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Background We examined whether a context and process-sensitive ‘intelligent' checklist increases compliance with best practice compared with a paper checklist during intensive care ward rounds. Methods We conducted a single-centre prospective before-and-after mixed-method trial in a 35 bed medical and surgical ICU. Daily ICU ward rounds were observed during two periods of 8 weeks. We compared paper checklists (control) with a dynamic (digital) clinical checklist (DCC, intervention). The primary outcome was compliance with best clinical practice, measured as the percentages of checked items and unchecked critical items. Secondary outcomes included ICU stay and the usability of digital checklists. Data are presented as median (interquartile range). Results Clinical characteristics and severity of critical illness were similar during both control and intervention periods of study. A total of 36 clinicians visited 197 patients during 352 ward rounds using the paper checklist, compared with 211 patients during 366 ward rounds using the DCC. Per ICU round, a median of 100% of items (94.4–100.0) were completed by DCC, compared with 75.1% (66.7–86.4) by paper checklist (P=0.03). No critical items remained unchecked by the DCC, compared with 15.4% (8.3–27.3) by the paper checklist (P=0.01). The DCC was associated with reduced ICU stay (1 day [1–3]), compared with the paper checklist (2 days [1–4]; P=0.05). Usability of the DCC was judged by clinicians to require further improvement. Conclusions A digital checklist improved compliance with best clinical practice, compared with a paper checklist, during ward rounds on a mixed ICU. Clinical trial registration NCT 03599856.

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly infectious, carries significant morbidity and mortality, and has rapidly resulted in strained health care system and hospital resources. In addition to patient-related care concerns in infected individuals, focus must also relate to diminishing community spread, protection of staff, case selection, and concentration of resources. The current document based on available data and consensus opinion addresses appropriate catheterization laboratory preparedness for treating these patients, including procedure-room readiness to minimize external contamination, safe donning and doffing of personal protective equipment (PPE) to eliminate risk to staff, and staffing algorithms to minimize exposure and maximize team availability. Case selection and management of both emergent and urgent procedures are discussed in detail, including procedures that may be safely deferred or performed bedside.

Background: Over recent years, sentinel lymph node biopsy (SLNB) recommendations in guidelines for cutaneous melanoma have changed considerably. We aimed to assess trends in enactment of SLNB to evaluate to what extent guidelines were adhered to, and to identify clinical and pathological determinants of (non-)adherence. Methods: Clinicopathological data from the Dutch nationwide network and registry of histopathology and cytopathology were retrieved from patients diagnosed with primary cutaneous melanoma in The Netherlands between 2003 and 2014. SLNB enactment was analyzed per year. Multivariable regression models were developed to assess the determinants of SLNB enactment. Results: A total of 51,510 primary cutaneous melanomas in 49,514 patients were diagnosed, of which 24,603 melanomas were eligible for SLNB as they were staged T1b or higher. In practice, only 9761 (39.7%) patients underwent SLNB, with an increasing trend from 39.1% in 2003 to 47.8% in 2014 (p < 0.001). A total of 759 (2.9%) of 26,426 patients without SLNB indication underwent SLNB anyway. Variables significantly associated with enactment of SLNB were male sex, younger age, and melanoma on sites other than the head and neck. Conclusions: Although there was an increasing trend in time in SLNB enactment, enactment of SLNB did not comply well with recommendations in (inter)national guidelines. Female sex, higher age, and melanoma located on the head and neck were associated with non-enactment of SLNB.

Many clinical practice guidelines recommend similar approaches for the assessment and management of low back pain. Recommendations include use of a biopsychosocial framework to guide management with initial non-pharmacological treatment, including education that supports self-management and resumption of normal activities and exercise, and psychological programmes for those with persistent symptoms. Guidelines recommend prudent use of medication, imaging, and surgery. The recommendations are based on trials almost exclusively from high-income countries, focused mainly on treatments rather than on prevention, with limited data for cost-effectiveness. However, globally, gaps between evidence and practice exist, with limited use of recommended first-line treatments and inappropriately high use of imaging, rest, opioids, spinal injections, and surgery. Doing more of the same will not reduce back-related disability or its long-term consequences. The advances with the greatest potential are arguably those that align practice with the evidence, reduce the focus on spinal abnormalities, and ensure promotion of activity and function, including work participation. We have identified effective, promising, or emerging solutions that could offer new directions, but that need greater attention and further research to determine if they are appropriate for large-scale implementation. These potential solutions include focused strategies to implement best practice, the redesign of clinical pathways, integrated health and occupational interventions to reduce work disability, changes in compensation and disability claims policies, and public health and prevention strategies.

RATIONALE, AIMS AND OBJECTIVES: Evidence-based guidelines constitute a foundation for medical decision making. It is often unclear whether recommendations in general guidelines also apply to older people. This study aimed to develop a methodology to increase the focus on older people in the development of guidelines.METHODS: The methodology distinguishes 4 groups of older people: (1) relatively healthy older people; (2) older people with 1 additional specific (interfering) comorbid condition; (3) older people with multimorbidity; and (4) vulnerable older people.RESULTS: The level of focus on older people required may be determined by the prevalence of the disease or condition, level of suffering, social relevance, and the expectation that a guideline may improve the quality of care. A specialist in geriatric medicine may be involved in the guideline process via participation, provision of feedback on drafts, or involvement in the analysis of problem areas. Regarding the patient perspective, it is advised to involve organisations for older people or informal carers in the inventory of problem areas, and additionally to perform literature research of patient values on the subject. If the guideline focuses on older people, then the relative importance of the various outcome measures for this target group needs to be explicitly stated. Search strategies for all the 4 groups are suggested. For clinical studies that focus on the treatment of diseases that frequently occur in older people, a check should be made regarding whether these studies produce the required evidence. This can be achieved by verifying if there is sufficient representation of older people in the studies and determining if there is a separate reporting of results applying to this age group.

