International consensus guidelines on the management of cytomegalovirus in solid organ transplantation.

Cytomegalovirus (CMV) remains one of the most common infections after solid organ transplantation, resulting in significant morbidity, graft loss, and occasional mortality. Management of CMV varies considerably among transplant centers. A panel of experts on CMV and solid organ transplant was convened by The Infectious Diseases Section of The Transplantation Society to develop evidence and expert opinion-based consensus guidelines on CMV management including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues.

De la recommandation d'un dépistage à son (non) implantation: le cas de l'anévrisme de l'aorte abdominale. [From guidelines for screening to their (poor) implementation: the case of the abdominal aortic aneurysm].

Suite à des essais cliniques randomisés démontrant l'efficacité du dépistage de l'anévrisme de l'aorte abdominale (AAA) par échographie, plusieurs recommandations ont été publiées dans de nombreux pays en faveur du dépistage dans une partie de la population générale. De plus, au-delà de la rupture aortique, le dépistage d'un petit AAA semble être une bonne occasion d'appliquer les stratégies de prévention secondaire, permettant une amélioration globale du pronostic cardiovasculaire du patient. Ces recommandations sont cependant peu suivies; les campagnes de dépistage systématique sont rares, laissant la responsabilité du dépistage au médecin généraliste. Cet article se propose de discuter les raisons de la non-implantation du dépistage de l'AAA. [Abstract] Following the evidence of benefits of ultrasound screening for abdominal aorta aneurysms (AAA), several guidelines support this screening in population. Beyond the prompt diagnosis of AAA prior to its rupture of grim vital prognosis, small AAA can beconsidered as a prognostic marker for cardiovascular diseases (CVD). Yet, its detection is an opportunity for secondary prevention to reduce CVD mortality. Despite, these guidelines are poorly applied: systematic screening campaigns are infrequent, making the screening of family physicians responsibility. While the major benefit from this screening strategy is to reduce AAA-related death (but only trivial effect on long-term total mortality), this explains only partially the lack of guidelines implementation. The reasons of the poor implementation of these guidelines are discussed herein.

How can we teach EBM in clinical practice? : an analysis of barriers to implementation of on-the-job EBM teaching and learning.

Introduction: Evidence-based medicine (EBM) improves the quality of health care. Courses on how to teach EBM in practice are available, but knowledge does not automatically imply its application in teaching. We aimed to identify and compare barriers and facilitators for teaching EBM in clinical practice in various European countries. Methods: A questionnaire was constructed listing potential barriers and facilitators for EBM teaching in clinical practice. Answers were reported on a 7-point Likert scale ranging from not at all being a barrier to being an insurmountable barrier. Results: The questionnaire was completed by 120 clinical EBM teachers from 11 countries. Lack of time was the strongest barrier for teaching EBM in practice (median 5). Moderate barriers were the lack of requirements for EBM skills and a pyramid hierarchy in health care management structure (median 4). In Germany, Hungary and Poland, reading and understanding articles in English was a higher barrier than in the other countries. Conclusion: Incorporation of teaching EBM in practice faces several barriers to implementation. Teaching EBM in clinical settings is most successful where EBM principles are culturally embedded and form part and parcel of everyday clinical decisions and medical practice.

EFNS guidelines on cognitive rehabilitation: report of an EFNS task force.

Disorders of language, spatial perception, attention, memory, calculation and praxis are a frequent consequence of acquired brain damage [in particular, stroke and traumatic brain injury (TBI)] and a major determinant of disability. The rehabilitation of aphasia and, more recently, of other cognitive disorders is an important area of neurological rehabilitation. We report here a review of the available evidence about effectiveness of cognitive rehabilitation. Given the limited number and generally low quality of randomized clinical trials (RCTs) in this area of therapeutic intervention, the Task Force considered, besides the available Cochrane reviews, evidence of lower classes which was critically analysed until a consensus was reached. In particular, we considered evidence from small group or single cases studies including an appropriate statistical evaluation of effect sizes. The general conclusion is that there is evidence to award a grade A, B or C recommendation to some forms of cognitive rehabilitation in patients with neuropsychological deficits in the post-acute stage after a focal brain lesion (stroke, TBI). These include aphasia therapy, rehabilitation of unilateral spatial neglect (ULN), attentional training in the post-acute stage after TBI, the use of electronic memory aids in memory disorders, and the treatment of apraxia with compensatory strategies. There is clearly a need for adequately designed studies in this area, which should take into account specific problems such as patient heterogeneity and treatment standardization.

