https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42765 2C receptor agonist, has shown potential at reducing the symptoms of substance use disorder. This pilot study (initiated prior to market withdrawal) examined feasibility and safety of lorcaserin treatment in people undergoing residential detoxification and treatment for AUD and MUD. This was an open label pilot study of lorcaserin where participants (n = 10 AUD; n = 8 MUD) received 10-mg lorcaserin daily for 4 days then twice daily for 1 month. Primary outcome measures included recruitment and reten tion rate, incidence of treatment-emergent events, incidence of methamphetamine or alcohol withdrawal-related events, heart rate, and blood pressure. Secondary measures included pharmacokinetic data and self-reported alcohol or methamphetamine use, craving, and psychological distress. AUD participants were recruited faster and had a greater retention rate compared with MUD participants. Lorcaserin did not alter vital signs, was well tolerated, and had a similar pharmacokinetic profile to individuals with obesity. Lorcaserin reduced self-reported alcohol and amphetamine-type sub stance use and craving in AUD and MUD participants, respectively. Self-reported psychological health also improved over the treatment period for all participants. Despite the pilot nature of this study, our data support the notion of 5-HT_2C receptors as a therapeutic target for drug and alcohol abuse.]]> Wed 28 Sep 2022 14:31:11 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54339 Wed 28 Feb 2024 15:10:12 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35202 Wed 23 Feb 2022 16:07:13 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46247 Wed 22 Mar 2023 19:04:56 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50573 30% of patients) of any grade were nausea and musculoskeletal pain. The only dose limiting toxicity (DLT) was diarrhoea in a patient receiving 200 mg NMP (overall DLT rate 8%; 95% CI 0–36%). Hence, the MTD was not defined. Median progression-free and overall survival were 57 (range 29–539) days and 33 (95% CI 9.7– > 44) months, respectively. The best response of stable disease (SD) was achieved in nine patients (69%; 95% CI 39–91%). PK analysis demonstrated proportional dose–concentrations up to 400 mg daily, with a more linear relationship above 500 mg. Maximum plasma concentrations (Cmax) of 16.7 mg/L at the 800 mg dose were below those predicted to inhibit BET-bromodomains. Peripheral blood immune-profiling demonstrated maintenance of natural killer (NK) cells, and a gene expression signature suggestive of enhanced T, B and NK cell functions; a subject with prolonged exposure manifested sustained recovery of B and NK cells at 12 months. Conclusions: NMP demonstrated potential disease stabilising and immunomodulatory activity at sub-BET inhibitory plasma concentrations and was well tolerated in RR–MM; an MTD was not determined up to a maximum dose of 1 g daily. Further dose-finding studies are required to optimise NMP dosing strategies for therapeutic intervention.]]> Wed 15 May 2024 15:53:05 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41685 Wed 10 Aug 2022 15:08:18 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54540 Tue 27 Feb 2024 20:42:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41786 Tue 23 Jan 2024 16:08:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54352 Tue 20 Feb 2024 16:21:02 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48282 Tue 14 Mar 2023 11:24:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34976 Tue 03 Sep 2019 18:17:48 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40111 Thu 28 Jul 2022 15:41:22 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48434 75%. This corresponded to an overall reduction in seizure frequency from 32 to 7.2 seizures per month. Ninety-one percent of adverse events were mild or moderate, and none required drug withdrawal. Sixty-two percent were judged to be unrelated to CBDV. Thirty-one percent of adverse events were identified as possibly related, of which nearly all were mild, and the remainder were later assessed as RTT symptoms. Hypersomnolence and drooling were identified as related to CBDV. No serious adverse events reported were related to CBDV. No significant change was noted in EEG or non-epilepsy-related symptoms of RTT. Significance: A dose of 10 mg/kg/day of CBDV is safe and well tolerated in a pediatric RTT cohort and suggests improved seizure control in children with MECP2-related RTT.]]