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The 1983 Orphan Drug Act in the United States (US) changed the landscape for development of therapeutics for rare or orphan diseases, which collectively affect approximately 300 million people worldwide, half of whom are children. The act has undoubtedly accelerated drug development for orphan diseases, with over 6,400 orphan drug applications submitted to the US Food and Drug Administration (FDA) from 1983 to 2023, including 350 drugs approved for over 420 indications. Drug development in this population is a global and collaborative endeavor. This position paper of the International Society for Central Nervous System Clinical Trials and Methodology (ISCTM) describes some potential best practices for the involvement of key stakeholder feedback in the drug development process. Stakeholders include advocacy groups, patients and caregivers with lived experience, public and private research institutions (including academia and pharmaceutical companies), treating clinicians, and funders (including the government and independent foundations). The authors articulate the challenges of drug development in orphan diseases and propose methods to address them. Challenges range from the poor understanding of disease history to development of endpoints, targets, and clinical trials designs, to finding solutions to competing research priorities by involved parties. [ABSTRACT FROM AUTHOR]

Background: Unhealthy diet is a key risk factor for Non-Communicable Diseases (NCDs) that contribute to increased morbidity and premature mortality. With increased computer literacy and mobile phone penetration, there is a high opportunity for mobile application-based interventions. The current study was conducted to develop a mobile application to monitor dietary intake and to assess its acceptability and effectiveness in diet control compared to a similar paper-based intervention. A mobile application was developed based on research evidence and opinions of local experts. The mobile application was introduced to a selected group of office workers who were in preparation, action, and maintenance stages of the Trans Theoretical Model (TTM) and a paper-based intervention was used as the comparator. Socio-demographic data were collected through a self-administered questionnaire. Participants were followed up for three months for adherence. The effectiveness of interventions was assessed at the end of three months by comparing the progressive change in the stage of change and the change from unhealthy to healthy dietary intake between two groups as primary and secondary outcomes respectively. Results: Among 123 office workers who participated in the study, 19.5% preferred the mobile intervention over the paper-based intervention. Younger, unmarried office workers and those who do not have children, had a higher acceptance for the mobile intervention (p < 0.05). There was no difference in adherence (in all three months) or outcomes between the two groups of intervention. Conclusion and recommendations: Mobile application-based interventions are better accepted among the young age group and further studies are recommended to explore their applicability. Trial registration: The study was registered in the Sri Lankan Clinical Trial Registry (Registration No. SLCTR/2020/025; Date 15th December 2020). [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has important implications for the safety of participants in clinical trials and the research staff caring for them and, consequently, for the trials themselves. Patients with heart failure may be at greater risk of infection with COVID-19 and the consequences might also be more serious, but they are also at risk of adverse outcomes if their clinical care is compromised. As physicians and clinical trialists, it is our responsibility to ensure safe and effective care is delivered to trial participants without affecting the integrity of the trial. The social contract with our patients demands no less. Many regulatory authorities from different world regions have issued guidance statements regarding the conduct of clinical trials during this COVID-19 crisis. However, international trials may benefit from expert guidance from a global panel of experts to supplement local advice and regulations, thereby enhancing the safety of participants and the integrity of the trial. Accordingly, the Heart Failure Association of the European Society of Cardiology on 21 and 22 March 2020 conducted web-based meetings with expert clinical trialists in Europe, North America, South America, Australia, and Asia. The main objectives of this Expert Position Paper are to highlight the challenges that this pandemic poses for the conduct of clinical trials in heart failure and to offer advice on how they might be overcome, with some practical examples. While this panel of experts are focused on heart failure clinical trials, these discussions and recommendations may apply to clinical trials in other therapeutic areas.

