Real-World Implications of Updated Surviving Sepsis Campaign Antibiotic Timing Recommendations.

OBJECTIVE: To evaluate real-world implications of updated Surviving Sepsis Campaign (SSC) recommendations for antibiotic timing. DESIGN: Retrospective cohort study. SETTING: Twelve hospitals in the Southeastern United States between 2017 and 2021. PATIENTS: One hundred sixty-six thousand five hundred fifty-nine adult hospitalized patients treated in the emergency department for suspected serious infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We determined the number and characteristics of patients affected by updated SSC recommendations for initiation of antibiotics that incorporate a risk- and probability-stratified approach. Using an infection prediction model with a cutoff of 0.5 to classify possible vs. probable infection, we found that 30% of the suspected infection cohort would be classified as shock absent, possible infection and thus eligible for the new 3-hour antibiotic recommendation. In real-world practice, this group had a conservative time to antibiotics (median, 5.5 hr; interquartile range [IQR], 3.2-9.8 hr) and low mortality (2%). Patients categorized as shock absent, probable infection had a median time to antibiotics of 3.2 hours (IQR, 2.1-5.1 hr) and mortality of 3%. Patients categorized as shock present, the probable infection had a median time to antibiotics 2.7 hours (IQR, 1.7-4.6 hr) and mortality of 17%, and patients categorized as shock present, the possible infection had a median time to antibiotics 6.9 hours (IQR, 3.5-16.3 hr) and mortality of 12%. CONCLUSIONS: These data support recently updated SSC recommendations to align antibiotic timing targets with risk and probability stratifications. Our results provide empirical support that clinicians and hospitals should not be held to 1-hour targets for patients without shock and with only possible sepsis.

Characterizing Program Delivery for an Effective Multicomponent Sepsis Recovery Intervention.

Rationale: A recent randomized controlled trial revealed that a multicomponent sepsis transition and recovery (STAR) program delivered through specialized nurse navigators was effective in reducing a composite of 30-day readmission and mortality. Better understanding of patterns of care provided by the STAR program is needed to promote implementation and dissemination of this effective program.Objectives: This study characterizes individual care activities and distinct "packages" of care delivered by the STAR program.Methods: We performed a secondary analysis of data from the intervention arm of the IMPACTS (Improving Morbidity during Post-Acute Care Transitions for Sepsis) randomized controlled trial, conducted at three urban hospitals in the southeastern United States from January 2019 to March 2020. We used a structured data collection process to identify STAR nurse navigator care activities from electronic health record documentation. We then used latent class analysis to identify groups of patients receiving distinct combinations of intervention components. We evaluated differences in patient characteristics and outcomes between groups receiving distinct intervention packages.Results: The 317 sepsis survivors enrolled into the intervention arm of the IMPACTS trial received one or more of nine unique care activities delivered by STAR nurse navigators (care coordination, health promotion counseling, emotional listening, symptom management, medication management, chronic disease management, addressing social determinants of health, care setting advice and guidance, and primary palliative care). Patients received a median of three individual care activities (interquartile range, 2-5). Latent class analysis revealed four distinct packages of care activities delivered to patients with different observable characteristics and different frequency of 30-day readmission and mortality.Conclusions: We identified nine care activities delivered by an effective STAR program and four distinct latent classes or packages of intervention delivery. These results can be leveraged to increase widespread implementation and provide targets to augment future program delivery.

Passing the SNF Test: A Secondary Analysis of a Sepsis Transition Intervention Trial Among Patients Discharged to Post-Acute Care.

