JMIR Publications

JMIR Research Protocols

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

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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 2016: 5.175)

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:

  • Study logo. Source: The Authors; Copyright: The Authors; URL: http://www.researchprotocols.org/2017/9/e184/; License: Creative Commons Attribution (CC-BY).

    Cancer Predisposition Cascade Screening for Hereditary Breast/Ovarian Cancer and Lynch Syndromes in Switzerland: Study Protocol

    Abstract:

    Background: Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland, affecting more than 12,000 individuals annually. Hundreds of these patients are likely to carry germline pathogenic variants associated with hereditary breast ovarian cancer (HBOC) or Lynch syndrome (LS). Genetic services (counseling and testing) for hereditary susceptibility to cancer can prevent many cancer diagnoses and deaths through early identification and risk management. Objective: Cascade screening is the systematic identification and testing of relatives of a known mutation carrier. It determines whether asymptomatic relatives also carry the known variant, needing management options to reduce future harmful outcomes. Specific aims of the CASCADE study are to (1) survey index cases with HBOC or LS from clinic-based genetic testing records and determine their current cancer status and surveillance practices, needs for coordination of medical care, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to serve as advocates for cancer genetic services to blood relatives, (2) survey first- and second-degree relatives and first-cousins identified from pedigrees or family history records of HBOC and LS index cases and determine their current cancer and mutation status, cancer surveillance practices, needs for coordination of medical care, barriers and facilitators to using cancer genetic services, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to participate in a study designed to increase use of cancer genetic services, and (3) explore the influence of patient-provider communication about genetic cancer risk on patient-family communication and the acceptability of a family-based communication, coping, and decision support intervention with focus group(s) of mutation carriers and relatives. Methods: CASCADE is a longitudinal study using surveys (online or paper/pencil) and focus groups, designed to elicit factors that enhance cascade genetic testing for HBOC and LS in Switzerland. Repeated observations are the optimal way for assessing these outcomes. Focus groups will examine barriers in patient-provider and patient-family communication, and the acceptability of a family-based communication, coping, and decision-support intervention. The survey will be developed in English, translated into three languages (German, French, and Italian), and back-translated into English, except for scales with validated versions in these languages. Results: Descriptive analyses will include calculating means, standard deviations, frequencies, and percentages of variables and participant descriptors. Bivariate analyses (Pearson correlations, chi-square test for differences in proportions, and t test for differences in means) will assess associations between demographics and clinical characteristics. Regression analyses will incorporate generalized estimating equations for pairing index cases with their relatives and explore whether predictors are in direct, mediating, or moderating relationship to an outcome. Focus group data will be transcribed verbatim and analyzed for common themes. Conclusions: Robust evidence from basic science and descriptive population-based studies in Switzerland support the necessity of cascade screening for genetic predisposition to HBOC and LS. CASCADE is designed to address translation of this knowledge into public health interventions. Clinical Trial: ClinicalTrials.gov NCT03124212; https://clinicaltrials.gov/ct2/show/NCT03124212 (Archived by WebCite at http://www.webcitation.org/6tKZnNDBt)

  • Source: Image created by the Authors; Copyright: The Authors; URL: http://www.researchprotocols.org/2017/9/e181/; License: Creative Commons Attribution (CC-BY).

    Assessing the Efficacy and Safety of an 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) in the Idiopathic Intracranial Hypertension Drug Trial,...

    Abstract:

    Background: Idiopathic intracranial hypertension (IIH) is a condition with few effective management options. So far, there have been no randomized controlled trials evaluating new treatments in IIH. Objectives: The purpose of this paper is to outline the trial design for the Idiopathic Intracranial Hypertension Drug Trial (IIH:DT), assessing an innovative medical treatment in IIH and the rationale for the chosen trial methodology. Methods: IIH:DT is a phase II double-blind randomized placebo-controlled trial recruiting 30 female participants with active IIH (intracranial pressure >25cm H2O and papilledema). Participants are randomized in a 1:1 ratio to 12 weeks of either AZD4017, an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, or a matching placebo. They receive either 400 mg of AZD4017 or placebo twice daily. Participants are followed up at Weeks 1, 2, 3, 4, 6, 8, 10, 12, and 16 postrandomization. The primary outcome is to examine the effect of AZD4017 on intracranial pressure, measured by lumbar puncture, over 12 weeks. Secondary outcome measures include IIH symptoms, visual function, papilledema, headache measures, safety, and tolerability. Cerebrospinal fluid, serum, plasma, urine, and adipose tissue are also taken for exploratory outcomes. Results: All participants were recruited between April 2014 and August 2016. Conclusions: IIH:DT is the first phase II double-blind randomized placebo-controlled trial assessing the efficacy and safety of the novel pharmacological intervention, AZD4017, for the treatment of IIH. Trial Registration: Clinicaltrials.gov NCT02017444; https://clinicaltrials.gov/ct2/show/NCT02017444 (Archived by WebCite at http://www.webcitation.org/6tVHesN6s)

