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Mechanical Ventilation of the Critically Ill Obese Patient-A Retrospective Cohort Study
No full textOBJECTIVE: Mechanical ventilation of severely ill obese patients can be difficult due to altered physiology, and clinical guidelines are lacking. This study aimed to investigate current practices for mechanical ventilation of obese patients in a Danish ICU.METHODS: This retrospective study analyzed data from the Metabolomics Cohort, a single-centre ICU cohort of critically ill patients. We included patients receiving mechanical ventilation > 12 h and estimated the effect of body mass index (BMI) on ventilator settings, ventilator measurements, and ventilation blood gas parameters. We used linear and mixed-effects linear regression for admission and 5-day changes and adjusted for age, gender, Simplified Acute Physiology Score III, pneumonia, chronic obstructive pulmonary disease, diabetes, and chronic heart disease.RESULTS: Of the 577 patients included in the Metabolomics Cohort, 242 (41.9%) were included in this study. A one-unit increase in BMI resulted in an increase in admission positive end-expiratory pressure (PEEP) of 0.14 cmH2O (95% CI: [0.07, 0.2], p < 0.01), minute volume of 0.08 L/min (95% CI: [0.03, 0.13], p < 0.01), peak inspiratory pressure of 0.23 cmH2O (95% CI: [0.12, 0.34], p < 0.01), mean pressure of 0.18 cmH2O (95% CI: [0.1, 0.27], p < 0.01) and a decrease in admission PaO2/FiO2 ratio of 0.38 (95% CI: [-0.64, -0.13], p < 0.01). During the first 5 days of mechanical ventilation, a one-unit increase in BMI resulted, on average, in an increase in PEEP of 0.14 cmH2O (95% CI: [0.08, 0.2], p < 0.01), minute volume of 0.09 L/min (95% CI: [0.05, 0.12], p < 0.01), tidal volume/kg predicted body weight (PBW) of 0.08 mL/kg PBW (95% CI: [0.05, 0.1], p < 0.01), peak inspiratory pressure of 0.23 cmH2O (95% CI: [0.13, 0.32], p < 0.01), mean pressure of 0.2 cmH2O (95% CI: [0.12, 0.27], p < 0.01), PaCO2 of 0.05 kPa (95% CI: [0.03, 0.07], p < 0.01) and a decrease in PaO2 of 0.07 kPa (95% CI: [-0.12, -0.03], p < 0.01).CONCLUSION: In critically ill patients, an increasing BMI was associated with higher ventilator settings, increased airway pressures, and impaired gas exchange, resulting in hypoxia and hypercapnia. Future research should clarify the clinical impact of this and the potential for improved treatment of obese patients in critical care.EDITORIAL COMMENT: This retrospective analysis, from a single center study cohort of critically ill obese patients requiring mechanical ventilatory support, and from the pre-pandemic period, characteristics of the cases and ventilatory parameters are presented. Patterns for ventilatory changes over time in the ICU are also shown.</p
Geosmin and 2-methylisoborneol exposure affects immune-related gene expression in rainbow trout (<i>Oncorhynchus mykiss</i>)
No full textThe terpenoid compounds geosmin (GSM) and 2-methylisoborneol (MIB), produced by a wide range of microorganisms, are abundant in many aquatic environments. Both compounds are easily detectable by humans (<5 ng/L), and they are often associated with an earthy and musty unpleasant odor in drinking water and aquatic food products (such as fish and shellfish, blue food), which are costly to circumvent. These compounds are well known to bioaccumulate in larger organisms, such as fish, but the interactions between immune responses and these off-flavor compounds are not well known. We evaluated if prior exposure to these compounds can affect immune gene expression in trout. Juvenile (∼9 g) rainbow trout (Oncorhynchus mykiss) were exposed to geosmin and MIB in environmentally relatable concentrations as well as a high concentration (10, 50, 500, 1000 ng/L) for 24 h before IP injection of lipopolysaccharide (LPS) eliciting inflammatory reactions in trout. Following another 24 h fish were euthanized and liver and spleen were sampled for gene expression measurements (qPCR). Both geosmin and MIB significantly altered expression of several immune-related genes in a tissue- and concentration-dependent manner. Geosmin exposure was associated with a dosage dependent down-regulation in the liver of genes encoding cytokines (IL-4/13a, IL-12, TNFα), acute phase proteins (SAA, precerebellin), antimicrobial peptides (cathelicidin 1 and 2), T cell markers (TCR, CD 8), and B cell marker (IgDm). This may have implications for fish in general, but is particularly notable for those living in eutrophicated waters.</p
Chapter 12 - Functional characteristics of achira (<i>Canna indica</i> L.), with an emphasis on aerial parts