OBJECTIVES: Sepsis survivors discharged to post-acute care facilities experience high rates of mortality and hospital readmission. This study compared the effects of a Sepsis Transition and Recovery (STAR) program vs usual care (UC) on 30-day mortality and hospital readmission among sepsis survivors discharged to post-acute care. DESIGN: Secondary analysis of a multisite pragmatic randomized clinical trial. SETTING AND PARTICIPANTS: Sepsis survivors discharged to post-acute care. METHODS: We conducted a secondary analysis of patients from the IMPACTS (Improving Morbidity During Post-Acute Care Transitions for Sepsis) randomized clinical trial who were discharged to post-acute care. IMPACTS evaluated the effectiveness of STAR, a nurse-navigator-led program to deliver best practice post-sepsis care. Subjects were randomized to receive either STAR or UC. The primary outcome was 30-day readmission and mortality. We also evaluated hospital-free days alive as a secondary outcome. RESULTS: Of 691 patients enrolled in IMPACTS, 175 (25%) were discharged to post-acute care [143 (82%) to skilled nursing facilities, 12 (7%) to long-term acute care hospitals, and 20 (11%) to inpatient rehabilitation]. Of these, 87 received UC and 88 received the STAR intervention. The composite 30-day all-cause mortality and readmission endpoint occurred in 26 (29.9%) patients in the UC group vs 18 (20.5%) in the STAR group [risk difference -9.4% (95% CI -22.2 to 3.4); adjusted odds ratio 0.58 (95% CI 0.28 to 1.17)]. Separately, 30-day all-cause mortality was 8.1% in the UC group compared with 5.7% in the STAR group [risk difference -2.4% (95% CI -9.9 to 5.1)] and 30-day all-cause readmission was 26.4% in the UC group compared with 17.1% in the STAR program [risk difference -9.4% (95% CI -21.5 to 2.8)]. CONCLUSIONS AND IMPLICATIONS: There are few proven interventions to reduce readmission among patients discharged to post-acute care facilities. These results suggest the STAR program may reduce 30-day mortality and readmission rates among sepsis survivors discharged to post-acute care facilities.

Clinical Subtypes of Sepsis Survivors Predict Readmission and Mortality after Hospital Discharge.

Rationale: Sepsis survivors experience adverse outcomes including high rates of postdischarge mortality and rehospitalization. Given the heterogeneity of the condition, using a person-centered framework to identify subtypes within this population with different risks of postdischarge outcomes may optimize postsepsis care. Objectives: To classify individuals into subtypes and assess the association of subtypes with 30-day rehospitalization and mortality. Methods: We conducted a retrospective observational study between January 2014 and October 2017 among 20,745 patients admitted to one of 12 southeastern U.S. hospitals with a clinical definition of sepsis. We used latent class analysis to classify sepsis survivors into subtypes, which were evaluated against 30-day readmission and mortality rates using a specialized regression approach. A secondary analysis evaluated subtypes against readmission rate for ambulatory care-sensitive conditions. Results: Among 20,745 patients, latent class analysis identified five distinct subtypes as the optimal solution. Clinical subtype was associated with 30-day readmission, with the subtype existing poor health with severe illness and complex needs after discharge demonstrating highest risk (35%) and the subtype low risk, barriers to care demonstrating the lowest risk (9%). Forty-seven percent of readmissions in the subtype poor functional status were for ambulatory care-sensitive conditions, whereas 17% of readmissions in the subtype previously healthy with severe illness and complex needs after discharge, barriers to care were for ambulatory care-sensitive conditions. Subtype was significantly associated with 30-day mortality: highest in for existing poor health with severe illness and complex needs after discharge (8%) and lowest for low risk, barriers to care (0.1%). Conclusions: Sepsis survivors can be classified into subtypes representing nuanced constellations of characteristics, with differential 30-day mortality and readmission risk profiles. Predischarge classification may allow an individualized approach to postsepsis care.

Effect of a Multicomponent Sepsis Transition and Recovery Program on Mortality and Readmissions After Sepsis: The Improving Morbidity During Post-Acute Care Transitions for Sepsis Randomized Clinical Trial.

