JMIR Publications

JMIR Research Protocols

Ongoing Trials, Grant Proposals, Formative Research, Methods, Early Results


Journal Description


JMIR Research Protocols (ISSN 1929-0748) publishes peer-reviewed, openly accessible research ideas and grant proposals, study and trial protocols, reports of ongoing research, current methods and approaches, and preliminary results from pilot studies or formative research informing the design of medical and health-related research and technology innovations.

  • JMIR Res Protoc is a new journal spin-off of JMIR, the worlds' leading medical journal in health sciences / health services research and health informatics (Impact Factor: 4.7)
  • JMIR Res Protoc publishes protocols and grant proposals in all areas of medicine (and their peer-review reports, if available), as well as feasibility studies, early reports and formative/process evaluations of ongoing studies and descriptions of the development and pilot evaluations of innovations and software applications or other interventions
  • JMIR Res Protoc is fully open access, with full text articles deposited in PubMed Central
  • Publishing research protocols, grant proposals, pilot/feasibility studies and early reports of ongoing and planned work encourages collaboration and early feedback, and reduces duplication of effort 
  • JMIR Res Protoc will be a valuable ressource for researchers who want to learn about current research methodologies and how to write a winning grant proposal
  • JMIR Res Protoc creates an early scientific record for researchers who have developed novel methodologies, software, innovations or elaborate protocols
  • JMIR Res Protoc faciliates subsequent publication of results demonstrating that the methodology has already been reviewed, and reduces the effort of writing up the results, as the protocol can be easily referenced
  • JMIR Res Protoc demonstrates to reviewers of subsequent results papers that authors followed and adhered to carefully developed and described a-priori methods
  • Studies whose protocols or grant proposal have been accepted in JMIR Res Protoc are "in principle accepted" for subsequent publication of results in other JMIR journals as long as authors adhere to their original protocol - regardless of study results (even if they are negative), reducing publication bias in medicine
  • Authors publishing their protocols in JMIR Res Protoc will receive a 20% discount on the article processing fee if they publish their results in another journal of the JMIR journal family (for example, JMIR for ehealth studies, i-JMR for others)

Recent Articles:

  • Source:; CC 2.0 Attribution: Brett Jordan; modified using image from authors.

    Development of the Lupus Interactive Navigator as an Empowering Web-Based eHealth Tool to Facilitate Lupus Management: Users Perspectives on Usability and...


    Background: Systemic Lupus Erythematosus (SLE) is a serious, complex, and chronic illness. Similar to most other chronic illness states, there is great interest in helping persons with SLE engage in their disease management. Objective: The objectives of this study were to (1) develop the Lupus Interactive Navigator (LIN), a web-based self-management program for persons with SLE, and (2) test the LIN for usability and acceptability. Methods: The LIN development platform was based on the results of preliminary comprehensive needs assessments and adapted from the Oncology Interactive Navigator, a web-based tool developed for persons with cancer. Medical researchers, writers, designers, and programmers worked with clinical experts and persons with SLE to develop content for the LIN. Usability and acceptability of the LIN was tested on individuals with SLE meeting American College of Rheumatology criteria, who were recruited from five Canadian SLE clinics. Participants were provided with access to the LIN and were asked to use it over a two-week period. Following the testing period, participants were contacted for a 30-minute telephone interview to assess usability and acceptability. Results: The content for the LIN was subdivided into six primary information topics with interview videos featuring rheumatologists, allied health professionals, and persons with SLE. Usability and acceptability of the LIN was tested on 43 females with SLE. Of these, 37 (86%) completed telephone interviews. The average age was 43.6 (SD 15.9) years and disease duration averaged 14.1 (SD 10.8) years. Median time spent on LIN was 16.3 (interquartile range [IQR]:13.7, 53.5) minutes and median number of sessions was 2 (IQR: 1, 3). Overall, Likert ratings (0=strongly disagree; 7=strongly agree) of website usability and content were very high, with 75% scoring >6 out of 7 on all items. All participants agreed that LIN was easy to use, would recommend it to others with SLE, and would refer to it for future questions about SLE. Very high ratings were also given to relevancy, credibility, and usefulness of the information provided. Overall, 73% of the participants rated all topics helpful to very helpful. Participants who reported more prior knowledge about SLE rated items regarding improvement in knowledge and helpfulness relatively lower than persons with less prior knowledge. Most participants commented that the LIN would be very useful to those newly diagnosed with SLE. Minor revisions were recommended. Conclusions: This study furthers the understanding of the needs in the SLE community and delivers a unique eHealth tool to promote self-management in persons with SLE. The LIN was found to be highly acceptable in content and usability. The information provided on LIN may be most helpful for individuals with less experience with the disease, such as those newly diagnosed, indicating the need to tailor the content for persons with more SLE experience.

