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The value of ustekinumab (UST) therapeutic drug monitoring (TDM) in clinical practice remains unclear. This study examined the impact of UST TDM on clinical decision making in patients with Crohn’s disease (CD). A total of 110 consecutive UST-treated CD patients were enrolled in this multicenter, single-arm cross-sectional study. During a single study visit, clinical decisions, disease characteristics, and serum and fecal samples were obtained. The primary outcome was congruency of the actual and two hypothetical clinical decisions based on provision of UST TDM (with and without fecal calprotectin [FCP]) to participating clinicians. Decisions were compared against those of a review panel. A sub-study retrospectively measured the associations of clinical outcomes at the next follow-up visit with serum UST concentration [UST]. No differences in the pattern of decisions by clinicians were observed before and after provision of UST TDM (P = 1.0) or UST TDM + FCP (P = 0.86). However, 39% (TDM) and 50% (TDM + FCP) of hypothetical decisions differed from the initial decisions. The review panel’s decisions differed with the addition of TDM + FCP (P = 0.0006), but not TDM alone (P = 0.16). The sub-study (n = 53) failed to detect an association between therapeutic serum [UST] at the initial study visit and clinical outcomes at the next visit. In consecutive CD patients treated with UST, the addition of TDM into routine clinical practice did not significantly impact clinical decisions and there was no association between short-term clinical outcomes and serum [UST]. Further studies are warranted before clinicians routinely implement UST TDM into clinical practice.

BACKGROUND Management of coagulopathy during major oncologic surgery can be multifactorial and challenging. Viscoelastic assays (VEAs) can be useful in providing vital data about the mechanism of coagulopathy in these dynamic circumstances. OBJECTIVES A prospective nonrandomized observational study with the aim of describing the coagulation parameters of patients undergoing major oncologic surgery using the Quantra® and TEG® 5000 systems. Our secondary objectives included the correlation between Quantra and TEG parameters, and the times to result for both technologies. METHODS This study included 74 adults undergoing oncologic surgery with an anticipated blood loss of more than 500 ml. For each subject, whole blood samples for each device were collected at multiple points perioperatively for comparison. RESULTS Correlation coefficients between Quantra and TEG parameters were 0.8 and above, indicating a very strong correlation (p

Proton density fat fraction (PDFF) is a validated biomarker of tissue fat quantification. However, validation has been limited to single-center or multi-center series using non-FDA-approved software. Thus, we assess the bias, linearity, and long-term reproducibility of PDFF obtained using commercial PDFF packages from several vendors. Over 35 months, 438 subjects and 16 volunteers from a multi-center observational trial underwent PDFF MRI measurements using a 3-T MR system from one of three different vendors or a 1.5-T system from one vendor. Fat-water phantom sets were measured as part of each subject’s examination. Manual region-of-interest measurements on the %fat image, then cross-sectional bias, linearity, and long-term reproducibility were assessed. Three hundred ninety-two phantom measurements were evaluable (90%). Bias ranged from 2.4 to - 3.8% for the lowest to the highest weight %fat. Regression fits of PDFF against synthesis weight %fat showed negligible non-linear effects and a linear slope of 0.94 (95% confidence interval: 0.938, 0.947). We observed significant vendor (p < 0.001) and field strength (p < 0.001) differences in bias and longitudinal variability. When the results were pooled across sites, vendors, and field strengths, the estimated reproducibility coefficient was 6.93% (95% CI: 6.25%, 7.81%). This study demonstrated good linearity, accuracy, and reproducibility for all investigated manufacturers and field strengths. However, significant vendor-dependent and field strength–dependent bias were found. While longitudinal PDFF measurements may be made using different field strength or vendor MR systems, if the MR system is not the same, based on these results, only PDFF changes ≥ 7% can be considered a true difference. • Phantom fat fraction (PDFF) MRI measurements over 35 months demonstrated good linearity, accuracy, and reproducibility for the vendor systems investigated. • Non-linear effects were negligible (linear slope of 0.94) over 0–100% fat; however, significant vendor (p < 0.001) and field strength (p

