RESUMO
Background: Cigarette smoke increases the metabolism of phenytoin, a widely used anti-epileptic agent, by inducing cytochrome P450 enzymes in the liver. Therefore, cigarette smoke may reduce the clinical effect of phenytoin. Switching from cigarettes to smoke-free products (e.g., heat-not-burn, snus and e-cigarettes) is likely to have an impact on phenytoin metabolism. The absence of tobacco combustion in these smoke-free products reduces the production of the chemicals that induce the metabolism of phenytoin. Objectives: The primary objective was to determine whether smoke-free products have a role to play in epileptic patients who take phenytoin and continue to smoke cigarettes. The secondary objectives were to assess: (1) the influence of cigarette smoke on phenytoin metabolism including the metabolic pathways involved, (2) the influence of nicotine on phenytoin metabolism including the metabolic pathways involved, if any, and (3) the influence of nicotine on epilepsy in humans, if any. Methods: The literature review was conducted in 2019 and 2020 using a structured search to identify relevant articles. The potential mechanisms underlying the effects of cigarette smoke and nicotine on phenytoin metabolism and the pathways for phenytoin metabolism were evaluated to determine overlapping mechanisms/pathways. The key methodological deficiencies in the studies were recorded, where applicable. Results: Thirty-five studies were reviewed. The literature showed that cigarette smoke influenced the metabolism of phenytoin by increasing the maximum metabolism rate of phenytoin by an average of 16% in humans. Cigarette smoke is known to contain several polycyclic aromatic hydrocarbons (PAHs), which can lead to faster elimination of numerous medicines, including phenytoin. There is no literature assessing the direct influence of nicotine on phenytoin metabolism in humans and animals. The metabolic pathways of phenytoin and nicotine do not overlap indicating that nicotine does not influence the metabolism of phenytoin. Hence, complete switching to smoke-free products with similar nicotine concentrations to cigarettes, may reduce the influence smoking has on phenytoin metabolism in epileptic patients who take phenytoin and smoke. There was also no evidence to demonstrate that nicotine has the potential to trigger epilepsy in humans. Conclusion: The literature showed that the increase in metabolic rate of phenytoin due to tobacco smoke is probably attributable to PAHs and not nicotine. The similar nicotine content between smoke-free products and cigarettes and the reduced levels of PAHs in smoke-free products indicate that there is a role for smoke-free products in epileptic patients who take phenytoin and smoke.
RESUMO
BACKGROUND: There has been no comprehensive study determining the financial burden of breast cancer in the South African (SA) public sector. OBJECTIVES: To develop a method to determine the cost of breast cancer treatment with chemotherapy per episode of care and to quantify the associated costs relating to chemotherapy at Groote Schuur Hospital (GSH), a government hospital in SA. These costs included costs associated with the management of adverse events arising from chemotherapy. METHODS: Retrospective patient-level data were collected for 200 patients from electronic databases and patient folders between 2013 and 2015. Direct medical costs were determined from the health funder's perspective. The information collected was categorised into the following cost components: chemotherapy medicines, support medicines, administration of chemotherapy, laboratory tests, radiology scans and imaging, doctor consultations and adverse events. Time-and-motion studies were conducted on a set of new patients and the data obtained were used for the study sample of 200 patients. All the above costs were used to determine the cost of chemotherapy per episode of care. The episode of care was defined as the care provided from 2 months prior to the date of commencing chemotherapy (pre-chemotherapy phase), during chemotherapy (treatment phase) and until 6 months after the date when the last cycle of chemotherapy was administered (follow-up phase). RESULTS: A method was developed to determine the episode-of-care costs for breast cancer at GSH. The total direct medical cost for treatment of breast cancer at GSH for 200 patients was ZAR3 154 877, and the average episode-of-care cost per patient was ZAR15 774. The average cost of management of adverse events arising from the various treatment modalities was ZAR13 133 per patient. It was found that the cost of treating a patient with adverse events was 1.8 times higher than the cost of treating a patient without adverse events. Of the patients, 86.5% managed to complete their prescribed chemotherapy treatment cycles, and the average cost of treatment of these patients was 1.3 times more than the average cost for patients who could not complete their treatment, based on the number of treatment cycles received. CONCLUSION: A comprehensive method to determine the costs associated with breast cancer management per episode of care was developed, and costs were quantified at GSH according to the treatment protocol used at the hospital.