  • Feed advertisement targeted to males over 45 years with diabetes.

    An Evaluation of Web- and Print-Based Methods to Attract People to a Physical Activity Intervention


    Background: Cost-effective and efficient methods to attract people to Web-based health behavior interventions need to be identified. Traditional print methods including leaflets, posters, and newspaper advertisements remain popular despite the expanding range of Web-based advertising options that have the potential to reach larger numbers at lower cost. Objective: This study evaluated the effectiveness of multiple Web-based and print-based methods to attract people to a Web-based physical activity intervention. Methods: A range of print-based (newspaper advertisements, newspaper articles, letterboxing, leaflets, and posters) and Web-based (Facebook advertisements, Google AdWords, and community calendars) methods were applied to attract participants to a Web-based physical activity intervention in Australia. The time investment, cost, number of first time website visits, the number of completed sign-up questionnaires, and the demographics of participants were recorded for each advertising method. Results: A total of 278 people signed up to participate in the physical activity program. Of the print-based methods, newspaper advertisements totaled AUD $145, letterboxing AUD $135, leaflets AUD $66, posters AUD $52, and newspaper article AUD $3 per sign-up. Of the Web-based methods, Google AdWords totaled AUD $495, non-targeted Facebook advertisements AUD $68, targeted Facebook advertisements AUD $42, and community calendars AUD $12 per sign-up. Although the newspaper article and community calendars cost the least per sign-up, they resulted in only 17 and 6 sign-ups respectively. The targeted Facebook advertisements were the next most cost-effective method and reached a large number of sign-ups (n=184). The newspaper article and the targeted Facebook advertisements required the lowest time investment per sign-up (5 and 7 minutes respectively). People reached through the targeted Facebook advertisements were on average older (60 years vs 50 years, P<.001) and had a higher body mass index (32 vs 30, P<.05) than people reached through the other methods. Conclusions: Overall, our results demonstrate that targeted Facebook advertising is the most cost-effective and efficient method at attracting moderate numbers to physical activity interventions in comparison to the other methods tested. Newspaper advertisements, letterboxing, and Google AdWords were not effective. The community calendars and newspaper articles may be effective for small community interventions. ClinicalTrial: Australian New Zealand Clinical Trials Registry: ACTRN12614000339651; (Archived by WebCite at

  • Construction workers. Image (c) Jeppe Ajslev at al., licensed under Creative Commons 2.0. Please cite as

    Reducing Physical Risk Factors in Construction Work Through a Participatory Intervention: Protocol for a Mixed-Methods Process Evaluation


    Background: Previous research has shown that reducing physical workload among workers in the construction industry is complicated. In order to address this issue, we developed a process evaluation in a formative mixed-methods design, drawing on existing knowledge of the potential barriers for implementation. Objective: We present the design of a mixed-methods process evaluation of the organizational, social, and subjective practices that play roles in the intervention study, integrating technical measurements to detect excessive physical exertion measured with electromyography and accelerometers, video documentation of working tasks, and a 3-phased workshop program. Methods: The evaluation is designed in an adapted process evaluation framework, addressing recruitment, reach, fidelity, satisfaction, intervention delivery, intervention received, and context of the intervention companies. Observational studies, interviews, and questionnaires among 80 construction workers organized in 20 work gangs, as well as health and safety staff, contribute to the creation of knowledge about these phenomena. Results: At the time of publication, the process of participant recruitment is underway. Conclusions: Intervention studies are challenging to conduct and evaluate in the construction industry, often because of narrow time frames and ever-changing contexts. The mixed-methods design presents opportunities for obtaining detailed knowledge of the practices intra-acting with the intervention, while offering the opportunity to customize parts of the intervention.

  • Image Source: New sit-stand workstation for my office, copyright John M,,
Licensed under Creative Commons Attribution cc-by 2.0

    Organizational-Level Strategies With or Without an Activity Tracker to Reduce Office Workers’ Sitting Time: Rationale and Study Design of a Pilot...


