Evaluation of the economic benefits, administration times, and patient preferences associated with the use of biotechnological drugs administered subcutaneously and intravenously in patients with cancer: a systematic review.

INTRODUCTION: Cancer imposes a high economic burden with medical care and medication costs. We evaluate the costs, the use of resources, the administration time, and the patient preferences associated with the use of biotechnological drugs in SC and IV presentations. METHODOLOGY: A systematic literature search was conducted in PubMed, Embase, and seven additional databases. The search was carried out in September 2021 and included only studies directly comparing SC and IV presentations. Evidence was synthesized narratively. RESULTS: 34 references were included, which only analyzed bortezomib, daratumumab, rituximab, and trastuzumab. Reduction in preparation costs of SC compared to IV presentations ranged from 6.6% to 50.1%, and in administration costs from 4.5% to 95.3%. SC administration of rituximab and trastuzumab resulted in less productivity loss. More than 68% of patients reported greater satisfaction with the SC route. A reduction of time in the infusion chair, lower costs of resources for preparation, and health personnel for the administration process were identified with SC administration. CONCLUSIONS: The use of SC daratumumab, rituximab, and trastuzumab in patients with cancer reduces direct and indirect costs and adverse events compared to IV use. Patients prefer the SC administration, perceiving more comfort, and less pain at the administration site.

Alectinib for treating patients with metastatic ALK-positive NSCLC: systematic review and network metanalysis.

Aim: To compare the efficacy and safety of alectinib with other ALK inhibitors in treating patients with metastatic or locally advanced ALK-positive NSCLC. Methods: A systematic literature review was conducted up to November 2021. Network meta-analyses were performed using the frequentist method (random effects). GRADE evidence profile was conducted. Results: 13 RCTs were selected. For overall survival, alectinib was found to reduce the risk of death compared with crizotinib. In progression-free survival, alectinib reduced the risk of death or progression compared with crizotinib and ceritinib. Subgroup analysis by brain metastasis at baseline showed the superiority of alectinib over crizotinib and a similar effect compared with second-and third-generation inhibitors. Alectinib showed a good safety profile compared with the other ALK inhibitors.

This article reports the results of a systematic literature review with network meta-analysis (NMA) that aimed to compare the efficacy and safety of alectinib with other ALK inhibitors in treating patients with metastatic or locally advanced ALK-positive NSCLC. The results show that alectinib reduces the risk of death and the risk of progression compared with crizotinib. For progression-free survival, further significant reductions were observed when compared with ceritinib. For the other ALK inhibitors, no statistically significant differences were found. Subgroup analysis according to the presence of CNS metastases at baseline were consistent in showing the superiority of alectinib over crizotinib and the absence of statistically significant differences compared with second-and third-generation inhibitors. Alectinib showed a good safety profile compared with the other ALK inhibitors, reducing the frequency of adverse events (AEs) compared with ceritinib, and with no statistically significant differences compared with lorlatinib, brigatinib, ensartinib and crizotinib for the frequency of serious AEs or discontinuation of treatment due to AEs. The results of this study suggest clinically relevant insights in decision-making based on patient survival and progression-free survival. Furthermore, considering the importance of reducing the risk of intracranial progression and the need for available therapies for patients who will inevitably progress, alectinib could be considered as a first-line treatment for patients with ALK-positive NSCLC.

Burden of disease of spinal muscular atrophy linked to chromosome 5q (5q-SMA) in Colombia.

OBJECTIVE: This article estimates the disease burden of 5q-SMA in Colombia by using the disability-adjusted life years (DALYs) metric. METHODS: Epidemiological data were obtained from local databases and medical literature and were adjusted in the DisMod II tool. DALYs were obtained by adding years of life lost due to premature death (YLL) and years lived with disability (YLD). RESULTS: The modeled prevalence of 5q-SMA in Colombia was 0.74 per 100,000 population. The fatality rate for all types was 14.1%. The disease burden of 5q-SMA was estimated at 4,421 DALYs (8.6 DALYs/100,000), corresponding to 4,214 (95.3%) YLLs and 207 (4.7%) YLDs. Most of the DALYs were accounted in the 2-17 age group. Of the total burden, 78% correspond to SMA type 1, 18% to type 2, and 4% to type 3. CONCLUSIONS: Although 5q-SMA is a rare disease, it is linked to a significant disease burden due to premature mortality and severe sequelae. The estimates shown in this article are important inputs to inform public policy decisions on how to ensure adequate health service provision for patients with 5q-SMA.

