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Abstract Software that employs screening prioritization through active learning (AL) has accelerated the screening process significantly by ranking an unordered set of records by their predicted relevance. However, failing to find a relevant paper might alter the findings of a systematic review, highlighting the importance of identifying elusive papers. The time to discovery (TD) measures how many records are needed to be screened to find a relevant paper, making it a helpful tool for detecting such papers. The main aim of this project was to investigate how the choice of the model and prior knowledge influence the TD values of the hard-to-find relevant papers and their rank orders. A simulation study was conducted, mimicking the screening process on a dataset containing titles, abstracts, and labels used for an already published systematic review. The results demonstrated that AL model choice, and mostly the choice of the feature extractor but not the choice of prior knowledge, significantly influenced the TD values and the rank order of the elusive relevant papers. Future research should examine the characteristics of elusive relevant papers to discover why they might take a long time to be found.

Abstract Background Academic paper writing holds significant importance in the education of medical students, and poses a clear challenge for those whose first language is not English. This study aims to investigate the effectiveness of employing large language models, particularly ChatGPT, in improving the English academic writing skills of these students. Methods A cohort of 25 third-year medical students from China was recruited. The study consisted of two stages. Firstly, the students were asked to write a mini paper. Secondly, the students were asked to revise the mini paper using ChatGPT within two weeks. The evaluation of the mini papers focused on three key dimensions, including structure, logic, and language. The evaluation method incorporated both manual scoring and AI scoring utilizing the ChatGPT-3.5 and ChatGPT-4 models. Additionally, we employed a questionnaire to gather feedback on students’ experience in using ChatGPT. Results After implementing ChatGPT for writing assistance, there was a notable increase in manual scoring by 4.23 points. Similarly, AI scoring based on the ChatGPT-3.5 model showed an increase of 4.82 points, while the ChatGPT-4 model showed an increase of 3.84 points. These results highlight the potential of large language models in supporting academic writing. Statistical analysis revealed no significant difference between manual scoring and ChatGPT-4 scoring, indicating the potential of ChatGPT-4 to assist teachers in the grading process. Feedback from the questionnaire indicated a generally positive response from students, with 92% acknowledging an improvement in the quality of their writing, 84% noting advancements in their language skills, and 76% recognizing the contribution of ChatGPT in supporting academic research. Conclusion The study highlighted the efficacy of large language models like ChatGPT in augmenting the English academic writing proficiency of non-native speakers in medical education. Furthermore, it illustrated the potential of these models to make a contribution to the educational evaluation process, particularly in environments where English is not the primary language.

Abstract Obesity is the one of the most important components of metabolic syndrome. Because obesity related hypertension accounts for two thirds of essential hypertension, managing obesity and metabolic syndrome is a crucial task in the management of hypertension. However, the current non-pharmacological therapies have limitations for achieving or maintaining ideal body weight. Recently, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated excellent weight control effects, accompanied by corresponding reductions in blood pressure. GLP1-RAs have shown cardiovascular and renal protective effects in cardiovascular outcome trials both in primary and secondary prevention. In this document, the Korean Society of Hypertension intends to remark the current clinical results of GLP1-RAs and recommend the government and health-policy makers to define obesity as a disease and to establish forward-looking policies for GLP1-RA treatment for obesity treatment, including active reimbursement policies.

Abstract Background Paediatric orthopaedics is a significant and difficult for undergraduate students to master. During the COVID-19 pandemic, we used the WeChat platform to combine the advantages offered by problem-based learning (PBL), case-based learning (CBL) and paper review teaching methods to establish a new blended online teaching model and demonstrated its feasibility and effectiveness. Objective This study aims to demonstrate the feasibility and effectiveness of a new blended pedagogical method that uses the WeChat platform and combines PBL, CBL and paper review. Methods We enrolled 22 students participating in the Department of Paediatric Orthopaedics. They participated in the WeChat blended pedagogy mode. Their departmental rotation examination scores were compared with those of 23 students who participated in the traditional teaching method. Moreover, an anonymous questionnaire was used to evaluate students’ perceptions and experiences. Results The total average scores of students who participated in the WeChat blended pedagogy mode and the traditional teaching method were 47.27 and 44.52, respectively. There were no statistically significant differences between the online teaching mode and the traditional teaching method in terms of possessing professional accomplishment, gaining knowledge and promoting interpersonal skills (P = 0.07, P = 0.12 and P = 0.65, respectively). In terms of independent clinical thinking, self-improving capability and improving clinical skills, the scores associated with the WeChat blended pedagogy mode were 8.00, 8.00 and 6.00, whereas those associated with the traditional teaching method were 6.70, 6.87 and 7.48. The overall satisfaction with the WeChat blended pedagogy mode reached 100%. A total of 64%, 86%, 68%, 64% and 59% of students chose very large or large in response to the items concerning professional accomplishment, knowledge absorption, independent clinical thinking skills, English reading and literature exploring capacity, as well as interpersonal skills, respectively. Fifteen participants claimed that the WeChat blended pedagogy mode was less helpful to them with regard to promoting the improvement of their clinical skills. Nine students claimed that the WeChat blended pedagogy mode was time-consuming. Conclusions Our study verified the feasibility and effectiveness of the WeChat blended pedagogy mode for undergraduate paediatric orthopaedics internships. Trial Registration Retrospectively registered.

