Delirium masquerading as depression.

OBJECTIVE: Despite the high prevalence of delirium in palliative care settings, this diagnosis is frequently missed, particularly in patients with hypoactive delirium. These patients are also commonly misdiagnosed with depression because of the overlap in symptoms between the two diagnoses. Failure to promptly diagnose delirium can have significant ramifications in terms of delirium reversal, subsequent patient involvement in end-of-life decision making, and the recognition and treatment of other symptoms. METHOD: We report a case of a 63-year-old French-speaking woman admitted to our inpatient palliative care unit with colorectal cancer and a history of depression. This case report highlights the major challenges associated with making the diagnosis of delirium in a patient with a complex medical history, including depression. RESULTS: The patient presented with symptoms of depressed mood and fluctuation in psychomotor activity, but failed to respond to an increase in her fluoxetine treatment in addition to methylphenidate and treatment of her hypothyroidism. A psychiatric assessment in her own language detected features of inattention and confirmed a diagnosis of delirium that was multifactorial, secondary to a combination of posterior reversible encephalopathy syndrome (PRES), hypothyroidism, hepatic dysfunction, and medication. SIGNIFICANCE OF RESULTS: Subsyndromal delirium may present with mood lability, and as delirium and depression can coexist, clinicians should perform a delirium screen for all patients presenting with symptoms of depression, preferably in the patient's first language. Cognitive testing can be particularly helpful in distinguishing delirium, especially hypoactive delirium, from depression.

Quality of clinical practice guidelines in delirium: a systematic appraisal.

OBJECTIVE: To determine the accessibility and currency of delirium guidelines, guideline summary papers and evaluation studies, and critically appraise guideline quality. DESIGN: Systematic literature search for formal guidelines (in English or French) with focus on delirium assessment and/or management in adults (≥18 years), guideline summary papers and evaluation studies.Full appraisal of delirium guidelines published between 2008 and 2013 and obtaining a 'Rigour of Development' domain screening score cut-off of >40% using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. DATA SOURCES: Multiple bibliographic databases, guideline organisation databases, complemented by a grey literature search. RESULTS: 3327 database citations and 83 grey literature links were identified. A total of 118 retrieved delirium guidelines and related documents underwent full-text screening. A final 21 delirium guidelines (with 10 being >5 years old), 12 guideline summary papers and 3 evaluation studies were included. For 11 delirium guidelines published between 2008 and 2013, the screening AGREE II 'Rigour' scores ranged from 3% to 91%, with seven meeting the cut-off score of >40%. Overall, the highest rating AGREE II domains were 'Scope and Purpose' (mean 80.1%, range 64-100%) and 'Clarity and Presentation' (mean 76.7%, range 38-97%). The lowest rating domains were 'Applicability' (mean 48.7%, range 8-81%) and 'Editorial Independence' (mean 53%, range 2-90%). The three highest rating guidelines in the 'Applicability' domain incorporated monitoring criteria or audit and costing templates, and/or implementation strategies. CONCLUSIONS: Delirium guidelines are best sourced by a systematic grey literature search. Delirium guideline quality varied across all six AGREE II domains, demonstrating the importance of using a formal appraisal tool prior to guideline adaptation and implementation into clinical settings. Adding more knowledge translation resources to guidelines may improve their practical application and effective monitoring. More delirium guideline evaluation studies are needed to determine their effect on clinical practice.

Identification of GAS-dependent interferon-sensitive target genes whose transcription is STAT2-dependent but ISGF3-independent.

Signal transducer and activator of transcription 2 (STAT2) is best known as a critical transactivator component of the interferon-stimulated gene factor 3 (ISGF3) complex that drives the expression of many interferon (IFN)-inducible genes. However, STAT2 is also involved in DNA binding in non-ISGF3 transcriptional complexes. We used a DNA microarray to survey the expression of genes regulated by IFN-inducible, STAT2-dependent DNA binding, and compared the cDNAs of IFN-treated cells overexpressing intact STAT2 to those of IFN-treated cells overexpressing mutated STAT2 lacking the DNA binding domain. The IFN-inducible expression of genes known to be regulated by ISGF3 was similar in both cases. However, a subset of IFN-inducible genes was identified whose expression was decreased in cells expressing the mutated STAT2. Importantly, these genes all contained gamma-activated sequence (GAS)-like elements in their 5' flanking sequences. Our data reveal the existence of a collection of GAS-regulated target genes whose expression is IFN-inducible and independent of ISGF3 but highly dependent on the STAT2 DNA binding domain. This report is the first analysis of the contribution of the STAT2 DNA binding domain to IFN responses on a global basis, and shows that STAT2 is required for the IFN-inducible activation of the full spectrum of GAS target genes.