Integrated Maternal Care Strategies in Low- and Middle-Income Countries: A Systematic Review.

Background and aim: Ineffective organisation of care leads to increased morbidity and mortality in neonates and their mothers. We aimed to identify and describe strategies used in low- and middle-income countries that attempt to deliver coherent, coordinated, and continuous services (i.e., integrated care) and how the various strategies affect the organisation of care. Methods: We conducted a systematic literature review to identify, appraise, and synthesise relevant evidence about strategies for integrating maternal care in low- and middle-income countries, searching multiple electronic databases. Results: Fourteen studies met our inclusion criteria. We identified five types of integration strategies: 1) organisational, 2) service/professional, 3) functional, 4) organisational combined with normative strategies, and 5) clinical combined with functional integration strategies. The most frequent types of strategies were organisational, and service/professional integration strategies. We did not identify any publications describing systemic integration strategies implemented in low- and middle-income countries. Conclusions: Most types of strategies described in theory have been implemented and studied in low- and middle-income countries. Our findings suggest that different types of strategies may lead to comparable organisational outcomes. For example, organisational integration strategies and professional or service integration strategies may similarly influence inter-organisational collaboration. Inter-organisational collaboration may play a particularly important role in the context of maternal care integration.

Natalizumab in patients with multiple sclerosis in Colombia: a case series / Natalizumab en pacientes con esclerosis múltiple en Colombia: una serie de casos

SUMMARY INTRODUCTION: Natalizumab is a humanized monoclonal antibody prescribed in the treatment of multiple sclerosis, the most prevalent chronic and inflammatory disease of the central nervous system (CNS). NEDA (no evidence of disease activity) status is the goal of multiple sclerosis treatment. METHODOLOGY: The clinical records of 22 patients with multiple sclerosis, followed for a mean of 9.2 years (range: 1.9 -18.3 years) between 2000 and 2018 were analyzed. These patients received treatment with natalizumab in a high-complexity neurological outpatient clinic in Bogotá, Colombia. RESULTS: Eighteen patients (82%) reached NEDA status within a median time of six months. Seven patients (32%) tested positive for anti-JC virus antibodies. However, none of them developed progressive multifocal leukoencephalopathy. During the evaluation period, five patients (23%) presented new lesions and 17 patients (77%) had relapses before reaching NEDA status. CONCLUSIONS: This study gave an exploratory analysis of the characteristics of a series of patients with MS in the Colombian context. In the retrospective analysis, it was observed that more than 80% of the studied sample that received treatment with natalizumab, reached NEDA status. Despite the methodological limitations inherent to this type of study and sample size, it suggests that natalizumab could be an appropriate medication for the management of multiple sclerosis in Colombia.

RESUMEN INTRODUCCIÓN: Natalizumab es un anticuerpo monoclonal humanizado empleado en el tratamiento de esclerosis múltiple, la enfermedad crónica e inflamatoria más prevalente del sistema nervioso central. El estado de NEDA (sin evidencia de actividad de la enfermedad) es el objetivo del tratamiento de la esclerosis múltiple. METODOLOGÍA: Se analizaron las historias clínicas de 22 pacientes con esclerosis múltiple que fueron seguidos durante una media de 9,2 años (rango: 1,9-18,3 años) entre 2000 y 2018. Estos pacientes recibieron tratamiento con natalizumab en una clínica ambulatoria neurológica de alta complejidad en Bogotá, Colombia. RESULTADOS: Dieciocho pacientes (82)% alcanzaron el estado NEDA en un tiempo medio de seis meses. Siete pacientes (32%) dieron positivo para anticuerpos anti-virus JC. Sin embargo, ninguno desarrolló leucoencefalopatía multifocal progresiva. Durante el periodo de seguimiento cinco pacientes (23%) presentaron nuevas lesiones y 17 pacientes (77%) tuvieron recaídas antes de alcanzar el estado NEDA. CONCLUSIONES: Este estudio provee un análisis exploratorio de las características de una serie de pacientes colombianos con esclerosis múltiple.. En el análisis retrospectivo, se observó que más de 80% de ellos alcanzó el estado NEDA. A pesar de las limitaciones metodológicas inherentes al tipo de estudio y el tamaño de la muestra, este estudio sugiere que natalizumab podría ser un medicamento apropiado para el tratamiento de la esclerosis múltiple. en Colombia.

Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable or metastatic melanoma with BRAF V600 mutation: A systematic review and network meta-analysis.

The current systematic review aimed to evaluate the efficacy and safety of dabrafenib plus trametinib (dabrafenib-trametinib) with those of other therapeutic alternatives in the treatment of patients with BRAF V600 mutation unresectable or metastatic melanoma. The search was carried out on four databases up to July-2018. Two separate network meta-analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF V600 mutation (NMA-pBRAFV600) and another with a mixed population (with or without the mutation: NMA-pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA-pMixed was assessed via sensitivity analysis. Five clinical trials were included in the NMA-pBRAFV600. In the NMA-pBRAFV600 population, dabrafenib-trametinib had a favorable effect on overall survival (OS) and progression-free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine, and on partial response rate (PRR) and overall response rate (ORR) compared with dacarbazine and vemurafenib. In the NMA-pMixed population, dabrafenib-trametinib had a positive effect on OS vs ipilimumab 3 mg/kg and on PFS and PRR vs ipilimumab (3 and 10 mg/kg), nivolumab, and pembrolizumab. However, dabrafenib-trametinib, and vemurafenib-cobimetinib were comparable in terms of clinical efficacy. In addition, dabrafenib-trametinib was associated with less grades 3 and 4 adverse events.

International Experience in Therapeutic Value and Value-Based Pricing: A Rapid Review of the Literature.

OBJECTIVES: To characterize at a global level the concept of therapeutic value (TV) and describe the experience of value-based pricing (VBP) policies in 6 reference countries. METHODS: We conducted a rapid review of the literature that addressed 2 exploratory research questions. A systematic and exhaustive search was carried out up to July 2018 in MEDLINE (Ovid), Embase, Scopus, and Web of Science. RESULTS: The concepts of TV and VBP are related; value frameworks for medicines should include social preferences, comparative effectiveness, safety, adoption viability, social impact, high quality of evidence, severity of illness, and innovation. The added therapeutic value (ATV) is the manner of measuring the therapeutic advantages of new medicines compared with existing ones in terms of comparative effectiveness and safety. There are variations in the mechanisms of reimbursement and drug pricing regulation between the countries of study. CONCLUSION: In a VBP system it is essential to establish the TV and ATV of a new medicine. Although there are no methodological guidelines for the implementation of VBP policies, the process implies from the beginning the definition of TV categories that will be included in the drug pricing and reimbursement systems. Agreements between the pharmaceutical industry and governments have become a useful tool as a negotiating mechanism in most countries.

Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable advanced/metastatic melanoma with BRAF-V600 mutation: A systematic review and network meta-analysis.

The current systematic review aimed to evaluate and compare the efficacy and safety of dabrafenib-trametinib with those of other therapeutic alternatives in the treatment of patients with unresectable advanced/metastatic melanoma with BRAF-V600 mutation. The search was carried out on four databases up to July 2018. Two separate network meta-analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF-V600 mutation (NMA-pBRAFV600) and another with mixed population (with or without the mutation: NMA-pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA-pMixed was assessed via a sensitivity analysis. Nine clinical trials were included in the NMA-pBRAFV600. Dabrafenib-trametinib was found to have a favorable effect on overall survival (OS) and progression-free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine and on partial response rate (PRR) and overall response rate compared with dacarbazine and vemurafenib. In the NMA-pMixed, dabrafenib-trametinib was found to have a positive effect on OS versus ipilimumab 3 mg/kg and on PFS and PRR versus ipilimumab, nivolumab, and pembrolizumab. However, dabrafenib-trametinib and vemurafenib-cobimetinib significantly differed in terms of efficacy. In addition, dabrafenib-trametinib has a favorable effect on Grades 3 and 4 adverse events.

Effectiveness assessment of maternal and neonatal health video clips in knowledge transfer using neuromarketing tools: A randomized crossover trial.

