[A conceptual framework for good preventive practices (or for quaternary prevention)]. / Uma articulação conceitual para boas práticas preventivas (ou para a prevenção quaternária).

Prevention is universally advocated, especially in the case of noncommunicable diseases. However, given the proliferation of preventive technologies, it does not seem defensible to generically encourage preventive behaviors and tests for healthcare professionals and users. In this essay, we articulate concepts, ideas and criteria for considering preventive measures, providing a minimum guide to be used by professionals (especially in primary healthcare) and managers. The concepts of primary, secondary and quaternary prevention are explored, as well as those of reductive and additive prevention, high-risk and population-based preventive strategies; evidence-based medicine and its contemporary crisis; the precautionary principle; health promotion, an expanded, person-centered approach and shared decision-making. This discussion was designed to improve competence in the evaluation of preventive measures, making clinical and health decisions more judicious and less iatrogenic regarding primary and secondary prevention.

A prevenção é consensualmente defendida, especialmente para as doenças crônicas não transmissíveis. Porém, dada a proliferação de tecnologias preventivas, não parece defensável estimular genericamente condutas e exames preventivos em profissionais de saúde e usuários. Neste ensaio, apresentamos uma articulação de conceitos, ideias e critérios para a consideração de medidas preventivas, como um roteiro mínimo a ser manejado pelos profissionais (especialmente os da atenção primária à saúde) e gestores. São articulados os conceitos de: prevenção primária, secundária e quaternária; prevenção redutiva e aditiva, estratégias preventivas de alto risco e populacional; medicina baseada em evidências e sua crise contemporânea; princípio da precaução; promoção da saúde, abordagem ampliada e centrada na pessoa e decisão compartilhada. Tal articulação foi concebida visando melhorar a competência na avaliação de medidas preventivas, tornando as decisões clínicas e sanitárias mais criteriosas e menos iatrogênicas quanto à prevenção primária e secundária.

La prevención es defendida consensuadamente, especialmente en las enfermedades crónicas no transmisibles. Sin embargo, dada la proliferación de tecnologías preventivas, no parece sostenible fomentar genéricamente conductas y exámenes preventivos entre los profesionales de la salud y los usuarios. En este ensayo, presentamos una articulación de conceptos, ideas y criterios para considerar medidas preventivas, como una guía mínima que manejar por parte de los profesionales (especialmente en la atención primaria de salud) y gestores. Se articulan los conceptos de prevención primaria, secundaria y cuaternaria; prevención reductiva y aditiva, estrategias preventivas de alto riesgo y poblacional; medicina basada en evidencias y su crisis contemporánea; principio de precaución; promoción de la salud, abordaje ampliado y centrado en la persona y toma de decisiones compartida. Esta articulación fue diseñada para mejorar la competencia en la evaluación de medidas preventivas, haciendo que las decisiones clínicas y de salud sean más juiciosas y menos iatrogénicas con relación a la prevención primaria y secundaria.

Practice determinants for adherence to the Guide for the Comprehensive Clinical Care of Dengue Patients, Urabá (Colombia). A multifaceted approach to implementation research.

INTRODUCTION: Dengue is a significant public health issue in the Urabá region, accounting for 37.5% of morbidity and 41.7% of mortality resulting from dengue in the department of Antioquia (Colombia) in 2018. Clinical Practice Guidelines (CPGs) are tools based on Evidence-Based Medicine, intended for medical personnel to bridge the gap between proven intervention efficacy and clinical decision-making. This study aims to identify barriers and facilitators in the implementation of CPGs for dengue patient care by healthcare officials in the municipalities of the banana axis in the Urabá region. METHODOLOGY: From a multifaceted approach to implementation research, a mixed method study that combines qualitative and quantitative approaches, was conducted during the years 2020 and 2021, using combined instruments to identify determinants (Guide Indicative Factors, Individual factors of health professionals, Patient factors, Professional interactions, Incentives and resources, Capacity for organizational change, and lastly Social, political, and legal factors) affecting adherence to the Comprehensive Clinical Care Guide for Patients with Dengue (GACIPD). Semi-structured interviews and focus groups with healthcare workers were conducted to assess determinants based on clinical experience. Questionnaires on determinants of GACIPD adherence, using an adapted version of the Chronic Disease Implementation Checklist (TICD), were also employed. Qualitative analysis of the interviews and focus groups used a concept-based coding framework. The questionnaire responses were analyzed using Likert scaling and frequency counts of determinants within and across domains. Participants included general practitioners, other health professionals, researchers, academics, and administrators. RESULTS: There was a total of 103 participants in focus groups, 7 in semi-structured interviews, and 136 participants through questionnaires. Among the domains studied, the identification of barriers and facilitators emphasized institutional factors and individual factors. Organizational change capacity was identified as a major barrier, with only 3.6% of respondents indicating that their institution adjusted the prioritization of adequate care according to the guideline. The GACIPD domain received the highest facilitator rating, with 66.7% acceptance due to its practicality, simplicity, clarity, documentation, and ease of implementation, despite this, only 10% of professionals completely agree that their work is in accordance with the GACIPD. The determinant of patient factors was significant in the negative perception of adherence to GACIPD. CONCLUSIONS: Although barriers outweighed facilitators for GACIPD adherence, determinants for its use were generally positive, as most participants reported it as being a complete, documented, and easy-to-implement guide. The lack of knowledge of the guidelines impacting health professional's decision making was identified as a potentially modifiable barrier, and educational strategies could be implemented to overcome it. The region requires greater emphasis on the management of chronic health conditions, comorbidities, and coinfections of dengue with other endemic diseases.