No full textAchira (Canna indica L.) is a versatile plant with diverse applications in nutrition, medicine, sustainability, and culture. Indigenous to the Andean region, its leaves have been historically used for medicinal purposes, packaging food, and supporting traditional diets. The phytochemical composition of achira leaves and flowers includes antioxidants, dietary fibers, amino acids, and organic acids, contributing to their therapeutic effects against ailments such as malaria, dysentery, and hepatitis. Additionally, the leaves serve as livestock fodder, green vegetables, and natural food wraps for traditional dishes, enhancing their cultural and dietary value. Achira leaves are integral to sustainable agriculture, functioning as biochar in wastewater treatment and providing potassium-enriched soil supplements. The seeds are highly valued to extract a purple dye and for their versatility in manufacturing crafts. The role of this plant in traditional medicine and modern pharmacology highlights its potential in treating conditions like cancer and cardiovascular diseases. Moreover, its bioactive properties make achira suitable for creating natural dyes and health-promoting food products. The continued exploration of achira’s multifunctional uses offers pathways to bolster food security, promote cultural preservation, and drive sustainability. With increasing global interest, achira exemplifies the intersection of traditional knowledge and contemporary innovation, holding promise for both local economies and global environmental management
Discrepancies in the therapeutic indications granted by the European Medicines Agency and the US Food and Drug Administration for new cancer drugs:An analysis of potential explanations
No full textBACKGROUND: Studies have found notable differences between the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) in indications granted to new cancer drugs. These discrepancies cause uncertainty regarding the clinical benefit for the patients treated with the drugs. It is unknown why they occur; therefore, we aimed to analyse if maturity of data or characteristics of the pivotal trials might be explanations.METHODS: All new cancer drugs approved by both EMA and the FDA with a final decision in at least one of the agencies between January 1, 2020, to December 31, 2022, were included in the analysis. The drugs were identified by searching the FDA and EMA websites.RESULTS: A total of 36 new cancer drugs were included. Notable differences between EMA and the FDA in the granted indication were found in 15 (42%) of the drugs. EMA often had more mature data than the FDA, but the proportions were similar when comparing drugs with and without notable differences. Furthermore, the results did not indicate that low level of evidence (e.g., early phase trial as the pivotal, single-arm design, or use of surrogate endpoints) was more common in the cancer drugs with notable differences in the indication.CONCLUSION: The frequent discrepancies in the granted indications between EMA and the FDA for new cancer drugs could not be explained by maturity of data at time of assessment or characteristics of the pivotal trials. Therefore, divergence in regulatory policies between the two agencies is considered a more likely explanation.POLICY SUMMARY: Discrepancies between regulatory agencies in the indications granted to new cancer drugs suggest a problematic extrapolation and thus uncertainty regarding the clinical benefit for the patients. The present study seeks to identify potential explanations for the discrepancies to reduce the misalignment in the future.</p
Developments in hydrogen/deuterium exchange mass spectrometry at sub-zero temperatures
No full textHDX-MS has become a popular and established method for studying the dynamic conformational landscape and interactions of proteins in solution. Over the years, HDX-MS has been used to analyze increasingly complex protein systems in terms of size, purity, and biologically relevant conditions. For example, HDX-MS has been employed to study membrane proteins in their native lipid membranes from bacteria, intact viruses, and individual proteins within living cells. However, these exciting and complex new applications pose significant challenges to traditional HDX-MS experiments, particularly the need to perform sample pretreatment and LC separation on a short timescale at zero degrees to prevent inadvertent deuterium labeling information loss (back-exchange). A promising development in HDX-MS is the use of sub-zero temperature separation to reduce back-exchange and enable extended chromatographic separation. In this review, we aim to provide an overview of the current state of sub-zero temperature HDX-MS and the challenges associated with its use
Emergent inflation-deflation cycles from minimalistic wage dynamics
No full textFisher's classical debt-deflation model outlined a sequence of events governing the positive feedback in economic downturns. This theory has been formative for modern economic policy, including the 2008 crisis. However, few quantitative models have been developed to incorporate positive feedback in cyclic economic dynamics. Here we present an agent-based model in which companies compete by adjusting wages, and workers probabilistically choose employers based on the wage offered. Despite omitting debt, unemployment, and other features in Fisher's model, the model generates endogenous inflation-deflation cycles, irregularly recurring recessions, and clustered bankruptcies. These dynamics emerge from feedback between wage growth, consumer demand, and company fragility, where high wages increase purchasing power but also raise vulnerability to shocks. The model qualitatively reproduces several empirical patterns, including inflation volatility, recession periods and durations, and asymmetric asset returns, though it diverges in firm size distributions and mortality rates. Our results demonstrate that complex macroeconomic behavior can arise from simple, wage-driven interactions alone
