Early Administration Research Articles

Early and high-volume administration of sodium bicarbonate in sepsis-associated acute kidney injury in patients with malignancies, during continuous renal replacement therapy

Introduction Sepsis is an uncontrolled systemic response to infection that leads to life-threatening organ dysfunction. The in-hospital mortality rate remains significantly high in septic shock patients with malignancies. This study investigates whether early and high-volume administration of sodium bicarbonate during continuous renal replacement therapy (CRRT) can reduce 28-day mortality, increase shock reversal rates, and shorten the duration of CRRT, mechanical ventilation, and intensive care unit (ICU) stays. The goal is to provide valuable clinical data for the management of cancer patients with sepsis-associated acute kidney injury (SAKI). Materials and methods A retrospective study was performed on 88 patients who were admitted to the ICU and received continuous renal replacement therapy (CRRT) for acute renal failure secondary to sepsis at the Cancer Center of Sun Yat-sen University from March 2010 to October 2021. Based on the initiation time of CRRT and the volume of sodium bicarbonate infusion, patients were divided into four groups: the early high-volume group, early low-volume group, late high-volume group, and late low-volume group. Results The results of this study showed that in the 28-day mortality model, established using the Cox proportional hazards method, early CRRT (HR 0.473; 95% CI 0.245–0.915, p = 0.026) and high-volume sodium bicarbonate infusion (HR 0.173; 95% CI 0.078–0.383, p < 0.001) were identified as two independent protective factors. The 28-day mortality rate in the early high-volume group (15.0%) was significantly lower than that of the other three groups (60.0%, 30.0%, and 75.0%, respectively; χ 2 = 23.822, p < 0.001). Additionally, the shock reversal rate in the early high-volume group (80.0%) was significantly higher compared to the other groups (35.0%, 45.0%, and 35.7%; χ 2 =13.576, p = 0.004). The duration of CRRT was shorter in the early high-volume group (35.0 ± 4.45 h) than in the other groups (70.0 ± 30.19 h, 48.0 ± 5.22 h, and 72.0 ± 19.84 h; χ 2 =11.278, p = 0.01). Furthermore, the duration of mechanical ventilation (7.0 ± 3.33 days) was lower in the early high-volume group compared to the other groups (8.0 ± 1.12 days,10.0 ± 1.11 days, and 8.0 ± 2.65 days; χ 2 =8.064, p = 0.045), as was the length of ICU stay (7.0 ± 0.89 days) compared to the other groups (13.0 ± 3.35 days, 10.0 ± 1.49 days, and10.0 ± 3.70 days; χ 2 = 9.184, p = 0.027). Conclusion Early and high-volume administration of sodium bicarbonate during CRRT may reduce 28-day mortality and improve shock reversal rates in patients with sepsis-associated acute kidney injury complicated by malignancy. Prospective randomized controlled large sample studies are needed to confirm this.

Importance of early use of tolvaptan in hyponatremic acutely decompensated heart failure patients, a retrospective study

BackgroundHyponatremia is one of the complicating findings in acute decompensated heart failure. Decrease in cardiac output and systemic blood pressure triggers activation of renin–angiotensin–aldosterone system, antidiuretic hormone, and norepinephrine due to the perceived hypovolemia. Fluid-overloaded heart failure patients are commonly treated with loop diuretics, acutely decompensated heart failure patients tend to be less responsive to conventional oral doses of a loop diuretic, while other different diuretics could work in different part of nephron circulation system. In this study, we aim to further examine the role of tolvaptan, a vasopressin receptor antagonist, in the treatment of hyponatremia secondary to acutely decompensated heart failure.ResultsA total of 71 patients with hyponatremia secondary to ADHF were included, and all patients were given tolvaptan. 37 patients were administered tolvaptan early (up until 5 th day of admission). 34 patients received tolvaptan after 5 th day of admission mean administration as 6.86 th day, and median administration was 5 th day. Analysis showed lower length of stay in patients receiving early administration of tolvaptan compared to late administration (8.86 ± 5.06 vs 18.5 ± 9.05 p0.001, respectively). Patients with early initiation of tolvaptan also achieved a larger net increase in sodium levels at discharge compared to admission (6.46 ± 6.69 vs 3.68 ± 4.70 p0.048, respectively).ConclusionsEarly administration of tolvaptan in treating hyponatremia in acutely decompensated heart failure patients is associated with a lower length of hospitalization and a higher increase in serum sodium of patients in hyponatremic ADHF patients.