  • Family with daughter with spina bifida. Source: The Authors; Copyright: Centers for Disease Control and Prevention; URL: https://www.cdc.gov/ncbddd/spinabifida/index.html; License: Public Domain (CC0).

    Understanding the Natural Progression of Spina Bifida: Prospective Study

    Abstract:

    Background: Spina bifida (SB) is monitored through birth defects surveillance across the United States and in most developed countries. Although much is known about the management of SB and its many comorbid conditions in affected individuals, there are few systematic, longitudinal studies on population-based cohorts of children or adults. The natural history of SB across the life course of persons with this condition is not well documented. Earlier identification of comorbidities and secondary conditions could allow for earlier intervention that might enhance the developmental trajectory for children with SB. Objective: The purpose of this project was to assess the development, health, and condition progression by prospectively studying children who were born with SB in Arizona and Utah. In addition, the methodology used to collect the data would be evaluated and revised as appropriate. Methods: Parents of children with SB aged 3-6 years were eligible to participate in the study, in English or Spanish. The actual recruitment process was closely documented. Data on medical history were collected from medical records; family functioning, child behaviors, self-care, mobility and functioning, and health and well-being from parent reports; and neuropsychological data from testing of the child. Results: In total, 152 individuals with SB were identified as eligible and their parents were contacted by site personnel for enrollment in the study. Of those, 45 (29.6%) declined to participate and 6 (3.9%) consented but did not follow through. Among 101 parents willing to participate, 81 (80.2%) completed the full protocol and 20 (19.8%) completed the partial protocol. Utah enrolled 72.3% (73/101) of participants, predominately non-Hispanic (60/73, 82%) and male (47/73, 64%). Arizona enrolled 56% (28/50) of participants they had permission to contact, predominately Hispanic (18/28, 64%) and male (16/28, 57%). Conclusions: We observed variance by site for recruitment, due to differences in identification and ascertainment of eligible cases and the required institutional review board processes. Restriction in recruitment and the proportion of minorities likely impacted participation rates in Arizona more than Utah.

  • Source: Image created by the Authors; Copyright: Poorna Kushalnagar; URL: https://www.researchprotocols.org/2017/9/e172/; License: Creative Commons Attribution (CC-BY).

    Health Information National Trends Survey in American Sign Language (HINTS-ASL): Protocol for the Cultural Adaptation and Linguistic Validation of a National...

    Abstract:

    Background: The Health Information National Trends Survey (HINTS) collects nationally representative data about the American’s public use of health-related information. This survey is available in English and Spanish, but not in American Sign Language (ASL). Thus, the exclusion of ASL users from these national health information survey studies has led to a significant gap in knowledge of Internet usage for health information access in this underserved and understudied population. Objective: The objectives of this study are (1) to culturally adapt and linguistically translate the HINTS items to ASL (HINTS-ASL); and (2) to gather information about deaf people’s health information seeking behaviors across technology-mediated platforms. Methods: We modified the standard procedures developed at the US National Center for Health Statistics Cognitive Survey Laboratory to culturally adapt and translate HINTS items to ASL. Cognitive interviews were conducted to assess clarity and delivery of these HINTS-ASL items. Final ASL video items were uploaded to a protected online survey website. The HINTS-ASL online survey has been administered to over 1350 deaf adults (ages 18 to 90 and up) who use ASL. Data collection is ongoing and includes deaf adult signers across the United States. Results: Some items from HINTS item bank required cultural adaptation for use with deaf people who use accessible services or technology. A separate item bank for deaf-related experiences was created, reflecting deaf-specific technology such as sharing health-related ASL videos through social network sites and using video remote interpreting services in health settings. After data collection is complete, we will conduct a series of analyses on deaf people’s health information seeking behaviors across technology-mediated platforms. Conclusions: HINTS-ASL is an accessible health information national trends survey, which includes a culturally appropriate set of items that are relevant to the experiences of deaf people who use ASL. The final HINTS-ASL product will be available for public use upon completion of this study.

