Helder Mota-Filipe

Background: Artificial intelligence (AI) is increasingly integrated into palliative medicine, offering opportunities to improve quality, efficiency, and patient-centeredness in end-of-life care. However, its use raises complex ethical issues, including privacy, equity, dehumanization, and decision-making dilemmas. Objective: We aim to critically analyze the main ethical implications of AI in end-of-life palliative care and examine the benefits and risks. We propose strategies for ethical and responsible implementation. Methods: We conducted an integrative review of studies published from 2020 to 2025 in English, Portuguese, and Spanish, identified through systematic searches in PubMed, Scopus, and Google Scholar. Inclusion criteria were studies addressing AI in palliative medicine focusing on ethical implications or patient experience. Two reviewers independently performed study selection and data extraction, resolving discrepancies by consensus. The quality of the papers was assessed using the Critical Appraisal Skills Programme checklist and the Hawker et al tool. Results: Six key themes emerged: (1) practical applications of AI, (2) communication and AI tools, (3) patient experience and humanization, (4) ethical implications, (5) quality of life perspectives, and (6) challenges and limitations. While AI shows promise for improving efficiency and personalization, consolidated real-world examples of efficiency and equity remain scarce. Key risks include algorithmic bias, cultural insensitivity, and the potential for reduced patient autonomy. Conclusions: AI can transform palliative care, but implementation must be patient-centered and ethically grounded. Robust policies are needed to ensure equity, privacy, and humanization. Future research should address data diversity, social determinants, and culturally sensitive approaches.

The Biomedical Ethics and Regulatory Capacity Building for Portuguese-Speaking African Countries Project (BERC-Luso) was a four-year project that aimed to enhance biomedical ethics and regulatory capacities in five Portuguese-Speaking African Countries (PSAC). BERC-Luso was developed considering the PSAC scarce number of clinical trials, exploring an untapped potential. The project's interventions focused on three primary areas: legislative, institutional, and capacity building. The common aim was to create attractive conditions for conducting clinical trials, guaranteeing population protection and benefit of the country. The project evaluated national legislative frameworks and recommended strengthening actions. Through implementing top-down and bottom-up approaches, BERC-Luso involved ministries, political stakeholders, policymakers, and diplomatic channels. These strategies prompted legislative initiatives and reforms. The outcomes evaluation reflected a high level of success rate, with 78.59% of the targets being achieved. The impact level was demonstrated by the engagement with stakeholders, resulting in activities that impacted over 71,149 professionals. The project emphasises the need for more investment in capacity-building, reinforcing best practices' implementation at legislative, institutional and training levels. BERC-Luso fostered collaboration between partner countries, contributing to a supportive environment of African biomedical research.

Rationale: Pharmacists' clinical responsibilities have been on a progressive rise, adopting a more person‐centered approach, and experiencing increased involvement in healthcare teams across all settings. The development and evolution of clinical pharmacy practice in each country depends on the existing facilitators and barriers, which are variable and highly context‐related. Aims and Objectives: To investigate the perspectives of global experts regarding the advancement of clinical pharmacy practice, with a specific focus on examining the factors contributing to success and their outlook on the future of clinical pharmacy. Methods: Semi‐structured interviews were conducted with academia and practice experts from 13 countries. Each expert was asked what they considered to be the future of clinical pharmacy education and practice, as well as what should be improved in the clinical pharmacy learning path to ensure that it keeps pace with the evolution of pharmacists' clinical responsibilities in practice. Success factors for change in clinical pharmacy practice were also explored. Interviews were transcribed verbatim and analyzed thematically. Results: Success factors for advancing clinical pharmacy practice included elements related to the healthcare and political landscape, such as remuneration, leadership, as well as willingness and readiness for change. Other success factors identified are directly related to the pharmacist, such as the use of reflective practice or the pharmacist's motivation. Perceived future directions include the existence of a multidisciplinary approach in practice, the expansion of clinical pharmacy services, as well as the delivery of clinical pharmacy services at the primary care level. Conclusion: The development of clinical pharmacy practice relies on a wide range of factors. The analysis carried out in this study of the success factors as well as the potential future directions of clinical pharmacy can serve as catalysts for the development of this pharmacy field at the country, regional, and global levels.

BACKGROUND Artificial intelligence (AI) is increasingly integrated into palliative medicine, offering opportunities to improve quality, efficiency, and patient-centeredness in end-of-life care. However, its use raises complex ethical issues, including privacy, equity, dehumanization, and decision-making dilemmas. OBJECTIVE We aim to critically analyze the main ethical implications of AI in end-of-life palliative care and examine the benefits and risks. We propose strategies for ethical and responsible implementation. METHODS We conducted an integrative review of studies published from 2020 to 2025 in English, Portuguese, and Spanish, identified through systematic searches in PubMed, Scopus, and Google Scholar. Inclusion criteria were studies addressing AI in palliative medicine focusing on ethical implications or patient experience. Two reviewers independently performed study selection and data extraction, resolving discrepancies by consensus. The quality of the papers was assessed using the Critical Appraisal Skills Programme checklist and the Hawker et al tool. RESULTS Six key themes emerged: (1) practical applications of AI, (2) communication and AI tools, (3) patient experience and humanization, (4) ethical implications, (5) quality of life perspectives, and (6) challenges and limitations. While AI shows promise for improving efficiency and personalization, consolidated real-world examples of efficiency and equity remain scarce. Key risks include algorithmic bias, cultural insensitivity, and the potential for reduced patient autonomy. CONCLUSIONS AI can transform palliative care, but implementation must be patient-centered and ethically grounded. Robust policies are needed to ensure equity, privacy, and humanization. Future research should address data diversity, social determinants, and culturally sensitive approaches.