Authors/Task Force Members: Christa Boer (EACTA Chairperson)(Netherlands), Michael I. Meesters (Netherlands), Milan Milojevic (Netherlands), Umberto Benedetto (UK), Daniel Bolliger (Switzerland), Christian von Heymann (Germany), Anders Jeppsson (Sweden), Andreas Koster (Germany), Ruben L. Osnabrugge (Netherlands), Marco Ranucci (Italy), Hanne Berg Ravn (Denmark), Alexander B.A. Vonk (Netherlands), Alexander Wahba (Norway), Domenico Pagano (EACTS Chairperson)(UK),. Document Reviewers: Moritz W.V. Wyler von Ballmoos (USA), Mate Petricevic (Croatia), Arie Pieter Kappetein (Netherlands), Miguel Sousa-Uva (Portugal), Georg Trummer (Germany), Peter M. Rosseel (Netherlands), Michael Sander (Germany), Pascal Colson (France), Adrian Bauer (Germany).

Background/Aims There is a need for a simple and practical tool adapted for the diagnosis of chronic constipation (CC) in the Asian population. This study compared the Asian Neurogastroenterology and Motility Association (ANMA) CC tool and Rome III criteria for the diagnosis of CC in Asian subjects. Methods This multicenter, cross-sectional study included subjects presenting at outpatient gastrointestinal clinics across Asia. Subjects with CC alert symptoms completed a combination Diagnosis Questionnaire to obtain a diagnosis based on 4 different diagnostic methods: self-defined, investigator`s judgment, ANMA CC tool, and Rome III criteria. The primary endpoint was the level of agreement/ disagreement between the ANMA CC diagnostic tool and Rome III criteria for the diagnosis of CC. Results The primary analysis comprised of 449 subjects, 414 of whom had a positive diagnosis according to the ANMA CC tool. Rome III positive/ANMA positive and Rome III negative/ANMA negative diagnoses were reported in 76.8% and 7.8% of subjects, respectively, resulting in an overall percentage agreement of 84.6% between the 2 diagnostic methods. The overall percentage disagreement between these 2 diagnostic methods was 15.4%. A higher level of agreement was seen between the ANMA CC tool and self-defined (374 subjects [90.3%]) or investigator`s judgment criteria (388 subjects [93.7%]) compared with the Rome III criteria. Conclusion This study demonstrates that the ANMA CC tool can be a useful for Asian patients with CC. (J Neurogastroenterol Motil 2017;23:262-272)

In August 2019, ESC published new guidelines on Chronic Coronary Syndromes including a new risk assessment paradigm for estimation of pre-test-probability. The CAD-score is an acoustic-based score for ruling-out of coronary artery disease (CAD). In the current letter to the editor we re-evaluate the re-classification potential the CAD-score in the view of the new guidelines.

Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand.

Although pain is one of the most prevalent and bothersome symptoms children with cancer experience, evidence-based guidance regarding assessment and management is lacking. With 44 international, multidisciplinary healthcare professionals and nine patient representatives, we aimed to develop a clinical practice guideline (following GRADE methodology), addressing assessment and pharmacological, psychological, and physical management of tumor-, treatment-, and procedure-related pain in children with cancer. In this paper, we present our thorough methodology for this development, including the challenges we faced and how we approached these. This lays the foundation for our clinical practice guideline, for which there is a high clinical demand.

Objectives. To determine whether Caribbean states vary in health policy performance in 11 different areas; to explore the association with sociodemographic, economical, and governance determinants; and to estimate the potential health gains of “best-practice” health policies. Methods. We selected 50 indicators that included data on mortality (latest available, 2010–2015), intermediate outcomes, and policy implementation to calculate a state’s health policy performance score. We related this score to country characteristics and calculated the potential number of avoidable deaths if the age-specific mortality rates of best-performer Martinique applied in all states. Results. We found large differences in health policy performance among Caribbean states. Martinique, Cuba, and Guadeloupe had the highest performance scores, and Guyana, Belize, and Suriname the lowest. Political affiliation, religious fractionalization, corruption, national income, and population density were associated with health policy performance. If the mortality rates of Martinique applied to all Caribbean states, an overall mortality reduction of 12% would be achieved. Conclusions. Differences in health outcomes between Caribbean states are partly attributable to variations in health policy implementation. Our results suggest that many deaths can be prevented if Caribbean governments adopt best-practice policies.