Guidelines for perioperative care for pancreaticoduodenectomy: Enhanced Recovery After Surgery (ERAS®) Society recommendations.

BACKGROUND & AIMS: Protocols for enhanced recovery provide comprehensive and evidence-based guidelines for best perioperative care. Protocol implementation may reduce complication rates and enhance functional recovery and, as a result of this, also reduce length-of-stay in hospital. There is no comprehensive framework available for pancreaticoduodenectomy. METHODS: An international working group constructed within the Enhanced Recovery After Surgery (ERAS®) Society constructed a comprehensive and evidence-based framework for best perioperative care for pancreaticoduodenectomy patients. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group. The quality of evidence was rated "high", "moderate", "low" or "very low". Recommendations were graded as "strong" or "weak". RESULTS: Comprehensive guidelines are presented. Available evidence is summarised and recommendations given for 27 care items. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations. CONCLUSIONS: The present evidence-based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy. A unified protocol allows for comparison between centres and across national borders. It facilitates multi-institutional prospective cohort registries and adequately powered randomised trials.

Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations.

BACKGROUND: This review aims to present a consensus for optimal perioperative care in colonic surgery and to provide graded recommendations for items for an evidenced-based enhanced perioperative protocol. METHODS: Studies were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts. For each item of the perioperative treatment pathway, available English-language literature was examined, reviewed and graded. A consensus recommendation was reached after critical appraisal of the literature by the group. RESULTS: For most of the protocol items, recommendations are based on good-quality trials or meta-analyses of good-quality trials (quality of evidence and recommendations according to the GRADE system). CONCLUSIONS: Based on the evidence available for each item of the multimodal perioperative-care pathway, the Enhanced Recovery After Surgery (ERAS) Society, International Association for Surgical Metabolism and Nutrition (IASMEN) and European Society for Clinical Nutrition and Metabolism (ESPEN) present a comprehensive evidence-based consensus review of perioperative care for colonic surgery.

First explicit criteria to decide on the appropriateness of therapy of ulcerative colitis: the European EPATUC panel

Background: Ulcerative colitis (UC) is a chronic disease with a wide variety of treatment options many of which are not evidence based. Supplementing available guidelines, which are often broadly defined, consensus-based and generally not tailored to specifically reflect the individual patient situation, we developed explicit appropriateness criteria to assist, and improve treatment decisions. Methods: We used the RAND appropriateness method which does not force consensus. An extensive literature review was compiled based on and supplementing, where necessary, the ECCO UC 2011 guidelines. EPATUC (endorsed by ECCO) was formed by 7 gastroenterologists, 2 surgeons and 2 general practitioners from throughout Europe. Clinical scenarios reflecting practice were rated on a 9-point scale from 1 (extremely inappropriate) to 9 (extremely appropriate), based on the expert's experience and the available literature. After extensive discussion, all scenarios were re-rated at a two-day panel meeting. Median and disagreement (D) were used to categorize ratings into 3 categories: appropriate (A), uncertain (U) and inappropriate (I). Results: 718 clinical scenarios were rated, structured in 13 main clinical presentations: not refractory (n = 64) or refractory (n = 33) proctitis, mild to moderate left-sided (n = 72) or extensive (n = 48) colitis, severe colitis (n = 36), steroid- dependant colitis (n = 36), steroid-refractory colitis (n = 55), acute pouchitis (n = 96), maintenance of remission (n = 248), colorectal cancer prevention (n = 9) and fulminant colitis (n = 9). Overall, 100 indications were judged appropriate (14%), 129 uncertain (18%) and 489 inappropriate (68%). Disagreement between experts was very low (6%). Conclusions: For the very first time, explicit appropriateness criteria for therapy of UC were developed that allow both specific and rapid therapeutic decision making and prospective assessment of treatment appropriateness. Comparison of these detailed scenarios with patient profiles encountered in the Swiss IBD cohort study indicates good concordance. EPATUC criteria will be freely accessible on the internet (epatuc.ch)

