Effectiveness of the 2023-2024 Formulation of the Coronavirus Disease 2019 mRNA Vaccine.

BACKGROUND: The purpose of this study was to evaluate whether the 2023-2024 formulation of the COVID-19 mRNA vaccine protects against COVID-19. METHODS: Employees of Cleveland Clinic in employment when the 2023-2024 formulation of the COVID-19 mRNA vaccine became available to employees, were included. Cumulative incidence of COVID-19 over the following 17 weeks was examined prospectively. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with time-dependent coefficients used to separate effects before and after the JN.1 lineage became dominant. The analysis was adjusted for the propensity to get tested, age, sex, pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses. RESULTS: Among 48210 employees, COVID-19 occurred in 2462 (5.1%) during the 17 weeks of observation. In multivariable analysis, the 2023-2024 formula vaccinated state was associated with a significantly lower risk of COVID-19 before the JN.1 lineage became dominant (HR, .58; 95% C.I., .49-.68, p-value < .001), and lower risk but one that did not reach statistical significance after (HR, .81; 95% C.I., .65-1.01, p-value 0.06). Estimated vaccine effectiveness (VE) was 42% (95% C.I., 32%-51%) before the JN.1 lineage became dominant, and 19% (C.I., -1%-35%) after. Risk of COVID-19 was lower among those previously infected with an XBB or more recent lineage, and increased with the number of vaccine doses previously received. CONCLUSIONS: The 2023-2024 formula COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 before the JN.1 lineage became dominant, and less protection after.

Association Between Causative Pathogen and Occurrence of Infection-Related Glomerulonephritis in Infective Endocarditis.

Among patients with pathologically proven infective endocarditis, the association of pathogen with occurrence of infection-related glomerulonephritis (IRGN) was examined in 48 case patients with IRGN and 192 propensity score-matched controls. Bartonella was very strongly associated with IRGN (odds ratio, 38.2 [95% confidence interval, 6.7-718.8]; P < .001); other microorganisms were not.

Duration of Severe Acute Respiratory Syndrome Coronavirus 2 Natural Immunity and Protection Against the Delta Variant: A Retrospective Cohort Study.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to be highly protective against reinfection and symptomatic disease. However, effectiveness against the Delta variant and duration of natural immunity remain unknown. METHODS: This retrospective cohort study included 325 157 patients tested for SARS-CoV-2 via polymerase chain reaction (PCR) from 9 March 2020 to 31 December 2020 (Delta variant analysis) and 152 656 patients tested from 9 March 2020 to 30 August 2020 (long-term effectiveness analysis) with subsequent testing through 9 September 2021. The primary outcome was reinfection, defined as a positive PCR test >90 days after the initial positive test. RESULTS: Among 325 157 patients tested before 31 December 2020, 50 327 (15.5%) tested positive. After 1 July 2021 (Delta dominant period), 40 (0.08%) initially positive and 1494 (0.5%) initially negative patients tested positive. Protection of prior infection against reinfection with Delta was 85.4% (95% confidence interval [CI], 80.0-89.3). For the long-term effectiveness analysis, among 152 656 patients tested before 30 August 2020, 11 186 (7.3%) tested positive. After at least 90 days, 81 (0.7%) initially positive and 7167 (5.1%) initially negative patients tested positive. Overall protection of previous infection was 85.7% (95% CI, 82.2-88.5) and lasted up to 13 months. Patients aged >65 years had slightly lower protection. CONCLUSIONS: SARS-CoV-2 infection is highly protective against reinfection with Delta. Immunity from prior infection lasts at least 13 months. Countries facing vaccine shortages should consider delaying vaccinations for previously infected patients to increase access.

Coronavirus Disease 2019 Vaccine Boosting in Previously Infected or Vaccinated Individuals.

