B.C. van Munster

The DSM-5 criteria, level of arousal and delirium diagnosis: Inclusiveness is safer

Delirium is a common and serious problem among acutely unwell persons. Alhough linked to higher rates of mortality, institutionalisation and dementia, it remains underdiagnosed. Careful consideration of its phenomenology is warranted to improve detection and therefore mitigate some of its clinical impact. The publication of the fifth edition of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-5) provides an opportunity to examine the constructs underlying delirium as a clinical entity. Altered consciousness has been regarded as a core feature of delirium; the fact that consciousness itself should be physiologically disrupted due to acute illness attests to its clinical urgency. DSM-5 now operationalises `consciousness’ as `changes in attention’. It should be recognised that attention relates to content of consciousness, but arousal corresponds to level of consciousness. Reduced arousal is also associated with adverse outcomes. Attention and arousal are hierarchically related; level of arousal must be sufficient before attention can be reasonably tested. Our conceptualisation of delirium must extend beyond what can be assessed through cognitive testing (attention) and accept that altered arousal is fundamental. Understanding the DSM-5 criteria explicitly in this way offers the most inclusive and clinically safe interpretation.BackgroundDelirium is a common and serious problem among acutely unwell persons. Alhough linked to higher rates of mortality, institutionalisation and dementia, it remains underdiagnosed. Careful consideration of its phenomenology is warranted to improve detection and therefore mitigate some of its clinical impact. The publication of the fifth edition of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-5) provides an opportunity to examine the constructs underlying delirium as a clinical entity.DiscussionAltered consciousness has been regarded as a core feature of delirium; the fact that consciousness itself should be physiologically disrupted due to acute illness attests to its clinical urgency. DSM-5 now operationalises `consciousness’ as `changes in attention’. It should be recognised that attention relates to content of consciousness, but arousal corresponds to level of consciousness. Reduced arousal is also associated with adverse outcomes. Attention and arousal are hierarchically related; level of arousal must be sufficient before attention can be reasonably tested.SummaryOur conceptualisation of delirium must extend beyond what can be assessed through cognitive testing (attention) and accept that altered arousal is fundamental. Understanding the DSM-5 criteria explicitly in this way offers the most inclusive and clinically safe interpretation.

Effectiveness of melatonin treatment on circadian rhythm disturbances in dementia. Are there implications for delirium? : A systematic review

Circadian rhythm disturbances, like sundowning, are seen in dementia. Because the circadian rhythm is regulated by the biological clock, melatonin might be effective in the treatment of these disturbances. We systematically studied the effect of melatonin treatment in patients with dementia. In addition, we elaborate on the possible effects one might expect of melatonin treatment in patients with delirium, since dementia and delirium are strongly related. Moreover, some evidence exists that sundowning in patients with dementia and the alterations in the sleep/wake cycle, seen in patients with delirium both originate from circadian rhythm disturbances.

Pharmacological Treatment of Dementia: A Scoping Review of Systematic Reviews

Background: Until now, multiple reviews on the pharmacological treatment of dementia have been published. Methods: We performed a scoping review to summarize research findings and to identify gaps in the existing literature. We searched the literature and assessed the risk of bias of the included reviews. A team of clinical experts assessed the fields in which more research is necessary. Fifty-five reviews with a low risk of bias were included, most of them concerning the treatment of cognitive decline (n = 16) and behavioral symptoms (n = 10) in Alzheimers disease (AD). For cognitive impairment, cholinesterase inhibitors (n = 13) and memantine (n = 7) were described most frequently. Little information was found about the treatment of depression in dementia. Conclusions: For many current treatments, there is sufficient evidence. New research should focus on the symptomatic treatment of the earliest and most salient complaints in AD as well as on disease-modifying interventions acting at the level of the amyloid cascade.

Development of an abbreviated version of the delirium motor subtyping scale (DMSS-4)

