Derivation and external validation of a simple risk score for predicting severe acute kidney injury after intravenous cisplatin: cohort study.

OBJECTIVE: To develop and externally validate a prediction model for severe cisplatin associated acute kidney injury (CP-AKI). DESIGN: Multicenter cohort study. SETTING: Six geographically diverse major academic cancer centers across the US. PARTICIPANTS: Adults (≥18 years) receiving their first dose of intravenous cisplatin, 2006-22. MAIN OUTCOME MEASURES: The primary outcome was CP-AKI, defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of intravenous cisplatin. Independent predictors of CP-AKI were identified using a multivariable logistic regression model, which was developed in a derivation cohort and tested in an external validation cohort. For the primary model, continuous variables were examined using restricted cubic splines. A simple risk model was also generated by converting the odds ratios from the primary model into risk points. Finally, a multivariable Cox model was used to examine the association between severity of CP-AKI and 90 day survival. RESULTS: A total of 24 717 adults were included, with 11 766 in the derivation cohort (median age 59 (interquartile range (IQR) 50-67)) and 12 951 in the validation cohort (median age 60 (IQR 50-67)). The incidence of CP-AKI was 5.2% (608/11 766) in the derivation cohort and 3.3% (421/12 951) in the validation cohort. Each of the following factors were independently associated with CP-AKI in the derivation cohort: age, hypertension, diabetes mellitus, serum creatinine level, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose. A simple risk score consisting of nine covariates was shown to predict a higher risk of CP-AKI in a monotonic fashion in both the derivation cohort and the validation cohort. Compared with patients in the lowest risk category, those in the highest risk category showed a 24.00-fold (95% confidence interval (CI) 13.49-fold to 42.78-fold) higher odds of CP-AKI in the derivation cohort and a 17.87-fold (10.56-fold to 29.60-fold) higher odds in the validation cohort. The primary model had a C statistic of 0.75 and showed better discrimination for CP-AKI than previously published models, the C statistics for which ranged from 0.60 to 0.68 (DeLong P<0.001 for each comparison). Greater severity of CP-AKI was monotonically associated with shorter 90 day survival (adjusted hazard ratio 4.63 (95% CI 3.56 to 6.02) for stage 3 CP-AKI versus no CP-AKI). CONCLUSION: This study found that a simple risk score based on readily available variables from patients receiving intravenous cisplatin could predict the risk of severe CP-AKI, the occurrence of which is strongly associated with death.

Therapeutic advances in COVID-19.

Over 2 years have passed since the start of the COVID-19 pandemic, which has claimed millions of lives. Unlike the early days of the pandemic, when management decisions were based on extrapolations from in vitro data, case reports and case series, clinicians are now equipped with an armamentarium of therapies based on high-quality evidence. These treatments are spread across seven main therapeutic categories: anti-inflammatory agents, antivirals, antithrombotics, therapies for acute hypoxaemic respiratory failure, anti-SARS-CoV-2 (neutralizing) antibody therapies, modulators of the renin-angiotensin-aldosterone system and vitamins. For each of these treatments, the patient population characteristics and clinical settings in which they were studied are important considerations. Although few direct comparisons have been performed, the evidence base and magnitude of benefit for anti-inflammatory and antiviral agents clearly outweigh those of other therapeutic approaches such as vitamins. The emergence of novel variants has further complicated the interpretation of much of the available evidence, particularly for antibody therapies. Importantly, patients with acute and chronic kidney disease were under-represented in many of the COVID-19 clinical trials, and outcomes in this population might differ from those reported in the general population. Here, we examine the clinical evidence for these therapies through a kidney medicine lens.

The N-terminal Helical Region of the Hepatitis C Virus p7 Ion Channel Protein Is Critical for Infectious Virus Production.

The hepatitis C virus (HCV) p7 protein is required for infectious virus production via its role in assembly and ion channel activity. Although NMR structures of p7 have been reported, the location of secondary structural elements and orientation of the p7 transmembrane domains differ among models. Furthermore, the p7 structure-function relationship remains unclear. Here, extensive mutagenesis, coupled with infectious virus production phenotyping and molecular modeling, demonstrates that the N-terminal helical region plays a previously underappreciated yet critical functional role, especially with respect to E2/p7 cleavage efficiency. Interrogation of specific N-terminal helix residues identified as having p7-specific defects and predicted to point toward the channel pore, in a context of independent E2/p7 cleavage, further supports p7 as a structurally plastic, minimalist ion channel. Together, our findings indicate that the p7 N-terminal helical region is critical for E2/p7 processing, protein-protein interactions, ion channel activity, and infectious HCV production.