Effect of timing of antibiotic use on premature rupture of membranes and its impact on reproductive tract infection and fetal membrane cell scorching indicators.

The study was designed to appraise the effects of early antibiotic administration on reproductive tract infections and fetal membrane cell scorching in instances of premature rupture of membranes (PROM). A total of 107 pregnant women diagnosed with PROM between July 2020 and June 2022 were randomly assigned to two groups: the Intervention (n=54), where ampicillin were administered within 24 hours of PROM onset, and the control group (n=53), where ampicillin were given 24-48 hours after PROM. Maternal and neonatal outcomes, incidence of reproductive tract infections, and fetal membrane cell scorching indicators (Caspase-1, Caspase -3, Caspase-9 and IL-β) were compared. The intervention group had significantly fewer adverse maternal and neonatal outcomes (p<0.05). Post-treatment, rates of Chlamydia trachomatis, Mycoplasma solium, and genital tract infections decreased in both groups, with lower rates in the intervention group (p<0.05). Positive expression rates of Caspase-1, -3, -9, and IL-β in placental tissues were also lower in the intervention group (p<0.05). We conclude that administering antibiotics within 12 hours of PROM reduces reproductive tract infections, lowers fetal membrane cell scorching, and improves maternal and neonatal outcomes, supporting early antibiotic use in the management of PROM.

Severe Generalized Tetanus Successfully Cared in the Intensive Care Unit (Case Report)

Generalized tetanus, caused by the tetanospasmin toxin from Clostridium tetani, remains a health issue in rural areas with low vaccination coverage. This case describes a 38-year-old man from Oaxaca, Mexico, who developed this infection. Treatment included antitetanus immunoglobulin, broad-spectrum antibiotics, invasive mechanical ventilation, and sedoanalgesia. After 14 days in the intensive care unit (ICU), the patient showed favorable progress. This case underscores the importance of an integrated, multidisciplinary approach aligned with best documented practices. Early administration of immunoglobulin and antibiotics was crucial for recovery, as well as the use of mechanical ventilation and tracheostomy to manage respiratory complications. Improving healthcare infrastructure and vaccination coverage in rural areas is essential to effectively prevent and treat tetanus and other preventable diseases.

Acetaminophen administration reduces acute kidney injury risk in critically ill patients with Clostridium difficile infection: A cohort study.

Acetaminophen serves as a standard antipyretic and analgesic agent in the intensive care unit (ICU). However, the association between its administration and acute kidney injury (AKI) among critically ill patients remains controversial, particularly lacking research in patients with Clostridioides difficile infection (CDI). Our aim was to explore the potential relationship between early acetaminophen administration and AKI in critically ill patients with concurrent CDI. Using data from the Medical Information Mart for Intensive Care (MIMIC) IV version 2.2 database, we performed a retrospective cohort study. AKI within 7 days of ICU admission was the main outcome that was measured. We utilized multivariable logistic regression models adjusted for potential confounders based on statistical significance and clinical relevance, to investigate the association between acetaminophen exposure and the risk of AKI in patients with CDI. Additionally, subgroup analyses and sensitivity analysis were conducted to assess the robustness of our primary findings. The average age of 984 participants was 66.8 ± 16.5 years, and 52.7% (519) were male. The overall proportion of patients who developed AKI was 75.4% (742/984). In patients without and with acetaminophen administration, AKI rates were 79.8% (380/476) and 71.3% (362/508), respectively. Compared to the non-acetaminophen administration group, the risk of AKI was lower in the acetaminophen administration group (absolute risk difference: -8.5%, 95%CI: -13.83%∼-3.17%, P < 0.01).After adjusting for potential confounders, acetaminophen administration was associated with a 32% reduction in the risk of AKI (OR = 0.68, 95%CI:0.48∼0.96, P = 0.027). Our study suggests that early acetaminophen administration may offer renal protection by reducing the risk of AKI in critically ill patients with CDI. Prospective, multicenter randomized controlled studies are needed to verify this finding.

Therapeutic effect of novel drug candidate, PRG-N-01, on NF2 syndrome-related tumor.

