Background Encephalopathy following Ifosfamide treatment is a well-described phenomenon that is typically treated with Methylene Blue (MB). Chloroacetaldehyde, a potentially neurotoxic metabolite of Ifosfamide is hypothesized to cause this encephalopathy. Current guidelines for treatment is to stop Ifosfamide and provide supportive care. MB acts to inhibit Chloroacetaldehyde formation and has been described as a therapy and prophylaxis for Ifosfamide-encephalopathy. MB is effective within 30 min and lasts up to 3 days. Prolonged encephalopathy and MB therapy has not been described in the literature as lasting longer than 30 days following treatment. Case presentation We present the case of an 11-year-old female with autistic spectrum disorder and recurrent episodes of severe somnolence for 7 months following Ifosfamide therapy for her Non-Germinomatous Germ Cell Tumor (GCT). Periods of somnolence occurred prior to receiving cranial RT. Administration of MB gave immediate but limited response, with resolution of somnolence lasting 1-2 days between administrations. The somnolence could not be explained by neuroimaging or laboratory evaluation, but EEG indicated persistent encephalopathy. Conclusion A literature review determines that neurotoxicity is a side effect of Ifosfamide, but this effect has not been described persisting longer than 30 days. Our case continued to require treatment with MB for 7 months following cessation of therapy. We report these novel clinical findings, and hypothesize that there could be a genetic/metabolic component linking this reaction to Ifosfamide with the case patient’s pre-existing autism. This possible association may also correlate to the already-established link between autism and the development of GCTs. This hypothesis leads to further discussion on the suitable usage of Ifosfamide in children with co-morbidities and the necessity of screening prior to its usage.
Background and aims Learning from error can have a negative impact on the staff involved in the error ('second victim phenomenon'). We created a project, based on the principles of the Learning from Excellence project, to learn from excellence and correct the imbalance of negative to positive feedback in the context of hospital practice. Methods and results Using a questionnaire, we surveyed staff on existing feedback mechanisms and morale. We then introduced a system where staff recorded and commented on examples of excellence in practice. Recipients and their supervisors received copies of these reports and the feedback was analysed and discussed with senior staff (consultant, senior charge nurse, managers). We re-audited the staff two months after starting this project and noted improvements in staff morale and in positive reporting. Conclusions This project has improved the process of giving and learning from positive feedback and had a significant impact on staff morale. We can also demonstrate an example of improved clinical practice (from feedback received) and will now attempt to measure clinical outcomes with a new prospective study. Finally, we hope to set up a regional programme of reporting excellence in South-East Scotland.
In this study, we aimed to quantify KREC (kappa-deleting recombination excision circle) levels and naive B cell output in healthy HIV-uninfected children, compared with HIV-infected South African children, before and after starting ART (antiretroviral therapy). Samples were acquired from a Child Wellness Clinic (n = 288 HIV-uninfected South African children, 2 weeks–12 years) and the Children with HIV Early Antiretroviral Therapy (CHER) trial (n = 153 HIV-infected South African children, 7 weeks–8 years). Naive B cell output was estimated using a mathematical model combining KREC levels to reflect B cell emigration into the circulation, flow cytometry measures of naive unswitched B cells to quantify total body naive B cells, and their rates of proliferation using the intracellular marker Ki67. Naive B cell output increases from birth to 1 year, followed by a decline and plateau into late childhood. HIV-infected children on or off ART had higher naive B cell outputs than their uninfected counterparts (p = .01 and p = .04). This is the first study to present reference ranges for measurements of KRECs and naive B cell output in healthy and HIV-infected children. Comparison between HIV-uninfected healthy children and HIV-infected children suggests that HIV may increase naive B cell output. Further work is required to fully understand the mechanisms involved and clinical value of measuring naive B cell output in children.
A 3 4 7 -A 7 6 6 outcomes of ENZ and AA for the treatment of chemotherapy-naïve patients with mCRPC in Brazil across a 1-year horizon. Methods: This analysis was performed from the perspective of the Brazilian supplementary healthcare system. ENZ and AA clinical outcome curves were extracted from PREVAIL and COU-AA-302 trials and compared indirectly. The outcome estimates for radiographic progression-free survival (rPFS), time to initiation of chemotherapy and overall survival (OS) were obtained at 12 months. The absolute differences between ENZ and AA were executed, and the NNT was calculated. Total costs-per-treated-patient were estimated by considering the costs for drug acquisition, patient monitoring, adverse-event management, post-progression and end of life care. Costs per additional patient with clinically meaningful outcome were calculated by multiplying the NNT by the incremental cost. Incremental cost was obtained from the difference between total costs per patient treated with ENZ and AA. Results: NNTs for rPFS, chemotherapydelayed rates and OS outcomes were 14, 26 and 91, respectively. NNT results reflect an additional patient with rPFS, chemotherapy delay or survival of > 1 year for ENZ treatment versus AA treatment. Total ENZ treatment cost (BRL 108,280) was BRL 3013 lower than AA (BRL 111,293) [1 USD= BRL 3.5485], resulting in ENZ being, overall, superior to AA. ConClusions: ENZ demonstrated positive NNT and lower treatment costs per patient versus AA. The findings support superior clinical outcomes at a lower cost for Brazilian patients with mCRPC treated with ENZ versus AA.objeCtives: Enzalutamide (ENZ) and abiraterone acetate (AA) are therapeutic options for treating patients with metastatic castration-resistant prostate cancer (mCRPC). Although published head-to-head trials directly evaluating both treatments are not currently available, it is possible to estimate the number needed to treat (NNT) and, thereby, indirectly compare differences between them. This analysis calculated the NNT and costs per additional patient by using clinically meaningful
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