Building a global consensus approach to chordoma: a position paper from the medical and patient community

Chordomas are very rare bone malignant tumours that have had a shortage of effective treatments for a long time. New treatments are now available for both the local and the metastatic phase of the disease, but the degree of uncertainty in selecting the most appropriate treatment remains high and their adoption remains inconsistent across the world, resulting in suboptimum outcomes for many patients. In December, 2013, the European Society for Medical Oncology (ESMO) convened a consensus meeting to update its clinical practice guidelines on sarcomas. ESMO also hosted a parallel consensus meeting on chordoma that included more than 40 chordoma experts from several disciplines and from both sides of the Atlantic, with the contribution and sponsorship of the Chordoma Foundation, a global patient advocacy group. The consensus reached at that meeting is shown in this position paper.

Current state of evidence on 'off-label' therapeutic options for systemic lupus erythematosus, including biological immunosuppressive agents, in Germany, Austria and Switzerland--a consensus report

Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include 'off-label' use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors' own experience with available drugs derived under very similar health care conditions. Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis). This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence.

Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach

Allogeneic hematopoietic SCT (HSCT) has been proposed as a treatment for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). HSCT has been performed in nine patients using different protocols with varying success. Based on this preliminary experience, participants of the first consensus conference propose a common approach to allogeneic HSCT in MNGIE. Standardization of the transplant protocol and the clinical and biochemical assessments will allow evaluation of the safety and efficacy of HSCT as well as optimization of therapy for patients with MNGIE.Bone Marrow Transplantation advance online publication, 3 May 2010; doi:10.1038/bmt.2010.100.

Practical approach to the use of daylight photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: a European consensus

INTRODUCTION Daylight-mediated photodynamic therapy has been shown to be an effective therapy for actinic keratoses (AKs) and a simple and tolerable treatment procedure in three randomized Scandinavian studies and two recent Phase III randomized controlled studies in Australia and Europe. OBJECTIVES To establish consensus recommendations for the use of daylight photodynamic therapy (DL-PDT) using topical methyl aminolaevulinate (MAL) in European patients with AKs. METHODS The DL-PDT consensus recommendations were developed on behalf of the European Society for Photodynamic Therapy in Dermatology and comprised of 10 dermatologists from different European countries with experience in how to treat AK patients with PDT. Consensus was developed based on literature review and experience of the experts in the treatment of AK using DL-PDT. RESULTS The recommendations arising from this panel of experts provide general guidance on the use of DL-PDT as a dermatological procedure with specific guidance regarding patient selection, therapeutic indications, when to treat, pre-treatment skin preparation, MAL application and daylight exposure for patients with AK in different countries of Europe. CONCLUSIONS This consensus recommendation provides a framework for physicians to perform DL-PDT with MAL cream while ensuring efficiency and safety in the treatment of patients with AK in different European countries.

The updated European Consensus 2009 on the use of Botulinum toxin for children with cerebral palsy

An interdisciplinary European group of clinical experts in the field of movement disorders and experienced Botulinum toxin users has updated the consensus for the use of Botulinum toxin in the treatment of children with cerebral palsy (CP). A problem-orientated approach was used focussing on both published and practice-based evidence. In part I of the consensus the authors have tabulated the supporting evidence to produce a concise but comprehensive information base, pooling data and experience from 36 institutions in 9 European countries which involves more than 10,000 patients and over 45,000 treatment sessions during a period of more than 280 treatment years. In part II of the consensus the Gross Motor Function Measure (GMFM) and Gross Motor Function Classification System (GMFCS) based Motor Development Curves have been expanded to provide a graphical framework on how to treat the motor disorders in children with CP. This graph is named "CP(Graph) Treatment Modalities - Gross Motor Function" and is intended to facilitate communication between parents, therapists and medical doctors concerning (1) achievable motor function, (2) realistic goal-setting and (3) treatment perspectives for children with CP. The updated European consensus 2009 summarises the current understanding regarding an integrated, multidisciplinary treatment approach using Botulinum toxin for the treatment of children with CP.

The Bernese Hypothermia Algorithm: a consensus paper on in-hospital decision-making and treatment of patients in hypothermic cardiac arrest at an alpine level 1 trauma centre

