Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of... Show moreIntroduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome. Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting. Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795. Show less
Batey, N.; Henry, C.; Garg, S.; Wagner, M.; Malhotra, A.; Valstar, M.; ... ; European Soc Paediat Res ESPR 2022
Advances in neonatal care have resulted in improved outcomes for high-risk newborns with technologies playing a significant part although many were developed for the neonatal intensive care unit.... Show moreAdvances in neonatal care have resulted in improved outcomes for high-risk newborns with technologies playing a significant part although many were developed for the neonatal intensive care unit. The care provided in the delivery room (DR) during the first few minutes of life can impact short- and long-term neonatal outcomes. Increasingly, technologies have a critical role to play in the DR particularly with monitoring and information provision. However, the DR is a unique environment and has major challenges around the period of foetal to neonatal transition that need to be overcome when developing new technologies. This review focuses on current DR technologies as well as those just emerging and further over the horizon. We identify what key opinion leaders in DR care think of current technologies, what the important DR measures are to them, and which technologies might be useful in the future. We link these with key technologies including respiratory function monitors, electoral impedance tomography, videolaryngoscopy, augmented reality, video recording, eye tracking, artificial intelligence, and contactless monitoring. Encouraging funders and industry to address the unique technological challenges of newborn care in the DR will allow the continued improvement of outcomes of high-risk infants from the moment of birth. Impact Technological advances for newborn delivery room care require consideration of the unique environment, the variable patient characteristics, and disease states, as well as human factor challenges. Neonatology as a speciality has embraced technology, allowing its rapid progression and improved outcomes for infants, although innovation in the delivery room often lags behind that in the intensive care unit. Investing in new and emerging technologies can support healthcare providers when optimising care and could improve training, safety, and neonatal outcomes. Show less
Herbolsheimer, F.; Ungar, N.; Portegijs, E.; Dallmeier, D.; Schaap, L.; Smith, T.; ... ; Pas, S. van der 2021
Opioids are complex drugs that produce profit (most importantly analgesia) as well as a myriad of adverse effects including gastrointestinal motility disturbances, abuse and addiction, sedation and... Show moreOpioids are complex drugs that produce profit (most importantly analgesia) as well as a myriad of adverse effects including gastrointestinal motility disturbances, abuse and addiction, sedation and potentially lethal respiratory depression (RD). Consequently, opioid treatment requires careful evaluation in terms of benefit on the one hand and harm on the other. Considering benefit and harm from an economic perspective, opioid treatment should lead to profit maximization with decision theory defining utility as (profit - loss). We here focus on the most devastating opioid adverse effect, RD and define opioid utility U = P(benefit) - P(harm), where P(benefit) is the probability of opioid-induced analgesia and P(harm) the probability of opioid-induced RD. Other utility functions are also discussed including the utility U = P(benefit AND NOT harm), the most wanted opioid effect, i.e., analgesia without RD, and utility surfaces, which depict the continuum of probabilities of presence or absence of analgesia in combination with the presence or absence of RD. Utility functions are constructed from pharmacokinetic and pharmacodynamic data sets, although pragmatic utility functions may be constructed when pharmacokinetic data are not available. We here discuss utilities of several opioids including the partial mu-opioid-receptor agonist buprenorphine, the full opioid receptor agonists fentanyl and alfentanil, and the bifunctional opioid cebranopadol, which acts at mu-opioid and nociception/orphanin FQ-receptors. We argue that utility functions give clinicians the opportunity to make an informed decision when opioid analgesics are needed for pain relief, in which opioids with a positive utility function are preferred over opioids with negative functions. Furthermore, utility functions of subpopulations will give an extra insight as a utility functions measured in one subgroup (e.g., patients with postoperative pain, good opioid responders) may not be mirrored in other patient subgroups ( e.g., neuropathic pain patients, poor opioid responders). Show less
Importance of the field: Worldwide the number of patients affected by chronic pain is growing and conventional treatment is often insufficient. Recently the importance of the N-methyl-D-aspartate... Show moreImportance of the field: Worldwide the number of patients affected by chronic pain is growing and conventional treatment is often insufficient. Recently the importance of the N-methyl-D-aspartate receptor (NMDAR) in the mechanisms and maintenance of chronic pain was established. Ketamine (introduced in the 1960s as an anesthetic) is the most studied NMDAR antagonist in the treatment of various chronic pain syndromes. Areas covered in this review: The pharmacology, safety and toxicology of ketamine are discussed. Further, electronic databases were scanned for prospective, randomized controlled trials that assessed ketamine's analgesic effect in patients with chronic pain. The focus of this review is on trials published after 2008 that applied long-term intravenous infusions. What the reader will gain: While most studies on intravenous ketamine show acute analgesic effects, three recent trials on long-term ketamine treatment (days to weeks) demonstrate the effectiveness of ketamine in causing long-term (months) relief of chronic pain. Despite these positive results, further studies are needed on safety/toxicity issues. Other administration modes are less effective in causing long-term pain relief. Take home message: There is now evidence form a limited number of studies that pain relief lasting for months is observed after long-term intravenous ketamine infusion, suggesting a modulatory effect of ketamine in the process of chronic pain, possibly via blockade of upregulated NMDAR. Show less
Olofsen, E.; Mooren, R.; Dorp, E. van; Aarts, L.; Smith, T.; Hartigh, J. den; ... ; Sarton, E. 2010
BACKGROUND: In pharmacokinetic pharmacodynamic modeling studies, venous plasma samples are sometimes used to derive pharmacodynamic model parameters. In the current study the extent of... Show moreBACKGROUND: In pharmacokinetic pharmacodynamic modeling studies, venous plasma samples are sometimes used to derive pharmacodynamic model parameters. In the current study the extent of arteriovenous concentration differences of morphine-6-glucuronide (M6G) was quantified. We used simulation studies to estimate possible biases in pharmacodynamic model parameters when linking venous versus arterial concentrations to effect. METHODS: Seventeen healthy volunteers received an IV 90-second infusion of 0.3 mg/kg morphine-6-glucuronide (M6G). Arterial and venous blood samples, from the radial artery and cubital vein, respectively, were obtained. An extended pharmacokinetic model was constructed linking arterial and venous compartments. The extent of bias in pharmacodynamic model parameter estimates was explored in simulation studies with NONMEM, simulating M6G effect using first-order effect-compartment inhibitory sigmoid E-MAX models. M6G effect was simulated at various values for the arterial blood-effect-site equilibration half-lifes (t(1/2)k(EO)), ranging from 5 to 240 minutes. RESULTS: Arteriovenous concentration differences were apparent, with higher arterial plasma concentrations just after infusion, whereas at later times (>60 minutes) venous M6G concentrations exceeded arterial concentrations. The extended pharmacokinetic model adequately described the data and consisted of 3 arterial compartments, 1 central venous compartment, and 1 peripheral venous compartment. The simulation studies revealed large biases in model parameters derived from venous concentration data. The biases were dependent on the value of t(1/2)k(EO). Assuming that the true values of M6G t(1/2)k(EO) range from 120 to 240 minutes (depending on the end point measured), we would have underestimated t(1/2)k(EO) by 30%, whereas the potency parameter would have been overestimated by about 40%, when using venous plasma samples. CONCLUSIONS: Because of large arteriovenous differences in M6G plasma, concentration biases in pharmacodynamic model parameters will occur when linking venous concentration to effect, using a traditional effect-compartment model. (Anesth Analg 2010;111:626-32) Show less
