Stable Adult Patients Research Articles

Population pharmacokinetics of tacrolimus whole blood and peripheral blood mononuclear cell concentrations in stable kidney-transplanted patients.

Therapeutic drug monitoring of tacrolimus based on whole blood drug concentrations is routinely performed. The concentration of tacrolimus in peripheral blood mononuclear cells (PMBCs) is likely to better reflect drug exposure at the treatment target site. We aimed to describe the relationship between tacrolimus whole blood and PBMC concentrations, and the influence of patient characteristics on this relationship by developing a population pharmacokinetic model. We prospectively enrolled 63 stable adult kidney-transplanted patients and collected dense (12-h, n = 18) or sparse (4-h, n = 45) pharmacokinetic profiles of tacrolimus. PBMCs were isolated from whole blood (Ficoll density gradient centrifugation), and drug concentrations in whole blood and PBMCs were analysed using liquid chromatography-mass spectrometry. Patient genotype (CYP3A4/5, ABCB1, NR1I2) was assessed with PCR. Population pharmacokinetic modelling and statistical evaluation was performed using NONMEM. Tacrolimus whole blood concentrations were well described using a two-compartment pharmacokinetic model with a lag-time and first-order absorption and elimination. Tacrolimus PBMC concentrations were best estimated from whole blood concentrations with the use of a scaling factor, the ratio of whole blood to PBMC concentrations (RC:PBMC), which was the extent of tacrolimus distribution into PBMC. CYP3A5*1 non-expressors and NR1I2-25 385T allele expressors demonstrated higher RC:PBMC ratios of 42.4% and 60.7%, respectively. Tacrolimus PBMC concentration could not be accurately predicted from whole blood concentrations and covariates because of significant residual unexplained variability in the distribution of tacrolimus into PBMCs and may need to be measured directly if required for future studies.

A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies.

Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.

Diagnostic Performance of GFAP, UCH-L1, and MAP-2 Within 30 and 60 Minutes of Traumatic Brain Injury.

Data on the performance of traumatic brain injury (TBI) biomarkers within minutes of injury are lacking. To examine the performance of glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and microtubule-associated protein 2 (MAP-2) within 30 and 60 minutes of TBI in identifying intracranial lesions on computed tomography (CT) scan, need for neurosurgical intervention (NSI), and clinically important early outcomes (CIEO). This cohort study is a biomarker analysis of a multicenter prehospital TBI cohort from the Prehospital Tranexamic Acid Use for TBI clinical trial conducted across 20 centers and 39 emergency medical systems in North America from May 2015 to March 2017. Prehospital hemodynamically stable adult patients with traumatic injury and suspected moderate to severe TBI were included. Blood samples were measured for GFAP, UCH-L1, and MAP-2. Data were analyzed from December 1, 2023, to March 15, 2024. The presence of CT lesions, diffuse injury severity on CT, NSI within 24 hours of injury, and CIEO (composite outcome including early death, neurosurgery, or prolonged mechanical ventilation ≥7 days) within 7 days of injury. Of 966 patients enrolled, 804 patients (mean [SD] age, 41 [19] years; 418 [74.2%] male) had blood samples, including 563 within 60 minutes and 375 within 30 minutes of injury. Among patients with blood drawn within 30 minutes of injury, 212 patients (56.5%) had CT lesions, 61 patients (16.3%) had NSI, and 112 patients (30.0%) had CIEO. Among those with blood drawn within 60 minutes, 316 patients (56.1%) had CT lesions, 95 patients (16.9%) had NSI, and 172 patients (30.6%) had CIEO. All biomarkers showed significant elevations with worsening diffuse injury on CT within 30 and 60 minutes of injury. Among blood samples taken within 30 minutes, GFAP had the highest area under the receiver operating characteristic curve (AUC) to detect CT lesions, at 0.88 (95% CI, 0.85-0.92), followed by MAP-2 (AUC, 0.78; 95% CI, 0.73-0.83) and UCH-L1 (AUC, 0.75; 95% CI, 0.70-0.80). Among blood samples taken within 60 minutes, AUCs for CT lesions were 0.89 (95% CI, 0.86-0.92) for GFAP, 0.76 (95% CI, 0.72-0.80) for MAP-2, and 0.73 (95% CI, 0.69-0.77) for UCH-L1. Among blood samples taken within 30 minutes, AUCs for NSI were 0.78 (95% CI, 0.72-0.84) for GFAP, 0.75 (95% CI, 0.68-0.81) for MAP-2, and 0.69 (95% CI, 0.63-0.75) for UCH-L1; and for CIEO, AUCs were 0.89 (95% CI, 0.85-0.93) for GFAP, 0.83 (95% CI, 0.78-0.87) for MAP-2, and 0.77 (95% CI, 0.72-0.82) for UCH-L1. Combining the biomarkers was no better than GFAP alone for all outcomes. At GFAP of 30 pg/mL within 30 minutes, sensitivity for CT lesions was 98.1% (95% CI, 94.9%-99.4%) and specificity was 34.4% (95% CI, 27.2%-42.2%). GFAP levels greater than 6200 pg/mL were associated with high risk of NSI and CIEO. In this cohort study of prehospital patients with TBI, GFAP, UCH-L1, and MAP-2 measured within 30 and 60 minutes of injury were significantly associated with traumatic intracranial lesions and diffuse injury severity on CT scan, 24-hour NSI, and 7-day CIEO. GFAP was the strongest independent marker associated with all outcomes. This study sets a precedent for the early utility of GFAP in the first 30 minutes from injury in future clinical and research endeavors.