    Background: The office workplace is a key setting in which to address excessive sitting time and inadequate physical activity. One major influence on workplace sitting is the organizational environment. However, the impact of organizational-level strategies on individual level activity change is unknown. Further, the emergence of sophisticated, consumer-targeted wearable activity trackers that facilitate real-time self-monitoring of activity, may be a useful adjunct to support organizational-level strategies, but to date have received little evaluation in this workplace setting. Objective: The aim of this study is to evaluate the feasibility, acceptability, and effectiveness of organizational-level strategies with or without an activity tracker on sitting, standing, and stepping in office workers in the short (3 months, primary aim) and long-term (12 months, secondary aim). Methods: This study is a pilot, cluster-randomized trial (with work teams as the unit of clustering) of two interventions in office workers: organizational-level support strategies (eg, visible management support, emails) or organizational-level strategies plus the use of a waist-worn activity tracker (the LUMOback) that enables self-monitoring of sitting, standing, and stepping time and enables users to set sitting and posture alerts. The key intervention message is to ‘Stand Up, Sit Less, and Move More.’ Intervention elements will be implemented from within the organization by the Head of Workplace Wellbeing. Participants will be recruited via email and enrolled face-to-face. Assessments will occur at baseline, 3, and 12 months. Time spent sitting, sitting in prolonged (≥30 minute) bouts, standing, and stepping during work hours and across the day will be measured with activPAL3 activity monitors (7 days, 24 hours/day protocol), with total sitting time and sitting time during work hours the primary outcomes. Web-based questionnaires, LUMOback recorded data, telephone interviews, and focus groups will measure the feasibility and acceptability of both interventions and potential predictors of behavior change. Results: Baseline and follow-up data collection has finished. Results are expected in 2016. Conclusions: This pilot, cluster-randomized trial will evaluate the feasibility, acceptability, and effectiveness of two interventions targeting reductions in sitting and increases in standing and stepping in office workers. Few studies have evaluated these intervention strategies and this study has the potential to contribute both short and long-term findings.

  • Source:, CC0 Public Domain.

    Prevalence, Motivations, and Social, Mental Health and Health Consequences of Cyberbullying Among School-Aged Children and Youth: Protocol of a Longitudinal...


    Background: While the online environment may promote important developmental and social benefits, it also enables the serious and rapidly growing issue of cyberbullying. Cyberbullying constitutes an increasing public health problem – victimized children and youth experience a range of health and mental health concerns, including emotional and psychosomatic problems, maladaptive behaviors, and increased suicidality. Perpetrators demonstrate a lack of empathy, and may also struggle with health and mental health issues. Objective: This paper describes the protocols applied in a longitudinal and multi-perspective mixed-methods study with five objectives: (1) to explore children/youth’s experiences, and children/youth’s, parents’, and teachers’ conceptions, definitions, and understanding of cyberbullying; (2) to explore how children/youth view the underlying motivations for cyberbullying; (3) to document the shifting prevalence rates of cyberbullying victimization, witnessing, and perpetration; (4) to identify risk and protective factors for cyberbullying involvement; and (5) to explore social, mental health, and health consequences of cyberbullying. Methods: Quantitative survey data were collected over three years (2012-2014) from a stratified random baseline sample of fourth (n=160), seventh (n=243), and tenth (n=267) grade children/youth, their parents (n=246), and their teachers (n=103). Quantitative data were collected from students and teachers during in-person school visits, and from parents via mail-in surveys. Student, parent, and teacher surveys included questions regarding: student experiences with bullying/cyberbullying; student health, mental health, and social and behavioral issues; socio-demographics; and information and communication technology use. In-depth semi-structured qualitative interviews were conducted twice with a sub-sample of students (n=57), purposively selected based on socio-demographics and cyberbullying experience, twice with their parents (n=50), and once with their teachers (n=30). Results: Data collection for this study is complete. Planned analyses include transition probabilities and repeated measures analyses to determine involvement in cyberbullying. Repeated measures analyses, including between-subject factors (eg, socio-demographics), will be utilized to determine factors that protect or increase risk of involvement in cyberbullying. Qualitative analysis utilizing grounded theory is planned, to permit rich understanding of participant experiences and perspectives. Results will be reported in 2016 and 2017. Conclusions: This study will offer insight into the contemporary phenomenon of cyberbullying while also informing interventions to curb cyberbullying and address its pervasive social, mental health, and health consequences. Knowledge mobilization strategies and implications for research and practice are discussed.

  • Image source and copyright: the authors.

    A Decision Aid for Women Considering Neoadjuvant Systemic Therapy for Operable Invasive Breast Cancer: Development and Protocol of a Phase II Evaluation...