  • Source: Image created by the Authors; Copyright: The Authors; URL: http://www.researchprotocols.org/2017/9/e183/; License: Creative Commons Attribution (CC-BY).

    A Multi-Level, Mobile-Enabled Intervention to Promote Physical Activity in Older Adults in the Primary Care Setting (iCanFit 2.0): Protocol for a Cluster...

    Abstract:

    Background: Most older adults do not adhere to the US Centers for Disease Control physical activity guidelines; their physical inactivity contributes to overweight and multiple chronic conditions. An urgent need exists for effective physical activity-promotion programs for the large number of older adults in the United States. Objective: This study presents the development of the intervention and trial protocol of iCanFit 2.0, a multi-level, mobile-enabled, physical activity-promotion program developed for overweight older adults in primary care settings. Methods: The iCanFit 2.0 program was developed based on our prior mHealth intervention programs, qualitative interviews with older patients in a primary care clinic, and iterative discussions with key stakeholders. We will test the efficacy of iCanFit 2.0 through a cluster randomized controlled trial in six pairs of primary care clinics. Results: The proposed protocol received a high score in a National Institutes of Health review, but was not funded due to limited funding sources. We are seeking other funding sources to conduct the project. Conclusions: The iCanFit 2.0 program is one of the first multi-level, mobile-enabled, physical activity-promotion programs for older adults in a primary care setting. The development process has actively involved older patients and other key stakeholders. The patients, primary care providers, health coaches, and family and friends were engaged in the program using a low-cost, off-the-shelf mobile tool. Such low-cost, multi-level programs can potentially address the high prevalence of physical inactivity in older adults.

  • Transportation through the corridor of the operating theater in virtual reality. Source: Image created by the Authors; Copyright: The Authors; URL: http://www.researchprotocols.org/2017/9/e174/; License: Creative Commons Attribution (CC-BY).

    Development of a Virtual Reality Exposure Tool as Psychological Preparation for Elective Pediatric Day Care Surgery: Methodological Approach for a...

    Abstract:

    Background: Preoperative anxiety in children is highly prevalent and is associated with adverse outcomes. Existing psychosocial interventions to reduce preoperative anxiety are often aimed at distraction and are of limited efficacy. Gradual exposure is a far more effective way to reduce anxiety. Virtual reality (VR) provides a unique opportunity to gradually expose children to all aspects of the operating theater. Objective: The aims of our study are (1) to develop a virtual reality exposure (VRE) tool to prepare children psychologically for surgery; and (2) to examine the efficacy of the VRE tool in a randomized controlled trial (RCT), in which VRE will be compared to care as usual (CAU). Methods: The VRE tool is highly realistic and resembles the operating room environment accurately. With this tool, children will not only be able to explore the operating room environment, but also get accustomed to general anesthesia procedures. The PREoperative Virtual reality Intervention to Enhance Wellbeing (PREVIEW) study will be conducted. In this single-blinded RCT, 200 consecutive patients (aged 4 to 12 years) undergoing elective day care surgery for dental, oral, or ear-nose-throat problems, will be randomly allocated to the preoperative VRE intervention or CAU. The primary outcome is change in child state anxiety level between baseline and induction of anesthesia. Secondary outcome measures include child’s postoperative anxiety, emergence delirium, postoperative pain, use of analgesics, health care use, and pre- and postoperative parental anxiety. Results: The VRE tool has been developed. Participant recruitment began March 2017 and is expected to be completed by September 2018. Conclusions: To our knowledge, this is the first RCT evaluating the effect of a VRE tool to prepare children for surgery. The VRE intervention is expected to significantly diminish preoperative anxiety, postoperative pain, and the use of postoperative analgesics in pediatric patients. The tool could create a less stressful experience for both children and their parents, in line with the modern emphasis on patient- and family-centered care. Trial Registration: Netherlands Trial Registry: NTR6116; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6116 (Archived by WebCite at http://www.webcitation.org/6ryke7aep)

  • Source: Pixabay; Copyright: Gerd Altmann; URL: https://pixabay.com/photo-513530/; License: Public Domain (CC0).

    Influence of Fear of Pain and Coping Strategies on Health-Related Quality of Life and Patient-Anticipated Outcomes in Patients With Chronic Pain:...