NF2-related schwannomatosis (NF2-SWN) is associated with multiple benign tumors in the nervous system. NF2-SWN, caused by mutations in the NF2 gene, has developed into intracranial and spinal schwannomas. Because of the high surgical risk and frequent recurrence of multiple tumors, targeted therapy is necessary. However, there are no approved drugs. We examined the action mechanism of PRG-N-01, a candidate molecule for NF2-SWN, through the direct binding assay and mass spectrometry. For in vitro anti-proliferative experiments, primary cells derived from NF2 mouse model and patient tumors, were treated with PRG-N-01. The in vivo therapeutic and preventive efficacy was validated via intraperitoneal and oral administration in NF2 mouse model (Postn-Cre; Nf2f/f). Gene expression profile in the DRG of mouse model was explored by RNA sequencing. The pharmacological properties of PRG-N-01 were analyzed through the preclinical study. PRG-N-01 binds to the N-terminal extremity of TGFβR1 (TβR1) kinase domain, where TβR1 and RKIP interact, inhibiting the binding and preventing degradation of RKIP. In vivo administration in the mouse model suppressed schwannoma progression in the DRG. Early oral administration of the PRG-N-01 also demonstrated preventive effects on NF2-SWN. PRG-N-01 treatment suppressed tumor growth genes while upregulating genes related to for normal cell metabolism and schwann cell differentiation in DRG. PRG-N-01 showed druggable properties through the preclinical study including ADME, pharmacodynamics, pharmacokinetics and toxicology. Together, our study provides the rationale and critical data for a prospective clinical trial of PRG-N-01 in NF2-SWN patients indicating PRG-N-01 as a promising candidate for the treatment.

Early neurological deterioration in acute ischemic minor stroke patients with large vessel occlusion following intravenous thrombolysis.

Early identification of risk factors associated with early neurological deterioration (END) in patients with acute minor stroke and large vessel occlusion (LVO) receiving intravenous thrombolysis (IVT) could assist in formulating treatment decisions. Consecutive patients with acute minor stroke and LVO were extracted from a single-center prospective database spanning January 2020 to December 2023. END was defined as an increase of ≥ 4 points in the National Institutes of Health Stroke Scale (NIHSS) score from baseline, or ≥ 2 points in any single NIHSS item, within 24 hours of the IVT. Multivariate logistic regression analysis, adjusted for confounding variables, was employed to identify risk factors associated with END. A total of 163 patients were included in this study, of which 36 (22.1%) patients encountered END. Patients in the END group had a higher proportion of isolated internal carotid artery (ICA) occlusion (30.6% vs. 6.3%), delayed antiplatelet therapy (88.9% vs. 66.1%), and a larger Tmax > 4s volume (142 vs. 114 ml) (all P < 0.05). Multivariate logistic regression analysis after adjusting for confounding factors showed that isolated (ICA) occlusion (adjusted odds ratio [aOR] = 2.49, 95% confidence interval [CI] = 1.97-4.41; P < 0.001) and delayed antiplatelet therapy (aOR = 1.46, 95% CI = 1.17-1.84; P < 0.001) were significantly associated with END. Isolated ICA occlusion and delayed antiplatelet therapy were significantly associated with END in minor stroke patients with LVO following IVT. Bridging thrombectomy or early administration of antiplatelet therapy may be considered reasonable strategies.

Outcomes of a 12-month course of early and late rituximab BCD020 biosimilar administration in juvenile systemic lupus erythematosus: A retrospective study.

Juvenile systemic lupus erythematosus (SLE) is a severe, life-threatening disease. However, the role of rituximab in managing juvenile SLE remains undefined, although early biological intervention may improve disease outcomes. To assess the differences in the outcomes of different types of rituximab administration (early and late). In this retrospective cohort study, the information of 36 children with SLE with early (less than 6 months from onset) rituximab administration (ERA), and late (more than 1 year) rituximab administration (LRA) was analyzed. We compared initial disease characteristics at onset, at baseline (start of rituximab), and at the end of the study (EOS) at 12 months, as well as outcomes and treatment characteristics. The main differences at baseline were a higher daily median dose of corticosteroids, increased MAS frequency, and a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the ERA group. No differences in the main SLE outcomes between groups at the EOS were observed. The part of lupus nephritis patients who achieved remission changed from 44% to 31% in ERA and 32% to 11% in the LRA group. Patients with ERA had a shorter time to achieve low daily corticosteroid dose (≤ 0.2 mg/kg) at 1.2 (0.9; 1.4) years compared to 2.8 (2.3; 4.0) years (P = 0.000001) and higher probability to achieve this low dose [hazard ratio (HR) = 57.8 (95% confidence interval (CI): 7.2-463.2), P = 0.00001 and remission (SLEDAI = 0); HR = 37.6 (95%CI: 4.45-333.3), P = 0.00001]. No differences in adverse events, including severe adverse events, were observed. ERA demonstrated a better steroid-sparing effect and a possibility of earlier remission or low disease activity, except for lupus nephritis. Further investigations are required.

