Optimising translational oncology in clinical practice: Strategies to accelerate progress in drug development.

Despite intense efforts, the socioeconomic burden of cancer remains unacceptably high and treatment advances for many common cancers have been limited, suggesting a need for a new approach to drug development. One issue central to this lack of progress is the heterogeneity and genetic complexity of many tumours. This results in considerable variability in therapeutic response and requires knowledge of the molecular profile of the tumour to guide appropriate treatment selection for individual patients. While recent advances in the molecular characterisation of different cancer types have the potential to transform cancer treatment through precision medicine, such an approach presents a major economic challenge for drug development, since novel targeted agents may only be suitable for a small cohort of patients. Identifying the patients who would benefit from individual therapies and recruiting sufficient numbers of patients with particular cancer subtypes into clinical trials is challenging, and will require collaborative efforts from research groups and industry in order to accelerate progress. A number of molecular screening platforms have already been initiated across Europe, and it is hoped that these networks, along with future collaborations, will benefit not only patients but also society through cost reductions as a result of more efficient use of resources. This review discusses how current developments in translational oncology may be applied in clinical practice in the future, assesses current programmes for the molecular characterisation of cancer and describes possible collaborative approaches designed to maximise the benefits of translational science for patients with cancer.

Joint Official Positions of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(®). Executive Summary of the 2010 Position Development Conference on Interpretation and use of FRAX® in clinical practice.

The International Society for Clinical Densitometry (ISCD) and the International Osteoporosis Foundation (IOF) convened the FRAX(®) Position Development Conference (PDC) in Bucharest, Romania, on November 14, 2010, following a two-day joint meeting of the ISCD and IOF on the "Interpretation and Use of FRAX(®) in Clinical Practice." These three days of critical discussion and debate, led by a panel of international experts from the ISCD, IOF and dedicated task forces, have clarified a number of important issues pertaining to the interpretation and implementation of FRAX(®) in clinical practice. The Official Positions resulting from the PDC are intended to enhance the quality and clinical utility of fracture risk assessment worldwide. Since the field of skeletal assessment is still evolving rapidly, some clinically important issues addressed at the PDCs are not associated with robust medical evidence. Accordingly, some Official Positions are based largely on expert opinion. Despite limitations inherent in such a process, the ISCD and IOF believe it is important to provide clinicians and technologists with the best distillation of current knowledge in the discipline of bone densitometry and provide an important focus for the scientific community to consider. This report describes the methodology and results of the ISCD-IOF PDC dedicated to FRAX(®).

Pharmacological treatment of behavioral and psychological symptoms of dementia (BPSD) in nursing homes: development of practice recommendations in a Swiss canton

OBJECTIVES: In 2002, the canton of Fribourg, Switzerland, implemented a coordinated pharmaceutical care service in nursing homes to promote rational drug use. In the context of this service, a project was conducted to develop recommendations for the pharmacological management of behavioral and psychological symptoms of dementia (BPSD) in nursing home residents. DESIGN AND METHODS: Selected evidence-based guidelines and meta-analysis sources related to the management of depression, insomnia, and agitation in dementia patients were systematically searched and evaluated. Evidence and controversies regarding the pharmacological treatment of the most common BPSD symptoms were reviewed, and treatment algorithms were developed. RESULTS: Ten evidence-based guidelines and meta-analyses for BPSD management were identified, with none specifically addressing issues related to nursing home residents. Based on this literature, recommendations were developed for the practice of pharmacological management of depression, sleep disturbances, and agitation in nursing home residents. For depression, SSRIs are considered the first choice if an antidepressant is required. No clear evidence has been found for sleep disturbances; the underlying conditions need to be investigated closely before the introduction of any drug therapy. Many drugs have been investigated for the treatment of agitation, and if necessary, antipsychotics could be used, although they have significant side effects. Several areas of uncertainty were identified, such as the current controversy about typical and atypical antipsychotic use or the appropriateness of cholinesterase inhibitors for controlling agitation. Treatment algorithms were presented to general practitioners, pharmacists, and medical directors of nursing homes in the canton of Fribourg, and will now be implemented progressively, using educational sessions, pharmaceutical counseling, and monitoring. CONCLUSION: Based on existing evidence-based studies, recommendations were developed for the practice of pharmacological management of depression, sleep disturbances, and agitation in nursing home residents. It should be further studied whether these algorithms implemented through pharmaceutical care services will improve psychotropic drug prescriptions and prevent drug-related problems in nursing home residents

Development of pharmaceutical care services in nursing homes: practice and research in a Swiss canton.