La Pregunta de Investigación y su Asociación con los Niveles de Evidencia y Grados de Recomendación en Estudios de Investigación Clínica / The Research Question and its Association with the Levels of Evidence and Grades of Recommendation in Clinical Research Studies

La mayoría de las preguntas de investigación (PI), conducirán a un proyecto que apunta a generar nuevo conocimiento, sin embargo el escenario, la población a estudio y la metodología pueden ser muy diferentes, lo que determinará que los resultados obtenidos y por ende, el nivel de evidencia (NE) y el grado de recomendación (GR) puedan variar notablemente. El objetivo de este artículo fue proporcionar recomendaciones para formular una PI asociada al NE y respectivos GR que se pueden desprender a partir de los resultados generados. Este artículo entregará algunos conocimientos sobre la PI y su relación con los NE y GR de la evidencia generada a partir de resultados obtenidos por un proceso de investigación en diferentes escenarios de investigación.

SUMMARY: Most research questions (RQ) will lead to a project that aims to generate new knowledge. However, the setting, study population and methodology may be very different, which will determine the results obtained and therefore, the level of evidence (LOE) and the grade of recommendation (GOR) may vary significantly. The aim of this study was to provide recommendations to formulate a RQ associated with the LOE and respective GOR that can be derived from the generated results. This article will provide some knowledge about the RQ and its relationship with the LEO and GOR of the generated evidence from results obtained by a research process in different research scenarios.

Expert consensus: Profiling and management of advanced or metastatic epithelial ovarian cancer / Consenso de expertos basado en la evidencia: perfilamiento y manejo del carcinoma epitelial de ovario de alto grado avanzado.

