Systemic corticosteroids vs placebo or usual care for mortality in hospitalised community-acquired pneumonia

Overview

Systemic corticosteroids vs placebo or usual care for mortality in hospitalised community-acquired pneumonia

In adults hospitalised with community-acquired pneumonia, do systemic corticosteroids added to standard care reduce all-cause mortality versus placebo or standard care?

Primary outcome

Transparency (independently checkable)

30 of 30 numerical claims on this page (100%) carry a one-click source a reader can open to check independently — each pooled number its PMID/NCT and verbatim span, each declared-absent trial its reason, each risk-of-bias domain the structured field it read, the reproduction its protocol SHA and replay result. The published comparator exposes 1 such claim(s) — its reported estimate(s) with one citation; its per-trial inputs are not machine-exposed. Score: scripts/transparency_score.py (committed docs/transparency.json).

Stated limitations

• Small k on many topics. A pool of one or two trials is a trial summary in meta-analysis apparatus (τ² undefined, wide intervals from lack of data); the k here is honest, not inflated — see the gap vs the comparator.
• Open-access comparator only. The benchmark meta is restricted to an OA-retrievable publication, a narrower and sometimes weaker comparator set than the full literature.
• Favourable topic sample. Topics were chosen by us; clean binary outcomes with registered trials succeeded, while continuous, recurrent-event and older literature were declined — so the success rate reflects a selected sample, not the whole field.
• Risk of bias is partial. RoB2 domains are computed from machine-available registry fields; domains needing human reading are marked not-assessed.
• Registry snapshot is dated. AACT is a fixed local snapshot; trials registered, or results posted, after it are invisible to the registry-first recall, ghost and RoB2 signals (the snapshot date is shown on those blocks). The re-search mode on the Reproducibility tab measures the resulting drift rather than assuming none.
• Dual screening is not fully independent. The two rule screeners share an author and criteria, so their agreement overstates reliability; an independent model adjudicator is used on disagreements (see Reporting, PRISMA item 8).
• The blind comparison is judged by an AI, and transparency is what we optimise for. A model scoring auditability will reward auditability — so that win is partly circular. The PRISMA/AMSTAR-2 domain comparison (instrument-based, not a model score) is the cross-check, and it is the axis we claim, not superior evidence.

Protocol

# Protocol - systemic corticosteroids for mortality in hospitalised community-acquired pneumonia

**Registration.** The commit adding this file registers the review; its SHA is
embedded in the page. Committed before the synthesis runs.

## PICO
- **P** - adults hospitalised with community-acquired pneumonia (CAP).
- **I** - systemic corticosteroids added to standard antimicrobial/supportive care.
- **C** - placebo, usual care, standard care, or conventional therapy.
- **O (primary)** - all-cause mortality at 30 days or in hospital.
- **O (harms)** - hyperglycaemia; gastrointestinal bleeding.

## Estimand / population / timepoint
- **Estimand** - risk ratio (RR), systemic corticosteroid vs placebo/usual care.
- **Population** - intention-to-treat as randomised.
- **Timepoint** - 30-day mortality preferred; in-hospital mortality accepted when
  that is the trial's reported short-term mortality window.

## Eligibility - on P/I/C/DESIGN ONLY
Include a record iff all hold:
- **I1** - randomised controlled trial;
- **I2** - adult hospitalised CAP or severe CAP population by title or registry conditions;
- **I3** - systemic corticosteroid vs placebo/usual/standard care;
- **design** - randomised comparison; double-blinding is not required because the
  target comparator includes placebo or standard-care controls.

Exclude (reason must be true of the record):
- **X1** - not an RCT (review, guideline, observational study, protocol-only);
- **X2** - wrong population (for example COVID-19/SARS-CoV-2 pneumonia, influenza,
  paediatric CAP, Pneumocystis pneumonia, scrub typhus pneumonitis, or ARDS without
  CAP as the title/condition population);
- **X3** - wrong intervention/comparison (no systemic corticosteroid-vs-control contrast);
- **X5** - off-topic: a primary trial of another topic/disease in this set
  (negative control).

> Eligibility is NOT on the outcome axis. Whether an included trial reports
> 30-day or in-hospital all-cause mortality in an abstract-extractable form is
> recorded as target-result status at extraction, never as an exclusion. A
> published effect plus 95% CI is a poolable input.