Abstract Background Misinformation regarding COVID-19 pandemic and vaccination is damaging COVID-19 vaccine trust and acceptance in Low- and Middle-Income Countries (LMIC). Identification of misinformation and designing locally acceptable solutions are needed to improve COVID-19 vaccine acceptance. This study aimed to utilize community-led co-design methodology to evaluate misinformation regarding COVID-19 and develop contextual interventions to address misinformation in a marginalized peri urban slum communities of Landhi town Karachi, Pakistan. Methods This study was conducted between January and December 2021, in marginalized peri-urban slum dwellers of Muslimabad Colony, Landhi Town Karachi, Pakistan. We used a community-centred co-design methodology embedded within mixed study design to identify misinformation, co-design, test and implement locally acceptable solutions. The co-design methodology involved five stages of the design thinking model: (1) Empathize, (2) Define, (3) Ideate, (4) Prototype, and (5) Test. The project involved active engagement and participation of wide range of stakeholders and community beneficiaries (end users) including local EPI vaccinators, informal healthcare workers, religious leaders (male and female), schoolteachers (male and female), local government representatives, community leaders, housewives, youth, and general population. To develop a trusting relationship, and understand local culture, values, practices, and traditions, we allowed one month of observation period (observe, engage, watch, and listen) in the beginning, followed by door-to-door survey along with focus group discussions (FGD) and in-depth interviews (IDI) at baseline. Co-design workshops (separate for male and female) were conducted at each stage of co-design methodology to design and test locally acceptable solutions. Conclusion Community-centred co-design methodology was not only successful in designing, testing, and evaluating locally acceptable solutions but it also actively engaged and empowered the marginalized population living in peri urban slum communities of Karachi, Pakistan.

Abstract Background Problem-based learning (PBL) remains a valid and effective tool for small-group medical education. Using Virtual patients (VP) case simulation in PBL is a recognizable educational method that has successfully prepared students to focus learning on core information that uses realistic patient-based cases relating to everyday clinical scenarios. Using other modalities as the virtual patient in PBL instead of the paper-based methods remains debatable. This study aimed to evaluate the effectiveness of using VP case simulation mannequin in PBL versus the PBL in paper-based cases in improving the cognitive skills by comparing the grades of a multiple-choice question test and assess its ability to reach students' satisfaction using questionnaire with Likert survey instrument. Methods The study was conducted on 459 fourth-year medical students studying in the pulmonology module of the internal medicine course, Faculty of Medicine, October 6 University. All students were divided into 16 PBL classes and randomly divided into groups A and B by simple manual randomization. The groups were parallel with a controlled cross-over study between paper-based and virtual patient PBL. Results The pre-test showed no significant difference between both, while post-test scores were significantly higher in both VP PBL cases 1 discussing COPD (6.25 ± 0.875) and case 2 discussing pneumonia (6.56 ± 1.396) compared to paper-based PBL (5.29 ± 1.166, 5.57 ± SD1.388, respectively) at p

Abstract Background Huntington’s disease is a complex neurodegenerative hereditary disease with symptoms in all domains of a person’s functioning. It begins after a healthy start in life and leads through the relentless progression over many years to complete care dependency and finally death. To date, the disease is incurable. The long progressive complex nature of the disease demands multiple disciplines for treatment and care of patient and family. These health care providers need inter- and multidisciplinary collaboration to persevere and be efficacious in this devastating disease trajectory. Discussion The position paper outlines current knowledge and experience alongside the experience and consensus of a recognised group of HD multidisciplinary experts. Additionally the patient’s voice is clear and calls for health care providers with a holistic view on patient and family. Building long-term trust is a cornerstone of the network around the patient. This paper describes a managed care network comprising all the needed professionals and services. In the health care system, the role of a central coordinator or case manager is of key importance but lacks an appropriate guideline. Other disciplines currently without guidelines are general practitioners, nurses, psychologists, and social workers. Guidelines for neurologists, psychiatrists, geneticists, occupational therapists, speech and language therapists, physiotherapists, dieticians, and dentists are being discussed. Apart from all these profession-specific guidelines, distinctive inter- and multidisciplinary collaboration requirements must be met. Conclusions and recommendations The complex nature of Huntington's disease demands multidisciplinary treatment and care endorsed by international regulations and the lay association. Available guidelines as reviewed in this paper should be used, made available by a central body, and updated every 3–5 years. Time needs to be invested in developing missing guidelines but the lack of this ‘proof’ should not prevent the ‘doing’ of good care.

