Tekin, Aysun

Introduction Community-acquired pneumonia (CAP) is common and remains the leading infectious cause of death worldwide. Antibiotics remain the mainstay of treatment, but organisms are often not identified, necessitating empirical treatment. Current treatment guidelines recommend combination therapy with beta-lactams and macrolides or monotherapy with fluoroquinolones for non-severe CAP. However, rising antibiotic resistance and safety concerns have led to increased doxycycline use, despite limited evidence supporting its efficacy. Our goal is to conduct a pragmatic, open-label, randomised clinical trial comparing the effectiveness of azithromycin with that of doxycycline in combination with beta-lactam therapy in adult patients hospitalised for CAP. Methods and analysis Patients presenting to the emergency department or directly referred to the hospital with a clinical presentation concerning for CAP and need for hospitalisation are eligible. We plan to enrol 1120 adults hospitalised at six hospitals across four states, including rural, suburban and urban settings and academic and community hospitals. Randomisation will be 1:1 using an electronic health record (EHR)-embedded screening and randomisation tool triggered by the treating clinician’s orders for azithromycin or doxycycline. Outcomes will be ascertained pragmatically via EHR-based data retrieval and will not require additional study visits. Our primary outcome is days alive and out of the hospital through day 28. Secondary outcomes include oxygen-free days; a composite of a need for advanced respiratory support or in-hospital mortality with analyses of each component separately; an ordinal measure of clinical deterioration defined by a prespecified severity scale; and 60-day and 180-day mortality. Safety outcomes are the incidence of Clostridioides difficile infection and QT prolongation. Analyses will follow an intention-to-treat framework, with per-protocol analyses for sensitivity. The primary endpoint will be compared between groups using a stratified van Elteren test, with supportive analyses using proportional odds regression and analysis of covariance adjusted for key covariates. Ethics and dissemination The Mayo Clinic Institutional Review Board reviewed and approved this protocol with a waiver of written consent, requiring verbal consent to be obtained by the clinician initiating the antibiotics (IRB# 24–0 06 503). Findings will be disseminated through peer-reviewed publications and international conference presentations. Trial registration number NCT07164131 .

Introduction Sepsis is a global health priority with nearly 50 million cases annually. Cardiovascular dysfunction is common, frequently manifesting as hypotension that persists despite fluid resuscitation. Most affected patients require the use of intravenous (IV) vasoactive agents, typically necessitating intensive care unit (ICU)-level monitoring, invasive interventions and contributing substantially to healthcare costs. Midodrine, an oral alpha-1 agonist approved for orthostatic hypotension, has increasingly been used off-label as a vasopressor-sparing (reducing IV vasopressor use) strategy in sepsis, despite limited and inconsistent evidence. This pragmatic, randomised, open-label trial evaluates the efficacy and safety of midodrine in patients with sepsis-associated hypotension. We hypothesise that, compared with standard care, midodrine administration will reduce the duration of IV vasopressor use. Methods and analysis A total of 308 adult patients with sepsis-associated hypotension will be enrolled (154 per arm). The intervention group will, in addition to standard of care, receive enteral midodrine 10 mg three times daily. Outcomes will be ascertained pragmatically via electronic health record-based data retrieval and adjudicated by research coordinators blinded to treatment assignment. The primary outcome is time alive and off IV vasopressors in the first 28 days (in hours) after randomisation. Secondary outcomes include cumulative vasopressor exposure; use and duration of central venous access; cumulative fluid balance over the first 48 hours and up to 7 days of ICU stay; ICU and hospital length of stay; and ICU-, hospital-, and organ support-free days through day 28. Safety outcomes include adverse events potentially attributable to midodrine during hospitalisation including acute kidney injury. Primary analyses will follow an intention-to-treat framework, including all randomised participants according to their assigned treatment groups. Primary and secondary outcomes will be compared using a van Elteren test stratified by randomisation factors. A predefined secondary Bayesian analysis of the primary outcome will provide complementary estimates of treatment effect. Safety outcomes will be summarised descriptively without formal between-arm hypothesis testing. Ethics and dissemination The Mayo Clinic Institutional Review Board approved this protocol and required written informed consent from all participants (IRB# 24–0 00 121). Findings will be disseminated through peer-reviewed publications and international conference presentations. Trial registration number NCT06319248 .

