Beyond Infection: Mortality and End-of-Life Care Associated with Infectious Disease Consultation in an Academic Health System.

BACKGROUND: Infectious diseases (ID) physicians are increasingly faced with the challenge of caring for patients with terminal illnesses or incurable infections. METHODS: This was a retrospective cohort of all patients with an ID consult within an academic health system 1/1/2014 - 12/31/2023, including community, general, and transplant ID consult services. RESULTS: There were 60,820 inpatient ID consults (17,235 community, 29,999 general, and 13,586 transplant) involving 37,848 unique patients. The number of consults increased by 94% and the rate rose from 5.0 to 9.9 consults per 100 inpatients (p<0.001). In total, 7.5% of patients receiving an ID consult died during admission, and 1,006 (2.6%) of patients were discharged to hospice. In-hospital mortality was 5.2% for community ID, 7.8% for general ID, and 10.7% for transplant ID patients (p<0.001). Six-month mortality was 9% for all non-obstetric admissions, , vs. 19% for community ID, 20.9% for general ID, and 22.3% for transplant ID.In total 2,866 (7.6%) of all patients receiving ID consultation also received palliative care consultation during the same hospitalization. The index ID consult preceded any palliative consult in the majority (69.5%) of cases. 16.3% of patients had a do-not-resuscitate order during the index hospitalization. 12.2% of all patients with a do-not-resuscitate order had this placed on the same day as the ID consult. CONCLUSIONS: Patients receiving ID consultation were increasingly complex and more likely to die soon after consultation. These results provide a framework for ID clinicians to consider their role in end-of-life care.

Clinical outcomes in patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection.

BACKGROUND: A small proportion of Escherichia coli and Klebsiella pneumoniae demonstrate in vitro non-susceptibility to piperacillin/tazobactam but retain susceptibility to ceftriaxone. Uncertainty remains regarding how best to treat these isolates. OBJECTIVES: We sought to compare clinical outcomes between patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection receiving definitive therapy with ceftriaxone versus an alternative effective antibiotic. METHODS: We retrospectively identified patients with a positive blood culture for piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae between 1 January 2013 and 31 December 2022. Patients were divided into one of two definitive treatment groups: ceftriaxone or alternative effective antibiotic. Our primary outcome was a composite of 90 day all-cause mortality, hospital readmission, or recurrence of infection. We used Cox proportional hazards models to compare time with the composite outcome between groups. RESULTS: Sixty-two patients were included in our analysis. Overall, median age was 63 years (IQR 49.5-71.0), the most common source of infection was intra-abdominal (25/62; 40.3%) and the median total duration of therapy was 12.0 days (IQR 9.0-16.8). A total of 9/22 (40.9%) patients in the ceftriaxone treatment group and 18/40 (45.0%) patients in the alternative effective antibiotic group met the composite endpoint. In an adjusted time-to-event analysis, there was no difference in the composite endpoint between groups (HR 0.67, 95% CI 0.30-1.50). The adjusted Bayesian posterior probability that the HR was less than or equal to 1 (i.e. ceftriaxone is as good or better than alternative therapy) was 85%. CONCLUSIONS: These findings suggest that ceftriaxone can be used to effectively treat bloodstream infections with E. coli or K. pneumoniae that are non-susceptible to piperacillin/tazobactam but susceptible to ceftriaxone.

The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19.

BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2. DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge. SETTING: 114 centers in 10 countries. PARTICIPANTS: Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms. MEASUREMENTS: Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively. RESULTS: Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity. LIMITATIONS: Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available. CONCLUSION: Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain. Objective: To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. Design, Setting, and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less. Interventions: Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607). Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28. Results: Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Antiplatelet Therapy in Staphylococcus aureus Bacteremia: No Time Like the Past?