Achtergrond Fibroadenoom van de borst is de meest voorkomende kwaal bij vrouwen met een aanzienlijk risico op overlijden. Uit de beschikbare literatuur blijkt dat borsttumoren verdwijnen door homeopathische behandeling. De huidige studie evalueerde de rol van homeopathische behandeling op borstfibroadenoma met behulp van ‘Triple assessment criteria’ (dubbel blind) en onderzoekt of homeopathische geneesmiddelen therapeutisch effect teweeg brengen door het veranderen van de oestrogeen en progesteron receptor (ER/PR) status op tumorweefsel. Materialen en Methoden Een open-label, prospectieve, single-arm, observationele studie werd uitgevoerd bij 64 vrouwelijke patiënten met fibroadenoom van de borst. Er werden drievoudige beoordelingscriteria gebruikt om de doeltreffendheid van de homeopathische behandeling van borstfibroadenomen te onderzoeken. Geïndividualiseerde homeopathische geneesmiddelen werden voorgeschreven. De meetresultaten vertoonden veranderingen in het klinisch beeld en het aantal en de omvang van de knobbels door middel van ultrasoonmammografie. ER/PR studie werd uitgevoerd door immunohistochemie met gebruik van quick score analyse. Resultaten Bij 23 gevallen (35,93%) van fibroadenomen was er na de behandeling geen knobbel meer meetbaar. Gedeeltelijke verbetering werd waargenomen in 22 gevallen (34,37%) met significante vermindering van de gemiddelde grootte (p Conclusie De studie toont aan dat de therapeutische effecten van toediening van geïndividualiseerde homeopathische geneesmiddelen een belangrijke rol spelen bij de behandeling van fibroadenomen van de borst. De resultaten van ER/PR laten een significante vermindering van ER zien, wat suggereert dat homeopathische geneesmiddelen een remmend effect hebben op ER.

BACKGROUND Preoperative use of platelet function tests contributes to the decrease of re-intervention rate due to bleeding and the necessity of transfusion in coronary artery bypass grafting (CABG) patients. The aim was to investigate the predictive value and to justify routine preoperative use of multiple electrode aggregometry in these patients. METHODS A prospective observational trial which included 416 consecutive patients subjected to elective isolated CABG was conducted. The Multiplate® test was used to assess platelet function. Platelet function test results, postoperative blood loss, and transfusion requirements were compared between high and low bleeding risk patients. Receiver operating characteristic analysis was performed to assess the sensitivity and specificity of the arachidonic acid (ASPI) and adenosine di-phosphate high sensitive (ADPHS) tests. RESULTS ADPHS and ASPI test results significantly predicted total bleeding > 1000 ml (AUC, 0.685, p

Introduction: Rates of pelvic cancer are growing globally with around half of these patients receiving radiotherapy. In a small proportion, radiotherapy results in significant late radiation tissue injury (LRTI) to surrounding tissue, most commonly affecting the bladder and bowel mucosa. We conducted a combined prospective and retrospective observational trial to establish the effectiveness of hyperbaric oxygen treatment (HBOT) in improving the symptoms and signs of LRTI in these patients. Methods: Fifty-two patients were included after receiving radiotherapy for cancers of the bowel, bladder, cervix, prostate or vulva. They received HBOT at 203-243 kPa (2.0-2.4 atmospheres absolute (atm abs)) for 90 minutes with the median number of treatments being 30 (IQR 1). Late effects normal tissues - subjective, objective, management, analytic (LENT-SOMA) scores were recorded before and after treatment. Results: The mean LENT-SOMA scores before and after HBOT were 11.7 (SD 5.3) and 8.1 (5.1) respectively. This reduction in score of 3.7 (95% CI 2.6 to 4.8) was statistically significant (P < 0.001). For radiation cystitis the mean reduction was 3.7 (95% CI 2.4 to 5.0, P < 0.001) and for radiation proctitis was 3.8 (95% CI 1.4 to 6.1, P = 0.004). There were no significant adverse effects recorded. Conclusions: Hyperbaric oxygen treatment may be an effective and safe treatment for pelvic late tissue radiation injury.

