1,721,033 research outputs found
Trimethoprim-sulfamethoxazole as Pneumocystis jiroveci pneumonia prevention in patients undergoing methotrexate therapy for hematological malignancies: A review of the literature
No full textMethotrexate is a cytotoxic agent that is commonly used to treat autoimmune diseases, and both solid and hematological malignancies. Drug interactions are of particular concern during methotrexate therapy, as they have the potential to alter the pharmacokinetics of methotrexate and lead to significant toxicity. One agent that has the potential to interact with methotrexate is the antimicrobial agent trimethoprim with sulfamethoxazole. Consideration of this interaction is of importance in patients that are undergoing high‐dose methotrexate therapy for hematological malignancies as trimethoprim/sulfamethoxazole is the preferred agent for Pneumocystis jiroveci pneumonia prophylaxis. Current Australian guidelines recommend avoiding concurrent administration of high‐dose methotrexate and trimethoprim/sulfamethoxazole, yet evidence to support this recommendation is unclear. This review investigates the current available evidence that focuses on the interaction between high‐dose methotrexate and trimethoprim/sulfamethoxazole and aims provide guidance for the use of this combination in clinical practice.No Full Tex
Cyclooxygenase-2 inhibitors delay relapse and reduce Prostate Specific Antigen (PSA) velocity in patients treated with radiotherapy for nonmetastatic prostate cancer: a pilot study
No full textIntroduction: A common treatment for localized prostate cancer (PCa) is radiotherapy; however, effectiveness is hampered because of toxicities and tumor resistance. Cyclooxygenase-2 (COX-2) inhibitors have been identified as potential agents that could improve treatment outcomes and have demonstrated ability to increase the radiosensitivity of many human carcinomas. This retrospective human study aims to investigate the ability of COX-2 inhibitors, celecoxib, and meloxicam, to improve treatment outcomes after radiotherapy.
Methods: Prostate Specific Antigen (PSA) data of eligible patients were obtained from Genesis Cancer Care, Southport, Australia. The primary outcome was the percentage of patients in each group that had reached biochemical relapse at two and five years after treatment. Secondary outcomes included time to biochemical relapse and PSA velocity.
Results: At two and five years after treatment, both the celecoxib (6.7%, 18.3%) and meloxicam (0.0%, 18.9%) showed lower relapse rates than the control (8.6%, 31.0%). Although not statistically significant, these results are clinically significant. In addition, the two treatment groups were found to increase the time to relapse, 46.20 months for celecoxib and 54.15 months for meloxicam, compared with the control group, 35.53 months. A similar trend was shown for PSA velocity with both treatment groups demonstrating lower PSA velocities compared with control.
Conclusions: This study provides further evidence to the potential for COX-2 inhibitors to address gaps in localizedz PCa treatment by demonstrating high clinical significance for the use of celecoxib and meloxicam. Further research should be conducted including larger retrospective studies and prospective studies to fully evaluate the benefits of COX-2 inhibitors in combination with radiotherapy for PCa.Full Tex
SIRT1 and SIRT2 modulators reduce LPS-induced inflammation in HAPI microglial cells and protect SH-SY5Y neuronal cells in vitro
No full textNeuroinflammation is associated with the development of depression. Deacetylases SIRT1 and SIRT2 are reported to exert neuroprotective effects in aging, neurogenesis, neurodegeneration and neuroinflammation. Therefore, this study aimed to investigate the effects of SIRT1 and SIRT2 modulators on LPS-induced neuroinflammation and neurodegeneration in vitro. To achieve this, HAPI rat microglial cells were pre-treated with the SIRT1 activator resveratrol (0.1–20 µM), the selective SIRT1 inhibitor EX527 (0.1; 1 µM), the dual SIRT1/SIRT2 inhibitor sirtinol (0.1–20 µM) and the SIRT2 inhibitor AGK2 (0.1; 1 µM), prior to exposure with LPS (5 ng/mL) for 20 h. The reference antidepressant drug