Efficacy and safety of faricimab for neovascular age-related macular degeneration: a systematic review and network meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of faricimab compared with other anti-vascular endothelial growth factor (anti-VEGF) agents in treating neovascular age-related macular degeneration (nAMD) patients. METHODS AND ANALYSIS: A systematic review (SR) was conducted up to January 2023. Network meta-analyses (NMA) were performed, including sensitivity and subgroup analyses for naïve population. Outcomes included changes in visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] letters), anatomical changes, frequency of injections and adverse events. The Cochrane Collaboration guidelines and the Confidence in Network Meta-Analysis framework were used for the SR and the certainty of evidence, respectively. RESULTS: From 4128 identified records through electronic databases and complementary searches, 63 randomised controlled trials (RCTs) met the eligibility criteria, with 42 included in the NMA. Faricimab showed a significant reduction in the number of annual injections compared with most fixed and flexible anti-VEGF treatment regimens, while showing no statistically significant differences in visual acuity through ETDRS letter gain, demonstrating a comparable efficacy. Retinal thickness results showed comparable efficacy to other anti-VEGF agents, and inferior only to brolucizumab. Results also showed that more patients treated with faricimab were free from post-treatment retinal fluid compared with aflibercept every 8 weeks, and both ranibizumab and bevacizumab, in the fixed and pro re nata (PRN) assessed schedules. Faricimab showed a comparable safety profile regarding the risk of ocular adverse events and serious ocular adverse events (SOAE), except for the comparison with brolucizumab quarterly, in which faricimab showed a significant reduction for SOAE risk. CONCLUSION: Faricimab showed a comparable clinical benefit in efficacy and safety outcomes, with a reduction in annual injections compared with fixed and flexible anti-VEGF drug regimens, representing a valuable treatment option for nAMD patients. PROSPERO REGISTRATION NUMBER: CRD42023394226.

A healthcare claims analysis to identify and characterize patients with suspected X-Linked Myotubular Myopathy (XLMTM) in the Brazilian Healthcare System.

BACKGROUND: X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital disease, which is not well-defined. To our knowledge, no studies characterizing the XLMTM disease burden have been conducted in Brazil. We identified and described patients with suspected XLMTM using administrative claims data from the Brazilian public healthcare system. METHODS: Data from 2015 to 2019 were extracted from the DATASUS database. As no XLMTM-specific ICD-10 code was available, a stepwise algorithm was applied to identify patients with suspected XLMTM by selecting male patients with a congenital myopathies code (G71.2), aged < 18 years at index date (first claim of G71.2), with an associated diagnostic procedure (muscle biopsy/genetic test) and without spinal muscular atrophy or Duchenne muscular dystrophy. We attempted to identify patients with suspected severe XLMTM based on use of both respiratory and feeding support, which are nearly universal in the care of XLMTM patients. Analyses were performed for the overall cohort and stratified by age at index date < 5 years old and ≥ 5 years old. RESULTS: Of 173 patients with suspected XLMTM identified, 39% were < 5 years old at index date. Nearly all (N = 166) patients (96%) were diagnosed by muscle biopsy (91% of patients < 5 years old and 99% of patients ≥ 5 years old), six (3.5%) were diagnosed by clinical evaluation (8% of patients < 5 years old and 1% of patients ≥ 5 years old), and one was diagnosed by a genetic test. Most patients lived in Brasilia (n = 55), São Paulo (n = 33) and Minas Gerais (n = 27). More than 85% of patients < 5 years old and approximately 75% of patients ≥ 5 years old had physiotherapy at the index date. In both age groups, nearly 50% of patients required hospitalization at some point and 25% required mobility support. Respiratory and feeding support were required for 3% and 12% of patients, respectively, suggesting that between 5 and 21 patients may have had severe XLMTM. CONCLUSION: In this real-world study, genetic testing for XLMTM appears to be underutilized in Brazil and may contribute to underdiagnosis of the disease. Access to diagnosis and care is limited outside of specific regions with specialized clinics and hospitals. Substantial use of healthcare resources included hospitalization, physiotherapy, mobility support, and, to a lesser extent, feeding support and respiratory support.

Factors Associated With Mortality During the First Year Post Infarction: Survival Analysis of Patients With Acute Myocardial Infarction in Colombia.