BACKGROUND Delirium is a common neuropsychiatric syndrome with considerable heterogeneity in clinical profile. Identification of clinical subtypes can allow for more targeted clinical and research efforts. We sought to develop a brief method for clinical subtyping in clinical and research settings. METHODS A multi-site database, including motor symptom assessments conducted in 487 patients from palliative care, adult and old age consultation-liaison psychiatry services was used to document motor activity disturbances as per the Delirium Motor Checklist (DMC). Latent class analysis (LCA) was used to identify the class structure underpinning DMC data and also items for a brief subtyping scale. The concordance of the abbreviated scale was then compared with the original Delirium Motor Subtype Scale (DMSS) in 375 patients having delirium as per the American Psychiatric Associations Diagnostic and Statistical Manual (4th edition) criteria. RESULTS Latent class analysis identified four classes that corresponded closely with the four recognized motor subtypes of delirium. Further, LCA of items (n = 15) that loaded >60% to the model identified four features that reliably identified the classes/subtypes, and these were combined as a brief motor subtyping scale (DMSS-4). There was good concordance for subtype attribution between the original DMSS and the DMSS-4 (κ = 0.63). CONCLUSIONS The DMSS-4 allows for rapid assessment of clinical subtypes in delirium and has high concordance with the longer and well-validated DMSS. More consistent clinical subtyping in delirium can facilitate better delirium management and more focused research effort.

On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points?

BACKGROUND Cancer societies and research cooperative groups worldwide have urged for the development of cancer trials that will address those outcome measures that are most relevant to older patients. We set out to determine the characteristics and study objectives of current clinical trials in hematological patients. METHOD The United States National Institutes of Health clinical trial registry was searched on 1 July 2013, for currently recruiting phase I, II or III clinical trials in hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. RESULTS In the 1207 clinical trials included in this overview, patient-centered outcome measures such as quality of life, health care utilization and functional capacity were only incorporated in a small number of trials (8%, 4% and 0.7% of trials, respectively). Even in trials developed exclusively for older patients, the primary focus lies on standard end points such as toxicity, efficacy and survival, while patient-centered outcome measures are included in less than one-fifth of studies. CONCLUSION Currently on-going clinical trials in hematological malignancies are unlikely to significantly improve our knowledge of the optimal treatment of older patients as those outcome measures that are of primary importance to this patient population are still included in only a minority of studies. As a scientific community, we cannot continue to simply acknowledge this issue, but must all participate in taking the necessary steps to enable the delivery of evidence-based, tailor-made and patient-focused cancer care to our rapidly growing elderly patient population.BACKGROUND Cancer societies and research cooperative groups worldwide have urged for the development of cancer trials that will address those outcome measures that are most relevant to older patients. We set out to determine the characteristics and study objectives of current clinical trials in hematological patients. METHOD The United States National Institutes of Health clinical trial registry was searched on 1 July 2013, for currently recruiting phase I, II or III clinical trials in hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. RESULTS In the 1207 clinical trials included in this overview, patient-centered outcome measures such as quality of life, health care utilization and functional capacity were only incorporated in a small number of trials (8%, 4% and 0.7% of trials, respectively). Even in trials developed exclusively for older patients, the primary focus lies on standard end points such as toxicity, efficacy and survival, while patient-centered outcome measures are included in less than one-fifth of studies. CONCLUSION Currently on-going clinical trials in hematological malignancies are unlikely to significantly improve our knowledge of the optimal treatment of older patients as those outcome measures that are of primary importance to this patient population are still included in only a minority of studies. As a scientific community, we cannot continue to simply acknowledge this issue, but must all participate in taking the necessary steps to enable the delivery of evidence-based, tailor-made and patient-focused cancer care to our rapidly growing elderly patient population.

Changing perspectives on delirium care: The new Dutch guideline on delirium

Both the patients and the caregivers perspectives are discussed. The guideline includes chapters on epidemiology, etiology and risk factors, and the non-pharmacological and pharmacological prevention and treatmentof delirium. Inaddition, onechapter is dedicated to the ‘organization of care’. This latter chapter was more heavily based on expert opinion than the other chapters.

Glucocorticoid Receptor Haplotype is Associated With a Decreased Risk of Delirium in the Elderly

Delirium is the most common mental disorder at older age in hospitals after acute admission. The pathogenesis of delirium is largely unknown. Hyperactivity of the hypothalamic‐pituitary‐adrenal axis, leading to increased cortisol levels, has been suggested to play a role in the development of delirium. The effects of cortisol, the most important glucocorticoid (GC) in humans, are mainly mediated by the GC receptor (GR). Several polymorphisms in the GR gene that alter the GC sensitivity are known. The aim of this study was to study the role of these GR polymorphisms in delirium in elderly patients. Patients aged 65 years and older admitted to the medical department or scheduled for hip surgery were included. Delirium was diagnosed using the Confusion Assessment Method. Five single nucleotide polymorphisms in the GC receptor gene were genotyped and haplotypes were constructed. Delirium was associated with impaired cognitive (P < 0.001) and functional function (P < 0.001), as well as with older age (P < 0.001). Homozygous carriers of haplotype 4, characterized by the presence of the BclI and TthIIII minor alleles, had a 92% decreased risk of developing delirium (P = 0.02), independent of age, cognitive, and functional state. Homozygous carriage of the BclI‐TthIIII haplotype of the GR gene is related to a reduced risk of developing delirium. This suggests that altered GC signaling may be involved in the pathogenesis and development of delirium in the elderly.