Background There is a high incidence of endotracheal tube malposition in neonates and small infants. Yet, verification of accurate endotracheal tube location via radiographic imaging involves radiation exposure. Aims This study aimed to identify demographic and clinical parameters associated with accurate endotracheal tube positioning. Methods We conducted a prospective single-center study with term and preterm neonates and small infants between January 2018 and November 2019. We investigated correlations between ten variables and accurate endotracheal tube position. Results One hundred and sixty eight nasal intubations in 139 patients (weight 390-5000 g) were analyzed. An accurate tube position was confirmed by radiographic imaging in 71.4% of the intubations. The endotracheal tube was high in 8.3% and low in 20.2% of the cases. Male gender was the only variable that significantly correlated with an accurate endotracheal tube position (OR 2.5; 95% CI: 1.3, 5.0; P = .010). Conclusion So far, no parameter has proven to be able to predict accurate endotracheal tube position in neonates reliably. These findings emphasize the indispensability of postintubation imaging in neonates and small infants.

Background HIT diagnosis typically uses complementary diagnostic assays (eg, a PF4‐dependent enzyme‐immunoassay [EIA] and a platelet activation assay such as the serotonin‐release assay [SRA]). Objectives To determine whether the combination of two automated assays—a latex immunoturbidimetric assay (LIA) that evaluates competitive inhibition of a HIT‐like monoclonal antibody and a chemiluminescence immunoassay (CLIA) for detecting anti‐PF4/heparin IgG—optimizes diagnostic sensitivity while also yielding good specificity, particularly at high assay reactivities. Patients/Methods We determined operating characteristics using combined LIA/CLIA results from a HIT observational trial (n = 430; derivation cohort) and 147 consecutive patients with HIT (n = 147; supplementary derivation cohort). We also evaluated 678 consecutive samples referred for HIT testing (replication cohort). LIA/CLIA reactivities were scored individually as “negative” (

OBJECTIVE To evaluate the diagnostic performance of perfusion pressure (PP) thresholds for fasciotomy. DESIGN Prospective observational study. SETTING Seven Level-1 trauma centers. PATIENTS/PARTICIPANTS One hundred fifty adults with severe leg injuries and ≥2 hours of continuous PP data who had been enrolled in a multicenter observational trial designed to develop a clinical prediction rule for acute compartment syndrome (ACS). MAIN OUTCOME MEASUREMENTS For each patient, a given PP criterion was positive if it was below the specified threshold for at least 2 consecutive hours. The diagnostic performance of PP thresholds between 10 and 30 mm Hg was determined using 2 reference standards for comparison: (1) the likelihood of ACS as determined by an expert panel who reviewed each patient's data portfolio or (2) whether the patient underwent fasciotomy. RESULTS Using the likelihood of ACS as the diagnostic standard (ACS considered present if median likelihood ≥70%, absent if

An amendment to this paper has been published and can be accessed via the original article.

