Todd C. Lee MD MPH FIDSA

Authors response: "Etomidate as an induction agent for endotracheal intubation in critically ill patients: A meta-analysis of randomized trials" Authors response: "Etomidate as an induction agent for endotracheal intubation in critically ill patients: A meta-analysis of randomized trials" J Crit Care. 2024 Feb:79:154411. doi: 10.1016/j.jcrc.2023.154411. Epub 2023 Sep 9. Authors Yuki Kotani 1 , Matthew W Semler 2 , Todd C Lee 3 , Giovanni Landoni 4 Affiliations 1 Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy; Department of Intensive Care Medicine, Kameda Medical Center, Kamogawa, Japan. Electronic address: kotani.yuki@kameda.jp. 2 Department of Medicine, Division of Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, United States; Vanderbilt Institute for …

BackgroundTracheal intubation is a high-risk intervention commonly performed in critically ill patients. Due to its favorable cardiovascular profile, ketamine is considered less likely to compromise clinical outcomes. This meta-analysis aimed to assess whether ketamine, compared with other agents, reduces mortality in critically ill patients undergoing intubation.MethodsWe searched MEDLINE, Embase, and the Cochrane Library from inception until April 27, 2023, for randomized controlled trials and matched observational studies comparing ketamine with any control in critically ill patients as an induction agent. The primary outcome was mortality at the longest follow-up available, and the secondary outcomes included Sequential Organ Failure Assessment score, ventilator-free days at day 28, vasopressor-free days at day 28, post-induction mean arterial pressure, and successful intubation on the first attempt. For the …

To the Editor On behalf of my coauthors and myself, I write to explain the correction of our Original Investigation,“Evaluation of Oseltamivir Used to Prevent Hospitalization in Outpatients With Influenza: A Systematic Review and Meta-Analysis,” 1 published online first on June 12, 2023, in JAMA Internal Medicine. This systematic review and meta-analysis included data from 15 randomized clinical trials and accurately concluded that oseltamivir was not associated with reduced risk of first hospitalization compared with placebo or standard of care. However, when we received a request to share our study data, 1 we realized that a number of inadvertent transcription and transposition errors had occurred in our response to peer review. These errors were primarily introduced by migrating back and forth between the intention-to-treat and intentionto-treat infected populations for the requested sensitivity analyses;“no …

Rationale & ObjectivePatients treated with dialysis are commonly prescribed multiple medications (polypharmacy), including some potentially inappropriate medications (PIMs). PIMs are associated with an increased risk of medication harm (eg, falls, fractures, hospitalization). Deprescribing is a solution that proposes to stop, reduce, or switch medications to a safer alternative. Although deprescribing pairs well with routine medication reviews, it can be complex and time-consuming. Whether clinical decision support improves the process and increases deprescribing for patients treated with dialysis is unknown. This study aimed to test the efficacy of the clinical decision support software MedSafer at increasing deprescribing for patients treated with dialysis.Study DesignProspective controlled quality improvement study with a contemporaneous control.Setting & ParticipantsPatients prescribed ≥5 medications in 2 …

Pneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of Pneumocystis jirovecii pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole …

In this issue of Clinical Microbiology and Infection, Stabholz and Paul [1] present a systematic review and meta-analysis comparing vancomycin, fidaxomicin, and metronidazole for the treatment of Clostridioides difficile infection (CDI) with all-cause mortality as a primary outcome, in addition to a range of other clinically relevant and patient-relevant outcomes. This study adds further nuance to the choice between fidaxomicin and vancomycin for treatment of an initial CDI episode. Separate guidelines published in 2021 by Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) and the European Society ofClinical Microbiology and Infectious Diseases (ESCMID) both recommended fidaxomicin over vancomycin on the basis of sustained cure without recurrence, although there was no difference in other outcomes assessed (initial clinical cure, drug-related adverse events …

Objectives:Hypotension is associated with adverse outcomes in critically ill and perioperative patients. However, these assumptions are supported by observational studies. This meta-analysis of randomized controlled trials aims to compare the impact of lower versus higher blood pressure targets on mortality.Data Sources:We searched PubMed, Cochrane, and Scholar from inception to February 10, 2024.Study Selection:Randomized trials comparing lower versus higher blood pressure targets in the management of critically ill and perioperative settings.Data Extraction:The primary outcome was all-cause mortality at the longest follow-up available. This review was registered in the Prospective International Register of Systematic Reviews, CRD42023452928.Data Synthesis:Of 2940 studies identified by the search string, 28 (12 in critically ill and 16 in perioperative settings) were included totaling 15,672 patients …

