H.J. Luijendijk

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.

Terminal illness and the increased mortality risk of conventional antipsychotics in observational studies: a systematic review.

Numerous large observational studies have shown an increased risk of mortality in elderly users of conventional antipsychotics. Health authorities have warned against use of these drugs. However, terminal illness is a potentially strong confounder of the observational findings. So, the objective of this study was to systematically assess whether terminal illness may have biased the observational association between conventional antipsychotics and risk of mortality in elderly patients.

Detecting delirium in elderly outpatients with cognitive impairment.

BACKGROUND Delirium may be more prevalent in elderly outpatients than has long been assumed. However, it may be easily missed due to overlap with dementia. Our aim was to study delirium symptoms and underlying somatic disorders in psycho-geriatric outpatients. METHODS We performed a case-control study among outpatients that were referred to a psychiatric institution between January 1st and July 1st 2010 for cognitive evaluation. We compared 44 cases with DSM-IV delirium (24 with and 20 without dementia) to 44 controls with dementia only. All participants were aged 70 years or older. We extracted from the medical files (1) referral characteristics including demographics, medical history, medication use, and referral reasons, (2) delirium symptoms, scored with the Delirium Rating Scale-Revised-98, and (3) underlying disorders categorized as: drugs/intoxication, infection, metabolic/endocrine disturbances, cardiovascular disorders, central nervous system disorders, and other health problems. RESULTS At referral, delirium patients had significantly higher numbers of chronic diseases and medications, and more often a history of delirium and a recent hospital admission than controls. Most study participants, including those with delirium, were referred for evaluation of (suspected) dementia. The symptoms that occurred more frequently in cases were: sleep disturbances, perceptual abnormalities, delusions, affect lability, agitation, attention deficits, acute onset, and fluctuations. Drug related (68%), infectious (61%), and metabolic-endocrine (50%) disturbances were often involved. CONCLUSIONS Detection of delirium and distinction from dementia in older outpatients was feasible but required detailed caregiver information about the presence, onset, and course of symptoms. Most underlying disorders could be managed at home.

Attention, arousal and other rapid bedside screening instruments for delirium in older patients: a systematic review of test accuracy studies

Objective delirium occurs frequently in frail patients but is easily missed. Screening with a rapid, easy-to-use and highly sensitive instrument might help improve recognition. The aim of this study was to review attention, arousal and other rapid bedside screening instruments for delirium in older patients. Methods a literature search was performed in PubMed, PsycINFO and Embase. We scrutinized forward citations in Google Scholar, and references of included articles and prior reviews. We included studies among older patients that investigated the sensitivity and specificity of delirium screening instruments that could be administered in 3 min or less, and did not require surrogate information. We extracted study characteristics, risk of bias, sensitivity and specificity. Results we identified 27 studies among 4,766 patients in hospitals and nursing homes. They tested many different single and several combined screening instruments. Prevalence of delirium varied between 4% and 57%. Only one study scored a low risk of bias on all domains. Sensitivity varied between 17% and 100%, and specificity between 38% and 99%. Of the 22 tests with sensitivity ≥90%, seven also had specificity ≥80% in older patients in general. These results were approximately reproduced for the Observational Scale of Level of Arousal (OSLA) and Richmond Agitation and Sedation Scale (RASS): sensitivity and specificity were >80%. Conclusion two arousal tests-OSLA and RASS-had reproduced high sensitivity and specificity in older patients. Nurses can administer these tests during daily interaction with patients. Test accuracy studies about rapid screening tools for delirium superimposed on dementia were scarce.

Baseline differences in the SAVOR trial

Dear Editor, The US Food and Drug Administration (FDA) has re-analysed the data from SAVOR, the saxagliptin safety trial, to investigate whether saxagliptin increases the risk of all-cause mortality compared with placebo [1]. The analyses were not adjusted for baseline differences. We believe this is necessary to avoid underestimation of the mortality risk of saxagliptin. First, despite randomization and the very large number of participants (>8000 per group), many baseline differences occurred. Moreover, as shown in Tables 2, 3 and 19 of the FDA report, the majority of characteristics that predict cardiovascular disease and death are distributed in favour of the saxagliptin versus the placebo group (younger age, more females, more people of white race, shorter duration of diabetes and less obesity) [1]. For each individual characteristic, the difference between the groups might appear small, but all differences taken together pose a risk of bias. Secondly, there is evidence that these baseline differences may matter. The pooled baseline differences of 20 other saxagliptin (efficacy) trials also favoured the mortality risk of the saxagliptin groups, but these seem larger than those in SAVOR (Table 19) [1]. Concordantly, the pooled risk of major adverse events in these trials was lower (hazard ratio 0.74; 95% confidence interval 0.45–1.25) [2] than that in SAVOR (hazard ratio 1.00; 95% confidence interval 0.89–1.12) [1]. Patient characteristics that predict mortality also predict glycaemic control. Again, the mean reduction in glycated haemoglobin (%) was lower in the efficacy trials (0.61; 95% CI 0.31–0.91) [3] than in SAVOR (0.24; 95% CI 0.19–0.28) [1]. Thirdly, if the results of SAVOR are pooled with those of the EXAMINE trial, the safety trial for alogliptin, the baseline differences will not be equalized. EXAMINE also shows baseline differences in favour of the mortality risk in the active treatment group [4]. Moreover, the direction of the baseline difference concurs for 9 of 12 patient characteristics that both trials report. Baseline differences can influence a drug’s apparent efficacy and safety, directly or through differential dropout. An adjustment method is needed that takes both sources of bias into account [5]. We kindly ask the FDA to present saxagliptin’s all-cause mortality risk in SAVOR, adjusted for baseline characteristics that affect mortality risk.

Efficacy of antipsychotics in dementia depended on the definition of patients and outcomes: a meta-epidemiological study

OBJECTIVES Postulating that efficacy of antipsychotics for agitation and psychosis in dementia is best estimated in trials among patients with these symptoms and with symptom-specific outcomes, we investigated whether clinically broader definitions affected the pooled efficacy. STUDY DESIGN AND SETTING Trials were searched in multiple databases and categorized according to patient population (agitated, psychotic, and mixed) and outcome scale (agitation, psychosis, and generic). Standardized mean differences with 95% confidence intervals were calculated for conventional and atypical antipsychotics separately. RESULTS Thirty trials met our inclusion criteria. Conventional antipsychotics might have a small effect in agitated patients on agitation scales (-0.44, -0.88, 0.01) and in psychotic patients on psychosis scales (-0.31, -0.61, -0.02). There was no effect on generic scales. Efficacy of atypical antipsychotics was not established in agitated patients on agitation scales (-0.15, -0.43, 0.13) and in psychotic patients on psychosis scales (-0.11, -0.20, -0.03) but was small in mixed patients on agitation scales (-0.29, -0.40, -0.18). CONCLUSION Pooled efficacy of antipsychotics for agitation and psychosis in dementia is biased when based on trials that included patients without these target symptoms or on results measured with generic scales. This finding is important for reviewers and guideline developers who select trials for reviews.