INTRODUCTION: Guidelines for the treatment of patients in severe hypothermia and mainly in hypothermic cardiac arrest recommend the rewarming using the extracorporeal circulation (ECC). However,guidelines for the further in-hospital diagnostic and therapeutic approach of these patients, who often suffer from additional injuries—especially in avalanche casualties, are lacking. Lack of such algorithms may relevantly delay treatment and put patients at further risk. Together with a multidisciplinary team, the Emergency Department at the University Hospital in Bern, a level I trauma centre, created an algorithm for the in-hospital treatment of patients with hypothermic cardiac arrest. This algorithm primarily focuses on the decision-making process for the administration of ECC. THE BERNESE HYPOTHERMIA ALGORITHM: The major difference between the traditional approach, where all hypothermic patients are primarily admitted to the emergency centre, and our new algorithm is that hypothermic cardiac arrest patients without obvious signs of severe trauma are taken to the operating theatre without delay. Subsequently, the interdisciplinary team decides whether to rewarm the patient using ECC based on a standard clinical trauma assessment, serum potassium levels, core body temperature, sonographic examinations of the abdomen, pleural space, and pericardium, as well as a pelvic X-ray, if needed. During ECC, sonography is repeated and haemodynamic function as well as haemoglobin levels are regularly monitored. Standard radiological investigations according to the local multiple trauma protocol are performed only after ECC. Transfer to the intensive care unit, where mild therapeutic hypothermia is maintained for another 12 h, should not be delayed by additional X-rays for minor injuries. DISCUSSION: The presented algorithm is intended to facilitate in-hospital decision-making and shorten the door-to-reperfusion time for patients with hypothermic cardiac arrest. It was the result of intensive collaboration between different specialties and highlights the importance of high-quality teamwork for rare cases of severe accidental hypothermia. Information derived from the new International Hypothermia Registry will help to answer open questions and further optimize the algorithm.

Consensus Document of the International Union of Angiology (IUA)-2013. Current concept on the management of arterio-venous management

Arterio-venous malformations (AVMs) are congenital vascular malformations (CVMs) that result from birth defects involving the vessels of both arterial and venous origins, resulting in direct communications between the different size vessels or a meshwork of primitive reticular networks of dysplastic minute vessels which have failed to mature to become 'capillary' vessels termed "nidus". These lesions are defined by shunting of high velocity, low resistance flow from the arterial vasculature into the venous system in a variety of fistulous conditions. A systematic classification system developed by various groups of experts (Hamburg classification, ISSVA classification, Schobinger classification, angiographic classification of AVMs,) has resulted in a better understanding of the biology and natural history of these lesions and improved management of CVMs and AVMs. The Hamburg classification, based on the embryological differentiation between extratruncular and truncular type of lesions, allows the determination of the potential of progression and recurrence of these lesions. The majority of all AVMs are extra-truncular lesions with persistent proliferative potential, whereas truncular AVM lesions are exceedingly rare. Regardless of the type, AV shunting may ultimately result in significant anatomical, pathophysiological and hemodynamic consequences. Therefore, despite their relative rarity (10-20% of all CVMs), AVMs remain the most challenging and potentially limb or life-threatening form of vascular anomalies. The initial diagnosis and assessment may be facilitated by non- to minimally invasive investigations such as duplex ultrasound, magnetic resonance imaging (MRI), MR angiography (MRA), computerized tomography (CT) and CT angiography (CTA). Arteriography remains the diagnostic gold standard, and is required for planning subsequent treatment. A multidisciplinary team approach should be utilized to integrate surgical and non-surgical interventions for optimum care. Currently available treatments are associated with significant risk of complications and morbidity. However, an early aggressive approach to elimiate the nidus (if present) may be undertaken if the benefits exceed the risks. Trans-arterial coil embolization or ligation of feeding arteries where the nidus is left intact, are incorrect approaches and may result in proliferation of the lesion. Furthermore, such procedures would prevent future endovascular access to the lesions via the arterial route. Surgically inaccessible, infiltrating, extra-truncular AVMs can be treated with endovascular therapy as an independent modality. Among various embolo-sclerotherapy agents, ethanol sclerotherapy produces the best long term outcomes with minimum recurrence. However, this procedure requires extensive training and sufficient experience to minimize complications and associated morbidity. For the surgically accessible lesions, surgical resection may be the treatment of choice with a chance of optimal control. Preoperative sclerotherapy or embolization may supplement the subsequent surgical excision by reducing the morbidity (e.g. operative bleeding) and defining the lesion borders. Such a combined approach may provide an excellent potential for a curative result. Conclusion. AVMs are high flow congenital vascular malformations that may occur in any part of the body. The clinical presentation depends on the extent and size of the lesion and can range from an asymptomatic birthmark to congestive heart failure. Detailed investigations including duplex ultrasound, MRI/MRA and CT/CTA are required to develop an appropriate treatment plan. Appropriate management is best achieved via a multi-disciplinary approach and interventions should be undertaken by appropriately trained physicians.

[Approach to prostate cancer in men older than 75 years: active or passive?]