Introduction and objective: The approach to patients with advanced or metastatic high-grade epithelial ovarian cancer (EOC) has evolved over time with the advent of new therapies and multimodal strategies. The objective of this consensus of experts is to generate national recommendations for the profiling and management of advanced or metastatic high-grade OEC, defined as stages III and IV of the "The International Federation of Gynecology and Obstetrics (FIGO) classification at the time of diagnosis to base on the literature review that included international evidence-based clinical practice guidelines (CPG). Material and methods: Eleven panelists (oncologists and gynecological oncologists) answered 8 questions about the profiling and management of advanced or metastatic ovarian epithelial carcinoma. The panelists were chosen for their academic profile and influence in national health institutions. Guidelines from the "ESMO Standardized Operating Procedures Consensus Conference" were used to develop the consensus. It was agreed that the level of agreement to accept a recommendation should be ≥ 80%. The document was peer reviewed. Results: Eight general recommendations are made, which are presented into five domains. Some of these recommendations are subdivided into specific recommendations. Initial treatment Recommendation 1.1 Complete primary cytoreduction (PCS) surgery is suggested as the initial therapy of choice for patients with high-grade or metastatic EOC, which should ideally be carried out in centers with experience, followed by adjuvant therapy. 1.2 Neoadjuvant chemotherapy followed by interval cytoreduction surgery (ICS) is suggested in those who are unlikely to achieve a complete cytoreduction in PCS either due to unresectable metastatic disease or who present unresectability criteria (imaging, laparoscopic and/or by laparotomy) and that have been defined by a gynecological oncologist and patients with poor functional status and comorbidities according to the criteria of the multidisciplinary team (clinical oncology, gynecological oncology, radiology, etc.). Recommendation 2. In patients with high-grade epithelial ovarian cancer (EOC), in stage III locally advanced or metastatic, who received neoadjuvant chemotherapy and achieved a complete or partial response (cytoreduction with tumor residue < 2.5 mm), the use of Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) could be considered as an alternative to standard platinum-based adjuvant intravenous chemotherapy during interval cytoreductive surgery, after discussion in a multidisciplinary tumor board, at a center experienced in treating this type of patients. Use of genetic testing. Recommendation 3. It is suggested at the time of diagnosis to offer molecular genetic testing to all patients with high-grade advanced or metastatic EOC regardless of family history. Recommendation 4. It is suggested to offer genetic counseling, by qualified personnel, to all patients with high-grade advanced or metastatic EOC who are ordered genetic testing. Recommendation 5. It is suggested that all patients with advanced or metastatic high-grade EOC undergo a germ panel that includes the Breast Cancer Susceptibility Genes 1/2 genes (BRCA 1/2) and the other susceptibility genes according to with institutional protocols and the availability of genetic testing panels; If it is negative, then somatic testing should be performed that includes the homologous recombination deficiency (HRD) status, regardless of family history. Adjuvant Therapy Recommendation 6. 6.1. It is suggested that all patients with advanced stage III/IV EOC, with PSC of (0-2), got adjuvant intravenous chemotherapy as standard treatment within six weeks after Prc. It is suggested paclitaxel/carboplatin. Recommendation 6.2. It is suggested to use standard chemotherapy base on platinum plus Bevacizumab as adjuvant chemotherapy to patients with high-risk disease (EOC stage IV or stage III with suboptimal tumor cytoreduction), following by bevacizumab as maintenance. The use of bevacizumab as maintenance therapy is not recommended if bevacizumab was not included in the first line of treatment. We suggested the dose used in GOG-0218 and ICON7 trials. Recommendation 6.3 It is suggested combined intravenous/intraperitoneal chemotherapy only for selected patients, with optimal cytoreduction (residual lesions < 1 cm), especially those without residual disease (R0) and who are evaluated in a multidisciplinary meeting. It is not considered standard treatment. Recommendation 6.4. 6.4.1 It is suggested to use Poly ADP ribose polymerase (PARP) inhibitors such as olaparib or niraparib as maintenance after receiving first-line chemotherapy in patients with stage III/IV BRCA1/2 positive EOC who received platinumbased chemotherapy and obtained complete response/partial response (CR/PR), 6.4.2 It is suggested to use olaparib alone or in combination with bevacizumab or niraparib in patients with stage III/IV BRCA1/2 positive EOC who received platinum-based chemotherapy plus bevacizumab and achieved CR/PR. 6.4.3 It is suggested to use niraparibin patients with stage III/IV BRCA1/2 negative or unknown EOC who received platinum-based chemotherapy and achieved CR/PR. 6.4.4 It is suggested to use bevacizumab or olaparib plus bevacizumab in patients with EOC stage III/IV BRCA1/2 negative or unknown (HRD positive) who received platinum-based chemotherapy plus bevacizumab and obtained CR/PR. Treatment of disease relapse Recommendation 7. Secondary cytoreductive surgery followed by chemotherapy is suggested for selected patients with high-grade advanced EOC in first relapse, platinum-sensitive (platinum-free interval ≥ 6 months), positive "Arbeitsgemeinschaft Gynäkologische Onkologie ­ AGO" score or "I-model" positive (< 4.7) with a potential resection to R0 in centers with access to optimal surgical and postoperative support. Note: Platinum-free interval and AGO score have only been developed as positive predictors of complete resection and not to exclude patients from surgery. Recommendation 8. 8.1 For patients with relapse advanced high-grade EOC platinum-sensitive, the following is suggested: Platinum-based combination chemotherapy: carboplatin/liposomal doxorubicin or carboplatin/paclitaxel or carboplatin/nab-paclitaxel or carboplatin/docetaxel or carboplatin/gemcitabine) for six cycles. If combination therapy is not tolerated, give carboplatin or cisplatin alone. Combination chemotherapy (carboplatin/gemcitabine or carboplatin/paclitaxel or carboplatin/doxorubicin liposomal) plus bevacizumab followed by bevacizumab as maintenance (until progression or toxicity). Recommendation 8.2 For patients with relapsed advanced high-grade EOC platinum-resistant, it is suggested: Sequential treatment with chemotherapy, preferably with a non-platinum single agent (weekly paclitaxel or pegylated liposomal doxorubicin or docetaxel or oral etoposide or gemcitabine or trabectidine or, topotecan). Weekly paclitaxel or pegylated liposomal doxorubicin or topotecan could be administrate with or without bevacizumab. Other agents are considered potentially active (capecitabine, cyclophosphamide, ifosfamide, irinotecan, oxaliplatin, pemetrexed, vinorelbine, cyclophosphamide) could be recommended for later lines. Hormone receptor-positive patients who do not tolerate or have no response to cytotoxic regimens may receive hormone therapy with tamoxifen or other agents, including aromatase inhibitors (anastrozole and letrozole) or leuprolide acetate, or megestrol acetate. Patients with a performance score ≥ 3 should be considered only for best supportive care. Recommendation 8.3 Maintenance therapy with PARP inhibitors: It is suggested in patients with relapse advanced high-grade EOC stage III/IV BRCA1/2 (positive, negative or unknown) who have received two or more lines of platinum-based chemotherapy and have achieved CR/PR, use olaparib, niraparib or rucaparib. Niraparib could be useful in BRCA 1/2 +/-/unknown patients, as rucaparib, however, the latter does not yet have approval from the regulatory office in Colombia. Conclusions: It is expected that the recommendations issued in this consensus will contribute to improving clinical care, oncological impact, and quality of life of these women.

