Annals of medicine
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The GRADE method (Grading of Recommendations, Assessment, Development, and Evaluation) provides a tool for rating the quality of evidence for systematic reviews and clinical guidelines. This article aims to analyse conceptually how well grounded the GRADE method is, and to suggest improvements. The eight criteria for rating the quality of evidence as proposed by GRADE are here analysed in terms of each criterion's potential to provide valid information for grading evidence. ⋯ It is concluded that three GRADE criteria have an appropriate conceptual basis to be used as indicators of confidence in research evidence in systematic reviews: internal validity of a study, consistency of the findings, and publication bias. In network meta-analyses, the indirectness of evidence may also be considered. It is here proposed that the grade for the internal validity of a study could in some instances justifiably decrease the overall grade by three grades (e.g. from high to very low) instead of the up to two grade decrease, as suggested by the GRADE method.
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Chronotherapy of cancer is one of the oldest examples of the clinical application of biological rhythms. Growing understanding of the importance of biological timing in physiology and pathophysiology of many diseases including cancer reforms our views on the role of biological clocks in cancer and cancer treatment. In the present issue the current progress in circadian clock-dependent mechanisms of cancer, polymorphism and mutations of clock gene in cancer, cancer-associated clock disruptions, and novel chronotherapeutic approaches are discussed.
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Resetting of the circadian clocks involves the heat shock pathway. Cryptochromes as the actual repressors take care of circadian alignment, and in addition they link the circadian clocks to temperature responses, metabolic homeostasis, and sleep homeostasis. In contrast, circadian misalignment redistributes rapid-eye-movement sleep and has ramifications for the insulin pathway, inflammation, weight control, and mood. Here, the second half of the night and the actions of cryptochromes are suggested to be a critical period and a key mechanism, respectively.
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Editorial Comparative Study
Attempted suicides: how should they be managed and suicide prevented?