    Background: Neoadjuvant systemic therapy is offered to selected women with large and/or highly proliferative operable breast cancers. This option adds further complexity to an already complex breast cancer treatment decision tree. Patient decision aids are an established method of increasing patient involvement and knowledge while decreasing decisional conflict. There is currently no decision aid available for women considering neoadjuvant systemic therapy. Objective: We aimed to develop a decision aid for women diagnosed with operable breast cancer and considered suitable for neoadjuvant systemic therapy, and the protocol for a multicenter pre-post study evaluating the acceptability and feasibility of the decision aid. Methods: The decision aid was developed through literature review, expert advisory panel, adherence to the International Patient Decision Aid Standards, and iterative review. The protocol for evaluation of the decision aid consists of the following: eligible women will undertake a series of questionnaires prior to and after using the decision aid. The primary endpoint is decision aid acceptability to patients and investigators and the feasibility of use. Secondary endpoints include change in decisional conflict, participant knowledge, and information involvement preference. Feasibility is defined as the proportion of eligible participants who use the decision aid to help inform their treatment decision. Results: This study has recruited 29 out of a planned 50 participants at four Australian sites. A 12-month recruitment period is expected with a further 12-months follow-up. Conclusions: The decision aid has the potential to allow patients with operable breast cancer, who have been offered neoadjuvant systemic therapy, decreased decisional conflict, and greater involvement in the decision. If this study finds that an online decision aid is feasible and acceptable, it will be made widely available for routine clinical practice. Trial Registration: Australian and New Zealand Clinical Trials Registry ACTRN12614001267640; (Archived by WebCite at

  • Source:; CC0 Public Domain, modified using image from authors.

    Developing a Web-Based Version of An Exercise-Based Rehabilitation Program for People With Chronic Knee and Hip Pain: A Mixed Methods Study


    Background: Osteoarthritis is highly prevalent and has enormous personal and socioeconomic impact. Enabling Self-management and Coping with Arthritic Pain through Exercise (ESCAPE-pain) is an integrated rehabilitation program that helps people understand how exercise can improve physical and psychosocial well-being. Unfortunately, its availability is limited. A Web-based version of the program could increase access for more people. Many Web-based resources are developed without end-user input and result in over-complex, unwanted, ineffective products with limited uptake. Objective: The objective of this study was to codesign a Web-based version of ESCAPE-pain that people with chronic joint pain find engaging, informative, and useful. Methods: To establish older persons' Internet use we conducted a postal survey of 200 people. To establish their opinions, likes or dislikes, and requirements for a Web-based version of the ESCAPE-pain program, we conducted two focus groups with 11 people who had participated in a program based on ESCAPE-pain and two with 13 people who had not. Information from the postal survey and focus groups was used to develop an online prototype website. People's opinions of the prototype website were gauged from thematic analysis of eight semistructured “think aloud” interviews. Results: The survey response rate was 42% (83/200), of whom 67% (56/83) were female and mean age was 67 years. Eighty-three percent of the people had used the Internet, 69% described themselves as either very confident or confident Internet users, and 77% had looked online for health information. With regard to participating online, 34% had read a commentary or watched a video of someone else’s experience of a health problem and 23% had tracked a health issue. Key qualitative themes emerged that included engagement, acceptability and usability, and structure and content of the program. Conclusions: Older people use the Internet as a source of health information but have concerns about safe use and quality of information. Users require a credible website that provides personalized information, support, monitoring, and feedback.

  • LHIV logo.  Source and Copyright Shabnam et al. Retrieved from

    Perspectives of People Living with HIV on Access to Health Care: Protocol for a Scoping Review


    Background: Strategies to improve access to health care for people living with human immunodeficiency virus (PLHIV) have demonstrated limited success. Whereas previous approaches have been informed by the views of health providers and decision-makers, it is believed that incorporating patient perspectives into the design and evaluations of health care programs will lead to improved access to health care services. Objective: We aim to map the literature on the perspectives of PLHIV concerning access to health care services, to identify gaps in evidence, and to produce an evidence-informed research action plan to guide the Living with HIV program of research. Methods: This scoping review includes peer-reviewed and grey literature from 1946 to May 2014 using double data extraction. Variations of the search terms “HIV”, “patient satisfaction”, and “health services accessibility” are used to identify relevant literature. The search strategy is being developed in consultation with content experts, review methodologists, and a librarian, and validated using gold standard studies identified by those stakeholders. The inclusion criteria are (1) the study includes the perspectives of PLHIV, (2) study design includes qualitative, quantitative, or mixed methods, and (3) outcome measures are limited to patient satisfaction, their implied needs, beliefs, and desires in relation to access to health care. The papers are extracted by two independent reviewers, including quality assessment. Data is then collated, summarized, and thematically analyzed. Results: A total of 12,857 references were retrieved, of which 326 documents were identified as eligible in pre-screening, and 64 articles met the inclusion criteria (56% qualitative studies, 38% quantitative studies and 6% mixed-method studies). Only four studies were conducted in Canada. Data synthesis is in progress and full results are expected in June, 2016. Conclusions: This scoping review will record and characterize the extensive body of literature on perspectives of PLHIV regarding access to health care. A literature repository will be developed to assist stakeholders, decision-makers, and PLHIV in developing and implementing patient-oriented health care programs.

  • Image Credit: from  under CC0 (public domain).