Introduction: The duration of labor and the immediate puerperium are affected by obstetric and maternal-fetal factors. Interventions to provide obstetric analgesia may prolong the hospital stay. Objective: To characterize the procedure for obstetric analgesia and describe the time elapsed between analgesia and delivery and postpartum surveillance in healthy mothers. Methods: Observational, descriptive trial. The time elapsed between analgesia and delivery, and postpartum surveillance were measured in healthy pregnant women with vaginal delivery and a prescription of a neuraxial analgesia technique. Results: 226 patients were included. The mean time elapsed between analgesia an delivery was 4 hours (IQR 3-7). 50.7 % (n=114) received early analgesia (neuraxial technique with ≤ 4 centimeters of cervical dilatation), of which 48.2 % (n = 109) experienced a duration of analgesia until delivery longer than expected. The mean cervical dilatation at the time of the neuraxial approach was 4 centimeters (IQR 4-6) and the epidural technique was the most frequently used - 92.9 % (n = 210). The mean postpartum surveillance was 20 hours (IQR 15-27). Conclusions: Half of the patients included received early analgesia and around fifty percent of them took longer than expected in completing delivery. The postpartum surveillance time was consistent with the provisions of the Ministry of Health and with the current trend of a short postpartum surveillance aimed at early hospital discharge and the benefits thereof. Resumen Introducción: La duración del trabajo de parto y del puerperio inmediato se afectan por factores obstétricos y maternofetales. Las intervenciones para brindar analgesia obstétrica pudieran prolongar el tiempo total de estancia hospitalaria. Objetivo: Caracterizar el procedimiento de analgesia obstétrica y describir los tiempos entre analgesia y parto y vigilancia posparto en maternas sanas. Métodos: Estudio descriptivo observacional. Se midieron los tiempos entre analgesia y parto y vigilancia posparto en gestantes sanas, cuya vía final del parto fuera vaginal con indicación y aplicación de alguna técnica de analgesia neuroaxial. Resultados: Se incluyeron 226 pacientes. La mediana del tiempo de analgesia hasta el parto fue de 4 horas (RIC 3-7); el 50,7 % (n = 114) recibió analgesia temprana (técnica neuroaxial a ≤ 4 centímetros de dilatación cervical), de las cuales el 48,2 % (n = 109) tuvo un tiempo de analgesia hasta el parto mayor al esperado. La mediana de dilatación cervical al momento del abordaje del neuroeje fue de 4 centímetros (RIC 4-6) y la técnica epidural fue la más frecuente, 92,9 % (n = 210). La mediana de tiempo de vigilancia posparto fue de 20 horas (RIC 15-27). Conclusiones: La mitad de las pacientes incluidas recibió analgesia temprana y cerca de la mitad tardó más de lo esperado en finalizar su gestación. El tiempo de vigilancia posparto fue acorde con lo establecido por el Ministerio de Salud y con la tendencia actual de una vigilancia posparto corta que apunte a un alta temprana y sus beneficios.

Background The role of image-derived biomarkers in recurrent oligometastatic Prostate Cancer (PCa) is unexplored. This paper aimed to evaluate [18F]FMCH PET/CT radiomic analysis in patients with recurrent PCa after primary radical therapy. Specifically, we tested intra-patient lesions similarity in oligometastatic and plurimetastatic PCa, comparing the two most used definitions of oligometastatic disease. Methods PCa patients eligible for [18F]FMCH PET/CT presenting biochemical failure after first-line curative treatments were invited to participate in this prospective observational trial. PET/CT images of 92 patients were visually and quantitatively analyzed. Each patient was classified as oligometastatic or plurimetastatic according to the total number of detected lesions (up to 3 and up to 5 or > 3 and > 5, respectively). Univariate and intra-patient lesions' similarity analysis were performed. Results [18F]FMCH PET/CT identified 370 lesions, anatomically classified as regional lymph nodes and distant metastases. Thirty-eight and 54 patients were designed oligometastatic and plurimetastatic, respectively, using a 3-lesion threshold. The number of oligometastic scaled up to 60 patients (thus 32 plurimetastatic patients) with a 5-lesion threshold. Similarity analysis showed high lesions' heterogeneity. Grouping patients according to the number of metastases, patients with oligometastatic PCa defined with a 5-lesion threshold presented lesions heterogeneity comparable to plurimetastic patients. Lesions within patients having a limited tumor burden as defined by three lesions were characterized by less heterogeneity. Conclusions We found a comparable heterogeneity between patients with up to five lesions and plurimetastic patients, while patients with up to three lesions were less heterogeneous than plurimetastatic patients, featuring different cells phenotypes in the two groups. Our results supported the use of a 3-lesion threshold to define oligometastatic PCa.