Intradialytic serum phosphate variations are associated with low PTH levels.

Numerous studies have explored the role of kidney replacement therapy (KRT) in phosphorus (P) control among prevalent hemodialysis (HD) patients. However, whether the reduction of P achieved during KRT affects parathyroid hormone (PTH) levels is still a matter of debate. We conducted a retrospective observational study on the prevalent HD population at the Division of Nephrology, University Hospital of Verona, from January to December 2022. We Included clinically stable adult patients undergoing HD for over 6 months, with multiple recorded visits during the follow-up. Demographic, clinical, laboratory, and medication data were collected. Time-varying variables were updated at each study visit. The primary outcome of interest was PTH levels. The absolute intra-HD change in P (intra-HD ∆P), defined as the difference between pre- and post-HD P levels, served as the main exposure. Multivariable adjusted linear mixed models were used to investigate the relationship between intra-HD ∆P and PTH levels. A total of 211 patients contributed to 904 study visits. A significant and positive relationship was observed between intra-HD ∆P and pre-HD P (β = 0.76, 95% CI 0.75, 0.78, p < 0.001) and urea reduction ratio (β = 0.38, 95% CI 0.35, 0.41; p < 0.001). An increase in intra-HD ∆P was significantly and independently associated with low PTH levels (β = -0.16, 95% CI -0.30, -0.03; p = 0.020). The extent of intra-HD P reduction significantly correlates with low PTH levels. Strategies focused on optimizing or enhancing depurative efficiency in KRT can exert a substantial impact on managing positive phosphorus balance and secondary hyperparathyroidism. The assessment of intra-HD P reduction may play a pivotal role in the management and follow-up of secondary hyperparathyroidism in HD patients.

Modulation of brain activity in brain-injured patients with a disorder of consciousness in intensive care with repeated 10-Hz transcranial alternating current stimulation (tACS): a randomised controlled trial protocol

IntroductionTherapeutic interventions for disorders of consciousness lack consistency; evidence supports non-invasive brain stimulation, but few studies assess neuromodulation in acute-to-subacute brain-injured patients. This study aims to validate the feasibility and...

Liver fibrosis detected by diffusion-weighted magnetic resonance imaging and its functional correlates in Fontan patients.

The evaluation of Fontan-associated liver disease is often challenging. Diffusion-weighted magnetic resonance imaging can detect hepatic fibrosis from capillary perfusion and diffusion abnormalities from extracellular matrix accumulation. This study investigated its role in the evaluation of liver disease in Fontan patients and explored possible diagnostic methods for early detection of advanced liver fibrosis. Stable adult Fontan patients who could safely be examined with magnetic resonance imaging were enrolled, and blood biomarkers, transient elastography were also examined. Forty-six patients received diffusion-weighted imaging; and 58.7% were diagnosed with advanced liver fibrosis (severe liver fibrosis, 37.0%, and cirrhosis 21.7%). Two parameters of hepatic dysfunction, platelet counts (Spearman's ρ: -0.456, P = 0.001) and cholesterol levels (Spearman's ρ: -0.383, P = 0.009), decreased with increasing severity of fibrosis. Using transient elastography, a cut-off value of 14.2 kPa predicted the presence of advanced liver fibrosis, but with a low positive predictive value. When we included platelet count, cholesterol, post-Fontan years and transient elastography values as a composite, the capability of predicting advanced liver fibrosis was the most satisfactory (C statistic 0.817 ± 0.071, P < 0.001). A cut-off value of 5.0 revealed a sensitivity of 78% and a specificity of 82%. In Fontan patients, diffusion-weighted imaging was helpful in detecting liver fibrosis that was correlated with hepatic dysfunction. A simple score was proposed for long-term surveillance and early detection of advanced liver disease in adult Fontan patients. For adult Fontan patients with a calculated score > 5.0, we may consider timely diffusion-weight imaging and early management for liver complications.