BACKGROUND: The purpose of this study was to determine whether boosting previously infected or vaccinated individuals with a vaccine developed for an earlier variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protects against the Omicron variant. METHODS: Employees of Cleveland Clinic, previously infected with or vaccinated against coronavirus disease 2019 (COVID-19) and working the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over 2 months during an Omicron variant surge. Protection provided by boosting was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate SARS-CoV-2 exposure. RESULTS: Among 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since proximate SARS-CoV-2 exposure, and boosting protected those >6 months since prior infection or vaccination. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those vaccinated but not previously infected (hazard ratio [HR], .43; 95% confidence interval [CI], .41-.46) as well as those previously infected (HR, .66; 95% CI, .58-.76). Among those previously infected, receipt of 2 compared with 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21-1.97). CONCLUSIONS: Administering a COVID-19 vaccine not designed for the Omicron variant >6 months after prior infection or vaccination protects against Omicron variant infection. There is no advantage to administering more than 1 dose of vaccine to previously infected persons.

Necessity of Coronavirus Disease 2019 (COVID-19) Vaccination in Persons Who Have Already Had COVID-19.

BACKGROUND: The aim was to evaluate the necessity of coronavirus disease 2019 (COVID-19) vaccination in persons with prior COVID-19. METHODS: Employees of the Cleveland Clinic working in Ohio on 16 December 2020, the day COVID-19 vaccination was started, were included. Anyone who tested positive for COVID-19 at least once before the study start date was considered previously infected. One was considered vaccinated 14 days after receiving the second dose of COVID-19 mRNA vaccine. Cumulative incidences of COVID-19, symptomatic COVID-19, and hospitalizations for COVID-19 were examined over the next year. RESULTS: Among 52 238 employees, 4718 (9%) were previously infected and 36 922 (71%) were vaccinated by the study's end. Cumulative incidence of COVID-19 was substantially higher throughout for those previously uninfected who remained unvaccinated than for all other groups, lower for the vaccinated than unvaccinated, and lower for those previously infected than those not. Incidence of COVID-19 increased dramatically in all groups after the Omicron variant emerged. In multivariable Cox proportional hazards regression, both prior COVID-19 and vaccination were independently associated with significantly lower risk of COVID-19. Among previously infected subjects, a lower risk of COVID-19 overall was not demonstrated, but vaccination was associated with a significantly lower risk of symptomatic COVID-19 in both pre-Omicron (HR, .60; 95% CI, .40-.90) and Omicron (HR, .36; 95% CI, .23-.57) phases. CONCLUSIONS: Both previous infection and vaccination provide substantial protection against COVID-19. Vaccination of previously infected individuals does not provide additional protection against COVID-19 for several months, but after that provides significant protection at least against symptomatic COVID-19.

Distribution of Transmission Potential During Nonsevere COVID-19 Illness.

BACKGROUND: Patients recovering from coronavirus disease 2019 (COVID-19) often continue to test positive for the causative virus by polymerase chain reaction (PCR) even after clinical recovery, thereby complicating return-to-work plans. The purpose of this study was to evaluate transmission potential of COVID-19 by examining viral load with respect to time. METHODS: Health care personnel (HCP) at Cleveland Clinic diagnosed with COVID-19, who recovered without needing hospitalization, were identified. Threshold cycles (Ct) for positive PCR tests were obtained and viral loads calculated. The association of viral load with days since symptom onset was examined in a multivariable regression model, which was reduced by stepwise backward selection to only keep variables significant at a level of .05. Viral loads by day since symptom onset were predicted using the model and transmission potential evaluated by examination of a viral load-time curve. RESULTS: Over 6 weeks, 230 HCP had 528 tests performed. Viral loads declined by orders of magnitude within a few days of symptom onset. The only variable significantly associated with viral load was time since onset of symptoms. Of the area under the curve (AUC) spanning symptom onset to 30 days, 96.9% lay within the first 7 days, and 99.7% within 10 days. Findings were very similar when validated using split-sample and 10-fold cross-validation. CONCLUSIONS: Among patients with nonsevere COVID-19, viral loads in upper respiratory specimens peak by 2 or 3 days from symptom onset and decrease rapidly thereafter. The vast majority of the viral load-time AUC lies within 10 days of symptom onset.