In some clinical applications in oncology randomized, double armed, and double-blind trials are not possible. In case of device applications, double-blinded conditions are nonrealistic, and with many times the randomization also has complications due to the high-line treatments where the reference cohort is not available; the active “arm” has mainly palliative initiative. Sometimes highly personalized therapies block the collection of the homogeneous group and limit its double-arm randomization. Our objective is to discuss the situations of the single arm evaluation and to give methods for the mining of information from this to increase the level of evidence of the measured dataset. The basic idea of the data-separation is the appropriate parameterization of the non-parametric Kaplan-Meier survival pattern by the poly-Weibull fit.

Background Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of death in China with a reported prevalence of 8.2% people aged ≥40 years. It is recommended that Chinese physicians follow Global Initiative for Chronic Obstructive Lung Disease (GOLD) and national guidelines, yet many patients with COPD in China remain undiagnosed. Furthermore, missed diagnoses and a lack of standardized diagnosis and treatment remain significant problems. The situation is further complicated by a lack of large-scale, long-term, prospective studies of real-world outcomes, including exacerbation rates, disease severity, efficacy of treatment, and compliance of COPD patients in China. Methods/design The REALizing and improving management of stable COPD in China (REAL) study is a 52-week multi-center, prospective, observational trial. REAL aims to recruit approximately 5000 outpatients aged ≥40 years with a clinical diagnosis of COPD per GOLD 2016. Outpatients will be consecutively recruited from approximately 50 tertiary and secondary hospitals randomly selected across six geographic regions to provide a representative population. Patients will receive conventional medical care as determined by their treating physicians. The primary objective is to evaluate COPD patient outcomes including lung function, health status, exacerbations, hospitalization rate, and dyspnea following 1 year of current clinical practice. Secondary objectives are to assess disease severity, treatment patterns, adherence to medication, and associated risk factors. Data will be collected at two study visits, at patients’ usual care visits, and by telephone interview every 3 months. Discussion Knowledge of COPD among physicians in China is poor. The REAL study will provide reliable information on COPD management, outcomes, and risk factors that may help improve the standard of care in China. Patient recruitment began on 30 June 2017 and the estimated primary completion date is 30 July 2019. Trial registration ClinicalTrials.gov identifier: NCT03131362. Registered on 20 March 2017.

This commentary introduces a new clinical trial construct, the Master Observational Trial (MOT), which hybridizes the power of molecularly based master interventional protocols with the breadth of real-world data. The MOT provides a clinical venue to allow molecular medicine to rapidly advance, answers questions that traditional interventional trials generally do not address, and seamlessly integrates with interventional trials in both diagnostic and therapeutic arenas. The result is a more comprehensive data collection ecosystem in precision medicine.

Background Rheumatological complaints including rheumatoid arthritis (RA) are frequently encountered conditions in homeopathy practice. On account of progressive destruction and disability of the joints, and troublesome side effects and dissatisfaction with the mainstream therapies, homeopathy remains one of the most sought-after therapies; however, it remained under-researched systematically. Aim of this trial was to evaluate the possible role of homeopathic treatment in RA by determining changes in severity of complaints and quality of life. Materials and Methods An open observational trial was performed on 50 patients suffering from RA (classified as per 2010 ACR/EULAR criteria) at National Institute of Homoeopathy, Kolkata and were assessed over 4 months of treatment. Disease Activity Score-28 (DAS28) and Rheumatoid Arthritis Disease Activity Index (RADAI) were used as the primary and secondary outcome measures respectively. Individualised medicines were prescribed on the basis of homeopathic principles. Results Six patients dropped out; 44 completed the trial. Intention-to-treat sample (n = 50) was analysed in the end. There were statistically significant reductions in both DAS28 score (6.8 ± 1.0 vs. 6.1 ± 1.2; mean reduction 0.7, 95% CI: 0.4–0.9, p Conclusion Individualised homeopathic medicines seemed to produce promising treatment effects by reducing DAS28 and RADAI scores significantly over 4 months. Further randomised trials are warranted with enhanced methodological rigor (Trial registration: CTRI/2017/06/008848).