Early Albumin Administration in Veno-Arterial Extracorporeal Membrane Oxygenation.

The clinical outcome and fluid balance of patients with veno-arterial extracorporeal membrane oxygenation (VA ECMO) or after extracorporeal cardiopulmonary resuscitation (eCPR) may be improved by addressing the high fluid demand with an early albumin administration. In this prospective observational study, patients supported with VA ECMO or eCPR received early albumin administration (25 g/L) to prime the VA ECMO system. These patients were compared to patients who received a regimen based solely on balanced crystalloids (crystalloid group) or a regimen based on a 1:4 volume mixture of albumin (10 g/L) and balanced crystalloids (albumin group). 660 VA ECMO patients (66.4% eCPR) treated between January 2017 and June 2021 were analyzed, whereby 265 patients received crystalloid fluid therapy, 269 patients received albumin therapy, and 126 patients received early albumin therapy. When compared to the albumin and crystalloid groups, patients in the early albumin treatment group had significantly lower cumulative fluid balances (p < 0.05). However, this effect was only observed in the group of eCPR patients and not in patients with cardiogenic shock. Logistic regression revealed albumin administration as an independent predictor of increased survival (Odds ratio 1.66 (1.11-2.47) [95%-CI], p = 0.013). Yet, only eCPR patients showed a survival benefit from albumin administration compared to the crystalloid group (survival of 29.4% vs. 18.8%, p = 0.024). Early albumin administration in eCPR patients was linked to a significant decline in fluid balance. Moreover, volume therapy with albumin application was an independent predictor for improved survival in eCPR patients.

Efficacy of melatonin for treatment and prevention ofneonatal necrotizing enterocolitis: a systematic review.

The purpose of this study was to systematically review the available literature evaluating the use of melatonin for preventing and treating neonatal necrotizing enterocolitis (NEC). A systematic review of studies examining the effect of melatonin on neonatal NEC was conducted. The databases of Medline, Scopus, WOS, Embase, and Cochrane Central Register of Controlled Trials were searched for relevant studies. For risk of bias and applicability, The ROB2 tool was used for randomized controlled trials, and the ROBINS-I tool was used for non-randomized controlled trials. Three studies, comprising 106 preterm neonates, were included in the review, whose mean gestational ages ranged from 31.8 to 33.53weeks. Melatonin doses varied among the studies. A randomized, double-blind, placebo-controlled study revealed that early administration of melatonin in preterm newborns resulted in a decrease in lipid peroxidation during the initial days of life. Two studies evaluated the role of melatonin in NEC. Both reported significant clinical and laboratory improvements in the melatonin groups, including reduced abdominal distension, metabolic acidosis, thrombocytopenia, hyponatremia, and lower mortality rates compared to control groups. This systematic review suggests that melatonin may be a potential therapeutic approach for NEC in preterm infants. However, further RCTS are needed to establish its therapeutic or preventive role.

Occupational therapy embedded in early childhood education (OTEEC): Developing a population-focused, place-based approach to early intervention through occupational therapy and early childhood education center partnerships

ABSTRACT Occupational therapy practices supporting population health are emphasized in the American Occupational Therapy Association’s Vision 2025 statement, yet limited examples of how practitioner’s design, construct, and evaluate health promotion practices exist in the literature. This manuscript describes how occupational therapy providers collaborated with early childhood education administrators, teachers, and parents to create a novel approach to supporting young children’s development and learning called the Occupational Therapy Embedded in Early Childhood Education (OTEEC) Partnership Model. Educational design research informed how the OTEEC Partnership Model was developed and refined via the integration of scientific inquiry within the context of program development. We completed literature reviews, conducted in-depth interviews with key decision-makers, hosted stakeholder focus groups, and engaged in critical reflection as an occupational therapy provider team to arrive at the foundational principles and unique practices of the OTEEC Partnership Model. Early childhood education center administrators, teachers, and parents believed the strengths of the OTEEC Partnership Model included universal access to an occupational therapy provider, collaborative partnerships with teachers and parents, and integrating occupational therapy practices within an early childhood classroom context. Occupational therapy providers can use the procedures described in this manuscript to develop innovative practices focused on population health and may consider if elevating their own classroom involvement, interprofessional collaboration, and partnerships with parents can enhance their current practices. Occupational therapists may also consider how to create new access pathways for children who might benefit from occupational therapy yet do not qualify for services within current practice guidelines.

