Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. The GRADE approach to developing recommendations.

This is the third and last article in the series about the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and the strength of recommendations in clinical practice guidelines and its application in the field of allergy. We describe the factors that influence the strength of recommendations about the use of diagnostic, preventive and therapeutic interventions: the balance of desirable and undesirable consequences, the quality of a body of evidence related to a decision, patients' values and preferences, and considerations of resource use. We provide examples from two recently developed guidelines in the field of allergy that applied the GRADE approach. The main advantages of this approach are the focus on patient important outcomes, explicit consideration of patients' values and preferences, the systematic approach to collecting the evidence, the clear separation of the concepts of quality of evidence and strength of recommendations, and transparent reporting of the decision process. The focus on transparency facilitates understanding and implementation and should empower patients, clinicians and other health care professionals to make informed choices.

Grading quality of evidence and strength of recommendations in clinical practice guidelines: Part 2 of 3. The GRADE approach to grading quality of evidence about diagnostic tests and strategies.

The GRADE approach to grading the quality of evidence and strength of recommendations provides a comprehensive and transparent approach for developing clinical recommendations about using diagnostic tests or diagnostic strategies. Although grading the quality of evidence and strength of recommendations about using tests shares the logic of grading recommendations for treatment, it presents unique challenges. Guideline panels and clinicians should be alert to these special challenges when using the evidence about the accuracy of tests as the basis for clinical decisions. In the GRADE system, valid diagnostic accuracy studies can provide high quality evidence of test accuracy. However, such studies often provide only low quality evidence for the development of recommendations about diagnostic testing, as test accuracy is a surrogate for patient-important outcomes at best. Inferring from data on accuracy that using a test improves outcomes that are important to patients requires availability of an effective treatment, improved patients' wellbeing through prognostic information, or - by excluding an ominous diagnosis - reduction of anxiety and the opportunity for earlier search for an alternative diagnosis for which beneficial treatment can be available. Assessing the directness of evidence supporting the use of a diagnostic test requires judgments about the relationship between test results and patient-important consequences. Well-designed and conducted studies of allergy tests in parallel with efforts to evaluate allergy treatments critically will encourage improved guideline development for allergic diseases.

Detection of intracranial aneurysms with multislice CT: comparison with conventional angiography.

We assessed the diagnostic accuracy of multislice CT in detection of intracranial aneurysms in patients presenting with subarachnoid or intracranial haemorrhage. Multislice CT and multiplanar digital subtraction angiography (DSA) images were obtained in 50 consecutive patients presenting with subarachnoid (SAH) and/or intracranial haemorrhage and reviewed by three neuroradiologists for the number, size and site of any aneurysms. The CT data were assessed using multiplanar reformats (MPR), maximum-intensity projections (MIP), surface-shaded display (SSD) and volume-rendering (VRT). In conventional angiography 51 aneurysms were detected in 41 patients. CT angiography (CTA) showed up to 48 aneurysms in 39 patients, depending on the observer. The overall sensitivity of multislice CT was 83.3% for small (< 4 mm), 90.6% for medium-size (5-12 mm) and 100% for large (> 13 mm) aneurysms. The sensitivity of multislice CTA to medium-size and large intracranial aneurysm is within the upper part of the range reported for helical single-slice CT. However, as small aneurysms may not be found, DSA remains the standard technique for investigation of SAH.

Detergent insolubility of alkaline phosphatase during biosynthetic transport and endocytosis. Role of cholesterol.

Alkaline phosphatase is anchored to the outer leaflet of the plasma membrane by a covalently attached glycosyl-phosphatidylinositol anchor. We have studied the biosynthetic transport and endocytosis of alkaline phosphatase in the choriocarcinoma cell line BeWo, which endogenously expresses this protein. It was demonstrated that the protein was synthesized as a Triton X-100-soluble precursor. During transport to the cell surface the enzyme was converted in a mature form, which was insoluble in Triton X-100 at 0 degrees C. Once at the cell surface 85% of alkaline phosphatase remained in the detergent-insoluble form. Under steady state conditions 15% of alkaline phosphatase was endocytosed. Most interestingly, this fraction of internalized alkaline phosphatase was completely soluble in Triton X-100 at 0 degrees C. After depletion of membrane cholesterol by saponin, alkaline phosphatase became completely soluble in Triton X-100 at 0 degrees C, suggesting that cholesterol plays a critical role in the formation and maintenance of Triton X-100-resistant membrane domains.

[Experimental induction of emotional states--does addition of music improve self disclosure?]. / Experimentelle Induktion emotionaler Zustände--Verbessert die zusätzliche Darbietung von Musik die Wirksamkeit selbstbezogener Aussagen?

Two procedures to experimentally induce negative and neutral emotional states are compared: self-referent emotional statements (Velten, 1968) presented alone vs. combined with music. For female subjects selected according to their baseline mood, it could be shown that negative statements alone induced anger whereas in combination with music they evoked sadness, i.e. dependent on the procedure applied, the quality of the induced negative emotion changed. For the induction of a neutral state the combined procedure proved to be superior, especially to reduce a positive baseline mood.