OBJECTIVES: To evaluate whether a nurse navigator-led, multicomponent Sepsis Transition And Recovery program improves 30-day mortality and readmission outcomes after sepsis hospitalization. DESIG: n: Multisite pragmatic randomized clinical trial. SETTING: Three hospitals in North Carolina from January 2019 to March 2020. PATIENTS: Eligible patients hospitalized for suspected sepsis and deemed high-risk for mortality or readmission by validated internal risk models. INTERVENTIONS: Patients were randomized to receive usual care alone (i.e., routine transition support, outpatient care; n = 342) or additional Sepsis Transition And Recovery support (n = 349). The 30-day intervention involved a multicomponent transition service led by a nurse navigator through telephone and electronic health record communication to facilitate best practice postsepsis care strategies during and after hospitalization including: postdischarge medication review, evaluation for new impairments or symptoms, monitoring comorbidities, and palliative care approach when appropriate. Clinical oversight was provided by a Hospital Medicine Transition Services team. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of mortality or hospital readmission at 30 days. Logistic regression models were constructed to evaluate marginal and conditional odds ratios (adjusted for prognostic covariates: age, comorbidity, and organ dysfunction at enrollment). Among 691 randomized patients (mean age = 63.7 ± 15.1 yr; 52% female), a lower percentage of patients in the Sepsis Transition And Recovery group experienced the primary outcome compared with the usual care group (28.7% vs 33.3%; risk difference, 4.7%; odds ratio, 0.80; 95% CI, 0.58-1.11; adjusted odds ratio, 0.80; 95% CI, 0.64-0.98). There were 74 deaths (Sepsis Transition And Recovery: 33 [9.5%] vs usual care: 41 [12.0%]) and 155 rehospitalizations (Sepsis Transition And Recovery: 71 [20.3%] vs usual care: 84 [24.6%]). CONCLUSIONS: In a multisite randomized clinical trial of patients hospitalized with sepsis, patients provided with a 30-day program using a nurse navigator to provide best practices for postsepsis care experienced a lower proportion of either mortality or rehospitalization within 30 days after discharge. Further research is needed to understand the contextual factors associated with successful implementation.

Deficits in Identification of Goals and Goal-Concordant Care After Sepsis Hospitalization.

In a recent study, identifying and supporting patients' care goals was named the highest priority in hospital medicine. Although sepsis is one of the leading causes of death and postdischarge morbidity among hospitalized patients, little is known about how frequently care goals are assessed prior to discharge and adhered to in the 90 days after sepsis hospitalization. Evaluating a cohort of 679 high-risk sepsis survivors enrolled in a clinical trial, we found that care goals were documented explicitly in a standardized tool in 130 patients; an additional 139 patients were identified using all available clinical documentation, resulting in only 269 (40%) patients with goals that could be ascertained from the electronic health record (EHR). Among those categorized, goals were classified as prioritizing longevity (35%), function (52%), and comfort (12%). Based on expert review of the care provided during the 90 days subsequent to discharge, goal-concordant care was identified in 184 (68%) cases for which goals were specified. Documentation of goals in a standardized EHR tool was associated with increased likelihood of receiving goal-concordant care (odds ratio, 3.6; 95% CI, 2.4-5.5). Hospitalization and peridischarge time points represent important opportunities to address deficits in the documentation of goals and provision of goal-concordant care for sepsis survivors.

First-to-second antibiotic delay and hospital mortality among emergency department patients with suspected sepsis.

OBJECTIVE: To evaluate whether delay between the first and second antibiotic administered for suspected sepsis is associated with hospital mortality. DESIGN: Retrospective cohort. SETTING: Twelve hospitals in Southeastern United States from 2014 to 2017. PATIENTS: 25,717 adults with suspected sepsis presenting to 12 Emergency Departments who received at least two antibiotics within 12 h. MEASUREMENTS AND MAIN RESULTS: The primary exposure was first-to-second antibiotic delay >1 h. We used generalized linear mixed models to model the association between first-to-second antibiotic delay and hospital death in the overall cohort, and in subgroups of patients with and without septic shock. Overall, 13,852 (54%) patients had first-to-second antibiotic delay >1 h and 1666 (7%) died. Adjusting for other risk factors, first-to-second antibiotic delay was associated with increased risk of hospital death in the subgroup of patients with septic shock (OR 1.34; 95% CI: 1.05-1.70), but not among patients without shock (OR 0.99; 95% CI: 0.88-1.12) or in the overall cohort (OR 1.08; 95% CI: 0.97-1.20). CONCLUSIONS: First-to-second antibiotic delay of greater than one hour was associated with an increased risk of hospital death among patients meeting criteria for septic shock but not all patients with suspected sepsis. Tracking and improving first-to-second antibiotic delays may be considered in septic shock.