    The Mobile Solutions for Immunization (M-SIMU) Trial: A Protocol for a Cluster Randomized Controlled Trial That Assesses the Impact of Mobile Phone Delivered...


    Background: Text message (short message service, SMS) reminders and incentives are two demand-side interventions that have been shown to improve health care–seeking behaviors by targeting participant characteristics such as forgetfulness, lack of knowledge, and transport costs. Applying these interventions to routine pediatric immunizations may improve vaccination coverage and timeliness. Objective: The Mobile Solutions for Immunization (M-SIMU) trial aims to determine if text message reminders, either with or without mobile phone–based incentives, sent to infant’s parents can improve immunization coverage and timeliness of routine pediatric vaccines in rural western Kenya. Methods: This is a four-arm, cluster, randomized controlled trial. Villages are randomized to one of four study arms prior to enrollment of participants. The study arms are: (1) no intervention (a general health-related text message will be texted to this group at the time of enrollment), (2) text message reminders only, (3) text message reminders and a 75 Kenyan Shilling (KES) incentive, or (4) text message reminders and a KES200 incentive. Participants assigned to study arms 2-4 will receive two text message reminders; sent 3 days before and one day before the scheduled immunization visit at 6, 10, and 14 weeks for polio and pentavalent (containing diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenza type b antigens) type b antigens) vaccines, and at 9 months for measles vaccine. Participants in incentive arms will, in addition to text message reminders as above, receive mobile phone–based incentives after each timely vaccination, where timely is defined as vaccination within 2 weeks of the scheduled date for each of the four routine expanded program immunization (EPI) vaccination visits. Mother-infant pairs will be followed to 12 months of age where the primary outcome, a fully immunized child, will be ascertained. A fully immunized child is defined as a child receiving vaccines for bacille Calmette-Guerin, three doses of pentavalent and polio, and measles by 12 months of age. General estimating equation (GEE) models that account for clustering will be employed for primary outcome analyses. Results: Enrollment was completed in October 2014. Twelve month follow-up visits to ascertain immunization status from the maternal and child health booklet were completed in February 2016. Conclusions: This is one of the first studies to examine the effect of text message reminders on immunization coverage and timeliness in a lower income country and is the first study to assess the effect of mobile money-based incentives to improve immunization coverage. Trial Registration: NCT01878435; (Archived by WebCite at

  • aMASE Study Logo.
Created by Ibidun Fakoya (author), who holds the copyright.

    Advancing Migrant Access to Health Services in Europe (AMASE): Protocol for a Cross-sectional Study


    Background: Migrants form a substantial proportion of the population affected by the human immunodeficiency virus (HIV) epidemic in Europe, yet HIV prevention for this population is hindered by poor understanding of access to care and of postmigration transmission dynamics. Objective: We present the design and methods of the advancing Migrant Access to health Services in Europe (aMASE) study, the first European cross-cultural study focused on multiple migrant populations. It aims to identify the structural, cultural, and financial barriers to HIV prevention, diagnosis, and treatment and to determine the likely country of HIV acquisition in HIV-positive migrant populations. Methods: We delivered 2 cross-sectional electronic surveys across 10 countries (Belgium, France, Germany, Greece, Italy, the Netherlands, Portugal, Spain, Switzerland, and United Kingdom). A clinic survey aimed to recruit up to 2000 HIV-positive patients from 57 HIV clinics in 9 countries. A unique study number linked anonymized questionnaire data to clinical records data (viral loads, CD4 cell counts, viral clades, etc). This questionnaire was developed by expert panel consensus and cognitively tested, and a pilot study was carried out in 2 countries. A Web-based community survey (n=1000) reached those living with HIV but not currently accessing HIV clinics, as well as HIV-negative migrants. It was developed in close collaboration with a community advisory group (CAG) made up of representatives from community organizations in 9 of the participating countries. The CAG played a key role in data collection by promoting the survey to higher-risk migrant groups (sub-Saharan Africans, Latin Americans, men who have sex with men, and people who inject drugs). The questionnaires have considerable content overlap, allowing for comparison. Questions cover ethnicity, migration, immigration status, HIV testing and treatment, health-seeking behavior, sexual risk, and drug use. The electronic questionnaires, which were available in 15 languages, allowed for complex routing, preventing respondents from answering irrelevant questions. Results: In total, we recruited 2249 participants from 57 HIV clinics as part of the clinic survey and retrieved 1637 complete responses as part of the community survey. Conclusions: The findings will provide much-needed information for improving HIV prevention interventions and access to services for migrant communities.

  • Tawazon App on Smartphone held by authors. Source and copyright: authors, Aroub Alnasser et al.