We aimed to provide comprehensive protocols and promote effective management of pregnant women with gynecological cancers. New insights and more experience have been gained since the previous guidelines were published in 2014. Members of the International Network on Cancer, Infertility and Pregnancy (INCIP), in collaboration with other international experts, reviewed existing literature on their respective areas of expertise. Summaries were subsequently merged into a manuscript that served as a basis for discussion during the consensus meeting. Treatment of gynecological cancers during pregnancy is attainable if management is achieved by collaboration of a multidisciplinary team of health care providers. This allows further optimization of maternal treatment, while considering fetal development and providing psychological support and long-term follow-up of the infants. Nonionizing imaging procedures are preferred diagnostic procedures, but limited ionizing imaging methods can be allowed if indispensable for treatment plans. In contrast to other cancers, standard surgery for gynecological cancers often needs to be adapted according to cancer type and gestational age. Most standard regimens of chemotherapy can be administered after 14 weeks gestational age but are not recommended beyond 35 weeks. C-section is recommended for most cervical and vulvar cancers, whereas vaginal delivery is allowed in most ovarian cancers. Breast-feeding should be avoided with ongoing chemotherapeutic, endocrine or targeted treatment. More studies that focus on the long-term toxic effects of gynecologic cancer treatments are needed to provide a full understanding of their fetal impact. In particular, data on targeted therapies that are becoming standard of care in certain gynecological malignancies is still limited. Furthermore, more studies aimed at the definition of the exact prognosis of patients after antenatal cancer treatment are warranted. Participation in existing registries (www.cancerinpregnancy.org) and the creation of national tumor boards with multidisciplinary teams of care providers (supplementary Box S1, available at Annals of Oncology online) is encouraged. ispartof: ANNALS OF ONCOLOGY vol:30 issue:10 pages:1601-1612 ispartof: location:England status: published

Tissue hypoxia plays a key role in the development and progression of many kidney diseases. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is the most promising imaging technique to monitor renal tissue oxygenation in humans. BOLD-MRI measures renal tissue deoxyhaemoglobin levels voxel by voxel. Increases in its outcome measure R2* (transverse relaxation rate expressed as per second) correspond to higher deoxyhaemoglobin concentrations and suggest lower oxygenation, whereas decreases in R2* indicate higher oxygenation. BOLD-MRI has been validated against micropuncture techniques in animals. Its reproducibility has been demonstrated in humans, provided that physiological and technical conditions are standardized. BOLD-MRI has shown that patients suffering from chronic kidney disease (CKD) or kidneys with severe renal artery stenosis have lower tissue oxygenation than controls. Additionally, CKD patients with the lowest cortical oxygenation have the worst renal outcome. Finally, BOLD-MRI has been used to assess the influence of drugs on renal tissue oxygenation, and may offer the possibility to identify drugs with nephroprotective or nephrotoxic effects at an early stage. Unfortunately, different methods are used to prepare patients, acquire MRI data and analyse the BOLD images. International efforts such as the European Cooperation in Science and Technology (COST) action 'Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease' (PARENCHIMA) are aiming to harmonize this process, to facilitate the introduction of this technique in clinical practice in the near future. This article represents an extensive overview of the studies performed in this field, summarizes the strengths and weaknesses of the technique, provides recommendations about patient preparation, image acquisition and analysis, and suggests clinical applications and future developments.

In 2017, the American College of Cardiology (ACC), the American Heart Association (AHA), and 9 other American societies released guidelines for the prevention, detection, evaluation, and management of high blood pressure (BP) in adults.1 These guidelines are perhaps the most controversial set of US guidelines—even more so than those attributed to some of the committee set up to produce the guidelines of the Eighth Joint National Committee in 2014.2 Before discussing the various controversial aspects of the ACC/AHA guidelines, the International Society of Hypertension would like to congratulate the authors on 3 counts. First, emphasis was placed on the appropriate technique of BP measurements and the increased need for out-of-office BP measurement. Second, the value of risk assessment was recognized and introduced for the first time in US guidelines and finally, perhaps in part because of the controversial nature of the document, awareness of the importance of BP as a global cause of morbidity and mortality has been raised. The central controversy around which several others arise is the redefining of hypertension—as a systolic BP ≥130 mm Hg or a diastolic BP ≥80 mm Hg. Although there is a clear dose-response relationship between increasing BP levels and adverse cardiovascular outcomes,3 this preempts the ability, based on predicting cardiovascular events, of precisely defining hypertension. However, the pragmatic definition proposed by Geoffrey Rose decades ago should perhaps be considered—viz: “that level of BP above which investigation and management does more good than harm.”4 Does the new BP level proposed in the ACC/AHA guidelines fully satisfy that criterion? Perhaps not. To date, the relevant data are inconsistent and hence controversial. The problem arises because the definition of hypertension, treatment thresholds, and BP targets should …

This perspective covers a novel area of research describing the inadequacies of current approaches for diagnosing dysglycaemia and proposes that the 1-hour post-load glucose level during the 75-g oral glucose tolerance test may serve as a novel biomarker to detect dysglycaemia earlier than currently recommended screening criteria for glucose disorders. Considerable evidence suggests that a 1-hour post-load plasma glucose value ≥155 mg/dl (8.6 mmol/L) may identify individuals with reduced β-cell function prior to progressing to prediabetes and diabetes and is highly predictive of those likely to progress to diabetes more than the HbA1c or 2-hour post-load glucose values. An elevated 1-hour post-load glucose level was a better predictor of type 2 diabetes than isolated 2-hour post-load levels in Indian, Japanese, and Israeli and Nordic populations. Furthermore, epidemiological studies have shown that a 1-hour PG ≥155 mg/dl (8.6 mmol/L) predicted progression to diabetes as well as increased risk for microvascular disease and mortality when the 2-hour level was