Introducción y objetivo: el abordaje de pacientes con cáncer epitelial de ovario (CEO) de alto grado avanzado o metastásico ha ido evolucionando a través del tiempo con el advenimiento de nuevas terapias y estrategias multimodales. El objetivo de este consenso de expertos es generar recomendaciones nacionales para el perfilamiento y manejo del CEO de alto grado avanzado o metastásico, definido como estadios III y IV de la clasificación de la Federación Internacional de Ginecología y Obstetricia (FIGO) al momento del diagnóstico, a partir de la revisión de la literatura que incluyó guías de práctica clínica (GPC) internacionales basadas en la evidencia. Materiales y métodos: once panelistas (oncólogos y ginecólogos oncólogos) respondieron ocho preguntas sobre el perfilamiento y manejo del carcinoma epitelial de ovario avanzado o metastásico. Los panelistas fueron escogidos por su perfil académico e influencia en instituciones de salud nacionales. Para el desarrollo del consenso se utilizaron los lineamientos de la "Conferencia de consenso de procedimientos operativos estandarizados de ESMO". Se definió que el nivel de acuerdo para aceptar una recomendación debía ser ≥ 80%. El documento fue revisado por pares. Resultados: Se hacen 8 recomendaciones generales, presentadas en cinco dominios; algunas de ellas se subdividen en recomendaciones específicas. Tratamiento inicial Recomendación 1 1.1. Como terapia inicial de elección para pacientes con CEO de alto grado o metastásico se sugiere la cirugía de citorreducción primaria (Cpr) completa que, idealmente, debe realizarse en centros con experiencia, seguida de terapia adyuvante. 1.2. Se sugiere quimioterapia neoadyuvante seguida de cirugía de citorreducción de intervalo (Cint) en quienes sea improbable alcanzar una citorreducción completa en la Cpr, bien sea por enfermedad metastásica no resecable o que presenten criterios de irresecabilidad (imagenológicos, laparoscópicos o por laparotomía) que hayan sido definidos por un ginecólogo oncólogo. También en pacientes con un pobre estado funcional y comorbilidades de acuerdo con el criterio del equipo multidisciplinario (oncología clínica, ginecología oncológica, radiología, etc.). Recomendación 2. En pacientes con CEO de alto grado, en estadio III localmente avanzado o metastásico, que recibieron quimioterapia neoadyuvante y alcanzaron respuesta completa o parcial (citorreducción con residuo tumoral < 2,5 mm), se podría evaluar el uso de la quimioterapia intraperitoneal hipertérmica (Hyperthermic IntraPeritoneal Chemotherapy - HIPEC) como alternativa a la quimioterapia IV adyuvante estándar basada en platinos durante la Cint, previa discusión en junta multidisciplinaria, en un centro de experiencia en este tipo de pacientes. Uso de pruebas genéticas Recomendación 3. Al momento del diagnóstico, se sugiere ofrecer testeo molecular genético a toda paciente con CEO de alto grado avanzado o metastásico, independientemente de la historia familiar. Recomendación 4. Se sugiere ofrecer asesoramiento genético, por parte de personal calificado, a toda paciente con CEO de alto grado avanzado o metastásico a quien se le ordene un testeo genético. Recomendación 5. Se sugiere que a toda paciente con CEO de alto grado avanzado o metastásico se le realice panel germinal que incluya los genes de susceptibilidad al cáncer de mama 1/2 (BRCA 1/2) y los otros genes de susceptibilidad de acuerdo con los protocolos institucionales y la disponibilidad de paneles de testeo genético; si es negativo entonces se debería realizar testeo somático que incluya el estatus de deficiencia de la recombinación homóloga (homologous recombination deficiency - HRD), independientemente de la historia familiar. Terapia adyuvante Recomendación 6 6.1. Se sugiere que a toda paciente con CEO estadios III/IV avanzado o metastásico, con estatus de desempeño (performance score care - PSC) de 0-2 se le administre como tratamiento estándar quimioterapia intravenosa (IV) adyuvante dentro de las seis semanas posteriores a la Cpr. Se sugiere administrar paclitaxel/carboplatino. 6.2. Se sugiere utilizar quimioterapia estándar basada en platino más bevacizumab como adyuvancia en pacientes con enfermedad de alto riesgo (CEO estadios IV o III con citorreducción tumoral subóptima), continuando con bevacizumab como mantenimiento. No se recomienda el uso de bevacizumab como terapia de mantenimiento si no se incluyó en la primera línea de tratamiento. Se sugiere seguir los esquemas de los estudios Gynecologic Oncology Group Study (GOG-0218) e International Collaborative Ovarian Neoplasm (ICON7). 