O artigo contribui na compreensão do acesso a medicamentos essenciais para a cobertura universal e equidade na saúde e as estratégias adotadas por países do norte e sul global. Tratou-se de uma pesquisa qualitativa de caráter descritivo como base a análise de dados secundários e primários. Os temas principais foram extraídos de uma Mesa redonda realizada pela Fiocruz e a Universidade de Aveiro em outubro de 2023. Resultados apontam dados da indústria farmacêutica global, regulação de medicamentos, avaliação de tecnologias em saúde e lista de medicamentos críticos. Conclui-se que a adoção de políticas públicas eficazes e o investimento em pesquisa e inovação são fundamentais para promoção e acesso universal dos medicamentos essenciais com uma saúde equitativa e de qualidade para todos, bem como o investimento em medicamentos inovadores. Configura-se como uma agenda essencial para os países como o Brasil e Portugal visando assegurar a sustentabilidade dos sistemas de saúde públicos.

Triple-negative breast cancer (TNBC) is an aggressive breast carcinoma with a poor prognosis. Current treatment options with platinum-(Pt)-based chemotherapeutics are limited by toxicity/acquired resistance, which has prompted the search for novel metal-based compounds. Dinuclear palladium(II)-spermine chelate (Pd₂Spm) has previously shown promising pharmacokinetics and in vivo antitumor effects. However, its impact on chemotherapy-resistant TNBC is still to be addressed. This work developed a cell model of cisplatin resistance and compared the anticancer/antiproliferative effects of cisplatin (reference Pt-based drug) and Pd₂Spm in TNBC cells sensitive (MDA-MB-231) and resistant to cisplatin (MDA-MB-231/R). Pd₂Spm displayed a similar antiproliferative potency in MDA-MB-231 and MDA-MB-231/R cells, while cisplatin showed ca. 18-fold lower potency towards MDA-MB-231/R cells. When focusing on cell death, the incubation of Pd₂Spm with either necrostatin-1 (necroptosis inhibitor), Z-VAD (apoptosis inhibitor), or 3-methyladenine (3-MA, autophagy inhibitor) showed that 3-MA could rescue Pd₂Spm-induced growth inhibition in MDA-MB-231 and MDA-MB-231/R cells. Furthermore, in MDA-MB-231 cells, Pd₂Spm triggered higher LC3-II levels and more profound Beclin-1 inhibition than cisplatin. Regarding apoptosis, Pd₂Spm did not induce the cleavage of caspase-3, and the co-incubation of both Pd₂Spm and Z-VAD yielded only marginal effects in preventing phosphatidylserine externalization compared to cisplatin. Thus, the present data provide more evidence on Pd₂Spm’s cell death mechanisms, which trigger a caspase-independent cell death with autophagy involvement. In addition, the potential of Pd₂Spm to overcome chemotherapy resistance is promising.

Pd₂Spm is a dinuclear palladium(II)-spermine chelate with promising anticancer properties against triple-negative breast cancer (TNBC), a breast carcinoma subset with poor prognosis and limited treatment options. The present study evaluated the in vitro and in vivo anticancer effects of Pd₂Spm compared to the reference metal-based drug cisplatin. Triple-negative breast cancer MDA-MB-231 cells, non-cancerous MCF-12A breast cells and chorioallantoic membrane (CAM) assay were used for antiproliferative, antimigratory and antiangiogenic studies. For an in vivo efficacy study, female CBA nude mice with subcutaneously implanted MDA-MB-231 breast tumors were treated with Pd₂Spm (5 mg/kg/day) or cisplatin (2 mg/kg/day) administered intraperitoneally during 5 consecutive days. Promising selective antiproliferative activity of Pd₂Spm was observed in MDA-MB-231 cells (IC₅₀ values of 7.3–8.3 µM), with at least 10-fold lower activity in MCF-12A cells (IC₅₀ values of 89.5–228.9 µM). Pd₂Spm inhibited the migration of MDA-MB-231 cells, suppressed angiogenesis in CAM and decreased VEGF secretion from MDA-MB-231 cells with similar potency as cisplatin. Pd₂Spm-treated mice showed a significant reduction in tumor growth progression, and tumors evidenced a reduction in the Ki-67 proliferation index and number of mitotic figures, as well as increased DNA damage, similar to cisplatin-treated animals. Encouragingly, systemic toxicity (hematotoxicity and weight loss) observed in cisplatin-treated animals was not observed in Pd₂Spm-treated mice. The present study reports, for the first time, promising cancer selectivity, in vivo antitumor activity towards TNBC and a low systemic toxicity of Pd₂Spm. Thus, this agent may be viewed as a promising Pd(II) drug candidate for the treatment of this type of low-prognosis neoplasia.