    Development of ‘Twazon’: An Arabic App for Weight Loss


    Background: Weight gain and its related illnesses have become a major public health issue across the world, with Saudi Arabia and other Gulf countries seeing dramatic increases in obesity and overweight, and yet there is very little information on how to intervene with this demographic due to cultural and linguistic barriers. As the use of smartphones and apps has also increased in the region, information communication technologies could be a cost-effective means of facilitating the delivery of behavior-modification interventions directly to the target population. Although there are existing apps that offer lifestyle-modification tools, they do not give consideration to the evidence-based practices for weight management. This offers an opportunity to create an Arabic language weight loss app that offers localized content and adheres to evidence-informed practices that are needed for effective weight loss. Objective: This paper describes the process of developing an Arabic weight loss app designed to facilitate the modification of key nutritional and physical activity behaviors among Saudi adults, while taking into consideration cultural norms. Methods: The development of the Twazon app involved: (1) reviewing all available Arabic weight loss apps and compared with evidence-based practices for weight loss, (2) conducting a qualitative study with overweight and obese Saudi women to ascertain their preferences, (3) selecting which behavioral change strategies and guidelines to be used in the app, (4) creating the Saudi Food Database, (5) deciding on graphic design for both iPhone operating system and Android platforms, including user interface, relational database, and programming code, and (6) testing the beta version of the app with health professionals and potential users. Results: The Twazon app took 23 months to develop and included the compilation of an original Saudi Food database. Eight subjects gave feedback regarding the content validity and usability of the app and its features during a pilot study. The predominant issue among the group was the lack of information explaining how to use the app. This has since been resolved through the implementation of a tutorial. No other changes were required to be made. Conclusions: Information communication technologies, such as smartphone apps, may be an effective tool for facilitating the modification of unhealthy lifestyle habits in Saudi; however, consideration must be given to the target population, cultural norms, and changing trends in the global market. The effectiveness of the app will be better determined during a 6-month intervention with 200 overweight and obese Saudi women.

  • Source:, CC-BY-3.0 Licensed.

    Determination of the Role of CBP- and p300-Mediated Wnt Signaling on Colonic Cells


    Background: The Wnt signaling pathway, mediated through active beta-catenin, is responsible for initiating the majority of cases of human colorectal cancer (CRC), and we have previously shown that hyperactivation of this pathway by histone deacetylase inhibitors (HDACis), such as butyrate, can induce the death of CRC cells. An important cellular switch that mediates the effects of Wnt-signaling activation is variation in the association between beta-catenin and the transcriptional coactivators cAMP response element binding (CREB) binding protein (CBP) and p300. Association of CBP with beta-catenin is thought to activate a set of genes linked to cell proliferation, while the p300-mediated Wnt genetic program is believed to promote cell differentiation. Small molecule agents have been discovered that modulate CBP/p300 Wnt transcriptional programs by altering the association of CBP and p300 to beta-catenin. ICG-001 and ICG-427 inhibit CBP- and p300-mediated Wnt activity, respectively, while IQ-1 prevents the shift from CBP-mediated to a p300-mediated Wnt activity. Objective: Aim 1 of this proposal is designed to determine the role of CBP- and p300-mediated Wnt signaling in the response of CRC cells to HDACis. Aim 2 is to determine the role of CBP and p300 in the maintenance of high- and low-Wnt fractions in CRC cell line. Aim 3 will compare the effects of CBP- and p300-mediated Wnt activity on CRC initiation and progression. Methods: In Aim 1, cells will be cotreated with HDACis and ICG-001, ICG-427, or IQ-1 and the levels of Wnt activity, apoptosis, proliferation, differentiation, and CBP- or p300-beta-catenin binding measured. Aim 2 of this proposal may mirror similar heterogeneity observed in human tumors and which may be of clinical significance. Aim 3 will use CRC cell line model systems of initiation and progression: the normal colon cell lines CCD-841CoN, the adenoma line LT97, the primary colon carcinoma cell line SW480, and the lymph node metastasis cell line SW620. Cells will be treated with HDACis and the small molecule agents, and assayed as described above. Results: We will also attempt to use changes in CBP- and p300-mediated Wnt signaling to shift colonic cells between cell type, modifying CBP- and p300-mediated gene expression in the LT97 adenoma line to shift the adenoma phenotype to more characteristic of the CCD-841CoN normal cells, or the SW480 carcinoma cells. We will use microarray analyses to determine the patterns of gene expression responsible for these CBP- or p300-mediated changes in colonic neoplastic phenotype. Conclusions: The findings generated from this study will lead to future, more in-depth projects to further dissect the action of CBP/p300 Wnt–mediated transcriptional programs in colonic neoplasia, with an emphasis on methods to modulate these genetic programs for chemopreventive effect.