6.3. Se sugiere la quimioterapia combinada IV/intraperitoneal (IP) solo para pacientes seleccionadas, con una citorreducción óptima (lesiones residuales < 1 cm), en especial aquellas sin enfermedad residual (R0) y que sean evaluadas en junta multidisciplinaria. La quimioterapia combinada IV/IP no se considera como tratamiento estándar. 6.4. 6.4.1. Se sugiere utilizar inhibidores de poli(ADP-ribosa) polimerasa (PARP) tales como olaparib o niraparib como mantenimiento después de recibir una primera línea de quimioterapia en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino y obtuvieron respuesta completa/respuesta parcial (RC/RP). 6.4.2. Se sugiere utilizar olaparib solo o en combinación con bevacizumab o niraparib en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. 6.4.3. Se sugiere utilizar niraparib en pacientes con CEO estadio III/IV BRCA1/2 negativo o desconocido que recibieron quimioterapia basada en platino y obtuvieron RC/RP. 6.4.4. Se sugiere utilizar bevacizumab u olaparib más bevacizumab en pacientes con CEO estadios III/IV BRCA1/2 negativo o desconocido (HRD positivo) que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. Tratamiento de la recaída de la enfermedad Recomendación 7. Se sugiere la realización de la cirugía de citorreducción secundaria (Csec), seguida de quimioterapia, a pacientes seleccionadas con CEO de alto grado avanzado o metastásico en primera recaída, platino-sensibles (intervalo libre de platinos ≥ 6 meses), puntuación Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) positiva o Integrate model (I-Model) positivo (< 4,7), y con una potencial resección a R0, en centros con acceso a soporte quirúrgico y posoperatorio óptimo. Nota: el intervalo libre de tratamiento con platinos y la puntuación AGO solo se han desarrollado como predictores positivos de resección completa y no para excluir a las pacientes de la cirugía. Recomendación 8 8.1. Para pacientes con CEO de alto grado avanzado o metastásico en recaída platino-sensibles se sugiere: Quimioterapia combinada basada en platino: carboplatino/doxorrubicina liposomal o carboplatino/paclitaxel o carboplatino/ nab-paclitaxel o carboplatino/docetaxel o carboplatino/gemcitabina, por seis ciclos. Si no se tolera la terapia combinada, dar carboplatino o cisplatino solo. Quimioterapia combinada: carboplatino/gemcitabina o carboplatino/paclitaxel o carboplatino/doxorubicina liposomal, más bevacizumab, seguida de bevacizumab como mantenimiento (hasta progresión o toxicidad). 8.2. Para pacientes con CEO de alto grado avanzado o metastásico en recaída, platino-resistentes, se sugiere: Tratamiento secuencial con quimioterapia, preferiblemente con un agente único que no sea un platino (paclitaxel semanal o doxorrubicina liposomal pegilada o docetaxel o etopósido oral o gemcitabina o trabectidina o topotecan). El paclitaxel semanal o la doxorrubicina liposomal pegilada o el topotecan pueden ser administrados con o sin bevacizumab. Existen otros agentes que se consideran potencialmente act ivos (capecitabina, ciclofosfamida, ifosfamida, irinotecán, oxaliplatino, pemetrexed, vinorelbina, ciclofosfamida), que se podrían recomendar para líneas posteriores. Las pacientes con receptores hormonales positivos que no toleran o no tienen respuesta a los regímenes citotóxicos pueden recibir terapia hormonal con tamoxifeno u otros agentes, incluidos los inhibidores de la aromatasa (anastrozol y letrozol) o acetato de leuprolide o acetato de megestrol. Pacientes con PSC ≥ 3 deberían ser consideradas solo para el mejor cuidado de soporte. 8.3. Terapia de mantenimiento con inhibidores PARP. Para pacientes con CEO de alto grado avanzado o metastásico en recaída estadios III/IV BRCA1/2 (positivo, negativo o desconocido), que hayan recibido dos o más líneas de quimioterapia basada en platino y hayan alcanzado RC/RP, se sugiere utilizar olaparib, niraparib o rucaparib. El niraparib podría ser útil en pacientes BRCA 1/2 +/-/desconocido, al igual que el rucaparib, sin embargo, este último no tiene aún aprobación del ente regulador en Colombia. Conclusiones: se espera que las recomendaciones emitidas en este consenso contribuyan a mejorar la atención clínica, el impacto oncológico y la calidad de vida de estas mujeres.