In this invited commentary, we reflect on the accompanying study by A. R. Caffrey, H. J. Appaneal, K. L. LaPlante, V. V. Lopes, et al. (Antimicrob Agents Chemother 66:e02117-21, 2022, https://doi.org/10.1128/aac.02117-21), which analyzed the impact of clopidogrel use on clinical outcomes in Staphylococcus aureus bacteremia.

COVID-19 Trials: Who Participates and Who Benefits?

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has disproportionately afflicted vulnerable populations. Older adults, particularly residents of nursing facilities, represent a small percentage of the population but account for 40% of mortality from COVID-19 in the United States. Racial and ethnic minority individuals, particularly Black, Hispanic, and Indigenous Americans have experienced higher rates of infection and death than the White population. Although there has been an unprecedented explosion of clinical trials to examine potential therapies, participation by members of these vulnerable communities is crucial to obtaining data generalizable to those communities. METHODS: We undertook an open-label, factorial randomized clinical trial examining hydroxychloroquine and/or azithromycin for hospitalized patients. RESULTS: Of 53 screened patients, 11 (21%) were enrolled. Ten percent (3/31) of Black patients were enrolled, 33% (7/21) of White patients, and 50% (6/12) of Hispanic patients. Forty-seven percent (25/53) of patients declined participation despite eligibility; 58%(18/31) of Black patients declined participation. Forty percent (21/53) of screened patients were from a nursing facility and 10% (2/21) were enrolled. Enrolled patients had fewer comorbidities than nonenrolled patients: median modified Charlson comorbidity score 2.0 (interquartile range 0-2.5), versus 4.0 (interquartile range 2-6) for nonenrolled patients (P = 0.006). The limitations of the study were the low participation rate and the multiple treatment trials concurrently recruiting at our institution. CONCLUSIONS: The high rate of nonparticipation in our trial of nursing facility residents and Black people emphasizes the concern that clinical trials for therapeutics may not target key populations with high mortality rates.

Reduction in Expected Survival Associated With Nontuberculous Mycobacterial Pulmonary Disease.

BACKGROUND: Nontuberculous mycobacteria (NTM) are opportunistically pathogenic bacteria that are found abundantly in the soil and water. Susceptible individuals exposed to NTM-containing aerosols from environmental sources may develop NTM pulmonary disease (NTM-PD). Reported survival after NTM-PD diagnosis varies widely among existing studies. Prior work has suggested that mortality among persons with NTM-PD is primarily driven by comorbidities rather than NTM-PD. METHODS: We retrospectively identified a cohort of patients in the Duke University Health System who were diagnosed with NTM-PD between 1996 and 2015. Hospitalizations and survival were compared among patients with NTM-PD with and without other comorbidities. Additionally, survival among patients with NTM-PD was compared with standardized mortality data for a similar cohort of the general population. RESULTS: Patients with NTM-PD without other comorbidities had 0.65 hospitalizations/1000 patient-days compared with 1.37 hospitalizations/1000 patient-days for patients with other comorbidities. Compared with a cohort of the general population, expected survival decreased by approximately 4 years for a diagnosis of NTM-PD without comorbidities and 8.6 years for a diagnosis of NTM-PD with comorbidities. Mortality 5 years after diagnosis was 25.0% and 44.9% among NTM patients without and with comorbidities, respectively, compared with 5.7% in the general-population cohort. CONCLUSIONS: NTM-PD was associated with significant morbidity that was worse in patients with comorbidities. Patients with NTM-PD, even without comorbidities, had worse survival than expected.

Social Disadvantage, Politics, and Severe Acute Respiratory Syndrome Coronavirus 2 Trends: A County-level Analysis of United States Data.