Audiovisual educational material has been used effectively as a knowledge translation strategy in patient education. Given the need to impact maternal mortality rates, 12 video clips related to maternal and neonatal health information were designed based on the results of a previous systematic review (SR). The content was formulated based on clinical practice guideline recommendations and validated following a formal consensus methodology. This study evaluated the effectiveness of knowledge transfer from the 12 video clips in terms of attention, emotional response, and recall by using neuroscience tools. In a randomized cross-over trial, 155 subjects (pregnant women, non-pregnant women, and men) received random sequences of 13 video clips, including a control video clip. Participants' attention levels were evaluated through eye tracking, their emotional reactions were monitored by electrodermal activity and pupillary diameter, and their recall was tested via a questionnaire. An analysis was performed to evaluate differences in the groups and between the video clips and the control clip using variance analysis models that considered period, sequence, and carry-over effects. Results revealed that fixation length was greater in women than in men, while the greatest emotional effects occurred in men. All three groups had good recall results, without any significant differences between them. Although the sequencing did influence attentional processes, no carry-over effect was demonstrated. However, a differential effect was noted among video clips in all three outcomes, that is, when adjusted for group, level of education, and having had children. The control clip generated less attention, emotional reaction, and recall than the experimental video clips. The video clips about maternal and neonatal health were shown to be effective in the transference and comprehension of information. Therefore, cognitive neuroscience techniques are useful in evaluating knowledge translation strategies through audiovisual formats.

Quality of life in refractory generalized myasthenia gravis: A rapid review of the literature.

Generalized myasthenia gravis (GMG) is a neuromuscular transmission disorder that creates a fluctuating weakness of the voluntary muscles. This study is aimed at understanding the effect that refractory GMG has on the quality of life of patients who suffer from it, and the effect of eculizumab on it. A systematic literature search was conducted in MEDLINE (Ovid), EMBASE and the Cochrane Database of Systematic Reviews (Ovid). Eligibility criteria were verified via the title and summary and afterward through the full text. The risk of bias of the included randomized clinical trials was evaluated and the data were synthesized in a descriptive manner. Nine studies were identified that evaluated the quality of life of patients with GMG. Regarding the effect of eculizumab, two studies were identified. The quality of life in patients with GMG is lower compared to ocular myasthenia gravis (MG) and MG in remission, especially in the domains of physical function, physical role, bodily pain, vitality, and social function. Patients treated with eculizumab had a better perception of their quality of life compared to those who received placebo. GMG affects the quality of life more than other types of MG. This outcome is of great importance for the choice of therapeutic options in patients with refractory GMG. Eculizumab generates improvements in the perception of patients' quality of life compared to placebo, making it a relevant therapeutic option in the management of refractory GMG.

Efectividad y seguridad de bortezomib y lenalidomida comparados con regímenes que no los contienen para pacientes con mieloma múltiple / Effectiveness and safety of bortezomib and lenalidomide compared to regimens that do not contain them for patients with multiple myeloma

Introducción: el mieloma múltiple (MM) es un desorden neoplásico de células plasmáticas que representa aproximadamente el 1% de las enfermedades neoplásicas y el 10% de las neoplasias hematológicas; la edad promedio de diagnóstico es de 70 años. Se clasifica como asintomático y sintomático, de acuerdo con el compromiso de órganos o tejidos, el cual se caracteriza por elevación del calcio sérico, insuficiencia renal, anemia y enfermedad ósea. La introducción del trasplante de progenitores hematopoyéticos (TPH) y la disponibilidad de nuevos medicamentos, ha modificado el tratamiento y mejorado su pronóstico. Objetivo: evaluar los beneficios y riesgos del uso de bortezomib y lenalidomida para el tratamiento de pacientes con mieloma múltiple. Metodología: se realizó una búsqueda de evidencia en las bases de datos: MEDLINE, EMBASE, la Librería Cochrane y LILACS. Dos evaluadores de manera independiente, tamizaron las referencias obtenidas, resolviendo las discrepancias por consenso. La calidad de los estudios seleccionados fue evaluada empleando la herramienta AMSTAR. Resultados: se identificaron 29 referencias, de las cuales se incluyeron 3 revisiones sistemáticas de alta calidad. Se presentan los datos de efectividad y seguridad de comparaciones entre regímenes que contienen bortezomib o lenalidomida con aquellos que no contienen estos agentes, en términos de parámetros de respuesta específica, supervivencia libre de progresión (SLP), supervivencia global (SG) y eventos adversos. Conclusiones: Tanto bortezomib como lenalidomida son alternativas terapéuticas efectivas para el tratamiento de inducción en pacientes con mieloma múltiple. Los eventos adversos más comúnmente relacionados con el uso de estos medicamentos son el herpes zoster y la neuropatía periférica para bortezomib, y trombosis venosa profunda para lenalidomida. (AU)

