Table 1.

Proposed outcomes for community-acquired pneumonia.

	Mechanism	Quantitative measures	Limitations	Solutions
Longer-term outcomes beyond 30 days	Cardiovascular, cognitive impairment, debilitation from acute diseases, dysbiosis, confounding comborbidities	90-Day, 180-day, 365-day mortality	Direct attribution to pneumonia may be difficult	Large populations, longitudinal
		Cardiovascular events
Modifiable mortality	Care processes	OBS: Propensity matched/weighted risk differences	Causal inference/confounding, dynamic/time-varying exposures	Large populations, granular data, prospective pragmatic trials/SMART
	Dx, Site of care, abx, resp/hemodynamic support	Trials: cluster-RCTs with bundled interventions?
Cardiovascular impairment	Endothelial inflammation, dysbiosis, stress axis	ACS events	Confounding
		Heart failure new diagnoses
Neurologic impairment	Endothelial inflammation, dysbiosis, delirium/post-ICU syndrome, hypoxemia/hypoperfusion	CVA events	Causal inference/confounding	Concurrent matched control population
		New diagnoses dementia	Ascertainment/
			Recall bias
Functional impairment	Debilitation/immobility, endothelial inflammation, post-ICU syndrome	Return to work, loss of independence, job loss, homelessness, separation/divorce	Recall bias	Concurrent control population
Patient experience	Care processes, organization factors, patient factors	Survey	Influenced by patient factors	Longitudinal pre/post data
		Healthcare engagement
Misdiagnosis	Patient complexity, provider/organizational factors	Diagnostic discordance
		Re-admission
		?Lung cancer dx
Surrogate endpoints:
CRP	Patient immune response
Procalcitonin	Patient immune response, pathogen (bacterial versus viral)
Clinical stability	Patient immune response, pathogen

abx, antibiotics; ACS, acute coronary syndrome; CRP, c-reactive protein; CVA, cerebrovascular accident; dx, diagnosis; ICU, intensive care unit; RCT, randomised controlled trial; SMART, Sequential, multiple assignment, randomized trials.