Background: Interest in and use of electronic consent (e-consent) in the conduct of academic clinical trials has increased since the COVID-19 pandemic. E-consent offers advantages including increased efficiency and accessibility, and reduced burden on site staff, which can be appealing to academic trialists anticipating challenges in recruitment to complex trial designs or with limited funding. However, there are many options to consider when using e-consent in a study protocol. This paper presents five case studies from Norwich Clinical Trials Unit, demonstrating how e-consent models can be effectively tailored to the needs of different trials. These examples illustrate the options around and benefits of e-consent, the acceptability of e-consent by participants, and the design considerations that were made during the development of the trial protocols. Case studies: Five randomised trials are presented, selected from a range of different trial designs, disease areas, interventions, and patient populations. E-consent was either offered as an alternative to paper consent, according to participant preference, or as the sole method of consent. E-consent was generally used to facilitate remote consent in decentralised trials but was also chosen to increase efficiency and reduce burden in an emergency department setting. The technical implementation of e-consent and detailed participant procedures were tailored to the needs of the trial settings and patient populations. For example, accompanying participant information sheets were provided in paper or electronic form, and electronic signatures could be typed or drawn. Administrative data on uptake of e-consent is presented where available. Conclusion: This paper demonstrates that the operational and technical aspects of implementing e-consent in clinical trials can be influenced by the trial design, the needs and characteristics of the trial population, financial/efficiency considerations, and level of risk. E-consent is not a one-size-fits-all tool for trials, and its use should be carefully considered during the development of the trial protocol, in conjunction with patient and public involvement contributors, site staff and other trial stakeholders. [ABSTRACT FROM AUTHOR]

Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.

Emerging evidence has shown that microRNAs play pivotal roles in wound healing. MicroRNA-21 (miR-21) was previously found to upregulate in order to fulfill an anti-inflammation role for wounds. Exosomal miRNAs have been identified and explored as essential markers for diagnostic medicine. However, the role of exosomal miR-21 in wounds has yet to be well studied. In order to facilitate the early management of poorly healing wounds, we developed an easy-to-use, rapid, paper-based microfluidic-exosomal miR-21 extraction device to determine wound prognosis in a timely manner. We isolated and then quantitatively examined exosomal miR-21 in wound fluids from normal tissues and acute and chronic wounds. Eight improving wounds displayed lower levels of exosomal miR-21 expression after wound debridement. However, four instances of increased exosomal miR-21 expression levels were notably associated with patients with poor healing wounds despite aggressive wound debridement, indicating a predictive role of tissue exosomal miR-21 for wound outcome. Paper-based nucleic acid extraction device provides a rapid and user-friendly approach for evaluating exosomal miR-21 in wound fluids as a means of monitoring wounds. Our data suggest that tissue exosomal miR-21 is a reliable marker for determining current wound status. [ABSTRACT FROM AUTHOR]

Abstract Background The Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) is a prevalent face-to-face interview method for measuring quality of life by integrating respondent-generated dimensions. To apply this method in clinical trials, a paper-administered alternative would be of interest. Therefore, our study aimed to analyze the agreement between the SEIQoL-DW and a paper questionnaire version (SEIQoL-PF/G). Methods In a crossover design, both measures were completed in a random sequence. 104 patients at a heart surgery hospital in Germany were randomly assigned to receive either the SEIQoL-DW or the SEIQoL-PF/G as the first measurement in the sequence. Patients were approached on their earliest stable day after surgery. The average time between both measurements was 1 day (mean 1.3; SD 0.8). Agreement regarding the indices, ratings, and weightings of nominated life areas (cues) was explored using Bland-Altman plots with 95% limits of agreement (LoA). Agreement of the SEIQoL indices was defined as acceptable if the LoA did not exceed a threshold of 10 scale points. Data from n = 99 patients were included in the agreement analysis. Results Both measures led to similarly nominated cues. The most frequently nominated cues were “physical health” and “family”. In the Bland-Altman plot, the indices showed a mean of differences of 2 points (95% CI, − 1 to 6). The upper LoA showed a difference of 36 points (95% CI, 30 to 42), and the lower LoA showed a difference of − 31 points (95% CI, − 37 to − 26). Thus, the LoAs and confidence intervals exceeded the predefined threshold. The Bland-Altman plots for the cue levels and cue weights showed similar results. The SEIQoL-PF/G version showed a tendency for equal weighting of cues, while the weighting procedure of the SEIQoL-DW led to greater variability. Conclusions For cardiac surgery patients, use of the current version of the SEIQoL-PF/G as a substitute for the SEIQoL-DW is not recommended. The current questionnaire weighting method seems to be unable to distinguish weighting for different cues. Therefore, the further design of a weighting method without interviewer support as a paper-administered measure of individual quality of life is desirable.

