Clinical Translation Of Research Findings Research Articles

20 years of improvement in stroke care: the rewards from finally funding more research

Substantial improvements have taken place in the outcomes of patients with cerebrovascular disease since the beginning of the 21st century. These improvements are mainly due to the rapid translation of clinical research findings into service provision, including the roll-out of urgent assessment and treatment of patients with suspected transient ischaemic attack or minor stroke, and the swift provision of thrombectomy for those with major ischaemic stroke.

\u201cIt\u2019s all about delivery\u201d: researchers and health professionals\u2019 views on the moral challenges of accessing neurobiological information in the context of psychosis

BackgroundThe convergence of neuroscience, genomics, and data science holds promise to unveil the neurobiology of psychosis and to produce new ways of preventing, diagnosing, and treating psychotic illness. Yet, moral challenges arise in neurobiological research and in the clinical translation of research findings. This article investigates the views of relevant actors in mental health on the moral challenges of accessing neurobiological information in the context of psychosis.MethodsSemi-structured individual interviews with two groups: researchers employed in the National Health Service (NHS) or a university in England (n = 14), and mental health professionals employed in NHS mental health services (n = 14). This article compares results in the two groups (total n = 28).ResultsThis article presents findings around three conceptual areas: (1) research ethics as mostly unproblematic, (2) psychosis, neurobiological information, and mental health care, and (3) identity, relationships, and the future. These areas are drawn from the themes and topics that emerged in the interviews across the two groups of participants. Researchers and health professionals provided similar accounts of the moral challenges of accessing—which includes acquisition, communication, and use of—neurobiological information in the context of psychosis. Acquiring neurobiological information was perceived as mostly unproblematic, provided ethical safeguards are put in place. Conversely, participants argued that substantive moral challenges arise from how neurobiological information is delivered—that is, communicated and used—in research and in clinical care. Neurobiological information was seen as a powerful tool in the process through which individuals define their identity and establish personal and clinical goals. The pervasiveness of this narrative tool may influence researchers and health professionals’ perception of ethical principles and moral obligations.ConclusionsThis study suggests that the moral challenges that arise from accessing neurobiological information in the context of psychosis go beyond traditional research and clinical ethics concerns. Reflecting on how accessing neurobiological information can influence individual self-narratives will be vital to ensure the ethical translation of neuroscience and genomics into mental health.Trial registrationThe study did not involve a health care intervention on human participants. It was retrospectively registered on 11 July 2018, registration number: researchregistry4255.

Ovine red cell concentrates for transfusion research – is the storage lesion comparable to human red cell concentrates?

Sheep are increasingly being used as a large in vivo animal model of blood transfusion because they provide several advantages over small animals. Understanding the effects of storage duration on ovine (ov) red cell concentrates (RCCs) and how these changes compare with stored human (hu) RCCs is necessary to facilitate clinical translation of research findings. OvRCCs (n=5) collected and processed in standard human blood collection packs, and equivalent huRCCs provided by Australian Red Cross Lifeblood (n=5), were stored at 2-6°C for 42days, with samples collected weekly. Haemolysis index was determined by measuring supernatant haemoglobin concentration. Biochemical parameters were evaluated using a blood gas analyser. Energy metabolites and biologically active lipids were measured using commercial assays. Osmotic fragility was determined by lysis in various saline concentrations. Extracellular vesicles were characterized by nanoparticle tracking analysis. Ovine red blood cells (RBCs) are double in number, smaller in size and more fragile than human RBCs. Haematological values were unchanged throughout storage. In contrast, biochemical and metabolic values, and haemolysis index in three of the five ovRCCs exceeded huRCCs licensing criteria by day 42. Accumulation of extracellular vesicles and biologically active lipids was comparable between huRCCs and ovRCCs. This study documents similarities and differences in the storage lesion of ovRCCs and huRCCs. This new information will guide the design of ovine transfusion models to enhance translation of findings to human transfusion settings.

Rethinking animal models of sepsis - working towards improved clinical translation whilst integrating the 3Rs.

Sepsis is a major worldwide healthcare issue with unmet clinical need. Despite extensive animal research in this area, successful clinical translation has been largely unsuccessful.We propose one reason for this is that, sometimes, the experimental question is misdirected or unrealistic expectations are being made of the animal model.As sepsis models can lead to a rapid and substantial suffering – it is essential that we continually review experimental approaches and undertake a full harm:benefit impact assessment for each study. In some instances, this may require refinement of existing sepsis models. In other cases, it may be replacement to a different experimental system altogether, answering a mechanistic question whilst aligning with the principles of reduction, refinement and replacement (3Rs).We discuss making better use of patient data to identify potentially useful therapeutic targets which can subsequently be validated in preclinical systems. This may be achieved through greater use of construct validity models, from which mechanistic conclusions are drawn. We argue that such models could provide equally useful scientific data as face validity models, but with an improved 3Rs impact. Indeed, construct validity models may not require sepsis to be modelled, per se. We propose that approaches that could support and refine clinical translation of research findings, whilst reducing the overall welfare burden on research animals.