The role of RObotic surgery in EMergency setting (ROEM): protocol for a multicentre, observational, prospective international study on the use of robotic platform in emergency surgery

BackgroundRobotic surgery has gained widespread acceptance in elective interventions, yet its role in emergency procedures remains underexplored. While the 2021 WSES position paper discussed limited studies on the application of robotics in emergency general surgery, it recommended strict patient selection, adequate training, and improved platform accessibility. This prospective study aims to define the role of robotic surgery in emergency settings, evaluating intraoperative and postoperative outcomes and assessing its feasibility and safety.MethodsThe ROEM study is an observational, prospective, multicentre, international analysis of clinically stable adult patients undergoing robotic surgery for emergency treatment of acute pathologies including diverticulitis, cholecystitis, and obstructed hernias. Data collection includes patient demographics and intervention details. Furthermore, data relating to the operating theatre team and the surgical instruments used will be collected in order to conduct a cost analysis. The study plans to enrol at least 500 patients from 50 participating centres, with each centre having a local lead and collaborators. All data will be collected and stored online through a secure server running the Research Electronic Data Capture (REDCap) web application. Ethical considerations and data governance will be paramount, requiring local ethical committee approvals from participating centres.DiscussionCurrent literature and expert consensus suggest the feasibility of robotic surgery in emergencies with proper support. However, challenges include staff training, scheduling conflicts with elective surgeries, and increased costs. The ROEM study seeks to contribute valuable data on the safety, feasibility, and cost-effectiveness of robotic surgery in emergency settings, focusing on specific pathologies. Previous studies on cholecystitis, abdominal hernias, and diverticulitis provide insights into the benefits and challenges of robotic approaches. It is necessary to identify patient populations that benefit most from robotic emergency surgery to optimize outcomes and justify costs.

#1819 Cardio-fistular recirculation in patients with chronic heart failure and preserved ejection fraction

Abstract Background and Aims Cardio-fistular recirculation (CFR)—ratio of cardiac output (CO) to AVF volume blood flow (Qa)—is a well-known risk factor for death and cardiovascular adverse events. Currently, there are no clear limits for this index that definitely indicate AVF cardiotoxicity. In most cases, an interval score of &amp;lt;20%, 20-30%, or &amp;gt;30% is used to denote low, medium, and high risk, respectively. Typically, the assessment is performed on the interdialysiс day. HD sessions can cause significant hemodynamic changes, which may be important for patients with chronic heart failure (CFH) and preserved ejection fraction (EF), in whom the risk may be underestimated. The aim of this prospective cohort study is to evaluate changes in heart structure and CFR in patients with СFH and preserved EF before and after an HD session. Method The study included 20 stable adult HD patients who met the inclusion criteria: CHF with preserved EF (50%), NYHA I-II, Qa ≥1 l/min, CFR &amp;lt; 30%, interdialysiс weight gain &amp;lt; 5%, eKt/V &amp;gt; 1.2. Non-inclusion criteria: arrhythmias (except grade I AV block), NYHA III-IV, valvular disease (except mitral regurgitation I-II), intradialytic hypo/hypertension. All patients underwent transthoracic ECHO-CG with tissue Doppler on the third day after the last HD session (Monday/Tuesday), one hour before and 2 hours after the HD session. In addition, we measured AVF volume blood flow—brachial artery Qa. Results Patient Descriptive Statistics: M/F 8/12, mean age 52.2 (SD 11.2, range 41-67) years, HD vintage 49 (11.1, 33-72) months, BMI 28.2 (3.8, 22.9-36.0) kg/m2, interdialysiс weight gain 3.2 (0.8, 1.9-4.7) kg, relative interdialysiс weight gain 4.1% (0.8, 2.9-4.9). A significant trend in ECHO-CG parameters was observed, indicating a decrease in cardiac preload (Table 1). Although there were no significant changes in EF, a pronounced decrease in CO was noted with a relatively stable Qa value. As a result, 5 out of 20 patients had a CFR value of more than 30% after HD, which assigned them to a high-risk group. As shown in Fig. 1, even patients with pre-HD CFR values less than 25% were classified as high-risk. Patients were intentionally examined after a long interdialysiс interval because this HD session is associated with the greatest hemodynamic changes. Some publications suggest that the risk of death after long interdialysic interval is significantly higher than that after short interval. Increase in CFR after HD probably has a synergistic deleterious effect with other risk factors. The severity of this influence is determined by both the maximum achieved CFR values and the rate of CO recovery. Conclusion Some patients have a significant increase in CFR after HD. However, the prognostic value of this phenomenon remains unclear. In patients with significant CHF symptoms and normal or subnormal CFR on an interdialytic day, it is recommended to perform a post-HD examination. This can serve as a “stress test” to reveal any latent hemodynamic disadvantage caused by the AVF cardiotoxic effect.