Background The 2017 ACC/AHA guidelines on hypertension management recommend the introduction of antihypertensive treatment for patients with new stage 1 hypertension thresholds (130–139/80–89 mm Hg) and with a cardiovascular disease or related condition. We compared the Swiss population and economic impact of antihypertensive treatment of the 2017 ACC/AHA guidelines with the 2013 European guidelines. Methods Analyses were based on 4438 participants (aged 45–85 years; 2448 women) of the CoLaus|PsyCoLaus study recruited between 2014-2017. Participants eligible for antihypertensive treatment according to the 2017 ACC/AHA and 2013 European guidelines were sex and age standardised using the Swiss population for 2016. In addition, we estimated the population-wide annual costs of antihypertensive treatment. Results Individuals eligible for antihypertensive treatment were 40.3% (95% confidence interval 38.5–42.1) and 31.3% (29.7–32.9) according to the 2017 ACC/AHA and 2013 European guidelines, respectively. That difference would translate into approximately 250,000 additional individuals eligible for antihypertensive treatment, corresponding to an additional annual cost of 72.5 million CHF (63.0 million EUR). Conclusion The 2017 ACC/AHA guidelines on the management of hypertension substantially increase the number of individuals eligible for antihypertensive treatment compared to the 2013 European guidelines. While implementation of the 2017 ACC/AHA guidelines is expected to lead to cost reduction by preventing cardiovascular diseases, that reduction might be mitigated by the costs incurred by antihypertensive treatments in a larger proportion of the population.

International audience; The EACVI/ASE/Industry Task Force to standardize deformation imaging prepared this consensus document to standardize definitions and techniques for using two-dimensional (2D) speckle tracking echocardiography (STE) to assess left atrial, right ventricular, and right atrial myocardial deformation. This document is intended for both the technical engineering community and the clinical community at large to provide guidance on selecting the functional parameters to measure and how to measure them using 2D STE.This document aims to represent a significant step forward in the collaboration between the scientific societies and the industry since technical specifications of the software packages designed to post-process echocardiographic datasets have been agreed and shared before their actual development. Hopefully, this will lead to more clinically oriented software packages which will be better tailored to clinical needs and will allow industry to save time and resources in their development.

Objectives: Although clinically highly relevant, the recognition and treatment of bipolar mixed states has played only an underpart in recent guidelines. This WFSBP guideline has been developed to supply a systematic overview of all scientific evidence pertaining to the acute and long-term treatment of bipolar mixed states in adults. Methods: Material used for these guidelines is based on a systematic literature search using various data bases. Their scientific rigour was categorised into six levels of evidence (A–F), and different grades of recommendation to ensure practicability were assigned. We examined data pertaining to the acute treatment of manic and depressive symptoms in bipolar mixed patients, as well as data pertaining to the prevention of mixed recurrences after an index episode of any type, or recurrence of any type after a mixed index episode. Results: Manic symptoms in bipolar mixed states appeared responsive to treatment with several atypical antipsychotics, the best evidence resting with olanzapine. For depressive symptoms, addition of ziprasidone to treatment as usual may be beneficial; however, the evidence base is much more limited than for the treatment of manic symptoms. Besides olanzapine and quetiapine, valproate and lithium should also be considered for recurrence prevention. Limitations: The concept of mixed states changed over time, and recently became much more comprehensive with the release of DSM-5. As a consequence, studies in bipolar mixed patients targeted slightly different bipolar subpopulations. In addition, trial designs in acute and maintenance treatment also advanced in recent years in response to regulatory demands. Conclusions: Current treatment recommendations are still based on limited evidence, and there is a clear demand for confirmative studies adopting the DSM-5 specifier with mixed features concept.

BACKGROUND: Bridging the gap between clinical research and everyday health-care practice requires effective communication strategies. To address current shortcomings in conveying practice recommendations and supporting evidence, we are creating and testing presentation formats for clinical practice guidelines (CPGs). METHODS: We carried out multiple cycles of brainstorming and sketching, developing a prototype. Physicians participating in the user testing viewed CPG formats linked to clinical scenarios and engaged in semistructured interviews applying a think-aloud method for exploring important aspects of user experience. RESULTS: We developed a multilayered presentation format that allows clinicians to successively view more in-depth information. Starting with the recommendations, clinicians can, on demand, access a rationale and a key information section containing statements on quality of the evidence, balance between desirable and undesirable consequences, values and preferences, and resource considerations. We collected feedback from 27 stakeholders and performed user testing with 47 practicing physicians from six countries. Advisory group feedback and user testing of the first version revealed problems with conceptual understanding of underlying CPG methodology, as well as difficulties with the complexity of the layout and content. Extensive revisions made before the second round of user testing resulted in most participants expressing overall satisfaction with the final presentation format. CONCLUSIONS: We have developed an electronic, multilayered, CPG format that enhances the usability of CPGs for frontline clinicians. We have implemented the format in electronic guideline tools that guideline organizations can now use when authoring and publishing their guidelines.

The selection of appropriate outcomes is crucial when designing clinical trials in order to compare the effects of different interventions directly. For the findings to influence policy and practice, the outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. It is now widely acknowledged that insufficient attention has been paid to the choice of outcomes measured in clinical trials. Researchers are increasingly addressing this issue through the development and use of a core outcome set, an agreed standardised collection of outcomes which should be measured and reported, as a minimum, in all trials for a specific clinical area. Accumulating work in this area has identified the need for guidance on the development, implementation, evaluation and updating of core outcome sets. This Handbook, developed by the COMET Initiative, brings together current thinking and methodological research regarding those issues. We recommend a four-step process to develop a core outcome set. The aim is to update the contents of the Handbook as further research is identified. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1978-4) contains supplementary material, which is available to authorized users.

