Clinical practice guidelines in Brazil - developing a national programme.

In Brazil, governmental and non-governmental organisations develop practice guidelines (PGs) in order to optimise patient care. Although important improvements have been made over the past years, many of these documents still lack transparency and methodological rigour. In order to conduct a critical analysis and define future steps in PG development in Brazil, we carried out a structured assessment of strengths, weaknesses, opportunities and threats (SWOT analysis) for the development of a national guideline programme. Participants consisted of academia, methodologists, medical societies and healthcare system representatives. In summary, the PG development process has improved in Brazil and current investments in methodological research and capacity-building are ongoing. Despite the centralised processes for public PGs, standardised procedures for their development are not well established and human resources are insufficient in number and capacity to develop the amount of trustworthy documents needed. Brazil's capacity could be strengthened and initial efforts have been made such as the adoption of standards proposed by world-renowned institutions in PG development and enhancement of the involvement of key stakeholders. Further steps involve the alignment between health technology assessment and PG processes for synergy and the development of a national network to promote the interaction between groups involved in the development of PGs. The lessons learned from this paper could be used to foster debate on guideline development, especially for countries facing similar threats on this topic.

Pneumoretroperitoneum, pneumomediastinum and subcutaneous emphysema after endoscopic submucosal dissection of a rectal lateral spreading tumor / Pneumorretroperitônio, pneumomediastino e enfisema subcutâneo após dissecção endoscópica da submucosa de lesão retal de crescimento lateral

Introduction: Endoscopic submucosal dissection (ESD) is an already established procedure in the treatment of gastric and esophageal cancer in its early stages. Colorectal lesions, initially approached by endoscopic mucosal resection en bloc or in fragments, are the current focus for submucosal approach, especially for superficial lateral spreading tumor of 20 mm-diameter. The experience of Japanese centers, which are reference in therapeutic endoscopy, demonstrates reduction in the rate of disease recurrence with this approach and, according to specific histopathological criteria, may avoid colectomy in some cases of malignant neoplasia. Case report: The patient was 50-year-old female. She underwent endoscopic submucosal dissection of a rectal lateral spreading tumor measuring 50 mm, located 8 cm from the anal margin. The procedure was performed without major complications, with just two points for muscle layer detachment, without gross perforation and closed with metal clips. However, the patient developed air leakage to the peritoneum, retroperitoneum, mediastinum and subcutaneous tissue, being only treated with clinical procedures and without additional intervention. Conclusion: It is vital to know and be able to apply the technique of ESD, in addition to addressing its complications, since despite the numerous benefits compared to surgery, ESD can result in serious outcomes. (AU)

Introdução: A dissecção endoscópica da submucosa (ESD) já é procedimento consagrado no tratamento do câncer gástrico e esofagiano em suas fases precoces. As lesões colorre-tais, inicialmente abordadas por mucossectomia, em bloco ou em fragmentos, são o foco atual para a abordagem submucosa, principalmente para os tumores de crescimento lateral superficial a partir de 20 mm de diâmetro. A experiência de centros japoneses, referências em endoscopia terapêutica, demonstram redução no índice de recidiva da doença com esta abordagem e, segundo critérios histopatológicos específicos, podem evitar uma colectomia em alguns casos de neoplasia maligna. Relato de caso: Trata-se de paciente de 50 anos, submetida à dissecção endoscópica da submucosa de lesão de crescimento lateral, com 50 mm, localizada no reto, a 8 cm da margem anal. O procedimento foi realizado sem maiores intercorrências, com apenas dois pontos de afastamento da muscular, sem perfuração grosseira, fechados com clipe. Entretanto, a paciente evoluiu com escape aéreo para peritônio, retroperitônio, mediastino e subcútis, sendo tratada sem intervenção adicional, apenas com manejo clínico. Conclusão: É de fundamental importância conhecer e saber aplicar a técnica da ESD, além de abordar suas complicações, uma vez que, mesmo repleta de benefícios em relação à cirurgia, ela pode apresentar desfechos graves. (AU)

In vitro and in vivo equivalence studies of alendronate monosodium tablets.