#2560 Intradialytic serum phosphate variations are associated with low PTH levels

Abstract Background and Aims Secondary hyperparathyroidism (SHPT) is one of the most common complications in patients with chronic kidney disease (CKD). The prevalence of SHPT progressively increases with the severity of CKD, affecting approximately 50-70% of patients on hemodialysis (HD). SHPT significantly impacts morbidity, mortality, hospitalization risks, healthcare costs, and the quality of life of CKD patients, making its management of paramount importance in this population. A positive serum phosphorus (P) balance is one of the critical determinants of SHPT, and the management of P levels in HD patients revolves around nutritional therapy, medications, and optimal kidney replacement therapy (KRT). Numerous studies have explored the role of KRT in P control among prevalent HD patients. However, whether the reduction of P achieved during KRT affects parathyroid hormone (PTH) levels is still a matter of debate. Currently, a direct evaluation of the relationship between intra-HD P reduction and PTH levels is lacking. Method We conducted a retrospective observational study on the prevalent HD population at the Division of Nephrology, University Hospital of Verona, from January to December 2022. We Included clinically stable adult patients undergoing HD for over 6 months, with multiple recorded visits during the follow-up. Demographic, clinical, laboratory, and medication data were collected. Time-varying variables were updated at each study visit. Food intake was assessed through a 3-day food record (HD day, non-HD day, and weekend day). Patients were instructed to maintain their usual ideally low-phosphate diet and to meticulously record and weigh all foods and preparations consumed. This assessment was conducted every 4 months during the observation period. From the 3-day food records, the dietary phosphorus intake was calculated using a national database and reported as mg of P per day. A dietitian evaluated dietary questionnaires. The primary outcome of interest was PTH levels. The absolute intra-HD change in P (intra-HD ∆P), defined as the difference between pre- and post-HD P levels, served as the main exposure. Multivariable adjusted linear mixed models were used to investigate the relationship between intra-HD ∆P and PTH levels. Potential confounders were included in the following three models of hierarchical adjustment: (i) Model 1, unadjusted; (ii) Model 2, adjusted for age and sex; (iii) Model 3, adjusted for all covariates in Model 2 plus URR, HD modality, active vitamin D, phosphate binders, calcimimetics, comorbidities. Since the relationship between intra-HD ∆P and PTH is influenced by the pre-HD P, all models were adjusted for pre-HD P. The association between PTH and intra-HD ∆P was also assessed in a subgroup of patients who provided a valid dietary diary. A multivariable linear mixed model adjusted for all covariates in Model 3 plus dietary phosphorus intake was used to assess this association. Results A total of 211 patients contributed to 904 study visits. A significant and positive relationship was observed between intra-HD ∆P and pre-HD P (β = 0.76, 95% CI 0.75, 0.78, p &amp;lt; 0.001) and urea reduction ratio (β = 0.38, 95% CI 0.35, 0.41; p &amp;lt; 0.001) (Figure). An increase in intra-HD ∆P was significantly and independently associated with low PTH levels (β = −0.17, 95% CI −0.30, −0.03; p = 0.016; Table). Overall, 86 out of 211 patients provided valid dietary data. The relationship between intra-HD ∆P and PTH levels was confirmed after additional adjustment for dietary P intake (p = 0.041). Conclusion The extent of intra-HD P reduction significantly correlates with low PTH levels. Strategies focused on optimizing or enhancing depurative efficiency in KRT can exert a substantial impact on managing positive phosphorus balance and secondary hyperparathyroidism (SHPT). The assessment of intra-HD P reduction may play a pivotal role in the management and follow-up of SHPT in HD patients.