    Abstract:

    Background: Fear of pain and coping strategies are emotional-behavioral responses to pain and are known to play an important role in the development and maintenance of pain. It is highly likely that fear of pain and coping strategies influence each other, potentially affecting the course of chronic pain. To our knowledge, the relationship between pain, fear of pain and coping strategies, and how they influence patient-anticipated outcomes and health-related quality of life, have not been investigated. Objective: The aims of this study are to test (1) if both fear of pain and/or coping strategies are sufficient causes for maintaining pain; and (2) whether fear of pain influences coping strategies and pain intensity. The study will also examine the impact of fear of pain and coping strategies on health-related quality of life and patient-anticipated outcomes. Methods: The cross-sectional study will be conducted using an online survey. The Fear of Pain Questionnaire-III (FPQ-III), the Brief Coping Inventory (COPE), and EuroQoL-5d (EQ-5D) validated questionnaires will be used to collect data. Information pertaining to demographic factors, pain-related factors, and patient-anticipated outcomes will also be collected. The study has ethics approval from the Human Research Ethics Committee of the University of Adelaide. Study participants will be individuals aged 18 years and above who are experiencing chronic pain (ie, pain lasting more than 6 months). Effect measure modification technique (EMMM) will be used to examine if fear of pain acts as a moderator or mediator between coping strategies and pain. Simple and multinomial logistic regression analysis will be used to examine the effect of fear of pain and coping strategies on health-related quality of life and patient-anticipated outcomes. Results: Recruitment began July 2017 and it is anticipated that data collection will be completed by October 2017. Findings from this study will help to extend our understanding of fear of pain and coping strategies, their interaction, and their impact on health-related quality of life and patient-anticipated outcomes. Conclusions: Fear of pain and coping strategies have significant influence on the experience of chronic pain and its course. This study will help enhance our understanding of the relationship between fear of pain and coping strategies, which may help in developing patient-centered care practices.

  • Source: Flickr; Copyright: Quinn Dombrowski; URL: https://www.flickr.com/photos/53326337@N00/5646117488; License: Creative Commons Attribution + ShareAlike (CC-BY-SA).

    Protocol for Usability Testing and Validation of the ISO Draft International Standard 19223 for Lung Ventilators

    Abstract:

    Background: Clinicians, such as respiratory therapists and physicians, are often required to set up pieces of medical equipment that use inconsistent terminology. Current lung ventilator terminology that is used by different manufacturers contributes to the risk of usage errors, and in turn the risk of ventilator-associated lung injuries and other conditions. Human factors and communication issues are often associated with ventilator-related sentinel events, and inconsistent ventilator terminology compounds these issues. This paper describes our proposed protocol, which will be implemented at the University of Waterloo, Canada when this project is externally funded. Objective: We propose to determine whether a standardized vocabulary improves the ease of use, safety, and utility as it relates to the usability of medical devices, compared to legacy medical devices from multiple manufacturers, which use different terms. Methods: We hypothesize that usage errors by clinicians will be lower when standardization is consistently applied by all manufacturers. The proposed study will experimentally examine the impact of standardized nomenclature on performance declines in the use of an unfamiliar ventilator product in clinically relevant scenarios. Participants will be respiratory therapy practitioners and trainees, and we propose studying approximately 60 participants. Results: The work reported here is in the proposal phase. Once the protocol is implemented, we will report the results in a follow-up paper. Conclusions: The proposed study will help us better understand the effects of standardization on medical device usability. The study will also help identify any terms in the International Organization for Standardization (ISO) Draft International Standard (DIS) 19223 that may be associated with recurrent errors. Amendments to the standard will be proposed if recurrent errors are identified. This report contributes a protocol that can be used to assess the effect of standardization in any given domain that involves equipment, multiple manufacturers, inconsistent vocabulary, symbology, audio tones, or patterns in interface navigation. Second, the protocol can be used to experimentally evaluate the ISO DIS 19223 for its effectiveness, as researchers around the world may wish to conduct such tests and compare results.

  • Cognition tests performed at home with coffee. Source: Image created by the authors; Copyright: Wilrike Pasman; URL: http://www.researchprotocols.org/2017/8/e169/; License: Creative Commons Attribution (CC-BY).