International Society on Thrombosis and Haemostasis clinical practice guideline for treatment of congenital hemophilia A and B based on the Grading of Recommendations Assessment, Development, and Evaluation methodology.

BACKGROUND: Hemophilia is a rare congenital bleeding disorder that results from complete or partial deficiency of blood coagulation factor (F)VIII (hemophilia A) or FIX (hemophilia B) due to pathogenic variants in their coding genes. Hemophilia requires complex management. To date, there is no evidence-based clinical practice guideline on hemophilia treatment based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. OBJECTIVES: This evidence-based clinical practice guideline from the International Society on Thrombosis and Haemostasis aims to provide an overview of evidence and support patients, caregivers, hematologists, pediatricians, other clinicians, researchers, and stakeholders in treatment decisions about congenital hemophilia A and B. METHODS: The International Society on Thrombosis and Haemostasis formed a multidisciplinary guideline panel of physicians and patients with global representation, balanced to minimize potential bias from conflicts of interest. The panel prioritized a set of clinical questions and outcomes according to their importance for clinicians and patients. A methodological team supported the guideline development process, including searching for evidence and performing systematic reviews. The GRADE approach was used, including GRADE Evidence to Decision frameworks. The recommendations were subject to public comment. RESULTS: The panel selected 13 questions, of which 11 addressed the treatment of hemophilia A and 2 the treatment of hemophilia B. Specifically, the panel addressed questions on prophylactic and episodic treatment with FVIII concentrates, bypassing agents, and nonfactor therapy (emicizumab) for hemophilia A (with and without inhibitors) as well as immune tolerance induction for hemophilia A. For hemophilia B, the panel addressed questions on prophylactic and episodic treatment of bleeding events with FIX concentrates. Agreement was reached for all 13 recommendations, of which 7 (54%) were based on evidence from randomized clinical trials, 3 (23%) on observational studies, and 3 (23%) on indirect comparisons. CONCLUSION: Strong recommendations were issued for prophylactic over episodic treatment for severe and moderately severe hemophilia A and B. Only conditional recommendations were issued for the remaining questions. Future research should focus on direct treatment comparisons and the treatment of hemophilia B with and without inhibitors. Future updates of this guideline will provide an updated evidence synthesis on the current questions and focus on new FVIII and FIX concentrates, novel nonfactor therapies, and gene therapy for severe and nonsevere hemophilia A and B.

II Brazilian Society of Rheumatology consensus for lupus nephritis diagnosis and treatment.

OBJECTIVE: To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN). METHODS: Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion. RESULTS: All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy. CONCLUSION: This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.

Efficiency and comparability of using new evidence platforms for updating recommendations: Experience with a type-2 diabetes guideline in Colombia.

Introduction: Updating recommendations for guidelines requires a comprehensive and efficient literature search. Although new information platforms are available for developing groups, their relative contributions to this purpose remain uncertain. Methods: As part of a review/update of eight selected evidence-based recommendationsfor type 2 diabetes, we evaluated the following five literature search approaches (targeting systematic reviews, using predetermined criteria): PubMed for MEDLINE, Epistemonikos database basic search, Epistemonikos database using a structured search strategy, Living overview of evidence (L.OVE) platform, and TRIP database. Three reviewers independently classified the retrieved references as definitely eligible, probably eligible, or not eligible. Those falling in the same "definitely" categories for all reviewers were labelled as "true" positives/negatives. The rest went to re-assessment and if found eligible/not eligible by consensus became "false" negatives/positives, respectively. We described the yield for each approach and computed "diagnostic accuracy" measures and agreement statistics. Results: Altogether, the five approaches identified 318 to 505 references for the eight recommendations, from which reviewers considered 4.2 to 9.4% eligible after the two rounds. While Pubmed outperformed the other approaches (diagnostic odds ratio 12.5 versus 2.6 to 5.3), no single search approach returned eligible references for all recommendations. Individually, searches found up to 40% of all eligible references (n = 71), and no combination of any three approaches could find over 80% of them. Kappa statistics for retrieval between searches were very poor (9 out of 10 paired comparisons did not surpass the chance-expected agreement). Conclusion: Among the information platforms assessed, PubMed appeared to be more efficient in updating this set of recommendations. However, the very poor agreement among search approaches in the reference yield demands that developing groups add information from several (probably more than three) sources for this purpose. Further research is needed to replicate our findings and enhance our understanding of how to efficiently update recommendations.