Abstract Background Personalised medicine (PM) has been fostered by technological and medical advances, but all stakeholders, including healthcare professionals, citizens and policy makers, should achieve adequate health literacy to promote PM implementation. The “Integrating China in the International Consortium for Personalised Medicine” (IC2PerMed) project, funded by the International Consortium for Personalised Medicine, focuses on this issue by highlighting the need to educate healthcare professionals and empower citizens. Within the aforementioned project, building on a mapping of European and Chinese policies in PM, experts in the field of PM participated in an online workshop and a following two-round Delphi survey, in order to identify the priority areas of intervention for healthcare professionals’ education and curricula, engagement and empowerment of citizens and patients. Results Nine experts completed the survey and reached a consensus on seventeen priorities: seven were related to health professionals’ education and curricula, whereas ten on citizen and patients’ awareness and empowerment. Conclusion These priorities emphasized the importance of education and health literacy, multidisciplinary and international collaboration, public trust, and consideration of ethical, legal, and social issues. The present experience highlights the relevance of the involvement of stakeholders in informing decision-makers, developing appropriate national plans, strategies, and policies, and ensuring the adequate implementation of PM in health systems.

Abstract Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder associated with increased immune activity and severe, progressive heterotopic ossification. We previously described a cohort of 32 patients with FOP who were either exposed to SARS-CoV-2 or received a COVID-19 vaccine1 and showed that these patients did not develop heterotopic ossification after COVID-19 vaccination. Here, we present additional clinical data from new subjects and additional long-term follow-up from the first cohort. We enrolled 15 new subjects between August 24th, 2021 and May 17th, 2022 and collected additional self-reported outcomes. The larger cohort with 47 individuals encompassing 49 events showed that patients with FOP exhibited no additional change in FOP disease activity or flare activity resulting from COVID-19 infection or after receipt of a SARS-CoV-2 vaccine. Thus, although any vaccination carries a risk of inducing heterotopic ossification in patients with FOP, our results show that patients with FOP who choose to receive a COVID-19 vaccination may be able to tolerate the procedure without a high risk of heterotopic ossification when following the published guidelines.

Abstract Background In recent years, significant advances have been made in the field of rare diseases (RDs). However, there is a large number of RDs without specific treatment and half of these treatments have public funding in Spain. The aim of the FINEERR project was to carry out a multidisciplinary strategic discussion on the challenge of funding and access to RD-targeted drugs in Spain, in order to agree on specific proposals for medium-term improvement and hence support decision-making in the Spanish National Healthcare System (SNHS). Results The FINEERR Project was organized around a CORE Advisory Committee, which provided an overview, agreed on the design and scope of the project, and selected the members within each of four working groups (WG). Overall, 40 experts discussed and reached a consensus on different relevant aspects, such as conditioning factors for initial funding and access, evaluation and access to RD-targeted therapies, funding of these therapies, and implementation of a new funding and access model. From these meetings, 50 proposals were defined and classified by their level of relevance according to the experts. A descriptive analysis of responses was performed for each proposal. Thereafter, experts completed another questionnaire where they ranked the 25 most relevant proposals according to their level of feasibility of being implemented in the SNHS. The most relevant and feasible proposals were to improve: process of referral of patients with RDs, control over monitoring mechanisms, and communication between healthcare professionals and patients. Conclusions The FINEERR project may provide a starting point for stakeholders involved in the process of funding and access to RD-targeted therapies in Spain to provide the necessary resources and implement measures to improve both the quality of life and life expectancy of patients with RDs.

Abstract Background In drug development, few molecules from a large pool of early candidates become successful medicines after demonstrating a favourable benefit-risk ratio. Many decisions are made along the way to continue or stop the development of a molecule. The probability of pharmacological success, or PoPS, is a tool for informing early-stage decisions based on benefit and risk data available at the time. Results The PoPS is the probability that most patients can achieve adequate pharmacology for the intended indication while minimising the number of subjects exposed to safety risk. This probability is usually a function of dose; hence its computation typically requires exposure–response models for pharmacology and safety. The levels of adequate pharmacology and acceptable risk must be specified. The uncertainties in these levels, in the exposure–response relationships, and in relevant translation all need to be identified. Several examples of different indications are used to illustrate how this approach can facilitate molecule progression decisions for preclinical and early clinical development. The examples show that PoPS assessment is an effective mechanism for integrating multi-source data, identifying knowledge gaps, and forcing transparency of assumptions. With its application, translational modelling becomes more meaningful and dose prediction more rigorous. Its successful implementation calls for early planning, sound understanding of the disease-drug system, and cross-discipline collaboration. Furthermore, the PoPS evolves as relevant knowledge grows. Conclusion The PoPS is a powerful evidence-based framework to formally capture multiple uncertainties into a single probability term for assessing benefit-risk ratio. In GSK, it is now expected for governance review at all early-phase decision gates.