    Effect of Caffeine on Attention and Alertness Measured in a Home-Setting, Using Web-Based Cognition Tests

    Abstract:

    Background: There is an increasing interest among nutritional researchers to perform lifestyle and nutritional intervention studies in a home setting instead of testing subjects in a clinical unit. The term used in other disciplines is ‘ecological validity’ stressing a realistic situation. This becomes more and more feasible because devices and self-tests that enable such studies are more commonly available. Here, we present such a study in which we reproduced the effect of caffeine on attention and alertness in an at-home setting. Objective: The study was aimed to reproduce the effect of caffeine on attention and alertness using a Web-based study environment of subjects, at home, performing different Web-based cognition tests. Methods: The study was designed as a randomized, placebo-controlled, double-blind, crossover study. Subjects were provided with coffee sachets (2 with and 2 without caffeine). They were also provided with a written instruction of the test days. Healthy volunteers consumed a cup of coffee after an overnight fast. Each intervention was repeated once. Before and 1 hour after coffee consumption subjects performed Web-based cognitive performance tests at home, which measured alertness and attention, established by 3 computerized tests provided by QuantifiedMind. Each test was performed for 5 minutes. Results: Web-based recruitment was fast and efficient. Within 2 weeks, 102 subjects applied, of whom 70 were eligible. Of the 66 subjects who started the study, 53 completed all 4 test sessions (80%), indicating that they were able to perform the do it yourself tests, at home, correctly. The Go-No Go cognition test performed at home showed the same significant improvement in reaction time with caffeine as found in controlled studies in a metabolic ward (P=.02). For coding and N-back the second block was performed approximately 10% faster. No effect was seen on correctness. Conclusions: The study showed that the effects of caffeine consumption on a cognition test in an at-home setting revealed similar results as in a controlled setting. The Go-No Go test applied showed improved results after caffeine intake, similar as seen in clinical trials. This type of study is a fast, reliable, economical, and easy way to demonstrate effectiveness of a supplement and is rapidly becoming a viable alternative for the classical randomized control trial to evaluate life style and nutritional interventions. Trial Registration: Clinicaltrials.gov NCT02061982; https://clinicaltrials.gov/ct2/show/NCT02061982 (Archived by WebCite at https://clinicaltrials.gov/ct2/show/NCT02061982)

  • Source: Pixabay; Copyright: Christian Northe; URL: https://pixabay.com/en/yoga-exercise-sport-fitness-1434787/; License: Public Domain (CC0).

    Study of Methods for Assessing Research Topic Elicitation and pRioritization (SMARTER): Study Protocol to Compare Qualitative Research Methods and Advance...

    Abstract:

    Background: Involving patients as partners in research is a defining characteristic of patient-centered outcomes research (PCOR). While patients’ experiential knowledge of a health condition or treatment may yield research priorities not reflected by researchers and policy makers, the methods for identifying and effectively collaborating with patients are still evolving. Patient registries and crowdsourcing may offer ease of access and convenience to both researchers and patients. Surveys and focus groups, including online modalities, have been described for prioritizing research topics. However, little is known about how these different methods compare in producing consistent priorities and similar perceptions of engagement quality among participants. Objective: The aims of this study are (1) to compare how different engagement methods used to elicit patient priorities for research perform as measured by rankings for priorities generated and participant satisfaction; and (2) to determine characteristics of individuals choosing to participate in research prioritization activities. Methods: Participants in the Back pain Outcomes using Longitudinal Data (BOLD) patient registry, established to evaluate the natural history of back pain among individuals 65 years and older, and participants on the Amazon Mechanical Turk (MTurk) crowdsourcing platform, to provide input on priorities for research via a questionnaire, are invited. For BOLD participants, we subsequently randomize interested respondents to 1 of 3 interactive prioritization activities to further develop priorities: a Delphi panel, an online crowd voting activity, or an in-person facilitated prioritization activity using nominal group technique (NGT). Participants involved in each activity complete a survey to evaluate the quality of the experience and a subset of these participants discuss their experience further in an interview. Descriptive statistics are used to characterize the rankings produced by each method and compare the top 5 rated topics resulting from each prioritization activity. We use rank-ordered logistic regression models to identify associations of the ranked priority topics with baseline patient characteristics. We analyze responses to the evaluation using a mixed-methods approach wherein we tabulate responses to Likert-scale questions and use content analysis to enumerate themes emerging from interviews for the 3 activities. Results: In Phase I, we invite approximately 3000 BOLD participants and 500 Amazon MTurk workers to complete a research topic prioritization survey. Based on these results, we include additional topics into a subsequent prioritization survey. In Phase II, we invite BOLD participants to join 1 of 3 activities: 90 participants for Delphi panel, 100 participants for crowd voting, and 60 participants for focus groups. Of the Phase II participants, 30 will be interviewed to evaluate the activities. Conclusions: This study informs decisions about how to conduct outreach to patient registry participants for providing input on research priorities, how individuals 65 years and older wish to participate in engagement activities, and how different research prioritization methods compare in terms of rankings generated and participant satisfaction.

