Effect Of Early Use Research Articles

Effectiveness of Early Thiopurine Use in Korean Patients With Moderate-to-Severe Ulcerative Colitis: A Prospective Multicenter Cohort (MOSAIK) Study.

Thiopurines play an important role in the management of steroid-refractory and steroid-dependent ulcerative colitis. However, the effectiveness of the early use of thiopurines in ulcerative colitis remains controversial. In this multicenter prospective cohort (MOSAIK) study, we divided patients with ulcerative colitis into those who underwent early (within 6mo of diagnosis) and late (6mo after diagnosis) thiopurine therapy to determine the effectiveness of early thiopurine treatment. The primary outcome was the cumulative rate of clinical relapse (Mayo score >2 points). Multivariate Cox proportional hazards regression was used to identify independent clinical factors associated with the outcomes. Overall, 333 patients with moderate-to-severe ulcerative colitis were included. Of the 118 patients treated with thiopurines, 65 (55.1%) and 53 (44.9%) received thiopurine therapy within and after 6 months of diagnosis. The cumulative use rate of thiopurines was 38.9% at 3 years after diagnosis. The median initial dose of thiopurines was 0.7mg/kg (0.3 to 2.0); the median maintenance dose was 1.1mg/kg (0.3 to 2.4). The cumulative rate of clinical relapse was not significantly different between patients who started thiopurine therapy within 6 months of diagnosis and those who started therapy 6 months after diagnosis (P=0.712). The presence of extraintestinal manifestations (hazard ratio: 4.674, 95% CI: 1.210-18.061, P=0.025) independently predicted an increased risk of clinical relapse. Patients with ulcerative colitis who received early thiopurine therapy did not differ significantly in terms of clinical relapse compared with those who received late therapy.

P631 Effectiveness of Early Thiopurine Use in Korean Patients with Moderate-to-Severe Ulcerative Colitis: A Prospective Multicenter Cohort (MOSAIK) study

Abstract Background Thiopurines play an important role in the management of steroid-refractory steroid-dependent ulcerative colitis (UC). However, the effectiveness of the early use of thiopurines in UC remains controversial. Methods In this multicenter prospective cohort study, we divided patients with UC into those who underwent early (within 6 months of diagnosis) and late (6 months after diagnosis) thiopurine therapy to determine the effectiveness of early thiopurine treatment. The primary outcome was the cumulative rate of clinical relapse (Mayo score >2 points). Multivariate Cox proportional hazards regression was used to identify independent clinical factors associated with the outcomes. Results Overall, 333 patients with moderate-to-severe UC were included in the MOSAIK study. Of the 118 patients treated with thiopurines, 65 (55.1%) and 53 (44.9%) received thiopurine therapy within and after 6 months of diagnosis. The cumulative use rate of thiopurines was 38.96% at 3 years after diagnosis. The median initial dose of thiopurines was 0.7 mg/kg (0.3–2.0), and the median maintenance dose was 1.1 mg/kg (0.3–2.4). The cumulative rate of clinical relapse was not significantly different between patients who started thiopurine therapy within 6 months of diagnosis and those who started therapy 6 months after diagnosis during a 3–year period (p = 0.712). Multivariate analysis showed that the presence of extraintestinal manifestations (hazard ratio [HR]: 4.674, 95% CI: 1.210–18.061, p = 0.025) independently predicted an increased risk of clinical relapse. Conclusion Patients with UC who received early thiopurine therapy did not differ significantly in terms of clinical relapse compared with those who received late therapy.

Effective early strategy to prevent olfactory and gustatory dysfunction in COVID-19: a randomized controlled trial.