Development and Safety Trial of the OstreaVent2™ Prototype for Mechanically Ventilated Adult Patients.

With the surge of COVID-19 infections, there were concerns about shortage of mechanical ventilator in several countries including the Philippines. To transform a locally made, low-cost, neonatal ventilator into a volume- and pressure-controlled, adult ventilator and to determine its safe use among ventilated, adult patients at the Philippine General Hospital. The modification of the neonatal ventilator (OstreaVent1) to the adult OstreaVent2 was based on the critical need for adult ventilators, in volume or pressure mode, in the Philippines due to the COVID-19 pandemic. The adult ventilator settings were calibrated and tested for two days to check for consistency and tolerance and then submitted to a third party for certification. Once certified, a safety trial of 10 stable adult patients on mechanical ventilator was conducted. The patients were placed on the OstreaVent2 for four hours while ventilator parameters, patient's vital signs, and arterial blood gases were monitored at baseline, during, and after placement on the OstreaVent2. A post-study chest radiograph was also done to rule out pulmonary complications, particularly atelectasis and pneumothorax. The prototype OstreaVent2 received an FDA Certification for Medical Listing after passing its third-party certification. Ten patients (60% male) recruited in the study had a mean age of 39.1 ± 11.6 years. Half of the patients had a diagnosis of non-COVID-19 pneumonia. During the 4-hour study period, the patients while on the OstreaVent2, had stable ventilator settings and most of the variabilities were within the acceptable tolerances. Vital signs were stable and arterial blood gases were within normal limits. One patient developed alar flaring which was relieved by endotracheal tube suctioning. No patient was withdrawn from the study. One patient who was already transferred out of the ICU subsequently deteriorated and died three days after transfer to the stepdown unit from a non-ventilator related cause. The new OstreaVent2 is safe to use among adults who need ventilator support. Variabilities in the ventilator's performance were within acceptable tolerances. Clinical and blood gas measurements of the patients were stable while on the ventilator.

Comparison of Observation Alone Versus Interventional Procedures in Hemodynamically Stable Patients With Pneumothorax: A Systematic Review and Meta-Analysis.

Several studies indicate that observation alone is sufficient for the management of stable pneumothorax. To compare clinical efficacy, tolerability, and safety outcomes for treating hemodynamically stable adult patients with pneumothorax, the present review compared observation alone versus interventional procedures. We searched PubMed and Google Scholar from inception until June 24, 2020, for randomized controlled trials (RCTs) comparing observational therapy with conventional therapy for the treatment of adult pneumothorax. The pediatric age group and patients with tension pneumothorax were not included. Four hundred and forty-six patients were enrolled in three RCTs. The failure rate (relative risk (RR) 4.30; 95% CI = 0.23-81.82, p = 0.33) and mortality (RR 1.01; 95% CI = 0.31-3.33, p = 0.98) of observation were comparable to those of the chest tube. Chest tube and observation both carried comparable risks of complications, including tension pneumothorax and empyema (RR 3.15; 95% CI = 0.67-1) and (RR 1.55; 95% CI = 0.21-11.56, p = 0.67), respectively. Between chest tubes and observation, there was no statistically significant difference in the duration of hospital stay. We conclude that observation is as safe and effective at treating adult patients with stable pneumothorax as a chest tube.

Do Causes Influence Functional Aspects and Quality of Life in Patients with Nonfibrocystic Bronchiectasis?

