Objetivo: Analisar as evidências científicas sobre as repercussões psiquiátricas associadas ao uso de tirzepatida em adultos com obesidade. Métodos: Revisão de escopo realizada entre dezembro de 2025 e janeiro de 2026, conduzida conforme as recomendações do Joanna Briggs Institute e reportada segundo o PRISMA-ScR, com protocolo previamente registrado na Open Science Framework. A pergunta norteadora foi estruturada pela estratégia PCC (População: adultos com obesidade em uso de tirzepatida; Conceito: repercussões psiquiátricas associadas ao tratamento; Contexto: uso clínico). Foram incluídos estudos completos, publicados nos últimos cinco anos, de acesso livre, em todos os idiomas, abrangendo ensaios clínicos, estudos observacionais, farmacovigilância e revisões. As buscas ocorreram nas bases PubMed, Medline, Scopus, Embase e Cochrane Library, com complementação no Google Acadêmico. A seleção e extração foram realizadas por dois revisores independentes, com síntese qualitativa dos achados. Resultados e Discussão: Doze estudos compuseram a amostra final. Ensaios clínicos indicaram eficácia consistente para perda ponderal e melhora metabólica, sem aumento robusto de ideação suicida, embora com limitação para detecção de eventos raros. Dados observacionais e de farmacovigilância revelaram baixa frequência de sintomas depressivos, ansiosos e suicidalidade, sem causalidade definida, coexistindo com relatos de melhora de bem-estar e qualidade de vida. Evidências mecanísticas sugerem possível modulação de circuitos de recompensa e processos inflamatórios, ainda sem confirmação clínica direta. Fatores como uso off-label, automedicação, produtos falsificados e alta prevalência de transtornos mentais reforçam a necessidade de triagem psiquiátrica prévia, monitorização longitudinal e fortalecimento da vigilância sanitária. Conclusão: A tirzepatida apresenta perfil global de segurança psiquiátrica favorável, porém com incertezas relacionadas a eventos raros e subgrupos vulneráveis. São necessários estudos prospectivos com desfechos psiquiátricos primários, comparações entre agonistas incretínicos e integração entre farmacovigilância, regulação e prática clínica, a fim de qualificar a avaliação de segurança mental no uso do fármaco.
Carpal tunnel release can be performed using the WALANT (Wide-Awake Local Anesthesia No Tourniquet) technique, in which epinephrine is commonly used to improve intraoperative hemostasis. However, concerns regarding vasoconstrictor-related complications persist. This study aimed to compare tranexamic acid (TA) with epinephrine for bleeding control during WALANT carpal tunnel release. A prospective randomized study including 53 patients with carpal tunnel syndrome was conducted. Patients were randomized to WALANT with epinephrine (n = 27) or tranexamic acid (n = 26). Surgical time, intraoperative hemostasis, patient satisfaction, and postoperative complications were recorded. Clinical outcomes were assessed using specific clinical tests and the Boston Carpal Tunnel Questionnaire preoperatively and at 30 days. No severe bleeding or ischemic complications were observed in either group. One infection occurred in the epinephrine group requiring surgical debridement. Greater difficulty in achieving intraoperative hemostasis was observed in the TA group, resulting in longer surgical times (29.3 ± 10.5 min vs. 21.4 ± 6.9 min; P < 0.001). Patient satisfaction and functional outcomes were high and comparable between groups. Carpal tunnel release performed using the WALANT technique with either epinephrine or tranexamic acid was associated with similar short-term functional improvement and patient satisfaction. No major complications were observed in either group. However, the use of tranexamic acid was associated with greater difficulty in achieving intraoperative hemostasis and longer surgical times. The trial protocol is available in the trial registry at Brazilian Clinical Trials Registry (ReBec) under registration number RBR2njtg49, date of registration 11/07/2025 (retrospectively registered). https://ensaiosclinicos.gov.br/rg/RBR2njtg49.
