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Early strong anticholinergic initiation and 30-day mortality in older inpatients with dementia: a target trial emulation
Liu J, Yuan H.. Research Square, 2026-09-08
Topic: Drug trials: efficacy and safety
Background Starting a strong anticholinergic during acute admission is an unresolved medication-safety decision for older people with dementia. We assessed whether linked routine-care data supported an interpretable admission-time estimate of 30-day mortality after initiation versus avoidance and examined a separate 48-hour landmark association. Methods We linked MIMIC-IV and MIMIC-IV-ED data. Admission was time zero. Strategies were confirmed initiation of a selected non-scopolamine strong anticholinergic within 48 hours versus avoidance. Clone-censor-weight methods addressed the grace period. We required a maximum absolute weighted standardised mean difference below 0.10 to report an effect. The secondary 48-hour landmark analysis used overlap weighting and patient-cluster bootstrap intervals. Results The primary cohort included 3,706 admissions from 1,861 patients and 47 initiators. Of 3,706 initiation-strategy clones, 3,657 (98.7%) were artificially censored. Maximum absolute weighted standardised mean difference was 1.499 and initiation-strategy effective sample size was 12.4; no strategy effect was reported. The landmark cohort included 2,572 admissions from 1,455 patients and 36 initiators. The direct overlap-weighted risk difference was − 0.33 percentage points (95% CI -7.90 to 5.38); the augmented estimate was 0.28 percentage points (95% CI -5.99 to 6.99). Maximum weighted imbalance was 0.092. Conclusions Rare confirmed initiation prevented a clinically interpretable admission-time strategy estimate. The separate landmark association was imprecise and cannot establish safety, equivalence or causality. Future studies need multicentre recruitment, verified administration and enough initiators to support both strategies.
Key findings
- We assessed whether linked routine-care data supported an interpretable admission-time estimate of 30-day mortality after initiation versus avoidance and examined a separate 48-hour landmark association.
- Strategies were confirmed initiation of a selected non-scopolamine strong anticholinergic within 48 hours versus avoidance.
- Results The primary cohort included 3,706 admissions from 1,861 patients and 47 initiators.
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Study details
- Participants3,706
- Effect size98.7%
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 37 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 23 of the 62 points we could judge it on, which is 37 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 3,706 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 23 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 23 of the 62 points we could judge it on is 37 out of 100. |
| Total | 37 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Liu, J., & Yuan, H. (2026). Early strong anticholinergic initiation and 30-day mortality in older inpatients with dementia: a target trial emulation. Research Square. https://doi.org/10.21203/rs.3.rs-10644330/v1
Vancouver
Liu J, Yuan H. Early strong anticholinergic initiation and 30-day mortality in older inpatients with dementia: a target trial emulation. Research Square. 2026. doi:10.21203/rs.3.rs-10644330/v1.
BibTeX
@article{liu2026-6e68a0ab,
author = {Liu, J. and Yuan, H.},
title = {{Early strong anticholinergic initiation and 30-day mortality in older inpatients with dementia: a target trial emulation}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10644330/v1},
url = {https://doi.org/10.21203/rs.3.rs-10644330/v1}
}
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