Massive Hemoptysis: An Unusual Complication of Left Atrial Appendage Occlusion Device in Two Patients.

Left atrial appendage occlusion (LAAO) devices have emerged as a promising alternative for stroke prevention in non-valvular atrial fibrillation (NVAF) patients with contraindications to chronic anticoagulation therapy. The most common life-threatening procedural complications described in the literature include pericardial effusion, air embolism, and stroke. We here present a case report of two patients who experienced identical but rare post-procedural complications of pulmonary venous bleed, presenting as hemoptysis.

The Effect of Sedation on Diagnostic Lumbar Medial Branch Blocks for Facetogenic Low Back Pain: An Observational Study.

BACKGROUND: Lumbar medial branch blocks (MBB) are some of the most commonly performed pain procedures in the United States. Diagnostic MBBs are performed to confirm if the generator of low back pain is the facet joint. However, with diagnostic injections, false positive blocks may occur. OBJECTIVES:   Our prospective observational study aims to investigate the effects of midazolam sedation on patients' perceived intensity of pain relief following lumbar MBB. STUDY DESIGN: This is a single-center multi-site prospective observational study registered on clinicaltrials.gov (NCT04453449). SETTING: The study was approved by the Henry Ford Health System Institutional Review Board (IRB) in June 2020 (IRB# 14010) and registered on clinicaltrials.gov in July 2020 (NCT04453449). This manuscript adheres to the applicable EQUATOR STROBE guidelines for an observational cohort study. METHODS: Patients that underwent MBB without sedation were compared to sedated patients. Patients were asked to complete the Numeric Rating Scale (NRS) at baseline, one day after their diagnostic blocks, as well as 4 weeks and 8 weeks after their lumbar radiofrequency ablation (RFA). The primary outcome is the difference between baseline NRS pain scores and the lowest reported score in the 8 hours following MBB. For patients who proceed to RFA, the frequency of false positive blocks was evaluated. A patient was considered to have a false positive block when they failed to achieve 50% pain relief from RFA after 2 successful sequential MBBs. RESULTS: There was no significant difference in the NRS pain score change between the sedated and non-sedated groups for diagnostic block one (P = 0.167) and diagnostic block 2 (P = 0.6145). There was no significant difference of false positive rates between non-sedation and sedation patients at 4-weeks post-RFA (P = 0.7178) and at 8-weeks post-RFA (P = 1.000). LIMITATIONS: Some of the limitations of this study include its nonrandomized design, patient self-reported pain scores, as well as the small variability in the injection technique of proceduralists and in the anatomical location of the injection site. CONCLUSIONS: This study showed that midazolam did not change patients' perceived intensity of pain following MBB, as well as false positive rates after RFA. Larger studies are required to draw definitive conclusions.

Comparative Analysis of Intravenous Opioids Versus Thoracic Epidural Anesthesia in Fractured Rib Pain Management: A Systematic Review and Meta-Analysis.

Rib fractures, common among trauma victims, lead to significant morbidity and mortality. Managing the associated pain is challenging, with IV opioids and thoracic epidural analgesia (TEA) being utilized. While epidural analgesia is often preferred for fractured rib pain, existing data encompasses both lumbar and thoracic approaches. This review aimed to compare TEA and IV opioids for persistent rib fracture pain. A comprehensive search across five databases yielded 987 articles, of which seven met the eligibility criteria. Outcomes were categorized into primary (pain reduction) and secondary (mortality, hospital/ICU stays, analgesia-related complications) endpoints. Analyzed with Review Manager (RevMan) Version 5.4.1 (2020; The Cochrane Collaboration, London, United Kingdom), the pooled data from two sources showed TEA significantly more effective in reducing pain than IV opioids (standardized mean difference (SMD): 2.23; 95%CI: 1.65-2.82; p < 0.00001). Similarly, TEA was associated with shorter ICU stays (SMD: 0.73; 95%CI: 0.33-1.13; p = 0.0004), while hospitalization duration showed no substantial difference (SMD: 0.82; 95%CI: -0.34-1.98). Mortality rates also did not significantly differ between TEA and IV opioids (risk ratio (RR): 1.20; 95%CI: 0.36-4.01; p = 0.77). Subgroup analysis revealed fewer pneumonia cases with TEA (RR: 2.06; 95%CI: 1.07-3.96; P = 0.03), with no notable disparities in other complications. While TEA's superiority in pain relief for rib fractures suggests it is the preferred analgesic, the recommendation's strength is tempered by the low methodological quality of supporting articles.