Abstract Background Health policy-makers must often make decisions in compressed time frames and with limited resources. Hence, rapid reviews have become a pragmatic alternative to comprehensive systematic reviews. However, it is important that rapid review methods remain rigorous to support good policy development and decisions. There is currently little evidence about which streamlined steps in a rapid review are less likely to introduce unacceptable levels of uncertainty while still producing a product that remains useful to policy-makers. Methods This paper summarizes current research describing commonly used methods and practices that are used to conduct rapid reviews and presents key considerations and options to guide methodological choices for a rapid review. Results The most important step for a rapid review is for an experienced research team to have early and ongoing engagement with the people who have requested the review. A clear research protocol, derived from a needs assessment conducted with the requester, serves to focus the review, defines the scope of the rapid review, and guides all subsequent steps. Common recommendations for rapid review methods include tailoring the literature search in terms of databases, dates, and languages. Researchers can consider using a staged search to locate high-quality systematic reviews and then subsequently published primary studies. The approaches used for study screening and selection, data extraction, and risk-of-bias assessment should be tailored to the topic, researcher experience, and available resources. Many rapid reviews use a single reviewer for study selection, risk-of-bias assessment, or data abstraction, sometimes with partial or full verification by a second reviewer. Rapid reviews usually use a descriptive synthesis method rather than quantitative meta-analysis. Use of brief report templates and standardized production methods helps to speed final report publication. Conclusions Researchers conducting rapid reviews need to make transparent methodological choices, informed by stakeholder input, to ensure that rapid reviews meet their intended purpose. Transparency is critical because it is unclear how or how much streamlined methods can bias the conclusions of reviews. There are not yet internationally accepted standards for conducting or reporting rapid reviews. Thus, this article proposes interim guidance for researchers who are increasingly employing these methods.

Abstract Background Rapid reviews have emerged as an approach to provide contextualized evidence in a timely and efficient manner. Three rapid review centers were established in Ethiopia, Lebanon, and South Africa through the Alliance for Health Policy and Systems Research, World Health Organization, to stimulate demand, engage policymakers, and produce rapid reviews to support health policy and systems decision-making. This study aimed to assess the experiences of researchers and policymakers engaged in producing and using rapid reviews for health systems strengthening and decisions towards universal health coverage (UHC). Methods Using a case study approach with qualitative research methods, experienced researchers conducted semi-structured interviews with respondents from each center (n = 16). The topics covered included the process and experience of establishing the centers, stimulating demand for rapid reviews, collaborating between researchers and policymakers, and disseminating and using rapid reviews for health policies and interventions and the potential for sustaining and institutionalizing the services. Data were analyzed using thematic analysis. Results Major themes interacted and contributed to shape the experiences of stakeholders of the rapid review centers, including the following: organizational structural arrangements of the centers, management of their processes as input factors, and the rapid reviews as the immediate policy-relevant outputs. The engagement process and the rapid review products contributed to a final theme of impact of the rapid review centers in relation to the uptake of evidence for policy and systems decision-making. Conclusions The experiences of policymakers and researchers of the rapid review centers determined the uptake of evidence. The findings of this study can inform policymakers, health system managers, and researchers on best practices for demanding, developing and using rapid reviews to support decision- and policymaking, and implementing the universal healthcare coverage agenda.

Abstract Background Transparent reporting of rapid reviews enables appropriate use of research findings and dissemination strategies can strengthen uptake and impact for the targeted knowledge users, including policy-makers and health system managers. The aim of this literature review was to understand reporting and dissemination approaches for rapid reviews and provide an overview in the context of health policy and systems research. Methods A literature review and descriptive summary of the reporting and disseminating approaches for rapid reviews was conducted, focusing on available guidance and methods, considerations for engagement with knowledge users, and optimizing dissemination. MEDLINE, PubMed, Google scholar, as well as relevant websites and reference lists were searched from January 2017 to March 2021 to identify the relevant literature with no language restrictions. Content was abstracted and charted. Results The literature review found limited guidance specific to rapid reviews. Building on the barriers and facilitators to systematic review use, we provide practical recommendations on different approaches and methods for reporting and disseminating expedited knowledge synthesis considering the needs of health policy and systems knowledge users. Reporting should balance comprehensive accounting of the research process and findings with what is “good enough” or sufficient to meet the requirements of the knowledge users, while considering the time and resources available to conduct a review. Typical approaches may be used when planning the dissemination of rapid review findings; such as peer-reviewed publications or symposia and clear and ongoing engagement with knowledge users in crafting the messages is essential so they are appropriately tailored to the target audience. Consideration should be given to providing different products for different audiences. Dissemination measures and bibliometrics are also useful to gauge impact and reach. Conclusions Limited guidance specific to the reporting and dissemination of rapid reviews is available. Although approaches to expedited synthesis for health policy and systems research vary, considerations for the reporting and dissemination of findings are pertinent to all.

Abstract Objective Electronic data collection (EDC) has become a suitable alternative to paper based data collection (PBDC) in biomedical research even in resource poor settings. During a survey in Nepal, data were collected using both systems and data entry errors compared between both methods. Collected data were checked for completeness, values outside of realistic ranges, internal logic and date variables for reasonable time frames. Variables were grouped into 5 categories and the number of discordant entries were compared between both systems, overall and per variable category. Results Data from 52 variables collected from 358 participants were available. Discrepancies between both data sets were found in 12.6% of all entries (2352/18,616). Differences between data points were identified in 18.0% (643/3580) of continuous variables, 15.8% of time variables (113/716), 13.0% of date variables (140/1074), 12.0% of text variables (86/716), and 10.9% of categorical variables (1370/12,530). Overall 64% (1499/2352) of all discrepancies were due to data omissions, 76.6% (1148/1499) of missing entries were among categorical data. Omissions in PBDC (n = 1002) were twice as frequent as in EDC (n = 497, p

