A comparison of the revised Delirium Rating Scale (DRS–R98) and the Memorial Delirium Assessment Scale (MDAS) in a palliative care cohort with DSM–IV delirium

Objective: Assessment of delirium is performed with a variety of instruments, making comparisons between studies difficult. A conversion rule between commonly used instruments would aid such comparisons. The present study aimed to compare the revised Delirium Rating Scale (DRS–R98) and Memorial Delirium Assessment Scale (MDAS) in a palliative care population and derive conversion rules between the two scales. Method: Both instruments were employed to assess 77 consecutive patients with DSM–IV delirium, and the measures were repeated at three-day intervals. Conversion rules were derived from the data at initial assessment and tested on subsequent data. Results: There was substantial overall agreement between the two scales [concordance correlation coefficient (CCC) = 0.70 (CI95 = 0.60–0.78)] and between most common items (weighted κ ranging from 0.63 to 0.86). Although the two scales overlap considerably, there were some subtle differences with only modest agreement between the attention (weighted κ = 0.42) and thought process (weighted κ = 0.61) items. The conversion rule from total MDAS score to DRS–R98 severity scores demonstrated an almost perfect level of agreement (r = 0.86, CCC = 0.86; CI95 = 0.79–0.91), similar to the conversion rule from DRS–R98 to MDAS. Significance of results: Overall, the derived conversion rules demonstrated promising accuracy in this palliative care population, but further testing in other populations is certainly needed

A pilot study of performance among hospitalised elderly patients on a novel test of visuospatial cognition: the letter and shape drawing (LSD) test.

peer-reviewedObjectives. Conventional bedside tests of visuospatial function such as the clock drawing (CDT) and intersecting pentagons tests (IPT) are subject to considerable inconsistency in their delivery and interpretation. We compared performance on a novel test – the letter and shape drawing (LSD) test –with these conventional tests in hospitalised elderly patients. Methods. The LSD, IPT, CDT and the Montreal Cognitive Assessment (MoCA) were performed in 40 acute elderly medical inpatients at University Hospital Limerick The correlation between these tests was examined as well as the accuracy of the visuospatial tests to identify significant cognitive impairment on the MoCA. Results. The patients (mean age 81.0±7.71; 21 female) had a median MoCA score of 15.5 (range = 1–29). There was a strong, positive correlation between the LSD and both the CDT (r = 0.56) and IPT (r = 0.71). The correlation between the LSD and MoCA (r = 0.91) was greater than for the CDT and IPT (both 0.67). The LSD correlated highly with all MoCA domains (ranging from 0.54 to 0.86) and especially for the domains of orientation (r = 0.86), attention (0.81) and visuospatial function (r = 0.73). Two or more errors on the LSD identified 90% (26/29) of those patients with MoCA scores of ⩽20, which was substantially higher than for the CDT (59%) and IPT (55%). Conclusion. The LSD is a novel test of visuospatial function that is brief, readily administered and easily interpreted. Performance correlates strongly with other tests of visuospatial ability, with favourable ability to identify patients with significant impairment of general cognition.PUBLISHEDpeer-reviewe

Liver X receptor inhibition potentiates mitotane induced adrenotoxicity in ACC

Adrenocortical carcinoma (ACC) is a rare aggressive malignancy with a poor outcome largely due to limited treatment options. Here, we propose a novel therapeutic approach through modulating intracellular free cholesterol via the liver X receptor alpha (LXRα) in combination with current first line pharmacotherapy, mitotane. H295R and MUC-1 ACC cell lines were pretreated with LXRα inhibitors in combination with mitotane. In H295R, mitotane (20, 40, 50µM) induced dose-dependent cell death, however, in MUC-1 this only occurred at a supratherapeutic concentration (200µM). LXRα inhibition potentiated mitotane-induced cytotoxicity in both cell lines. This was confirmed through use of the CompuSyn model which showed moderate pharmacological synergism and was indicative of apoptotic cell death via an increase in annexinV and cleaved-caspase 3 expression. Inhibition of LXRα was confirmed through downregulation of cholesterol efflux pumps ABCA1 and ABCG1, however, combination treatment with mitotane attenuated this effect. Intracellular free cholesterol levels were associated with increased cytotoxicity in H295R (r2=0.5210) and MUC-1 (r2=0.9299) cells. While both cell lines exhibited similar levels of free cholesterol at baseline, H295R were cholesterol ester rich whereas MUC-1 were cholesterol ester poor. We highlight the importance of LXRα mediated cholesterol metabolism in the management of ACC, drawing attention to its role in the therapeutics of mitotane sensitive tumours. We also demonstrate significant differences in cholesterol storage between mitotane sensitive and resistant disease.</jats:p

Attention! A good bedside test for delirium?