Early initiation of intravenous cyclophosphamide and one-year outcome in super-refractory cryptogenic-new onset refractory status epilepticus.

To explore the potential efficacy of early initiation of intravenous cyclophosphamide (IVCPA), we reviewed consecutive four cases of super-refractory cryptogenic-new onset refractory status epilepticus (C-NORSE) between 2015 and 2023. We compared functional outcomes at 3 months and 1 year after the onset between patients who received IVCPA within 20 days (early-treated) and those who received it later (late-treated). All patients (median age: 43 years) had a prodromal fever. Brain MRI revealed symmetrically increased FLAIR signals in the medial temporal lobes of all patients. Despite initiating antiseizure medications (ASMs) and first-line immunotherapy (intravenous-methylprednisolone and immunoglobulins) within a median of 3 days from onset, SE persisted >5 days. The diagnosis of C-NORSE was suggested based on a high C-NORSE score (6/6). Thus, all patients received IVCPA a median of 15.5 days after seizure onset (three within 20 days and one at 31 days). One of the three early-treated patients also received tocilizumab. Early-treated patients exhibited shorter sedation periods (median 29 vs. 75 days) and better 1 year functional status (mRS 1-2 vs. mRS 4) compared to the late-treated patient. Early initiation of IVCPA and/or tocilizumab, along with ASMs, may contribute to a better one-year functional status in super-refractory C-NORSE patients. PLAIN LANGUAGE SUMMARY: This study demonstrates the potential efficacy of early administration of intravenous cyclophosphamide on one-year functional status in patients with super-refractory cryptogenic-new onset refractory status epilepticus. "Early-treated patients" who received it within 20 days of seizure onset achieved a good one-year functional status. The "late-treated patient" (Case 4) who received it later did not achieve a good functional status. Early initiation of cyclophosphamide, along with antiseizure medications, may contribute to a better one-year functional status in this population.

The efficacy and safety of stepwise oral food challenge in children with hen’s egg allergy

BackgroundOral food challenge (OFC) is the gold standard for diagnosing food allergies (FAs) but carries the risk of anaphylactic reaction. Stepwise OFC, starting with a low dose of allergen and progressing to medium and full doses, is effective in determining a tolerable dose. We retrospectively evaluated the results of a stepwise OFC for hen’s egg (HE) to demonstrate its safety and efficacy. We discuss whether early low-dose administration of HE induces early immune tolerance in HE allergy.MethodsWe included 2,058 children (median, 2.6 years) who underwent HE-OFC between 2017 and 2021 at two institutes in Japan. The target challenge dose of OFC was classified as low (less than 1/8 of a cooked egg), medium (1/8 or more but less than 1/2), or full (1/2 or more). If the low-dose OFC was negative, subjects were allowed to consume the same dose of HE and underwent medium-dose OFC within 12 months. Even if positive, individuals were recommended to consume previously-tolerated amounts of HE and repeat OFC at the same dose within 12 months. We evaluated the correlation between their OFC results and response.ResultsA total of 526 (25.6%) children presented positive reactions. There were no cases of anaphylactic shock. Higher serum egg white (EW)- (P < 0.001) and ovomucoid (OVM)- specific IgE (P < 0.001) (sIgE) levels were associated with positive OFC. The low-dose OFC group had more positive reactions (P < 0.001), younger children (P < 0.001), higher EW-sIgE (P < 0.001) and OVM-sIgE (P < 0.001), and more histories of anaphylaxis (P = 0.014). OFC-positive children were younger than OFC-negative children, particularly in low-dose OFC (P = 0.010). OFC results between complete and partial elimination of HE groups across all EW- or OVM-sIgE classes were similar (P > 0.05).ConclusionsStepwise OFC is safe and effective in diagnosing HE allergy and facilitates the earlier introduction of HE in children. This study suggests the limited potential of early consumption of lower doses of HE to induce earlier immune tolerance, such that other strategies to induce earlier tolerance in infants with HE allergy should be considered.

