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

Development of Pharmaceutically Acceptable Crystalline Forms of Drug Substances via Solid-State Solvent Exchange

In the pharmaceutical industry, solid form screening plays an important role to discover forms that exhibit desired physicochemical properties for drug product development. This work describes an approach to meet this objective by the transformation of undesirable solvates to hydrates or cosolvates with water via solid-state solvent exchange. Case studies of two drug substances, imatinib mesylate and linagliptin, are discussed, where linaglipitin methanol/ethanol solvate was converted to an iso-structural hydrate and, similarly, imatinib mesylate methanol–water cosolvate was converted to a predominantly water-containing cosolvate. Through quality by design based optimization, temperature and relative humidity were identified as critical process parameters that impacted the rate of solvent exchange during humidification. In addition, crystallization parameters that impacted the crystal size were found to play a key role in determining the extent of solvent exchange. This unexpected effect of crystal size was investigated through single crystal structure elucidation and molecular modeling, which showed the solvent to be residing in channels oriented along the length of the crystal. The dimensions of these channels determined the ease of solvent exchange by controlling the rate and extent of diffusion of solvent molecules. With these case studies, this paper provides insight on robust process development for solid-state solvent exchange with an in-depth understanding of molecular level phenomena and critical process parameters

Retrospective delirium ascertainment from case notes: a retrospective cohort study

Objectives This study sets out to ascertain if recognition of delirium impacts on patient outcomes. Design Retrospective cohort study. Setting Unscheduled admissions to acute care trust/secondary care UK hospitals. Participants Six hundred and fifty-six older adults aged ≥65 years admitted on 14 September 2018. Measurements Delirium was ascertained retrospectively from case notes using medical notes. Documented delirium was classified as recognised delirium and retrospectively ascertained delirium was classified as unrecognised delirium. Primary and secondary outcome measures Primary outcome measure: inpatient mortality. Secondary outcome measures: length of stay, discharge destination. Results Delirium was present in 21.1% (132/626) of patients at any point during admission. The presence of delirium was associated with increased mortality (HR 2.65, CI 1.40 to 5.01). Recognition of delirium did not significantly impact on outcomes. Conclusions Delirium is associated with adverse outcomes in hospitalised older adults. However, there is insufficient evidence that recognition of delirium affects outcomes. However, delirium recognition presents an opportunity to discuss a person’s overall prognosis and discuss this with the patient and their family. Further research is needed to assess the pathophysiology of delirium to enable development of targeted interventions towards improved outcomes in patients with delirium