Review Article:Extending the Frontiers of Intestinal Ultrasound Knowledge, Performance and Expansion
No full textBACKGROUND: Intestinal ultrasonography (IUS) is increasingly utilised for diagnosing and monitoring IBD. Despite its cost-effectiveness, patient tolerance and suitability for serial bedside assessments, broad adoption has been limited by knowledge gaps in evidence, training and standardisation.AIMS: To summarise key knowledge gaps in the assessment of luminal disease activity, postoperative recurrence, complications, pouch-related disorders and the use of IUS in paediatrics, contrast enhancement, elastography, as well as education, training and future applications involving artificial intelligence.METHODS: We conducted a systematic umbrella review, following PRISMA guidelines, to map the current landscape of high-quality evidence and identify gaps in IUS research relevant to IBD. We searched MEDLINE from inception to February 2025 for systematic reviews, meta-analyses and consensus statements. We extracted data from eligible studies on design, outcomes and identified research gaps. Gaps were categorised by insufficient information, bias, inconsistency or lack of relevant data.RESULTS: Sixty of 507 studies met inclusion criteria. Key gaps included lack of validated and standardised IUS activity indices for Crohn's disease and ulcerative colitis, limited evidence for IUS in post-operative recurrence, paediatric populations and perianal or pouch disease. Data on the use of contrast-enhanced ultrasound and elastography were sparse. Small sample sizes, heterogeneous designs and inadequate follow-up limited most studies. Training, competency assessment and integration of artificial intelligence remain underexplored.CONCLUSIONS: Sizable gaps persist in the evidence base for IUS in IBD. Addressing these gaps through robust, multicentre studies and consensus-driven frameworks is essential to optimise the clinical and research utility of IUS in IBD management.</p
Impact of quality clusters on antibiotic prescribing patterns. A difference-in-differences study from Danish general practice
No full textGlobally, a more rational use of antibiotics is needed to face the threat of antimicrobial resistance. In 2018, quality clusters were introduced in Danish general practice as a new quality improvement initiative. In the clusters, general practitioners engage in self-selected quality improvement topics, such as antibiotics prescribing. This study investigates whether engaging with antibiotics as a topic in quality clusters improves antibiotics prescribing, and whether choice and number of quality improvement strategies matter for behaviour change. We link register data on redeemed antibiotics prescriptions from Danish general practice from 2015–2020 with survey data from 2020 on whether, when, and how practices in clusters engaged with antibiotics as a quality improvement topic. We use a difference-in-differences approach including general practice fixed effects and practice-averaged time-varying patient population characteristics in linear regressions models. We find that practices engaged with antibiotics as a quality improvement topic increase their proportion of narrow spectrum antibiotics prescriptions compared to other practices, while there is no difference in changes in the total number of prescribed antibiotics. Neither the choice nor the number of surveyed quality improvement strategies seem to influence the behavioural outcomes. In conclusion, engaging in antibiotics in quality clusters to some extent improved antibiotic prescribing.Globally, a more rational use of antibiotics is needed to face the threat of antimicrobial resistance. In 2018, quality clusters were introduced in Danish general practice as a new quality improvement initiative. In the clusters, general practitioners engage in self-selected quality improvement topics, such as antibiotics prescribing. This study investigates whether engaging with antibiotics as a topic in quality clusters improves antibiotics prescribing, and whether choice and number of quality improvement strategies matter for behaviour change. We link register data on redeemed antibiotics prescriptions from Danish general practice from 2015–2020 with survey data from 2020 on whether, when, and how practices in clusters engaged with antibiotics as a quality improvement topic. We use a difference-in-differences approach including general practice fixed effects and practice-averaged time-varying patient population characteristics in linear regressions models. We find that practices engaged with antibiotics as a quality improvement topic increase their proportion of narrow spectrum antibiotics prescriptions compared to other practices, while there is no difference in changes in the total number of prescribed antibiotics. Neither the choice nor the number of surveyed quality improvement strategies seem to influence the behavioural outcomes. In conclusion, engaging in antibiotics in quality clusters to some extent improved antibiotic prescribing.</p