Olfactory and gustatory dysfunctions (OGDs) are key symptoms of coronavirus disease 2019 (COVID-19), which may lead to neurological complications, and lack of effective treatment. This may be because post-disease treatments may be too late to protect the olfactory and gustatory functions. To evaluate the effectiveness of early use of saline nasal irrigation (SNI), corticosteroid nasal spray, and saline or chlorhexidine gluconate mouthwash for preventing OGDs in COVID-19. This study was a double-blind randomized controlled trial. The study was conducted from 5 May to 16 June 2022. We recruited patients from three hospitals who were admitted with COVID-19 but without OGDs on the day of admission. Olfactory and gustatory functions were evaluated using the Taste and Smell Survey and the numerical visual analog scale. Participants were randomized to the saline, drug or control groups. The control group received no intervention, saline group received SNI plus saline nasal spray and mouthwash, and the trial group received SNI plus budesonide nasal spray and chlorhexidine gluconate mouthwash. Participants were assessed again on the day of discharge. A total of 379 patients completed the trial. The prevalence of OGDs was significantly lower in the saline (11.8%, 95% CI, 6.6-19.0%; P < 0.001) and drug (8.3%, 95% CI, 4.1-14.8%; P < 0.001) groups than in the control group (40.0%, 95% CI, 31.8-48.6%). Additionally, both interventions reduced the severity of OGDs. We demonstrated effective strategies for preventing COVID-19-related OGDs, and the findings may guide early management of severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection to reduce the incidence of COVID-19-related complications.

Association between prolonged corticosteroids use in COVID-19 and increased mortality in hospitalized patients: a retrospective study with inverse probability of treatment weighting analysis

BackgroundPrevious studies have demonstrated a beneficial effect of early use of corticosteroids in patients with COVID-19. This study aimed to compare hospitalized patients with COVID-19 who received short-course corticosteroid treatment with those who received prolonged-course corticosteroid treatment to determine whether prolonged use of corticosteroids improves clinical outcomes, including mortality.MethodsThis is a retrospective cohort study including adult patients with positive testing for Sars-CoV-2 hospitalized for more than 10 days. Data were obtained from electronic medical records. Patients were divided into two groups, according to the duration of treatment with corticosteroids: a short-course (10 days) and a prolonged-course (longer than 10 days) group. Inverse probability treatment weighting (IPTW) analysis was used to evaluate whether prolonged use of corticosteroids improved outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were hospital infection and the association of different doses of corticosteroids with hospital mortality. Restricted cubic splines were used to assess the nonlinear association between mortality and dose and duration of corticosteroids use.ResultsWe enrolled 1,539 patients with COVID-19. Among them, 1127 received corticosteroids for more than 10 days (prolonged-course group). The in-hospital mortality was higher in patients that received prolonged course corticosteroids (39.5% vs. 26%, p < 0.001). The IPTW revealed that prolonged use of corticosteroids significantly increased mortality [relative risk (RR) = 1.52, 95% confidence interval (95% CI): 1.24–1.89]. In comparison to short course treatment, the cubic spline analysis showed an inverted U-shaped curve for mortality, with the highest risk associated with the prolonged use at 30 days (RR = 1.50, 95% CI 1.21–1.78).ConclusionsProlonged course of treatment with corticosteroids in hospitalized patients with COVID-19 was associated with higher mortality.

Effects of Antidepressants on COVID-19 Outcomes: Retrospective Study on Large-Scale Electronic Health Record Data.

Antidepressants exert an anticholinergic effect in varying degrees, and various classes of antidepressants can produce a different effect on immune function. While the early use of antidepressants has a notional effect on COVID-19 outcomes, the relationship between the risk of COVID-19 severity and the use of antidepressants has not been properly investigated previously owing to the high costs involved with clinical trials. Large-scale observational data and recent advancements in statistical analysis provide ample opportunity to virtualize a clinical trial to discover the detrimental effects of the early use of antidepressants. We primarily aimed to investigate electronic health records for causal effect estimation and use the data for discovering the causal effects of early antidepressant use on COVID-19 outcomes. As a secondary aim, we developed methods for validating our causal effect estimation pipeline. We used the National COVID Cohort Collaborative (N3C), a database aggregating health history for over 12 million people in the United States, including over 5 million with a positive COVID-19 test. We selected 241,952 COVID-19-positive patients (age >13 years) with at least 1 year of medical history. The study included a 18,584-dimensional covariate vector for each person and 16 different antidepressants. We used propensity score weighting based on the logistic regression method to estimate causal effects on the entire data. Then, we used the Node2Vec embedding method to encode SNOMED-CT (Systematized Nomenclature of Medicine-Clinical Terms) medical codes and applied random forest regression to estimate causal effects. We used both methods to estimate causal effects of antidepressants on COVID-19 outcomes. We also selected few negatively effective conditions for COVID-19 outcomes and estimated their effects using our proposed methods to validate their efficacy. The average treatment effect (ATE) of using any one of the antidepressants was -0.076 (95% CI -0.082 to -0.069; P<.001) with the propensity score weighting method. For the method using SNOMED-CT medical embedding, the ATE of using any one of the antidepressants was -0.423 (95% CI -0.382 to -0.463; P<.001). We applied multiple causal inference methods with novel application of health embeddings to investigate the effects of antidepressants on COVID-19 outcomes. Additionally, we proposed a novel drug effect analysis-based evaluation technique to justify the efficacy of the proposed method. This study offers causal inference methods on large-scale electronic health record data to discover the effects of common antidepressants on COVID-19 hospitalization or a worse outcome. We found that common antidepressants may increase the risk of COVID-19 complications and uncovered a pattern where certain antidepressants were associated with a lower risk of hospitalization. While discovering the detrimental effects of these drugs on outcomes could guide preventive care, identification of beneficial effects would allow us to propose drug repurposing for COVID-19 treatment.