Background Training in advanced endoscopic techniques such as endoscopic retrograde cholangiopancreatography (ERCP) should be driven by key performance measures and standardized competence assessment in order to provide safe and high-quality interventions. We aimed to determine whether the involvement of trainees influences the outcome of the procedure and the incidence of ERCP-related adverse events. Methods This was an international, multicenter, prospective, observational study conducted at six high- and low-volume centers across Europe between October 2016 and October 2018, and included independent operators and their trainees. Standard report forms documenting indication, trainee involvement, technical outcome, and complications over a 30-day follow-up of consecutive ERCP procedures were included in the analysis. Technical success of the procedure and procedure-related adverse events were compared between procedures in the trainee group and the control group using bivariable and multivariable analysis. Results 21 trainees and 16 control endoscopists performed 1843 ERCPs during the study period. Trainee involvement in ERCP procedures did not decrease technical success (92.4 % vs. 93.7 %; P = 0.30) or increase the risk of adverse events (14.7 % vs. 14.6 %; P > 0.99). Conversely, there were significantly more moderate or severe adverse events in the control group compared with the trainee group (6.2 % vs. 3.4 %, P = 0.01). On multivariable analysis, only increased bilirubin levels, time to cannulation, and procedure difficulty level increased the risk of any procedure-related adverse event. Conclusion Trainee involvement in ERCP interventions within a proper teaching setting is safe and does not compromise the success of the procedure.

Objectives This study sought to determine (1) the association between the length of preoperative clopidogrel discontinuation, blood loss, and transfusion requirements and (2) whether preoperative platelet function testing predicts excessive postoperative bleeding in patients undergoing coronary artery bypass grafting (CABG) surgery. Methods In this retrospective analysis, patients undergoing CABG were divided into three groups with regard to the period between preoperative clopidogrel cessation and surgery: group 1 (n = 94, ≤3 days), group 2 (n = 100, 4–5 days), and group 3 (n = 83, 6–7 days), respectively. Impedance aggregometry (Multiplate) with arachidonic acid (ASPI) test assay (used for platelets stimulation) and adenosine diphosphate (ADP) test (used for platelets stimulation) was performed before the surgery. Primary outcome was 24 hours chest tube output (CTO) and transfusion requirements (red blood cell concentrate [RBCC], platelet concentrate [PC], fibrinogen concentrate [FC], and fresh-frozen plasma [FFP]) were considered as secondary outcomes. Results CTO during 24 hours was significantly higher in group 1 as compared with groups 2 and 3, respectively (p = 0.003). Considering secondary outcomes, RBCC (p = 0.043), PC (p = 0.001), FC (p = 0.003), and FFP (p = 0.010) were more frequently transfused in group 1 as compared with groups 2 and 3, respectively. Multiple electrode aggregometry ASPI and ADP tests were significantly correlated with the 24-hour CTO (ASPI test—rho = −0.258, p Conclusion Excessive postoperative bleeding occurred less frequently if the period between clopidogrel discontinuation and surgery was longer than 3 days, as compared with shorter waiting time. Inadequate recovery of the platelets function following clopidogrel cessation in preoperative period was associated with increased bleeding risk. Platelet function testing was found to be a useful tool for postoperative bleeding management in our hands.

Background: Acute secondary peritonitis is afflicted with a high morbidity and mortality. Intensive care therapy, antibiotics and surgical procedures are mandatory. Continuous negative pressure the...

