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OBJECTIVES: Fluoropyrimidine-based therapies, 5-fluorouracil (5-FU) and its oral prodrugs, capecitabine and tegafur/oteracil/gimeracil (S-1), are pivotal drugs to treat gastric cancer. Fluoropyrimidines are associated with cardiotoxicity including ischemic cardiopathy. The mechanisms of ischemic cardiopathy are considered to be multifactorial, potentially involving metabolites of 5-FU generated by the dihydropyrimidine dehydrogenase (DPD). By using Vigibase®, the World Health Organization pharmacovigilance database, we aimed to investigate the implication of the 5-FU metabolites induced by DPD in the occurrence of ischemic cardiopathy in patients with gastric cancer using capecitabine. METHODS: In Vigibase®, we included serious reports of ischemic cardiopathy with capecitabine and S-1 from January 1st, 2013, to September 16th, 2023. Among patients with gastric cancer, we calculated the reporting odds ratio (ROR) of ischemic cardiopathy to compare capecitabine (a prodrug without DPD antagonist) with S-1 (a prodrug associated with a DPD antagonist). The ROR was also calculated regardless of the drug indication. An ancillary analysis based on the French pharmacovigilance database was also performed. We evaluated the ROR of serious cardiac disorders induced by 5-FU intravenous infusion according to the DPD status (no deficiency versus complete or partial deficiency). RESULTS: In gastric cancer, 1843 reports (including 23 ischemic cardiopathy) for capecitabine and 2225 reports (including 17 ischemic cardiopathy) for S-1 were included. Median time-to-onset was 7 (3-26) days for capecitabine and 22 (13.25-30) days for S-1. Capecitabine was associated with an increased ROR of ischemic cardiopathy compared with S-1 in gastric cancer (ROR=1.6; [95% CI=1.5-1.8]) and regardless of the indication (7.3; [95% CI=6.6-8.0]). In the ancillary analysis, among 5-FU users, the lack of DPD deficiency increased the ROR for cardiac disorders (2.1; [95% CI=1.9-2.3]) compared to the DPD deficiency. CONCLUSION: This work supports the role of toxic 5-FU metabolites generated by dihydropyrimidine dehydrogenase in the occurrence of ischemic cardiopathy among patients with gastric cancer using capecitabine.
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INTRODUCTION: The prevalence of people with complex chronic conditions is increasing. This population's high social and health needs require person-centred integrated approaches to care. METHODS: To collect data about experiences with the health system and identify priorities for care, we conducted 2 focus groups and 15 semi-structured interviews involving patients with multimorbidity and advanced conditions, caregivers, and representatives of patients' associations. To design the programme, we combined this information with evidence-based recommendations from local healthcare and social care professionals. RESULTS: Patients' and caregivers' main priorities were to ensure (a) comprehension of information provided by healthcare professionals; (b) coordination between patients, caregivers, and professionals; (c) access to social services; (d) support to caregivers in managing situations; (e) perceived support throughout the healthcare process; (f) home care, when available; and (d) a patient-centred approach. These dimensions were included in 37 of 63 clinical actions of the programme to cover the whole care trajectory: identifying high needs, defining, and providing care plans, managing crises, and providing transitional care and end-of-life care. CONCLUSION: We developed an evidence-based integrated care programme tailored to high-need patients combining input from patients, caregivers, and healthcare and social care professionals.
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AIM: To evaluate the immunogenicity and safety of 3 doses of the combined diphtheria-tetanus toxoids-acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) vaccine (Infanrix hexa) when coadministered with a CRM197-conjugated meningococcal C vaccine (Meningitec) at different injection sites during the same visit or during separate visits. METHODS: Healthy infants were randomized in an open randomized multicenter study to receive either the DTPa-HBV-IPV/Hib and meningococcal C conjugate vaccines during the same vaccination visit at 2, 4 and 6 months of age (coadministration group) or the DTPa-HBV-IPV/Hib vaccine at 2, 4 and 6 months of age and the meningococcal C conjugate vaccine at 3, 5 and 7 months of age (separate administration group). RESULTS: The immunogenicity analysis included 452 infants, 228 in the coadministration group and 224 in the separate administration group. One month after primary vaccination, 99.1% of subjects in both groups achieved anti-polyribosylribitol phosphate antibody concentrations >/=0.15 microg/mL. The vaccine response against pertussis antigens was at least 99.1% in both groups. For all other DTPa-HBV-IPV/Hib vaccine antigens, at least 97.8% of all subjects of both groups were seroprotected. In addition, 99.5% of all subjects had meningococcal C bactericidal antibody titers >/=1/8 and 99.1% >/=1/128. Coadministration of both vaccines did not result in an increased local or general reactogenicity compared with separate administration. CONCLUSION: Coadministration of the combined DTPa-HBV-IPV/Hib vaccine and the meningococcal C conjugate vaccine during the same vaccination visit was immunogenic and safe.