The impact of early therapies for COVID-19 on death, hospitalization and persisting symptoms: a retrospective study

PurposeOral antivirals (nirmatrelvir/ritonavir and molnupiravir), intravenous short treatment of remdesivir and anti-SARS-CoV-2 monoclonal antibodies (mAbs) have been used for early COVID-19 treatments in high risk of disease progression patients. The term long COVID has been used to refer to a range of new, returning, or ongoing symptoms after SARS-CoV-2 infection. Little is known about the impact of such therapies on long COVID.MethodsThis is a retrospective observational study, including all outpatients evaluated from April 2021 to March 2022 in Brescia, Lombardy, northern Italy. Patients were stratified in three groups: (a) treated with mAbs, (b) treated with antivirals drugs and (c) controls (patients eligible for a or b who refused treatment). Data were collected at baseline and at month 1 and 3 (data on self-reported symptoms were collected using a telephone-administered questionnaire). We assessed early COVID-19 therapies effectiveness in preventing hospitalization, death at 1 or 3 months and persisting symptoms at 3 months after the onset of SARS-CoV-2 infection.ResultsA total of 649 patients were included in the study, of which 242 (37.3%) were treated with mAbs, 197 (30.3%) with antiviral drugs and 210 (32.4%) were not treated. Patients most frequently reported cerebro-cardiovascular diseases (36.7%) followed by obesity (22%). Overall, 29 patients (4.5%) died or were hospitalized at 1 or 3-month follow-up. Death or hospitalization was positively associated with older ages, with a significant linear trend (OR 3.05; 95% CI 1.16–8.06, for patients aged 80 or more years compared to those aged less than 65). Data on long COVID at 3 months were available for 323 (49.8%) patients. A positive association emerged for females compared to men, with an OR of 2.14 (95% CI 1.30–3.53) for any symptoms. Conversely, inverse associations were found for treatment groups as compared to the control one, with significant estimates among patients treated with antiviral drugs for any symptoms (OR 0.43, 95% CI 0.21–0.87) and patients treated with mAbs for any neuro-behavioral symptoms (OR 0.48, 95% CI 0.25–0.92).ConclusionsWe report beneficial effect of early use of anti-SARS-CoV-2 antivirals and mAbs on long COVID.

Impact of early initiation of renin-angiotensin blockade on renal function and clinical outcomes in patients with hypertensive emergency: a retrospective cohort study