Resource Use by Hospital Type for Frequent Inpatient Pediatric Conditions.

BACKGROUND: Children's hospitals (CHs) deliver care to underserved, critically ill, and medically complex patients. However, non-CHs care for the majority of children with frequently occurring conditions. In this study, we aimed to examine resource use across hospitals where children receive care for frequent inpatient conditions. METHODS: This was a cross-sectional, observational analysis of pediatric hospitalizations for 8 frequent inpatient conditions (pneumonia, asthma, bronchiolitis, mood disorders, appendicitis, epilepsy, skin and soft tissue infections, and fluid and electrolyte disorders) in the 2016 Kids' Inpatient Database. Primary outcomes were median length of stay (LOS) and median total cost. The primary independent variable was hospital type: nonchildren's, nonteaching; nonchildren's, teaching (NCT); and freestanding CHs. Multivariable linear regression was used to assess differences in mean LOS and costs. RESULTS: There were 354 456 pediatric discharges for frequent inpatient conditions. NCT hospitals cared for more than one-half of all frequent inpatient conditions. CHs and NCT hospitals cared for the majority of patients with higher illness severity and medical complexity. After controlling for patient and hospital factors, discharges for frequent inpatient conditions at CHs had 0.48% longer mean LOS and 61% greater costs compared with NCT hospitals (P < .01). CONCLUSIONS: CHs revealed higher estimated costs in caring for frequent inpatient conditions despite controlling for patient- and hospital-level factors but also cared for higher illness severity and medical complexity. Further research is warranted to explore whether we lack sufficient measures to control for patient-level factors and whether higher costs are justified by the specialized care at CHs.

The Association Between Antibiotic Delay Intervals and Hospital Mortality Among Patients Treated in the Emergency Department for Suspected Sepsis.

OBJECTIVES: Rapid delivery of antibiotics is a cornerstone of sepsis therapy, although time targets for specific components of antibiotic delivery are unknown. We quantified time intervals comprising the task of antibiotic delivery and evaluated the association between interval delays and hospital mortality among patients treated in the emergency department for suspected sepsis. DESIGN: Retrospective cohort. SETTING: Twelve hospitals in Southeastern United States from 2014 to 2017. PATIENTS: Twenty-four thousand ninety-three encounters among 20,026 adults with suspected sepsis in 12 emergency departments. MEASUREMENTS AND MAIN RESULTS: We divided antibiotic administration into two intervals: time from emergency department triage to antibiotic order (recognition delay) and time from antibiotic order to infusion (administration delay). We used generalized linear mixed models to evaluate associations between these intervals and hospital mortality. Median time from emergency department triage to antibiotic administration was 3.4 hours (interquartile range, 2.0-6.0 hr), separated into a median recognition delay (time from emergency department triage to antibiotic order) of 2.7 hours(interquartile range, 1.5-4.7 hr) and median administration delay (time from antibiotic order to infusion) of 0.6 hours (0.3-1.2 hr). Adjusting for other risk factors, both recognition delay and administration delay were associated with mortality, but pairwise comparison with a no-delay reference group was not significant for up to 6 hours of recognition delay or up to 1.5 hours of administration delay. CONCLUSIONS: Both recognition delays and administration delays were associated with increased hospital mortality, but only for longer delays. These results suggest that both metrics may be important to measure and improve for patients with suspected sepsis but do not support targets less than 1 hour.

Awake Prone Positioning Strategy for Nonintubated Hypoxic Patients with COVID-19: A Pilot Trial with Embedded Implementation Evaluation.