Accuracy of procalcitonin for diagnosing sepsis in adult patients admitted to the emergency department: a systematic review and meta-analysis.

BACKGROUND: Differentiating sepsis from non-infectious systemic inflammatory response syndrome (SIRS) is challenging. Biomarkers like procalcitonin (PCT) aid early risk assessment and guide antibiotic use. This study aims to ascertain PCT's accuracy as a sepsis biomarker among adult emergency department admissions. METHOD: The PRISMA guidelines were followed to search for relevant articles in five electronic databases between April 14th and August 4th, 2023: PubMed, Cochrane Library, ProQuest, EMBASEs, and ScienceDirect. Studies had to be published in English to avoid directly translating scientific terms. Besides, the inclusion criteria were based on the diagnosis of sepsis in adult patients admitted to an emergency department. QUADAS-2 tool provided by the Review Manager version 5.4.1 was utilized to assess the risk of bias in included studies. STATA (v. 16) software was used to perform the meta-analysis. RESULTS: Ten of 2457 studies were included. We sampled 2980 adult sepsis patients for the under-investigated role of PCT in ED sepsis diagnosis. PCT emerged as the primary early diagnostic biomarker with high levels (29.3 ± 85.3 ng/mL) in sepsis patients. Heterogeneity in outcomes, possibly due to bias in cohort and observational studies, was observed. CONCLUSION: PCT tests offer moderate accuracy in diagnosing sepsis and stand out for rapidly and precisely distinguishing between viral and bacterial inflammations.

Safety and feasibility of rotational atherectomy (RA) versus conventional stenting in patients with chronic total occlusion (CTO) lesions: a systematic review and meta-analysis.

BACKGROUND AND AIM: Interventional cardiologists face challenges in managing chronic total occlusion (CTO) lesions, with conflicting results when comparing rotational atherectomy (RA) to conventional PCI. This meta-analysis aims to provide a critical evaluation of the safety and feasibility of RA in CTO lesions. METHODS: PubMed, Scopus, Web of Science, Ovid, and Cochrane central library until April 2023 were searched for relevant studies. MACE was our primary outcomes, other outcomes were all cause of death, cardiac death, MI, and TVR. Also, we reported angiographic outcomes as technical success, procedural success, and procedural complications in a random effect model. The pooled data was analyzed using odds ratio (OR) with its 95% CI using STATA 17 MP. RESULTS: Seven studies comprising 5494 patients with a mean follow-up of 43.1 months were included in this meta-analysis. Our pooled analysis showed that RA was comparable to PCI to decrease the incidence of MACE (OR = 0.98, 95% CI [0.74 to 1.3], p = 0.9). Moreover, there was no significant difference between RA and conventional PCI in terms of other clinical or angiographic outcomes. CONCLUSION: Our study showed that RA had comparable clinical and angiographic outcomes as conventional PCI in CTO lesions, which offer interventional cardiologists an expanded perspective when addressing calcified lesions. PROSPERO REGISTRATION: CRD42023417362.

Exploring Clinical Trajectories and the Continuum of Care for Patients With Acute Coronary Syndrome in the United Kingdom: A Thorough Cross-Sectional Analysis.

The United Kingdom (UK) has a sustainable healthcare system. Nonetheless, the burden of acute coronary syndrome (ACS) is still a significant challenge. A scarcity of literature primarily focuses on the continuum of care for ACS patients in the UK. Moreover, limited research studies highlight the clinical trajectories of ACS patients across the UK. Therefore, the current study was designed to explore clinical trajectories and the continuum of care for patients with ACS in the UK. Secondary data was obtained from the Myocardial Ischaemia National Audit Project (MINAP) database. The latest data available in the MINAP database was used. As our objective was to explore clinical trajectories and the continuum of care for patients, we retrieved data regarding the care received by ACS patients admitted to hospitals across the UK.  The data of 85574 ACS patients was retrieved. A large number (n=47035) of patients were estimated to be eligible for the angiogram; however, an angiogram was performed for 87.15% (n=40995) of eligible patients. Angioplasty within 72 hours of admission was required for most (n=26313) ACS patients. Nonetheless, angioplasty within 72 hours of admission was performed for 59.7% (n=15703) of the eligible patients. There was a significant difference (P<0.05) between different regions of the UK and the percentage of patients for whom angioplasty was performed within 72 hours of admission. Primary percutaneous coronary intervention (PCI) was performed for 23923 ACS patients, of which the door-to-balloon interval for 17590 (73.5%) patients was ≤60 minutes while the door-to-balloon interval for 3086 (12.9%) patients was ≤90 minutes. Out of the total 85574 ACS patients, 65959 (77.08%) patients were discharged on appropriate medications, while 19615 (22.92%) were transferred to another hospital or died there. A total of 75361 were eligible to be referred to cardiac rehabilitation settings. Nonetheless, 64518 (85.61%) were referred to cardiac rehabilitation. About 85000 patients were reported in the UK (England, Northern Ireland, Wales). Optimal care was provided to most patients in the UK. However, some patients received sub-optimal care, highlighting the disparity in the healthcare system. There is a need to explore further the factors that might be responsible for the sub-optimal care to the patients.