Value of perioperative inhaled epoprostenol with low tidal volume ventilation for complex endocarditis surgery.

BACKGROUND AND AIM: To compare outcomes of patients treated with inhaled epoprostenol and low tidal volume ventilation during cardiopulmonary bypass with those who did not receive this medication in the operating room at all, and those who received it as a rescue therapy at the end of the case. METHODS: Retrospective chart review between 2014 and 2017, follow-up included the entire hospital stay. RESULTS: Seventy-one patients were included, and mean age was 54 years. 78.9% of the patients were male. Procedures included 96% (n = 68) aortic valve replacement, 28% (n = 20) reconstruction of the intravalvular fibrosa, and 13% (n = 9) repair of an endocarditis-related intracardiac fistula. Patients who received epoprostenol (iEpo) (treatment and rescue groups), when compared with the control group had more intra-aortic balloon pump placement (23% vs 2.5%, P = .018), open chest after surgery (32% vs 7.5%, P = .012), and duration of mechanical ventilation (8.3 ± 2.7 vs. 2.4 ± 0.4 days, P = 0.01). There was no significant difference between the two groups in terms of extracorporeal circulatory support (6.5% vs 2.5%, P = .577) and hospital death (13% vs 10%, P = .72). In a subanalysis, hospital death and duration of mechanical ventilation were higher in the recue group when compared with the treatment group (P = .004 and .056, respectively). CONCLUSIONS: Prophylactic application of iEpo with low tidal volume ventilation for an anticipated complex endocarditis operation may contribute to favorable outcome when compared with postoperative epoprostenol rescue.

Emergency department visits during outpatient parenteral antimicrobial therapy: a retrospective cohort study.

Objectives: Patients receiving outpatient parenteral antimicrobial therapy (OPAT) may require emergency department (ED) visits to manage complications. This study's purpose was to identify risk factors for ED visits during OPAT and risk factors for hospitalization among patients with ED visits. Methods: All OPAT courses initiated between 1 January 2013 and 1 January 2017 at Cleveland Clinic were identified. The first OPAT course per patient was included. For these, ED visits within 30 days were identified. Reasons and risk factors for these visits were sought, as were risk factors for hospitalization among patients visiting the ED. Results: Among 8263 patients on OPAT, 381 (4.6%) had at least one ED visit, an additional 1133 (14%) were hospitalized and an additional 50 (0.6%) died, within 30 days. One hundred and ninety-three ED visits (51%) were OPAT related. In a multivariable subdistribution proportional hazards competing risks regression model, prior ED visit (preceding year) was most strongly associated with ED visits (HR 2.29, 95% CI 1.76-2.98, P = 8.1 × 10-10). Eighty-five visits (22%) led to hospitalization. Compared with non-OPAT-related reasons, visits for vascular access complications were associated with lower odds of hospitalization (OR 0.36, 95% CI 0.14-0.83, P = 0.022) and visits for worsening infection with higher odds (OR 18.95, 95% CI 5.50-79.85, P = 1.2 × 10-7). Conclusions: Compared with patients without, patients with prior ED visit have a 2.3-fold higher hazard of an ED visit within 30 days of OPAT initiation. Visits for worsening infection are much more likely to result in hospitalization than those for vascular access complications.

Outcomes of Outpatient Parenteral Antimicrobial Therapy in Patients With Injection Drug Use.

BACKGROUND: Historically, there has been a restrictive approach toward outpatient parenteral antimicrobial therapy (OPAT) in patients with injection drug use (IDU) due to the fear that they might utilize the intravenous catheter to inject illicit substances. OBJECTIVE: We tested the hypothesis that patients with current IDU on OPAT would have less favorable treatment outcomes compared to those without current IDU. METHODS: In this retrospective cohort chart review study of Cleveland Clinic OPAT registry, we identified patients with current IDU by both electronic and manual review. For each patient with current IDU, we identified 3 matched controls among those on OPAT and without current IDU, by propensity score matching on age, sex, OPAT year, and OPAT diagnosis. We compared treatment failure, infection relapse, line infection, hospital readmission, number of emergency room visits, and 90-day mortality, for patients with current IDU and their matched controls. RESULTS: We identified 39 patients with current IDU and 117 matched controls. Most patients with current IDU (82%) were discharged to skilled nursing facilities, whereas the majority of the control group (74%) was treated at home (p < 0.01). There was no significant difference in the examined treatment outcomes between the 2 groups. CONCLUSIONS: Patients with current IDU on OPAT did not have less favorable treatment outcomes compared to those without current IDU. Although the reason for this finding could potentially be related to difference in disposition, more studies need to be done to assess safety of home disposition among these patients.