Neostigmine Versus Sugammadex for Reversal of Neuromuscular Blockade in Elderly Patients:A Blinded Randomised Study
No full textINTRODUCTION: Reversal of rocuronium-induced neuromuscular blockade (NMB) is possible with either neostigmine or sugammadex to prevent residual NMB. In adults, sugammadex provides faster reversal and has fewer side effects compared to neostigmine, even when combined with glycopyrrolate. In elderly patients, rocuronium has a longer onset time and duration of action; however, little is known about the reversal of rocuronium-induced NMB with either sugammadex or neostigmine and the recovery of muscle function postoperatively. The aim of this study was to determine the time to full recovery of neuromuscular function, defined as Train of Four ratio (TOF) ≥ 0.9 after reversal with either neostigmine 50 μg kg-1 or sugammadex 2 mg kg-1 in elderly patients aged 75 years or above undergoing total intravenous anaesthesia with rocuronium-induced moderate NMB. We hypothesised that sugammadex 2 mg kg-1 provides a shorter time to TOF ≥ 0.9 compared to neostigmine 50 μg kg-1.METHODS: We included 41 patients aged ≥ 75 years with American Society of Anesthesiologists (ASA) physical health classes I-IV scheduled for robotic-assisted laparoscopic surgery under total intravenous anaesthesia with rocuronium. Patients were randomised to reversal with neostigmine/glycopyrrolate 50/10 μg kg-1 or sugammadex 2 mg kg-1 if the depth of NMB was within the range from TOF count of 2 to a TOF ratio < 0.60. The primary outcome was time to TOF ≥ 0.9, measured from the start of administration of the reversal agent. Secondary outcomes were signs of residual NMB within 90 min after administration of the reversal agent.RESULTS: A total of 40 patients were evaluated for the primary outcome. A total of 17 patients received neostigmine/glycopyrrolate and 23 patients received sugammadex. Time to TOF ≥ 0.9 was significantly shorter with sugammadex: 147 s (SD 100) vs. 573 s (SD 501) with a difference of 427 s (95% CI: 205 to 648). No difference was found in the occurrence of clinical signs of residual NMB.CONCLUSION: Time to TOF ≥ 0.9 was shorter after reversal with sugammadex 2 mg kg-1 compared to neostigmine/glycopyrrolate 50/10 μg kg-1 in elderly patients administered rocuronium during total intravenous anaesthesia. For neostigmine a large variation in time to recovery was detected. No significant difference in clinical signs of residual NMB was found.EDITORIAL COMMENT: This trial in an elderly surgical cohort assessed reversal times for rocuronium comparing sugammadex and neostigmine. Sugammadex demonstrated faster and more predictable reversal effects in this cohort.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06228092.</p
The influence of tablet size and weight on water-based microwave-induced in situ amorphization
No full textMicrowave-induced in situ amorphization is an innovative technology that enables the direct preparation of amorphous solid dispersions (ASDs) in the final dosage form. This approach offers significant advantages in addressing the challenges related to the long-term physical stability and downstream processing of ASDs. However, most previous studies have primarily focused on regular tablet sizes intended for adult patients. In light of the unique considerations and challenges associated with paediatric formulations, this study aimed to investigate the impact of tablet sizes with varying weights on microwave-induced in situ amorphization. The overall objective was to establish a novel platform for personalized formulations that cater specifically to paediatric patients with improved drug dissolution rate and enhanced patient compliance. Indomethacin (IND) was chosen as a model drug while PVP/VA 64 was selected as the polymeric carrier to prepare ASDs with 20 % (w/w) drug loading. Different-sized tablets (6 mm, 4 mm, and 2 mm which were considered as mini-tablets intended for paediatric patients) were characterized using a combination of imaging, structural and thermal analyses, followed by in vitro dissolution testing. With 2 mm mini-tablets, in particular, varying numbers of mini-tablets (one to five) were placed into an HPMC capsule which was then exposed to microwave irradiation. It was observed that a complete amorphization accompanied with an improved dissolution rate was achieved for formulations of all tablet sizes in this study. Regardless of tablet size, there were no significant differences in the extent of dissolution rate enhancement. In addition, a white-to-yellow colour change indicating amorphization of IND and a marked tablet deformation were observed in all formulations after microwaving. Among all 2 mm mini tablet formulations in capsules, the 5-in-1 formulation showed the highest amorphization rate. Overall, the in-situ amorphization platform proposed in this study can be applied to tablets with varying diameters down to 2 mm and weights down to 4 mg, indicating a promising paediatric formulation strategy.</p