Abstract Approaches for rapid reviews that focus on streamlining systematic review methods are not always suitable for exploring complex policy questions, as developing and testing theories to explain these complexities requires configuring diverse qualitative, quantitative, and mixed methods studies. Our objective was therefore to provide a guide to selecting approaches for rapidly (i.e., within days to months) addressing complex questions related to health policy and system issues. We provide a two-stage, transdisciplinary collaborative process to select a rapid review approach to address complex policy questions, which consists of scoping the breadth and depth of the literature and then selecting an optimal approach to synthesis. The first stage (scoping the literature) begins with a discussion with the stakeholders requesting evidence to identify and refine the question for the review, which is then used to conduct preliminary searches and conceptually map the documents identified. In the second stage (selection of an optimal approach), further stakeholder consultation is required to refine and tailor the question and approach to identifying relevant documents to include. The approach to synthesizing the included documents is then guided by the final question, the breadth and depth of the literature, and the time available and can include a static or evolving conceptual framework to code and analyze a range of evidence. For areas already covered extensively by existing systematic reviews, the focus can be on summarizing and integrating the review findings, resynthesizing the primary studies, or updating the search and reanalyzing one or more of the systematic reviews. The choice of approaches for conducting rapid reviews is intertwined with decisions about how to manage projects, the amount of work to be done, and the knowledge already available, and our guide offers support to help make these strategic decisions.

Abstract Background When a journal receives a duplicate publication, the ability to identify the submitted work as previously published, and reject it, is an assay to publication ethics best practices. The aim of this study was to evaluate how three different types of journals, namely open access (OA) journals, subscription-based journals, and presumed predatory journals, responded to receiving a previously published manuscript for review. Methods We performed a quasi-experimental study in which we submitted a previously published article to a random sample of 602 biomedical journals, roughly 200 journals from each journal type sampled: OA journals, subscription-based journals, and presumed predatory journals. Three hundred and three journals received a Word version in manuscript format, while 299 journals received the formatted publisher’s PDF version of the published article. We then recorded responses to the submission received after approximately 1 month. Responses were reviewed, extracted, and coded in duplicate. Our primary outcome was the rate of rejection of the two types of submitted articles (PDF vs Word) within our three journal types. Results We received correspondence back from 308 (51.1%) journals within our study timeline (32 days); (N = 46 predatory journals, N = 127 OA journals, N = 135 subscription-based journals). Of the journals that responded, 153 received the Word version of the paper, while 155 received the PDF version. Four journals (1.3%) accepted our paper, 291 (94.5%) journals rejected the paper, and 13 (4.2%) requested a revision. A chi-square test looking at journal type, and submission type, was significant (χ 2 (4) = 23.50, p

Abstract Background The development of new genetic testing methods and the approval of the first treatments raises questions regarding when and how to perform screening for inherited neuromuscular conditions. Screening directives and access to the different techniques is not uniform across Europe. The patient advisory board of the European reference network for rare neuromuscular diseases (NMD) conducted a qualitative study to understand the state of play of screening for inherited NMD in Europe and patients’ needs. Results We collected answers from 30 patient organisations (POs) from 18 European countries. Fifteen acknowledge the existence of pre-implantation genetic diagnosis in their country. Regarding prenatal screening, we had 25 positive answers and 5 negative ones. Twenty-four POs mentioned that newborn screening was available in their country. We had some contradictory answers from POs from the same country and in some cases; diseases said to be part of the screening programmes were not hereditary disorders. Twenty-eight organisations were in favour of screening tests. The reasons for the two negative answers were lack of reimbursement and treatment, religious beliefs and eventual insurance constrains. Most POs (21) were in favour of systematic screening with the option to opt-out. Regarding the timing for screening, “at birth”, was the most consensual response. The main priority to perform screening for NMDs was early access to treatment, followed by shorter time to diagnostic, preventive care and genetic counselling. Conclusions This is the first study to assess knowledge and needs of POs concerning screening for NMDs. The knowledge of POs regarding screening techniques is quite uneven. This implies that, even in communities highly motivated and knowledgeable of the conditions they advocate for, there is a need for better information. Differences in the responses to the questions “how and when to screen” shows that the screening path depends on the disease and the presence of a disease modifying treatment. The unmet need for screening inherited NMDs should follow an adaptive pathway related to the fast moving medical landscape of NMDs. International coordination leading to a common policy would certainly be a precious asset tending to harmonize the situation amongst European countries.

Abstract Smartphone technology has spread rapidly around the globe. According to a report released by the Korea Information Society Development Institute, about 95% of Koreans aged more than 30 years old owned smartphones. Recently, blood pressure (BP) measurement using a photoplethysmography-based smartphone algorithm paired with the smartwatch is continuously evolving. In this document, the Korean Society of Hypertension intends to remark the current results of smartphone / smartwatch-based BP measurement and recommend optimal BP measurement methods using a smartphone device. We aim to increase the likelihood of success in implementing these new technologies into improved hypertension awareness, diagnosis, and control.