Evaluation of Antimicrobial Stewardship-Related Alerts Using a Clinical Decision Support System.

Background: Information technology, including clinical decision support systems (CDSS), have an increasingly important and growing role in identifying opportunities for antimicrobial stewardship-related interventions. Objective: The aim of this study was to describe and compare types and outcomes of CDSS-built antimicrobial stewardship alerts. Methods: Fifteen alerts were evaluated in the initial antimicrobial stewardship program (ASP) review. Preimplementation, alerts were reviewed retrospectively. Postimplementation, alerts were reviewed in real-time. Data collection included total number of actionable alerts, recommendation acceptance rates, and time spent on each alert. Time to de-escalation to narrower spectrum agents was collected. Results: In total, 749 alerts were evaluated. Overall, 306 (41%) alerts were actionable (173 preimplementation, 133 postimplementation). Rates of actionable alerts were similar for custom-built and prebuilt alert types (39% [53 of 135] vs 41% [253 of 614], P = .68]. In the postimplementation group, an intervention was attempted in 97% of actionable alerts and 70% of interventions were accepted. The median time spent per alert was 7 minutes (interquartile range [IQR], 5-13 minutes; 15 [12-17] minutes for actionable alerts vs 6 [5-7] minutes for nonactionable alerts, P < .001). In cases where the antimicrobial was eventually de-escalated, the median time to de-escalation was 28.8 hours (95% confidence interval [CI], 10.0-69.1 hours) preimplementation vs 4.7 hours (95% CI, 2.4-22.1 hours) postimplementation, P < .001. Conclusions: CDSS have played an important role in ASPs to help identify opportunities to optimize antimicrobial use through prebuilt and custom-built alerts. As ASP roles continue to expand, focusing time on customizing institution specific alerts will be of vital importance to help redistribute time needed to manage other ASP tasks and opportunities.

Vascular access complications during outpatient parenteral antimicrobial therapy at home: a retrospective cohort study.

OBJECTIVES: The need for indwelling vascular access for outpatient parenteral antimicrobial therapy (OPAT) places patients at risk of vascular access complications. The purpose of this study was to describe vascular access complications during OPAT at home, and identify factors associated with their occurrence. METHODS: All OPAT courses carried out at home for patients at Cleveland Clinic in 2013 were identified from the institution's OPAT registry. The first OPAT course per patient was included. Vascular access complications that occurred during the treatment course were abstracted from the electronic medical record. Only complications that triggered a clinical intervention were included. RESULTS: The 1461 included OPAT courses encompassed 33,579 OPAT days of treatment. One-hundred-and-forty-four vascular access complications occurred in 131 OPAT courses (9% of OPAT courses, 4.29 complications per 1000 OPAT days). The most common complication was occlusion (53% of all complications). Hickman catheters [incidence rate ratio (IRR) 0.20, 95% CI 0.03-0.63] and indwelling ports (IRR 0.25, 95% CI 0.04-0.78) were associated with lower complication rates than peripherally inserted central catheters, as was increasing age (IRR 0.99, 95% CI 0.98-1.00). Log OPAT duration (IRR 1.60, 95% CI 1.28-2.03), female sex (IRR 1.62, 95% CI 1.16-2.28) and injection drug use (IRR 3.32, 1.16-7.46) were associated with increased risk of vascular access complications. CONCLUSIONS: Nine percent of OPAT courses at home have at least one vascular access complication requiring clinical intervention. Longer OPAT duration, younger age, female sex and injection drug use are associated with increased risk of vascular access complications.