OBJECTIVE: The aim of this study was to test the bioequivalence of two alendronate tablets (CAS 121268-17-5; Marvil 10 and Marvil 70 as test formulations, in short "test"; reference formulation, in short "reference") in vitro and in vivo in healthy adult male subjects and to describe a mode for researching the bisphosphonate oral formulation pharmaceutical quality. METHODS: Two dissolution tests with 10-mg and 70-mg alendronate tablets, a preliminary clinical test with 10-mg tablets (n = 10) and a bioequivalence study with 70-mg tablets (n = 23) were performed. Clinical studies were single-dose, open, cross-over, randomized, including a four-week wash-out period. Alendronate was assessed by HPLC in urine after 6 (UE6) and 24 (UE24) h post-intake. In all the experiments the reference was the one that had proved efficacy and safety in international regulatory clinical trials. RESULTS: The dissolution test showed a comparable release profile between reference and test, of both, the 10-mg and 70-mg tablet, the difference (f1) and similarity (f2) factors being within the acceptance values. The clinical trials showed great variability in urinary recovery, from one third the average figure up to 2-3 fold. The amount recovered with the 70-mg tablet was 11-15 fold higher than with the 10-mg tablets, suggesting higher (test/reference) was found to be 72-122% for UE24, and when analyzed in individuals with apparent steady bone metabolism during the wash-out period (n = 19), it was 86-137%. Both margins are considered acceptable in view of the particular kinetic and dynamic features of bisphosphonates, their very high inter- and intra-individual variability, extremely low absorption, time-changeable bone compartment, high margin of safety and long-term achievable therapeutic benefits. CONCLUSION: Test is bioequivalent to reference.

Tolerabilidad digestiva de los bisfosfonatos orales en pacientes con osteoporosis y otras osteopatias medicas / Tolerability of oral bisphosponates in patients with osteoporosis and other osteopathies

Pamidronato, atendronato y olpadronato son eficaces bisfosfonatos nitrogenados. Su baja biodisponibilidad y solubilidad en el contenido del tracto digestivo favorecen los efectos colaterales esófago-gastro-intestinales. Ademßs, las cantidades administradas, la potencialidad ulcerogUnica de cada compuesto y el grado de contacto con las mucosas mßs sensibles son los factores que mayormente influyen en la tolerabilidad digestiva. Sin embargo, debido a la interacción de estos factores, ninguno de ellos analizado particularmente permite anticipar quU bisfosfonato serß el mejor tolerado a largo plazo. Los datos clYnicos disponibles son incompletos y no comparativos, pues se tratan de estudios abiertos o comparados con placebo solamente. No obstante, 3 estudios que incluyen a una población numerosa, muestran un perfil de efectos colaterales similar para el pamidronato (cuando este es administrado en cßpsulas con cubierta entUrica) y el alendronato. El conocimiento de los factores influyentes en la tolerabilidad de cada preparación, facilitarß el manejo clYnico de estos bisfosfonatos cuando varios de ellos estUn disponibles para utilizarlos opcionalmente según la sensibilidad y carcterYsticas de cada paciente. (AU)

Tolerabilidad digestiva de los bisfosfonatos orales en pacientes con osteoporosis y otras osteopatias medicas / Tolerability of oral bisphosponates in patients with osteoporosis and other osteopathies

Pamidronato, atendronato y olpadronato son eficaces bisfosfonatos nitrogenados. Su baja biodisponibilidad y solubilidad en el contenido del tracto digestivo favorecen los efectos colaterales esófago-gastro-intestinales. Ademßs, las cantidades administradas, la potencialidad ulcerogÚnica de cada compuesto y el grado de contacto con las mucosas mßs sensibles son los factores que mayormente influyen en la tolerabilidad digestiva. Sin embargo, debido a la interacción de estos factores, ninguno de ellos analizado particularmente permite anticipar quÚ bisfosfonato serß el mejor tolerado a largo plazo. Los datos clÝnicos disponibles son incompletos y no comparativos, pues se tratan de estudios abiertos o comparados con placebo solamente. No obstante, 3 estudios que incluyen a una población numerosa, muestran un perfil de efectos colaterales similar para el pamidronato (cuando este es administrado en cßpsulas con cubierta entÚrica) y el alendronato. El conocimiento de los factores influyentes en la tolerabilidad de cada preparación, facilitarß el manejo clÝnico de estos bisfosfonatos cuando varios de ellos estÚn disponibles para utilizarlos opcionalmente según la sensibilidad y carcterÝsticas de cada paciente.