OBJECTIVE: The aim of this study was to assess the implementation process and economic impact of a new pharmaceutical care service provided since 2002 by pharmacists in Swiss nursing homes. SETTING: The setting was 42 nursing homes located in the canton of Fribourg, Switzerland under the responsibility of 22 pharmacists. METHOD: We developed different facilitators, such as a monitoring system, a coaching program, and a research project, to help pharmacists change their practice and to improve implementation of this new service. We evaluated the implementation rate of the service delivered in nursing homes. We assessed the economic impact of the service since its start in 2002 using statistical evaluation (Chow test) with retrospective analysis of the annual drug costs per resident over an 8-year period (1998-2005). MAIN OUTCOME MEASURES: The description of the facilitators and their implications in implementation of the service; the economic impact of the service since its start in 2002. RESULTS: In 2005, after a 4-year implementation period supported by the introduction of facilitators of practice change, all 42 nursing homes (2,214 residents) had implemented the pharmaceutical care service. The annual drug costs per resident decreased by about 16.4% between 2002 and 2005; this change proved to be highly significant. The performance of the pharmacists continuously improved using a specific coaching program including an annual expert comparative report, working groups, interdisciplinary continuing education symposia, and individual feedback. This research project also determined priorities to develop practice guidelines to prevent drug-related problems in nursing homes, especially in relation to the use of psychotropic drugs. CONCLUSION: The pharmaceutical care service was fully and successfully implemented in Fribourg's nursing homes within a period of 4 years. These findings highlight the importance of facilitators designed to assist pharmacists in the implementation of practice changes. The economic impact was confirmed on a large scale, and priorities for clinical and pharmacoeconomic research were identified in order to continue to improve the quality of integrated care for the elderly.

Influence de deux milieux séquentiels pour la culture d'embryons sur la production d'hormone gonadotrophine chorionique et de progestérone par des cellules JEG-3 et BeWo [Effects of different embryo development media on hCG and progesterone release by JEG-3 and BeWo cells]

Current in vitro fertilisation (IVF) practice requires synchronisation between the¦environment of cultured oocytes and embryos and the surroundings to what they would have¦been exposed to in vivo. Commercial, sequential media follow this requirement but their exact¦composition is not available. We have compared two widely used IVF culture media systems using¦the two choriocarcinoma cell lines JEG-3 and BeWo. The two hormones hCG and progesterone¦were determined in the culture supernatants as endpoints. In both cell lines, but in a more¦pronounced way in JEG-3, progesterone rather than hCG production was stimulated, and a¦higher hormone release was observed in the fertilisation than in the cleavage media. Differences¦between manufacturers were small and did not favour one system over the other. We conclude¦that both sequential media systems can be equally well used in current IVF laboratory practice.¦© 2012 Elsevier Masson SAS. All rights reserved.

Traitement pharmacologique de la schizophrénie: évaluation comparative de la qualité des recommandations de pratique clinique [Comparative evaluation of clinical practice guidelines for the treatment of schizophrenia]

INTRODUCTION: Many clinical practice guidelines (CPG) have been published in reply to the development of the concept of "evidence-based medicine" (EBM) and as a solution to the difficulty of synthesizing and selecting relevant medical literature. Taking into account the expansion of new CPG, the question of choice arises: which CPG to consider in a given clinical situation? It is of primary importance to evaluate the quality of the CPG, but until recently, there has been no standardized tool of evaluation or comparison of the quality of the CPG. An instrument of evaluation of the quality of the CPG, called "AGREE" for appraisal of guidelines for research and evaluation was validated in 2002. AIM OF THE STUDY: The six principal CPG concerning the treatment of schizophrenia are compared with the help of the "AGREE" instrument: (1) "the Agence nationale pour le développement de l'évaluation médicale (ANDEM) recommendations"; (2) "The American Psychiatric Association (APA) practice guideline for the treatment of patients with schizophrenia"; (3) "The quick reference guide of APA practice guideline for the treatment of patients with schizophrenia"; (4) "The schizophrenia patient outcomes research team (PORT) treatment recommendations"; (5) "The Texas medication algorithm project (T-MAP)" and (6) "The expert consensus guideline for the treatment of schizophrenia". RESULTS: The results of our study were then compared with those of a similar investigation published in 2005, structured on 24 CPG tackling the treatment of schizophrenia. The "AGREE" tool was also used by two investigators in their study. In general, the scores of the two studies differed little and the two global evaluations of the CPG converged; however, each of the six CPG is perfectible. DISCUSSION: The rigour of elaboration of the six CPG was in general average. The consideration of the opinion of potential users was incomplete, and an effort made in the presentation of the recommendations would facilitate their clinical use. Moreover, there was little consideration by the authors regarding the applicability of the recommendations. CONCLUSION: Globally, two CPG are considered as strongly recommended: "the quick reference guide of the APA practice guideline for the treatment of patients with schizophrenia" and "the T-MAP".