Complementary Effects of Host Defense Peptides Piscidin 1 and Piscidin 3 on DNA and Lipid Membranes: Biophysical Insights into Contrasting Biological Activities.

Piscidins were the first antimicrobial peptides discovered in the mast cells of vertebrates. While two family members, piscidin 1 (p1) and piscidin 3 (p3), have highly similar sequences and α-helical structures when bound to model membranes, p1 generally exhibits stronger antimicrobial and hemolytic activity than p3 for reasons that remain elusive. In this study, we combine activity assays and biophysical methods to investigate the mechanisms underlying the cellular function and differing biological potencies of these peptides, and report findings spanning three major facets. First, added to Gram-positive (Bacillus megaterium) and Gram-negative (Escherichia coli) bacteria at sublethal concentrations and imaged by confocal microscopy, both p1 and p3 translocate across cell membranes and colocalize with nucleoids. In E. coli, translocation is accompanied by nonlethal permeabilization that features more pronounced leakage for p1. Second, p1 is also more disruptive than p3 to bacterial model membranes, as quantified by a dye-leakage assay and (2)H solid-state NMR-monitored lipid acyl chain order parameters. Oriented CD studies in the same bilayers show that, beyond a critical peptide concentration, both peptides transition from a surface-bound state to a tilted orientation. Third, gel retardation experiments and CD-monitored titrations on isolated DNA demonstrate that both peptides bind DNA but p3 has stronger condensing effects. Notably, solid-state NMR reveals that the peptides are α-helical when bound to DNA. Overall, these studies identify two polyreactive piscidin isoforms that bind phosphate-containing targets in a poised amphipathic α-helical conformation, disrupt bacterial membranes, and access the intracellular constituents of target cells. Remarkably, the two isoforms have complementary effects; p1 is more membrane active, while p3 has stronger DNA-condensing effects. Subtle differences in their physicochemical properties are highlighted to help explain their contrasting activities.

Desire for fertility among HIV-seroconcordant and -discordant couples in Lusaka, Zambia.

Pregnancy rates and the desire to conceive are increasing among women living with HIV in Africa. However, attempts to conceive may increase the risk of HIV transmission or reinfection. A better understanding of factors influencing fertility desires would significantly contribute to programmes to meet the reproductive needs of women living with HIV. Using a couples-based approach, this paper explored fertility desires among HIV-seroconcordant and -discordant couples in Lusaka, Zambia. Participants were 208 heterosexual couples recruited from community health clinics and their respective catchment areas. Couples completed assessments on demographics, condom use, relationship quality and communication. Desire for children was often shared among couple members, and the strongest predictor of participants' desire for children was having a partner who wanted children. Additionally, the number of children participants had, their own reports of positive communication, and their partner's HIV serostatus influenced reproductive desires. Results support the involvement of both couple members in pre-conception counselling and pregnancy planning interventions. The inclusion of both partners may be a more effective strategy to respond to the reproductive needs of couples affected by HIV, enabling them to safeguard the health of both partners and infants.

High-resolution structures and orientations of antimicrobial peptides piscidin 1 and piscidin 3 in fluid bilayers reveal tilting, kinking, and bilayer immersion.

While antimicrobial peptides (AMPs) have been widely investigated as potential therapeutics, high-resolution structures obtained under biologically relevant conditions are lacking. Here, the high-resolution structures of the homologous 22-residue long AMPs piscidin 1 (p1) and piscidin 3 (p3) are determined in fluid-phase 3:1 phosphatidylcholine/phosphatidylglycerol (PC/PG) and 1:1 phosphatidylethanolamine/phosphatidylglycerol (PE/PG) bilayers to identify molecular features important for membrane destabilization in bacterial cell membrane mimics. Structural refinement of (1)H-(15)N dipolar couplings and (15)N chemical shifts measured by oriented sample solid-state NMR and all-atom molecular dynamics (MD) simulations provide structural and orientational information of high precision and accuracy about these interfacially bound α-helical peptides. The tilt of the helical axis, τ, is between 83° and 93° with respect to the bilayer normal for all systems and analysis methods. The average azimuthal rotation, ρ, is 235°, which results in burial of hydrophobic residues in the bilayer. The refined NMR and MD structures reveal a slight kink at G13 that delineates two helical segments characterized by a small difference in their τ angles (<10°) and significant difference in their ρ angles (~25°). Remarkably, the kink, at the end of a G(X)4G motif highly conserved among members of the piscidin family, allows p1 and p3 to adopt ρ angles that maximize their hydrophobic moments. Two structural features differentiate the more potent p1 from p3: p1 has a larger ρ angle and less N-terminal fraying. The peptides have comparable depths of insertion in PC/PG, but p3 is 1.2 Å more deeply inserted than p1 in PE/PG. In contrast to the ideal α-helical structures typically assumed in mechanistic models of AMPs, p1 and p3 adopt disrupted α-helical backbones that correct for differences in the amphipathicity of their N- and C-ends, and their centers of mass lie ~1.2-3.6 Å below the plane defined by the C2 atoms of the lipid acyl chains.

