Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

A comparison between the EQ-5D and the SF-6D in patients with chronic obstructive pulmonary disease (COPD).

The appropriate use of generic preference-based measures determines the accuracy of disease assessment and further decision on healthcare policy using quality adjusted life years. The discriminative capacity of different instruments would differ across disease groups. Our study was to examine the difference in utility scores for COPD patients measured by EQ-5D and SF-6D and to assist the choice of a proper instrument in this disease group.Differences of mean utility scores of EQ-5D and SF-6D in groups defined by socio-demographic characteristics, comorbidities, health service utilisation and severity of illness were tested using Mann-Whitney test, t-test, Kruskal-Wallis test, Pearson's correlation coefficient and ANOVA, as appropriate. The discriminative properties of the two instruments were compared against indicators of quality of life using receiver operating characteristic curves. The statistical significance of the area under the curves (AUC) was tested by ANOVA and F-statistics used to compare the efficiency with which each instrument discriminated between disease severity groups.Mean utility scores of EQ-5D and SF-6D were 0.644 and 0.629 respectively in the 154 subjects included in the analysis. EQ-5D scores were significantly higher than SF-6D in groups less severe and these differences corresponded to a minimally important difference of greater than 0.03 (p<0.001). EQ-5D and SF-6D scores were strongly correlated across the whole sample (r = 0.677, p<0.001) and in pre-defined groups (r>0.5 and p<0.05 for all correlation coefficients). AUCs were above 0.5 against the indicators of health-related quality of life for both instruments. F-ratios suggested SF-6D was more efficient in discriminating cases of different disease severity than EQ-5D.Both EQ-5D and SF-6D appeared to be valid preference-based measures in Chinese COPD patients. SF-6D was more efficient in detecting differences among subgroups with differing health status. EQ-5D and SF-6D measured different things and might not be used interchangeably in COPD patients

In vitro and in vivo evaluations of intestinal barriers for the zwitterion L-767,679 and its carboxyl ester prodrug L-775,318: roles of efflux and metabolism. Drug Metab Dispos 26:520–527

This paper is available online at http://www.dmd.org ABSTRACT: The barriers to oral delivery of the hydrophilic zwitterion L-767,679 (I) and its carboxyl ester prodrug L-775,318 (II) were examined. In the Caco-2 cell model, transport of II, but not I, was strongly oriented in the secretory direction. The basal-to-apical transport of II displayed saturable kinetics and was markedly inhibited by verapamil and quinidine, known P-glycoprotein inhibitors. In Caco-2 cells, metabolism of I was not observed, whereas hydrolysis of II was modest (&lt;20%). In the in situ rat intestinal loop model, verapamil did not affect the absorption of I but significantly increased the absorption of II. I was resistant to intestinal metabolism, whereas II underwent hydrolysis partially in rat lumen but more extensively in rat intestinal tissue and blood. In vitro metabolism studies indicated that verapamil also inhibited the hydrolysis of II in rats. The inhibition was relatively specific for the intestinal and not the luminal esterases. These results suggested that the intestinal absorption of I was limited not by intestinal efflux or metabolism but more likely by the low lipophilicity of I. However, an efflux system, likely mediated by P-glycoprotein, played an important role in limiting the absorption of II. In rats, metabolism served as an additional barrier to the absorption of II. Verapamil increased the intestinal absorption of the prodrug by inhibiting the efflux system in the two models studied, as well as possibly inhibiting metabolism in rats. For the first time, secretory transport was identified as a cause of the failure to increase the absorption of a lipophilic and cationic prodrug developed to overcome the absorption problem

Distribution of EQ-5D, SF-6D (UK), SF-6D (HK) and SGRQ scores.

<p>Distribution of EQ-5D, SF-6D (UK), SF-6D (HK) and SGRQ scores.</p

Distribution of EQ-5D, SF-6D (UK & HK), EQ-VAS and SGRQ scores in the sample subjects and their correlations with SGRQ.

¶<p>EQ-5D, SF-6D and EQ-VAS correlated with SGRQ; p<0.001 for all Pearson’s correlation coefficient.</p><p>Note: SGRQ  =  Saint George’s Respiratory Questionnaire.</p><p>Distribution of EQ-5D, SF-6D (UK & HK), EQ-VAS and SGRQ scores in the sample subjects and their correlations with SGRQ.</p

Scatter plots of SF-6D vs. SGRQ, EQ-5D vs. SGRQ (above) and difference (SF-6D – EQ-5D) vs. SGRQ (below).

<p>Scatter plots of SF-6D vs. SGRQ, EQ-5D vs. SGRQ (above) and difference (SF-6D – EQ-5D) vs. SGRQ (below).</p

Scatter plot of EQ-5D and SF-6D.

<p>Scatter plot of EQ-5D and SF-6D.</p

Characteristics of the study sample (n = 154).

∏<p>Presence with any following disease: hypertension, heart diseases, pneumonia, diabetes, asthma, rheumatoid arthritis, liver disease, cancers and other chronic diseases.</p>¶<p>p<0.001, significance was tested by t-test.</p>‡<p>p<0.05, significance was tested by chi-square test.</p><p>Note: COPD  =  Chronic Obstructive Pulmonary Disease.</p><p>Characteristics of the study sample (n = 154).</p