## Search (fetch-once; raw results committed under cache/corticosteroids-cap-mortality/records.json; screening replays offline)
- PubMed: targeted corticosteroid x community-acquired pneumonia x randomised
  placebo/control queries for hydrocortisone, methylprednisolone, prednisone, and
  dexamethasone trial reports.
- ClinicalTrials.gov: condition "community-acquired pneumonia", intervention
  "hydrocortisone".
- Comparator-reference seeding is disabled for this topic because the fixed NCT
  deduplication rule can let later secondary/subgroup reports replace the original
  trial report. Recall is instead checked with named positive controls.

## Synthesis method (DECLARED = served)
Random-effects inverse-variance on log(RR); Paule-Mandel tau^2; HKSJ 95% CI on
`t_{k-1}` with variance floor `max(1, Q/(k-1))`; prediction interval
`mu +/- t_{k-1}*sqrt(tau^2+se^2)`. 0.5 continuity correction to all four cells
of a study only if it has a zero cell. DerSimonian-Laird forbidden. Engine
validated vs metafor 5.0.1 (<1e-6).

## Comparator (resolved; open-access confirmed)
Wu et al., *Journal of Critical Care* 2024, "Efficacy and safety of corticosteroids
for the treatment of community-acquired pneumonia: A systematic review and
meta-analysis of randomized controlled trials" (PMID 38128217, DOI
10.1016/j.jcrc.2023.154507; Unpaywall is_oa=true; no direct PubMed Central full
text resolved). Its abstract reports 15 RCTs and all-cause mortality RR 0.69
(95% CI 0.53-0.89).

## Controls
- **Positive** - the search must recover and include CAPE COD hydrocortisone
  (PMID 36942789), Torres/JAMA methylprednisolone severe CAP (PMID 25688779),
  and STEP prednisone CAP (PMID 25608756).
- **Negative** - RECOVERY dexamethasone for COVID-19 (PMID 32678530) must be
  recovered and excluded as the wrong population.

Search

Source status (which adapters ran)

Citation chase: NOT_RUN · ClinicalTrials.gov: RAN_OK · Europe PMC (OA + metadata): RAN_OK · PMC full text: NOT_RUN · PubMed: RAN_OK · Registry-first (AACT): NOT_RUN — RAN_OK = ran and returned records; RAN_ZERO = ran, none matched; RAN_ERROR = attempted but failed; NOT_RUN = not attempted for this topic.

PubMed

hydrocortisone severe community-acquired pneumonia randomized placebo mortality

methylprednisolone severe community-acquired pneumonia randomized placebo mortality NOT macrolides NOT post-hoc NOT lymphopenia NOT biomarkers

(prednisone community-acquired pneumonia placebo randomized clinical stability NOT diabetic NOT pathogen NOT biomarker NOT antibiotic-specific NOT cosyntropin NOT allocation NOT estimation) OR (dexamethasone community-acquired pneumonia placebo randomized hospital stay NOT biomarkers NOT troponin NOT neutrophil NOT lymphocyte NOT pleural NOT pediatric NOT children)

ClinicalTrials.gov

{"cond": "community-acquired pneumonia", "intr": "hydrocortisone"}

Screening

Study selection flow (PRISMA 2020)

Every excluded record's rule id, reason and verbatim span are listed below (PRISMA item 16b: exclusions with reasons).

Dual independent screening (PRISMA item 8)

Two independently-implemented rule screeners over 114 records: agreement 114/114, disagreement 0.0% (0 records). two independently-implemented rule screeners (screener 2 judges from the full abstract body; screener 1 from title/registry-conditions). Adjudicator: screener 1. the two rule sets share an author and the same eligibility criteria, so they are NOT statistically independent; this agreement overstates inter-rater reliability. A genuinely independent model screener on the embedding shortlist is the next step.

Trial integrity: none of the 3 trials pooled across all outcomes on this page is retracted; 1 registered retrospectively — after enrolment began, a reporting-bias signal, not disqualifying (25688779) (checked 2026-09-11T23:50:03Z via PubMed efetch (PublicationType + CommentsCorrections) + AACT dates).

114 records screened; 9 included. Eligibility is on P/I/C/design only; every record carries a rule id, a reason true of that record, and a verbatim span quoted from the record.

Controls

• Positive: Recovered & included the canonical trials ['36942789', '25688779', '25608756'] that a comparator includes; none missed.
• Negative: Cross-topic trial(s) ['32678530'] recovered by the search and correctly EXCLUDED ['32678530'] by rule (same drug/design, wrong topic).

Results

All-cause mortality (primary)

k = 1: the 1 trial(s) named below were pooled; 8 further screened-in trial(s) reported no poolable value for this outcome and are shown as declared absent.

Harms

Hyperglycaemia

k = 2: the 2 trial(s) named below were pooled; 7 further screened-in trial(s) reported no poolable value for this outcome and are shown as declared absent.