INTRODUCTION: Cardiovascular diseases account for over 80% of global deaths. Risk factors and social determinants influence mortality in patients post acute myocardial infarction (AMI). OBJECTIVE: To evaluate factors associated with post-AMI mortality during the one-year follow-up. MATERIALS AND METHODS: The study is a prospective cohort study of adults aged 18 years and older with type 1 AMI conducted between October 2021 and January 2024. Intrahospital and outpatient information was collected. Statistical analyses included the Kaplan-Meier survival curve and Cox regression analysis. Proportional hazards and model predictive capacity were evaluated. RESULTS: A total of 1873 patients were included, with a 9.4% mortality rate in the first year. At one year, the estimated survival probability was 88.61% (95% CI: 86.82-90.18). Cox analysis identified several factors associated with mortality, highlighting age (HR = 1.04, 95% CI: 1.02-1.06, p = 0.001), diabetes (HR = 1.77, 95% CI: 1.09-2.87, p = 0.020), renal insufficiency (HR = 2.25, 95% CI: 1.32-3.84, p = 0.003), and type of intervention. The model evaluation showed strong predictive capacity. CONCLUSIONS: It is essential to emphasize the importance of comprehensive management in AMI patients with risk factors such as diabetes and chronic kidney disease, as they are significant predictors of mortality during the first year post infarction.

La carga económica de la hipertensión arterial en Colombia: un análisis de microcosteo / The economic burden of pulmonary arterial hypertension in Colombia: a micro-costing analysis

Resumen Introducción: De acuerdo con el Ministerio de Salud y Protección Social de Colombia, la hipertensión arterial pulmonar (HAP) es una enfermedad huérfana. Aunque existen estudios de costo de la HAP en Colombia, es necesario hacer una actualización del costo de enfermedad. Materiales y método: Este estudio estimó el costo anual de la HAP en Colombia utilizando metodologías de los manuales de evaluación de tecnologías. Resultados: Según la consulta a expertos clínicos y líderes de opinión, alrededor del 81% de los pacientes se encontraban en estadio moderado de la enfermedad (FC II y III) y la terapia más frecuente es sildenafilo en monoterapia o combinación. El costo de diagnóstico promedio en Colombia fue de COP $2,904,724.51, mientras que el costo anual de tratamiento promedio asciende a COP $71,410,480. En general, los costos y hospitalizaciones son mayores en etapas avanzadas de la enfermedad. Conclusiones: Según este estudio, aunque la medicación para el tratamiento de la HAP tiene un alto costo, administrar la terapia adecuada puede mejorar la calidad de vida y reducir la progresión de la enfermedad, las hospitalizaciones y el requerimiento de medicación adicional, lo cual lleva a reducir el costo asociado a la enfermedad. Esto requiere la creación de centros de referencia, y la difusión de información sobre esta patología a los profesionales de la salud.

Abstract Introduction: Pulmonary arterial hypertension (PAH) is an orphan disease according to the Colombian Ministry of Health. Although there is evidence of studies assessing the cost of PAH in Colombia, update of the cost of illness estimation is necessary. Method: This study´s objective was to estimate the annual cost of PAH in Colombia using the Colombian´s Health Technology Assessment Agency methodology. Results: Clinical experts and opinion leaders consulted indicated that about 81% of the patients were in a moderate stage of the disease (FC II and III) and that the most frequent therapy is sildenafil in monotherapy or in combination. The average cost of diagnosing the disease in Colombia was US $ $2,088.23(COP $ 2,904,724.51), while the average annual treatment cost amounts to US $51,337.52(COP $71,410,480). Overall, costs and hospital admissions are higher in advanced stages of the disease. Conclusions: The results of this study indicate that even though drug therapy in PAH is expensive, administering adequate therapy can lead to an improvement in quality of life, a reduction in disease progression, hospitalizations and need for additional medication; reducing costs associated with the disease. This requires the creation of reference centers, and the dissemination of information about this pathology to health care professionals.

Measuring the economic burden of neuromyelitis optica spectrum disorder in Colombia.