  • Vulvar Paget disease. Source: Image created by the Authors; Copyright: The Authors; URL: http://www.researchprotocols.org/2017/9/e178/; License: Creative Commons Attribution (CC-BY).

    The Paget Trial: A Multicenter, Observational Cohort Intervention Study for the Clinical Efficacy, Safety, and Immunological Response of Topical 5% Imiquimod...

    Abstract:

    Background: Vulvar Paget disease is a rare skin disorder, which is most common in postmenopausal Caucasian women. They usually present with an erythematous plaque that may show fine or typical “cake icing” scaling or ulceration that may cause itching, pain, irritation, or a burning sensation. Although most cases are noninvasive, vulvar Paget disease may be invasive or associated with an underlying vulvar or distant adenocarcinoma. The histological evidence of so-called “Paget cells” with abundant pale cytoplasm in the epithelium confirms the diagnosis. The origin of these Paget cells is still unclear. Treatment of choice is wide local excision with negative margins. Obtaining clear surgical margins is challenging and may lead to extensive and mutilating surgery. Even then, recurrence rates are high, ranging from 15% to 70%, which emphasizes the need for new treatment options. A number of case reports, retrospective case series, and one observational study have shown promising results using the topical immune response modifier imiquimod. Objective: This study aims to investigate the efficacy, safety, and immunological response in patients with noninvasive vulvar Paget disease using a standardized treatment schedule with 5% imiquimod cream. Methods: Topical 5% imiquimod cream might be an effective and safe treatment alternative for vulvar Paget disease. The Paget Trial is a multicenter observational cohort study including eight tertiary referral hospitals in the Netherlands. It is ethically approved by the Medical-Ethical Committee of Arnhem-Nijmegen and registered in the Central Committee on Research Involving Human Subjects (CCMO) Register by as NL51648.091.14. Twenty patients with (recurrent) noninvasive vulvar Paget disease will be treated with topical 5% imiquimod cream three times a week for 16 weeks. The primary efficacy outcome is the reduction in lesion size at 12 weeks after end of treatment. Secondary outcomes are safety, immunological response, and quality of life. Safety will be assessed by evaluation of adverse events and tolerability of treatment. To evaluate the immunological response, various immunological markers will be tested on biopsy specimens taken before, during, and after treatment. Quality of life will be assessed with three questionnaires taken before, during, and after treatment. Results: First results are expected in the summer of 2018. Trial Registration: ClinicalTrials.gov NCT02385188; https://clinicaltrials.gov/ct2/show/NCT02385188 (Archived by WebCite at http://www.webcitation.org/6sXygHuhP).

  • Blood pressure lowering medication. Source: Pixabay; Copyright: Steve Buissinne; URL: https://pixabay.com/en/hypertension-high-blood-pressure-867855/; License: Public Domain (CC0).

    Legacy Effect of Delayed Blood Pressure-Lowering Pharmacotherapy in Middle-Aged Individuals Stratified by Absolute Cardiovascular Disease Risk: Protocol for...

    Abstract:

    Background: Many national and international guidelines recommend that the initiation of blood pressure (BP)-lowering drug treatment for the primary prevention of cardiovascular disease (CVD) should no longer be based on BP level alone, but on absolute cardiovascular risk. While BP-lowering drug treatment is beneficial in high-risk individuals at any level of elevated BP, clinicians are concerned about legacy effects on patients with low-to-moderate risk and mildly elevated BP who remain “untreated”. Objective: We aim to investigate the legacy effect of delayed BP-lowering pharmacotherapy in middle-aged individuals (45-65 years) with mildly elevated BP (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg) stratified by absolute risk for primary prevention of CVD, but particularly in the low-risk (<10% five-year absolute risk) group. Methods: Randomized trials of BP-lowering therapy versus placebo or pretreated subjects in active comparator studies with posttrial follow-up will be identified using a 2-step process. First, randomized trials of BP-lowering therapy will be identified by (1) retrieving the references of trials included in published systematic reviews of BP-lowering therapy, (2) retrieving studies published by the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC), and (3) checking studies referenced in the 1993 World Health Organization/International Society of Hypertension meeting memorandum on BP management. Posttrial follow-up studies will then be identified by forward citation searching the randomized trials identified in step 1 through Web of Science. The search will include randomized controlled trials with at least 1-year in-trial period and a posttrial follow-up phase. Age is the major determinant of absolute cardiovascular risk, so the participants in our review will be restricted to middle-aged adults who are more likely to have a lower cardiovascular risk profile. The primary outcome will be all-cause mortality. Secondary outcomes will include cardiovascular mortality, fatal stroke, fatal myocardial infarction, and death due to heart failure. Results: The searches for existing systematic reviews and BPLTTC studies were piloted and modified. The study is expected to be completed before June 2018. Conclusions: The findings of this study will contribute to the body of knowledge concerning the beneficial, neutral, or harmful effects of delayed BP-lowering drug treatment on the primary prevention of CVD in patients with mildly elevated BP and low-to-moderate CVD risk. Trial Registration: PROSPERO International Prospective Register of Systematic Reviews: CRD42017058414; https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017058414 (Archived by WebCite® at http://www.webcitation.org/6t6sa8O2Q)