Introducción: La actualización de recomendaciones de las guías de práctica clínica requiere búsquedas bibliográficas exhaustivas y eficientes. Aunque están disponibles nuevas plataformas de información para grupos desarrolladores, su contribución a este propósito sigue siendo incierta. Métodos: Como parte de una revisión/actualización de 8 recomendaciones basadas en evidencia seleccionadas sobre diabetes tipo 2, evaluamos las siguientes cinco aproximaciones de búsqueda bibliográfica (dirigidas a revisiones sistemáticas, utilizando criterios predeterminados): PubMed para MEDLINE; Epistemonikos utilizando una búsqueda básica; Epistemonikos utilizando una estrategia de búsqueda estructurada; plataforma (L.OVE) y TRIP . Tres revisores clasificaron de forma independiente las referencias recuperadas como definitivamente o probablemente elegibles/no elegibles. Aquellas clasificadas en las mismas categorías "definitivas" para todos los revisores, se etiquetaron como "verdaderas" positivas/negativas. El resto se sometieron a una nueva evaluación y, si se consideraban por consenso elegibles/no elegibles, se convirtieron en "falsos" negativos/positivos, respectivamente. Describimos el rendimiento de cada aproximación, junto a sus medidas de "precisión diagnóstica" y las estadísticas de acuerdo. Resultados: En conjunto, las cinco aproximaciones identificaron 318-505 referencias para las 8 recomendaciones, de las cuales los revisores consideraron elegibles el 4,2 a 9,4% tras las dos rondas. Mientras que Pubmed superó a las otras aproximaciones (odds ratio de diagnóstico 12,5 versus 2,6 a 53), ninguna aproximación de búsqueda identificó por sí misma referencias elegibles para todas las recomendaciones. Individualmente, las búsquedas identificaron hasta el 40% de todas las referencias elegibles (n=71), y ninguna combinación de cualquiera de los tres enfoques pudo identificar más del 80% de ellas. Las estadísticas Kappa para la recuperación entre búsquedas fueron muy pobres (9 de cada 10 comparaciones pareadas no superaron el acuerdo esperado por azar). Conclusiones: Entre las plataformas de información evaluadas, Pubmed parece ser la más eficiente para actualizar este conjunto de recomendaciones. Sin embargo, la escasa concordancia en el rendimiento de las referencias exige que los grupos desarrolladores incorporen información de varias fuentes (probablemente más de tres) para este fin. Es necesario seguir investigando para replicar nuestros hallazgos y mejorar nuestra comprensión de cómo actualizar recomendaciones de forma eficiente.

The impact of an online course on agreement rates of the certainty of evidence assessment using Grading of Recommendations, Assessment, Development, and Evaluation Approach: a before-and-after study.

BACKGROUND AND OBJECTIVE: The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach is a systematic method for assessing the certainty of evidence (CoE) and strength of recommendations in health care. We aimed to verify the effects of an online-based GRADE course on multirater consistency in the evaluation of the CoE in systematic reviews (SRs) analysis. STUDY DESIGN AND SETTINGS: Sixty-five Brazilian methodologists and researchers participated in an online course over 8 weeks. Asynchronous lessons and weekly synchronous meetings addressed the GRADE system in the context of CoE assessment. We asked participants to evaluate the CoE of random SRs (two before and another two after the course). Analyzes focused on the multirater agreement with a standard response, in the interrater agreement, and before-after changes in the proportion of participants that rated down the domains. RESULTS: 48 individuals completed the course. Participants presented improvements in the raters' assessment of the CoE using the GRADE approach after the course. The multirater consistency of indirectness, imprecision, and the overall CoE increased after the course, as well as the agreement between raters and the standard response. Furthermore, interrater reliability increased for risk of bias, inconsistency, indirectness, publication bias, and overall CoE, indicating progress in between-raters consistency. After the course, approximately 78% of individuals rated down the overall CoE to a low/very low degree, and participants presented more explanations for the judgment of each domain. CONCLUSION: An online GRADE course improved the consistency and agreement of the CoE assessment by Brazilian researchers. Online training courses have the potential to improve skills in guideline methodology development.

