Efficacy of Non-Pharmacological Interventions to Prevent and Treat Delirium in Older Patients : A Systematic Overview. The SENATOR project ONTOP Series

The research leading to these results has received funding from the European Union Seventh Framework program (FP7/2007-2013) under grant agreement n° 305930 (SENATOR). The funders had no role in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.Peer reviewedPublisher PD

Zofenopril or irbesartan plus hydrochlorothiazide in elderly patients with isolated systolic hypertension untreated or uncontrolled by previous treatment: a double-blind, randomized study

OBJECTIVE: To compare zofenopril + hydrochlorothiazide (Z + H) vs. irbesartan + hydrochlorothiazide (I + H) efficacy on daytime SBP in elderly (>65 years) patients with isolated systolic hypertension (ISH), untreated or uncontrolled by a previous monotherapy. METHODS: After a 1-week run-in, 230 ISH patients (office SBP ≥ 140 mmHg and DBP < 90 mmHg + daytime SBP ≥ 135 mmHg and daytime DBP < 85 mmHg) were randomized double-blind to 18-week treatment with Z + H (30 + 12.5 mg) or I + H (150 + 12.5 mg) once daily, in an international, multicenter study. Z and I doses could be doubled after 6 and 12 weeks, and nitrendipine 20 mg added at 12 weeks in nonnormalized patients. RESULTS: In the full analysis set (n = 216) baseline-adjusted average (95% confidence interval) daytime SBP reductions after 6 weeks (primary study end point) were similar (P = 0.888) with Z + H [7.7 (10.7, 4.6) mmHg, n = 107] and I + H [7.9 (10.7, 5.0) mmHg, n = 109]. Daytime SBP reductions were sustained during the study, and larger (P = 0.028) with low-dose Z + H at study end [16.2 (20.0, 12.5) mmHg vs. 11.2 (14.4, 7.9) mmHg I + H]. Daytime SBP normalization (<135 mmHg) rate was similar under Z + H and I + H at 6 and 12 weeks, but more common under Z + H at 18 weeks (68.2 vs. 56.0%, P = 0.031). Both drugs equally reduced SBP in the last 6 h of the dosing interval and homogeneously reduced SBP throughout the 24 h. The proportion of patients reporting drug-related adverse events was low (Z + H: 4.4% vs. I + H: 6.0%; P = 0.574). CONCLUSION: Elderly patients with ISH respond well to both low and high-dose Z or I combined with H

Flow diagram of literature search and study selection.

<p>Flow diagram of literature search and study selection.</p

Forest plot of risk ratios comparing multicomponent non-pharmacological interventions vs usual care for delirium prevention in older patients in medical setting.

<p>Forest plot of risk ratios comparing multicomponent non-pharmacological interventions vs usual care for delirium prevention in older patients in medical setting.</p

Risk of Bias of Primary Studies of Multicomponent Non-Pharmacological Interventions for Prevention and Treatment of Delirium.

<p>✔low risk of bias? unclear risk of bias <b>X</b> high risk of bias; RCT, Randomized Controlled Trial; CCT, Controlled Clinical Trial; BAS before-after studies (*) post-acute skilled nursing facilities.</p

Characteristics of Included Systematic Reviews/Meta-analyses.

<p>Characteristics of Included Systematic Reviews/Meta-analyses.</p

Elements of the multicomponent non-pharmacological interventions across primary studies.

<p>RCT, randomized controlled trial; CCT, controlled clinical trial; BAS, before-after study;</p><p>(*) studies that evaluated non-pharmacological interventions to treat delirium</p><p>Elements of the multicomponent non-pharmacological interventions across primary studies.</p

Characteristics of Primary Studies.

<p>DSI, Delirium Symptom Interview; CAM, Confusion Assessment Method; MDAS, the Memorial Delirium Assessment Scale; MMS, Mini-Mental State Examination; OBS, Organic Brain Syndrome</p><p>Non-Pharmacological Interventions for Delirium Prevention in Surgical Setting.</p

GRADE quality of evidence summary table for the comparisons of multicomponent non-pharmacological interventions with usual care for delirium prevention or treatment.

<p>^(a) Allocation concealment not clear in one study (Lundstrom 2007); both studies exposed to performance bias.</p><p>^(b) Unclear blinding of outcome assessor and large confidence interval.</p><p>^(c) Allocation concealment inadequate; unclear blinding of outcome assessor; per-protocol analysis; and large confidence interval.</p><p>^(d) Not randomized, controlled clinical trials.</p><p>^(e) Two studies with unclear/inadequate allocation concealment; 3 studies did not report data on delirium improvement, inconsistency of results (1 study in favor of the experimental treatment and 1 with non-significant results).</p><p>^(f) Two studies with unclear/inadequate allocation concealment; 2 of the 4 studies did not report data on functional status.</p><p>GRADE quality of evidence summary table for the comparisons of multicomponent non-pharmacological interventions with usual care for delirium prevention or treatment.</p

Characteristics of Primary Studies—Non-Pharmacological Interventions for Delirium Prevention in Medical Setting.

<p>CAM, Confusion Assessment Method; ICU, Intensive care unit</p><p>Characteristics of Primary Studies—Non-Pharmacological Interventions for Delirium Prevention in Medical Setting.</p