BackgroundHypertensive emergency is a critical disease that causes multifaceted sequelae, including end-stage kidney disease and cardiovascular disease. Although the renin–angiotensin–aldosterone (RAA) system is enormously activated in this disease, there are few reports that attempt to characterize the effect of early use of RAA inhibitors (RASi) on the temporal course of kidney function.MethodsThis retrospective cohort study was conducted to clarify whether the early use of RASi during hospitalization offered more favorable benefits on short-term renal function and long-term renal outcomes in patients with hypertensive emergencies. We enrolled a total of 49 patients who visited our medical center with acute severe hypertension and multiple organ dysfunction between April 2012 and August 2020. Upon admission, the patients were treated with intravenous followed by oral antihypertensive drugs, including RASi and Ca channel blockers (CCB). Kidney function as well as other laboratory and clinical parameters were compared between RASi-treated and CCB- treated group over 2 years.ResultsAntihypertensive treatment effectively reduced blood pressure from 222 ± 28/142 ± 21 to 141 ± 18/87 ± 14 mmHg at 2 weeks and eGFR was gradually restored from 33.2 ± 23.3 to 40.4 ± 22.5 mL/min/1.73m2 at 1 year. The renal effect of antihypertensive drugs was particularly conspicuous when RASi was started in combination with other conventional antihypertensive drugs at the early period of hospitalization (2nd day [IQR: 1–5.5]) and even in patients with moderately to severely diminished eGFR (< 30 mL/min/1.73 m2) on admission. In contrast, CCB modestly restored eGFR during the observation period. Furthermore, renal survival probabilities were progressively deteriorated in patients who had manifested reduced eGFR (< 15 mL/min/1.73 m2) or massive proteinuria (urine protein/creatinine ≥ 3.5 g/gCr) on admission. Early use of RASi was associated with a favorable 2-year renal survival probability (0.90 [95%CI: 0.77–1.0] vs. 0.63 [95%CI: 0.34–0.92] for RASi ( +) and RASi (-), respectively, p = 0.036) whereas no apparent difference in renal survival was noted for CCB.ConclusionsEarly use of RASi contributes to the renal functional recovery from acute reduction in eGFR among patients with hypertensive emergencies. Furthermore, RASi offers more favorable effect on 2-year renal survival, compared with CCB.

A pilot study on the effects of early use of valproate sodium on neuroinflammation after traumatic brain injury

To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI). A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge. Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF-α, and IL-1β on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1β on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1β than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05). Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI.

Real-world effectiveness of sotrovimab and remdesivir for early treatment of high-risk hospitalized COVID-19 patients:Apropensity score adjusted retrospective cohort study.

Early treatment of high-risk COVID-19 patients may prevent disease progression. However, there are limited data to support treatment of hospitalized or fully vaccinated patients with mild-to-moderate disease. In this retrospective cohort study, we studied the effect of early use of sotrovimab and remdesivir in high-risk hospitalized COVID-19 patients. We included PCR-confirmed COVID-19 patients admitted to the National Centre for Infectious Diseases who presented within the first 5 days of illness, and who were not requiring oxygen or ICU care at presentation. Sotrovimab- and remdesivir-treated groups were compared with control (no early treatment). A multiple propensity-score adjusted multivariable regression analysis was conducted with a composite primary endpoint of in-hospital deterioration (oxygen requirement, ICU admission, or mortality). Of 1118 patients, 841 were in the control group, 106 in the sotrovimab group and 169 in the remdesivir group. The median age was 63 years (IQR 46-74 years) and 505 (45.2%) were female. In unvaccinated patients, both remdesivir and sotrovimab treatment were protective (adjusted odds ratio [aOR] 0.19, 95% CI 0.064-0.60 and 0.18 [95% CI 0.066-0.47]), respectively. Contrarily, among the vaccinated patients there was no significant treatment effect with early remdesivir treatment (aOR 2.51, 95% CI 0.83-7.57, p = 0.10). Remdesivir and sotrovimab treatment, given early in the disease course to unvaccinated high-risk patients, was effective in reducing the risk of in-hospital deterioration and severe disease. This effect was not seen in fully vaccinated patients, which may be due to a small sample size or residual confounding.

EE147 Estimating the Causal Effect of Early Use of Erythropoietic Stimulating Agents in Intermediate-1 to Low-Risk MDS Patients: An Application of the Longitudinal Targeted Maximum Likelihood Estimation

To demonstrate the use of Longitudinal Targeted Maximum Likelihood Estimation (LTMLE) methods to derive causal average treatment effect estimates for survival and health-related quality of life (measured by the EQ5D) outcomes from longitudinal real-world data with risk of bias from immortal-time and time-varying confounding.