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    Date Submitted: May 27, 2016

    Open Peer Review Period: May 27, 2016 - Jun 10, 2016

    Background: Portuguese population is ageing. The lack of data on older adults’ nutritional status as well as the lack of nutrition knowledge of health professionals, caregivers, and older adults the...

    Background: Portuguese population is ageing. The lack of data on older adults’ nutritional status as well as the lack of nutrition knowledge of health professionals, caregivers, and older adults themselves, remains a challenge. Objective: To reduce nutritional inequalities in the Portuguese older population and to improve the knowledge on Portuguese older adults’ nutritional status, specifically on undernutrition, obesity, sarcopenia, frailty, hydration, sodium and vitamin D status. Methods: A representative sample of Portuguese older adults was selected. Socio-demographic, lifestyles, anthropometric, functional and clinical data were collected. Sodium excretion, hydration and vitamin D status were assessed. Results: Data collection (n = 1,500) took place between December 2015 and May 2016. Results will be disseminated in national and international scientific journals as well in the Portuguese media. Conclusions: Nutrition UP 65 results will provide evidence for the design and implementation of effective preventive public health strategies regarding elderly. This will represent unequivocal health gains and costs savings.

  • Conventional cognitive behaviour therapy facilitated by an internet-based support system: a feasibility study at a psychiatric outpatient clinic

    Date Submitted: May 27, 2016

    Open Peer Review Period: May 27, 2016 - Jun 10, 2016

    Background: Cognitive behaviour therapies (CBT) have been shown to be effective for a variety of psychiatric and somatic disorders, but some obstacles can be noted in regular psychiatric care, e.g. lo...

    Background: Cognitive behaviour therapies (CBT) have been shown to be effective for a variety of psychiatric and somatic disorders, but some obstacles can be noted in regular psychiatric care, e.g. low adherence to treatment protocols may undermine effects. Treatments delivered via the internet have shown promising results, and it is an open question if the blend of internet-delivered and conventional face-to-face CBT may help to overcome some of the barriers of evidence-based treatments in psychiatric care. Objective: In the present study we evaluated the feasibility of an internet-based support system at an outpatient psychiatric clinic in Sweden. For instance, the support system made it possible to send messages, and share information between the therapist and the patient before and after therapy sessions at the clinic. Methods: Nine clinical psychologists participated and 33 patients were enrolled in the current study. We evaluated the usability and technology acceptance after 12 weeks of access. Moreover, clinical data on common psychiatric symptoms was assessed before and after the presentation of the support system. Results: In line with our previous study in a university setting, the internet-based support system appears to be feasible also when delivered in a regular psychiatric setting. Notably, some components in the system were less frequently used. We also found that the patients improved on common outcome measures for depressive and anxious symptoms (effect sizes, as determined by Cohen´s d, ranged from 0.29 to 0.66). Conclusions: This study adds to the literature showing that modern information technology can be aligned with conventional face-to-face services.

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    Date Submitted: May 26, 2016

    Open Peer Review Period: May 27, 2016 - Jun 10, 2016

    Background: Adverse drug events (ADEs) are unintended and harmful events related to medication use. Up to 30% of serious ADEs recur within only six months because culprit drugs are unintentionally re-...

    Background: Adverse drug events (ADEs) are unintended and harmful events related to medication use. Up to 30% of serious ADEs recur within only six months because culprit drugs are unintentionally re-prescribed and re-dispensed. Improving the electronic communication of adverse drug event information between care providers and across care settings has the potential to reduce recurrent ADEs. Objective: To describe the methods used to design a novel electronic ADE reporting system that can be leveraged to prevent unintentional re-exposures to harmful drugs. Methods: To develop the new system, we will use action research, an approach that employs social scientific research methods and practitioner participation to generate insight into work settings and resolve problems, and participatory design. We will develop a systematic search strategy to review existing ADE reporting systems identified in academic and grey literature, and analyze the content of these systems to identify ‘core’ data fields used to communicate ADE information. We will observe care providers in the emergency departments and on the wards of two urban tertiary and one urban community hospital, in a rural ambulatory care centre, and in three community pharmacies in British Columbia, Canada. We will also conduct participatory workshops with providers to understand their needs and priorities related to communicating ADEs and preventing erroneous re-prescribing or re-dispensing of culprit medications. These methods will inform the iterative development of a preliminary paper-based reporting form which we will then pilot test with providers in a real-world setting. Results: This is an ongoing project with results being published as analysis is completed. The systematic review has been completed; field observations, focus groups, and pilot testing of a preliminary paper-based design is ongoing. Results will inform the development of software that will enable clinically useful user-friendly documentation and communication ADEs. Conclusions: We take this approach with the recognition that information technology-based solutions in health care often fall short of expectations as a result of designers’ failure to account for organizational and work practice considerations and the needs of end-users. We describe how integrating qualitative methods into an iterative participatory design process, planned in partnership with end-users, will allow us to address specific clinical needs, conceptualize linkages between systems, integrate the reporting system into clinicians’ workflow, and design the system to optimize its uptake into practice.