Targeted temperature management (TTM) is recommended postcardiac arrest. The cooling method with the highest safety and efficacy is unknown. The COOL-ARREST pilot trial aimed to evaluate the safety and efficacy of the most contemporary ZOLL Thermogard XP Intravascular Temperature Management (IVTM) system for providing mild TTM postcardiac arrest. This multicenter, prospective, single-arm, observational pilot trial enrolled patients at eight U.S. hospitals between July 28, 2014, and July 24, 2015. Adult (≥18 years old), out-of-hospital cardiac arrest subjects of presumed cardiac etiology who achieved return of spontaneous circulation (ROSC) were considered for inclusion. Patients were excluded if (1) awake or consistently following commands after ROSC, (2) significant prearrest neurological dysfunction, (3) terminal illness or advanced directives precluding aggressive care, and (4) severe hemodynamic instability or shock. Patient temperature was maintained at 33.0°C ± 0.3°C for a total of 24 hours followed by controlled rewarming (0.1-0.2°C/h). Logistic regressions were used to assess association of good functional outcome (modified Rankin Scale ≤3) measured at the time of hospital discharge with shockable rhythm (yes/no), age, gender, race/ethnicity, lay-rescuer cardiopulmonary resuscitation, time to basic life support (minutes), time to ROSC (minutes), lactate (mg/dL), and pH on admission. The ZOLL IVTM system was effective at inducing TTM (median time to target temperature from initiation, 89 minutes [interquartile range 42-155]). Adverse events most often included electrolyte abnormalities and dysrhythmias. Of patients surviving to hospital discharge, 16/20 patients had a good functional outcome. A total of 18 patients survived through 90-day follow-up, at which time 94% (17/18) of patients had good functional outcome. The COOL-ARREST pilot trial demonstrates high safety and efficacy of the ZOLL Thermogard XP IVTM system in the application of mild TTM postcardiac arrest. This observational trial also revealed noteworthy variability in the management of postcardiac arrest patients, particularly with the use of early withdrawal of life-sustaining therapy.

Introduction Trauma is a leading cause of death throughout the world, with hemorrhage being responsible for more than 35% of pre-hospital trauma deaths and more than 40% of deaths within the first 24 hours after injury. Despite first aid having a demonstrable effect on mortality from trauma, relatively little research has compared the best methods for bleeding control in the prehospital first aid setting. The most common first-line therapy for external bleeding control in the pre-hospital first aid setting is direct manual compression (DMC). However, a prior study demonstrated that the primary cause of failure in a simulated model of life-threatening bleeding was the inability to maintain adequate direct pressure for three minutes. In this study, we evaluated the effect of fatigue on DMC for the duration of a typical urban emergency medical services (EMS) response time. Methods We conducted a prospective observational trial of 33 participants, 18 years of age or older to measure the pressure generated on a model of life-threatening bleeding over an eight-minute period using a “CPR posture” for applying pressure. The primary analyses were longitudinal two-level multilevel models (MLM) with repeated measures of outcome (i.e., CPR posture pressure) nesting within participants. The demographic factors of gender, age, and weight were included as moderators in the analyses and each was analyzed independently. Results The participants’ average age was 31 (SD = 11) and the average weight was 161 pounds (SD = 31). The sample consisted of 18 female participants (54.5%) and 15 male participants (45.5%). Applied DMC pressure declined over time, more sharply initially from the beginning to approximately 250 seconds, at which point the decrease in pressure was gradual. Of the demographic factors, gender was associated with a difference in cardiopulmonary resuscitation (CPR) posture pressure over time. Conclusion Rescuers should be aware that fatigue may occur and may affect the quality of direct manual compression for control of life-threatening bleeding. Further research is needed to define the external pressures needed to control life-threatening bleeding and the extent that rescuer fatigue affects this pressure.