Mitroflow aortic pericardial bioprosthesis--clinical performance.

OBJECTIVE: Advancing life expectancy with the increased prevalence of aortic valve degenerative disease brings the need for an aortic bioprosthesis with excellent haemodynamic performance and comparable durability. The Mitroflow bioprosthesis has been on the worldwide market, except in the United States, since 1982, while the current model (1991) has only recently gained regulatory approval in the latter country. This study was primarily performed to determine the durability of the current Mitroflow bioprosthesis. METHODS: The contemporary Mitroflow bioprosthesis was implanted in 381 patients in three centres. The mean age was 76.4 years (range 53-91 years) and the mean follow-up period was 5.4+/-3.4 years, a total of 2048.7 years of evaluation. Prosthesis-patient mismatch (PPM) was classified by reference effective orifice area index categories: normal > or = 0.85 cm(2) m(-2) (53.9%), mild 0.84-0.76 cm(2) m(-2) (33.9%), moderate < or = 0.75-0.66 cm(2) m(-2) (11.7%) and severe < or = 0.65 cm(2) m(-2) (0.5%). RESULTS: The survival, at 10 years, was 39.9+/-7.9% for 50-69 years, 27.0+/-3.7% for 70-79 years and 16.6+/-4.4% for > or = 80 years (p=0.011). There was a trend (p=0.063) influencing survival for moderate-to-severe PPM. Of the independent predictors influencing survival--moderate-to-severe projected effective orifice area index (pEOAI) (Hazard Ratio (HR) 1.6, p=0.0142) and left ventricular dysfunction (ejection fraction < 35%) (HR 1.9, p=0.0193) were included. The 10-year freedom from structural valve deterioration (SVD) at explant assessing the same age groups as survival was not different (p=0.081). The 10-year actual/actuarial freedom from SVD, at explant was for > or = 60 years--94.4+/-1.4% (85.2+/-3.9%), for > or = 65 years--94.2+/-1.4% (85.0+/-4.0%), for 61-70 years--97.4+/-2.6% (95.7+/-4.3%) and for > 70 years--94.0+/-1.5% (83.2+/-4.6%). CONCLUSIONS: The Mitroflow external mounted, pericardial aortic bioprosthesis with documented excellent haemodynamics (especially for the small aortic root), demonstrates that prosthesis-patient mismatch in moderate and severe categories can essentially be eliminated, with durability performance comparable to other heterograft (porcine and pericardial) bioprostheses.

Epiploic appendagitis in a 24-year-old woman.

Epiploic appendagitis is a very rare condition that results from acute inflammation of an appendix epiploica. We report a case involving a 24-year-old woman who presented to the emergency department with abdominal pain localized to the left lower quadrant. The patient was diagnosed with epiploic appendagitis, which was confirmed through findings obtained from a contrast-study computed tomography of the abdomen. The patient was subsequently taken to the operating room for a diagnostic laparoscopy due to persistent pain. Necrotic epiploic appendagitis was found on the descending colon, which was removed laparoscopically.

Delay in admission for elective coronary-artery bypass grafting is associated with increased in-hospital mortality.

