Perspectivas Atuais sobre Terapias para a Doença de Alzheimer: Uma Análise da Literatura Contemporânea

The article provides a comprehensive review of current and emerging therapeutic strategies for the treatment of Alzheimer's disease (AD), an increasingly prevalent neurodegenerative condition in the elderly. The multifaceted complexity of treatment is highlighted, encompassing both pharmacological and non-pharmacological approaches. Acetylcholinesterase inhibitors are commonly used to improve cholinergic neurotransmission, while immunotherapy, including vaccines against beta-amyloid, is in clinical trial phase. Additionally, potential treatments such as antidiabetic agents, serotonergic psychedelics, and gene therapy are discussed. Inflammation is recognized as a crucial component in the pathogenesis of AD, and anti-inflammatory agents show promise in reducing neuroinflammation. However, challenges persist, such as validating results in humans, the lack of reliable biomarkers for early diagnosis, and the need to find effective therapeutic targets that can modify the disease's progression.O artigo oferece uma revisão abrangente das estratégias terapêuticas atuais e emergentes para o tratamento da doença de Alzheimer (DA), uma condição neurodegenerativa cada vez mais prevalente em idosos. Destaca-se a complexidade multifacetada do tratamento, que abrange tanto abordagens farmacológicas quanto não farmacológicas. Os inibidores da acetilcolinesterase são comumente usados para melhorar a neurotransmissão colinérgica, enquanto a imunoterapia, incluindo vacinas contra o beta-amiloide, está em fase de testes clínicos. Além disso, são discutidos potenciais tratamentos como agentes antidiabéticos, psicodélicos serotoninérgicos e terapia genética. A inflamação é reconhecida como um componente crucial na patogênese da DA, e os anti-inflamatórios mostram promessa na redução da neuroinflamação. No entanto, persistem desafios, como a validação de resultados em humanos, a falta de biomarcadores confiáveis para o diagnóstico precoce e a necessidade de encontrar alvos terapêuticos eficazes que possam modificar a progressão da doença

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)