Population Pharmacokinetic Model of N-Acetylcysteine During Periods of Recurrent Hypoglycemia in Healthy Volunteers.

Recurrent hypoglycemia leads to impaired awareness of hypoglycemia where the blood glucose threshold that elicits the counterregulatory response is lowered. Hypoglycemia-induced oxidative stress is hypothesized to contribute to impaired awareness of hypoglycemia development and hypoglycemia-associated autonomic failure. Our group conducted a randomized, double-blinded, placebo-controlled, crossover study in healthy individuals undergoing experimentally induced recurrent hypoglycemia to evaluate the impact of intravenous N-acetylcysteine (NAC) during experimental hypoglycemia to preserve the counterregulatory response to subsequent hypoglycemia. The work presented herein aimed to characterize the NAC pharmacokinetics and its effects on oxidative stress. Whole blood and plasma samples were collected at specified time points during separate NAC and placebo infusions from 10 healthy volunteers. Samples were analyzed for NAC, cysteine, and glutathione (GSH) concentrations. A 2-compartment population NAC pharmacokinetic model was developed. Estimates for central compartment clearance and volume of distribution were 19.8 L/h, and 12.2 L, respectively, for a 70-kg person. Peripheral compartment clearance and volume of distribution estimates were 34.9 L/h and 13.1 L, respectively, for a 70-kg person. The PK parameters estimated here were different from those reported in the literature, suggesting a higher NAC clearance during hypoglycemic episodes. NAC leads to a significant increase in circulating cysteine concentration in a NAC concentration-dependent manner, suggesting rapid biotransformation. A transient decrease in plasma GSH was observed, supporting the hypothesis that NAC can act as a reducing agent displacing glutathione from the disulfide bond allowing for increased clearance and/or distribution of GSH.

Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica.

Designing a robust direct compression (DC) formulation for an active pharmaceutical ingredient (API) with poor flow and compaction properties at a high API load is challenging. This study tackled two challenges: the unfavorable flow characteristics and tableting problems associated with a high-drug-loading canagliflozin (CNG), facilitating high-speed DC tableting. This was accomplished through a single-step dry coating process using hydrophilic nano-sized colloidal silica. A 32 full-factorial experimental design was carried out to optimize the independent process variables, namely, the weight percent of silica nanoparticles (X1) and mixing time (X2). Flow, bulk density, and compaction properties of CNG-silica blends were investigated, and the optimized blend was subsequently compressed into tablets using the DC technique. A regression analysis exhibited a significant (p ≤ 0.05) influence of both X1 and X2 on the characteristics of CNG with a predominant effect of X1. Additionally, robust tablets were produced from the processed powders in comparison with those from the control batch. Furthermore, the produced tablets showed significantly lower tablet ejection forces than those from the control batch, highlighting the lubrication impact of the silica nanoparticles. Interestingly, these tablets displayed improved disintegration time and dissolution rates. In conclusion, a dry coating process using silica nanoparticles presents a chance to address the poor flow and tableting problems of CNG, while minimizing the need for excessive excipients, which is crucial for the effective development of a small-sized tablet and the achievement of a cost-effective manufacturing process.

Perioperative Autonomic Dysfunction in a Patient With Charcot-Marie-Tooth Disease: A Case Report.

Autonomic dysfunction can lead to unexpected hemodynamic instability during surgery, and best practices for the perioperative care of patients with this condition are not well-defined. We report the case of a 63-year-old woman with Charcot-Marie-Tooth disease who experienced perioperative autonomic dysfunction characterized by severe fluctuations in blood pressure while under spinal anesthesia. However, <1 month later, a second hip surgery performed under general anesthesia with special precautions resulted in an uncomplicated perioperative course, with only mild fluctuations in blood pressure.

