Stroke is the second leading cause of death and a top cause of disability worldwide (~12 million events and ~6.5 million deaths a year). This oracle estimates the causal reduction in stroke death or dependency (modified Rankin Scale 3–6) across acute reperfusion, systems-of-care and secondary-prevention strategies, all acting through cerebral ischaemic injury — with decompressive surgery separated as a life-saving mass-effect path. Effect sizes are from named trials. For education, not individual medical advice.
Tick the interventions to combine. Each shows its trial effect estimate, 95% confidence interval (CI), E-value, mechanism, and citation. ★ = in the current Pareto effective set but not yet ticked.
Headline is the front-door estimate: shared infarct overlap removed via dose-response saturation; residual direct-effect overlap removed via the eigenvalue model at ρ̄.
Under monotonicity + exogeneity (E-value bounds the exogeneity assumption).
Faithful causal directed acyclic graph (DAG). Prevention (avoid the infarct) and acute reperfusion (salvage tissue) act through the shared mediator cerebral ischaemic injury / infarct burden, which drives neurological deficit and thence death or dependency (Y). Decompressive hemicraniectomy acts by relieving mass effect (survival), not by reducing infarct. Named confounders — subtype, time-to-treatment, baseline severity — open back-door paths (adjusted). Mediator cascade: interventions attach to the node they act on (acute → secondary → organised → decompressive), which converge on the disease state and thence the endpoint — drawing the intermediate mediators explicitly is what exposes d-separation and per-channel saturation.
Eigenvalue diagnostics for the selected interventions under an equicorrelation matrix (off-diagonal ρ̄). A large λmax relative to k signals redundancy; n_eff is the effective number of independent interventions actually contributing.
On mechanistic grounds ρ̄ ≈ 0.30 is defensible: the reperfusion arms (thrombolysis, thrombectomy) and the antithrombotic prevention arms overlap on the ischaemic pathway, so combining them is partly redundant. ρ̄ is user-adjustable because acute reperfusion and long-term risk-factor control act at very different times and mechanisms. Most of the overlap is now handled structurally by the mediator nodes (same-node substitutes saturate); ρ̄ governs only the residual correlation among direct effects.
Minimum-effective-set analysis. Set a target combined risk reduction; the model finds the smallest set of interventions — accounting for front-door mediator overlap — that reaches it, and highlights them. If the target exceeds what all interventions together can achieve, the full set is shown (never an empty one). "Apply" ticks exactly that set.
Monte Carlo propagation. Each selected intervention's log-effect is sampled from a normal distribution implied by its 95% CI; samples are combined with the same eigenvalue overlap discount. 5,000 draws.
Intervening on the selected set S with Pearl's do-operator (setting the interventions, not merely observing them). Contrast against do(∅) = no intervention.
For each intervention: "if not for this one, the combined front-door effect would be…". Isolates each intervention's marginal causal contribution after mediator-overlap removal, so shared-pathway agents are not double-credited.
| If not for… | HR without it | HR with full set | marginal RRR lost |
|---|
One-at-a-time sensitivity. Each intervention's effect is swung across its 95% confidence interval (others held at point estimate); the bar is the resulting swing in the combined front-door effect. A long bar means the combined estimate leans heavily on that single trial's precision.
Front-door (mediation) decomposition. Prevention and reperfusion act through one shared mediator — cerebral ischaemic injury. Each log-effect is split into an infarct-mediated (indirect) and a direct part. Indirect parts are pooled through the mediator with dose-response saturation, removing the mediator cross-correlation; direct parts keep the residual eigenvalue correlation at ρ̄. Decompressive hemicraniectomy, which improves survival by relieving mass effect rather than reducing infarct, is NOT discounted against the reperfusion / prevention arms. Here mediated effects are pooled WITHIN each cascade node (dose-response saturation of substitutes) and composed in SERIES across nodes (d-separated channels), with the per-node reductions reported so the channel structure is visible.
| Intervention | HR | %infarct↓ | med-frac | indirect log | direct log |
|---|
Which % of cross-correlation is appropriate? Not one number. The mediator overlap is fixed empirically by the infarct saturation (currently removing — of the summed mediated effect when interventions are stacked). Note a domain caveat: reperfusion and antithrombotic arms are partly redundant on the ischaemic pathway, whereas hemicraniectomy adds a distinct mass-effect mechanism. Infarct-mediated fractions are transparent, adjustable priors.
Front-door caveat (antithesis): the acute therapies reach only a fast-triaged minority (thrombolysis <4.5 h; thrombectomy LVO-only), survival from hemicraniectomy often means dependency, anticoagulation’s benefit is offset by bleeding, and globally the burden is an access problem best addressed by blood-pressure control and stroke units.
Select interventions to generate a plain-language summary.