peer-reviewedBackground Routine delirium screening could improve delirium detection, but it remains unclear as to which screening tool is most suitable. We tested the diagnostic accuracy of the following screening methods (either individually or in combination) in the detection of delirium: MOTYB (months of the year backwards); SSF (Spatial Span Forwards); evidence of subjective or objective 'confusion'.Methods We performed a cross-sectional study of general hospital adult inpatients in a large tertiary referral hospital. Screening tests were performed by junior medical trainees. Subsequently, two independent formal delirium assessments were performed: first, the Confusion Assessment Method (CAM) followed by the Delirium Rating Scale-Revised 98 (DRS-R98). DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria were used to assign delirium diagnosis. Sensitivity and specificity ratios with 95% CIs were calculated for each screening method.Results 265 patients were included. The most precise screening method overall was achieved by simultaneously performing MOTYB and assessing for subjective/objective confusion (sensitivity 93.8%, 95% CI 82.8 to 98.6; specificity 84.7%, 95% CI 79.2 to 89.2). In older patients, MOTYB alone was most accurate, whereas in younger patients, a simultaneous combination of SSF (cutoff 4) with either MOTYB or assessment of subjective/objective confusion was best. In every case, addition of the CAM as a second-line screening step to improve specificity resulted in considerable loss in sensitivity.Conclusions Our results suggest that simple attention tests may be useful in delirium screening. MOTYB used alone was the most accurate screening test in older people.PUBLISHEDpeer-reviewe

Can suicides be identified from case records? A case-control study using blind rating

A majority of case control studies of suicide risks in psychiatric patients reveal an excess of risk factors in cases. None of the case control studies has been conducted blind to case identity. The present study examined the possibility that skilled clinicians could identify suicides blind from case records of last episode of care. Records of 39 suicides of psychiatric patients and their matched controls (N = 78) were abstracted blind and dichotomously rated for suicide by seven raters. Success in identification of cases approximated to chance expectation. Pending replication, these disappointing findings call in question the clinical utility of risk factor findings to date, their validity as a basis for significant change in service provision and the medico-legal significance of records in suicide-related civil law suits.<br/

Motion analysis in delirium: A discrete approach in determining physical activity for the purpose of delirium motoric subtyping

The purpose of this study was to determine the use and feasibility of accelerometry-based monitoring and to examine a discrete multi-resolution signal analysis technique to determine motoric subtypes in patients with DSM-IV delirium. Forty consecutive patients receiving palliative care (23 male, 17 female, mean age ± standard deviation 68.4 ± 11.9 years) were assessed using 24-h accelerometer-based monitoring. The total amount of time spent per activity of sitting/lying, standing and stepping were calculated. This was achieved through the multilevel decomposition and reconstruction of the accelerometer signals by means of the discrete wavelet transform. Both the reconstructed approximations and details of the discrete transform were used for motoric subtyping. This was compared to a validated activity monitor for validation purposes. Demographic and clinical data per patient were also collected. Of the 40 patients selected for accelerometry, complete 24-h readings were available for 34 patients and analyses were confined to this group. Of the 34 patients included, 25 met criteria for DSM-IV delirium while 9 were non-delirious comparison subjects with equivalent medical diagnoses receiving treatment in the same setting. It was concluded that accelerometry-based measurement of a delirious cohort within a palliative setting is both a reliable and feasible method of continuous monitoring. Of the activities performed by the patients, periods of standing proved to be the most discriminatory in determining between each subtype

Mycobacterium marinum infection contracted from seaweed wrap in a psoriasis patient undergoing treatment with adalimumab

We report a patient with psoriasis who developed Mycobacterium marinum (M. marinum) infection after seven years of treatment with adalimumab, a human anti-TNF (tumor necrosis factor) monoclonal antibody. TNF is a pro-inflammatory cytokine that plays a central role in the pathogenesis of psoriasis and a number of other immune-mediated inflammatory diseases. TNF plays an important role in granuloma formation and host defense against mycobacterial infections. Several cases of atypical mycobacterial infections in patients on TNF inhibitors have been reported. To our knowledge, this is the second reported case of M. marinum infection in a patient on adalimumab for the treatment of psoriasis

Motion analysis in delirium: A wavelet based approach for sub classification

The usefulness of motor subtypes of delirium is unclear due to inconsistency in sub-typing methods and a lack of validation with objective measures of motor activity levels. Patients were studied with hyperactive, hypoactive, and mixed presentations of delirium. The patient's activity was determined with 24 hour accelerometer-based monitoring and a continuous wavelet transform was applied with a wavelet deemed suitable to distinguish between these motor presentations. The procedures were well tolerated and motor presentations were readily distinguished using the accelerometry-based measurements