Prevention of adverse drug reactions in hospitalized older patients with multi-morbidity and polypharmacy: the SENATOR* randomized controlled clinical trial.

BACKGROUND: Multi-morbidity and polypharmacy increase the risk of non-trivial adverse drug reactions (ADRs) in older people during hospitalization. Despite this, there are no established interventions for hospital-acquired ADR prevention. METHODS: We undertook a pragmatic, multi-national, parallel arm prospective randomized open-label, blinded endpoint (PROBE) controlled trial enrolling patients at six European medical centres. We randomized 1,537 older medical and surgical patients with multi-morbidity and polypharmacy on admission in a 1:1 ratio to SENATOR software-guided medication optimization plus standard care (intervention, n = 772, mean number of daily medications = 9.34) or standard care alone (control, n = 765, mean number of daily medications = 9.23) using block randomization stratified by site and admission type. Attending clinicians in the intervention arm received SENATOR-generated advice at a single time point with recommendations they could choose to adopt or not. The primary endpoint was occurrence of probable or certain ADRs within 14 days of randomization. Secondary endpoints were primary endpoint derivatives; tertiary endpoints included all-cause mortality, re-hospitalization, composite healthcare utilization and health-related quality of life. RESULTS: For the primary endpoint, there was no difference between the intervention and control groups (24.5 vs. 24.8%; OR 0.98; 95% CI 0.77-1.24; P = 0.88). Similarly, with secondary and tertiary endpoints, there were no significant differences. Among attending clinicians in the intervention group, implementation of SENATOR software-generated medication advice points was poor (~15%). CONCLUSIONS: In this trial, uptake of software-generated medication advice to minimize ADRs was poor and did not reduce ADR incidence during index hospitalization.

The 4-DSD: A New Tool to Assess Delirium Superimposed on Moderate to Severe Dementia.

OBJECTIVES: The purpose of this study was to create, standardize, and validate a new instrument, named 4-DSD, and determine its diagnostic accuracy in the diagnosis of delirium in subjects with moderate to severe dementia. DESIGN: Multicenter cross-sectional observational study. SETTING AND PARTICIPANTS: Older patients consecutively admitted to acute and rehabilitation hospital wards. MEASURES: The DSM-5 was used as the reference standard delirium assessment. The presence and severity of dementia was defined using the AD8 and the Global Deterioration Scale (GDS). The 4-DSD is a 4-item tool that ranges from 0 to 12. Item 1 measures alertness, item 2 altered function, item 3 attention, and item 4 acute change or fluctuation in mental status. RESULTS: A total of 134 patients were included in the study. Most of the patients were enrolled in acute hospital wards (60%), with 40% in rehabilitation settings. A minority of the patients were categorized with moderate dementia, with a GDS score of 5 (4%). Most of the patients were in the moderate-severe stage with a GDS score ≤6 (77%); 19% were classed as severe, with a GDS score of 7. A 4-DSD cutoff score ≥5 had a sensitivity of 80% and specificity of 80% with a positive predictive value (PPV) of 67% and a negative predictive value (NPV) of 89%. In the subgroup with moderate-severe dementia (n = 108), the sensitivity and the specificity were 79% and 82%, respectively, with a PPV and NPV of 62% and 92%. In the subgroup with severe dementia (n = 26) the sensitivity was 82% and the specificity 56% with a PPV of 78% and a NPV of 63%. CONCLUSIONS AND IMPLICATIONS: The availability of a specific tool to detect delirium in patients with moderate-severe dementia has important clinical and research implications, allowing all health care providers to improve their ability to identify it.