ß1-adrenergic receptor polymorphisms: a possible genetic predictor of bisoprolol response in acute coronary syndrome.

Aim: To investigate the association between beta1-adrenergic receptor (ADRB1) polymorphisms and response to bisoprolol treatment in beta-blocker naive patients with acute coronary syndrome (ACS). Patients & methods: Seventy-seven patients received bisoprolol for four weeks. Blood pressure and heart rate were measured at baseline and during treatment. TaqMan allelic discrimination method was utilized for ADRB1 Ser49Gly and Arg389Gly genotyping. Results: Arg389Arg carriers showed greater reductions in systolic and diastolic blood pressure (-8.5% ± 7.8% vs -0.76% ± 8.7%, p = 0.000218), and (-9.5% ± 9.7% vs -0.80% ± 11.5%, p = 0.000149), respectively, compared with Gly389 carriers. No statistical difference was found for study's outcomes based on codon 49. Conclusion: Arg389Gly polymorphism is a promising bisoprolol response predictor in ACS patients.

Pharmacogenetics is a field of study that explores how our genes can affect how well certain medicines work. In this study, scientists looked at a specific gene called beta1-adrenergic receptor to see how it can influence a drug called bisoprolol. They wanted to find out if some people's genes made bisoprolol work better for them. They studied 77 patients with a heart problem called acute coronary syndrome (ACS) who were taking bisoprolol for 4 weeks. The researchers discovered that people with a particular gene piece called Arg389Arg responded better to bisoprolol. They had bigger reductions in their blood pressure compared with those who had a different gene called Gly389. This finding suggests that by looking at a person's genes, doctors might be able to predict how well bisoprolol will work for them. This way, doctors can choose the best treatment for each patient, making sure they get the most benefit from the medicine.

The beneficial use of nitric oxide during cardiopulmonary bypass on postoperative outcomes in children and adult patients: a systematic review and meta-analysis of 2897 patients.

PURPOSE: Investigate inhaled nitric oxide's influence on mortality rates, mechanical ventilation and cardiopulmonary bypass duration, and length of stay in the intensive care unit and hospital when administered during cardiopulmonary bypass. METHODS: Following the PRISMA guidelines, we searched four electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science) up to 4th March 2023. The protocol was registered in the PROSPERO database with ID: CRD42023423007. Using Review Manager software, we reported outcomes as risk ratios (RRs) or mean difference (MD) and confidence intervals (CIs). RESULTS: The meta-analysis included a total of 17 studies with 2897 patients. Overall, there were no significant differences in using nitric oxide over control concerning mortality (RR = 1.03, 95% CI 0.73 to 1.45; P = 0.88) or cardiopulmonary bypass duration (MD = -0.14, 95% CI - 0.96 to 0.69; P = 0.74). The intensive care unit days were significantly lower in the nitric oxide group than control (MD = -0.80, 95% CI - 1.31 to -0.29; P = 0.002). Difference results were obtained in terms of the length of stay in the hospital according to sensitivity analysis (without sensitivity [MD = -0.41, 95% CI - 0.79 to -0.02; P = 0.04] vs. with sensitivity [MD = -0.31, 95% CI - 0.69 to 0.07; P = 0.11]. Subgroup analysis shows that, in children, nitric oxide was favored over control in significantly reducing the duration of mechanical ventilation (MD = -4.58, 95% CI - 5.63 to -3.53; P < 0.001). CONCLUSION: Using inhaled nitric oxide during cardiopulmonary bypass reduces the length of stay in the intensive care unit, and for children, it reduces the duration of mechanical ventilation.

Prone Vs. Supine Position Ventilation in Intubated COVID-19 Patients: A Systematic Review and Meta-Analysis.