Rationale: Prone positioning is an appealing therapeutic strategy for nonintubated hypoxic patients with coronavirus disease (COVID-19), but its effectiveness remains to be established in randomized controlled trials. Objectives: To identify contextual factors relevant to the conduct of a definitive clinical trial evaluating a prone positioning strategy for nonintubated hypoxic patients with COVID-19. Methods: We conducted a cluster randomized pilot trial at a quaternary care teaching hospital. Five inpatient medical service teams were randomly allocated to two treatment arms: 1) usual care (UC), consisting of current, standard management of hypoxia and COVID-19; or 2) the Awake Prone Positioning Strategy (APPS) plus UC. Included patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing or suspected COVID-19 pneumonia and oxygen saturation less than 93% or new oxygen requirement of 3 L per minute or greater and no contraindications to prone positioning. Oxygenation measures were collected within 48 hours of eligibility and included nadir oxygen saturation to fraction of inspired oxygen (S/F) ratio and time spent with S/F ratio less than 315. Concurrently, we conducted an embedded implementation evaluation using semistructured interviews with clinician and patient participants to determine contextual factors relevant to the successful conduct of a future clinical trial. The primary outcomes were drawn from an implementation science framework including acceptability, adoption, appropriateness, effectiveness, equity, feasibility, fidelity, and penetration. Results: Forty patients were included in the cluster randomized trial. Patients in the UC group (n = 13) had a median nadir S/F ratio over the 48-hour study period of 216 (95% confidence interval [95% CI], 95-303) versus 253 (95% CI, 197-267) in the APPS group (n = 27). Patients in the UC group spent 42 hours (95% CI, 13-47) of the 48-hour study period with an S/F ratio below 315 versus 20 hours (95% CI, 6-39) for patients in the APPS group. Mixed-methods analyses uncovered several barriers relevant to the conduct of a successful definitive randomized controlled trial, including low adherence to prone positioning, large differences between physician-recommended and patient-tolerated prone durations, and diffusion of prone positioning into usual care. Conclusions: A definitive trial evaluating the effect of prone positioning in nonintubated patients with COVID-19 is warranted, but several barriers must be addressed to ensure that the results of such a trial are informative and readily translated into practice.

Modeling COVID-19 Latent Prevalence to Assess a Public Health Intervention at a State and Regional Scale: Retrospective Cohort Study.

BACKGROUND: Emergence of the coronavirus disease (COVID-19) caught the world off guard and unprepared, initiating a global pandemic. In the absence of evidence, individual communities had to take timely action to reduce the rate of disease spread and avoid overburdening their health care systems. Although a few predictive models have been published to guide these decisions, most have not taken into account spatial differences and have included assumptions that do not match the local realities. Access to reliable information that is adapted to local context is critical for policy makers to make informed decisions during a rapidly evolving pandemic. OBJECTIVE: The goal of this study was to develop an adapted susceptible-infected-removed (SIR) model to predict the trajectory of the COVID-19 pandemic in North Carolina and the Charlotte Metropolitan Region, and to incorporate the effect of a public health intervention to reduce disease spread while accounting for unique regional features and imperfect detection. METHODS: Three SIR models were fit to infection prevalence data from North Carolina and the greater Charlotte Region and then rigorously compared. One of these models (SIR-int) accounted for a stay-at-home intervention and imperfect detection of COVID-19 cases. We computed longitudinal total estimates of the susceptible, infected, and removed compartments of both populations, along with other pandemic characteristics such as the basic reproduction number. RESULTS: Prior to March 26, disease spread was rapid at the pandemic onset with the Charlotte Region doubling time of 2.56 days (95% CI 2.11-3.25) and in North Carolina 2.94 days (95% CI 2.33-4.00). Subsequently, disease spread significantly slowed with doubling times increased in the Charlotte Region to 4.70 days (95% CI 3.77-6.22) and in North Carolina to 4.01 days (95% CI 3.43-4.83). Reflecting spatial differences, this deceleration favored the greater Charlotte Region compared to North Carolina as a whole. A comparison of the efficacy of intervention, defined as 1 - the hazard ratio of infection, gave 0.25 for North Carolina and 0.43 for the Charlotte Region. In addition, early in the pandemic, the initial basic SIR model had good fit to the data; however, as the pandemic and local conditions evolved, the SIR-int model emerged as the model with better fit. CONCLUSIONS: Using local data and continuous attention to model adaptation, our findings have enabled policy makers, public health officials, and health systems to proactively plan capacity and evaluate the impact of a public health intervention. Our SIR-int model for estimated latent prevalence was reasonably flexible, highly accurate, and demonstrated efficacy of a stay-at-home order at both the state and regional level. Our results highlight the importance of incorporating local context into pandemic forecast modeling, as well as the need to remain vigilant and informed by the data as we enter into a critical period of the outbreak.