Age of onset and alcohol and cannabis use disorders among Mexican American young adults: Robust substance-specific effects of early use as a risk factor

We investigated the substance-specific and cross-substance risk associated with early onset (before age 15) of drunkenness and cannabis use in the subsequent development of alcohol (AUD) and cannabis use disorder (CUD) in Mexican American young adults. Survival analyses employed Cox proportional hazards models for AUD and CUD, separately. In cross-risk analyses, we modeled estimates for those participants reporting lifetime use of both substances. Early onset of drunkenness and early onset of cannabis use were associated with shorter time to AUD and CUD, respectively, even after accounting for psychiatric disorders. While there were no cross-risk associations, adjusting for psychiatric disorders and early onset cannabis use attenuated the association of early drunkenness with AUD.

Early Use of Methylene Blue in Vasoplegic Syndrome: A 10-Year Propensity Score-Matched Cohort Study.

Background: Vasoplegic syndrome is associated with increased morbidity and mortality in patients undergoing cardiac surgery. This retrospective, single-center study aimed to evaluate the effect of early use of methylene blue (MB) on hemodynamics after an intraoperative diagnosis of vasoplegic syndrome (VS). Methods: Over a 10-year period, all patients diagnosed with intraoperative VS (hypotension despite treatment with norepinephrine ≥0.3 μg/kg/min and vasopressin ≥1 IE/h) while undergoing heart surgery and cardiopulmonary bypass were identified, and their data were examined. The intervention group received MB (2 mg/kg intravenous) within 15 min after the diagnosis of vasoplegia, while the control group received standard therapy. The two groups were matched using propensity scores. Results: Of the 1022 patients identified with VS, 221 received MB intraoperatively, and among them, 60 patients received MB within 15 min after the diagnosis of VS. After early MB application, mean arterial pressure was significantly higher, and vasopressor support was significantly lower within the first hour (p = 0.015) after the diagnosis of vasoplegia, resulting in a lower cumulative amount of norepinephrine (p = 0.018) and vasopressin (p = 0.003). The intraoperative need of fresh frozen plasma in the intervention group was lower compared to the control group (p = 0.015). Additionally, the intervention group had higher creatinine values in the first three postoperative days (p = 0.036) without changes in dialysis incidence. The 90-day survival did not differ significantly (p = 0.270). Conclusion: Our results indicate the additive effects of MB use during VS compared to standard vasopressor therapy only. Early MB administration for VS may significantly improve the patients’ hemodynamics with minor side effects.

Effect of Early Use of Maternal Iron and Folic Acid Supplements on Neonatal Survival: A Community-Based Cluster Randomised Controlled Trial in Rural Bangladesh (Shonjibon Trial)

Effect of Early Use of Maternal Iron and Folic Acid Supplements on Neonatal Survival: A Community-Based Cluster Randomised Controlled Trial in Rural Bangladesh (Shonjibon Trial)

Interventions to enable communication for adult patients requiring an artificial airway with or without mechanical ventilator support.