Abstract Background With the development of molecular high-throughput assays (i.e. next generation sequencing), the knowledge on the contribution of genetic and epigenetic alterations to the etiology of inherited endocrine disorders has massively expanded. However, the rapid implementation of these new molecular tools in the diagnostic settings makes the interpretation of diagnostic data increasingly complex. Main body This joint paper of the ENDO-ERN members aims to overview chances, challenges, limitations and relevance of comprehensive genetic diagnostic testing in rare endocrine conditions in order to achieve an early molecular diagnosis. This early diagnosis of a genetically based endocrine disorder contributes to a precise management and helps the patients and their families in their self-determined planning of life. Furthermore, the identification of a causative (epi)genetic alteration allows an accurate prognosis of recurrence risks for family planning as the basis of genetic counselling. Asymptomatic carriers of pathogenic variants can be identified, and prenatal testing might be offered, where appropriate. Conclusions The decision on genetic testing in the diagnostic workup of endocrine disorders should be based on their appropriateness to reliably detect the disease-causing and –modifying mutation, their informational value, and cost-effectiveness. The future assessment of data from different omic approaches should be embedded in interdisciplinary discussions using all available clinical and molecular data.

Abstract Objective Stool repositories are a valuable resource for retrospective analyses including quantitative PCR assays to distinguish between asymptomatic shedding and clinical disease. The suitability of archival specimens for this purpose is unclear and requires assessment. We conducted a pilot study to evaluate pathogen detection by TaqMan Array Card (TAC) in travelers’ diarrhea (TD) stool specimens stored for 1–13 years, as well as the impact of transporting specimens on Whatman FTA Elute cards (FTA Cards) on detection. Results The positive percent agreement (PPA) for TAC on stool vs. microbiologic testing was lower than our a priori PPA estimate of 80% for most pathogens: Shigella spp. (100% [95%CI 69–100%]), enterotoxigenic E coli (ETEC) (63% [95%CI 49–75%]), Campylobacter spp. (66% [95%CI 43–85%]) and Norovirus (37% [95%CI 16–61%]). Use of the FTA card resulted in a further reduction of PPA. Our findings suggest that archival specimens may lead to insensitive detection on quantitative PCR assays due to degradation of nucleic acid with prolonged storage, although our limited sample size precluded us from evaluating the impact of storage duration on nucleic acid yield. Additional studies are needed to understand the impact of storage duration on quantitative PCR data.

Abstract Background Functional somatic symptoms and disorders are common and complex phenomena involving both bodily and brain processes. They pose major challenges across medical specialties. These disorders are common and have significant impacts on patients’ quality of life and healthcare costs. Main body We outline five problems pointing to the need for a new classification: (1) developments in understanding aetiological mechanisms; (2) the current division of disorders according to the treating specialist; (3) failure of current classifications to cover the variety of disorders and their severity (for example, patients with symptoms from multiple organs systems); (4) the need to find acceptable categories and labels for patients that promote therapeutic partnership; and (5) the need to develop clinical services and research for people with severe disorders. We propose ‘functional somatic disorders’ (FSD) as an umbrella term for various conditions characterised by persistent and troublesome physical symptoms. FSDs are diagnosed clinically, on the basis of characteristic symptom patterns. As with all diagnoses, a diagnosis of FSD should be made after considering other possible somatic and mental differential diagnoses. We propose that FSD should occupy a neutral space within disease classifications, favouring neither somatic disease aetiology, nor mental disorder. FSD should be subclassified as (a) multisystem, (b) single system, or (c) single symptom. While additional specifiers may be added to take account of psychological features or co-occurring diseases, neither of these is sufficient or necessary to make the diagnosis. We recommend that FSD criteria are written so as to harmonise with existing syndrome diagnoses. Where currently defined syndromes fall within the FSD spectrum – and also within organ system-specific chapters of a classification – they should be afforded dual parentage (for example, irritable bowel syndrome can belong to both gastrointestinal disorders and FSD). Conclusion We propose a new classification, ‘functional somatic disorder’, which is neither purely somatic nor purely mental, but occupies a neutral space between these two historical poles. This classification reflects both emerging aetiological evidence of the complex interactions between brain and body and the need to resolve the historical split between somatic and mental disorders.

Abstract Background Experiential peers are increasingly involved in the development and delivery of interventions for individuals who are engaged in delinquent behavior. Experiential peer support, which is the provision of support to an individual engaged in delinquent behavior by someone who has previously also practiced such behavior, is one such application. Little is known, however, about its effects on desistance, or the mechanisms that explain these effects. On the basis of theoretical papers, program descriptions, and interviews with experts, we developed an initial program theory. We propose seven mechanisms that might play a role in the (potential) effects of support by experiential peers: (1) empathy and acceptance, (2) social learning, (3) social bonding, (4) social control, (5) narrative and identity formation, (6) hope and perspective, and (7) translation and connection. In addition, in this protocol paper, we describe the methods of a systematic realist literature review that will be conducted in order to investigate the evidence base for this program theory. Methods The study described in this protocol paper is a realist review, which is a suitable approach to study complex interventions and fits the explanatory purpose of the study. We outline the steps to be taken for the systematic realist review, including the selection and assessment of studies and the methods for synthesizing the findings. Discussion Investigating the effects and the underlying mechanisms of support by experiential peers for individuals with delinquent behavior is relevant because the forensic setting has some unique features, and the involvement of service users might create even more tension than in other settings due to stigma and perceived risks. The findings that will be reported in the realist review will contribute to the knowledge of the effects of support by experiential peers and will provide insight into which aspects remain to be studied. It might also provide formal care institutions with guidance on whether to involve experiential peers in the delivery of their services and the conditions under which these interventions are likely to lead to positive results.