BACKGROUND: Many health care systems now use priority wait lists for scheduling elective coronary artery bypass grafting (CABG) surgery, but there have not yet been any direct estimates of reductions in in-hospital mortality rate afforded by ensuring that the operation is performed within recommended time periods. METHODS: We used a population-based registry to identify patients with established coronary artery disease who underwent isolated CABG in British Columbia, Canada. We studied whether postoperative survival during hospital admission for CABG differed significantly among patients who waited for surgery longer than the recommended time, 6 weeks for patients needing semi-urgent surgery and 12 weeks for those needing non-urgent surgery. RESULTS: Among 7316 patients who underwent CABG, 97 died during the same hospital admission, for a province-wide death rate at discharge of 1.3%. The observed proportion of patients who died during the same admission was 1.0% (27 deaths among 2675 patients) for patients treated within the recommended time and 1.5% (70 among 4641) for whom CABG was delayed. After adjustment for age, sex, anatomy, comorbidity, calendar period, hospital, and mode of admission, patients with early CABG were only 2/3 as likely as those for whom CABG was delayed to experience in-hospital death (odds ratio 0.61; 95% confidence interval [CI] 0.39 to 0.96). There was a linear trend of 5% increase in the odds of in-hospital death for every additional month of delay before surgery, adjusted OR = 1.05 (95% CI 1.00 to 1.11). CONCLUSION: We found a significant survival benefit from performing surgical revascularization within the time deemed acceptable to consultant surgeons for patients requiring the treatment on a semi-urgent or non-urgent basis.

Survival benefit of coronary-artery bypass grafting accounted for deaths in those who remained untreated.

BACKGROUND: Currently there are no direct estimates of mortality reduction afforded by coronary-artery bypass grafting (CABG) that take into account the deaths among patients for whom coronary revascularization was indicated but who did not undergo the treatment. The objective of this analysis was to compare survival after the treatment decision between patients who underwent CABG and those who remained untreated. METHODS: We used a population-based registry to identify patients with established coronary artery disease who were to undergo first-time isolated CABG. We measured the effect of surgical revascularization on survival after the treatment decision in two cohorts of patients categorized by symptoms, coronary anatomy, and left ventricular function. RESULTS: One in 10 patients died during the five years after treatment decision. The hazard of death among patients who underwent CABG was 51 percent of that for the untreated group, the adjusted hazard ratio was 0.51 (95 percent confidence interval, 0.43 to 0.61). The effect was stronger when CABG was performed within the recommended time: adjusted hazard ratios were 0.43 (95 percent confidence interval, 0.35 to 0.53) and 0.58 (95 percent confidence interval, 0.48 to 0.70) for early and late intervention, respectively; chi-square for the difference between hazard ratios was 12.2 (P < 0.001). CONCLUSION: Estimates that account for patients who died before they could undergo a required CABG indicate a significant survival benefit of performing early surgical revascularization even for patients registered to undergo the operation on the non-urgent basis.

Do women spend longer on wait lists for coronary bypass surgery? Analysis of a population-based registry in British Columbia, Canada.

BACKGROUND: Studies have shown patients who are delayed for surgical cardiac revascularization are faced with increased risks of symptom deterioration and death. This could explain the observation that operative mortality among persons undergoing coronary artery bypass surgery (CABG) is higher among women than men. However, in jurisdictions that employ priority wait lists to manage access to elective cardiac surgery, there is little information on whether women wait longer than men for CABG. It is therefore difficult to ascertain whether higher operative mortality among women is due to biological differences or to delayed access to elective CABG. METHODS: Using records from a population-based registry, we compared the wait-list time between women and men in British Columbia (BC) between 1990 and 2000. We compared the number of weeks from registration to surgery for equal proportions of women and men, after adjusting for priority, comorbidity and age. RESULTS: In BC in the 1990 s, 9,167 patients aged 40 years and over were registered on wait lists for CABG and spent a total of 136,071 person-weeks waiting. At the time of registration for CABG, women were more likely to have a comorbid condition than men. We found little evidence to suggest that women waited longer than men for CABG after registration, after adjusting for comorbidity and age, either overall or within three priority groups. CONCLUSION: Our findings support the hypothesis that higher operative mortality during elective CABG operations observed among women is not due to longer delays for the procedure.

Changing outcomes of coronary revascularization in British Columbia, 1995-2001.