Efectividad y seguridad de lenalidomida comparada con terapia de soporte sin lenalidomida en pacientes con síndrome mielodisplásico y deleción 5q / Effectiveness and safety of lenalidomide compared to supportive therapy without lenalidomide in patients with myelodysplastic syndrome and 5q deletion

Introducción: los síndromes mielodisplásicos (SMD) representan un grupo de neoplasias hematológicas de las células progenitoras hematopoyéticas que comparten características comunes como la presencia de citopenias y un riesgo variable de evolucionar a leucemia mieloblástica aguda (LMA). Se origina a partir de células madre hematopoyéticas con aberraciones genéticas adquiridas, dentro de las cuales se encuentra la deleción aislada del 5q, presente en aproximadamente el 10% de los casos y que se caracteriza por un curso benigno y de bajo riesgo. El objetivo terapéutico en los pacientes con SMD de alto riesgo es modificar la historia natural de la enfermedad y prolongar la supervivencia, y en los pacientes con SMD de bajo riesgo, mejorar la sintomatología y la calidad de vida. Objetivo: evaluar los beneficios y riesgos del uso de lenalidomida para el tratamiento de pacientes con síndrome mielodisplásico y deleción 5q. Metodología: se realizó una búsqueda de evidencia en las bases de datos: MEDLINE, EMBASE, la Librería Cochrane, LILACS, CENTRAL y en el Registro International de ensayos clínicos. Dos evaluadores de manera independiente, tamizaron las referencias obtenidas, resolviendo las discrepancias por consenso. La calidad de los estudios seleccionados fue evaluada empleando la herramienta de riesgo de sesgo de la colaboración Cochrane. Resultados: se identificó un único ensayo clínico aleatorizado, controlado fase 3 y 4 ensayos clínicos fase 2. Se presentan los datos de efectividad y seguridad de la comparación de lenalidomida con placebo, en términos de parámetros de respuesta, supervivencia libre de progresión (SLP), supervivencia global (SG) y eventos adversos. Conclusiones: lenalidomida es un tratamiento efectivo para el manejo de pacientes con síndrome mielodisplásico y deleción 5q. Los eventos adversos más comúnmente relacionados con el uso de este medicamento son neutropenia y trombocitopenia.(AU)

Utilidad diagnóstica del examen molecular de los genes PPA, PSEN-1 y PSEN-2 en Enfermedad de Alzheimer de inicio temprano / Diagnostic utility of the molecular examination of the genes PPA, PSEN-1 and PSEN-2 in early onset Alzheimer's disease

INTRODUCCIÓN: la enfermedad de Alzheimer (EA) es una enfermedad neurodegenerativa de evolución progresiva que representa el tipo más común de demencia. El riesgo de presentar enfermedad de Alzheimer familiar (EAF) puede aumentar 2 a 4 veces entre los individuos que tienen un familiar de primer grado con la enfermedad, para la cual se han identificado mutaciones en tres genes, definidas como causales (PSEN-1, PSEN-2 y APP). OBJETIVO: evaluar la utilidad del estudio molecular de los genes PSEN-1, PPA, PSEN-2 (cromosomas 14, 21 y 1) en el diagnóstico de enfermedad de Alzheimer de inicio temprano (EAIT). METODOLOGÍA: se realizó una búsqueda de evidencia en las bases de datos: MEDLINE, EMBASE, la Librería Cochrane y LILACS. Dos evaluadores de manera independiente, tamizaron las referencias obtenidas, resolviendo las discrepancias por consenso. Se identificaron únicamente estudios descriptivos, a partir de los cuales se basan los resultados del presente informe. RESULTADOS: se identificaron 5 estudios descriptivos. Los estudios confirman la identificación de los 3 genes determinantes en la aparición de la enfermedad de EAIT; las mutaciones más frecuentemente identificadas son las pertenecientes al gen PSEN-1. CONCLUSIONES: el estudio molecular de los genes PSEN-1, PSEN-2 y PPA en pacientes con demencia de inicio temprano (< de 65 años) e historia familiar de demencia, se considera el patrón de oro para el diagnóstico de EAIT de transmisión autosómico dominante.(AU)