Background: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach. Objective: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials. Methods: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory. Results: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages. Conclusion: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges. [ABSTRACT FROM AUTHOR]

Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.

The safety and efficacy of pharmacotherapy in children, particularly preterms, neonates and infants, is limited by a paucity of good‐quality data from prospective clinical drug trials. A specific challenge is the establishment of valid biomarkers. OMICs technologies may support these efforts by complementary information about targeted and nontargeted molecules through systematic characterization and quantitation of biological samples. OMICs technologies comprise at least genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiomics in addition to the patient's phenotype. OMICs technologies are in part hypothesis‐generating, allowing an in depth understanding of disease pathophysiology and pharmacological mechanisms. Application of OMICs technologies in paediatrics faces major challenges before routine adoption. First, developmental processes need to be considered, including a subdivision into specific age groups as developmental changes clearly impact OMICs data. Second, compared to the adult population, the number of patients is limited as are the type and amount of necessary biomaterial, especially in neonates and preterms. Thus, advanced trial designs and biostatistical methods, noninvasive biomarkers, innovative biobanking concepts including data and samples from healthy children, as well as analytical approaches (eg liquid biopsies) should be addressed to overcome these obstacles. The ultimate goal is to link OMICs technologies with innovative analysis tools, such as artificial intelligence at an early stage. The use of OMICs data based on a feasible approach will contribute to the identification complex phenotypes and subpopulations of patients to improve the development of medicines for children with potential economic advantages. [ABSTRACT FROM AUTHOR]

The inclusion of pharmacists in the healthcare system of a developing country like Pakistan has always been a subject of debate among the healthcare professionals (HCPs), especially physicians, who have long ruled the healthcare system alone and who have had a long-held position of supremacy. The common argument against the inclusion of pharmacists is the dynamics of the healthcare system, and patients being physician oriented, hence, consider the inclusion of pharmacists as no good. Although the trend of defiance is changing, it is worthwhile mentioning here that the concept of the inclusion of pharmacist was implemented in developed countries by an evidence-based approach, i.e., to actually involve pharmacists in the disease state management of a patient and conducting a trial. This opinion calls for the same to be implemented in a developing country like Pakistan to evaluate its significance.

Background: There is an often-held assumption that the engagement of clinicians and healthcare organizations in research improves healthcare performance at various levels. Previous reviews found up to 28 studies suggesting a positive association between the engagement of individuals and healthcare organizations in research and improvements in healthcare performance. The current study sought to provide an update. Methods: We updated our existing published systematic review by again addressing the question: Does research engagement (by clinicians and organizations) improve healthcare performance? The search covered the period 1 January 2012 to March 2024, in two phases. First, the formal updated search ran from 1 January 2012 to 31 May 2020, in any healthcare setting or country and focussed on English language publications. In this phase two searches identified 66 901 records. Later, a further check of key journals and citations to identified papers ran from May 2020 to March 2024. In total, 168 papers progressed to full-text appraisal; 62 were identified for inclusion in the update. Then we combined papers from our original and updated reviews. Results: In the combined review, the literature is dominated by papers from the United States (50/95) and mostly drawn from the Global North. Papers cover various clinical fields, with more on cancer than any other field; 86 of the 95 papers report positive results, of which 70 are purely positive and 16 positive/mixed, meaning there are some negative elements (i.e. aspects where there is a lack of healthcare improvement) in their findings. Conclusions: The updated review collates a substantial pool of studies, especially when combined with our original review, which are largely positive in terms of the impact of research engagement on processes of care and patient outcomes. Of the potential engagement mechanisms, the review highlights the important role played by research networks. The review also identifies various papers which consider how far there is a "dose effect" from differing amounts of research engagement. Additional lessons come from analyses of equity issues and negative papers. This review provides further evidence of contributions played by systems level research investments such as research networks on processes of care and patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy for lung cancer has been a hot research area for years. This bibliometric analysis aims to present the research trends on lung cancer immunotherapy. Method: On 1 July, 2022, the authors identified 2,941 papers on lung cancer immunotherapy by the Web of Science and extracted their general information and the total number of citations. A bibliometric analysis was carried out to present the research landscape, demonstrate the research trends, and determine the most cited papers (top papers) as well as major journals on lung cancer immunotherapy. After that, recent research hotspots were analyzed based on the latest publications in major journals. Results: These 2,941 papers were cited a total of 122,467 times. “Nivolumab vs. docetaxel in advanced non–squamous non–small–cell lung cancer” published in 2015 by Borghaei H et al. was the most cited paper (5,854 citations). Among the journals, New England Journal of Medicine was most influential. Corresponding authors represented China took part in most articles (904) and papers with corresponding authors from the USA were most cited (139.46 citations per paper). Since 2015, anti–PD–(L)1 has become the hottest research area. Conclusions: This bibliometric analysis comprehensively and quantitatively presents the research trends and hotspots based on thousands of publications, and further suggests future research directions. Moreover, the results can benefit researchers to select journals and find potential collaborators. This study can help researchers get a comprehensive impression of the research landscape, historical development, and recent hotspots in lung cancer immunotherapy and provide inspiration for further research. [ABSTRACT FROM AUTHOR]