OBJECTIVES: To examine outcomes following all first coronary revascularization procedures, isolated coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) on British Columbia (BC) resident adults from 1995 to 2001. METHODS: CABG and PCI data were obtained from the BC Cardiac Registry, and mortality data were obtained from the BC Vital Statistics Agency. Analysis was performed by annual cohorts, and the rates reported are unadjusted. RESULTS: An increasing percentage of revascularization procedures was performed with PCI (62% in 1995 to 73% in 2001; P<0.001) due to the increased use of PCI procedures. Except in emergent cases, 30-day mortality improved after PCI (1.8% to 1.1%; P=0.02) and CABG (1.8% to 1.2%; P=0.01). Emergent cases accounted for 9.0% of PCIs and 2.7% of CABGs, the percentage treated by CABG decreasing from 14.5% in 1995 to 7.5% by 2001 (P<0.001). Mortality rates among emergent cases was higher at 30 days, with no trend in PCI mortality (12%) but a substantial reduction in 30-day mortality after CABG (28% to 10%; P=0.003). One-year survival free from repeat revascularization following PCI increased from 73% in 1995 to 83% in 2001 (P<0.001) and from 94% to 95% (P<0.005) following CABG. CONCLUSIONS: Improvements in procedure-related mortality observed in trials have extended to clinical practice. With respect to emergent cases, an increasing proportion were treated by PCI with no change in PCI mortality but associated with a drop in surgical mortality. There has been a consistent and substantial drop in the need for repeat procedures within one year for patients selected for PCI.

Unplanned emergency surgery in relation to length of wait lists at registration.

OBJECTIVE: To compare the cumulative incidence of emergency surgery between two groups of patients classified according to the length of wait lists at the time of their registration for coronary artery bypass grafting (CABG) and to test for significant differences in the risk of emergency surgery resulting from registration on a longer wait list. METHODS: A prospective study of all adult British Columbia residents who registered to undergo isolated CABG. We compared the time-dependent cumulative incidence for undergoing planned surgery through unplanned emergency admission before or during a certain wait-list week between two categories of wait-list size. The list size was a simple count of patients with higher or equal urgency to undergo CABG who were on a wait list at the time of registration of a new patient. RESULTS: Wait lists with one month or less of clearance time were observed in all urgent patients and were more prevalent in semi-urgent than non-urgent patients (79.1% vs 44.7%, respectively). The patients registered on a list with a clearance time of more than one month had a rate of unplanned emergency admission similar to those on a list with a clearance time of one month or less, OR = 1.07 (95% CI, 0.78-1.47) after adjustment for age, sex, comorbidity, calendar period, urgency and week on the list. During fifty-two weeks of the wait-list follow-up, an equal proportion of patients underwent unplanned emergency surgery after registration on lists in both clearance-time categories, OR = 1.03 (95% CI, 0.78-1.37) after adjustment. The number of patients who underwent CABG without having been registered on a wait list in the same hospital exerted no independent effect. CONCLUSIONS: The length of a wait list at registration had no effect on the probability that a semi-urgent or non-urgent patient would undergo CABG through unplanned emergency admission before or during a certain wait-list week.

Cumulative incidence for wait-list death in relation to length of queue for coronary-artery bypass grafting: a cohort study.

BACKGROUND: In deciding where to undergo coronary-artery bypass grafting, the length of surgical wait lists is often the only information available to cardiologists and their patients. Our objective was to compare the cumulative incidence for death on the wait list according to the length of wait lists at the time of registration for the operation. METHODS: The study cohort included 8966 patients who registered to undergo isolated coronary-artery bypass grafting (82.4% men; 71.9% semi-urgent; 22.4% non-urgent). The patients were categorized according to wait-list clearance time at registration: either "1 month or less" or "more than 1 month". Cumulative incidence for wait-list death was compared between the groups, and the significance of difference was tested by means of regression models. RESULTS: Urgent patients never registered on a wait list with a clearance time of more than 1 month. Semi-urgent patients registered on shorter wait lists more often than non-urgent patients (79.1% vs. 44.7%). In semi-urgent and non-urgent patients, the observed proportion of wait-list deaths by 52 weeks was lower in category "1 month or less" than in category "more than 1 month" (0.8% [49 deaths] vs. 1.6% [39 deaths], P < 0.005). After adjustment, the odds of death before surgery were 64% higher in patients on longer lists, odds ratio [OR] = 1.64 (95% confidence interval [CI] 1.02-2.63). The observed death rate was higher in category "more than 1 month" than in category "1 month or less", 0.79 (95%CI 0.54-1.04) vs. 0.58 (95% CI 0.42-0.74) per 1000 patient-weeks, the adjusted OR = 1.60 (95%CI 1.01-2.53). Longer wait times (log-rank test = 266.4, P < 0.001) and higher death rates contributed to a higher cumulative incidence for death on the wait list with a clearance time of more than 1 month. CONCLUSION: Long wait lists for coronary-artery bypass grafting are associated with increased probability that a patient dies before surgery. Physicians who advise patients where to undergo cardiac revascularization should consider the risk of pre-surgical death that is associated with the length of a surgical wait list.