Background Adherence to evidence-based care processes and patient outcomes in intensive care units (ICUs) can be influenced by staffing and resource availability. We aimed to evaluate if there is a weekend effect on adherence to evidence-based care processes, and hospitalization outcomes and whether a checklist implementation could mitigate potential differences. Methods Post hoc analysis of the Checklist for Early Recognition and Treatment of Acute Illness and Injury (CERTAIN) study dataset collected before and after checklist implementation in 34 ICUs across 15 countries (2013-2017). Admission days were classified as ‘weekend/holidays’ or ‘weekdays’ according to local work schedules and public holidays. The primary outcome was the omission of 10 evidence-based care processes addressed in the checklist. Mortality and length of stay differences between weekend/holiday and weekday admissions were evaluated as secondary outcomes. Results 4256 patients contributed 1141 weekend versus 3501 weekday observation days pre-intervention, and 2014 versus 6507 post-intervention. Pre-intervention, peptic ulcer prophylaxis was omitted more frequently on weekends/holidays than weekdays (adjusted rate ratio [aRR], 0.58 [95%–confidence interval [CI] 0.38-0.88), whereas head-of-bed elevation was omitted more often on weekdays than on weekends/holidays (aRR, 3.17 [1.14-8.86]). Post-intervention, peptic ulcer prophylaxis omission rates became similar (aRR, 1.03 [0.68-1.56], but head-of-bed elevation became omitted more often on weekends than on weekdays (aRR, 0.63 [0.45-0.88]). Post-intervention, oral care was omitted more frequently on weekends/holidays than in weekdays (aRR, 0.63 [0.45-0.9]), and central catheter removal was more frequent on weekdays than in weekends/holidays (aRR, 1.11 [1.02-1.21]). No significant differences in mortality or length of stay were found. Conclusion A weekend effect influenced adherence to some care processes. While checklist implementation improved overall adherence, some disparities diminished, while new ones emerged. Organizational, cultural, and temporal factors should be further studied to optimize care delivery across all times and settings. Clinical Trial Registration Number NCT01973829

Abstract Background Doxycycline is a frequently used alternative treatment for community-acquired pneumonia (CAP) in hospitalized patients; however, the evidence base is limited. We aimed to compare outcomes in CAP patients treated with doxycycline or azithromycin in combination with beta-lactams. Methods We evaluated patients with CAP admitted to Mayo Clinic hospitals from May 2018 to September 2022 and treated with either azithromycin or doxycycline in combination with a beta-lactam. Patients who received both antibiotics or were on either antibiotic as chronic therapy prior to admission were excluded. The primary outcome was mortality. Patients were 1-to-1 matched according to the presence of congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, human immunodeficiency virus infection, recent immunosuppressant use, and pneumonia severity index class. Results Among 8492 patients (5810 for azithromycin, 2682 for doxycycline), 2671 doxycycline-treated patients were matched with azithromycin-treated patients. In-hospital mortality was significantly lower in the azithromycin group than in the doxycycline group (odds ratio, 0.71; 95% confidence interval [CI], .56–.9), as was 90-day mortality (hazard ratio, 0.83; 95% CI, .73–.95). Patients on azithromycin also had significantly more hospital-free days (HFDs) than those on doxycycline (estimate, 1.37; 95% CI, .99–1.74). Conclusions Among hospitalized patients with CAP, azithromycin was associated with lower mortality and more HFDs compared with doxycycline in combination with beta-lactams. Randomized, controlled trials are needed to assess the effectiveness of each regimen and to compare their potential side effects.

Objectives There is substantial practice variation in the management strategies for atrial fibrillation (AF) with rapid ventricular rate (RVR) and hemodynamic instability in critically ill patients. This study aimed to evaluate the use and effectiveness of direct current cardioversion (DCCV) for unstable AF RVR in the intensive care unit (ICU). Design Multicenter retrospective cohort study. Setting Non-cardiac/cardiovascular surgery ICUs of the Mayo Clinic Hospitals in Minnesota, Wisconsin, Florida, and Arizona. Patients Adult patients who developed paroxysmal AF RVR with hemodynamic instability (heart rate ≥ 130 beats per minute and a documented SBP ≤ 90 mmHg or the need for vasopressors) during ICU stay. Interventions Emergency DCCV. Measurements and Main Results Primary outcomes were in-hospital mortality, hospital-, ICU-, and organ support-free days. Secondary outcomes were return to sinus rhythm rate before and after discharge. Among 691 patients eligible for inclusion, 47 (6.8%) received emergent DCCV in the ICU. The frequency of DCCV was higher for patients located in surgical ICUs (14.5% vs 6.1%, P = .04). Patients were 1:2 propensity-score matched. The comparative analyses were conducted on 141 patients. Those who underwent DCCV were more likely to restore sinus rhythm (odds ratio [95% confidence interval], 5.2 [1.30 20.8]). However, DCCV was not associated with increased odds of having sinus rhythm at discharge, lower mortality, or higher number of ICU-, or hospital-free days. The number of organ support-free days was significantly lower in the DCCV group (estimate ± standard error, −5.0 ± 2.0, P = .012). Conclusions Emergency DCCV is rarely used to treat unstable AF in non-cardiac ICUs. Despite increased likelihood of immediate sinus rhythm restoration, DCCV was not associated with improvement in patient-centered outcomes. Prospective studies are warranted to evaluate harms and benefits of DCCV in non-cardiac critically ill patients with unstable AF where the driver of hemodynamic instability is often an underlying condition rather than arrhythmia per se.