Objective: To determine the level of knowledge and attitudes of physicians in Tijuana based on Clinical Practice Guidelines (CPG) for the prevention, diagnosis and treatment of Nonspecific Low Back Pain (NLBP). Methods: Prospective, cross-sectional, descriptive study. Data were obtained from doctors who practice in clinics, private surgeries, and/or government institutions. Results: Of a total of 56 doctors surveyed, 37 were men and 19 women. None of the doctors said they had not seen a patient with Back Pain. 49% knew the GPC, and 51% did not know of its existence. Conclusions: Although some physicians reported knowledge of the GPC, according to the results, there was a lack of full knowledge of, and adherence to these guidelines. Not knowing the GPC did not make it impossible to complete the questionnaire. The doctors felt more connected to the health system, but with less confidence in the management of cases of NLBP. Objetivo: Determinar o nível de conhecimentos e a conduta dos médicos de Tijuana, com base nas Diretivas de Prática Clínica (DPC) para prevenção, diagnóstico e tratamento da dor lombar não específica (DLNE). Métodos: Estudo prospectivo, transversal e descritivo. Os dados foram obtidos junto a médicos que prestam serviços em clínicas, consultórios particulares e/ou instituições governamentais. Resultados: Atingiu-se um total de 56 médicos entrevistados, dos quais 37 eram homens e 19 mulheres. Nenhum médico disse que não atende um paciente com dor lombar. Do total, 49% conhecem as DPC e 51% não sabiam da sua existência. Conclusões: Apesar de alguns médicos relatarem conhecer as DPC, de acordo com os resultados obtidos, falta-lhes maior domínio e conformidade com relação a essas diretivas. Não conhecer as DPC não impossibilita responder ao questionário. Os médicos sentem-se mais conectados ao sistema de saúde, mas com menos confiança na conduta em casos DLI. Objetivo: Determinar el nivel de conocimientos y las actitudes de los médicos en Tijuana, con base en la Guía de Práctica Clínica (GPC) para la prevención, diagnóstico y tratamiento del Dolor Lumbar Inespecífico (DLI). Métodos: Estudio prospectivo, transversal y descriptivo. Los datos fueron obtenidos de los médicos que prestan sus servicios en clínicas, consultorios privados y/o instituciones de gobierno. Resultados: Se obtuvo un total de 56 médicos encuestados, 37 hombres y 19 mujeres. Ningún médico contestó que no atiende un paciente con dolor lumbar. El 49% conocen la GPC y el 51% no saben de su existencia. Conclusiones: A pesar de que algunos médicos refieren conocer la GPC, según los resultados obtenidos falta mayor dominio y apego de la misma. El no conocer la GPC no hace imposible contestar el cuestionario. Los médicos se sienten más conectados con el sistema de salud, pero con menor autoconfianza en el manejo del DLI.

In the past 8 years, both the International Working Group (IWG) and the US National Institute on AgingAlzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.

Background Screening for, diagnosis and management of intrauterine growth restriction (IUGR) is often performed in multidisciplinary collaboration. However, variation in screening methods, diagnosis and management of IUGR may lead to confusion. In the Netherlands two monodisciplinary guidelines on IUGR do not fully align. To facilitate effective collaboration between different professionals in perinatal care, we undertook a Delphi study with uniform recommendations as our primary result, focusing on issues that are not aligned or for which specifications are lacking in the current guidelines. Methods We conducted a Delphi study in three rounds. A purposively sampled selection of 56 panellists participated: 27 representing midwife-led care and 29 obstetrician-led care. Consensus was defined as agreement between the professional groups on the same answer and among at least 70% of the panellists within groups. Results Per round 51 or 52 (91% - 93%) panellists responded. This has led to consensus on 27 issues, leading to four consensus based recommendations on screening for IUGR in midwife-led care and eight consensus based recommendations on diagnosis and eight on management in obstetrician-led care. The multidisciplinary project group decided on four additional recommendations as no consensus was reached by the panel. No recommendations could be made about induction of labour versus expectant monitoring, nor about the choice for a primary caesarean section. Conclusions We reached consensus on recommendations for care for IUGR within a multidisciplinary panel. These will be implemented in a study on the effectiveness and cost-effectiveness of routine third trimester ultrasound for monitoring fetal growth. Research is needed to evaluate the effects of implementation of these recommendations on perinatal outcomes.

Guidelines are increasingly used in an effort to standardize and systematize health practices at the local level and to promote evidence-based practice. The implementation of guidelines frequently faces problems, however, and standardization processes may in general have other outcomes than the ones envisioned by the makers of standards. In 2012, the Danish National Health Authorities introduced a set of health promotion guidelines that were meant to guide the decision making and priority setting of Denmark's 98 local governments. The guidelines provided recommendations for health promotion policies and interventions and were structured according to risk factors such as alcohol, smoking and physical activity. This article examines the process of implementation of the new Danish health promotion guidelines. The article is based on qualitative interviews and participant observation, focusing on the professional practices of health promotion officers in four local governments as well as the field of Danish health promotion more generally. The analysis highlights practices and episodes related to the implementation of the guidelines and takes inspiration from Timmermans and Epstein's sociology of standards and standardization. It remains an open question whether or not the guidelines lead to more standardized policies and interventions, but we suggest that the guidelines promote a risk factor-oriented approach as the dominant frame for knowledge, reasoning, decision making and priority setting in health promotion. We describe this process as a case of epistemic standardization.