Improvement of cardiovascular risk prediction: time to review current knowledge, debates, and fundamentals on how to assess test characteristics.

Cardiovascular risk assessment might be improved with the addition of emerging, new tests derived from atherosclerosis imaging, laboratory tests or functional tests. This article reviews relative risk, odds ratios, receiver-operating curves, posttest risk calculations based on likelihood ratios, the net reclassification improvement and integrated discrimination. This serves to determine whether a new test has an added clinical value on top of conventional risk testing and how this can be verified statistically. Two clinically meaningful examples serve to illustrate novel approaches. This work serves as a review and basic work for the development of new guidelines on cardiovascular risk prediction, taking into account emerging tests, to be proposed by members of the 'Taskforce on Vascular Risk Prediction' under the auspices of the Working Group 'Swiss Atherosclerosis' of the Swiss Society of Cardiology in the future.

Bewertung des Risikos für Bias in kontrollierten Studien [Assessment of risk of bias in controlled studies].

BACKGROUND: Practicing physicians are faced with many medical decisions daily. These are mainly influenced by personal experience but should also consider patient preferences and the scientific evidence reflected by a constantly increasing number of medical publications and guidelines. With the objective of optimal medical treatment, the concept of evidence-based medicine is founded on these three aspects. It should be considered that there is a high risk of misinterpreting evidence, leading to medical errors and adverse effects without knowledge of the methodological background. OBJECTIVES: This article explains the concept of systematic error (bias) and its importance. Causes and effects as well as methods to minimize bias are discussed. This information should impart a deeper understanding, leading to a better assessment of studies and implementation of its recommendations in daily medical practice. CONCLUSION: Developed by the Cochrane Collaboration, the risk of bias (RoB) tool is an assessment instrument for the potential of bias in controlled trials. Good handling, short processing time, high transparency of judgements and a graphical presentation of findings that is easily comprehensible are among its strengths. Attached to this article the German translation of the RoB tool is published. This should facilitate the applicability for non-experts and moreover, support evidence-based medical decision-making.

Guidelines for Perioperative Care for Pancreaticoduodenectomy: Enhanced Recovery After Surgery (ERAS(®)) Society Recommendations.

BACKGROUND: Protocols for enhanced recovery provide comprehensive and evidence-based guidelines for best perioperative care. Protocol implementation may reduce complication rates and enhance functional recovery and, as a result of this, also reduce length-of-stay in hospital. There is no comprehensive framework available for pancreaticoduodenectomy. METHODS: An international working group constructed within the Enhanced Recovery After Surgery (ERAS(®)) Society constructed a comprehensive and evidence-based framework for best perioperative care for pancreaticoduodenectomy patients. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group. The quality of evidence was rated "high", "moderate", "low" or "very low". Recommendations were graded as "strong" or "weak". RESULTS: Comprehensive guidelines are presented. Available evidence is summarised and recommendations given for 27 care items. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations. CONCLUSIONS: The present evidence-based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy. A unified protocol allows for comparison between centres and across national borders. It facilitates multi-institutional prospective cohort registries and adequately powered randomised trials.

Iron-deficiency anemia and hematochezia: when is colonoscopy appropriate?