Early-life IL-4 administration induces long-term changes in microglia in the cerebellum and prefrontal cortex.

Microglia are crucial for brain development and their function can be impacted by postnatal insults, such as early-life allergies. These are characterized by an upregulation of interleukin (IL)-4 levels. Allergies share a strong comorbidity with Autism Spectrum Disorders (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). We previously showed that early-life allergic asthma induces hyperactive and impulsive behaviors in mice. This phenotype was reproduced in animals administered with IL-4 in the second postnatal week. Mechanistically, elevated IL-4 levels prevented microglia-mediated engulfment of neurons in the cerebellum, resulting in a surplus of granule cells and consequent dysfunction in cerebellar connectivity. Here, we aimed to further understand the impact of early IL-4 administration in microglia of the cerebellum and the prefrontal cortex (PFC), two brain regions with protracted developmental programs and susceptible to immune system malfunction after birth. While IL-4 administration induced differential short-term effects on microglia in the cerebellum and PFC, both regions presented similar microglial features in adult mice. Although Sholl analysis did not reveal significant alterations in overall microglia morphology at postnatal day (P)10, the density of microglia was decreased in the cerebellum at this age, especially in the granular layer (GL), but remained unaltered in the PFC. Interestingly, the presence of microglia with phagocytic cups, morphological features important for whole-cell engulfment, was decreased in both regions. When assessing the long-term consequences of IL-4 administration, cerebellar and PFC microglia were hypo-ramified and exhibited increased overall density. Importantly, microglia alterations were exclusive to the GL of the cerebellum and the infralimbic region of the PFC. Our results show that postnatal elevated levels of IL-4 impair the percentage of microglia engaged in cell clearing in two brain regions with protracted developmental programs. Interestingly, IL-4-exposed microglia adapt a similar phenotype in the adult cerebellum and PFC. Our data suggest that this early-life increase in IL-4 levels is sufficient to elicit long-lasting alterations in microglia, potentially increasing cell susceptibility to later insults.

Impact of time-of-day administration of immunotherapy on survival in metastatic renal cell carcinoma: the MOUSEION-09 meta-analysis.

Studies conducted in the last few years have suggested a connection between clinical outcomes and the time of immune checkpoint inhibitors (ICIs) infusion. However, few data are available regarding the differences between early and late time-of-day (ToD) administration in metastatic renal cell carcinoma (mRCC) patients receiving immunotherapy and immune-based combinations. In this meta-analysis, we aimed to fully investigate the influence of timing of administration on the efficacy of mRCC immunotherapy, by comparing early ToD versus late ToD dosing in this setting. The present systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Overall Survival (OS) was measured as Hazard Ratios (HRs) and 95% confidence intervals (CIs). Our search resulted in the identification of 1429 potentially relevant reports, which were subsequently restricted to four following independent evaluation of three authors. The pooled HR for OS in RCC patients receiving early ToD versus late ToD dosing was 0.62 (95% Confidence Interval, 0.50-0.72; p < 0.001). According to our findings, a statistically significant improvement in terms of OS for mRCC patients receiving early ToD administration compared with late ToD dosing was observed, with a reduction of death by 38%. Well-designed, randomized clinical and translational trials are required to clarify this issue and to establish recommendations for personalized treatments according to ToD.

Door-to-Diuretic Time and Outcomes in Acute Heart Failure: A Scoping Review.

Inadequate decongestion remains an unmet need in the management of patients with heart failure. The concept of door-to-diuretic (D2D) time to improve outcomes has been proposed for patients with heart failure (HF), but the trial results have been mixed. We utilized Preferred Reporting Instrument for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) for scoping reviews with an extensive a priori search strategy for databases: PubMed and Scopus between January 2015 and November 2023. We used the key search terms "door-to-diuretic time" OR "door-to-furosemide time" OR "acute heart failure decongestion". Early D2D time was defined as intravenous (IV) diuretic administration within 30-120 min of patient arrival to the healthcare facility. Articles were included if they met our criteria, were written in the English language, and investigated door-to-diuretic or furosemide time as a decongestive strategy to improve outcomes in patients with acute HF. From 588 articles, 13 articles fulfilled the inclusion criteria after excluding duplicates and articles that did not meet our inclusion criteria. Of these studies, there was 1 meta-analysis and 12 observational cohort/registry-based studies (10 were positive trials and 2 were neutral). The most common outcomes examined were mortality and rehospitalization with early diuretic administration. First, early treatment was associated with lower in-hospital mortality and shorter hospital length of stay. Second, higher doses of furosemide were associated with improved HF symptoms and decreased hospitalization, at the cost of transiently worsening renal function. Third, the evidence is mixed for long-term mortality benefits. Although the impact of early D2D time on HF outcomes is mixed, early diuretic administration appears to be an effective and safe strategy that warrants further investigation in large-scale pragmatic comparative effectiveness trials. Future trials should consider utilizing diuretic efficiency-guided dose escalation and augmented diuresis using high-dose or combination diuretic therapy.