The denomination of noncystic fibrosis bronchiectasis (NCFB) includes several causes, and differences may be expected between the patient subgroups regarding age, comorbidities, and clinical and functional evolution. This study sought to identify the main causes of NCFB in a cohort of stable adult patients and to investigate whether such conditions would be different in their clinical, functional, and quality of life aspects. Between 2017 and 2019, all active patients with NCFB were prospectively evaluated searching for clinical data, past medical history, dyspnea severity grading, quality of life data, microbiological profile, and lung function (spirometry and six-minute walk test). There was a female predominance; mean age was 54.7 years. Causes were identified in 82% of the patients, the most frequent being postinfections (n = 39), ciliary dyskinesia (CD) (n = 32), and chronic obstructive pulmonary disease (COPD) (n = 29). COPD patients were older, more often smokers (or former smokers) and with more comorbidities; they also had worse lung function (spirometry and oxygenation) and showed worse performance in the six-minute walk test (6MWT) (walked distance and exercise-induced hypoxemia). Considering the degree of dyspnea, in the more symptomatic group, patients had higher scores in the three domains and total score in SGRQ, besides having more exacerbations and more patients in home oxygen therapy. Causes most identified were postinfections, CD, and COPD. Patients with COPD are older and have worse pulmonary function and more comorbidities. The most symptomatic patients are clinically and functionally more severe, besides having worse quality of life.

Role of Arterial Lactate and Lactate Clearance in Risk Stratification of Patients with Upper Gastrointestinal Bleeding Presenting to the Emergency Department for use at Primary Health Care Level

Abstract Background: Upper gastrointestinal bleeding is a common presenting complaint in the emergency department (ED) and carries a small but significant mortality rate. In spite of the availability of various scoring systems, risk stratification for in hospital morbidity and mortality remains difficult. There is no single test that can reliably predict active bleeding from the upper gastrointestinal tract for use at primary health level. Aims and Objectives: To study the role of lactate clearance as a predictor of active bleeding and also to determine whether an ED arterial lactate can predict adverse outcomes like increased hospital length of stay, in hospital, 30-day and 60-day mortality. Methods and Material: Prospective single centre observational study at a tertiary hospital in north Kerala that included all stable adult patients who presented with the complaints of hematemesis, melena or both to the ED Arterial lactate was drawn at the bedside, a priori initial arterial lactate cut-off value of 2.2 mmol/L was selected and in patients with lactate value above the cut-off, a second lactate was measured to calculate lactate clearance. Results: Lactate clearance ≤13.39% was found to be associated with a high risk for active bleeding (odds ratio: 23.33; 95% CI = 4.337 to 125.512, P &lt; 0.001). Optimal cut-off points for lactate as well as lactate clearance were derived using receiver operating characteristics curve. Conclusions: Lactate clearance can reliably rule in as well as rule out active bleeding in patients who might seem hemodynamically stable at the initial presentation to the ED.

The prevalence of depression and anxiety among cardiovascular patients at University of Gondar specialized hospital using beck's depression inventory II and beck anxiety inventory: A cross-sectional study

Psychosocial issues are leading factor as well as consequences of cardiovascular disease. Identifying factors associated with depression facilitate service quality improvement for inpatients. This study assessed the prevalence and identified associated factors with depression and anxiety among patients with cardio vascular disease. MethodAn institution-based cross-sectional study was conducted with a convenience sample of 370 stable adult patients from June 1 to July 30, 2020 among cardiovascular disease patients at the University of Gondar Specialized Hospital Ethiopia. Data were collected by using structured questionnaires. Data analyses were conducted using SPSS version 21. The statistical significance declared at p-value <0.05. ResultIn this study, among 370 Cardiovascular diseases patients, 228 (61.6 %) suffer from anxiety, and 53.51 % (198) suffer with depression. There was a significant mean difference in the level of depression and anxiety between male and female Cardiovascular diseases patients. The females' scores of depression (mean = 28, p < 0.01) and anxiety (mean = 25.3, p < 0.01) were more than that of males ‘scores of depression (mean = 15.1, p < 0.01) and anxiety (mean = 12.3, p < 0.01). Cardiovascular diseases patients aged greater than 60 years have the highest rate of prevalence of depression in all age group. Being in the age category of greater than 60 years was 1.16 (0.57–2.32) times more likely to have depression than the age category of 18–24 years. Depression and anxiety were significantly associated with being woman, widowed, being single, unable to read and write, and possess mental disorders history.