Inability to communicate in a manner that can be understood causes extreme distress for people requiring an artificial airway and has implications for care quality and patient safety. Options for aided communication include non-vocal, speech-generating, and voice-enabling aids. To assess effectiveness of communication aids for people requiring an artificial airway (endotracheal or tracheostomy tube), defined as the proportion of people able to: use a non-vocal communication aid to communicate at least one symptom, need, or preference; or use a voice-enabling communication aid to phonate to produce at least one intelligible word. To assess time to communication/phonation; perceptions of communication; communication quality/success; quality of life; psychological distress; length of stay and costs; and adverse events. We searched the Cochrane Library (Wiley version), MEDLINE (OvidSP), Embase (OvidSP), three other databases, and grey literature from inception to 30 July 2020. We included randomised controlled trials (RCTs), quasi-RCTs, cluster-RCTs, controlled non-randomised parallel group, and before-after studies evaluating communication aids used in adults with an artificial airway. We used standard methodological procedures recommended by Cochrane. Two review authors independently performed data extraction and assessment of risk of bias. We included 11 studies (1931 participants) conducted in intensive care units (ICUs). Eight evaluated non-vocal communication aids and three voice-enabling aids. Usual care was the comparator for all. For six studies, this comprised no aid; usual care in the remaining five studies comprised use of various communication aids. Overall, our confidence in results regarding effectiveness of communication interventions was very low due to imprecision, measurement heterogeneity, inconsistency in results, and most studies at high or unclear risk of bias across multiple domains. No non-vocal aid studies reported our primary outcome. We are uncertain of the effects of early use of a voice-enabling aid compared to routine use on ability to phonate at least one intelligible word (risk ratio (RR) 3.03, 95% confidence interval (CI) 0.18 to 50.08; 2 studies; very low-certainty evidence). Compared to usual care without aids, we are uncertain about effects of a non-vocal aid (communication board) on patientsatisfaction (standardised mean difference (SMD) 2.92, 95% CI 1.52 to 4.33; 4 studies; very low-certainty evidence). No studies of non-vocal aids reported quality of life. Low-certainty evidence from two studies suggests early use of a voice-enabling aid may have no effect on quality of life (MD 2.27, 95% CI -7.21 to 11.75). Conceptual differences in measures of psychological distress precluded data pooling; however, intervention arm participants reported less distress suggesting there might be benefit, but our certainty in the evidence is very low. Low-certainty evidence suggest voice-enabling aids have little or no effect on ICU length of stay; we were unable to determine effects of non-vocal aids. Three studies reported different adverse events (physical restraint use, bleeding following tracheostomy, and respiratory parameters indicating respiratory decompensation). Adverse event rates were similar between arms in all three studies. However, uncertainty remains as to any harm associated with communication aids. Due to a lack of high-quality studies, imprecision, inconsistency of results, and measurement heterogeneity, the evidence provides insufficient information to guide practice as to which communication aid is more appropriate and when to use them. Understanding effectiveness of communication aids would benefit from development of a core outcome measurement set.

Efficacy of tranexamic acid in bleeding pediatric trauma patients in emergency department

 Pediatric injuries are the main cause of death among children in the United States. Up to 70% of pediatric patients even die before reaching a specialized trauma center. Pediatric injuries represent the majority of hospital admissions and visits to Emergency Department (ED). The physical and psychological needs of any traumatized child and his family must be considered, as any minor injuries may have a long-term impact physically and mentally, and could impair children’s quality of life.  TXA is an antifibrinolytic drug used to reduce surgical bleeding and the need for perioperative blood transfusion. TXA is reversibly bind to lysine-binding receptors on plasminogen, displacing plasminogen from the surface of fibrin and reducing the conversion of plasminogen to plasmin. Thus help to prevent fibrin and clot degradation and preserve the fibrin matrix framework. Aim of the Work The aim of this study is to evaluate the effect of early use of tranexamic acid (TXA) on outcomes of pediatric trauma patients in the Emergency Department.