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    Open Peer Review Period: Sep 17, 2017 - Oct 1, 2017

    Background: The oral cavity is a common site of complications related to the cytotoxic effect of high-dose chemotherapy and radiation therapy. Considering our limited understanding of the burden of i...

    Background: The oral cavity is a common site of complications related to the cytotoxic effect of high-dose chemotherapy and radiation therapy. Considering our limited understanding of the burden of illness in the oral cavity from various cytotoxic therapies, it is difficult to produce evidence-based, preventive and management protocols. A prospective multicenter study is necessary to collect data on the burden of illness from various cytotoxic regimens. Objective: The objectives of this prospective international observational multicenter study in hematopoi-etic stem cell transplant (HSCT) patients are to establish the nature, incidence and temporal re-lationship of oral complications related to conditioning regimens (chemotherapy with or with-out total body irradiation-TBI), stem cell transplantation and the immunologic reactions (main-ly GVHD) that may follow, and to determine what subjective and objective oral complica-tions related to treatment can predict negative clinical and economic outcomes and reduced quality of life (QoL). Methods: Adult patients at six study sites receiving full intensity conditioning (FIC), reduced intensity conditioning (RIC) or non-myeloablative conditioning (NMA), followed by autologous or al-logeneic hematopoietic stem cell infusion, are included. A pre-treatment assessment includes medical conditions, planned chemo- and radiation therapy regimen, medications, allergies, so-cial history, patient report of oral problems, dental history, subjective oral complaints, objec-tive measures of oral conditions, current laboratory values, dental treatment recommended and untreated dental disease. Starting 1-3 days after hematopoietic stem cell infusion, a bedside assessment is completed 3 days/week until resolution of neutropenia. A patient questionnaire is also completed during hospitalization. Beyond this time, patients with continued oral mu-cositis or other oral problems are followed 1 day/week in an inpatient or outpatient setting. Additional visits for urgent care for acute oral problems after hospitalization are documented. Autologous transplant patients are being followed up at 100 days ±30 days and at 1 year ±30 days post-transplantation to identify any long-term side effects. Patients treated with alloge-neic transplantation are being followed at 100 days ±30 days, 6 months ±30 days, and 12 months ±30 days. The follow-up assessments include cancer response to therapy, current med-ical conditions, medications, subjective and objective oral findings, QoL measures and labora-tory values. Results: A total of 211 participants have been enrolled. We anticipate enrollment of 109 additional par-ticipants to obtain the sample size of 320. Conclusions: The results of the ongoing prospective study will provide a unique dataset to understand the impact of oral complications on patients undergoing HSCT and provide needed information with forming more evidence-based guidelines regarding the management of this patient co-hort.

  • Investigating the Impact of Hearing Aid Use and Auditory Training on Cognition, Mood and Social Interaction in Older Adults with Hearing Loss: the Study Protocol of a Crossover Trial

    Date Submitted: Sep 11, 2017

    Open Peer Review Period: Sep 15, 2017 - Sep 29, 2017

    Background: Sensorineural type of hearing loss is the most common sensory deficit among older adults. Some of the psychosocial consequences of this condition include difficulty in understanding speech...

