942 research outputs found
Dreamers of the Dark: Kerry Bolton and the Order of the Left Hand Path, a Case-study of a Satanic/Neo-Nazi Synthesis
In 1990 a small self-published journal/magazine called The Watcher was distributed among New Zealand's occult underground. The Watcher described itself as 'the New Zealand Voice of the Left Hand Path', and was published as the journal of the Order of the Left Hand Path. The Watcher and the Order directed its attentions towards those occultists who identified themselves as Satanists and, as such, the journal articulated a distinctly Satanic philosophy and perspective. However, as the journal evolved and developed, renaming itself as The Heretic and The Nexus in later years, there arose alongside Satanic philosophy an increasing emphases on what could be called esoteric Nazism or esoteric Nationalism. Given that the editor of The Watcher was Kerry Bolton, a man who has been immersed in New Zealand's Nationalist/neo-Nazi movement since the early 1970s, such an increasingly political orientation was perhaps unsurprising.
This thesis examines the way in which the Order bought Satanic and neo-Nazi ideologies together and the resulting synthesis. It also looks at the transition from being a Satanic order led by a neo-Nazi to an openly neo-Nazi Order that uses Satanic philosophy to justify and popularise its conception of National Socialism
Letter to the editor: Comments on ‘A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation’
Tissue plasminogen activator (tPA) in the management of predominantly hemorrhagic age-related macular degeneration, milligram/milliliter or microgram/milliliter?
Combatting the rising costs of cancer drugs; interventions from a university hospital’s perspective
Rapid increase in cost continues to have negative impact on patients’ accessibility to life-changing anticancer medications. Moreover, the rising cost does not equate to similar increase in medication effectiveness. We recognise our responsibility as a university hospital to tackle this imbalance and strive to provide high quality, sustainable, affordable and accessible care. An active approach in cost containment of expensive and innovative cancer drugs was adopted in our organisation to safeguard accessibility and improve quality of life for patients. In this article, we described four inverventions: 1) identify right patient and minimise overtreatment, 2) in-house medicine production for selected indications, 3) minimise medicine spillages and 4) effective procurement strategies. We call on other hospitals to take action and, favourably, to collaborate on a European level. Together, we will safeguard the current and future care of our patients.</p
Influence of enzalutamide on cabazitaxel pharmacokinetics: A Drug–Drug interaction study in metastatic castration-resistant prostate cancer (mCRPC) patients
Purpose: In ongoing clinical research on metastatic castration-resistant prostate cancer (mCRPC) treatment, the potential enhanced efficacy of the combination of taxanes with AR-targeted agents, that is, enzalutamide and abiraterone, is currently being explored. Because enzalutamide induces the CYP3A4 enzyme and taxanes are metabolized by this enzyme, a potential drug–drug interaction needs to be investigated. Experimental Design: Therefore, we performed a pharmacokinetic cross-over study in mCRPC patients who were scheduled for treatment with cabazitaxel Q3W (25 mg/m2). Patients were studied for three consecutive cabazitaxel cycles. Enzalutamide (160 mg once daily) was administered concomitantly after the first cabazitaxel cycle, during 6 weeks. Primary endpoint was the difference in mean area under the curve (AUC) between the first (cabazitaxel monotherapy) and third cabazitaxel cycle, when enzalutamide was added. Results: A potential clinically relevant 22% (95% CI, 9%–34%; P ¼ 0.005) reduction in cabazitaxel exposure was found with concomitant enzalutamide use. The geometric mean AUC0–24h of cabazitaxel was 181 ngh/mL (95% CI, 150–219 ngh/mL) in cycle 3 and 234 ngh/mL (95% CI, 209–261 ngh/mL) in cycle 1. This combination did not result in excessive toxicity, whereas PSA response was promising. Conclusions: We found a significant decrease in cabazitaxel exposure when combined with enzalutamide. In an era of clinical trials on combination strategies for mCRPC, it is important to be aware of clinically relevant drug–drug interactions. Because recent study results support the use of a lower standard cabazitaxel dose of 20 mg/m2, the clinical relevance of this interaction may be substantial, because the addition of enzalutamide may result in subtherapeutic cabazitaxel exposure
Drug interactions between tyrosine-kinase inhibitors and acid suppressive agents:More than meets the eye-Authors' reply
Drug-drug interactions with tyrosine-kinase inhibitors:A clinical perspective
In the past decade, many tyrosine-kinase inhibitors have been introduced in oncology and haemato-oncology. Because this new class of drugs is extensively used, serious drug-drug interactions are an increasing risk. In this Review, we give a comprehensive overview of known or suspected drug-drug interactions between tyrosine-kinase inhibitors and other drugs. We discuss all haemato-oncological and oncological tyrosine-kinase inhibitors that had been approved by Aug 1, 2013, by the US Food and Drug Administration or the European Medicines Agency. Various clinically relevant drug interactions with tyrosine-kinase inhibitors have been identified. Most interactions concern altered bioavailability due to altered stomach pH, metabolism by cytochrome P450 isoenzymes, and prolongation of the QTc interval. To guarantee the safe use of tyrosine-kinase inhibitors, a drugs review for each patient is needed. This Review provides specific recommendations to guide haemato-oncologists, oncologists, and clinical pharmacists, through the process of managing drug-drug interactions during treatment with tyrosine-kinase inhibitors in daily clinical practice
Effect of alternative dosing strategies of pembrolizumab and nivolumab on health-care emissions in the Netherlands:a carbon footprint analysis
Background: Hospitals contribute substantially to greenhouse gas emissions and face a moral obligation to prioritise emission reduction. Drugs constitute an important component of the greenhouse gas emissions of hospitals. Alternative dosing strategies (ADS) have been implemented to improve the cost-effectiveness of pembrolizumab and nivolumab. However, the impact of these ADS on greenhouse gas emissions remains unknown. Therefore, we aimed to analyse the effect of ADS implementation on the carbon emissions of treatment with pembrolizumab and nivolumab. Methods: We used a process-based lifecycle assessment to quantify the environmental impact of pembrolizumab and nivolumab, focused on equivalent carbon dioxide emissions (CO2e). Lifecycle inventory and impact data from Erasmus University Medical Center (Rotterdam, Netherlands) were used to calculate the CO2e for pembrolizumab and nivolumab, their dosing intervals, and the impact of ADS on CO2e. The functional unit of the study was the administration of a single dose of pembrolizumab or nivolumab. Findings: In 2022, the annual carbon emissions related to pembrolizumab and nivolumab treatment in the Erasmus University Medical Center were 445 tons of CO2e, averaging 94 kg of CO2e per dose. Pharmaceutical production was the main driver of treatment-related carbon emissions (mean 92·9% of total emissions). Applying ADS resulted in 21–26% and 9–11% CO2e reductions for pembrolizumab and nivolumab, respectively. Interpretation: This study shows the environmental impact of pembrolizumab and nivolumab treatment and calls for further implementation of ADS for pembrolizumab, nivolumab, and other anti-PD-(L)1 monoclonal antibodies, and more sustainable pharmaceutical production processes. Our findings create environmental awareness and contribute to the promotion and understanding of health-care practices with lower carbon emissions. </p
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