Southport College

Abstract Introduction Obstructive sleep apnoea (OSA) frequently causes excessive daytime sleepiness (EDS). EDS impairs quality-of-life and can induce motor vehicle accidents or workplace injuries. Treatment dogma would suggest that CPAP (continuous positive airway pressure), the gold standard treatment, should abolish EDS, but up to 22% of CPAP-treated OSA patients can have residual EDS. Our tertiary health service serves a large catchment within the eastern coast of Australia. We aimed to examine the prevalence and precipitating causes of post-CPAP residual EDS in our local OSA population. Methods This was a single-centre retrospective study. Data set was compiled from the medical records of patients aged ≥18 years presenting to outpatients with OSA diagnosis in 2019-2024. Results Out of 354 patients, 35 (10%) had residual EDS on post-CPAP commencement follow-up. Median age was 58 years (IQR 54-75); 60% (n = 21) were males. Chronic pain and mental health co-morbidities were prevalent in 46%. Median Epworth Sleepiness Scale and Apnoea-Hypopnoea Index at diagnosis were 14 and 31.7, respectively. Most had home-based diagnostic study (n = 20) and lab-based CPAP titration (n = 24). 6 repeat in-lab titration studies and 3 vigilance tests were performed to evaluate residual EDS. Co-existing insomnia and CPAP-related issues were commonly identified as causing residual EDS. Conclusion OSA treatment is often undertaken to improve patients’ daytime somnolence and quality-of-life. Therefore, from the outset, patients should be informed about the CPAP acclimatisation process and of co-existing non-OSA conditions that may be perpetuating their EDS. Insomnia is not uncommon in modern society and should be screened for at index clinic reviews for OSA.

IntroductionMany patients presenting to hospital with lower gastrointestinal bleeding (LGIB) are elderly and co-morbid. British Society of Gastroenterology (BSG) guidelines recommend LGI endoscopy for all patients admitted with LGIB. As the majority of LGIB ceases spontaneously and risks of endoscopy increase with patient age, a ‘watch and wait’ management approach may be appropriate for older patients.MethodsPatients aged ≥75 years presenting with LGIB to seven hospital trusts from June 1st– September 1st 2019 were included. Data on presentation, management and outcomes were recorded, then compared to current BSG guidelines.Results127 patients were included. 47% were male with a mean age 84 (range 75-96), 73.2% of patients had ≥2 listed co-morbidities. Mean Shock Index (SI) on presentation was 0.69, with a SI >1 being rare (7.0%) and reduced to 2.4% following resuscitation. Of stable patients (SI<1), 94.3% were classified as having a major bleed (Oakland Score >8). 96.1% of presenting patients were admitted, while 3.9% were discharged from A&E. 80% of these discharged patients had an Oakland Score >8. 21 (17.2%) of admitted patients received an inpatient lower GI endoscopy; 19% of which received endoscopic therapy. The most commonly identified cause of LGIB was diverticulosis (23.8%). Overall, 82.8% of admitted patients received no inpatient lower GI endoscopy and were managed conservatively. Comparing those who underwent LGI endoscopy versus a watch and wait approach, there was no difference in inpatient mortality (0% vs 4%, p=1.0) or 30-day re-admission rate (9.5% vs 22.8%, p= 0.24). However, undergoing inpatient LGI endoscopy was associated with greater median length of stay (8 days vs 3 days, p=0.0002) PTU-50 Figure 1Serial cholangiograms from one patietConclusionsAge and co-morbidities complicate risk stratification in the elderly as many will score highly regardless of bleed severity, limiting the role of the Oakland Score. Endoscopic assessment of all elderly patients presenting with LGIB is not performed in real world practice, may not be necessary or even appropriate. Although not in keeping with current guidelines, this watch and wait approach does not appear to be associated with adverse outcomes in the elderly.

Synchrotron-based X-ray spectroscopy is a powerful technique for investigating vanadium speciation in marine sediment.

In vitro bioassays are increasingly used for water quality monitoring. Surface water samples often need to be enriched to observe an effect and solid-phase extraction (SPE) is commonly applied for this purpose. The applied methods are typically optimised for the recovery of target chemicals and not for effect recovery for bioassays. A review of the few studies that have evaluated SPE recovery for bioassays showed a lack of experimentally determined recoveries. Therefore, we systematically measured effect recovery of a mixture of 579 organic chemicals covering a wide range of physicochemical properties that were spiked into a pristine water sample and extracted using large volume solid-phase extraction (LVSPE). Assays indicative of activation of xenobiotic metabolism, hormone receptor-mediated effects and adaptive stress responses were applied, with non-specific effects determined through cytotoxicity measurements. Overall, effect recovery was found to be similar to chemical recovery for the majority of bioassays and LVSPE blanks had no effect. Multi-layer SPE exhibited greater recovery of spiked chemicals compared to LVSPE, but the blanks triggered cytotoxicity at high enrichment. Chemical recovery data together with single chemical effect data were used to retrospectively estimate with reverse recovery modelling that there was typically less than 30% effect loss expected due to reduced SPE recovery in published surface water monitoring studies. The combination of targeted experiments and mixture modelling clearly shows the utility of SPE as a sample preparation method for surface water samples, but also emphasizes the need for adequate controls when extraction methods are adapted from chemical analysis workflows.

Heparan sulfate is identified as a ligand receptor for polynuclear platinum anti-cancer agents through sulfate cluster binding. We present a new biological role for platinum and coordination compounds and a new target for metal-based drugs while presenting a new chemotype for heparanase and growth factor inhibition through modulation (metalloshielding) of their interactions. Masking of extracellular (ECM)-resident heparan sulfate (HS) through metalloshielding results in very effective inhibition of physiologically critical HS functions including enzyme (heparanase, HPSE) and protein growth factor recognition. The interaction of the highly cationic polynuclear platinum complexes (PPCs) with the highly sulfated pentasaccharide Fondaparinux (FPX, in this case as a model HS-like substrate) results in inhibition of its cleavage by the HS-related enzyme heparanase. Binding of the fibroblast growth factor FGF-2 to HS is also inhibited with consequences for downstream signalling events as measured by a reduction in accumulation of phospho-S6 ribosomal protein in human colon tumor HCT-116 cells. The end-point of inhibition of HPSE activity and growth factor growth factor signaling is the prevention of cell invasion and angiogenesis. Finally these events culminate in inhibition of HCT-116 cell invasion at sub-cytotoxic concentrations and the process of angiogenesis. A competition assay shows that Fondaparinux can sequester the 8+ TriplatinNC from bound DNA, emphasising the strength of PPC-HS interactions. Altering the profile of platinum agents from cytotoxic to anti-metastatic has profound implications for future directions in the development of platinum-based chemotherapeutics.