    Background: Sensorineural type of hearing loss is the most common sensory deficit among older adults. Some of the psychosocial consequences of this condition include difficulty in understanding speech, depression and social isolation. Studies have shown that older adults with hearing loss show some age-related cognitive decline. There is no clinically proven method to predict the onset of this condition, as its occurrence is slow and progressive, affecting both ears equally. Although hearing aid use and auditory training have been proven as successful interventions to alleviate sensorineural hearing loss, no research has been designed to look at the effect of simultaneous hearing aid use and auditory training on cognitive performance in older adults. Objective: The objective of this research study is to investigate in a randomized crossover trial, the impact of hearing aid use coupled with auditory training on cognition, mood, and social interaction, for older adults with sensorineural hearing loss. The rationale for this study is based on the hypothesis that, in older adults with sensorineural hearing loss, hearing aids in combination with auditory training will be more effective for improving cognition, mood, and social interaction, than auditory training on its own. Methods: This is a crossover trial targeting elderly men and women between 50 and 90 years with either mild or moderate symmetric sensorineural hearing loss. Consented, willing participants will undergo a six month intensive auditory training program (active control), as a rigorous means of examining the impact of hearing aid use on cognition, mood and social interaction. Participants will be assigned in random order to receive hearing aid (intervention) for either the first three or last three months of the six month auditory training program. Each participant will be tested at baseline, three and six months on a battery of computer based cognitive assessments, together with mood, and social engagement measures. The primary outcome, cognitive performance, will be determined by a neuropsychological test battery. Secondary outcomes include mood and social interaction. The effectiveness of hearing aids and auditory training will be evaluated using an online speech perception test and the Abbreviated Profile of Hearing Aid Benefit (APHAB) Inventory. Results: This investigation is funded by the Australian Research Council and Blamey and Saunders Hearing Pty Ltd under the Industry Transformation Training Centre Scheme (ARC Project No. IC140100023) and it attained ethics approval on July 22, 2016 (Swinburne University Human Research Ethics Committee protocol number SHR Project 2016/159). Conclusions: This study will investigate whether using a hearing aid coupled with auditory training can improve a person’s cognition and learning abilities, relationships with family and friends, and quality of life. Results from the study will inform strategies for aural rehabilitation, hearing aid delivery and future hearing loss intervention trials. Clinical Trial: This trial is retrospectively registered at ClinicalTrials.gov, on April 13, 2017, identifier: NCT03112850.

  • Gut Hormone and Anti-Inflammatory Pathways Underlying Probiotic-effects on Glycaemic Control, Gut Microbiota and Quality of Life among Type 2 Diabetes Mellitus Patients: A Study Protocol

    Date Submitted: Sep 7, 2017

    Open Peer Review Period: Sep 9, 2017 - Sep 23, 2017

    Type 2 diabetes mellitus (T2DM) is a hyperglycaemic condition characterised with systemic inflammation and high oxidation level. Recently, imbalanced gut microbiota has been identified as one of the c...

    Type 2 diabetes mellitus (T2DM) is a hyperglycaemic condition characterised with systemic inflammation and high oxidation level. Recently, imbalanced gut microbiota has been identified as one of the contributing factors in the development of T2DM. Modulation of gut microbiota in favour of good bacteria is essential for the management of T2DM. Probiotics are being increasingly recognised for their ability in modulating microbiota shift. This beneficial effect could potentially increase secretion of gut hormones, reduce systemic inflammation and oxidative stress among T2DM patients. The present clinical trial aims to determine the effects of probiotics on glycaemic control in T2DM patients. This trial will also elucidate the role of probiotics on anti-inflammatory markers, anti-oxidants, gut hormone regulation as well as alteration of intestinal microbiota composition in T2DM patients. Furthermore, this study evaluates changes in quality of life of the T2DM patients upon probiotics intake. A double-centre, double-blinded, placebo-controlled, randomised trial will be conducted at the Primary Care Medicine (PCM) clinics of the Clinical Training Centre (CTC) Sungai Buloh and the CTC Selayang, Universiti Teknologi MARA (UiTM), Selangor Darul Ehsan, Malaysia. One hundred T2DM adult patients will be recruited and will be randomly assigned into two groups, receiving either one capsule of probiotics (Chr Hansen, Denmark) or one capsule of placebo twice daily for 24 weeks. Changes in glycaemic parameters [i.e. glycosylated haemoglobin (HbA1c) as the primary outcome], levels of anti-inflammatory markers, anti-oxidants, gut hormone, anthropometric parameters, gut microbiota composition and quality of life will be determined. Both blood (all patients) and stool (20 patients only) samples will be collected during baseline assessment (prior to commencement of the clinical trial), week 12 and week 24 follow-up. Assessment of compliance and adverse events will be conducted throughout the study. It is anticipated that probiotics may induce beneficial changes in the gut microbiota, reduce systemic inflammatory state and oxidative stress as well as increase secretion of gut hormone, all of which may lead to improved glycaemic control and quality of life in T2DM patients. 100 subjects were estimated to be enrolled for this study. This study was initiated in December 2015. Currently, it is now at the stage of data collection and expected to complete by May 2018. Australian New Zealand Clinical Trial Registry (ANZCTR) Identifier: (ACTRN12615001135505)

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