Whether prone positioning of patients undergoing mechanical ventilation for COVID-19 pneumonia has benefits over supine positioning is not clear. We conducted a systematic review with meta-analysis to determine whether prone versus supine positioning during ventilation resulted in different outcomes for patients with COVID-19 pneumonia. We searched Ovid Medline, Embase, and Web of Science for prospective and retrospective studies up through April 2023. We included studies that compared outcomes of patients with COVID-19 after ventilation in prone and supine positions. The primary outcomes were three mortality measures: hospital, overall, and intensive care unit (ICU). Secondary outcomes were mechanical ventilation days, intensive care unit (ICU) length of stay, and hospital length of stay. We conducted risk of bias analysis and used meta-analysis software to analyze results. Mean difference (MD) was used for continuous data, and odds ratio (OR) was used for dichotomous data, both with 95% CIs. Significant heterogeneity (I2) was considered if I2 was >50%. A statistically significant result was considered if the p-value was <0.05. Of 1787 articles identified, 93 were retrieved, and seven retrospective cohort studies encompassing 5216 patients with COVID-19 were analyzed. ICU mortality was significantly higher in the prone group (OR 2.22, 95% CI 1.43-3.43; p=0.0004). No statistically significant difference was observed between prone and supine groups for hospital mortality (OR, 0.95; 95% CI, 0.66-1.37; p=0.78) or overall mortality (OR, 1.08; 95% CI, 0.72-1.64; p=0.71). Studies that analyzed primary outcomes had significant heterogeneity. Hospital length of stay was significantly higher in the prone than in the supine group (MD, 6.06; 95 % CI, 3.15-8.97; p<0.0001). ICU length of stay and days of mechanical ventilation did not differ between the two groups. In conclusion, mechanical ventilation with prone positioning for all patients with COVID-19 pneumonia may not provide a mortality benefit over supine positioning.

Plasma exchange (PE) versus intravenous immunoglobulin (IVIG) for the treatment of Guillain-Barré syndrome (GBS) in patients with severe symptoms: A systematic review and meta-analysis.

Background and purpose: Guillain- Barré syndrome (GBS) is a neuropathic condition that leads to the rapid development of impairments and is characterized by weakness and numbness or tingling sensation in the legs and arms and sometimes loss of movement and feeling in the legs, arms, upper body, and face. Currently, the cure for the disease is yet to be developed. However, treatment options such as intravenous immunoglobulin (IVIG) and plasma exchange (PE) have been used to minimize the symptoms and duration of the disease. Therefore, this systematic review and meta-analysis compared the efficacy of IVIG and PE in treating GBS patients with severe symptoms. Methodology: Six electronic databases, including PubMed, Embase, Scopus, ScienceDirect, Medline, and Google scholar, were scoured for articles related and relevant to our research. Additionally, more studies were obtained through the reference lists of the studies retrieved from these electronic databases. Quality assessment and statistical data analysis were conducted using Review Manager software (RevMan 5.4.1). Results: The search for relevant articles resulted in 3253 articles, of which only 20 were included for review in the current study. A sub-group analysis indicated no significant difference in the curative effect (Hughes score reduces by at least one score 4 weeks after GBS treatment; OR: 1.00; 95% CI: 0.66-1.52; p = 1.00 and Achieving grade 0 or 1 on Hughes scale; OR: 1.03; 95% CI: 0.27-3.94; p = 0.97). Similarly, the statistical showed that the difference in length of hospitalization and duration of mechanical ventilation was insignificant between the IVIG and PE group (Standard Mean Difference (SMD): -0.45; 95% CI: -0.92, 0.02; I2 = 91%; p = 0.06 and SMD: -0.54; 95% CI: -1.67, 0.59; I2 = 93%; p = 0.35, respectively). Moreover, the meta-analysis did not find any significant difference in the risk of GBS relapse (RR: 0.47; 95% CI: 0.20-1.14; p = 0.10) and risk of complications related to the treatment regimens (RR: 1.03; 95% CI: 0.71-1.48; p = 0.89). However, the statistical analysis of outcomes from 3 studies showed that the risk of discontinuation was significantly lower in the IVIG group than in the PE group (RR: 0.22; 95% CI: 0.06-0.88; p = 0.03). Conclusion: Our study suggests that IVIG and PE have similar curative effects. Similarly, IVIG seems easier to use and thus can be preferred for treating GBS.

Differentiating Lung Nodules Due to Coccidioides from Those Due to Lung Cancer Based on Radiographic Appearance.