> Thu 16 Mar 2023 14:17:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39890 Thu 14 Jul 2022 14:21:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37016 Thu 09 Dec 2021 11:04:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44058 Thu 06 Oct 2022 09:55:23 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29616 1000). Conclusion: Although data from randomised clinical trials on the clinical impact of sunitinib TDM are lacking, our findings support implementation of sunitinib TDM in clinical practice. For rare cancers with well-defined exposure–response relationships, modelling and simulation might allow the optimisation of dosing strategies when clinical trials cannot be performed due to low number of patients.]]> Thu 03 Feb 2022 12:18:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51077 Mon 21 Aug 2023 11:09:07 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51769 Mon 18 Sep 2023 14:29:45 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31928 Mon 09 Apr 2018 08:51:09 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46877 Mon 05 Dec 2022 09:47:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36056 Mon 03 Feb 2020 11:52:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45500 Fri 28 Oct 2022 16:00:31 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45449 Fri 28 Oct 2022 14:15:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52679 Fri 20 Oct 2023 09:30:21 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49507 Fri 19 May 2023 16:35:01 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53882 0.872; correlation coefficient, r = 0.87, P < 0.0001). Conclusions: DBS provides an alternative sampling strategy for the TDM of many anticancer drugs. Further research is required to establish a standardized approach for sampling and processing DBS samples to allow future implementation.]]> Fri 19 Jan 2024 14:22:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40009 n = 61) were analysed using non-linear mixed modelling. Covariate analysis was performed to investigate the impact of standard and novel patient characteristics of carboplatin pharmacokinetics. A Monte Carlo simulation of 100,000 representative NSCLC patients evaluated the ability of the Calvert formula and novel dosing strategies to achieve the targeted therapeutic range. The associations between systemic inflammation and chemotherapy drug utilisation (cycles received, relative dose intensity (RDI) and second-line uptake) and clinical endpoints were also investigated in the pharmacokinetic cohort, and two independent cohorts of people with advanced NSCLC from the Chemotherapy Dosing in Cancer-Related Inflammation (CDCRI) database that were administered carboplatin–paclitaxel (n  = 37) or carboplatin–gemcitabine (n  = 358). Results: In all cohorts, 25–53% of people had elevated systemic inflammation (NLR > 5 or PLR > 300). In the pharmacokinetic cohort, no patients achieved the desired therapeutic target of carboplatin. Carboplatin exposure was related to renal function, as estimated using the Cockcroft–Gault formula, albumin and inflammation (NLR). In the pharmacokinetic cohort, increasing carboplatin area under the curve (AUC) correlated with greater reductions in red blood cells and haemoglobin. In this cohort, the average measured AUC of partial responders was 2.4 mg·min/mL. Also in the pharmacokinetic cohort, only 12% of people with an NLR > 5 received four or more cycles of chemotherapy, compared with 62% of patients with an NLR ≤ 5 (p < 0.001). For people in the CDCRI cohort receiving carboplatin–gemcitabine, those with an NLR > 5 also received less cycles (four or more cycles, 41% vs. 60%; p < 0.01) as well as less second-line chemotherapy (46% vs. 60%; p = 0.02) compared with patients without inflammation. People in the pharmacokinetic cohort with an NLR > 5 had 12 months less median survival compared with people with an NLR ≤ 5 (6.5 vs. 18 months; p = 0.08). Similarly, overall survival was significantly shortened in people in the CDCRI cohort receiving carboplatin–gemcitabine with an NLR > 5 compared with those with an NLR ≤ 5 (7 vs. 12 months; p < 0.001), and Cox regression analysis showed a 1.5-fold (1.3–2.1; p < 0.001) increased hazard of death associated with the increased systemic inflammation. Simulations of the newly developed model-based and Calvert dosing assessed the ability to reach this study’s proposed actual target AUC of 2.2–2.6 mg·min/mL. These showed current Calvert dosing was predicted to result in substantial overexposure in patients with high systemic inflammation. The newly developed model showed equivalent levels of carboplatin therapeutic target achievement across the spectrum of inflammation observed in the lung cancer population. Conclusion: An alternate model-based dosing strategy for carboplatin was developed and is predicted to result in consistent drug exposure across the population and improve attainment of therapeutic targets. Further studies of this new model are warranted in people with advanced NSCLC.]]> Fri 15 Jul 2022 11:35:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43007 Fri 09 Sep 2022 14:24:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32031 Fri 01 Apr 2022 09:23:38 AEDT ]]>