BackgroundSignificant variations in the variables collected in clinical studies focusing on bacteraemia lead to inconsistency in the evaluation of risk factors for mortality.ObjectiveWe aimed to define a minimum set of risk factors that should be assessed and reported in all studies assessing survival in bacteraemia.Study eligibilityWe conducted a systematic review including observational prospective and retrospective cohort studies that assessed all-cause mortality among patients with bacteraemia. We included only studies computing an adjusted analysis for mortality, with >500 participants.ExposuresIndependently significant risk factors for all-cause, preferably 30-day, mortality.Data sourcesPubMed was used to identify eligible studies published between 2000 and 2020. A Delphi survey among experts was used to evaluate and prioritize the factors identified by the systematic review.Risk of biasSIGN checklist …

Background Omalizumab is an anti-IgE monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties. Objective We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for COVID-19 pneumonia. Methods This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab versus placebo (in addition to standard of care) in hospitalized COVID-19 patients. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization. Results Of 41 patients recruited, 40 were …

IntroductionInformed consent forms (ICFs) for randomised clinical trials (RCTs) can be onerous and lengthy. The process has the potential to overwhelm patients with information, leading them to miss elements of the study that are critical for an informed decision. Specifically, overly long and complicated ICFs have the potential to increase barriers to trial participation for patients with mild cognitive impairment, those who do not speak English as a first language or among those with lower medical literacy. In turn, this can influence trial recruitment, completion and external validity.Methods and analysisSIMPLY-SNAP is a pragmatic, multicentre, open-label, two-arm parallel-group superiority RCT, nested within a larger trial, the Staphylococcus aureus Network Adaptive Platform (SNAP) trial. We will randomise potentially eligible participants of the SNAP trial 1:1 to a full-length ICF or a SIMPlified LaYered (SIMPLY …

RationaleAcute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair.ObjectiveTo map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis.MethodsWe analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC–MS/MS and DI-MS/MS …

The spectre of severe invasive infections caused by Streptococcus pyogenes and 45 Staphylococcus aureus haunt clinicians and patients alike. They are the quintessential causes 46 of devastating high profile ‘front page sepsis’ cases affecting children and adults, often without 47 recognised risk factors, and typically associated with toxic shock syndromes (TSS) and 48 necrotizing soft tissue infections (NSTI), as seen in the global surge of invasive S. pyogenes 49 disease from late 2022.(1) These fulminant clinical syndromes demand rapid empiric antibiotic 50 treatment and urgent surgical intervention for source control. Empiric adjunctive therapies are 51 often recommended by guidelines and are widely used despite a lack of evidence. Classical 52 examples include antibiotics to inhibit toxin production (eg, clindamycin, linezolid) and 53 intravenous immunoglobulin (IVIG).(2, 3) Empiric broad-spectrum antibiotic …

In Reply We thank the authors of 2 letters who sent in reflections on our systematic review and meta-analysis of oseltamivir to prevent hospitalization. 1 Both submissions highlighted 2 key concepts that emerge from the finding that oseltamivir was not associated with reduced hospitalizations. The first key concept highlights that the main study result was inconclusive (underpowered) and thus calls for a large, adequately powered, randomized clinical trial in a population at sufficiently elevated risk to benefit. We agree this is needed. The reason a trial must be large stems from the fact that if any benefit exists, it is so small that clinicians would subsequently need to decide whether it is important. Benefit is in the eye of the beholder: a 0.2% absolute reduction in hospitalizations (number needed to treat, 500) may be deemed of benefit on a societal level during an overwhelming pandemic but is likely not relevant during a …

The ACP presents recommendations for outpatient treatment of COVID-19 based on Sommer and colleagues' systematic review. The editorialists commend the authors of the recommendations and review for trying to summarize the rapidly evolving literature and discuss the challenges of updating reviews and associated recommendations as new evidence emerges and relevant outcomes evolve.