Relapse in clinically stable adult patients with schizophrenia or schizoaffective disorder: evidence-based criteria derived by equipercentile linking and diagnostic test accuracy meta-analysis

There is no consensus on defining relapse in schizophrenia, and scale-derived criteria with unclear clinical relevance are widely used. We aimed to develop an evidence-based scale-derived set of criteria to define relapse in patients with schizophrenia or schizoaffective disorder. We searched the Yale University Open Data Access (YODA) for randomised controlled trials (RCTs) in clinically stable adults with schizophrenia or schizoaffective disorder, and obtained individual participant data on Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity (CGI-S), Personal and Social Performance (PSP), and Social and Occupational Functioning Assessment Scale (SOFAS). Our main outcomes were PANSS-derived criteria based on worsening in PANSS total score. We examined their relevance using equipercentile linking with CGI-S and functioning scales, and their test-performance in defining relapse with diagnostic test accuracy meta-analysis against CGI-S worsening (≥1-point increase together with a score ≥4 points) and psychiatric hospitalisation. Based on data from seven RCTs (2354 participants; 1348 men [57·3%] and 1006 women [42·7%], mean age of 39·5 years [SD 12·0, range 17-89]; 303 Asian [12.9%], 255 Black [10.8%], 1665 White [70.7%], and other or unspecified 131 [5.6%]), an increase of 12 points or more in PANSS total (range 30-210 points) corresponded to clinically important deterioration in global severity of illness (≥1 point increase in CGI-S, range 1-7) and functioning (≥10 points decline in PSP or SOFAS, range 1-100). The interpretation of percentage changes varied importantly across different baseline scores. An increase of 12 points or more in PANSS total had good sensitivity and specificity using CGI-S as reference standard (sensitivity 82·1% [95% CI 77·1-86·4], specificity 86·9% [82·9-90·3]), as well as good sensitivity but lower specificity compared to hospitalisation (sensitivity 81·7% [74·1-87·7], specificity 69·2% [60·5-76·9]). Requiring either an increase in PANSS total or in specific items for positive and disorganization symptoms further improved test-performance. Cutoffs for situations where high sensitivity or specificity is needed are presented. An increase of either 12 points or more in the PANSS total score, or worsening of specific positive and disorganisation symptom items could be a reasonable evidence-based definition of relapse in schizophrenia, potentially linking symptoms used to define remission and relapse. Percentage changes should not be used to define relapse because their interpretation depends on baseline scores. German Research Foundation (grant number: 428509362).

CYP3A5*3 and CYP3A4*22 Cluster Polymorphism Effects on LCP-Tac Tacrolimus Exposure: Population Pharmacokinetic Approach.

The aim of the study is to develop a population pharmacokinetic (PopPK) model and to investigate the influence of CYP3A5/CYP3A4 and ABCB1 single nucleotide polymorphisms (SNPs) on the Tacrolimus PK parameters after LCP-Tac formulation in stable adult renal transplant patients. The model was developed, using NONMEM v7.5, from full PK profiles from a clinical study (n = 30) and trough concentrations (C0) from patient follow-up (n = 68). The PK profile of the LCP-Tac formulation was best described by a two-compartment model with linear elimination, parameterized in elimination (CL/F) and distributional (CLD/F) clearances and central compartment (Vc/F) and peripheral compartment (Vp/F) distribution volumes. A time-lagged first-order absorption process was characterized using transit compartment models. According to the structural part of the base model, the LCP-Tac showed an absorption profile characterized by two transit compartments and a mean transit time of 3.02 h. Inter-individual variability was associated with CL/F, Vc/F, and Vp/F. Adding inter-occasion variability (IOV) on CL/F caused a statistically significant reduction in the model minimum objective function MOFV (p < 0.001). Genetic polymorphism of CYP3A5 and a cluster of CYP3A4/A5 SNPs statistically significantly influenced Tac CL/F. In conclusion, a PopPK model was successfully developed for LCP-Tac formulation in stable renal transplant patients. CYP3A4/A5 SNPs as a combined cluster including three different phenotypes (high, intermediate, and poor metabolizers) was the most powerful covariate to describe part of the inter-individual variability associated with apparent elimination clearance. Considering this covariate in the initial dose estimation and during the therapeutic drug monitoring (TDM) would probably optimize Tac exposure attainments.