Introduction: Flexibility is an essential component of muscle function, and insufficient muscle flexibility may lead to muscle injuries. Decreased hamstring flexibility is one of the frequently reported risk factors for a hamstring strain and diminished athletic performance. Stretching is a commonly used intervention for increasing muscle length. There is a lack of evidence concerning the possible effects of hamstring stretching in balance and gait biomechanics. So, this study was designed to investigate the potential effects of static hamstring stretching on the range of motion (ROM), dynamic balance, and biomechanical variables of gait in athletes with hamstring tightness. Materials and Methods: This study is a single-group, pretest-posttest clinical trial performed on semi-professional female athletes. Twelve female athletes aged 20 to 35 years with bilateral hamstring tightness received a single session of unilateral static hamstring stretching on their randomly selected side. All subjects were assessed for straight leg raise, popliteal angle (using standard goniometry), perceived hamstring tightness (using a visual analog scale). They completed single-leg standing and 15-m walking and running tasks before and immediately after the intervention. The biomechanical parameters, including gait-line length, swing duration, and stance duration in walking tasks, maximum total force and mean total force in running task, and center of pressure (COP) displacement and standard deviation during balance task were measured using OpenGo sensor insole system. The pre-post values were compared using the paired sample t-test, and the level of significance was 0.05. Results: The values for straight leg raise and popliteal angle significantly increased (P<0.05) compared with the baseline, while perceived tightness significantly decreased following stretching (P<0.001). The amplitude (P₌0.006) and standard deviation (P₌0.016) of COP displacement in the mediolateral direction during the single leg stance balance task were significantly decreased after the intervention. Stance duration in slow walking (P₌0.004), as well as stance duration (P₌0.012) and swing duration (P<0.001) in fast walking, were significantly decreased (P<0.05) after stretching. No change was observed in gait biomechanical variables during the running test (P>0.05). Conclusion: The results of this study indicate that static hamstring stretching can be a promising intervention not just for increasing hamstring flexibility but also for improving balance ability. [ABSTRACT FROM AUTHOR]

Great expectations have been set around the clinical potential of regenerative and reparative medicine in the treatment of cardiovascular diseases [i.e. in particular, heart failure (HF)]. Initial excitement, spurred by encouraging preclinical data, resulted in a rapid translation into clinical research. The sobering outcome of the resulting clinical trials suggests that preclinical testing may have been insufficient to predict clinical outcome. A number of barriers for clinical translation include the inherent variability of the biological products and difficulties to develop potency and quality assays, insufficient rigour of the preclinical research and reproducibility of the results, manufacturing challenges, and scientific irregularities reported in the last years. The failure to achieve clinical success led to an increased scrutiny and scepticism as to the clinical readiness of stem cells and gene therapy products among clinicians, industry stakeholders, and funding bodies. The present impasse has attracted the attention of some of the most active research groups in the field, which were then summoned to analyse the position of the field and tasked to develop a strategy, to re-visit the undoubtedly promising future of cardiovascular regenerative and reparative medicine, based on lessons learned over the past two decades. During the scientific retreat of the ESC Working Group on Cardiovascular Regenerative and Reparative Medicine (CARE) in November 2018, the most relevant and timely research aspects in regenerative and/or reparative medicine were presented and critically discussed, with the aim to lay out a strategy for the future development of the field. We report herein the main ideas and conclusions of that meeting. [ABSTRACT FROM AUTHOR]