Epidémiologie clinique: définitions, utilités et raisons pour un développement en Suisse. [Clinical epidemiology: definitions, uses and reasons for development in Switzerland].

Clinical epidemiology is the most currently used name for a comparatively new branch of medicine covering a certain number of activities related to the practice of clinical medicine, but using epidemiological techniques and methods. Clinical epidemiology has only just begun to be known in Europe, whereas units are being increasingly developed and expanded in North America, particularly within the clinical departments of hospitals. The methods it offers are valid for both practicing physicians and hospital doctors (or those being trained in hospitals) and serve the purpose of promoting a better quality medical service, especially where a more adequate evaluation of the effectiveness of diagnostic methods, therapy and prognosis in medicine is concerned. Clinical epidemiology proposes a methodology of medical reasoning and of decision-making, as well as techniques intended to facilitate the indispensable task of keeping up with advances in medical knowledge.

Acute pain in adults admitted to the emergency room: development and implementation of abbreviated guidelines.

AIM: Although acute pain is frequently reported by patients admitted to the emergency room, it is often insufficiently evaluated by physicians and is thus undertreated. With the aim of improving the care of adult patients with acute pain, we developed and implemented abbreviated clinical practice guidelines (CG) for the staff of nurses and physicians in our hospital's emergency room. METHODS: Our algorithm is based upon the practices described in the international literature and uses a simultaneous approach of treating acute pain in a rapid and efficacious manner along with diagnostic and therapeutic procedures. RESULTS: Pain was assessed using either a visual analogue scale (VAS) or a numerical rating scale (NRS) at ER admission and again during the hospital stay. Patients were treated with paracetamol and/or NSAID (VAS/NRS <4) or intravenous morphine (VAS/NRS > or =04). The algorithm also outlines a specific approach for patients with headaches to minimise the risks inherent to a non-specific treatment. In addition, our algorithm addresses the treatment of paroxysmal pain in patients with chronic pain as well as acute pain in drug addicts. It also outlines measures for pain prevention prior to minor diagnostic or therapeutic procedures. CONCLUSIONS: Based on published guidelines, an abbreviated clinical algorithm (AA) was developed and its simple format permitted a widespread implementation. In contrast to international guidelines, our algorithm favours giving nursing staff responsibility for decision making aspects of pain assessment and treatment in emergency room patients.

Wissensvermehrung durch Konzeptentwicklung? Das Beispiel Vergänglichkeit [The contibution of concept development to nursing knowledge? The example of Transitoriness].

To provide nursing practice with evidence, it is important to understand nursing phenomena in detail. Therefore, good descriptions including the identification of characteristics and attributes of nursing phenomena on various levels of abstraction, i. e., concepts, are needed. In this article the significance of concept development for nursing science will be demonstrated by drawing on the example of 'transitoriness'. The evolutionary concept analysis proposed by Rodgers (2000) is introduced in more detail. Drawing on transitoriness, the phenomenon is presented with the help of the evolutionary concept analysis by Rodgers (2000). The phenomenon's characteristics and attributes are identified, as well as potential areas of application. Moreover, areas are outlined, in which interventions for nursing practice can be developed, implemented and evaluated. Thus, nursing practice is updated to include new findings and innovation. Through concept analysis nursing phenomena can be described in more detail, enhanced or broadened for use in nursing practice. Such structured processes as concept analysis can be employed successfully for other nursing phenomena. Concept analyses can lead to the identification of tasks for the respective scientific discipline and professionals. Thus, concept analyses can lead to the concretisation of tasks in nursing.

