five-point Likert scales. An example item is ‘I worry about the crying of my baby’. Answer options range from ‘Strongly agree’ to ‘Strongly disagree’. On another five-point Likert scale, parents can rate if they worry about other things concerning the baby (‘Strongly agree’ to ‘Strongly disagree’), followed by an open text field where they can list things concerning the baby where they worry about.In order to control for possible group differences and to aid a correct interpretation of the results, we assess a variety of relevant background variables and possible confounders. Characteristics that are assessed with regard to the responding parent and the family include: date of birth, gender, country of birth of the responding parent and his/her parents, educational level, relationship status, living situation (living with/without partner), health, sleep, anxiety and depressive symptoms  includes questions concerning frequency, duration, content of and satisfaction with the infant massage intervention. The semi-structured logbooks the intervening professionals (nurses) complete after each intervention session, consist of pre-structured registration booklets. Amongst other things, the nurses are asked to indicate to what extent the goals of the session have been achieved, if they deviated from the standard procedure and if so, why and in what way, and whether the contact and cooperation with the parents was pleasant. Finally, interviews are conducted with five to ten parents who participated in the intervention and 4–6 professionals, focused on their experiences with the intervention, recommendations, and preconditions for (further) implementation.All data will be handled strictly confidentially and in accordance with the guidelines of the EU General Data Protection Regulation. All procedures with regard to handling of the data are described in a Data Management Plan, which is submitted to the grant provider ZonMw.Data used for analyses is pseudonymized after data collection, by giving each respondent a respondent number. The list of names with respondent numbers is kept separately from the research data. All digital data is stored in a secured vault at (TNO) SharePoint Online, with access restricted for project members only. The data is located within the European Union (Ireland and the Netherlands). Access to the information is only possible through Multi Factor Authentication. TNO makes a daily back-up of the information. Both for SharePoint Online and for the backup use is made of encryption 'in transit' and 'at rest’. Paper questionnaires are marked with the respondent number. After completion, the papers are scanned and subsequently destroyed. The answers are entered into the digital datasets. Both the scanned questionnaires and the datasets are stored in the secured vault at (TNO) SharePoint Online as described above. Collected hair samples are marked with the respondent number, and are securely stored in areas with limited access, both at the PCH locations and at TNO until the samples are sent away to the lab (Dresden LabService GmbH) to be analyzed and subsequently discarded.p-value) is set at p < 0.05 in all analyses.All data is to be handled according to standard procedures. Demographic characteristics and study outcomes will be described for each group, using means and standard deviations for continuous outcomes and proportions for categorical data. The comparability of the groups at baseline (T0) will be explored. Differences will be taken into account during further analyses. The pattern of missingness will be checked before the analyses. All measures will be controlled for outliers and checked for normality. Skewed continuous outcomes will be transformed. The level of significance (T-tests and (multilevel and multivariate) analyses of (co)variance. Differences between the intervention group and the control group at T1 and at T2 will be assessed, while correcting for the baseline measures (T0). Additionally, we will correct for possible differences between the groups by adding covariates or by applying propensity score weighting [Primary and secondary outcomes will be compared between the intervention and control groups using eighting . In the The results of the study will be shared with relevant stakeholders in a number of deliverables. The findings will be used to update the intervention registration in the Dutch intervention database  and willDutch PCH professionals have the opportunity to support vulnerable families in early life, since they are in regular contact with most parents of young children. However, there is a lack of available, easily accessible evidence-based interventions for this target group . The preThis study protocol presents the design of a non-randomized trial to evaluate the effects and the intervention process of Individual Shantala Infant Massage in the daily practice of PCH. It is hypothesized that the intervention will lead to an increase in parental sensitive responsiveness, lower reported and physiological stress of the parent and improved child growth and development in the intervention group, compared to a control group where the intervention is not part of the standard PCH care offer. Secondary hypotheses are that the intervention will lead to increased parenting confidence and a decrease of parental concerns . An exploratory secondary research question is whether specific subgroups profit more or less from this intervention. The intervention process is evaluated based on logbooks of professionals, questionnaires for parents and interviews.This study has several strengths. First, it is conducted in the daily practice of the PCH, which enables us to investigate the intervention in ‘real life’ rather than in an experimental