The risk of death associated with delayed coronary artery bypass surgery.

BACKGROUND: The detrimental effect of delaying surgical revascularization has been estimated in randomized trials and observational studies. It has been argued that the Kaplan-Meier method used in quantifying the hazard of delayed treatment is not appropriate for summarizing the probability of competing outcomes. Therefore, we sought to improve the estimates of the risk of death associated with delayed surgical treatment of coronary artery disease. METHODS: Population-based prospective study of 8,325 patients registered to undergo first time isolated coronary artery bypass grafting (CABG) in any of the four tertiary hospitals that provide cardiac care to adult residents of British Columbia, Canada. The cumulative incidence of pre-operative death, the cumulative incidence of surgery, and the probability that a patient, who may die or undergo surgery, dies if not operated by certain times over the 52-week period after the decision for CABG were estimated. The risks were quantified separately in two groups: high-severity at presentation were patients with either persistent unstable angina or stable angina and extensive coronary artery disease, and low-severity at presentation were stable symptomatic patients with limited disease. RESULTS: The median waiting time for surgery was 10 weeks (interquartile range [IQR] 15 weeks) in the high-severity group and 21 weeks (IQR 30 weeks) in the low-severity group. One percent of patients died before surgery: 54 in the high-severity and 26 in the low-severity group. For 58 (72.5%) patients, death was related to CVD (acute coronary syndrome, 33; chronic CVD, 16; other CVD, 4; and sudden deaths, 5). The overall death rate from all causes was 0.61 (95% CI 0.48-0.74) per 1,000 patient-weeks, varying from 0.62 (95% CI 0.45-0.78) in the high-severity group to 0.59 (95% CI 0.37-0.82) in the low-severity group. After adjustment for age, sex, and comorbidity, the all-cause death rate in the low-severity group was similar to the high-severity group (OR = 1.02, 95% CI 0.64-1.62). The conditional probability of death was greater in the high-severity group than in the low-severity group both for all-cause mortality (p = 0.002) and cardiovascular deaths (p <0.001). CONCLUSION: The probability of death conditional on not having undergone a required CABG increases with time spent on wait lists.

Do longer delays for coronary artery bypass surgery contribute to preoperative mortality in less urgent patients?

BACKGROUND: Priority wait lists are common for managing access to cardiac surgery in publicly funded health systems. We evaluated whether longer delays contribute to the probability of death before surgery among patients prioritized into the less urgent category. METHODS: We studied records of 9233 patients registered for isolated coronary artery bypass graft (CABG) in British Columbia, Canada. The primary outcome was death before surgery. We estimated the probability that a patient, who could be removed from the list as a result of surgery, death, or other competing events, dies on or before a certain wait-list week. RESULTS: Despite similar death rates in semiurgent and nonurgent groups, 0.63 (95% confidence interval, 0.46-0.80) versus 0.58 (0.36-0.80) per 1000 patient-weeks, nonurgent patients were remaining on the list longer, which contributed to higher cumulative incidence of all-cause death than in semiurgent group (adjusted odds ratio = 1.66; 1.03-2.68). By 52 weeks on the wait list, 0.9% (0.6-1.1) and 1.3% (0.8-1.8) of patients died in semiurgent and nonurgent groups, respectively (P < 0.01). Similar proportions of deaths related to cardiovascular disease estimated over wait-list time in both groups (P = 0.40) were the result of shorter delays in the semiurgent group despite a higher rate of death resulting from cardiovascular disease (0.50 [0.36-0.65] vs. 0.34 [0.17-0.51] per 1000 patient-weeks). CONCLUSION: Queuing according to urgency of treatment contributed to a higher proportion of CABG candidates dying before surgery from all causes in the nonurgent compared with the semiurgent group despite similar weekly death rates observed in both groups. However, similar probabilities of death resulting from cardiovascular disease observed in both groups over wait-list time were the result of shorter delays in the semiurgent group despite a higher rate of cardiovascular death.