Efficiency and comparability of using new evidence platforms for updating recommendations: experience with a type-2 diabetes guideline in Colombia / Eficiencia y comparabilidad del uso de nuevas plataformas de evidencia para la actualización de recomendaciones: experiencia con una guía de diabetes tipo 2 en Colombia

INTRODUCTION: Updating recommendations for guidelines requires a comprehensive and efficient literature search. Although new information platforms are available for developing groups, their relative contributions to this purpose remain uncertain. METHODS: As part of a review/update of eight selected evidence-based recommendationsfor type 2 diabetes, we evaluated the following five literature search approaches (targeting systematic reviews, using predetermined criteria): PubMed for MEDLINE, Epistemonikos database basic search, Epistemonikos database using a structured search strategy, Living overview of evidence (L.OVE) platform, and TRIP database. Three reviewers independently classified the retrieved references as definitely eligible, probably eligible, or not eligible. Those falling in the same "definitely" categories for all reviewers were labelled as "true" positives/negatives. The rest went to re-assessment and if found eligible/not eligible by consensus became "false" negatives/positives, respectively. We described the yield for each approach and computed "diagnostic accuracy" measures and agreement statistics. RESULTS: Altogether, the five approaches identified 318 to 505 references for the eight recommendations, from which reviewers considered 4.2 to 9.4% eligible after the two rounds. While Pubmed outperformed the other approaches (diagnostic odds ratio 12.5 versus 2.6 to 5.3), no single search approach returned eligible references for all recommendations. Individually, searches found up to 40% of all eligible references (n = 71), and no combination of any three approaches could find over 80% of them. Kappa statistics for retrieval between searches were very poor (9 out of 10 paired comparisons did not surpass the chance-expected agreement). CONCLUSION: Among the information platforms assessed, PubMed appeared to be more efficient in updating this set of recommendations. However, the very poor agreement among search approaches in the reference yield demands that developing groups add information from several (probably more than three) sources for this purpose. Further research is needed to replicate our findings and enhance our understanding of how to efficiently update recommendations.

INTRODUCCIÓN: La actualización de recomendaciones de las guías de práctica clínica requiere búsquedas bibliográficas exhaustivas y eficientes. Aunque están disponibles nuevas plataformas de información para grupos desarrolladores, su contribución a este propósito sigue siendo incierta. MÉTODOS: Como parte de una revisión/actualización de 8 recomendaciones basadas en evidencia seleccionadas sobre diabetes tipo 2, evaluamos las siguientes cinco aproximaciones de búsqueda bibliográfica (dirigidas a revisiones sistemáticas, utilizando criterios predeterminados): PubMed para MEDLINE; Epistemonikos utilizando una búsqueda básica; Epistemonikos utilizando una estrategia de búsqueda estructurada; plataforma (L.OVE) y TRIP . Tres revisores clasificaron de forma independiente las referencias recuperadas como definitivamente o probablemente elegibles/no elegibles. Aquellas clasificadas en las mismas categorías "definitivas" para todos los revisores, se etiquetaron como "verdaderas" positivas/negativas. El resto se sometieron a una nueva evaluación y, si se consideraban por consenso elegibles/no elegibles, se convirtieron en "falsos" negativos/positivos, respectivamente. Describimos el rendimiento de cada aproximación, junto a sus medidas de "precisión diagnóstica" y las estadísticas de acuerdo. RESULTADOS: En conjunto, las cinco aproximaciones identificaron 318-505 referencias para las 8 recomendaciones, de las cuales los revisores consideraron elegibles el 4,2 a 9,4% tras las dos rondas. Mientras que Pubmed superó a las otras aproximaciones (odds ratio de diagnóstico 12,5 versus 2,6 a 53), ninguna aproximación de búsqueda identificó por sí misma referencias elegibles para todas las recomendaciones. Individualmente, las búsquedas identificaron hasta el 40% de todas las referencias elegibles (n=71), y ninguna combinación de cualquiera de los tres enfoques pudo identificar más del 80% de ellas. Las estadísticas Kappa para la recuperación entre búsquedas fueron muy pobres (9 de cada 10 comparaciones pareadas no superaron el acuerdo esperado por azar). CONCLUSIONES: Entre las plataformas de información evaluadas, Pubmed parece ser la más eficiente para actualizar este conjunto de recomendaciones. Sin embargo, la escasa concordancia en el rendimiento de las referencias exige que los grupos desarrolladores incorporen información de varias fuentes (probablemente más de tres) para este fin. Es necesario seguir investigando para replicar nuestros hallazgos y mejorar nuestra comprensión de cómo actualizar recomendaciones de forma eficiente.

Evidence-Based Learning Strategies in Medicine Using AI.

Unlabelled: Large language models (LLMs), like ChatGPT, are transforming the landscape of medical education. They offer a vast range of applications, such as tutoring (personalized learning), patient simulation, generation of examination questions, and streamlined access to information. The rapid advancement of medical knowledge and the need for personalized learning underscore the relevance and timeliness of exploring innovative strategies for integrating artificial intelligence (AI) into medical education. In this paper, we propose coupling evidence-based learning strategies, such as active recall and memory cues, with AI to optimize learning. These strategies include the generation of tests, mnemonics, and visual cues.