Assessing the Effect of a Pandemic on Emergency Medical Service Response Times and Interventions for Out-of-Hospital Cardiac Arrest.

The coronavirus disease 2019 (COVID-19) pandemic has significantly disrupted emergency medical service (EMS) prehospital care for patients with out-of-hospital cardiac arrest (OHCA), necessitating a thorough assessment of its effects on prehospital time and emergency interventions. Therefore, we aimed to analyze the changes in EMS operations before and after the onset of the pandemic and their potential effects on patient care. We retrospectively reviewed OHCA cases between January 2017 and December 2022, categorizing them into pre-pandemic and pandemic phases. We examined the prehospital time from call intake to hospital arrival, analyzing time segments in detail (on-scene arrival, patient contact, loading, and departure) and procedural frequency/location. Changes in prehospital time, requests for hospital admission, laryngeal tube insertion, and venous line establishment were assessed using a multivariate analysis. Among the 925 OHCA cases, the pandemic phase (n = 467) experienced a 3-minute average prehospital delay compared with the pre-pandemic phase (n = 458) (P < 0.0001). Specifically, on-scene arrival time (adjusted odds ratio (aOR): 2.06; 95% confidence interval (CI): 1.36-3.11), laryngeal tube insertions (aOR: 3.2; 95% CI: 2.1-4.9), and post-transport venous access placements (aOR: 1.67; 95% CI: 1.06-2.63) increased. Hospital admission requests also increased significantly (aOR: 9.5; 95% CI: 2.78-32.7). These findings indicate that pandemic conditions delayed EMS responses and altered clinical practices, highlighting the urgent need for EMS system enhancements to improve on-site interventions. Therefore, addressing these challenges, particularly through strategies that expedite early adrenaline administration, is essential for optimizing patient outcomes.

Early combination of sotrovimab with nirmatrelvir/ritonavir or remdesivir is associated with low rate of persisting SARS CoV-2 infection in immunocompromised outpatients with mild-to-moderate COVID-19: a prospective single-centre study

Background Immunocompromised patients are at high risk of developing persisting/prolonged COVID-19. Data on the early combined use of antivirals and monoclonal antibodies in this population are scarce. Research design and methods We performed an observational, prospective study, enrolling immunocompromised outpatients with mild-to-moderate COVID-19, treated with a combination of sotrovimab plus one antiviral (remdesivir or nirmatrelvir/ritonavir) within 7 days from symptom onset. Primary outcome was hospitalization within 30 days. Secondary outcomes were: needing for oxygen therapy; development of persistent infection; death within 60 days and reinfection or relapse within 90 days. Results We enrolled 52 patients. No patient was hospitalized within 30 days of disease onset, required oxygen administration, died within 60 days, or experienced a reinfection or clinical relapse within 90 days. The clearance rates were 67% and 97% on the 14th day after the end of therapy and at the end of the follow-up period, respectively. Factors associated with longer infection were initiation of therapy 3 days after symptom onset and enrollment for more than 180 days from the beginning of the study. However, only the latter factor was independently associated with a longer SARS-CoV-2 infection, suggesting a loss of efficacy of this strategy with the evolution of SARS-CoV-2 variants. Conclusions Early administration of combination therapy with a direct antiviral and sotrovimab seems to be effective in preventing hospitalization, progression to severe COVID-19, and development of prolonged/persisting SARS-CoV-2 infection in immunocompromised patients.

