The RAI-C and RAI-A represent effective tools for measuring frailty in surgical populations with predictive ability on par with other frailty tools. Moderate correlation between the measures suggests convergent validity. The RAI-C offers the advantage of prospective, preoperative assessment that is proved feasible for large-scale screening in clinical practice. However, further efforts should be directed at determining the optimal components of preoperative frailty assessment.
IMPORTANCE Patients with frailty have higher risk for postoperative mortality and complications; however, most research has focused on small groups of high-risk procedures. The associations among frailty, operative stress, and mortality are poorly understood.OBJECTIVE To assess the association between frailty and mortality at varying levels of operative stress as measured by the Operative Stress Score, a novel measure created for this study. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study included veterans in the Veterans Administration Surgical Quality Improvement Program from April 1, 2010, through March 31, 2014, who underwent a noncardiac surgical procedure at Veterans Health Administration Hospitals and had information available on vital status (whether the patient was alive or deceased) at 1 year postoperatively. A Delphi consensus method was used to stratify surgical procedures into 5 categories of physiologic stress. EXPOSURES Frailty as measured by the Risk Analysis Index and operative stress as measured by the Operative Stress Score. MAIN OUTCOMES AND MEASURES Postoperative mortality at 30, 90, and 180 days. RESULTS Of 432 828 unique patients (401 453 males [92.8%]; mean (SD) age, 61.0 [12.9] years), 36 579 (8.5%) were frail and 9113 (2.1%) were very frail. The 30-day mortality rate among patients who were frail and underwent the lowest-stress surgical procedures (eg, cystoscopy) was 1.55% (95% CI, 1.20%-1.97%) and among patients with frailty who underwent the moderate-stress surgical procedures (eg, laparoscopic cholecystectomy) was 5.13% (95% CI, 4.79%-5.48%); these rates exceeded the 1% mortality rate often used to define high-risk surgery. Among patients who were very frail, 30-day mortality rates were higher after the lowest-stress surgical procedures (10.34%; 95% CI, 7.73%-13.48%) and after the moderate-stress surgical procedures (18.74%; 95% CI, 17.72%-19.80%). For patients who were frail and very frail, mortality continued to increase at 90 and 180 days, reaching 43.00% (95% CI, 41.69%-44.32%) for very frail patients at 180 days after moderate-stress surgical procedures. CONCLUSIONS AND RELEVANCEWe developed a novel operative stress score to quantify physiologic stress for surgical procedures. Patients who were frail and very frail had high rates of postoperative mortality across all levels of the Operative Stress Score. These findings suggest that frailty screening should be applied universally because low-and moderate-stress procedures may be high risk among patients who are frail.
Peripheral artery disease (PAD) is a leading cause of cardiovascular morbidity and mortality1; however, the extent to which genetic factors increase risk for PAD is largely unknown. Using electronic health record data, we performed a genome-wide association study in the Million Veteran Program testing ~32 million DNA sequence variants with PAD (31,307 cases and 211,753 controls) across veterans of European, African, and Hispanic ancestry. The results were replicated in an independent sample of 5,117 PAD cases and 389,291 controls from UK Biobank. We identified 19 PAD loci, 18 of which have not been previously reported. 11 of the 19 loci were associated with disease in three vascular beds (coronary, cerebral, peripheral), including LDLR, LPL, and LPA, suggesting that therapeutic modulation of LDL cholesterol, the LPL pathway or circulating lipoprotein(a) may be efficacious for multiple atherosclerotic disease phenotypes. Conversely, 4 of the variants appeared to be specific for PAD, including F5 p.R506Q, highlighting the pathogenic role of thrombosis in the peripheral vascular bed and providing genetic support for Factor Xa inhibition as a therapeutic strategy for PAD. Our results highlight mechanistic similarities and differences among coronary, cerebral, and peripheral atherosclerosis and provide therapeutic insights.
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