Abstract Background Overviews of systematic reviews (SRs) attempt to systematically retrieve and summarise the results of multiple systematic reviews. This is the second of two papers from a study aiming to develop a comprehensive evidence map of the methods used in overviews. Our objectives were to (a) develop a framework of methods for conducting, interpreting and reporting overviews (stage I)—the Methods for Overviews of Reviews (MOoR) framework—and (b) to create an evidence map by mapping studies that have evaluated overview methods to the framework (stage II). In the first paper, we reported findings for the four initial steps of an overview (specification of purpose, objectives and scope; eligibility criteria; search methods; data extraction). In this paper, we report the remaining steps: assessing risk of bias; synthesis, presentation and summary of the findings; and assessing certainty of the evidence arising from the overview. Methods In stage I, we identified cross-sectional studies, guidance documents and commentaries that described methods proposed for, or used in, overviews. Based on these studies, we developed a framework of possible methods for overviews, categorised by the steps in conducting an overview. Multiple iterations of the framework were discussed and refined by all authors. In stage II, we identified studies evaluating methods and mapped these evaluations to the framework. Results Forty-two stage I studies described methods relevant to one or more of the latter steps of an overview. Six studies evaluating methods were included in stage II. These mapped to steps involving (i) the assessment of risk of bias (RoB) in SRs (two SRs and three primary studies, all reporting evaluation of RoB tools) and (ii) the synthesis, presentation and summary of the findings (one primary study evaluating methods for measuring overlap). Conclusion Many methods have been described for use in the latter steps in conducting an overview; however, evaluation and guidance for applying these methods is sparse. The exception is RoB assessment, for which a multitude of tools exist—several with sufficient evaluation and guidance to recommend their use. Evaluation of other methods is required to provide a comprehensive evidence map.

Abstract Objective We conducted a trial embedded within the German National Cohort comparing the responses to study invitations sent in recycled envelopes of grey color vs. envelopes of white color. We analyzed paradata for reactions to the invitation letters by potential subjects, the duration between mailing date of the invitation and active responses, and study participation. Results Grey envelopes only slightly increased the chance of active responses (OR 1.16, 95% CI 0.83, 1.62) to the invitation letter. Potential study subjects with German nationality (OR 3.75, 95% CI 2.07, 7.66) and age groups above 50 years (50–59: OR 1.78, 95% CI 1.19, 2.69; 60–69: OR 2.25, 95% CI 1.48, 3.43) were more likely to actively respond to the invitation letter. The duration between mailing date of the invitation and active response was not associated with envelope color, sex, nationality, or age. Our trial replicates previous observations that the color of the envelope of a study invitation does not influence the likelihood of an active response or study participation.

Abstract Background Overviews of systematic reviews attempt to systematically retrieve and summarise the results of multiple systematic reviews. Methods for conducting, interpreting and reporting overviews are in their infancy. To date, there has been no evidence map of the methods used in overviews, thus making it difficult to determine the gaps and priorities for methods research. Our objectives were to develop and populate a comprehensive framework of methods for conducting, interpreting and reporting overviews (stage I) and to create an evidence map by mapping studies that have evaluated overview methods to the framework (stage II). Methods We searched methods collections (e.g. Cochrane Methodology Register, Meth4ReSyn library, AHRQ Effective Health Care Program) to identify eligible studies for both stages of this research. In stage I, cross-sectional studies, guidance documents and commentaries that described methods proposed for, or used in, overviews were used to develop and populate the framework of methods. Drafts and multiple iterations of the framework were discussed and refined by all authors. In stage II, we identified and described studies evaluating overview methods and mapped these evaluations to the framework. Results In this paper, we present results for the four initial steps of conducting an overview: (a) specification of the purpose, objectives and scope, (b) specification of the eligibility criteria, (c) search methods and (d) data extraction. Twenty-nine studies mentioned or described methods relevant to one or more of these steps. In the developed framework, identified methods and approaches were grouped according to the steps an overview author would need to undertake. Fifteen studies evaluated identified methods, all of which mapped to the search methods step. These studies either reported the development and evaluation of a new search filter to retrieve systematic reviews or compared the performance of multiple filters. Conclusion Gaps in the evaluation of methods were found for the majority of steps in the framework. More empirical studies are needed to evaluate the methods outlined and provide a comprehensive evidence map. The framework is useful for planning these evaluations and for planning methods required to deal with challenges that arise when conducting an overview.