Appropriateness of respiratory care: development of evidence-based guidelines in an acute care hospital

Background: Respiratory care is universally recognised as useful, but its indications and practice vary markedly. In order to improve appropriateness of respiratory care in our hospital, we developed evidence-based local guidelines in a collaborative effort involving physiotherapists, physicians, and health services researchers. Methods: Recommendations were developed using the standardised RAND appropriateness method. A literature search was performed for the period between 1995 and 2008 based on terms associated with guidelines and with respiratory care. Publications were assessed according to the Oxford classification of quality of evidence. A working group prepared proposals for recommendations which were then independently rated by a multidisciplinary expert panel. All recommendations were then discussed in common and indications for procedures were rated confidentially a second time by the experts. Each indication for respiratory care was classified as appropriate, uncertain, or inappropriate, based on the panel median rating and the degree of intra-panel agreement. Results: Recommendations were formulated for the following procedures: non-invasive ventilation, continuous positive airway pressure, intermittent positive pressure breathing, intrapulmonary percussive ventilation, mechanical insufflation-exsufflation, incentive spirometry, positive expiratory pressure, nasotracheal suctioning, noninstrumental airway clearance techniques. Each recommendation referred to a particular medical condition, and was assigned to a hierarchical category based on the quality of evidence from literature supporting the recommendation and on the consensus of experts. Conclusion: Despite a marked heterogeneity of scientific evidence, the method used allowed us to develop commonly agreed local guidelines for respiratory care. In addition, this work fostered a closer relationship between physiotherapists and physicians in our institution.

Community introduction of practice parameters for autistic spectrum disorders: Advancing early recognition.

OBJECTIVES: Within a strong interdisciplinary framework, improvement in the quality of care for children with autistic spectrum disorders through a 2 year implementation program of Practice Parameters, aimed principally at improving early detection and intervention. METHOD: We developed Practice Parameters (PPs) for Pervasive Developmental Disorders and circulated the PPs to all child and adolescent psychiatrists practicing in the region. RESULTS: PP development and parallel information strategies resulted in a significant decrease of 1.5 years in the mean-age-at-diagnosis. However, further analysis indicated that improvement was only transient. CONCLUSION: Despite the encouraging improvement in mean-age-at-diagnosis 2 years after PP implementation, other indicators showed a failure to maintain the improvements. A systematic screening program would be the most reliable method to reinforce the PPs.

Interpretation and use of FRAX in clinical practice.

The introduction of the WHO FRAX® algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. Its use in fracture risk prediction has strengths, but also limitations of which the clinician should be aware and are the focus of this review INTRODUCTION: The International Osteoporosis Foundation (IOF) and the International Society for Clinical Densitometry (ISCD) appointed a joint Task Force to develop resource documents in order to make recommendations on how to improve FRAX and better inform clinicians who use FRAX. The Task Force met in November 2010 for 3 days to discuss these topics which form the focus of this review. METHODS: This study reviews the resource documents and joint position statements of ISCD and IOF. RESULTS: Details on the clinical risk factors currently used in FRAX are provided, and the reasons for the exclusion of others are provided. Recommendations are made for the development of surrogate models where country-specific FRAX models are not available. CONCLUSIONS: The wish list of clinicians for the modulation of FRAX is large, but in many instances, these wishes cannot presently be fulfilled; however, an explanation and understanding of the reasons may be helpful in translating the information provided by FRAX into clinical practice.

Effective continuing professional development for translating shared decision making in primary care: A study protocol.

Background: Shared decision making (SDM) is a process by which a healthcare choice is made jointly by the healthcare professional and the patient. SDM is the essential element of patient-centered care, a core concept of primary care. However, SDM is seldom translated into primary practice. Continuing professional development (CPD) is the principal means by which healthcare professionals continue to gain, improve, and broaden the knowledge and skills required for patient-centered care. Our international collaboration seeks to improve the knowledge base of CPD that targets translating SDM into the clinical practice of primary care in diverse healthcare systems. Methods: Funded by the Canadian Institutes of Health Research (CIHR), our project is to form an international, interdisciplinary research team composed of health services researchers, physicians, nurses, psychologists, dietitians, CPD decision makers and others who will study how CPD causes SDM to be practiced in primary care. We will perform an environmental scan to create an inventory of CPD programs and related activities for translating SDM into clinical practice. These programs will be critically assessed and compared according to their strengths and limitations. We will use the empirical data that results from the environmental scan and the critical appraisal to identify knowledge gaps and generate a research agenda during a two-day workshop to be held in Quebec City. We will ask CPD stakeholders to validate these knowledge gaps and the research agenda. Discussion: This project will analyse existing CPD programs and related activities for translating SDM into the practice of primary care. Because this international collaboration will develop and identify various factors influencing SDM, the project could shed new light on how SDM is implemented in primary care.