| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 3. |
- Paterson, Ross W, et al.
(författare)
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Serum and cerebrospinal fluid biomarker profiles in acute SARS-CoV-2-associated neurological syndromes.
- 2021
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Ingår i: Brain communications. - : Oxford University Press (OUP). - 2632-1297. ; 3:3
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Tidskriftsartikel (refereegranskat)abstract
- Preliminary pathological and biomarker data suggest that SARS-CoV-2 infection can damage the nervous system. To understand what, where and how damage occurs, we collected serum and CSF from patients with COVID-19 and characterized neurological syndromes involving the PNS and CNS (n=34). We measured biomarkers of neuronal damage and neuroinflammation, and compared these with non-neurological control groups, which included patients with (n=94) and without (n=24) COVID-19. We detected increased concentrations of neurofilament light, a dynamic biomarker of neuronal damage, in the CSF of those with CNS inflammation (encephalitis and acute disseminated encephalomyelitis) [14800pg/ml (400, 32400)], compared to those with encephalopathy [1410pg/ml (756, 1446)], peripheral syndromes (Guillain-Barré syndrome) [740pg/ml (507, 881)] and controls [872pg/ml (654, 1200)]. Serum neurofilament light levels were elevated across patients hospitalized with COVID-19, irrespective of neurological manifestations. There was not the usual close correlation between CSF and serum neurofilament light, suggesting serum neurofilament light elevation in the non-neurological patients may reflect peripheral nerve damage in response to severe illness. We did not find significantly elevated levels of serum neurofilament light in community cases of COVID-19 arguing against significant neurological damage. Glial fibrillary acidic protein, a marker of astrocytic activation, was not elevated in the CSF or serum of any group, suggesting astrocytic activation is not a major mediator of neuronal damage in COVID-19.
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| 4. |
- Hens, Bart, et al.
(författare)
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Formulation predictive dissolution (fPD) testing to advance oral drug product development : An introduction to the US FDA funded '21st Century BA/BE' project
- 2018
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 548:1, s. 120-127
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Forskningsöversikt (refereegranskat)abstract
- Over the past decade, formulation predictive dissolution (fPD) testing has gained increasing attention. Another mindset is pushed forward where scientists in our field are more confident to explore the in vivo behavior of an oral drug product by performing predictive in vitro dissolution studies. Similarly, there is an increasing interest in the application of modern computational fluid dynamics (CFD) frameworks and high-performance computing platforms to study the local processes underlying absorption within the gastrointestinal (GI) tract. In that way, CFD and computing platforms both can inform future PBPK-based in silico frameworks and determine the GI-motility-driven hydrodynamic impacts that should be incorporated into in vitro dissolution methods for in vivo relevance. Current compendial dissolution methods are not always reliable to predict the in vivo behavior, especially not for biopharmaceutics classification system (BCS) class 2/4 compounds suffering from a low aqueous solubility. Developing a predictive dissolution test will be more reliable, cost-effective and less time-consuming as long as the predictive power of the test is sufficiently strong. There is a need to develop a biorelevant, predictive dissolution method that can be applied by pharmaceutical drug companies to facilitate marketing access for generic and novel drug products. In 2014, Prof. Gordon L. Amidon and his team initiated a far-ranging research program designed to integrate (1) in vivo studies in humans in order to further improve the understanding of the intraluminal processing of oral dosage forms and dissolved drug along the gastrointestinal (GI) tract, (2) advancement of in vitro methodologies that incorporates higher levels of in vivo relevance and (3) computational experiments to study the local processes underlying dissolution, transport and absorption within the intestines performed with a new unique CFD based framework. Of particular importance is revealing the physiological variables determining the variability in in vivo dissolution and GI absorption from person to person in order to address (potential) in vivo BE failures. This paper provides an introduction to this multidisciplinary project, informs the reader about current achievements and outlines future directions.
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| 6. |
- Sinko, Patrick D., et al.
(författare)
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Particle Size, Dose, and Confinement Affect Passive Diffusion Flux through the Membrane Concentration Boundary Layer
- 2023
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 21:1, s. 201-215
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Tidskriftsartikel (refereegranskat)abstract
- The authors present a steady-state-, particle-size-, and dose-dependent dissolution-permeation model that describes particle dissolution within the concentration boundary layer (CBL) adjacent to a semipermeable surface. It is critical to understand how particle size and dose affect the behavior of dissolving particles in the presence of a CBL adjacent to a semipermeable surface both in vivo and in vitro. Control of particle size is ubiquitous in the pharmaceutical industry; however, traditional pharmaceutical assumptions of particle dissolution typically ignore particle dissolution within the length scale of the CBL. The CBL does not physically prevent particles from traveling to the semipermeable surface (mucus, epithelial barrier, synthetic membrane, etc.), and particle dissolution can occur within the CBL thickness (delta(C)) if the particle is sufficiently small (similar to d(particle) <= delta(C)). The total flux (the time rate transport of molecules across the membrane surface per unit area) was chosen as a surrogate parameter for measuring the additional mass generated by particles dissolving within the donor CBL. Mass transfer experiments aimed to measure the total flux of drug using an ultrathin large-area membrane diffusion cell described by Sinko et al. with a silicone-based membrane (). Suspensions of ibuprofen, a model weak-acid drug, with three different particle-size distributions with average particle diameters of 6.6, 37.4, and 240 mu m at multiple doses corresponding to a range of suspension concentrations with dimensionless dose numbers of 2.94, 14.7, 147, and 588 were used to test the model. Experimentally measured total flux across the semipermeable membrane/CBL region agreed with the predictions from the proposed model, and at a range of relatively low suspension concentrations, dependent on the average particle size, there was a measurable effect on the flux due to the difference in delta(C) that formed at the membrane surface. Additionally, the dose-dependent total flux across the membrane was up to 10% higher than the flux predicted by the standard Higuchi-Hiestand dissolution model where the effects of confinement were ignored as described by Wang et al. ().
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