We aimed to assess the prognostic role of the neutrophil/lymphocyte ratio (NLR) in community-acquired pneumonia (CAP) via a single-center retrospective cohort of hospitalized adult patients from 1/2009 to 12/2019. Patients were dichotomized into lower NLR (≤12) and higher NLR (>12). The primary outcome was mortality. ICU admission and hospital- and ICU-free days were secondary outcomes. The pneumonia severity index (PSI) and the NLR’s ability to predict outcomes was also tested. An NLR ≤12 was observed in 2513 (62.2%) patients and >12 in 1526 (37.8%). After adjusting for PSI, the NLR was not associated with hospital mortality (odds ratio [OR] 1.115; 95% confidence interval [CI] 0.774, 1.606; p = 0.559), but it was associated with a higher risk of ICU admission (OR 1.405; 95% CI 1.216, 1.624; p < 0.001). The PSI demonstrated acceptable discrimination for mortality (area under the receiver operating characteristic curve [AUC] 0.78; 95% CI 0.75, 0.82) which was not improved by adding the NLR (AUC 0.78; 95% CI 0.75, 0.82, p = 0.4476). The PSI’s performance in predicting ICU admission was also acceptable (AUC 0.75; 95% CI 0.74, 0.77) and improved by including the NLR (AUC 0.76, 95% CI 0.74, 0.77, p = 0.008), although with limited clinical significance. The NLR was not superior to the PSI for predicting mortality in hospitalized CAP patients.

Pulmonary auscultation is essential for detecting abnormal lung sounds during physical assessments, but its reliability depends on the operator. Machine learning (ML) models offer an alternative by automatically classifying lung sounds. ML models require substantial data, and public databases aim to address this limitation. This systematic review compares characteristics, diagnostic accuracy, concerns, and data sources of existing models in the literature. Papers published from five major databases between 1990 and 2022 were assessed. Quality assessment was accomplished with a modified QUADAS-2 tool. The review encompassed 62 studies utilizing ML models and public-access databases for lung sound classification. Artificial neural networks (ANN) and support vector machines (SVM) were frequently employed in the ML classifiers. The accuracy ranged from 49.43% to 100% for discriminating abnormal sound types and 69.40% to 99.62% for disease class classification. Seventeen public databases were identified, with the ICBHI 2017 database being the most used (66%). The majority of studies exhibited a high risk of bias and concerns related to patient selection and reference standards. Summarizing, ML models can effectively classify abnormal lung sounds using publicly available data sources. Nevertheless, inconsistent reporting and methodologies pose limitations to advancing the field, and therefore, public databases should adhere to standardized recording and labeling procedures.

AbstractBackgroundPneumocystis pneumonia (PCP) is a growing concern as the immunocompromised population expands. Current laboratory approaches are limited. This systematic review aimed to evaluate metagenomic next-generation sequencing (MNGS) tests’ performance in detecting PCP.MethodsFive databases were searched through December 19, 2022, to identify original studies comparing MNGS with clinically diagnosed PCP. To assess the accuracy, symmetric hierarchical summary receiver operating characteristic models were used.ResultsEleven observational studies reporting 1442 patients (424 with PCP) were included. Six studies focused exclusively on recipients of biologic immunosuppression (none with HIV-associated immunosuppression). Six were exclusively on bronchoalveolar lavage, while 1 was on blood samples. The sensitivity of MGNS was 0.96 (95% CI, 0.90–0.99), and specificity was 0.96 (95% CI, 0.92–0.98), with negative and positive likelihood ratios of 0.02 (95% CI, 0.01–0.05) and 19.31 (95% CI, 10.26–36.36), respectively. A subgroup analysis of studies exclusively including bronchoalveolar lavage (BAL) and blood samples demonstrated a sensitivity of 0.94 (95% CI, 0.78–0.99) and 0.93 (95% CI, 0.80–0.98) and a specificity of 0.96 (95% CI, 0.88–0.99) and 0.98 (95% CI, 0.76–1.00), respectively. The sensitivity analysis on recipients of biologic immunosuppression showed a sensitivity and specificity of 0.96 (95% CI, 0.90–0.98) and 0.94 (95% CI, 0.84–0.98), respectively. The overall confidence in the estimates was low.ConclusionsDespite the low certainty of evidence, MNGS detects PCP with high sensitivity and specificity. This also applies to recipients of biologic immunosuppression and tests performed exclusively on blood samples without the need for BAL. Further studies are required in individuals with HIV-associated immunosuppression.