Background: Colonoscopy is usually proposed for the evaluation of lower gastrointestinal blood loss (hematochezia) or iron deficiency anemia (IDA). Clinical practice guidelines support this approach but formal evidence is lacking. Real clinical scenarios made available on the web would be of great help in decision-making in clinical practice as to whether colonoscopy is appropriate for a given patient. Method: A multidisciplinary multinational expert panel (EPAGE II) developed appropriateness criteria based on best published evidence (systematic reviews, clinical trials, guidelines) and experts' judgement. Using the explicit RAND Appropriateness Method (3 round of experts' votes and a panel meeting) 102 clinical scenarios were judged inappropriate, uncertain, appropriate, or necessary. Results: In IDA, colonoscopy was appropriate in patients >50 years and necessary in the presence of lower abdominal symptoms. In both men and women aged <50 years, colonoscopy was appropriate if prior sigmoidoscopy and/or gastroscopy did not explain the IDA, and necessary if lower gastrointestinal symptoms were present. In women <50 years with a potential gynecological cause, additional lower gastrointestinal symptoms rendered colonoscopy appropriate. In patients >50 years with hematochezia, colonoscopy was always appropriate and mostly necessary, except if a prior colonoscopy was normal within the previous 5 years. Under age 50 years, the presence of any risk factor for colorectal cancer (CRC) and no previous normal colonoscopy (within the last 5 years) made this procedure appropriate and necessary. Conclusion: Colonoscopy is appropriate and even necessary for many indications related to iron deficiency anemia or hematochezia, in particular in patients aged >50 years. The main factors influencing appropriateness are age, results of prior investigations (sigmoidoscopy, gastroscopy, previous colonoscopy), CRC risk and sex. EPAGE II appropriateness criteria are available on www.epage.ch

AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011.

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint eff ort.

AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011.

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate- and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint effort.

Public health impact of statin prescribing strategies based on JUPITER Modeling study from a population-based study.

OBJECTIVE: To evaluate the public health impact of statin prescribing strategies based on the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin Study (JUPITER). METHODS: We studied 2268 adults aged 35-75 without cardiovascular disease in a population-based study in Switzerland in 2003-2006. We assessed the eligibility for statins according to the Adult Treatment Panel III (ATPIII) guidelines, and by adding "strict" (hs-CRP≥2.0mg/L and LDL-cholesterol <3.4mmol/L), and "extended" (hs-CRP≥2.0mg/L alone) JUPITER-like criteria. We estimated the proportion of CHD deaths potentially prevented over 10years in the Swiss population. RESULTS: Fifteen % were already taking statins, 42% were eligible by ATPIII guidelines, 53% by adding "strict", and 62% by adding "extended" criteria, with a total of 19% newly eligible. The number needed to treat with statins to avoid one CHD death over 10years was 38 for ATPIII, 84 for "strict" and 92 for "extended" JUPITER-like criteria. ATPIII would prevent 17% of CHD deaths, compared with 20% for ATPIII+"strict" and 23% for ATPIII + "extended" criteria (+6%). CONCLUSION: Implementing JUPITER-like strategies would make statin prescribing for primary prevention more common and less efficient than it is with current guidelines.

Recommendations for term and late preterm infants at risk for perinatal bacterial infection.

Since publication of the initial guidelines for the prevention of group B streptococcal disease in 1996, the incidence of perinatal infection has decreased significantly. Intrapartum antibiotic prophylaxis together with appropriate management of neonates at increased risk for early-onset sepsis not only reduces morbidity and mortality, but also decreases the burden of unnecessary or prolonged antibiotic therapy. This article provides healthcare workers in Switzerland with evidence-based and best-practice derived guidelines for the assessment and management of term and late preterm infants (>34 weeks) at increased risk for perinatal bacterial infection. Management of neonates at increased risk for early-onset sepsis depends on clinical presentation and risk factors. Asymptomatic infants with risk factors for early-onset sepsis should be observed closely in an inpatient setting for the first 48 hours of life. Symptomatic neonates must be treated promptly with intravenous antibiotics. As clinical and laboratory signs of neonatal infection are nonspecific, it is mandatory to reevaluate the need for continued antibiotic therapy after 48 hours.