fluoxetine and the nonsteroidal anti-inflammatory drug ibuprofen were also evaluated in the same paradigm, both at 1 μM. Resveratrol and sirtinol inhibited TNF-α production to a greater degree than either fluoxetine or ibuprofen. Resveratrol, sirtinol, EX527 and AGK2 significantly reduced PGE2 production by up to 100% in microglia. Then, the supernatant was transferred to treat SH-SY5Y cells for 24 h. In all cases, SIRT modulator pretreatment significantly protected undifferentiated SH-SY5Y human neuroblastoma cells from the insult of LPS-stimulated HAPI supernatant by up to 40%. Moreover, resveratrol and sirtinol also showed significantly better neuroprotection than fluoxetine or ibuprofen by up to 83 and 69%, respectively. In differentiated SH-SY5Y cells, only sirtinol (20, 10 µM) and AGK2 (0.1 µM) pretreatment protected the cells from LPS-stimulated HAPI supernatant. This study suggests that SIRT1 and SIRT2 modulators are effective in inhibiting LPS-stimulated production of TNF-α and PGE2 in HAPI microglial cells and protecting SH-SY5Y cells from inflammation. Thus, we provide proof of concept for further investigation of the therapeutic effect of SIRT1 and SIRT2 modulators and combination with current antidepressant medication as a treatment option.Full Tex
Improved delivery of care to stroke presentations by an Australian emergency department as measured by time performance indicators
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Signalling transduction of O-GlcNAcylation and PI3K/AKT/mTOR-axis in prostate cancer
No full textHexosamine biosynthetic (HBP) and PI3K/AKT/mTOR pathways are found to predominate the proliferation and survival of prostate cancer cells. Both these pathways have their own specific intermediates to propagate the secondary signals in down-stream cascades and besides having their own structured network, also have shared interconnecting branches. These interconnections are either competitive or co-operative in nature depending on the microenvironmental conditions. Specifically, in prostate cancer HBP and mTOR pathways increases the expression and protein level of androgen receptor in order to support cancer cell proliferation, advancement and metastasis. Pharmacological inhibition of a single pathway is therefore insufficient to stop disease progression as the cancer cells manage to alter the signalling channel. This is one of the primary reasons for the therapeutic failure in prostate cancer and emergence of chemoresistance. Inhibition of these multiple pathways at their common junctures might prove to be of benefit in men suffering from an advanced disease state. Hence, a thorough understanding of these cellular intersecting points and their significance with respect to signal transduction mechanisms might assist in the rational designing of combinations for effective management of prostate cancer.No Full Tex
Time to Stable Therapeutic Range on Initiation of Warfarin as an Indicator of Control
No full textObjectives: Warfarin remains widely used with a time in therapeutic range (TiTR) above 65% recommended for best outcomes. Patients not achieving or maintaining this warfarin control may be better suited to alternate anticoagulants. Despite this, there is limited data defining a suitable trial time in patients initiating warfarin therapy, therefore the aim of this study was to determine the mean time to stable therapeutic range (TtSTR).
Materials and Methods: Retrospective data was collected for patients with atrial fibrillation enrolled in a dedicated warfarin program at a private pathology practice within 7 days of warfarin initiation. TiTR at specified timepoints was calculated and median TtSTR determined as defined by TiTR ≥ 65% over three months. Comparisons were made of populations with TtSTR above or below the median.
Results: The 566 patients included in the study had a mean TiTR of 64.9±16.5% at month three and median TtSTR of six months. Patients with TtSTR≤6 months achieved a mean TiTR of 68.9±12.8% at month two and maintained a TiTR over 75% from month 3 to 24. Patients with a TtSTR>6 months obtained a TiTR of 66.4±10.6% at month nine and continued to achieve lower TiTR throughout the 24 months study period.