OBJECTIVE: To assess the economic burden of neuromyelitis optica spectrum disorder (NMOSD) in the Colombian context. METHODS: Analyses were conducted from a societal perspective using the prevalence-based approach. Costs were expressed in 2022 US dollars (1 USD = $3,914.46 COP). Direct medical costs were assessed from a bottom-up approach. Indirect costs included loss of productivity of the patient and their caregivers. The economic burden of NMOSD in Colombia was estimated as the sum of direct and indirect costs. RESULTS: The direct cost of treating a patient with NMOSD was USD$ 8,149.74 per year. When projecting costs nationwide, NMOSD would cost USD$ 7.2 million per year. Of these costs, 53.5% would be attributed to relapses and 34.4% to pharmacological therapy. Indirect costs potentially attributed to NMOSD in Colombia were estimated at USD$ 1.5 million per year per cohort. Of these, 78% are attributable to loss of patient productivity, mainly due to reduced access to the labor market and premature mortality. CONCLUSIONS: The NMOSD has a representative economic burden at the patient level, with direct costs, particularly related to relapses and medicines, being the main component of total costs. These findings are useful evidence that requires attention from public policymakers in Colombia.

[Vitamin D in a pediatric population after the end of home lockdown: a prospective study]. / Vitamina D en pediatría tras el fin del confinamiento domiciliario: estudio prospectivo.

Home confinement during the onset of the SARS-CoV-2 pandemic decreased sunlight exposure, the main source of vitamin D in the body. OBJECTIVE: To evaluate the impact of SARS-CoV-2 confinement on 25-hydroxyvitamin D (25-OH-VD) levels in a pediatric population. PATIENTS AND METHODS: Observational study in a Spanish pediatric population between June and October 2020. 25-OH- VD levels were measured by electrochemiluminescence and several related variables were collected (anthropometry, sex, skin phototype, date, calcium level, inorganic phosphorus, parathormone, and alkaline phosphatase). The child's companion answered a survey that included the following aspects: access to open air in the house where the confinement took place, hours of sunlight per day received by the child after the end of the confinement, regular use of sunscreen with outdoor exposure, skin phototype of the child, type of milk the child usually drinks, 25-OH-VD supplementation intake, and if so, dosage and adherence to treatment. RESULTS: 123 children participated, mean age 8.15 years (95%CI 7.52-8.79), and 56.1% were female. The median 25-OH-VD was 27.70 ng/ml (RIC 22.7533.60), and 14% presented 25-OH-VD insufficiency (< 20 ng/ml). 25-OH-VD levels presented an ascending correlation slope as the date moved away from the end of confinement (Rho 0.467; p < 0.001), being related to sunshine hours (Rho 0.368; p < 0.001). 25-OH-VD levels were higher in patients with photoprotection (median 29.9 vs 23.5 ng/ml, p = 0.005), with differences according to skin phototype (p = 0.032), but were not related to age, weight z-score, height z-score, body mass index z-score, or the presence of a balcony or garden at home. CONCLUSION: The rate of 25-OH-VD insufficiency at the end of confinement was not higher than in previous studies. 25-OH-VD levels increased progressively in relation to the hours of sunlight exposure and to the summer months. Interestingly, 25-OH-VD levels were higher in children using phot.

Microplastics in Seabird Feces from Coastal Areas of Central Chile.

Pollution from plastic waste thrown into the ocean affects all levels of the food chain. Marine species of birds are affected by plastic particles of different sizes, especially the mesoplastics (1 to 10 mm) found in their digestive tract, which mainly cause obstructions. In the case of microplastics (1.000 µm to 1 mm), their presence in the digestive tract of these species has been widely reported. We studied fecal samples of the Dominican gull (Larus dominicanus) (n = 14), Magellanic penguins (Spheniscus magellanicus) (n = 8), and Humboldt penguin (Spheniscus humboldti) (n = 1) obtained from the Wildlife Rehabilitation Center of the Biobío region, Chile. Microfibers of various colors were present in the feces of Dominican gulls and Magellanic penguins, corresponding mainly in composition to polypropylene (PP) (83%) and rayon (77%). These results demonstrate that microplastic particles occur in the coastal environments of central Chile and suggest that they are probably circulating in the food chain.

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.

Cost-utility and budget impact analysis of CPAP therapy compared to no treatment in the management of moderate to severe obstructive sleep apnea in Colombia from a third-party payer perspective.