Improving Health Education for Women Who Carry an FMR1 Premutation.

Women who carry an FMR1 (i.e., fragile X) premutation have specific health risks over their lifetime. However, little is known about their experience understanding these risks and navigating their health needs. The aim of this study was to use qualitative analysis to uncover both barriers and facilitators to personal healthcare using a framework of the Health Belief Model. Five focus groups were conducted with a total of 20 women who carry the FMR1 premutation using a semi-structured discussion guide. All sessions were transcribed verbatim and independently coded by two researchers. The coders used a deductive - inductive approach to determine the prominent themes related to the participants' experiences seeking healthcare for premutation-related conditions. Salient barriers to personal healthcare included difficult clinical translation of research findings, lack of knowledge among healthcare providers and among the women themselves, different priorities, and shortage of premutation-specific support and targeted educational materials. Facilitators included family members, national and community support organizations, research studies, compassionate physicians, and other premutation carriers. Addressing barriers to personal healthcare through up-to-date educational materials can help diminish misperceptions regarding health risks. Targeted educational materials will aid in information sharing and awareness for women who carry the FMR1 premutation and their physicians.

How psychiatry journals support the unbiased translation of clinical research. A cross-sectional study of editorial policies.

IntroductionReporting guidelines (e.g. CONSORT) have been developed as tools to improve quality and reduce bias in reporting research findings. Trial registration has been recommended for countering selective publication. The International Committee of Medical Journal Editors (ICMJE) encourages the implementation of reporting guidelines and trial registration as uniform requirements (URM). For the last two decades, however, biased reporting and insufficient registration of clinical trials has been identified in several literature reviews and other investigations. No study has so far investigated the extent to which author instructions in psychiatry journals encourage following reporting guidelines and trial registration.MethodPsychiatry Journals were identified from the 2011 Journal Citation Report. Information given in the author instructions and during the submission procedure of all journals was assessed on whether major reporting guidelines, trial registration and the ICMJE’s URM in general were mentioned and adherence recommended.ResultsWe included 123 psychiatry journals (English and German language) in our analysis. A minority recommend or require 1) following the URM (21%), 2) adherence to reporting guidelines such as CONSORT, PRISMA, STROBE (23%, 7%, 4%), or 3) registration of clinical trials (34%). The subsample of the top-10 psychiatry journals (ranked by impact factor) provided much better but still improvable rates. For example, 70% of the top-10 psychiatry journals do not ask for the specific trial registration number.DiscussionUnder the assumption that better reported and better registered clinical research that does not lack substantial information will improve the understanding, credibility, and unbiased translation of clinical research findings, several stakeholders including readers (physicians, patients), authors, reviewers, and editors might benefit from improved author instructions in psychiatry journals. A first step of improvement would consist in requiring adherence to the broadly accepted reporting guidelines and to trial registration.

Editorial: Translational research in practice

Readers will now be familiar with the notion of 'translational research'. According to its generally acknowledged progenitor, the National Institutes of Health (NIH) in the US, this is a kind of research agenda focused on translating or applying the research findings from basic/preclinical studies to human studies and perhaps most especially treatment trials; and, the translation of clinical research findings to the community so that evidence-based best practice is adopted.

Ex vivo culture of human prostate tissue and drug development

Although an array of new therapeutics exist for prostate cancer, the development of agents that can improve outcomes for men with prostate cancer remains inefficient, costly, and frustratingly slow. A major impediment to the clinical translation of research findings is the lack of preclinical models that can accurately predict the clinical efficacy of new drugs and, therefore, enable the selection of agents that are most suitable for clinical trials. An approach that is gaining popularity in the prostate cancer community is ex vivo culture of primary human tissues, which retains the native tissue architecture, hormone responsiveness, and cell-to-cell signalling of the tumour microenvironment in a dynamic and manipulable state. Ex vivo culture systems recapitulate the structural complexity and heterogeneity of human prostate cancers in a laboratory setting, making them an important adjunct to current cell-line-based and animal-based models. When incorporated into preclinical studies, ex vivo cultured tissues enable robust quantitative evaluation of clinically relevant end points representing drug efficacy, investigation of therapy resistance, and biomarker discovery. By providing new clinically relevant insights into prostate carcinogenesis, it is likely that ex vivo culture will enhance drug development programmes and improve the translational 'hit rate' for prostate cancer research.