Association of laboratory test result availability and rehospitalizations in an outpatient parenteral antimicrobial therapy programme.

OBJECTIVES: Laboratory tests are usually requested for monitoring during outpatient parenteral antimicrobial therapy (OPAT), but these recommendations are not always followed. The purpose of this study was to determine whether rehospitalization during the OPAT course is associated with the availability of these test results to the treating physician. METHODS: Electronic health records (EHRs) from all patients in the Cleveland Clinic OPAT registry with start dates from 1 January to 28 February 2011 were reviewed in a retrospective cohort study. Comprehensive data on patient and OPAT characteristics were obtained for the first OPAT course per patient. Availability of laboratory test results was defined as documentation of results of at least one recommended test in the health system's EHR. Proportions of patients rehospitalized were compared for OPAT courses with test results available and non-available. Adjustments were made for patient age, hospital length of stay, anticipated OPAT duration, OPAT site and Charlson comorbidity index score. RESULTS: Four hundred patients received OPAT during the study period; 60% at home, 36% in skilled nursing facilities or long-term acute care facilities and 4% in other settings. Recommended monitoring laboratory test results were available to infectious disease physicians in 291 (73%) OPAT episodes. There were 82 patient readmissions (21%) while on OPAT. In a multivariable logistic regression model, non-availability of recommended test results was independently associated with readmissions while on OPAT (adjusted OR 2.53; 95% CI 1.36-4.73). CONCLUSIONS: Non-availability of recommended test results to treating physicians for patients on OPAT is associated with increased readmissions during OPAT.

Adverse events, healthcare interventions and healthcare utilization during home infusion therapy with daptomycin and vancomycin: a propensity score-matched cohort study.

OBJECTIVES: Vancomycin and daptomycin are the two most frequently prescribed parenteral antimicrobials for resistant Gram-positive bacterial infections. The purpose of this study was to compare antimicrobial adverse event rates and associated healthcare interventions and healthcare utilization in patients treated with the two antimicrobials. METHODS: All patients aged ≥18 years, discharged home from Cleveland Clinic on outpatient parenteral antimicrobial therapy (OPAT) with daptomycin or vancomycin between 1 July 2007 and 30 June 2010 were screened. Logistic regression models were built to calculate propensity to be treated with daptomycin for each patient. Propensity score-matched vancomycin-treated controls were identified for each daptomycin-treated patient. Adverse event, healthcare intervention and healthcare utilization rates during OPAT were compared in the matched cohort using negative binomial regression models. RESULTS: One thousand, two hundred and eighty-eight patients were identified. Three-to-one matching provided the best matching characteristics and identified 119 daptomycin-treated subjects (2518 OPAT days) and 357 vancomycin-treated controls (6649 OPAT days). The mean patient age was 56 years and the mean OPAT duration was 19 days. Antimicrobial adverse event rates for the daptomycin and vancomycin groups were 3.2 and 7.7 per 1000 OPAT days, respectively [relative risk (RR) 0.38; 95% CI 0.15-0.86; P = 0.02]. Antimicrobial intervention rates were 5.6 and 27.1 per 1000 OPAT days, respectively (RR 0.21; 95% CI 0.11-0.36; P < 0.001). Readmissions for worsening infection or treatment complication were not significantly different between daptomycin (5%) and vancomycin (7%). CONCLUSIONS: Patients receiving daptomycin at home have 60% fewer antimicrobial adverse events and require 80% fewer antimicrobial interventions than similar patients receiving vancomycin.

Clinical utility of cerebral angiography in the preoperative assessment of endocarditis.