setting, which supports the generalizability of our findings. Second, the study has a mixed-method design, combining information from multiple sources, including questionnaires, a physiological measurement of parental stress, PCH data on child growth and development, and an evaluation questionnaire, logbooks of the intervention sessions and interviews with both parents and professionals. However, the study also has limitations that need to be noted. The study is non-randomized, which may affect the comparability of the groups. In order to reduce the potential effects of non-randomization, we use a pre-post design. Furthermore, we attempt to control for possible group differences by assessing the most important confounders. However, the possibility of residual confounding remains and should be taken into account when interpreting the results. We also expect to encounter some challenges. The target group of the intervention, and thereby of this study, consists of parents with a young baby who may be vulnerable. This is a group where inclusion may be difficult and drop-out is to be expected. We hope to overcome this challenge by recruiting participants through and in close collaboration with PCH professionals who already are in direct contact with these parents. Furthermore, we try to lower the threshold to participate by making the study information accessible and comprehensible, by minimizing the burden by selecting questionnaires that are as short and as simple as possible, and by maintaining low-key contact with participants.This is the first controlled effect and process evaluation of the intervention Individual Shantala Infant Massage. The study can contribute to the evidence base of individual infant massage as applied in Dutch preventive child healthcare practice. As a result, the intervention may be acknowledged at a higher level of effectiveness in the national intervention database. Study results can inform parents, PCH professionals, researchers, and policy makers, both inside and outside the Netherlands, on the feasibility and effectiveness of the Individual Shantala Infant Massage intervention. A strengthened evidence base and insights on implementation and required conditions can help to facilitate a broader implementation of this intervention by other PCH organizations in the future. This contributes to easily accessible support for vulnerable families in order to reduce (effects) of stress and to improve positive parenting and parent-infant relationships.


Various physical and sporting activities involve immersion in water, and therefore confrontation with the specific constraints of the aquatic environment. Resistance to movement and forward motion is thus increased, and competitive and recreational swimming is the prime example. For this reason, and because it has an impact on the metabolism and general physiology of living organisms, water immersion is a physical activity frequently used to achieve specific goals, including in the field of performance. Moreover, by counteracting the effects of gravity (Archimedes’ buoyancy principle), immersion allows for the execution of muscular activity with reduced joint constraints, making it beneficial for rehabilitation purposes. The aquatic environment is also frequently used for recovery, as in the case of cold-water immersion to promote thermal losses. Finally, immersion appears to have a relaxing effect, justifying its application for therapeutic purposes. The Research Topic focuses on aspects of physiology, training, performance enhancement and rehabilitation in and through physical and sporting activities in water.Rudnik et al. found no significant differences between men and women’s reaction time but the total start time (15-m), the duration of component parts (5 and 10-m), and almost all of the time periods of starting phases were shorter in male swimmers. This study defines which variables should be considered while evaluating start performance in male and female swimmers separately. The management of swimming training planning must not only take sex into account, but also age. As participation in swimming can start at a very young age and continue into the advanced years, because it is an “unloaded” sport , the question of early specialization arises. By comparing the model of performance progression (between 2006 and 2017) for countries grouped by continent, Yustres Amores et al. showed that, with the exception of America, swimmers who have already taken part in the world junior championships perform better in the same competition in the senior category than their counterparts who have not.The aquatic environment is conducive to various forms of physical activity. Due to the increased resistance to movements, its counterbalancing effect on gravity, and its thermal conductivity, water immersion is also regularly used in the context of rehabilitation or recovery after sport and exercise. It has been shown that sex has a significant impact on sports performance. During swimming an increase in energy cost with distance was higher for men than women independent of the differences in body composition . In thei3−) beetroot juice increases blood nitric oxide concentration promoting capillary vasodilatation and muscle perfusion. Consequently beetroot is a dietary supplement regularly used by participants in various physical activities .Because of the increase in competitiveness in high-level sport, any increase in performance, however small can make the difference during high level competition. Since it contains high levels of inorganic nitrate  to adapt to the specific properties of the aquatic environment. Integrative research is needed to deepen our knowledge in this field and continue to offer practical applications.