Psychological and behavioral approaches to cardiac patients facing specific adjustment challenges

To some extent, all cardiac patients are challenged by their heart disease. Challenging issues concern the adjustment of patients to the cardiovascular disease and involve the physical, psychological, behavioral, and social dimensions of the person. Clearly, heart disease, its physical impact and the clinical sequelae (treatment and rehabilitation procedures) challenge patients at multiple levels by critically upsetting the homeostasis of their bio-psycho-social systems. Challenges may be very easy as well as very hard to accomplish and this variability does not depend only on the seriousness of the cardiac illness or on the impact of the correlated clinical and rehabilitation procedures, but it is also related to the psychosocial characteristics of patients, including personality and coping styles. When patients have difficulties in facing the multi-dimensional challenges of heart disease, they may show high levels of stress, anxiety, and depression as well as problematic behaviors such as resistance and poor adherence to treatment and preventive prescriptions, including behavioral modifications such as smoking cessation and physical exercise improvement. Given the huge amount of empirical evidence supporting the fact that smoking, physical inactivity, unhealthy diet, harmful use of alcohol as well as psychological distress are modifiable risk factors for cardiovascular morbidity and mortality, patients showing difficulties in adjusting to cardiac illness and the correlated clinical demands should be detected and then helped with behavioral and psychological interventions in facing the multi-dimensional challenges they are not able to overcome themselves. This book, edited by an experienced health psychologist in the field of “behavioral cardiology” and written by an international group of outstanding researchers and clinicians working in the expanding area of bio-psycho-social approaches to cardiac patients, covers firstly the psychological challenges and management needs of patients affected by specific cardiovascular conditions. With few exceptions, all chapters in the first part deserve particular consideration for their specialty contents. Clinicians working with cardiac patients affected by specific cardiovascular conditions such as ICD implantation for ventricular fibrillation, atrial fibrillation, heart failure, Takotsubo syndrome, and cardiac transplantation, may find in them extensive information about the unique psychological challenges and difficulties of living with such conditions and they may also acquire specialty knowledge on tailored psychological approaches to specific needs management. In the second and last part of the book, various psychological and behavioral interventions for cardiac patients are described. With the exception of the review chapter about anxiety and depression as risk factors for cardiovascular disease, whose inclusion in this section is questionable, the great part of issues that are covered along the second half of this book were rarely or never addressed in other similar publications. Bright spots are the chapters on computerized therapies and on the management of sleep problems, while a missing issue is the psychological and behavioral management of obese patients with heart disease, for which tailored multi-disciplinary interventions have already been planned and assessed (Manzoni et al., 2010, 2011). The declared purpose of this book is to inform clinicians who practice on the front line of the psychological and behavioral management of cardiac patients on topics where the research findings have not yet caught with practice and, at the same time, to provide them concrete, immediately applicable, translation of clinical research findings into tailored practical approaches (Castelnuovo, 2010a,b). It is noteworthy that clinicians whose this book is addressed will find in it all that was promised.

Developing organized level of biomedical evidence: evidence-based biomedicine

OPINION article Front. Physiol., 08 November 2012Sec. Clinical and Translational Physiology Volume 3 - 2012 | https://doi.org/10.3389/fphys.2012.00428

Genetics of schizophrenia: communicating scientific findings in the clinical setting

The expected identification of susceptibility genes for psychiatric disorders may bring new opportunities and expectations from patients and families for the clinical translation of research findings in psychiatric genetics. In this article information is provided about familial risk of schizophrenia with the theory behind individualizing risk of recurrence highlighted. Recent new findings regarding the new genetic frontier, Copy Number Variations (CNV), are summarized and the genetic architecture of familial and sporadic schizophrenia applicable to the clinical situation is reviewed. A scenario in which genetic testing could be applied in velocardiofacial syndrome (VCFS) type schizophrenia is debated. Referring to genetic discrimination in mental disorders, reference is made to the implementation of the Federal Genetic Information non-discrimination Act (GINA) of 2008 in the USA and the Mental Health Care Act of 2002 in SA.