BACKGROUND: Coccidioidomycosis (cocci) is an endemic fungal disease that can cause asymptomatic or post-symptomatic lung nodules which are visible on chest CT scanning. Lung nodules are common and can represent early lung cancer. Differentiating lung nodules due to cocci from those due to lung cancer can be difficult and lead to invasive and expensive evaluations. MATERIALS AND METHODS: We identified 302 patients with biopsy-proven cocci or bronchogenic carcinoma seen in our multidisciplinary nodule clinic. Two experienced radiologists who were blinded to the diagnosis read the chest CT scans and identified radiographic characteristics to determine their utility in differentiating lung cancer nodules from those due to cocci. RESULTS: Using univariate analysis, we identified several radiographic findings that differed between lung cancer and cocci infection. We then entered these variables along with age and gender into a multivariate model and found that age, nodule diameter, nodule cavitation, presence of satellite nodules and radiographic presence of chronic lung disease differed significantly between the two diagnoses. Three findings, cavitary nodules, satellite nodules and chronic lung disease, have sufficient discrimination to potentially be useful in clinical decision-making. CONCLUSIONS: Careful evaluation of the three obtained radiographic findings can significantly improve our ability to differentiate benign coccidioidomycosis infection from lung cancer in an endemic region for the fungal disease. Using these data may significantly reduce the cost and risk associated with distinguishing the cause of lung nodules in these patients by preventing unnecessary invasive studies.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure. METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents. Participants were randomly assigned with a web-based application. For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated. For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo. Aviptadil was administered as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3. Remdesivir was administered as a 200 mg loading dose, followed by 100 mg daily maintenance doses for up to a 10-day total course. For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes. For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead. Mortality up to day 90 was a key secondary outcome. The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. On June 9, 2022, the sponsor stopped the trial of remdesivir due to slow enrolment. The trial is registered with ClinicalTrials.gov, NCT04843761. FINDINGS: Between April 21, 2021, and May 24, 2022, we enrolled 473 participants in the study. For the aviptadil comparison, 471 participants were randomly assigned to aviptadil or matched placebo. The modified intention-to-treat population comprised 461 participants who received at least a partial infusion of aviptadil (231 participants) or aviptadil matched placebo (230 participants). For the remdesivir comparison, 87 participants were randomly assigned to remdesivir or matched placebo and all received some infusion of remdesivir (44 participants) or remdesivir matched placebo (43 participants). 85 participants were included in the modified intention-to-treat analyses for both agents (ie, those enrolled in the 2 x 2 factorial). For the aviptadil versus placebo comparison, the median age was 57 years (IQR 46-66), 178 (39%) of 461 participants were female, and 246 (53%) were Black, Hispanic, Asian or other (vs 215 [47%] White participants). 431 (94%) of 461 participants were in an intensive care unit at baseline, with 271 (59%) receiving high-flow nasal oxygen or non-invasive ventiliation, 185 (40%) receiving invasive mechanical ventilation, and five (1%) receiving ECMO. The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died. The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78). The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10). INTERPRETATION: Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy. FUNDING: National Institutes of Health.

An innovative biomass-driven energy systems for green energy and freshwater production with less CO2 emission: Environmental and technical approaches.

Considering the current crisis of fossil energies, the exploitation of renewables and green technologies is necessary and unavoidable. Additionally, the design and development of integrated energy systems with two or more output products and the maximum usage of thermal losses in order to improve efficiency can boost the yield and acceptability of the energy system. In this regard, this paper develops a comprehensive multi-aspect assessment of the operation of a new solar and biomass energies-driven multigeneration system (MGS). The main units installed in MGS are three electric energy generation units based on a gas turbine process, a solid oxide fuel cell unit (SOFCU) and an organic Rankine cycle unit (ORCU), a biomass energy conversion unit to useful thermal energy, a seawater conversion unit into useable freshwater, a unit for converting water and electricity into hydrogen energy and oxygen gas, a unit for converting solar energy into useful thermal energy (based on Fresnel collector), and a cooling load generation unit. The planned MGS has a novel configuration and layout that has not been considered by researchers recently. The current article is based on presenting a multi-aspect evaluation to study thermodynamic-conceptual, environmental and exergoeconomic analyzes. The outcomes indicated that the planned MGS can produce about 6.31 MW of electrical power and 0.49 MW of thermal power. Furthermore, MGS is able to produce various products such as potable water (∼0.977 kg/s), cooling load (∼0.16 MW), hydrogen energy (∼1.578 g/s) and sanitary water (∼0.957 kg/s). The total thermodynamic indexes were calculated as 78.13% and 47.72%, respectively. Also, the total investment and unit exergy costs were 47.16 USD per hour and 11.07 USD per GJ, respectively. Further, the content of CO2 emitted from the desgined system was equal to 10.59 kmol per MWh. A parametric study has been also developed to identify influencing parameters.