Research infra-structure is essential for conducting phase III cancer clinical trials as its lack precludes trial availability and its maturity may influence the portfolio of available options. Several studies have highlighted global disparities, but none has ever mapped the worldwide network of research facilities conducting such trials. We extracted all research sites within recruiting phase III cancer interventional trials from the ClinicalTrials.gov database on July 23, 2024. Address components were combined and queried through the Google Maps API for standardized identification. Matched pairs were subsequently screened for inconsistencies, and Google Maps entries within 1,000 meters were grouped if they represent the same facility. We compared research facilities’ number, density (per 1M inhabitants), size, and portfolio of available trials across World Development Index regions, and modelled the number of available trials and research facilities per country with log-log linear models (elasticity coefficient [β] estimand). Of 77,625 listed sites from 1,287 trials, 65,736 (84.7%) were mapped to 6,634 unique research facilities across 84 countries. We found a strong correlation between the number of research facilities and trials by country (R 2 =0.86, p-value<0.001, β=0.95, 95%CI 0.87-1.04). The United States and China had the largest number of facilities (2,626, 39.6%) and available trials (624, 48.5%) respectively. All the 100 largest research facilities in size were from high-income countries or China, and 16 of the top 20 countries by density were located in Europe and Central Asia. Latin America and Caribbean, South Asia Region, and Sub-Saharan Africa had the highest proportion of facilities running only multiregional (>93%, p-value<0.001), industry-sponsored (>90%, p-value<0.001), and systemic therapy trials (>80%, p-value<0.001). Phase III cancer trials are directly limited and responsive to physical institutional growth. Outside high-income countries, research capacity remains substantially constrained, largely focused on systemic therapies and frequently reliant on industry-sponsored, multiregional trials. None We searched the Pubmed/EMBASE database for studies investigating cancer clinical trials and research facilities distribution worldwide using the search terms “trials OR clinical trials”, “cancer”, “distribution OR barriers OR access OR inequalit*” between inception to November 1st, 2025. Several studies have consistently shown a higher concentration and availability of cancer clinical trials in high-income countries (HIC) compared to lower-income regions. In addition, cancer clinical trials in lower middle-income countries (LMIC) are predominantly phase III, industry-sponsored, and led by HIC. However, most of this evidence is derived from country-level aggregate data, which collapse heterogeneous research infrastructures within countries into single summary measures and therefore lack the resolution needed to describe, and ultimately explain the underlying drivers of these disparities. Only a small number of studies have examined cancer trial distribution at finer geographic scales, and these have generally been limited to city or county-level analyses or to single-country settings. Therefore, there remains no comprehensive mapping of the research infrastructure responsible for conducting cancer clinical trials, even though this infrastructure is a key determinant of national trial availability and study profiles. This is the first study to map and profile research facilities conducting phase III cancer clinical trials worldwide. We show that the availability of phase III cancer clinical trials is linearly correlated with the absolute number of research facilities on a log-log scale, such that a 1% increase in research facilities is associated with a 0.95% (95%CI, 0.87–1.04) increase in phase III trial availability within countries. The United States had the largest share of research facilities (N=2,626, 39%) while China had the highest number of available phase III clinical trials (N=624), driven by a high number of single-center studies (N=398). Of the largest 100 research facilities in size (median [IQR] number of phase III cancer trials 62 [57-73.25]), all were from HIC or China. Of the top 20 countries by density (per million people), 80% were located in Europe and Central Asia (ECA). In Latin America and Caribbean (LAC), South Asia Region (SAR) and Sub-Saharan Africa (SSA), research facilities are found in fewer numbers and smaller sizes, and are predominantly running only multiregional (>93%), industry-sponsored (>90%), and systemic therapy trials (>80%). Global disparities in cancer clinical trials are perpetuated by constrained research infrastructure in less developed regions, reflected not only in the limited number of research facilities but also in their profiles, which often have little experience beyond industry-sponsored trials, as we have shown. While investments in research facilities are crucial and are associated with increased trial availability, particularly during the early stages of infrastructure development, they are not sufficient on their own. Complementary strategies are needed, including financial incentives to support locally designed trials (i.e., investigator-initiated grants) and sustained investment in human resources to design and conduct them. Aligning infrastructure expansion with workforce development is essential to improve both the quantity and the profile of available cancer clinical trials, enhance local leadership, and ensure that research is relevant and generalisable to diverse populations.