Cerebral angiography is an invasive procedure utilized without supporting guidelines in preoperative evaluations of infective endocarditis (IE). It is used to identify mycotic intracranial aneurysm, which is suspected to increase the risk of intracranial bleeding during cardiac surgery. Our objectives were to: (1) assess the utility of cerebral angiography by determining which subset of IE patients benefit from its performance; and (2) identify clinical and noninvasive screening tests that can preclude the need for invasive cerebral angiography. Retrospective analysis was performed of all patients treated surgically for IE from 7/2007 to 1/2012 and discharged with medical treatment for IE from 7/2007 to 7/2009 presenting to a large academic center. Of the 151 patients who underwent cerebral angiography, mycotic aneurysm was identified in seven (prevalence=4.6%; 95% CI 2.3-9.3%). Five had viridans group streptococci as the causative IE microorganism (p=0.0017). Noninvasive imaging and particularly absence of intracranial bleed on magnetic resonance imaging conveys a negative predictive value (NPV) of 0.977 (95% CI 0.879-0.996). Absence of a focal neurologic deficit or altered mental status convey a NPV of 0.990 (95% CI 0.945-0.998) and 0.944 (95% CI 0.883-0.974), respectively. Clinical suspicion for mycotic aneurysm and thus utilization of cerebral angiography is likely necessary only in the setting of acute neurologic deficits and when noninvasive imaging demonstrates acute intracranial bleed. A novel association between viridans group streptococci and intracranial mycotic aneurysm is demonstrated.

Evolution of serious and life-threatening COVID-19 pneumonia as the SARS-CoV-2 pandemic progressed: an observational study of mortality to 60 days after admission to a 15-hospital US health system.

OBJECTIVE: In order to predict at hospital admission the prognosis of patients with serious and life-threatening COVID-19 pneumonia, we sought to understand the clinical characteristics of hospitalised patients at admission as the SARS-CoV-2 pandemic progressed, document their changing response to the virus and its variants over time, and identify factors most importantly associated with mortality after hospital admission. DESIGN: Observational study using a prospective hospital systemwide COVID-19 database. SETTING: 15-hospital US health system. PARTICIPANTS: 26 872 patients admitted with COVID-19 to our Northeast Ohio and Florida hospitals from 1 March 2020 to 1 June 2022. MAIN OUTCOME MEASURES: 60-day mortality (highest risk period) after hospital admission analysed by random survival forests machine learning using demographics, medical history, and COVID-19 vaccination status, and viral variant, symptoms, and routine laboratory test results obtained at hospital admission. RESULTS: Hospital mortality fell from 11% in March 2020 to 3.7% in March 2022, a 66% decrease (p<0.0001); 60-day mortality fell from 17% in May 2020 to 4.7% in May 2022, a 72% decrease (p<0.0001). Advanced age was the strongest predictor of 60-day mortality, followed by admission laboratory test results. Risk-adjusted 60-day mortality had all patients been admitted in March 2020 was 15% (CI 3.0% to 28%), and had they all been admitted in May 2022, 12% (CI 2.2% to 23%), a 20% decrease (p<0.0001). Dissociation between observed and predicted decrease in mortality was related to temporal change in admission patient profile, particularly in laboratory test results, but not vaccination status or viral variant. CONCLUSIONS: Hospital mortality from COVID-19 decreased substantially as the pandemic evolved but persisted after hospital discharge, eclipsing hospital mortality by 50% or more. However, after accounting for the many, even subtle, changes across the pandemic in patients' demographics, medical history and particularly admission laboratory results, a patient admitted early in the pandemic and predicted to be at high risk would remain at high risk of mortality if admitted tomorrow.

Infective Endocarditis in Patients Addicted to Injected Opioid Drugs.