BACKGROUND: Understanding the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for public health control efforts. Social, demographic, and political characteristics at the United States (US) county level might be associated with changes in SARS-CoV-2 case incidence. METHODS: We conducted a retrospective analysis of the relationship between the change in reported SARS-CoV-2 case counts at the US county level during 1 June-30 June 2020 and social, demographic, and political characteristics of the county. RESULTS: Of 3142 US counties, 1023 were included in the analysis: 678 (66.3%) had increasing and 345 (33.7%) nonincreasing SARS-CoV-2 case counts between 1 June and 30 June 2020. In bivariate analysis, counties with increasing case counts had a significantly higher Social Deprivation Index (median, 48 [interquartile range {IQR}, 24-72]) than counties with nonincreasing case counts (median, 40 [IQR, 19-66]; P = .009). Counties with increasing case counts were significantly more likely to be metropolitan areas of 250 000-1 million population (P < .001), to have a higher percentage of black residents (9% vs 6%; P = .013), and to have voted for the Republican presidential candidate in 2016 by a ≥10-point margin (P = .044). In the multivariable model, metropolitan areas of 250 000-1 million population, higher percentage of black residents, and a ≥10-point Republican victory were independently associated with increasing case counts. CONCLUSIONS: Increasing case counts of SARS-CoV-2 in the US during June 2020 were associated with a combination of sociodemographic and political factors. Addressing social disadvantage and differential belief systems that may correspond with political alignment will play a critical role in pandemic control.

Surgical infection prophylaxis prior to left ventricular assist device implantation: A survey of clinical practice.

BACKGROUND: Short duration, antimicrobial prophylaxis that includes antistaphylococcal activity is recommended at the time of left ventricular assist device (LVAD) implantation to reduce infection-related complications. There continues to be wide variability in surgical infection prophylaxis (SIP) regimens among implantation centers. The aim of this study is to characterize current SIP regimens at different LVAD centers. METHODS: A survey study was conducted from 26 September 2017 to 25 October 2017. Surveys were distributed electronically to LVAD coordinators and infectious diseases specialists at 75 US medical centers identified as having an LVAD program. Data collection included information about antimicrobial selection, duration, Staphylococcus aureus screening, and decolonization procedures. RESULTS: We received 29 survey responses. The majority of surveys were completed by infectious diseases physicians (72.4% [21 out of 29]). Most responding centers reported LVAD programs established for greater than 10 years (20 out of 29 [69%]). Cardiac transplantation was performed in 28 out of 29 (96%) centers. Of centers reporting a defined SIP regimen for non-penicillin allergic patients (96% [28 out of 29]), 17.9% (5 out of 28) reported a four-drug regimen, 35.7% (10 out of 28) reported a three-drug regimen, and 46.4% (13 out of 28) reported a two-drug regimen, while no centers reported a single-drug regimen. Empiric fluconazole was common (50% [14 out of 28]) and 96.4% (27 out of 28) of regimens included vancomycin. Duration of antimicrobial prophylaxis (24 hours to 5 days), S. aureus screening, decolonization procedures, and alterations due to drug allergies varied across participating centers. CONCLUSIONS: Our survey results indicate wide variation in SIP regimens among participating LVAD centers. These results highlight the need for studies evaluating the implications of SIP regimens, and whether clinical factors that prolong antimicrobial duration impact postoperative infection rates.

Real-world implications of QT prolongation in patients receiving voriconazole and amiodarone.

Objectives: Voriconazole, a triazole antifungal, is frequently prescribed in a complex patient population with comorbidities that require concomitant administration of QT interval-prolonging medications. We sought to evaluate QT interval prolongation in patients receiving concomitant therapy with voriconazole and amiodarone and to assess the development of any potentially fatal cardiac arrhythmias as a result. Methods: We conducted a retrospective observational study of patients who had received amiodarone and voriconazole concomitantly between 2005 and 2015, with a prior period of monotherapy, who had ECG data during monotherapy (baseline) and concomitant therapy (follow-up). Results: We included 46 patients in our final analysis. Overall, the mean change in QT corrected (QTc) from baseline to follow-up was 49.0 ms (P < 0.001). Eighteen (39.1%) patients had a follow-up QTc interval ≥500 ms, with 17 (37.0%) having a change in QTc interval ≥60 ms from baseline to follow-up. Men were more likely to have a follow-up QTc interval of ≥500 ms. In multivariate analysis, only low serum potassium concentration and concomitant 'possible' QT-prolonging drugs were associated with a follow-up QTc interval ≥500 ms and a lower baseline QTc interval was associated with a change in QTc interval of ≥60 ms. Discharge diagnoses of cardiac arrhythmias and events were assessed and none was found to be related to concomitant therapy. Conclusions: Concomitant therapy with amiodarone and voriconazole significantly prolonged the QTc interval to a degree greater than that on monotherapy. However, no clinically significant cardiac events were observed.