Groningen frailty indicator in older patients with end-stage renal disease

Abstract Background: Currently over 55% of end-stage renal disease (ESRD) patients are aged ≥60 years and patients >75 years represent the fastest growing segment of the dialysis population. We aimed to assess whether the Groningen frailty indicator (GFI) can be used to distinguish fit older ESRD patients, likely able to tolerate and benefit from dialysis, from frail older patients who need further evaluation with a geriatrician’s comprehensive assessment. Methods: All patients aged ≥65 years visiting the pre-dialysis unit at the Gelre hospital between 2007 and 2013 were included and underwent the GFI (n = 65). Patients with GFI ≥ 4 (frail) were referred for geriatric consultation (n = 13). Results of the GFI and nephrologists’ evaluation were compared with geriatrician’s assessment. Survival rates and outcomes after one year of follow up were recorded. Results: Twenty patients (32%) were identified as frail. Of the problems identified by the geriatrician in 13 patients, 55% were not reported in the nephrologists’ notes. The first year after inclusion, 30% of patients with a GFI ≥ 4 died, compared to 9% of fit patients (p = 0.04). Moreover, 90% of frail patients had been hospitalized one or more times, compared to 53% in the fit group (p = 0.005). Conclusion: Although the GFI can be a useful instrument to identify ESRD patients at risk, both the GFI and the nephrologists’ assessment failed to identify specific geriatric impairments. Further research is needed to develop a specific frailty indicator for ESRD patients and to determine the value and effect of a comprehensive geriatric assessment in ESRD patients.

A Longitudinal Study of Delirium Motor Subtypes in Elderly Hip Surgery Patients: Frequency and Determinants.

Introduction Delirium is a common neuropsychiatric syndrome with considerable heterogeneity that includes a variety of clinical (motor) subtypes. Because delirium is typically highly fluctuating, understanding the longitudinal stability of subtypes is crucial to evaluating their relevance to treatment and outcome. Aims to examine the changes (variability) in motor subtype profile in patients with delirium over serial assessment using the Delirium Motor Subtype Scale, and to investigate predictors of variability. Methods We studied motor subtype profile of patients with delirium assessed daily over a week in elderly patients undergoing hip fracture surgery. A Generalized Estimating Equations Model examined possible predictors of change in motor subtype status, including baseline variables and delirium course. Results We included 118 patients developing DSM-IV delirium after hip-surgery [mean age 87.0±6.5 years; range 65–102; 66% females]. At first assessment, hyperactive subtype was most common (49%), followed by hypoactive (31%) and mixed subtype (14%), with 6% of delirious patients not fulfilling criteria of any DMSS-defined motor subtype. Almost two-thirds (n=69) of these patients underwent at least one more assessment, and for these 45 (57%) remained stable in motor subtype over time, while the rest 34 (43%) underwent change. A range of baseline characteristics were not significant predictors of variability in subtype profile. Conclusions Motor subtype profile is typically stable for orthopaedic patients with delirium. Thus evidence from cross-sectional studies of motor subtypes can be applied to many patients with delirium. Further longitudinal studies can clarify the stability of motor subtypes across different clinical populations.

Polymorphisms in the Melatonin Receptor 1B Gene and the Risk of Delirium

Background/Aims: A disturbed sleep-wake rhythm cycle can be seen in delirium and as melatonin regulates this cycle via melatonin receptors, genetic variations in these receptors may contribute to susceptibility to delirium. The purpose of this study was to investigate whether genetic variants in the melatonin receptor 1B (MTNR1B) gene are associated with delirium. Methods: Elderly medical and hip surgery patients were included in the study. Five single-nucleotide polymorphisms (SNPs) were determined in the MTNR1B gene, i.e. rs18030962, rs3781638, rs10830963, rs156244 and rs4753426. Results: In total, 53% of 171 hip fracture patients and 33% of 699 medical patients were diagnosed with delirium. None of the polymorphisms were found to be associated with the occurrence of delirium. Conclusion: Future research could focus on sequencing this gene to look for other functional SNPs in relation to delirium.