Where Is the Implementation Science? An Opportunity to Apply Principles During the COVID-19 Pandemic.

The coronavirus disease 2019 pandemic represents a global crisis that has received extraordinary response from healthcare workers and scientists. One critical but potentially overlooked field in a pandemic is implementation science-the study of methods to reduce the research-to-practice gap. In this Viewpoint, we discuss the important role of implementation science during this and future pandemics and highlight considerations to maximize the utility of implementation research.

Association between Adherence to Recommended Care and Outcomes for Adult Survivors of Sepsis.

Rationale: Postsepsis care recommendations target specific deficits experienced by sepsis survivors in elements such as optimization of medications, screening for functional impairments, monitoring for common and preventable causes of health deterioration, and consideration of palliative care. However, few data are available regarding the application of these elements in clinical practice.Objectives: To quantify the delivery of postsepsis care for patients discharged after hospital admission for sepsis and evaluate the association between receipt of postsepsis care elements and reduced mortality and hospital readmission within 90 days.Methods: We conducted a retrospective chart review of a random sample of patients who were discharged alive after an admission for sepsis (identified from International Classification of Diseases, 10th Revision discharge codes) at 10 hospitals during 2017. We used a structured chart abstraction to determine whether four elements of postsepsis care were provided within 90 days of hospital discharge, per expert recommendations. We used multivariable logistic regression to evaluate the association between receipt of care elements and 90-day hospital readmission and mortality, adjusted for age, comorbidity, length of stay, and discharge disposition.Results: Among 189 sepsis survivors, 117 (62%) had medications optimized, 123 (65%) had screening for functional or mental health impairments, 86 (46%) were monitored for common and preventable causes of health deterioration, and 110 (58%) had care alignment processes documented (i.e., assessed for palliative care or goals of care). Only 20 (11%) received all four care elements within 90 days. Within 90 days of discharge, 66 (35%) patients were readmitted and 33 (17%) died (total patients readmitted or died, n = 82). Receipt of two (odds ratio [OR], 0.26; 95% confidence interval [95% CI], 0.10-0.69) or more (three OR, 0.28; 95% CI, 0.11-0.72; four OR, 0.12; 95% CI, 0.03-0.50) care elements was associated with lower odds of 90-day readmission or 90-day mortality compared with zero or one element documented. Optimization of medications (no medication errors vs. one or more errors; OR, 0.44; 95% CI, 0.21-0.92), documented functional or mental health assessments (physical function plus swallowing/mental health assessments vs. no assessments; OR, 0.14; 95% CI, 0.05-0.40), and documented goals of care or palliative care screening (OR, 0.52; 95% CI, 0.25-1.05; not statistically significant) were associated with lower odds of 90-day readmission or 90-day mortality.Conclusions: In this retrospective cohort study of data from a single health system, we found variable delivery of recommended postsepsis care elements that were associated with reduced morbidity and mortality after hospitalization for sepsis. Implementation strategies to efficiently overcome barriers to adopting recommended postsepsis care may help improve outcomes for sepsis survivors.

Predictive Accuracy of Quick Sequential Organ Failure Assessment for Hospital Mortality Decreases With Increasing Comorbidity Burden Among Patients Admitted for Suspected Infection.