Tolerability profile of the current antifungal armoury.

The tolerability of available antifungal agents is essential to the final outcome of the management of invasive mycoses. There are limited classes of antifungal agents for use, and they can have serious direct toxicities and/or drug-drug interactions. In this review, we examine the common toxicities noted for antifungal agents and attempt to both identify the issues around the adverse events and provide clinical context for their occurrence in these fragile patients.

The war on cryptococcosis: A Review of the antifungal arsenal.

Cryptococcal meningitis is the most common central nervous system infection in the world today. It occurs primarily, but not exclusively, in immunocompromised individuals and despite substantial improvement in management of clinical events like AIDS, the numbers of cases of cryptococcosis remain very high. Unfortunately, despite several antifungal agents available for treatment, morbidity and mortality rates remain high with this fungal infection. In this Review, we will describe the treatments and strategies for success, identify the failures, and provide insights into the future developments / improvements for management. This sugar-coated yeast can play havoc within the human brain. Our goals must be to either prevent or diagnose disease early and treat aggressively with all our clinical tools when disease is detected.

CIRCULATING microRNAs: POTENTIAL BIOMARKERS IN CANCER DETECTION, DIAGNOSIS AND PROGNOSIS.

A large family of small 18-25 nucleotide long non coding RNA molecules now known as microRNA (miRNA) was described two decades ago, and has been recently es- tablished as post-transcriptional gene regulators. miRNAs were shown to be involved in the regulation of diverse phys- iological and developmental processes. Moreover, dysregula- tion of specific miRNAs has been implicated later in several pathologies including cancer. Owing to their presence and stability in body fluids, miRNAs have been investigated as novel circulating non-invasive biomarkers. Accordingly, their role as potential diagnostic, prognostic or predictive biomark- ers for many cancer types has recently emerged. This review tackles the use of circulating miRNAs in cancer detection, diagnosis and prognosis, giving examples using common solid tumors and discussing the advantages of their use, the challenges facing this novel circulating biomarker and recorn- mendatidns to overcome them.

Adverse reactions to infliximab and the outcome of desensitization.

BACKGROUND: Infliximab is a highly effective monoclonal antibody against tumor necrosis factor, which is a major inflammatory mediator in certain gastrointestinal, rheumatic, and skin diseases. In some patients, infliximab infusion causes systemic adverse reactions that often lead to discontinuation of therapy even in responsive patients. OBJECTIVE: To investigate the frequency and characteristics of adverse reactions to infliximab at the authors' institution and the outcome of their management, including desensitization. METHODS: This was a single-center retrospective study of patients who were treated with infliximab, primarily for inflammatory bowel disease, from January 1, 2000 to March 31, 2014. Data included age, sex, underlying disease, infliximab therapy duration before the first reaction, manifestation of reaction, onset, and management. RESULTS: There were 336 patients with inflammatory bowel disease who were treated with infliximab during the study period. Thirty patients (8.9%) developed a systemic adverse reaction to infliximab, which was discontinued in 15 patients (50%) and was continued in 3 patients after premedication and/or decreased infusion rate. Twelve patients (40%) underwent infliximab desensitization with gradually increasing doses starting at a dilution of 0.1 mg/mL to reach the full treatment dose over approximately 4 to 6 hours. It was successful in all 12 patients, who continued to receive up to 26 infliximab infusions, mostly without premedication. CONCLUSION: Infliximab can trigger systemic reactions that hinder its administration. The present desensitization protocol appears to be safe and effective and it can be considered in patients whose inflammatory bowel disease responds well to infliximab but who develop systemic adverse reactions.