CONTEXT: Mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene cause the X-linked IGSF1 deficiency syndrome consisting of central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency, and occasionally transient partial GH deficiency. Since our first reports, we discovered 20 new families with 18 new pathogenic IGSF1 mutations. OBJECTIVE: We aimed to share data on the largest cohort of patients with IGSF1 deficiency to date and formulate recommendations for clinical management. METHODS: We collected clinical and biochemical characteristics of 69 male patients (35 children, 34 adults) and 56 female IGSF1 mutation carriers (three children, 53 adults) from 30 unrelated families according to a standardized clinical protocol. At evaluation, boys were treated with levothyroxine in 89%, adult males in 44%, and females in 5% of cases. RESULTS: Additional symptoms in male patients included small thyroid gland volume (74%), high birth weight (25%), and large head circumference (20%). In general, the timing of pubertal testicular growth was normal or even premature, in contrast to a late rise in T levels. Late adrenarche was observed in patients with prolactin deficiency, and adult dehydroepiandrosterone concentrations were decreased in 40%. Hypocortisolism was observed in 6 of 28 evaluated newborns, although cortisol concentrations were normal later. Waist circumference of male patients was increased in 60%, but blood lipids were normal. Female carriers showed low free T4 (FT4) and low-normal FT4 in 18% and 60%, respectively, delayed age at menarche in 31%, mild prolactin deficiency in 22%, increased waist circumference in 57%, and a negative correlation between FT4 concentrations and metabolic parameters. CONCLUSION: IGSF1 deficiency represents the most common genetic cause of central hypothyroidism and is associated with multiple other characteristics. Based on these results, we provide recommendations for mutational analysis, endocrine work-up, and long-term care.

BACKGROUND Switzerland recommends individuals who originate from high-prevalence countries to be screened for hepatitis C virus (HCV) infection. However, not all these persons are equally at risk. We thus aimed to describe the number and characteristics of persons with HCV infection born outside of Switzerland. METHODS We compared characteristics of anti-HCV-positive individuals in the Swiss Hepatitis C Cohort Study (SCCS) and of HCV cases reported to the Federal Office of Public Health (FOPH), with those of the general population in Switzerland. Persons who inject drugs (PWID) and persons who do not inject drugs (non-PWID) were compared by age groups for different countries of origin (represented by ≥1% of participants in the SCCS or FOPH). RESULTS We included 4,199 persons from the SCCS and 26,610 cases from the FOPH. Both groups had similar characteristics. In both data sources non-PWID were more frequent in foreign-born than in Swiss-born persons (63% versus 34% in the SCCS). The only subgroup with a clearly higher proportion both in the SCCS and FOPH than in the general population were persons over 60 years from Italy and Spain, with a 3.7- and 2.8-fold increase in the SCCS. These persons were non-PWID (99%), less frequently HIV- and anti-HBc positive and more often female than PWID from Italy and Spain; cirrhosis at enrolment was frequent (31%). Their HCV genotypes were consistent with those observed in elderly non-PWID of their birth countries. In the FOPH a higher proportion than in the general population was also seen for cases from Georgia and Russia. CONCLUSION The identification of subgroups in which HCV infection is particularly frequent might allow for better targeting HCV screening among foreign-born persons in Switzerland and elsewhere.

An increasing number of organizations worldwide are using new and improved standards for developing trustworthy clinical guidelines. One of such approaches, developed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group, offers systematic and transparent guidance in moving from evidence to recommendations. The GRADE strategy concentrates on four factors: the balance between benefits and harms, the certainty of the evidence, values and preferences, and resource considerations. However, it also considers issues around feasibility, equity, and acceptability of recommendations. GRADE distinguishes two types of recommendations: strong and weak. Strong recommendations reflect a clear preference for one alternative and should apply to all or almost all patients, obviating the need for a careful review of the evidence with each patient. Weak recommendations are appropriate when there is a close balance between desirable and undesirable consequences of alternative management strategies, uncertainty regarding the effects of the alternatives, uncertainty or variability in patients' values and preferences, or questionable cost-effectiveness. Weak recommendations usually require accessing the underlying evidence and a shared decision-making approach. Clinicians using GRADE recommendations should understand the meaning of the strength of the recommendation, be able to critically appraise the recommendation, and apply trustworthy recommendations according to their strength. (C) 2016 Elsevier Inc. All rights reserved.

This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.

The Latin American MS Experts' Forum has developed practical recommendations on the initiation and optimization of disease-modifying therapies in patients with relapsing–remitting multiple sclerosis (RRMS). The recommendations reflect the unique epidemiology of MS and the clinical practice environment in Latin American countries. Treatment response may be evaluated according to changes in relapses; progression, as assessed by the Expanded Disability Status Scale and the Timed 25-foot Walk; and lesion number on magnetic resonance imaging. Follow-up assessments are recommended every six months, or annually for stable patients. Cognitive function should be evaluated in all RRMS patients at baseline and annually thereafter. These recommendations are intended to assist clinicians in Latin America in developing a rational approach to treatment selection and sequencing for their RRMS patients.

Numerous guidelines and recommendations exist for the treatment of psoriasis in various populations. One important population is patients with psoriatic arthritis (PsA) who have symptoms of both joint and skin disease. In patients with both facets of psoriatic disease, skin and joints must be treated separately, but also simultaneously. As several systemic therapies are approved for either one or both, the concept of treating both facets with the same drug is feasible. This review summarizes evidence from studies in patients with PsA on the efficacy of these drugs on psoriatic skin disease in these patients.