MO373EXPERIENCE OF EXTRACORPOREAL BLOOD PURIFICATION METHODS APPLICATION TO PATIENTS WITH SEVERE COVID - 19

Background and AimsIn the rapidly changing conditions of life due to the COVID - 19 pandemic, the medical society around the world have faced with the question of treatment previously unknown, multi-faceted and insidious infection. The coronavirus infection has forced doctors to reconsider the tactics of intensive care patients in critical condition. To date, overall mortality rate from COVID – 19 varied from 8.11 to 120.85 per 100.000 population (Johns Hopkins University mortality analyses). Mortality rate in extremely severe cases exceeds 60% - 78% (Yang et al., Lancet Respiratory Medicine, 2020. Zhou et al., Lancet, 2020).We would like to share our clinical experience of extracorporeal blood purification methods application to patients in ICU with various clinical manifestations, as well as the presence of comorbid pathology.MethodWe conducted a retrospective analysis of 239 medical records of patients hospitalized in the ICU of JSC NRCSC Nur-Sultan, Kazakhstan because of severe course of COVID 19. Period of hospitalization from 16.06.2020 to 29.09.2020, the total number of beds - 97, in the ICU - 25.ResultsThe total number of patients with COVID -19 - 239 patients. In ICU -67 patients. Patients required in renal replacement therapy (RRT) – 31 patients.Among patients on RRT males-28 (90.3%) - female-3 (9.67%).Mean age-60 years.Distribution of the comorbid pathology.NOComorbid pathologyN = 31Diabetes insipidus10 (32,2%)Sepsis5 (16.1%)MODS6 (19.3%)Acute kidney damage 2 (KDIGO 2018)9 (29%)Acute kidney damage 3 (KDIGO 2018)5 (16.1%)Anuria11 (35.48%)Acute respiratory failure 324 (77.4%)ARDS19 (61.29%)Artificial lung ventilation28 (90.32%)COPD3 (9.67%)Hypertension9 (29%)Ischemic heart disease6 (19.3%)Obesity9 (29%)Cytokine storm19 (61.29%)ECMO15 (48.38%)LVAD1 (3.22%)Gastric ulcer1 (3.22%)Indications for RRT: acute respiratory failure in the absence of heart failure or fluid overload; presence of diffuse alveolar damage (DAD) (detected by high-resolution CT); PaO2 / FiO2 ≤ 300 mm Hg Duration:> 6-24 hours per column with a blood flow rate of 80-120 ml/min. In addition, indications for the urgent start of extracorporeal treatment are:signs of severe coronavirus infection (respiratory rate ≥ 30 per minute and / or blood oxygen saturation ≤ 93% and / or PO2/FiO2 index ≤ 200 mmHg;detection of lung lesion progression using one of the imaging methods ≥10% per day;progressive increase in the level of inflammatory markers (CRP, IL-6, etc.).The duration of hospitalization in the ICU – 12.54 days.Combinations and duration of the procedures.Name of the procedure(n)Duration (in hour)HP HA330 + CVVHF/CVVHDF 2+1+1 (n=33)> 1224 чHP Cytosorb© + CVVHF/CVVHDF 1+1+1(n=5)> 24 чHP HA330II+ CVVHF/CVVHDF 2+1+1 (n=31)> 1224 чPE + CVVHF/CVVHDF 2+1+1(n=7)> 624 чHP2+1+1(n=14)> 3-6 чFootnote: combinations and duration of use are in accordance with the recommendations of Ronco C. et al. (2020).Laboratory data - Leukocyte, CRP, Interleukine, procalcitonin, Creatinin, presepsin in dynamics.Laboratory dataBefore blood purificationAfter the 1st procedureAfter the 2nd procedureAfter the 3d procedurep valueLeukocyte15.3013.3110.688.230.01CRP17.9116.1214.1013.020.02Il - 6260.77205.82201.188188.90.027PCT26.5812.134.345.560.01Creat2.331.771.891.340.01Presepsin2420.242788.811783.562063.410.18General Mortality – 37 from 239 (15.5%)Mortality in ICU – 37 from 67 (55.2%)According to literature review, the mortality rate of patients with severe COVID - 19 in the ICU (Fawad Rahim et al, Cureus . 2020 Oct 12;12(10):e10906. doi: 10.7759/cureus.10906.) without the use of CRRT exceeds 70-77%.)ConclusionOur analysis had showed a positive effect of early use (1 day of hospitalization) of extracorporeal methods of blood purification, on a decreasing of inflammation indicators, as well as positive survival rate of patients with severe COVID-19 course in ICU conditions.

Life saving effect of early use of convalescent plasma in Covid-19 treatment

Life saving effect of early use of convalescent plasma in Covid-19 treatment

Effect of early use of ivabradine on left ventricular remodeling after primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction: A pilot test.

ObjectiveTo investigate the effect of early use of ivabradine on left ventricular remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST‐segment elevation myocardial infarction (STEMI).MethodsA total of 66 STEMI patients with sinus rhythm and the resting heart rate ≥80 bpm after successful emergency PCI were included. The patients in the test group were treated with ivabradine combined with metoprolol at 12 hr after PCI, while the control group was given only metoprolol orally. Their resting heart rate was controlled to <70 bpm at discharge and followed for 180 days. Heart rate and blood pressure were measured regularly. Echocardiogram was performed. N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), high sensitivity troponin T, high sensitivity troponin I, and high sensitivity C‐reactive protein were measured. The major adverse cardiovascular events during hospitalization and follow‐up period were recorded.ResultsCompared with the control group, the heart rate of the test group decreased significantly (p < .05). Compared with the control group, the left ventricular end‐diastolic volume and left ventricular end‐systolic volume were significantly decreased while left ventricular ejection fraction was significantly increased in the test group at 90 days after operation. NT‐proBNP of the test group was significantly lower than that of the control group at 7 days after operation (p < .05).ConclusionFor STEMI patients, early use of ivabradine combined with standard therapy such as β‐blocker after successful reperfusion can achieve effective heart rate control, with great safety and tolerance. But the effect of ivabradine on left ventricular remodeling is uncertain.