Background Although corticosteroids have become the standard of care for patients with coronavirus disease-2019 (COVID-19) on supplemental oxygen, there is growing evidence of differential treatment response. This study aimed to evaluate if there was an association between biomarker-concordant corticosteroid treatment and COVID-19 outcomes. Methods This registry-based cohort study included adult COVID-19 hospitalized patients between January 2020 and December 2021 from 109 institutions. Patients with available C-reactive protein (CRP) levels within 48 h of admission were evaluated. Those on steroids before admission, stayed in the hospital for <48 h, or were not on oxygen support were excluded. Corticosteroid treatment was biomarker-concordant if given with high baseline CRP ≥150 mg/L or withheld with low CRP (<150 mg/L) and vice-versa was considered discordant (low CRP with steroids, high CRP without steroids). Hospital mortality was the primary outcome. Sensitivity analyses were conducted using varying CRP level thresholds. The model interaction was tested to determine steroid effectiveness with increasing CRP levels. Results Corticosteroid treatment was biomarker-concordant in 1778 (49%) patients and discordant in 1835 (51%). The concordant group consisted of higher-risk patients than the discordant group. After adjusting for covariates, the odds of in-hospital mortality were significantly lower in the concordant group than the discordant (odds ratio [95% confidence interval (C.I.)] = 0.71 [0.51, 0.98]). Similarly, adjusted mortality difference was significant at the CRP thresholds of 100 and 200 mg/L (odds ratio [95% C.I.] = 0.70 [0.52, 0.95] and 0.57 [0.38, 0.85], respectively), and concordant steroid use was associated with lower need for invasive ventilation for 200 mg/L threshold (odds ratio [95% C.I.] = 0.52 [0.30, 0.91]). In contrast, no outcome benefit was observed at CRP threshold of 50. When the model interaction was tested, steroids were more effective at reducing mortality as CRP levels increased. Conclusion Biomarker-concordant corticosteroid treatment was associated with lower odds of in-hospital mortality in severe COVID-19.

ImportanceThe conflict in Ukraine has forced civilian hospitals with limited trauma and battlefield medicine experience to care for casualties of war, placing significant strain on the health care system. Using the Checklist for Early Recognition and Treatment of Acute Illness and Injury (CERTAIN) program, a multimodal trauma critical care knowledge-exchange platform was created for clinicians practicing in these institutions.ObjectivesTo describe the development and implementation of the CERTAIN for Ukraine program and to evaluate the reach of this intervention, together with participant engagement and satisfaction.Design, Setting, and ParticipantsThis quality improvement study included clinicians caring for critically ill patients during the ongoing Ukrainian conflict who were part of a community developed using a messaging app. The program was implemented by a group of international trauma and critical care experts in collaboration with critical care leaders from the Shupyk National Healthcare University in Kyiv, Ukraine. This study evaluates data collected from the CERTAIN for Ukraine program from its launch on April 9, 2022, to August 31, 2022.InterventionsThe initiative comprised a longitudinal series of interactive tele-education sessions, a webpage containing the CERTAIN approach and current trauma critical care guidelines translated into Ukrainian and Russian, and a private messaging chat for asynchronous discussion.Main Outcomes and MeasuresParticipant engagement and satisfaction were tracked using multimedia analytics and a post-session survey.ResultsSince program launch, 838 participants have joined the messaging group, and 6 tele-education sessions have been delivered, with 1835 total views. The CERTAIN website has had 3527 visits, mainly from Ukraine (1378 [39%]) and the United States (1060 [30%]). Of the 74 completed postsession surveys, 65 respondents (88%) rated the course content excellent or very good, and 73 (99%) recommended it to others.Conclusions and RelevanceThe findings of this quality improvement study indicate that, using widely available and low-cost platforms, knowledge was shared rapidly and efficiently to a large community of clinicians practicing in a wartime environment with broad-based engagement and a high level of learner satisfaction.