BACKGROUND The Antithrombotic Therapy and the Prevention of Thrombosis, 9th Edition: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (AT9) represent trustworthy international guidelines for antithrombotic treatment and thromboprophylaxis. We describe major changes to the format and content resulting from applying new strategies for guideline adaptation and dissemination. METHODS A Norwegian guideline panel of 46 experts completed a structured and systematic adaptation process, updated the recommendations based on new evidence, and rewrote the recommendations in an electronic multilayered presentation format. We published the adapted guideline using the web-based Making GRADE the Irresistible Choice Guideline Authoring and Publication Platform. RESULTS We applied a novel presentation format to 333 recommendations from 11 of the 15 management chapters in AT9 and condensed and restructured them into 249 recommendations in a multilayered format. We added additional relevant information, such as 29 best-practice statements about new oral anticoagulants and practical information sections for 121 recommendations. Common reasons for modifications included feasibility of the recommendations in a national context, disagreement with applied baseline risk estimates, and reevaluation of the balance between the benefits and harms of interventions in relation to assumed typical patient preferences and values. The adapted guideline was published and disseminated online in November 2013. CONCLUSIONS New strategies for adapting, updating, and disseminating trustworthy guidelines proved feasible and will provide Norwegian health-care professionals and patients with up-to-date guidance tailored to national circumstances.

Adaptation of guidelines for use at the national or local level can facilitate their implementation. We developed and evaluated an adaptation process in adherence with standards for trustworthy guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, aiming for efficiency and transparency. This article is the first in a series describing our adaptation of Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines for a Norwegian setting.Informed by the ADAPTE framework, we developed a five-step adaptation process customized to guidelines developed using GRADE: (1) planning, (2) initial assessment of the recommendations, (3) modification, (4) publication, and (5) evaluation. We developed a taxonomy for describing how and why recommendations from the parent guideline were modified and applied a mixed-methods case study design for evaluation of the process.We published the adapted guideline in November 2013 in a novel multilayered format. The taxonomy for adaptation facilitated transparency of the modification process for both the guideline developers and the end users. We excluded 30 and modified 131 of the 333 original recommendations according to the taxonomy and developed eight new recommendations. Unforeseen obstacles related to acquiring a licensing agreement and procuring a publisher resulted in a 9-month delay. We propose modifications of the adaptation process to overcome these obstacles in the future.This case study demonstrates the feasibility of a novel guideline adaptation process. Replication is needed to further validate the usefulness of the process in increasing the organizational and methodologic efficiency of guideline adaptation.

Valvular regurgitation represents an important cause of cardiovascular morbidity and mortality. Echocardiography has become the primary non-invasive imaging method for the evaluation of valvular regurgitation. The echocardiographic assessment of valvular regurgitation should integrate the quantification of the regurgitation, assessment of the valve anatomy and function, as well as the consequences of valvular disease on cardiac chambers. In clinical practice, the management of patients with valvular regurgitation thus largely integrates the results of echocardiography. It is crucial to provide standards that aim at establishing a baseline list of measurements to be performed when assessing regurgitation.

Standards and guidance for developing trustworthy clinical practice guidelines are now available, and a number of leading guidelines adhere to the key standards. Even current trustworthy guidelines, however, generally suffer from a cumbersome development process, suboptimal presentation formats, inefficient dissemination to clinicians at the point of care, high risk of becoming quickly outdated, and suboptimal facilitation of shared decision-making with patients. To address these limitations, we have--in our innovative research program and nonprofit organization, MAGIC (Making GRADE the Irresistible Choice)--constructed a conceptual framework and tools to facilitate the creation, dissemination, and dynamic updating of trustworthy guidelines. We have developed an online application that constitutes an authoring and publication platform that allows guideline content to be written and structured in a database, published directly on our web platform or exported in a computer-interpretable language (eg, XML) enabling dissemination through a wide range of outputs that include electronic medical record systems, web portals, and applications for smartphones/tablets. Modifications in guidelines, such as recommendation updates, will lead to automatic alterations in these outputs with minimal additional labor for guideline authors and publishers, greatly facilitating dynamic updating of guidelines. Semiautomated creation of a new generation of decision aids linked to guideline recommendations should facilitate face-to-face shared decision-making in the clinical encounter. We invite guideline organizations to partner with us (www.magicproject.org) to apply and further improve the tools for their purposes. This work will result in clinical practice guidelines that we cannot only trust, but also easily share and use.

OBJECTIVE: Identify and evaluate current treatment recommendations in Europe for the care of children with diabetes in view of the European Union (EU) recommendations for Reference Centers. METHODS: A questionnaire was sent in 2008 to representatives of all EU countries and Norway, all known to be actively involved in pediatric diabetes care. Participants were asked whether specific guidelines were recommended and applied in their countries; when possible, they were invited to forward their national guidelines. As a second step, we evaluated the guideline mostly used in relationship to the recommendations of the EU. RESULTS: Information was obtained from all EU countries (including Scotland and Norway). National guidelines, as available, were forwarded for review. A 15/29 reported to use the International Society for Pediatric and Adolescent Diabetes (ISPAD) Clinical Practice Consensus Guidelines (CPCG), whereas 10 reported using national guidelines. These national guidelines were partly based on and/or compatible with ISPAD guidelines, but in most cases were far less detailed. The size and presentation differed (web based, booklet, page or chapter in adult guidelines). In four countries, no specific guidelines were used. As ISPAD CPCG were used most frequently, its content was evaluated within the EU Centres of Reference recommendations and minor changes were made in agreement with the ISPAD editor. DISCUSSION: Differences between guidelines may influence surveillance and quality of care in pediatric diabetes within Europe. Although a majority of countries is using or at least mentioning the ISPAD CPCG, their implementation as EU standard needs further endorsement. As language difficulties may hamper its implementation on a wider scale, further translation of the ISPAD guidelines should be endorsed to render it accessible to all healthcare professionals. With respect to the content, some changes were then made in agreement with the editors, adjusting them to the European context. For European Reference Centers, some further guidance on research may be included. Once implemented on an EU wide level, benchmarking of carefully defined robust quality of care and quality of life indicators will allow us to improve these guidelines on a regular basis ensuring an evidence-based care for all children with diabetes.