Hydroxychloroquine (HCQ) was initially promoted as an oral therapy for early treatment of coronavirus disease 2019 (COVID‐19). Conventional meta‐analyses cannot fully address the heterogeneity of different designs and outcomes of randomized controlled trials (RCTs) assessing the efficacy of HCQ in outpatients with mild COVID‐19. We conducted a pooled analysis of individual participant data from RCTs that evaluated the effect of HCQ on hospitalization and viral load reduction in outpatients with confirmed COVID‐19. We evaluated the overall treatment group effect by log‐likelihood ratio test (−2LL) from a generalized linear mixed model to accommodate correlated longitudinal binary data. The analysis included data from 11 RCTs. The outcome of virological effect, assessed in 1560 participants (N = 795 HCQ, N = 765 control), did not differ significantly between the two treatment groups (−2LL = 7.66; p = 0 …

Background Previous trials have demonstrated the effects of fluvoxamine alone and inhaled budesonide alone for prevention of disease progression among outpatients with COVID-19. Objective To determine whether the combination of fluvoxamine and inhaled budesonide would increase treatment effects in a highly vaccinated population. Design Randomized, placebo-controlled, adaptive platform trial. (ClinicalTrials.gov: NCT04727424) Setting 12 clinical sites in Brazil. Participants Symptomatic adults with confirmed SARS-CoV-2 infection and a known risk factor for progression to severe disease. Intervention Patients were randomly assigned to either fluvoxamine (100 mg twice daily for …

Despite improvements over the past 20 years [1], the morbidity and mortality associated with Staphylococcus aureus bacteremia are substantial with up to a 20% mortality rate at 30 days. S. aureus has a predilection toward deep-seated infections, which are not always clinically apparent, thus contributing to inadequate treatment or recurrence. The complex nature of S. aureus bacteremia has benefitted from interventions to standardize processes of care, such as automatic consultation with an infectious diseases specialist [2] and the implementation of care bundles [3]. In theory, improved outcomes have been mediated through guidance related to appropriate antibiotic therapy (eg, class, dose, optimal pharmacokinetics, route, and duration) and recommendations to obtain and operationalize source control (eg, line removal or drainage of abscesses). It follows that better identification of clinically silent foci of infection …

The COVID-19 pandemic presents substantial challenges for governments and providers keen to provide effective treatments. The tensions between supply, uncertainty of which patient populations optimally benefit, time-limited effectiveness (due to need for rapid initiation of treatment on an individual level, and viral evolution and potential development of resistance on a population level), and action bias (ie, most providers to want to ‘do something’for an ailing patient) have incentivised rapid authorisation of therapeutic agents with relatively broad use criteria. 1 Nirmatrelvir/ritonavir (Paxlovid, Pfizer) is a combination protease inhibitor that prevents viral replication of SARS-CoV-2 and was authorised for emergency use in December 2021 for patients age≥ 12 and weight≥ 40 kg who have proven mild to moderate COVID-19 and who are considered at high risk for progression to severe disease. 2 This analysis …

What Is Deprescribing? It is common for people to be prescribed many medications and also to take over-the-counter treatments, vitamins, or supplements. Medications are often started for a good reason, but sometimes they are continued when they are no longer helpful and may cause adverse effects. Slowly and carefully cutting down on unnecessary medications with a health care professional is called deprescribing.Why Might My Medications Be Deprescribed? Your health care professional may advise you to reduce the dose or stop taking a medication because it is not providing substantial benefit, or because the medication carries considerable risk of negative health effects. Deprescribing might happen in the emergency department or hospital, especially if a medication adverse effect caused an acute health problem.

The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a multifactorial Bayesian adaptive platform trial that aims to improve the way that S. aureus bloodstream infection, a globally common and severe infectious disease, is treated. In a world first, the SNAP trial will simultaneously investigate the effects of multiple intervention modalities within multiple groups of participants with different forms of S. aureus bloodstream infection. Here, we formalise the trial structure, modelling approach, and decision rules that will be used for the SNAP trial. By summarising the statistical principles governing the design, our hope is that the SNAP trial will serve as an adaptable template that can be used to improve comparative effectiveness research efficiency in other disease areas.Trial registrationNCT05137119. Registered on 30 November 2021.