Early Restrictive vs Liberal Oxygen for Trauma Patients

Early administration of supplemental oxygen for all severely injured trauma patients is recommended, but liberal oxygen treatment has been associated with increased risk of death and respiratory complications. To determine whether an early 8-hour restrictive oxygen strategy compared with a liberal oxygen strategy in adult trauma patients would reduce death and/or major respiratory complications. This randomized controlled trial enrolled adult trauma patients transferred directly to hospitals, triggering a full trauma team activation with an anticipated hospital stay of a minimum of 24 hours from December 7, 2021, to September 12, 2023. This multicenter trial was conducted at 15 prehospital bases and 5 major trauma centers in Denmark, the Netherlands, and Switzerland. The 30-day follow-up period ended on October 12, 2023. The primary outcome was assessed by medical specialists in anesthesia and intensive care medicine blinded to the randomization. In the prehospital setting or on trauma center admission, patients were randomly assigned 1:1 to a restrictive oxygen strategy (arterial oxygen saturation target of 94%) (n = 733) or liberal oxygen strategy (12-15 L of oxygen per minute or fraction of inspired oxygen of 0.6-1.0) (n = 724) for 8 hours. The primary outcome was a composite of death and/or major respiratory complications within 30 days. The 2 key secondary outcomes, death and major respiratory complications within 30 days, were assessed individually. Among 1979 randomized patients, 1508 completed the trial (median [IQR] age, 50 [31-65] years; 73% male; and median Injury Severity Score was 14 [9-22]). Death and/or major respiratory complications within 30 days occurred in 118 of 733 patients (16.1%) in the restrictive oxygen group and 121 of 724 patients (16.7%) in the liberal oxygen group (odds ratio, 1.01 [95% CI, 0.75 to 1.37]; P = .94; absolute difference, 0.56 percentage points [95% CI, -2.70 to 3.82]). No significant differences were found between groups for each component of the composite outcome. Adverse and serious adverse events were similar across groups, with the exception of atelectasis, which was less common in the restrictive oxygen group compared with the liberal oxygen group (27.6% vs 34.7%, respectively). In adult trauma patients, an early restrictive oxygen strategy compared with a liberal oxygen strategy initiated in the prehospital setting or on trauma center admission for 8 hours did not significantly reduce death and/or major respiratory complications within 30 days. ClinicalTrials.gov Identifier: NCT05146700.

Effect of Early Oral Administration of Doxycycline on Macrolide Resistance in Children with Mycoplasma Pneumoniae Pneumonia: A Retrospective Study

Aims/Background Mycoplasma pneumoniae pneumonia (MPP) is typically a benign and self-limiting disease. This study aimed to investigate the effect of early oral administration of doxycycline on macrolide resistance in children with MPP. Methods This study retrospectively analyzed the clinical data of 173 MPP children treated with macrolides at the Second Affiliated Hospital of Mudanjiang Medical University from March 2020 to March 2023. Nine cases that did not meet the inclusion criteria were excluded, leaving 164 children. They were divided into Group A (early oral administration of doxycycline + macrolide treatment) (n = 85) and Group B (macrolide treatment alone) (n = 79) based on whether early oral administration of doxycycline was given. Drug sensitivity results and adverse reactions after treatment were statistically analyzed. Based on the drug sensitivity results, the MPP children were classified as having either macrolide-resistant mycoplasma pneumoniae (MRMP) or macrolide-sensitive mycoplasma pneumoniae (MSMP) infections. A stratified analysis was performed to compare the disappearance time of fever, disappearance time of shortness of breath, disappearance time of rales, and symptom improvement time on chest X-ray examination, and to further explore the clinical efficacy of early oral administration of doxycycline in different groups of children. Results No significant differences were found in baseline data such as age, sex, and weight between the two groups (p &gt; 0.05). A total of 112 out of 164 children developed macrolide resistance (68.29%), with 47 cases in Group A and 65 cases in Group B, indicating a significant difference between the two groups (p &lt; 0.05). The two groups showed a significant difference in macrolide sensitivity levels after treatment (p &lt; 0.05), with no significant difference in the incidence of adverse reactions (p &gt; 0.05). After treatment, the time to the disappearance of febrile fever, time to disappearance time of fever, disappearance time of shortness of breath, disappearance time of rales, symptom improvement time on chest X-ray examination, and time to administration of macrolides after treatment were shorter in children with MRMP in group A than in children with MRMP in group B (p &lt; 0.05). In contrast, MSMP children in both groups exhibited no significant differences in symptom disappearance time and duration of macrolides treatment (p &gt; 0.05). Conclusion Early oral administration of doxycycline is a safe and effective treatment for MPP. It helps relieve symptoms in MRMP children, shortens the duration of macrolide use, and reduces the incidence of macrolide resistance.