The Metabolic Effects of Pre-probiotic Supplementation After Roux-en-Y Gastric Bypass (RYGB) Surgery: a Prospective, Randomized Controlled Study.

Following Roux-en-Y gastric bypass (RYGB), positive alterations are observed in gut microbiota and intestinal peptides. Previous studies demonstrated similar alterations observed in cases when pre-probiotics are used without surgery. The aim of this trial was to evaluate the effectiveness of early use of pre-probiotics after RYGB. The operation and follow-up of the patients were performed at Istanbul University Medical Faculty. Thirty-two patients who had undergone RYGB were randomized to pre-probiotic group (PreProBG, n = 16; 200g/day yogurt plus 10g/day inulin+oligofructose) and probiotic group (ProBG, n = 16; 200g/day yogurt only) for 6months. Blood samples (glucose, insulin, A1c, GLP-1, PYY), anthropometric measurements, and appetite ratings have been evaluated at baseline and 3 (m3) and 6 (m6) months after RYGB. Initial anthropometric measurements and appetite ratings decreased significantly after surgery and there were no significant differences between the groups. The decrease of area under the curve(insulin) was less and has a positive correlation with the changes in anthropometric measurements in PreProBG. GLP-1 and PYY which increased dramatically after surgery in all patients were higher in PreProBG. But this increase had a negative correlation with the changes in anthropometric measurements during the study. Increased insulin, GLP-1, and PYY secretion was more enhanced by pre-probiotic use in early postoperative period. But this increase not only in anthropometric measurements but also in appetite ratings affects negatively, contrary to expectations. In summary, it should be investigated with new studies that use of pre-probiotics in the late postoperative period may be more effective in patients with weak insulin and incretin response and therefore insufficient weight loss. Trial Registration clinicaltrials.gov Identifier: NCT03517345.

Adolescent Externalizing Psychopathology and Its Prospective Relationship to Marijuana Use Development from Age 14 to 30: Replication Across Independent Longitudinal Twin Samples.

Externalizing psychopathology in early adolescence is a highly heritable risk factor for drug use, yet how it relates to marijuana use development is not well-characterized. We evaluate this issue in independent twin samples from Colorado (N = 2608) and Minnesota (N = 3630), assessed from adolescence to early adulthood. We used a biometric latent growth model of marijuana use frequency with data from up to five waves of assessment from ages 14 to 30, to examine change in marijuana use and its relationship with a factor model of adolescent externalizing psychopathology. The factor structure of adolescent externalizing psychopathology was similar across samples, as was the association between that common factor and early marijuana use (Minnesota r = 0.67 [0.60, 0.75]; Colorado r = 0.69 [0.59, 0.78]), and increase in use (Minnesota r = 0.18 [0.10, 0.26]; Colorado r = 0.20 [0.07, 0.34]). Early use was moderately heritable in both samples (Minnesota h2 = 0.57 [0.37, 0.79]; Colorado h2 = 0.42 [0.14, 0.73]). Increase in use was highly heritable in Minnesota (h2 = 0.82 [0.72, 0.88]), less so in Colorado (h2 = 0.22 [0.01, 0.66]), and shared environmental effects were larger in Colorado (c2 = 0.55 [0.14, 0.83]) than Minnesota (c2 = 0 [0, 0.06]). We found moderate genetic correlations between externalizing psychopathology and early use in both samples. Finally, additional analyses in the Minnesota sample indicated that marijuana use decreased during the late 20s. This decline is strongly heritable (h2 = 0.73 [0.49, 0.91]) and moderately negatively correlated with adolescent externalizing psychopathology (r = - 0.41 [- 0.54, - 0.28]). Adolescent externalizing psychopathology is genetically correlated with change in late adolescent marijuana use (late teens, early 20s), as well as maintenance of use in early adulthood (late 20 s) even after controlling for the effects of early use.