Conclusions: A majority of patients can achieve a stable TiTR above 65% within six months so review at six to nine months is likely to be a good indicator of warfarin control and to determine if patients should continue warfarin or switch to alternate anticoagulant therapy.No Full Tex
In Vitro Evaluation of Vancomycin-Induced Toxicity in Human Primary Knee Chondrocytes
No full textSeptic arthritis as a complication of orthopaedic joint surgery can have catastrophic outcomes for patients. To minimise infection risk associated with elective orthopaedics, topical vancomycin during surgery has become increasingly common. Evidence suggests that high concentrations of vancomycin, following direct application of the drug to the joint, are toxic towards various local cell types in the joint, including chondrocytes. However, the mechanism of this vancomycin tissue toxicity is yet to be determined. The aim of this study was to evaluate the toxicity of vancomycin on chondrocytes and the mechanisms of cell death involved. Human primary knee chondrocytes were exposed to vancomycin (1.25–10 mg/mL) for 24 h and their viability assessed using the resazurin reduction assay in vitro. Specific cell death mechanisms and their contributors, including reactive oxygen species (ROS) production and apoptosis, were measured. This study showed that high concentrations of vancomycin (5 and 10 mg/mL) were toxic towards human primary knee chondrocyte cells, while lower concentrations (1.25 and 2.5 mg/mL) were not. Cell death studies found that this occurred through an apoptotic pathway. This study provides additional support that vancomycin in high doses is toxic towards chondrocytes and preliminary evidence that this toxicity occurs via apoptotic cell death mechanisms.Full Tex
Learner attitudes towards a virtual microbiology simulation for pharmacy student education
No full textIntroduction: Simulation for education has become popular, but much literature on this modality fails to critically examine the learner's experience, focusing instead on learning outcomes. Learner attitudes should be scrutinised and monitored to appraise a technology-enhanced learning experience as student perceived educational benefits of technology-enhanced learning is reported to be more important than the intrinsic characteristics of any particular medium or tool. This study sought to evaluate pharmacy students' attitudes toward a virtual microbiology simulation. Methods: The virtual microbiology simulation (VUMIE) was compared with a traditional wet laboratory (lab) in a second-year integrated pharmacotherapeutics course for bachelor of pharmacy students. Data were collected using surveys deployed at baseline (pre-intervention), post-intervention (VUMIE or wet lab), and endpoint (post-interventions). Statistical and qualitative thematic analyses were performed. Results: Learners found the simulation valuable, and outcomes suggest that it is possible for technology-enhanced learning activities to replace face-to-face instruction to some extent, which may be useful given the current challenges with in-person education resulting from COVID-19. More students reported a specific preference for the wet lab rather than VUMIE. Conclusions: Although technology-enhanced simulation can produce a similar learning experience to a traditional wet lab, this evidence is not sufficient to completely replace the traditional lab experience for clinical courses of study. Technology-enhanced simulation could be considered for just-in-time training before exposure to traditional lab activities, for specific skill acquisition using deliberate practice, and perhaps for standardised assessment for clinical microbiology education.No Full Tex
SIRT1 and SIRT2 Modulators: Potential Anti-Inflammatory Treatment for Depression?
No full textDepression is a psychiatric disorder that has a significant health burden on patients and their families. Unfortunately, the current antidepressant medications that mainly target monoamine neurotransmitters have limited efficacy. Recent evidence has indicated that neuroinflammation participates in the genesis and development of depression, and interacts with other factors involved in depression. Therefore, exploring effective anti-inflammatory medications could be beneficial for the development of new treatment options for depression. Sirtuins are a unique class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, which have seven members that can affect multiple downstream targets by deacetylation activity. Among these seven members, SIRT1 and SIRT2 have been shown to participate in the pathophysiology of inflammation in numerous studies. Thus, in this short article, we review the association of SIRT1 and SIRT2 activity and depression, and evidence of the effects of SIRT1 and SIRT2 modulators on inflammation in vitro and depressive-like behaviours in vivo
Anticoagulant Initiation During Hospital Admissions for Atrial Fibrillation in South-East Queensland, Australia
No full textBackground: Anticoagulation reduces stroke risk in patients with atrial fibrillation (AF) but under-prescribing in eligible patients has been commonly reported. Introduction of the direct acting oral anticoagulants (DOACs) was considered to potentially improve prescribing due to increased anticoagulant options. At the time of release to the Australian market, there were limited studies investigating anticoagulant usage during hospitalisations for AF. Therefore, the aim of this study was to investigate prescribing of oral anticoagulants during hospitalisation admissions for AF during the time of DOAC introduction to the Australian market. Method: A retrospective study was conducted of admissions to a tertiary Queensland hospital during 1 July 2012 to 10 June 2015. Patients were categorised according to oral anticoagulant therapy on both hospital admission and discharge. Changes to therapy and patient factors associated with prescribing were analysed. Results: A total of 1,911 patients were included with 3,396 admissions during the study period. There was a significant increase in the number of patients initiated on anticoagulant therapy during their first admission with higher rates of initiation of DOACs compared to warfarin. Ischaemic heart disease and high bleed risk were significantly associated with reduced prescribing of anticoagulant therapy on first and second admission respectively, while patients with a history of stroke or transient ischaemic attack were significantly more likely to receive therapy. Conclusion: The introduction of the DOACs to the Australian market increased initiation of anticoagulants to hospitalised patients with AF across all stroke risk categories. The availability of greater anticoagulant options has increased initiation of therapy but there remains potential to further optimise anticoagulant prescribing by targeting therapy according to guidelines and patient factors.Full Tex
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