OBJECTIVES: Evaluate the accuracy of the quick Sequential Organ Failure Assessment tool to predict mortality across increasing levels of comorbidity burden. DESIGN: Retrospective observational cohort study. SETTING: Twelve acute care hospitals in the Southeastern United States. PATIENTS: A total of 52,187 patients with suspected infection presenting to the Emergency Department between January 2014 and September 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospital mortality. We used electronic health record data to calculate quick Sequential Organ Failure Assessment risk scores from vital signs and laboratory values documented during the first 24 hours. We calculated Charlson Comorbidity Index scores to quantify comorbidity burden. We constructed logistic regression models to evaluate differences in the performance of quick Sequential Organ Failure Assessment greater than or equal to 2 to predict hospital mortality in patients with no documented (Charlson Comorbidity Index = 0), low (Charlson Comorbidity Index = 1-2), moderate (Charlson Comorbidity Index = 3-4), or high (Charlson Comorbidity Index ≥ 5) comorbidity burden. Among the cohort, 2,030 patients died in the hospital (4%). No comorbidities were documented for 5,038 patients (10%), 9,235 patients (18%) had low comorbidity burden, 12,649 patients (24%) had moderate comorbidity burden, and 25,265 patients (48%) had high comorbidity burden. Overall model discrimination for quick Sequential Organ Failure Assessment greater than or equal to 2 was the area under the receiver operating characteristic curve of 0.71 (95% CI, 0.69-0.72). A model including both quick Sequential Organ Failure Assessment and Charlson Comorbidity Index had improved discrimination compared with Charlson Comorbidity Index alone (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.76-0.78 vs area under the curve, 0.61; 95% CI, 0.59-0.62). Discrimination was highest among patients with no documented comorbidities (quick Sequential Organ Failure Assessment area under the receiver operating characteristic curve, 0.84; 95% CI; 0.79-0.89) and lowest among high comorbidity patients (quick Sequential Organ Failure Assessment area under the receiver operating characteristic curve, 0.67; 95% CI, 0.65-0.68). The strength of association between quick Sequential Organ Failure Assessment and mortality ranged from 30.5-fold increased likelihood in patients with no comorbidities to 4.7-fold increased likelihood in patients with high comorbidity. CONCLUSIONS: The accuracy of quick Sequential Organ Failure Assessment to predict hospital mortality diminishes with increasing comorbidity burden. Patients with comorbidities may have baseline abnormalities in quick Sequential Organ Failure Assessment variables that reduce predictive accuracy. Additional research is needed to better understand quick Sequential Organ Failure Assessment performance across different comorbid conditions with modification that incorporates the context of changes to baseline variables.

Association between Time on Protease Inhibitors and the Incidence of Squamous Cell Carcinoma of the Anus among U.S. Male Veterans.

Protease inhibitors (PIs) have been shown to have anti-tumor activity in addition to their antiretroviral properties. We sought to assess the association between PI use and the incidence of squamous cell carcinoma of the anus (SCCA) in HIV-infected individuals. We performed a retrospective cohort study among male US veterans diagnosed with HIV who were diagnosed between 1985 and 2010, using the Veterans Affairs HIV Clinical Case Registry (CCR). We calculated hazards ratios associated with PI use (both as percent time on PI and as 12-month intervals of PI use), utilizing time-dependent Cox models. We adjusted for risk factors, including age, race, year of enrolment into CCR, recent and nadir CD4, and percent time undetectable HIV viral load. A total of 28, 886 HIV-infected men met inclusion criteria. Of these, 373 were newly diagnosed with SCCA during the study period. In multivariate analysis, increasing percent time on PIs was associated with an increased risk of SCCA (aHR 1.07; 95% CI = 1.03-1.10 per 10% increase in time on PI). Poor immunologic recovery and virologic control, a history of condylomata acuminata, and CCR enrolment in the late combined antiretroviral therapy era were also associated with increased SCCA risk. Increasing percent time on a PI-based combined antiretroviral therapy regimen may be associated with an increased risk of developing SCCA in HIV-infected male US veterans. Future studies, better accounting for HIV control and treatment compliance, are necessary to further clarify this association.