  • A Cross-Sectional Comparison of Drugable Mutations in Primary Tumors, Metastatic Tissue, Circulating Tumor Cells and Cell-Free Circulating DNA in Patients with Metastatic Breast Cancer: The MIRROR Study Protocol

    Date Submitted: May 24, 2016

    Open Peer Review Period: May 24, 2016 - Jun 1, 2016

    Background: Characterization of the driver mutations in an individual metastatic breast cancer (MBC) patient is critical to selecting effective targeted therapies. Currently, it is believed that the l...

    Background: Characterization of the driver mutations in an individual metastatic breast cancer (MBC) patient is critical to selecting effective targeted therapies. Currently, it is believed that the limited efficacy of many targeted drugs may be due to the expansion of drug resistant clones with different genotypes that were already present in the primary tumor. Identifying the genomic alterations of these clones and introducing combined or sequential targeted regimens could lead to a significant increase in the efficacy of currently available targeted therapies. Objective: The primary objective of this study is to assess the concordance/discordance of mutations between the primary tumor and metastatic tissue in these patients. Secondary objectives include comparing the genomic profiles of circulating tumor cells (CTCs) and circulating free DNA (cfDNA) from peripheral blood with those of the primary tumor and metastatic tissue for each patient, evaluating these mutations in the signaling pathways that are relevant to the disease, and testing the feasibility of introducing liquid biopsy as a translational laboratory tool in clinical practice. Methods: The multicenter, transversal, observational MIRROR study is currently ongoing in 3 participating hospitals. All consecutive patients with MBC confirmed by radiologic findings, either at first relapse or with tumor regrowth while on treatment for metastatic disease, will be screened for eligibility. Results: Patient’s recruitment is currently ongoing. To date, 41 patients have a complete set of tissue samples available (plasma, CTCs, and formalin-fixed, paraffin-embedded primary tumor and metastatic tumor). However, none of these samples have undergone nucleic acids extraction and targeted deep sequencing yet. Conclusions: The results of this study might have a significant influence on the practical management of patients with MBC, as they may provide clues to clinicians towards a better stratification of patients so that they receive more selective and less toxic treatments. Additionally, if genomic mutations found in metastatic tissues are similar to those detected in CTCs and/or cfDNA, then liquid biopsy could be a more convenient, non-invasive and easily accessible source of genomic material for the analysis of mutations and other genomic aberrations in MBC. Clinical Trial: NCT02626039

  • Study Protocol of Carotid Endarterectomy and Carotid Artery Stenting in Brazil: An Observational Registry

    Date Submitted: May 20, 2016

    Open Peer Review Period: May 20, 2016 - Jun 3, 2016

    Introdution: Carotid artery stenting (CAS) and carotid endarterectomy (CEA) are alternative strategies for stroke prevention in patients with atherosclerotic carotid disease. CEA has been considered t...

    Introdution: Carotid artery stenting (CAS) and carotid endarterectomy (CEA) are alternative strategies for stroke prevention in patients with atherosclerotic carotid disease. CEA has been considered the first-line treatment for carotid stenosis worldwide, and the safety and efficacy of CAS compared with CEA remain in question. The purpose of this study is to compare the practice and outcomes of CAS and CEA in a real-world setting within public university hospitals in Brazil. Methods and Analysis: This will be a prospective 5-year analysis of treatment for atherosclerotic carotid stenosis with CEA and CAS performed at 5 centres affiliated with the Vascular Study Group at public university hospitals in Brazil. The indications for the procedure will be determined by each surgeon’s individual discretion, in accordance with preoperative risk evaluation. The primary outcome measures are (1) any in-hospital stroke or death and (2) any per-procedural stroke, death, or myocardial infarction (MI). Patients undergoing CEA in conjunction with cardiac surgery will be excluded. Multivariate logistic regression will be performed to identify predictors of stroke or death in patients undergoing CEA and CAS. All tests of significance will be performed at the 0.05 level. Ethics and Dissemination: This study was approved by Committee of Ethics in Research of University Hospital of Ribeirao Preto Medical School and in all other participating institutions linked to National Research System and National Board of Health in BRAZIL (Process 15695/2011) and the recruitment is currently on-going, the last patient is expected to be included by the end of 2018. The analysis of the primary end point and all others variables of the study are expected to be published in 2019 in a peer reviewed journal and results will also be presented at scientific meetings and summary results published online. .