Background: The lack of a clear answer regarding the efficacy of physiotherapy in the treatment of cubital tunnel syndrome (CuTS) has led to attempts to critically assess the scientific studies conducted to date. Materials and Methods: Two databases (MEDLINE via PubMed and PEDro) and Google Scholar were used to search for papers. The inclusion criteria were randomized controlled trials, case series, and case reports that evaluate the effects of physiotherapy in the treatment of patients with CuTS. Results: A total of 18 studies met the eligibility criteria, capturing a total of 425 participants. Seven papers were randomized controlled trials, three more described prospective studies without a control group, and eight papers contained case reports. An analysis of the literature evaluating the effectiveness of various forms of broadly defined physiotherapy indicates that their use can have a beneficial effect in reducing many subjective and objective symptoms and improving function. In the majority of papers included in this review, their authors indicated positive therapeutic effects. Only one randomized controlled trial reported no change following therapy. It can therefore be stated that the results of the research conducted so far are optimistic. However, only 7 of the 18 papers were randomized controlled trials, while 3 were prospective studies, and 8 papers were case studies, in which 23 people with CuTS were studied. Conclusions: The small number of randomized clinical trials and their considerable heterogeneity do not allow firm conclusions to be drawn about the effectiveness of physiotherapy in the conservative treatment of CuTS. [ABSTRACT FROM AUTHOR]

The phenomenon of acute behavioral disturbance is an under-recognized and potentially life-threatening syndrome, and sometimes an emergency in psychiatric settings. Patients presenting to the Italian Emergency Departments (EDs) with acute behavioral disturbances account for approximately 3.2% of all ED visits. The spectrum of behaviors and of the signs overlaps with many clinical diseases. In addition to patients with behavioral problems related to mental disorders or substance abuse and toxicity, there is also a large group whose behavioral emergencies result from a medical illness. The complexity of these patients, as well as the interdisciplinary nature of their care, requires a clear and consensual framework for the appropriate medical management. A network of Italian scientific societies developed ten recommendations for good clinical practice. The main purpose is to draw up a document that presents a standardized method for the organization of the care of patients with acute behavioral disorders in EDs. [ABSTRACT FROM AUTHOR]

Background: Overall survival is the "gold standard" endpoint in cancer clinical trials. It plays a key role in determining the clinical- and cost-effectiveness of a new intervention and whether it is recommended for use in standard of care. The assessment of overall survival usually requires trial participants to be followed up for a long period of time. In this time, they may stop receiving the trial intervention and receive subsequent anti-cancer treatments, which also aim to extend survival, during trial follow-up. This can potentially change the interpretation of overall survival in the context of the clinical trial. This review aimed to determine how overall survival has been assessed in cancer clinical trials and whether subsequent anti-cancer treatments are considered. Methods: Two searches were conducted using MEDLINE within OVID© on the 9th of November 2021. The first sought to identify papers publishing overall survival results from randomised controlled trials in eight reputable journals and the second to identify papers mentioning or considering subsequent treatments. Papers published since 2010 were included if presenting or discussing overall survival in the context of treating cancer. Results: One hundred and thirty-four papers were included. The majority of these were presenting clinical trial results (98, 73%). Of these, 45 (46%) reported overall survival as a (co-) primary endpoint. A lower proportion of papers including overall survival as a (co-) primary endpoint compared to a secondary endpoint were published in recent years. The primary analysis of overall survival varied across the papers. Fifty-nine (60%) mentioned subsequent treatments. Seven papers performed additional analysis, primarily when patients in the control arm received the experimental treatment during trial follow-up (treatment switching). Discussion: Overall survival has steadily moved from being the primary to a secondary endpoint. However, it is still of interest with papers presenting overall survival results with the caveat of subsequent treatments, but little or no investigation into their effect. This review shows that there is a methodological gap for what researchers should do when trial participants receive anti-cancer treatment during trial follow-up. Future research will identify the stakeholder opinions, on how this methodological gap should be addressed. [ABSTRACT FROM AUTHOR]