Abstract Background Mental contrasting is a self-regulation strategy that is required for strong goal commitment. In mental contrasting, individuals firstly imagine a desired future or health goal that contrasted with the reality proceeding the goal state, which after reflection is viewed as an obstacle (Oettingen et al. J Pers Soc Psychol 80:736–753, 2001). Mentally contrasting a positive future with reality enables individuals to translate positive attitudes and high efficacy into strong goal commitment. Methods A systematic review of the literature is proposed to explore the efficacy of mental contrasting as a behaviour change technique (Michie et al., Ann Behav Med 46: 81-95, 2013) for health. The review also aims to identify the effects of mental contrasting on health-related behaviour, as well as identifying mediator and moderator variables. Discussion This will be the first systematic review of mental contrasting as a health behaviour change technique. With sufficient studies, a meta-analysis will be conducted with sensitivity and sub group analyses. If meta-analysis is not appropriate, a narrative synthesis of the reviewed studies will be conducted. Systematic review registration Review protocol registered on PROSPERO reference CRD42016034202 .

Abstract Background Computer-based examinations (CBE) ensure higher efficiency with respect to producibility and assessment compared to paper-based examinations (PBE). However, students often have objections against CBE and are afraid of getting poorer results in a CBE. The aims of this study were (1) to assess the readiness and the objections of students to a CBE vs. PBE (2) to examine the acceptance and satisfaction with the CBE on a voluntary basis, and (3) to compare the results of the examinations, which were conducted in different formats. Methods Fifth year medical students were introduced to an examination-player and were free to choose their format for the test. The reason behind the choice of the format as well as the satisfaction with the choice was evaluated after the test with a questionnaire. Additionally, the expected and achieved examination results were measured. Results Out of 98 students, 36 voluntarily chose a CBE (37%), 62 students chose a PBE (63%). Both groups did not differ concerning sex, computer-experience, their achieved examination results of the test, and their satisfaction with the chosen format. Reasons for the students' objections against CBE include the possibility for outlines or written notices, a better overview, additional noise from the keyboard or missing habits normally present in a paper based exam. The students with the CBE tended to judge their examination to be more clear and understandable. Moreover, they saw their results to be independent of the format. Conclusions Voluntary computer-based examinations lead to equal test scores compared to a paper-based format.

Abstract Introduction The vast difference in the abundance of different proteins in biological samples limits the determination of the complete proteome of a cell type, requiring fractionation of proteins and peptides before MS analysis. Methods We present a method consisting of electrophoresis of complex mixtures of peptides using a strip of filter paper cut into 20 sections laid end to end over a 24-cm-long IPG strip, the pH gradient of which would drive the electrophoresis. Peptides absorbed onto individual paper pads after electrophoresis are subsequently recovered into a buffer solution, thus dividing a complex peptide mixture according to pI into 20 liquid fractions. This paper-based IEF method (PIEF) was compared side-by-side with a similar but liquid-based Offgel electrophoresis (OGE) by analyzing iTRAQ-labeled peptide mixtures of membrane proteins from four different cell types. Results PIEF outperformed OGE in resolving acidic peptides, whereas OGE did a better job in recovering relatively basic peptides. OGE and PIEF were quite comparable in their coverage, identifying almost equal number of distinct proteins (PIEF =1174; OGE = 1080). Interestingly, however, only 675 were identified by both of them, each method identifying many unique proteins (PIEF = 499; OGE = 415). Thus, the two methods uncovered almost 40% more proteins compared to what is obtained by only one method. Conclusion: This initial investigation demonstrates the technical feasibility of PIEF for complementing OGE. PIEF uses standard IPG IEF equipment, requires no specialized apparatus (e.g., OGE fractionator) and may be integrated into peptide mapping strategies for clinical samples.

Abstract Keeping up with the rapidly growing literature has become virtually impossible for most scientists. This can have dire consequences. First, we may waste research time and resources on reinventing the wheel simply because we can no longer maintain a reliable grasp on the published literature. Second, and perhaps more detrimental, judicious (or serendipitous) combination of knowledge from different scientific disciplines, which would require following disparate and distinct research literatures, is rapidly becoming impossible for even the most ardent readers of research publications. Text mining -- the automated extraction of information from (electronically) published sources -- could potentially fulfil an important role -- but only if we know how to harness its strengths and overcome its weaknesses. As we do not expect that the rate at which scientific results are published will decrease, text mining tools are now becoming essential in order to cope with, and derive maximum benefit from, this information explosion. In genomics, this is particularly pressing as more and more rare disease-causing variants are found and need to be understood. Not being conversant with this technology may put scientists and biomedical regulators at a severe disadvantage. In this review, we introduce the basic concepts underlying modern text mining and its applications in genomics and systems biology. We hope that this review will serve three purposes: (i) to provide a timely and useful overview of the current status of this field, including a survey of present challenges; (ii) to enable researchers to decide how and when to apply text mining tools in their own research; and (iii) to highlight how the research communities in genomics and systems biology can help to make text mining from biomedical abstracts and texts more straightforward.