Optimization of a near-zero-emission energy system for the production of desalinated water and cooling using waste energy of fuel cells.

In the present study, a biomass-based multi-purpose energy system that can generate power, desalinated water, hydrogen, and ammonia is presented. The gasification cycle, gas turbine, Rankine cycle, PEM electrolyzer, ammonia production cycle using the Haber-Bosch process, and MSF water desalination cycle are the primary subsystems of this power plant. On the suggested system, a thorough thermodynamic and thermoeconomic evaluation has been conducted. For the analysis, the system is first modeled and investigated from an energy point of view, after which it is similarly studied from an exergy point of view before the system is subjected to economic analysis (exergoeconomic analysis). The system is evaluated and modeled using artificial intelligence to aid in the system optimization process after energy, exergy, and economic modeling and analysis. The resulting model is then optimized using a genetic algorithm to maximize system efficiency and reduce system expenses. EES software does the first analysis. After that, it sends the data to MATLAB program for optimization and to see how operational factors affect thermodynamic performance and overall cost rate. To find the best solution with the maximum energy efficiency and lowest total cost, multi-objective optimization is used. In order to shorten computation time and speed up optimization, the artificial neural network acts as a middleman in the process. In order to identify the energy system's optimal point, the link between the objective function and the choice factors has been examined. The results show that increasing the flow of biomass enhances efficiency, output, and cost while raising the temperature of the gas turbine's input decreases cost while simultaneously boosting efficiency. Additionally, according to the system's optimization results, the power plant's cost and energy efficiency are 37% and 0.3950$/s, respectively, at the ideal point. The cycle's output is estimated at 18900 kW at this stage.

Simulation of CO2 capture from natural gas by cyclic pressure swing adsorption process using activated carbon.

This work presented modeling and simulation of CO2 from natural gas. One of the most promising technologies is Pressure Swing Adsorption (PSA), which is an energy-efficient and cost-effective process for separating and capturing CO2 from industrial processes and power plants. This paper provides an overview of the PSA process and its application for CO2 capture, along with a discussion of its advantages, limitations, and future research directions. This process is pressure swing adsorption (PSA) with four adsorption beds. The adsorption bed columns fill with activated carbon as adsorbent. In this simulation momentum, mass and energy balance are solved simultaneously. The process was designed with two beds in adsorption conditions and the other two beds in desorption conditions. The desorption cycle includes blow-down and purge steps. The linear driving force (LDF) estimates the adsorption rate in modeling this process. The extended Langmuir isotherm is used for the equilibrium between solid and gas phases. The temperature changes by heat transfer from the gas phase to solid and axial heat dispersion. The set of partial differential equations is solved using implicit finite difference.

Development and Optimization of Sildenafil Orodispersible Mini-Tablets (ODMTs) for Treatment of Pediatric Pulmonary Hypertension Using Response Surface Methodology.

The availability of age-appropriate oral dosage forms for pediatric patients has remained a challenge. Orodispersible mini-tablets (ODMTs) are a promising delivery system for pediatric patients. The purpose of this work was the development and optimization of sildenafil ODMTs as a new dosage form for the treatment of pulmonary hypertension in children using a design-of-experiment (DoE) approach. A two-factor, three levels (32) full-factorial design was employed to obtain the optimized formulation. The levels of microcrystalline cellulose (MCC; 10-40% w/w) and partially pre-gelatinized starch (PPGS; 2-10% w/w) were set as independent formulation variables. In addition, mechanical strength, disintegration time (DT), and percent drug release were set as critical quality attributes (CQAs) of sildenafil ODMTs. Further, formulation variables were optimized using the desirability function. ANOVA analysis proved that MCC and PPGS had a significant (p < 0.05) impact on CQAs of sildenafil ODMTs with a pronounced influence of PPGS. The optimized formulation was achieved at low (10% w/w) and high (10% w/w) levels of MCC and PPGS, respectively. The optimized sildenafil ODMTs showed crushing strength of 4.72 ± 0.34 KP, friability of 0.71 ± 0.04%, DT of 39.11 ± 1.03 s, and sildenafil release of 86.21 ± 2.41% after 30 min that achieves the USP acceptance criteria for ODMTs. Validation experiments have shown that the acceptable prediction error (<5%) indicated the robustness of the generated design. In conclusion, sildenafil ODMTs have been developed as a suitable oral formulation for the treatment of pediatric pulmonary hypertension using the fluid bed granulation process and the DoE approach.