Introduction: Sustained Attention (SA) failure is one of the main characteristics of Specific Learning Disorders (SLD). Recent studies have reported a positive effect of Cognitive Rehabilitation (CR) and Neurofeedback (NFB) on SA in SLD. Thus, the effectiveness of CR and NFB is well understood. This preliminary study aimed to compare the effects of CR and NFB on SA among the elementary school students with SLD, using a randomized controlled clinical trial. Methods: In this preliminary randomized controlled clinical trial, 53 eligible students with SLD (based on DSM-5) within the age range of 7 to 10 years were randomly assigned in the NFB (n=18), CR (n=18), and control group (n=17). All the participants were evaluated for SA using the Continuous Performance Test (CPT), at the time of entry to the study, and one month later. The intervention groups participated in 20 sessions of CR and 20 sessions of NFB, while the control group was evaluated without any intervention. Results: A total number of 24 boys and 36 girls in four groups (n=15) completed the study. The Mean±SD age of the participants in the CR, NFB, and control groups were 8.66±1.48 years, 8.40±1.73 years, and 8.53±1.63 years, respectively. Results showed a significant difference in the variables of the CPT between the study groups (P<0.05). Also, the CPT scores of the CR group were higher than that of the NFB group (P<0.001). Conclusion: This study supports that CR is more effective than NFB on SA in students with SLD. [ABSTRACT FROM AUTHOR]

This is a position paper of the Radiopharmacy Committee of the EANM (European Association of Nuclear Medicine) addressing toxicology studies for application of new diagnostic and therapeutic radiopharmaceuticals (RP) that are not approved (i.e., not having a marketing authorization or a monograph in the European Pharmacopoeia), excluding endogenous and ubiquitous substances in humans. This paper discusses the requirements for clinical trials with radiopharmaceuticals for clinical research applications, not necessarily intended to aim at a marketing authorization. If marketing authorization is intended, scientific advice of the competent authorities is mandatory and cannot be replaced by this position paper. The position paper reflects the view of the Radiopharmacy Committee of the EANM and can be used as a basis for discussions with the responsible authorities. [ABSTRACT FROM AUTHOR]

Summary: After more than 120 hand‐upper extremity and 37 face transplant procedures performed worldwide, vascularized composite allotransplantation (VCA) now falls under the scope of organ transplant legislation in Europe and the United States. While in the USA, VCA has been considered as standard care since 2014, VCA in Europe is still performed through clinical research trials, except in United Kingdom. However, after two decades of favourable experience with upper extremity transplantation (UET), professionals in Europe are proposing hand allotransplantation as "controlled standard" care, as opposed to face transplantation (FT), which is still a challenging activity. The European Committee on Organ Transplantation (CD‐P‐TO) has elaborated a position paper to provide recommendations concerning regulatory aspects for UET and FT. It is aimed at Health Authorities in charge of the oversight – and coordination – of organ donation and transplantation, and at professional groups to help them manage such complex and costly programs dedicated to properly selected patients. [ABSTRACT FROM AUTHOR]