Achieving High Research Reporting Quality Through the Use of Computational Ontologies

Systematic reviews and meta-analyses constitute one of the central pillars of evidence-based medicine. However, clinical trials are poorly reported which delays meta-analyses and consequently the translation of clinical research findings to clinical practice. We propose a Center of Excellence in Research Reporting in Neurosurgery (CERR-N) and the creation of a clinically significant computational ontology to encode Randomized Controlled Trials (RCT) studies in neurosurgery. A 128 element strong computational ontology was derived from the Trial Bank ontology by omitting classes which were not required to perform meta-analysis. Three researchers from our team tagged five randomly selected RCT's each, published in the last 5 years (2004-2008), in the Journal of Neurosurgery (JoN), Neurosurgery Journal (NJ) and Journal of Neurotrauma (JoNT). We evaluated inter and intra observer reliability for the ontology using percent agreement and kappa coefficient. The inter-observer agreement was 76.4%, 75.97% and 74.9% and intra-observer agreement was 89.8%, 80.8% and 86.56% for JoN, NJ and JoNT respectively. The inter-observer kappa coefficient was 0.60, 0.54 and 0.53 and the intra-observer kappa coefficient was 0.79, 0.82 and 0.79 for JoN, NJ and JoNT journals respectively. The high degree of inter and intra-observer agreement confirms tagging consistency in sections of a given scientific manuscript. Standardizing reporting for neurosurgery articles can be reliably achieved through the integration of a computational ontology within the context of a CERR-N. This approach holds potential for the overall improvement in the quality of reporting of RCTs in neurosurgery, ultimately streamlining the translation of clinical research findings to improvement in patient care.

Translating “Nondiabetic” A1C Levels to Clinical Practice

It is well recognized that there is a significant delay from the time clinical research findings are first reported and when the results become an integral part of clinical care. With the understanding that the prevalence and incidence of diabetes is increasing worldwide, and that the resulting complications are a major contributor to morbidity and mortality, the need for more rapid clinical translation of research findings for diabetes could not be greater. Specifically, a large amount of clinical research data has been reported in the recent past that is of great interest to the provider caring for individuals with diabetes. Much of the emphasis for research has been devoted to understanding the contribution of hyperglycemia and its treatment on macrovascular disease. For example, within the last decade, we have not only recognized the pivotal role that chronic hyperglycemia, as assessed with A1C levels, contributes to the development of microvascular complications, but we have recognized the importance of glycemia in contributing to cardiovascular disease (CVD) (1,2). Observations from large-scale prospective trials over the last couple of years have reported that in high-risk subjects, intensive therapy to lower A1C levels below suggested targets may not be beneficial or may increase mortality (3–5). However, as observed from these studies, we also learned that certain subsets of patients with type 2 diabetes may actually benefit from intensive glycemic control (3). The most recent analysis, reported in May 2010, has now suggested that mortality may actually be greater for those who maintain a higher A1C level despite attempts at intensive glycemic management …

Le conseil génétique en psychiatrie

There are several lines of evidence supporting the role of genetic factors in major psychiatric disorders. The evidence is mainly provided by family and twin studies. These have documented the familiality of disorders such as autism, schizophrenia, bipolar disorder or major depression. These data are relevant in providing information about familial risk of illness. Nevertheless, the available information is still limited and this probably justifies the little attention paid to genetic counselling for psychiatric disorders. However, probably related to the recent high profile of genetics, clinicians are now confronted with questions from patients and their families regarding risks of disorders for themselves and/or their relatives. Despite the difficulty to precise the risk of recurrence for psychiatric disorders and since having a family history of the disorder is currently the best predictor for the development of these disorders, it is noteworthy that the American Psychiatric Association guidelines for the treatment of bipolar disorder suggest that genetic counselling is helpful for patients who are considering having children. In the coming years the expected identification of susceptibility genes for psychiatric disorders may bring new opportunities and expectations from patients and families for the clinical translation of research findings in psychiatric genetics. We review evidence for possible increasing demand for genetic counselling, particularly if specific genes related to psychiatric disorders are identified. We also explore both the potential role of genetic counselling for psychiatric disorders and the issues involved in conveying genetic information in the clinical setting. The psychiatry genetics is currently in its infancy, but with accelerating advances in understanding the genetic basis of psychiatric disorders, psychiatrists will certainly be called upon to incorporate genetic information into clinical practice.

Genetic Counseling in Psychiatry

While psychiatrists may commonly discuss family history in clinical practice, there has been little systematic research documenting the role and effectiveness of genetic counseling for psychiatric disorders. In the coming years, the expected identification of susceptibility genes for psychiatric disorders may bring new opportunities and expectations from patients and families for the clinical translation of research findings in psychiatric genetics. We review evidence for possible increasing demand for genetic counseling, particularly if specific genes related to psychiatric disorders are identified. We then explore both the potential role of genetic counseling for psychiatric disorders and the issues involved in conveying genetic information in the clinical setting. Further research regarding the effectiveness of counseling interventions, as well as additional efforts directed at genetics education for clinicians, will be needed if emerging advances in genetic research are to be incorporated into clinical practice.