BACKGROUND: Persons who inject drugs and require surgery for infective endocarditis have 2 potentially lethal diseases. Current postoperative rehabilitation efforts seem ineffective in preventing loss to follow-up, injection drug use relapse (relapse), and death. OBJECTIVES: The purpose of this study was to characterize drug use, psychosocial issues, surgical outcome, and postoperative addiction management, as well as loss to follow-up, relapse, and mortality and their risk factors. METHODS: From January 2010 to June 2020, 227 persons who inject drugs, age 36 ± 9.9 years, underwent surgery for infective endocarditis at a quaternary hospital having special interest in developing addiction management programs. Postsurgery loss to follow-up, relapse, and death were assessed as competing risks and risk factors identified parametrically and by machine learning. CIs are 68% (±1 SE). RESULTS: Heroin was the most self-reported drug injected (n = 183 [81%]). Psychosocial issues included homelessness (n = 56 [25%]), justice system involvement (n = 150 [66%]), depression (n = 118 [52%]), anxiety (n = 104 [46%]), and post-traumatic stress disorder (n = 33 [15%]). Four (1.8%) died in-hospital. Medication for opioid use disorder prescribed at discharge increased from 0% in 2010 to 100% in 2020. At 1 and 5 years, conditional probabilities of loss to follow-up were 16% (68% CI: 13%-22%) and 59% (68% CI: 44%-65%), relapse 32% (68% CI: 28%-34%) and 79% (68% CI: 74%-83%), and mortality 21% (68% CI: 18%-23%) and 68% (68% CI: 62%-72%). Younger age, heroin use, and lower education level were predictors of relapse. CONCLUSIONS: Infective endocarditis surgery can be performed with low mortality in persons who inject drugs, but addiction is far more lethal. Risk of loss to follow-up and relapse require more effective addiction strategies without which this major loss to society will continue.

Risk of Coronavirus Disease 2019 (COVID-19) among those up-to-date and not up-to-date on COVID-19 vaccination by US CDC criteria.

BACKGROUND: The CDC recently defined being "up-to-date" on COVID-19 vaccination as having received at least one dose of a COVID-19 bivalent vaccine. The purpose of this study was to compare the risk of COVID-19 among those "up-to-date" and "not up-to-date". METHODS: Employees of Cleveland Clinic in Ohio, USA, in employment when the COVID-19 bivalent vaccine first became available, and still employed when the XBB lineages became dominant, were included. Cumulative incidence of COVID-19 since the XBB lineages became dominant was compared across the"up-to-date" and "not up-to-date" states, by treating COVID-19 bivalent vaccination as a time-dependent covariate whose value changed on receipt of the vaccine. Risk of COVID-19 by vaccination status was also evaluated using multivariable Cox proportional hazards regression adjusting for propensity to get tested for COVID-19, age, sex, most recent prior SARS-CoV-2 infection, and number of prior vaccine doses. RESULTS: COVID-19 occurred in 1475 (3%) of 48 344 employees during the 100-day study period. The cumulative incidence of COVID-19 was lower in the "not up-to-date" than the "up-to-date" state. On multivariable analysis, being "up-to-date" was not associated with lower risk of COVID-19 (HR, 1.05; 95% C.I., 0.88-1.25; P-value, 0.58). Results were very similar when those 65 years and older were only considered "up-to-date" after 2 doses of the bivalent vaccine. CONCLUSIONS: Since the XBB lineages became dominant, adults "up-to-date" on COVID-19 vaccination by the CDC definition do not have a lower risk of COVID-19 than those "not up-to-date", bringing into question the value of this risk classification definition.

Aortic allograft infection risk.

OBJECTIVE: Intrinsic risk of infection of cryopreserved allograft aortic root replacements remains poorly understood despite their long history of use. The objective of this study was to determine this intrinsic risk of allograft infection and its risk factors when allografts are implanted for both nonendocarditis indications and infective endocarditis. METHODS: From January 1987 to January 2017, 2042 patients received 2110 allograft aortic valves at a quaternary medical center, 1124 (53%) for nonendocarditis indications and 986 (47%) for endocarditis indications (670 [68%] prosthetic valve endocarditis). Staphylococcus aureus caused 193 of 949 cases of endocarditis (20%), 71 (7.3%) in persons who injected drugs. Periodic surveillance and cross-sectional follow-up achieved 85% of possible follow-up time. The primary end point was allograft infection in patients with nonendocarditis and endocarditis indications. Risk factors were identified by hazard function decomposition and machine learning. RESULTS: During follow-up, 30 allografts (26 explanted) became infected in patients in the nonendocarditis group and 49 (41 explanted) in patients with endocarditis. At 20 years, the probability of allograft infection was 5.6% in patients in the nonendocarditis group and 14% in patients with endocarditis. Risk factors for allograft infection in patients in the nonendocarditis group were younger patient age and older donor age. Risk factors for allograft infection in patients with endocarditis were earlier implant year, injection drug use, and younger age. In patients with endocarditis, 18% of allograft infections were caused by the original organism. CONCLUSIONS: The low infection rates, both in patients without and with endocarditis, support continued use of allografts in the modern era, in particular for the treatment of invasive endocarditis of the aortic root.