International audience; INTRODUCTION: Timely diagnosis of invasive candidiasis (IC) remains difficult as the clinical presentation is not specific and blood cultures lack sensitivity and need a long incubation time. Thus, non-culture-based methods for diagnosing IC have been developed. Mannan antigen (Mn) and anti-mannan antibodies (A-Mn) are present in patients with IC. On behalf of the Third European Conference on Infections in Leukemia, the performance of these tests was analysed and reviewed. METHODS: The literature was searched for studies using the commercially available sandwich enzyme-linked immunosorbent assays (Platelia™, Bio-Rad Laboratories, Marnes-la-Coquette, France) for detecting Mn and A-Mn in serum. The target condition of this review was IC defined according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity, specificity and diagnostic odds ratios (DOR) were calculated for Mn, A-Mn and combined Mn/A-Mn testing. RESULTS: Overall, 14 studies that comprised 453 patients and 767 controls were reviewed. The patient populations included in the studies were mainly haematological and cancer cases in seven studies and mainly intensive care unit and surgery cases in the other seven studies. All studies but one were retrospective in design. Mn sensitivity was 58% (95% confidence interval [CI], 53-62); specificity, 93% (95% CI, 91-94) and DOR, 18 (95% CI 12-28). A-Mn sensitivity was 59% (95% CI, 54-65); specificity, 83% (95% CI, 79-97) and DOR, 12 (95% CI 7-21). Combined Mn/A-Mn sensitivity was 83% (95% CI, 79-87); specificity, 86% (95% CI, 82-90) and DOR, 58 (95% CI 27-122). Significant heterogeneity of the studies was detected. The sensitivity of both Mn and A-Mn varied for different Candida species, and it was the highest for C. albicans, followed by C. glabrata and C. tropicalis. In 73% of 45 patients with candidemia, at least one of the serological tests was positive before the culture results, with mean time advantage being 6 days for Mn and 7 days for A-Mn. In 21 patients with hepatosplenic IC, 18 (86%) had Mn or A-Mn positive test results at a median of 16 days before radiological detection of liver or spleen lesions. CONCLUSIONS: Mn and A-Mn are useful for diagnosis of IC. The performance of combined Mn/A-Mn testing is superior to either Mn or A-Mn testing.

Although most surgical and invasive procedures can be performed safely in patients with haemophilia, the optimal level and duration of replacement therapy required to prevent bleeding complications have not been established conclusively. For providing more insight into optimal therapy during invasive procedures, a literature review of surgical procedures in patients with haemophilia was conducted. Concomitantly, current practice was surveyed in 26 European Haemophilia Comprehensive Care Centres, representing 15 different countries. The review identified 110 original papers published between 1965 and 2007. Of these, only two studies were randomized controlled trials. Target levels and the duration of replacement therapy in the published studies were as follows. For major orthopaedic surgery: preoperative targets were 80-90%; postoperative targets showed a high degree of variation, with trough levels ranging from 20% to 80%, duration 10-14 days; for liver biopsy, 70-100%, 1-7 days; tonsillectomy: 90-100%, 5-11 days; indwelling venous access device insertion: 100%, 3-10 days; circumcision: 50-60%, 2-4 days; dental surgery: 30-50%, single treatment. With the exception of dental surgery, current practice in Europe, as assessed by the survey, was largely in agreement with published data. In conclusion, this study provides both a comprehensive review and a large survey of replacement therapy in patients with haemophilia undergoing invasive procedures; these data have informed the consensus practical treatment recommendations made in this paper. This study highlights the need for better-designed studies in order to better define minimal haemostatic levels of replacement therapy and optimal treatment duration.

OBJECTIVE: To assess agreement between Cochrane Neonatal Group reviews and clinical practice guidelines in Denmark.DESIGN: Retrospective analysis of clinical guidelines for newborn infants.MATERIALS: All Cochrane neonatal reviews and Danish clinical guidelines for newborn infants.MAIN OUTCOME MEASURES: The recommendations from the Cochrane reviews and local clinical guidelines were compared and classified as being in agreement, in partial agreement or in disagreement. Authors of guidelines were asked whether Cochrane reviews had been considered during guideline development and reasons for any disagreements. Heterogeneity among departments was assessed.RESULTS: 173 interventions evaluated in Cochrane neonatal reviews were included. All 17 Danish neonatal departments agreed to participate, but only 14 (82%) delivered data. Agreement between reviews and guidelines was observed for a median of 132 interventions (76%) (range 129-134), partial agreement was observed for 31 interventions (18%) (range 29-33), and disagreement was observed for 10 interventions (6%) (range 8-13) (kappa = 0.56, range 0.53-0.59). Most of the latter 10 interventions were not recommended in the reviews but were recommended in the guidelines. There were numerous reasons for disagreement, the most common being usage of evidence with higher bias risks than randomised trials in guidelines development. Overall, Cochrane reviews were rarely (10%) used during guideline development. For nine guideline topics (5%) there was diversity among the Danish departments' recommendations.CONCLUSIONS: There is good agreement between Cochrane reviews and neonatal guidelines in Denmark. However, Cochrane reviews were rarely used for guideline development. Heterogeneity among guidelines produced by the various neonatal departments seems moderate.