A 17-month-old patient with severe anemia and respiratory distress.

Anemia can be caused by, or be associated with, many clinical conditions, including pulmonary diseases, some of which are rare and can be misdiagnosed. Nontraumatic pulmonary bleeding may be caused by a variety of conditions and results in anemia and pulmonary hemosiderosis, even when it is subtle. The differential diagnosis in such cases is extensive. We present the case of a diagnostic dilemma in a 17-month-old child hospitalized for severe anemia and respiratory distress in which the diagnosis was settled through an allergy/immunology consultation.

Who Benefits? An Assessment of Resident Benefits at Top 50 Academic Institutions.

OBJECTIVE: Residency serves as a crucial time in the professional and personal development of young physicians. Extensive effort is devoted to the clinical training of residents across the country. However, many residents report concerns with compensation, quality of life, and benefits during their clinical training. We sought to evaluate the benefits packages of resident physicians in comparison with other full-time employees at their institutions. SETTING: "Top 50" Residency programs in Medicine, Surgery, and Pediatrics in the United States. DESIGN: To accomplish this task we selected the, "Top-50," institutions for medicine, pediatrics, and surgery using Doximity's Residency Navigator and compared the benefits of residents at these institutions with full-time employees by accessing benefits offerings listed on institutional websites. RESULTS: We found that residents were more likely to receive parking benefits and gym memberships, while full-time employees were more likely to be offered flexible spending accounts, retirement benefits, and tuition support. CONCLUSIONS: Residents receive different benefits packages than their colleagues employed in full time positions at the same institutions. Further discussion regarding the benefits offered to physicians, and the role that benefits play in resident wellbeing is warranted in light of these findings.

Effect of Montelukast vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) is uncertain. Objective: To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. Design Setting and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate the effectiveness of repurposed medications in treating mild to moderate COVID-19. Between January 27, 2023, and June 23, 2023, 1250 participants ≥30 years of age with confirmed SARS-CoV-2 infection and ≥2 acute COVID-19 symptoms for ≤7 days, were included across 104 US sites to evaluate the use of montelukast. Interventions: Participants were randomized to receive montelukast 10 mg once daily or matched placebo for 14 days. Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID clinical progression scale; and difference in mean time unwell. Results: Among participants who were randomized and received study drug, the median age was 53 years (IQR 42-62), 60.2% were female, 64.6% identified as Hispanic/Latino, and 56.3% reported ≥2 doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR] 1.02; 95% credible interval [CrI] 0.92-1.12; P(efficacy) = 0.63]). Unadjusted median time to sustained recovery was 10 days (95% confidence interval 10-11) in both groups. No deaths were reported and 2 hospitalizations were reported in each group; 36 participants reported healthcare utilization events (a priori defined as death, hospitalization, emergency department/urgent care visit); 18 in the montelukast group compared with 18 in the placebo group (HR 1.01; 95% CrI 0.45-1.84; P(efficacy)=0.48). Five participants experienced serious adverse events (3 with montelukast and 2 with placebo). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with montelukast does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov ( NCT04885530 ).

Dexamethasone for Inpatients With COVID-19 in a National Cohort.