Based on the exponential aging of the population and the increasing life expectancy in industrialized western countries, prostate cancer (PCa) in elderly men is becoming a disease of increasing significance. Consensus exists that men over the age of 75 years should not be screened for PCa; however, higher age as a single parameter should not exclude men from being diagnosed with prostate cancer and treated accordingly. It is well-known that overdiagnosis and overtreatment are frequent in this age group. Competing mortality risks of men older than 75 years may supersede the risk of dying from PCa several fold. Both the treating physician and the patient himself should therefore balance the possible risks and benefits of diagnosing and treating prostate cancer concerning the impact on quality of life. This is of special importance when taking into account that the complication rates of curative treatment modalities are higher in older patients than in younger men and that hormonal treatment might have negative effects especially in older men.Age, existing comorbidities, cognitive and physical status in combination with specific tumor parameters are useful tools for an individualized treatment.Therapy should be considered for healthy, active men aged 75 years or older who present with high-risk PCa and/or with a PSA doubling time <12 months. Elderly men who are unfit or have low to intermediate risk PCa will most likely not benefit from treatment.

Implants and/or teeth: consensus statements and recommendations

In August 23-25, 2007, the Scandinavian Society for Prosthetic Dentistry in collaboration with the Danish Society of Oral Implantology arranged a consensus conference on the topic 'Implants and/or teeth'. It was preceded by a workshop in which eight focused questions were raised and answered in eight review articles using a systematic approach. Twenty-eight academicians and clinicians discussed the eight review papers with the purpose to reach consensus on questions relevant for the topic. At the conference the consensus statements were presented as well as lectures based on the review articles. In this article the methods used at the consensus workshop are briefly described followed by the statements with comments.

Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children

Primary ciliary dyskinesia (PCD) is associated with abnormal ciliary structure and function, which results in retention of mucus and bacteria in the respiratory tract, leading to chronic oto-sino-pulmonary disease, situs abnormalities and abnormal sperm motility. The diagnosis of PCD requires the presence of the characteristic clinical phenotype and either specific ultrastructural ciliary defects identified by transmission electron microscopy or evidence of abnormal ciliary function. Although the management of children affected with PCD remains uncertain and evidence is limited, it remains important to follow-up these patients with an adequate and shared care system in order to prevent future lung damage. This European Respiratory Society consensus statement on the management of children with PCD formulates recommendations regarding diagnostic and therapeutic approaches in order to permit a more accurate approach in these patients. Large well-designed randomised controlled trials, with clear description of patients, are required in order to improve these recommendations on diagnostic and treatment approaches in this disease.

Diagnosis and Treatment of Venous Malformations Consensus Document of the International Union of Phlebology (IUP): updated 2013

Venous malformations (VMs) are the most common vascular developmental anomalies (birth defects) . These defects are caused by developmental arrest of the venous system during various stages of embryogenesis. VMs remain a difficult diagnostic and therapeutic challenge due to the wide range of clinical presentations, unpredictable clinical course, erratic response to the treatment with high recurrence/persistence rates, high morbidity following non-specific conventional treatment, and confusing terminology. The Consensus Panel reviewed the recent scientific literature up to the year 2013 to update a previous IUP Consensus (2009) on the same subject. ISSVA Classification with special merits for the differentiation between the congenital vascular malformation (CVM) and vascular tumors was reinforced with an additional review on syndrome-based classification. A "modified" Hamburg classification was adopted to emphasize the importance of extratruncular vs. truncular sub-types of VMs. This incorporated the embryological origin, morphological differences, unique characteristics, prognosis and recurrence rates of VMs based on this embryological classification. The definition and classification of VMs were strengthened with the addition of angiographic data that determines the hemodynamic characteristics, the anatomical pattern of draining veins and hence the risk of complication following sclerotherapy. The hemolymphatic malformations, a combined condition incorporating LMs and other CVMs, were illustrated as a separate topic to differentiate from isolated VMs and to rectify the existing confusion with name-based eponyms such as Klippel-Trenaunay syndrome. Contemporary concepts on VMs were updated with new data including genetic findings linked to the etiology of CVMs and chronic cerebrospinal venous insufficiency. Besides, newly established information on coagulopathy including the role of D-Dimer was thoroughly reviewed to provide guidelines on investigations and anticoagulation therapy in the management of VMs. Congenital vascular bone syndrome resulting in angio-osteo-hyper/hypotrophy and (lateral) marginal vein was separately reviewed. Background data on arterio-venous malformations was included to differentiate this anomaly from syndrome-based VMs. For the treatment, a new section on laser therapy and also a practical guideline for follow up assessment were added to strengthen the management principle of the multidisciplinary approach. All other therapeutic modalities were thoroughly updated to accommodate a changing concept through the years.