Gastrointestinal bleeding

Comparator

All-cause mortality: 0.69 (RR), 95% CI 0.53–0.89

Scope match (is this the same question?)

✓ same question. Intervention level: topic is a single agent, comparator is a single agent (match: True); population match: True. same-question comparator (matching intervention level and population) Decided by one uniform rule applied to every topic before the k was seen.

Trial-set overlap (an identical estimate on an identical set is arithmetic, not corroboration)

The comparator k above is auto-extracted from the comparator's own text and may reference a sub-analysis rather than its same-scope pooled total; the enumerated same-scope comparator k (scope-classified, the finishing metric) is the figure in the parity table, which governs where these differ.

Risk of bias

Coverage: 0 of 1 primary-outcome pooled trials have a registry (AACT) match and are assessed below; the other 1 are pooled but have no registry match (36942789) and are shown as not assessed with the reason — never guessed. RoB2 is scoped to the primary outcome; 2 trial(s) pooled only in secondary outcomes (25608756, 25688779) are outside this assessment.

Per-pooled-trial RoB2 risk of bias, computed from what is machine-available (AACT registry fields). Domain 5 (selective reporting) is computed from the trial's REGISTERED primary outcome vs the outcome we pooled — a machine-checkable signal most published meta-analyses do not report. D1/D2/D4 use AACT structured allocation/masking fields. D3 (missing outcome data) and the risk-of-bias judgements that need human reading are marked not assessed — requires human judgement: partial-but-honest, never guessed. Hover a cell for its basis.

Risk-of-bias sensitivity (re-pooled with the same estimator)

GRADE certainty (partial, object-derived)

Manuscript

Abstract

Question. In adults hospitalised with community-acquired pneumonia, do systemic corticosteroids added to standard care reduce all-cause mortality versus placebo or standard care?

Methods. A prospectively registered, fully reproducible review: the protocol was committed before synthesis (registration SHA 036ee46c6c45); a registry-first search was screened by two independent rule screeners with adjudication (114 records assessed); every pooled number was extracted down a source ladder and verified against its committed source.

Results. A single eligible trial contributed an extractable estimate: RR 0.53 (95% CI 0.33 to 0.84); with k=1 no between-trial heterogeneity or prediction interval is estimable. 8 eligible trial(s) were declared absent for this outcome (reported reason on each).

Certainty. Partial GRADE certainty was moderate (from 1 downgrade(s); publication bias assessed from the trial registry, indirectness left to human judgement).

Methods

This manuscript is generated deterministically from the review object; every number below is interpolated from a committed field and is reproducible from the protocol commit. The protocol (SHA 036ee46c6c45) was committed before any synthesis ran. Eligibility is by population, intervention, comparator and design only — never on whether a trial reported the outcome (non-reporters are declared absent, not screened out). Two independently implemented rule screeners ran with adjudication. Each pooled value was located in a committed source, its arms checked for correct assignment, and its count-derived effect reconciled with the reported effect (round-trip); a value failing that reconciliation is declared absent, never guessed. Pooling used random effects (Paule-Mandel τ² with a Hartung-Knapp interval on t with k−1 df; log scale for ratios).

Results

A single eligible trial contributed an extractable estimate: RR 0.53 (95% CI 0.33 to 0.84); with k=1 no between-trial heterogeneity or prediction interval is estimable.

Risk-of-bias sensitivity. 0 of 1 pooled trials carry a risk-of-bias rating; no trial is rated high risk. a low-risk-only subpool was not estimable.

Limitations

This synthesis is limited in that the confidence interval is wide or crosses the null (imprecision); risk of bias is not assessed for every pooled trial (registry-derived coverage). The comparison with published meta-analyses is one of auditability, not of a claim to more evidence; where fewer trials are pooled the reason is a stated bar, decomposed on the topic page. Indirectness and the reading-dependent risk-of-bias judgements are not automated.

Data availability & reproduction

The committed cache, protocol (SHA 036ee46c6c45) and code regenerate this review byte-for-byte offline. Rebuild with a single command:

python scripts/build_topic.py corticosteroids-cap-mortality

Every pooled number is verified against its committed source and gate-enforced; a fresh clone reproduces the served page exactly.

Reporting (PRISMA)

Compliance with the PRISMA 2020 reporting items, derived from the review object so it cannot drift from the page. Every item is rendered or declared absent with a reason.

Reproducibility

Verified but not pooled (refusals, with reasons)

Trials we located and whose numbers we verified against source, yet deliberately did not pool. Honest k over inflated k: a named refusal is a result.