Abstract Background Our current understanding of the pathophysiology and management of sepsis is associated with a lack of progress in clinical trials, which partly reflects insufficient appreciation of the heterogeneity of this syndrome. Consequently, more patient-specific approaches to treatment should be explored. Aims To summarize the current evidence on precision medicine in sepsis, with an emphasis on translation from theory to clinical practice. A secondary objective is to develop a framework enclosing recommendations on management and priorities for further research. Sources A global search strategy was performed in the MEDLINE database through the PubMed search engine (last search December 2017). No restrictions of study design, time, or language were imposed. Content The focus of this Position Paper is on the interplay between therapies, pathogens, and the host. Regarding the pathogen, microbiologic diagnostic approaches (such as blood cultures (BCs) and rapid diagnostic tests (RDTs)) are discussed, as well as targeted antibiotic treatment. Other topics include the disruption of host immune system and the use of biomarkers in sepsis management, patient stratification, and future clinical trial design. Lastly, personalized antibiotic treatment and stewardship are addressed (Fig. 1). Implications A road map provides recommendations and future perspectives. RDTs and identifying drug-response phenotypes are clear challenges. The next step will be the implementation of precision medicine to sepsis management, based on theranostic methodology. This highly individualized approach will be essential for the design of novel clinical trials and improvement of care pathways. [ABSTRACT FROM AUTHOR]

Modulation of vessel growth holds great promise for treatment of cardiovascular disease. Strategies to promote vascularization can potentially restore function in ischaemic tissues. On the other hand, plaque neovascularization has been shown to associate with vulnerable plaque phenotypes and adverse events. The current lack of clinical success in regulating vascularization illustrates the complexity of the vascularization process, which involves a delicate balance between pro- and anti-angiogenic regulators and effectors. This is compounded by limitations in the models used to study vascularization that do not reflect the eventual clinical target population. Nevertheless, there is a large body of evidence that validate the importance of angiogenesis as a therapeutic concept. The overall aim of this Position Paper of the ESC Working Group of Atherosclerosis and Vascular biology is to provide guidance for the next steps to be taken from pre-clinical studies on vascularization towards clinical application. To this end, the current state of knowledge in terms of therapeutic strategies for targeting vascularization in post-ischaemic disease is reviewed and discussed. A consensus statement is provided on how to optimize vascularization studies for the identification of suitable targets, the use of animal models of disease, and the analysis of novel delivery methods. [ABSTRACT FROM AUTHOR]

Introduction: Lumbar stiffness is a common complaint of patients with low back pain. The Muscle Energy Technique (MET) is a common intervention to treat the spine and sacroiliac joint dysfunctions and their resulting disability in daily activities. This research aimed to evaluate the effects of MET on pain, functional disability, and lumbar stiffness of patients with sacroiliac joint dysfunctions by considering the type of dysfunction and the orientation of the correcting maneuver. Materials and Methods: Fifty women with ant innominate or post innominate dysfunctions were recruited for the research and randomly divided into two groups (n=25). One group received one session of MET, and the other group received the sham position. Visual Analogue Scale (VAS), lumbar Stiffness Disability Index (SDI) and Oswestry Disability Index (ODI) were used for the evaluation of the participants before, 24 hours after and one week after the intervention. Results: According to the results, MET significantly decreased the mean range of VAS and ODI, 24 hours, and a week after the intervention (P<0.01). We did not see any significant difference in SDI values before, 24 hours, and one week after MET in the patients (P>0.01). Conclusion: Applying MET regarding the kind of dysfunction may reduce the patient's pain and disability. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to investigate the effects of shortened-length versus through-range exercise training on upper quarter posture in primary school students with Forward Head Posture (FHP). Materials and Methods: Sixty pain-free participants with FHP were randomly allocated to one of three groups; shortened-length training (n=20), through-range training (n=20), and notreatment control group (n=20). The shortened-length and through-range groups participated in training programs 3 times per week for 8 weeks. Upper quarter postures, including Craniovertebral Angle (CVA), Shoulder Angle (SA), Cranial Angle (CA), and thoracic kyphosis were measured by photogrammetry before and after the training. The confidence level was set at 95% (P<0.05). Results: After training, both exercise groups showed significant changes in CVA (P=0.001), SA (P=0.001), CA (P=0.001), and thoracic kyphosis (P=0.001) compared to the control group. Besides, CVA changed more in the shortened-length exercise group compared to the throughrange exercise group (P=0.003) (effect size =0.446). Conclusion: Both through-range and shortened-length exercises altered upper quarter alignment. The shortened-length training resulted in a more significant change in CVA. These changes were small, and more studies are needed to investigate the effects of such training programs among people with pain. [ABSTRACT FROM AUTHOR]