Management of postpartum hemorrhage (PPH): algorithm of the interdisciplinary D-A-CH consensus group PPH (Germany – Austria – Switzerland)

Postpartum hemorrhage (PPH) is one of the main causes of maternal deaths even in industrialized countries. It represents an emergency situation which necessitates a rapid decision and in particular an exact diagnosis and root cause analysis in order to initiate the correct therapeutic measures in an interdisciplinary cooperation. In addition to established guidelines, the benefits of standardized therapy algorithms have been demonstrated. A therapy algorithm for the obstetric emergency of postpartum hemorrhage in the German language is not yet available. The establishment of an international (Germany, Austria and Switzerland D-A-CH) "treatment algorithm for postpartum hemorrhage" was an interdisciplinary project based on the guidelines of the corresponding specialist societies (anesthesia and intensive care medicine and obstetrics) in the three countries as well as comparable international algorithms for therapy of PPH.The obstetrics and anesthesiology personnel must possess sufficient expertise for emergency situations despite lower case numbers. The rarity of occurrence for individual patients and the life-threatening situation necessitate a structured approach according to predetermined treatment algorithms. This can then be carried out according to the established algorithm. Furthermore, this algorithm presents the opportunity to train for emergency situations in an interdisciplinary team.

ISVI-IUA consensus document - diagnostic guidelines on vascular anomalies: vascular malformations and hemangiomas.

The diagnostic approach to vascular anomalies should include the distinction between vascular tumors (i.e. hemangiomas) and congential vascular malformations (CVMs). This step is based more on history and clinical examination rather than on instrumental evaluation. In children Duplex ultrasound and histology can be helpful to separate hypervasularized tumors from CVMs. Appropriate record of objective measures as size or flow volume is required in order to evaluate the progress of the pathology and/or to assess the results of adopted therapeutic interventions. The anatomic, pathological and hemodynamic characteristics, the secondary effects on the surrounding tissues and the systemic manifestations should be defined. Basic diagnostic tools are Duplex sonography followed by MRI or CT scanning. The definition of the vascular anomaly should be according to the Hamburg classification and should separate vascular tumors from vacular malformations followed by separation of high flow from low flow CVMs. Diagnostic investigations are best undertaken at centers where subsequent therapeutic interventions will be performed.

A practical approach to designing syndromic surveillance systems for livestock and poultry

The field of animal syndromic surveillance (SyS) is growing, with many systems being developed worldwide. Now is an appropriate time to share ideas and lessons learned from early SyS design and implementation. Based on our practical experience in animal health SyS, with additions from the public health and animal health SyS literature, we put forward for discussion a 6-step approach to designing SyS systems for livestock and poultry. The first step is to formalise policy and surveillance goals which are considerate of stakeholder expectations and reflect priority issues (1). Next, it is important to find consensus on national priority diseases and identify current surveillance gaps. The geographic, demographic, and temporal coverage of the system must be carefully assessed (2). A minimum dataset for SyS that includes the essential data to achieve all surveillance objectives while minimizing the amount of data collected should be defined. One can then compile an inventory of the data sources available and evaluate each using the criteria developed (3). A list of syndromes should then be produced for all data sources. Cases can be classified into syndrome classes and the data can be converted into time series (4). Based on the characteristics of the syndrome-time series, the length of historic data available and the type of outbreaks the system must detect, different aberration detection algorithms can be tested (5). Finally, it is essential to develop a minimally acceptable response protocol for each statistical signal produced (6). Important outcomes of this pre-operational phase should be building of a national network of experts and collective action and evaluation plans. While some of the more applied steps (4 and 5) are currently receiving consideration, more emphasis should be put on earlier conceptual steps by decision makers and surveillance developers (1-3).

Consensus on the Need for a Hierarchical List of Patient-reported Pain Outcomes for Metaanalyses of Knee Osteoarthritis Trials: An OMERACT Objective.

OBJECTIVE Although protocol registration for systematic reviews is still not mandatory, reviewers should be strongly encouraged to register the protocol to identify the methodological approach, including all outcomes of interest. This will minimize the likelihood of biased decisions in reviews, such as selective outcome reporting. A group of international experts convened to address issues regarding the need to develop hierarchical lists of outcome measurement instruments for a particular outcome for metaanalyses. METHODS Multiple outcome measurement instruments exist to measure the same outcome. Metaanalysis of knee osteoarthritis (OA) trials, and the assessment of pain as an outcome, was used as an exemplar to assess how Outcome Measures in Rheumatology (OMERACT), the Cochrane Collaboration, and other international initiatives might contribute in this area. The meeting began with formal presentations of background topics, empirical evidence from the literature, and a brief introduction to 2 existing hierarchical lists of pain outcome measurement instruments recommended for metaanalyses of knee OA trials. RESULTS After discussions, most participants agreed that there is a need to develop a methodology for generation of hierarchical lists of outcome measurement instruments to guide metaanalyses. Tools that could be used to steer development of such a prioritized list are the COSMIN checklist (Consensus-based Standards for the selection of health status Measurement Instruments) and the OMERACT Filter 2.0. CONCLUSION We list meta-epidemiological research agenda items that address the frequency of reported outcomes in trials, as well as methodologies to assess the best measurement properties (i.e., truth, discrimination, and feasibility).