Effectiveness of the Coronavirus Disease 2019 Bivalent Vaccine.

Background: The purpose of this study was to evaluate whether a bivalent coronavirus disease 2019 (COVID-19) vaccine protects against COVID-19. Methods: The study included employees of Cleveland Clinic in employment when the bivalent COVID-19 vaccine first became available. Cumulative incidence of COVID-19 over the following 26 weeks was examined. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with change in dominant circulating lineages over time accounted for by time-dependent coefficients. The analysis was adjusted for the pandemic phase when the last prior COVID-19 episode occurred and the number of prior vaccine doses. Results: Among 51 017 employees, COVID-19 occurred in 4424 (8.7%) during the study. In multivariable analysis, the bivalent-vaccinated state was associated with lower risk of COVID-19 during the BA.4/5-dominant (hazard ratio, 0.71 [95% confidence interval, .63-79]) and the BQ-dominant (0.80 [.69-.94]) phases, but decreased risk was not found during the XBB-dominant phase (0.96 [.82-.1.12]). The estimated vaccine effectiveness was 29% (95% confidence interval, 21%-37%), 20% (6%-31%), and 4% (-12% to 18%), during the BA.4/5-, BQ-, and XBB-dominant phases, respectively. The risk of COVID-19 also increased with time since the most recent prior COVID-19 episode and with the number of vaccine doses previously received. Conclusions: The bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 while the BA.4/5 lineages were the dominant circulating strains, afforded less protection when the BQ lineages were dominant, and effectiveness was not demonstrated when the XBB lineages were dominant.

The Implementation and Effect of Weekend Pharmacy-Driven Antimicrobial Stewardship Services at a Large Academic Medical Center.

BACKGROUND: In September 2018, pharmacy antimicrobial stewardship (AMS) services were expanded to include weekends at this academic medical center. Activities performed by AMS pharmacists on the weekends include blood culture rapid diagnostic (RDT) review, antiretroviral therapy (ART) review, prospective audit and feedback (PAF) utilizing clinical decision support, vancomycin dosing, and operational support. The purpose of this study was to assess the operational and clinical impact of these expanded AMS services. METHODS: This single-center, quasi-experimental study included data from weekends before (9/2017-11/2017) and after (9/2018-11/2018) implementation. The descriptive primary outcome was the number of activities completed for each AMS activity type in the post-implementation group only. Secondary outcomes were time to AMS opportunity resolution, time to escalation or de-escalation following PAF or RDT alert, time to resolution of miscellaneous AMS related opportunities, length of stay (LOS), and antimicrobial use outcomes. RESULTS: During the post-implementation period 1258 activities were completed, averaging 97/weekend. Inclusion criteria for time to resolution outcomes were met by 72 patients pre-implementation and 59 patients post. The median (IQR) time to AMS opportunity resolution decreased from 18.5 hours pre-intervention (7.7-35.7) to 8.5 hours post-intervention (IQR 1.8-14.0), p < 0.01. Time to escalation was 11.6 hours compared to 1.7 hours (p = 0.1), de-escalation 16.7 hours compared to 10.8 hours (p = 0.03), and miscellaneous opportunity 40.8 hours compared to 13.2 hours (p = 0.01). No differences were observed in LOS or antimicrobial use outcomes. CONCLUSION: Presence of pharmacist-driven weekend AMS services significantly reduced time to resolution of AMS opportunities. These data support the value of weekend AMS services.