Objective:

To evaluate the independent association between frailty and diagnostic discordance between the presumptive emergency department (ED) diagnosis and the adjudicated discharge diagnosis among adults presenting with suspected infection, while accounting for age, comorbidity, and other patient-, disease-, and context-related factors.

Approach:

• Study Design: Retrospective analysis of the prospectively collected Sepsis 2-3 cohort. After duplicate ED presentations were excluded, 646 unique adults presenting with suspected infection at a tertiary academic center in the Netherlands were included.
• Statistical Analysis: Categorical variables were compared using chi-squared or Fisher’s exact tests and continuous variables using the Mann-Whitney U test. Determinants of diagnostic discordance were evaluated using forward multivariable logistic regression.
• Frailty Assessment: Frailty was retrospectively assessed using the Clinical Frailty Scale (CFS), with CFS <5 categorized as nonfrail and CFS ≥5 as frail.

Key Findings:

• Diagnostic discordance between the presumptive ED diagnosis and adjudicated discharge diagnosis occurred in 163 of 646 patients (25%).
• Discordance was more frequent among frail than nonfrail patients (31.3% vs 21.8%; P = 0.007).
• Frailty was independently associated with diagnostic discordance after adjustment (adjusted odds ratio [aOR], 1.622; 95% CI, 1.094-2.405; P = 0.016). A higher age-adjusted Charlson Comorbidity Index was also independently associated with discordance (aOR, 1.105; 95% CI, 1.013-1.204; P = 0.024).
• Age was not independently associated with diagnostic discordance after adjustment, suggesting that diagnostic complexity attributed to older age may be more closely related to frailty and multimorbidity than chronological age alone.

Interpretation:

Frailty independently identifies ED patients with suspected infection who are at greater risk of diagnostic discordance, even after accounting for age and comorbidity. The association should not be interpreted as causal or as evidence that discordance necessarily represents diagnostic error; rather, frailty may serve as a marker of greater diagnostic complexity and support careful evaluation and repeated clinical reassessment.

Limitations:

• Adjudication of the discharge diagnosis was partly subjective and potentially susceptible to human error and hindsight bias, despite the structured procedure and high interrater agreement.
• Treating upper and lower respiratory tract infections as concordant may have underestimated diagnostic discordance.
• The retrospective analysis was limited to documented variables, leaving the possibility of residual confounding from unmeasured factors such as physician experience or contextual decision-making.
• The single-center setting and Sepsis-2/SIRS-based inclusion criteria may limit generalizability to other healthcare settings and contemporary diagnostic pathways.

Conclusion:

Frailty and comorbidity were independently associated with diagnostic discordance among ED patients with suspected infection. Although the findings do not establish causality, recognition of frailty may help identify patients in whom infection diagnosis is more challenging and should prompt careful diagnostic evaluation, consideration of alternative diagnoses, and repeated reassessment as additional clinical information becomes available.