Background: Data on the lung respiratory mechanics and gas exchange in the time course of COVID-19-associated respiratory failure is limited. This study aimed to explore respiratory mechanics and gas exchange, the lung recruitability and risk of overdistension during the time course of mechanical ventilation. Methods: This was a prospective observational study in critically ill mechanically ventilated patients (n=116) with COVID-19 admitted into Intensive Care Units of Sechenov University. The primary endpoints were: «optimum» positive end-expiratory pressure (PEEP) level balanced between the lowest driving pressure and the highest SpO2 and number of patients with recruitable lung on Days 1 and 7 of mechanical ventilation. We measured driving pressure at different levels of PEEP (14, 12, 10 and 8 cmH2O) with preset tidal volume, and with the increase of tidal volume by 100 ml and 200 ml at preset PEEP level, and calculated static respiratory system compliance (CRS), PaO2/FiO2, alveolar dead space and ventilatory ratio on Days 1, 3, 5, 7, 10, 14 and 21.Results: The «optimum» PEEP levels on Day 1 were 11.0 (10.0-12.8) cmH2O and 10.0 (9.0-12.0) cmH2O on Day 7. Positive response to recruitment was observed on Day 1 in 27.6% and on Day 7 in 9.2% of patients. PEEP increase from 10 to 14 cmH2O and VT increase by 100 and 200 ml led to a significant decrease in CRS from Day 1 to Day 14 (p2/FiO2 was 105.5 (76.2-141.7) mmHg in non-survivors on Day 1 and 136.6 (106.7-160.8) in survivors (p=0.002). In survivors, PaO2/FiO2 rose on Day 3 (p=0.008) and then between Days 7 and 10 (p=0.046). Conclusion: Lung recruitability was low in COVID-19 and decreased during the course of the disease, but lung overdistension occurred at «intermediate» PEEP and VT levels. In survivors gas exchange improvements after Day 7 mismatched CRS.Trial registration: ClinicalTrials.gov, NCT04445961. Registered 24 June 2020 - Retrospectively registered, http://https://clinicaltrials.gov/ct2/show/NCT04445961?cond=COVID-19&cntry=RU&city=Moscow&draw=3&rank=23

Introductionnasogastric tube (NGT) placement is a common procedure performed in critical care setting. Chest X-Ray is the diagnostic gold-standard to confirm correct placement, with the downsides of both the need for critical care patients’ mobilization and intrinsic actinic risk. Other potential methods to confirm NGT placement have shown lower accuracy compared to chest X-ray; ETCO2 and pH analysis have singularly yet investigated as an alternative to the gold standard. Aim of this study was to determine thresholds in combine measurements of ETCO2 and pH values, at which correct NGT positioning can be confirmed with the highest accuracy.Material & Methodsa prospective, multicenter, observational trial; a continuous cohort of eligible patients was allocated to two arms, to identify clear cut-off threshold able to detect correct NGT tip positioning with the maximal accuracy. Patients underwent general anesthesia and orotracheal intubation; in the first group difference between tracheal and esophageal ETCO2 values were assessed. In the second group difference between esophageal and gastric pH values were determined.Resultsfrom November 2020 to March 2021, 85 consecutive patients were enrolled: 40 in the ETCO2 group and 45 in the pH group. The ETCO2 ROC analysis for predicting NGT tracheal misplacement demonstrate an optimal ETCO2 cutoff value of 25.5 mmHg, where both sensitivity than specificity reach 1.0 (AUC 1.0, p < 0.001). The pH ROC analysis for predicting NGT correct gastric placement demonstrated the optimal pH cutoff value at 4.25, with a mild diagnostic accuracy (AUC 0.79, p < 0.001).DiscussionA device capable of combining the presence of a negative marker with a positive marker could be accurate enough in identifying the correct NGTs positioning. Further studies are required to validate the reproducibility of these results by a specific device, whose accuracy also ought to be compared with standard chest X-ray.Trial number: NCT03934515 (www.clinicaltrials.gov)