Importance: Limited effective therapeutics are available to hospitalized patients with COVID-19. Clinical trials and observational studies have shown varying effects of systemic corticosteroids, including dexamethasone, in hospitalized patients with COVID-19, with limited descriptions of important patient subgroups. Objective: To examine the clinical use of dexamethasone for hospitalized patients with COVID-19 respiratory illness and to explore the heterogeneity of treatment outcomes across different subgroups. Design, Setting, and Participants: This is a retrospective, propensity score-weighted cohort study of adult patients hospitalized for at least 48 hours for COVID-19 respiratory illness between July 1, 2020, and October 31, 2021, at a large health care network of 156 hospitals across the US. Data analysis was performed from March 2022 to February 2023. Exposures: Systemic dexamethasone administered within 48 hours of either admission or escalation in oxygen support. Main Outcomes and Measures: All-cause in-hospital mortality or discharge to hospice. Results: A total of 80 699 patients who met the eligibility criteria were identified (median [IQR] age, 64 [52-76] years; 37 606 women [46.6%]); 13 230 patients (16.4%) identified as Black, 49 222 (60.9%) as White, 18 247 (22.6%) as other race, and 20 340 (25.2%) as Hispanic ethnicity. Of these patients, 13 040 (16.2%) did not require supplemental oxygen within 48 hours of admission, 56 368 (69.8%) required supplemental oxygen, 7618 (9.4%) required noninvasive positive pressure ventilation (NIPPV), and 3673 (4.6%) required mechanical ventilation (MV) and/or extracorporeal membrane oxygenation (ECMO). After adjustment by propensity score overlap weighting, early use of dexamethasone was associated with reduction in a composite outcome of in-hospital mortality or discharge to hospice for patients receiving supplemental oxygen (aOR, 0.92; 95% CI, 0.86-0.98) and MV and/or ECMO (aOR, 0.82; 95% CI, 0.68-0.99). In contrast, all-cause inpatient mortality or discharge to hospice was not lower for patients who received dexamethasone in the no supplemental oxygen group (aOR, 0.90; 95% CI, 0.78-1.03) and in the NIPPV group (aOR, 0.87; 95% CI, 0.73-1.04). Importantly, patients with more comorbidities had greater benefit from dexamethasone use. Conclusions and Relevance: In this national multicenter cohort study of inpatients with COVID-19, early administration of dexamethasone was associated with significantly reduced odds of mortality or discharge to hospice in those requiring supplemental oxygen or MV and/or ECMO but not in those requiring no supplemental oxygen or NIPPV. These results support the continued use of systemic dexamethasone in patients hospitalized with COVID-19.

Scoping review of percutaneous mechanical aspiration for valvular and cardiac implantable electronic device infective endocarditis.

BACKGROUND: Percutaneous mechanical aspiration (PMA) of intravascular vegetations is a novel strategy for management of patients with infective endocarditis (IE) who are at high risk of poor outcomes with conventional cardiac surgery. However, clear indications for its use as well as patient outcomes are largely unknown. OBJECTIVES: To conduct a scoping review of the literature to summarize patient characteristics and outcomes of those undergoing PMA for management of IE. METHODS: Two independent reviewers screened abstracts and full text for inclusion and independently extracted data. DATA SOURCES: MEDLINE, Embase, and Web of Science. STUDY ELIGIBILITY CRITERIA: Studies published until February 21, 2023, describing the use of PMA for management of patients with cardiac implantable electronic device (CIED) or valvular IE were included. ASSESSMENT OF RISK OF BIAS: As this was a scoping review, risk of bias assessment was not performed. METHODS OF DATA SYNTHESIS: Descriptive data was reported. RESULTS: We identified 2252 titles, of which 1442 abstracts were screened, and 125 full text articles were reviewed for inclusion. Fifty-one studies, describing a total of 294 patients who underwent PMA for IE were included in our review. Over 50% (152/294) of patients underwent PMA to debulk cardiac implantable electronic device lead vegetations prior to extraction (152/294), and 38.8% (114/294) of patients had a history of drug use. Patient outcomes were inconsistently reported, but few had procedural complications, and all-cause in-hospital mortality was 6.5% (19/294). CONCLUSIONS: While PMA is a promising advance in the care of patients with IE, higher quality data regarding patient outcomes are needed to better inform the use of this procedure.