QOL-25. FOR THE LOVE OF WORK: NOVEL STUDY OF VOCATIONAL COGNITIVE REHABILITATION IN PRIMARY BRAIN TUMOR

Abstract BACKGROUND Primary brain cancer survivors live longer, yet experience distress and cognitive impairments that negatively impact their quality of life (QOL), including at work. We present a novel study of vocational tele-cognitive rehabilitation in primary brain cancer survivors. METHODS Retrospective review, post-treatment, radiologically stable adult primary brain cancer patients who completed standardized neuropsychological, psychological, vocational, and QOL assessments. Wilcoxon rank sum and Fisher’s exact or Chi-square tests assessed between-group and within-group comparisons. Tests were two-sided and statistically significant for p &amp;lt; 0.05. RESULTS 79 patients with known baseline work status assessed for between-group comparisons (working versus not). Working (n = 38) and not working (n = 41) subgroups had similar ages, tumor grade/type, and history of radiotherapy. Working had worse executive functioning (p = .05). Not working (n = 41) had worse cognitive function (executive function, attention, verbal learning all p &amp;lt; 0.05) and more engagement in survivorship services (p &amp;lt; 0.04). Of the 79 work-status known patients, 38 underwent vocational tele-cognitive rehabilitation (median 11 sessions) treatment for within-group comparisons. 82% of the treatment group had improved work status compared to 34% in non-treatment. Baseline work status and age were not related to occupational improvements (all p &amp;gt;0.20). Higher dose high radiotherapy dose inversely related to rehab improvements (p&amp;lt; .05). Higher verbal memory (p = 0.05), processing speed (p = .06), executive functioning (p = 0.02), IDH mutation status (p = .06), and motivation for treatment (p = .04) was associated with improvement. Those with depressive symptoms who engaged in clinically indicated psychotherapeutic services significantly improved their work status (p = .01). CONCLUSION Occupational functioning improved after cognitive rehabilitation. Cognitive impairments, IDH mutation status, higher dose radiotherapy, and treatment motivation are important. Not working at baseline, despite more cognitive impairments, improved similar to their working counterparts. Those with depression benefitted from psychotherapeutic support. Vocational tele-cognitive rehabilitation shows promise for improving the work-based abilities of primary brain tumor patients and warrants further investigation.

Comparison of vest-recorded electrocardiogram versus conventional electrocardiogram concerning ST-deviation in acute coronary syndrome

Abstract Background and Aim With the 12 lead ECG being the cornerstone in the diagnosis of ACS Development of a home-based, user-friendly recording of a 12 lead ECG will be a breakthrough in combating delay in diagnosing Acute Coronary Syndrome (ACS). This study evaluates the potential of a wearable vest 12-lead ECG (V-ECG) compared with the gold standard, conventional 12-lead ECGs (C-ECG) in diagnosing ACS. Methodology A prospective single-centre observational study conducted in a tertiary care centre. C-ECG and wearable V-ECG were recorded in hemodynamically stable adult patients and patients with normal ECG. The location of the electrodes in the vest included ten specific torso positions. Two independent physicians interpreted all the ECGs in a blinded fashion. Results Out of 241 patients, the vest fitted 236 patients (97.9%). Among 234 patients (72.5% males, 27.5% females; mean age 57.5 years), 154 had ACS. Three patients had an additional set of ECGs recorded, given their dynamic ECG changes during hospitalisation. The sensitivity and specificity of V-ECG, compared with the gold standard C-ECG for the diagnosis of ACS, were 98.7% ( CI 95.36-99.77) and 96.5% (CI 90.2-99.1), respectively. Among patients with STEMI, the sensitivity of V-ECG went up to 100% (CI 95.9-100). V-ECG has correctly identified anterior and inferior STEMI patients with 100% accuracy. Conclusion 12 lead ECG recording by a wearable garment using novel torso positions is feasible in the vast majority, including both genders, and reasonably accurate for diagnosing ACS. Highlights Commercial availability of this vest might enable an otherwise lay person to record an ECG in an out-of-hospital setting (even at home), thus leading to an expedited diagnosis of ACS and saving precious time and lives.

The main Optimal Post rTpa-Iv Monitoring in Ischemic Stroke Trial (OPTIMISTmain): Protocol for a Pragmatic, Stepped Wedge, Cluster Randomized Controlled Trial

Introduction: Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low risk of symptomatic intracerebral hemorrhage (sICH) and other complications. Methods: OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe, and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically stable adult patients with mild AIS (defined by a NIHSS <10) who do not require intensive care within 2 h post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, USA, and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7,200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 min for 2 h, 2 hourly (vs. every 30 min) for 8 h, and 4 hourly (vs. every 1 h) until 24 h, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH, and serious adverse events. Conclusion: OPTIMISTmain will provide level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS.

Furosemide versus placebo for fluid overload in intensive care patients-The randomised GODIF trial second version: Statistical analysis plan.

Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.