OBJECTIVES: To conduct cost-utility and budget impact analysis of providing Continuous Positive Airway Pressure (CPAP) therapy versus no treatment for moderate to severe obstructive sleep apnea (OSA) in Colombia from a third-party payer perspective. METHODS: We used a Markov model to assess the cost-utility and budget impact analysis of CPAP in patients over 40 years old with moderate to severe OSA. Data on effectiveness and utility values were obtained from published literature. A discount rate of 5% was applied for outcomes and costs. ICER was calculated and compared against the threshold estimated for Colombia, which is 86% of the GDP per capita. RESULTS: Over a lifetime horizon, the base case analysis showed the incremental cost per quality-adjusted life-years (QALYs) gained with CPAP therapy was COP$3,503,804 (USD$1,011 in 2020 prices). The budget impact analysis showed that the adoption of CPAP therapy in the target population would lead to a cumulative net budget impact of COP$411,722 million (USD$118,784,412 in, 2020 prices) over five years of time horizon. CONCLUSIONS: CPAP was cost-effective compared to no-treatment in OSA. According to the budget impact analysis, adopting this technology would require a budget allocation that is partially offset by reduced number of strokes and traffic accident events.

Carga económica de la degeneración macular neovascular y el edema macular diabético en Colombia / Economic burden of neovascular macular degeneration and diabetic macular edema in Colombia

Antecedentes: La pérdida de visión tiene consecuencias tanto en la salud como en la estabilidad económica, ya que promueve retrasos en el desarrollo emocional, social, además de reducciones en la productividad laboral. Objetivo: Estimar la carga económica de la degeneración macular asociada a la edad neovascular (DMAEn) y el edema macular diabético (EMD) en Colombia para el año 2022. Método: Para una perspectiva social se incluyeron costos directos utilizando la aproximación de Bottom-up y costos indirectos relacionados con la pérdida de productividad. Resultados: El costo directo de un paciente con DMAEn fue 5.974 USD$ desde una base teórica. A nivel nacional, la DMAEn costaría 179,9 millones USD$. Los costos indirectos de DMAEn se estimaron en 13,9 millones USD$. Los costos directos teóricos en EMD fueron 741,6 millones USD$. El costo nacional sería de 132,04 millones USD$. Para los costos indirectos de EMD, se estimó un costo de 93,3 millones USD$. Conclusiones: La DMAEn y el EMD tienen un alto impacto para el sistema de salud y la sociedad.

Background: The vision loss has consequences for both health and economic stability, since it promotes delays in emotional and social development, as well as reductions in labor productivity. Objective: To estimate the economic burden of age-related macular degeneration (AMD) and diabetic macular edema (DME) in Colombia for 2022. Method: For a social perspective, direct costs were included using the bottom-up approach, and indirect costs related to lost productivity. Results: The direct costs of treating a patient with AMD were USD $5,974 from a theoretical background. At national level, the AMD would cost USD $179.9 million. The AMD indirect cost in Colombia was estimated in USD $13.9 million. Patients theoretical direct cost of DME was USD $741.6 million. The cost at national level is USD $132.04 million. Regarding the indirect costs result for DME, a cost of USD $93.31 million was estimated. Conclusions: The AMD and the DME have a considerable impact on the health system and society.

Damage control surgery for thoracic outlet vascular injuries: the new resuscitative median sternotomy plus REBOA.

Thoracic vascular trauma is associated with high mortality and is the second most common cause of death in patients with trauma following head injuries. Less than 25% of patients with a thoracic vascular injury arrive alive to the hospital and more than 50% die within the first 24 hours. Thoracic trauma with the involvement of the great vessels is a surgical challenge due to the complex and restricted anatomy of these structures and its association with adjacent organ damage. This article aims to delineate the experience obtained in the surgical management of thoracic vascular injuries via the creation of a practical algorithm that includes basic principles of damage control surgery. We have been able to show that the early application of a resuscitative median sternotomy together with a zone 1 resuscitative endovascular balloon occlusion of the aorta (REBOA) in hemodynamically unstable patients with thoracic outlet vascular injuries improves survival by providing rapid stabilization of central aortic pressure and serving as a bridge to hemorrhage control. Damage control surgery principles should also be implemented when indicated, followed by definitive repair once the correction of the lethal diamond has been achieved. To this end, we have developed a six-step management algorithm that illustrates the surgical care of patients with thoracic outlet vascular injuries according to the American Association of the Surgery of Trauma (AAST) classification.

El trauma vascular torácico está asociado con una alta mortalidad y es la segunda causa más común de muerte en pacientes con trauma después del trauma craneoencefálico. Se estima que menos del 25% de los pacientes con una lesión vascular torácica alcanzan a llegar con vida para recibir atención hospitalaria y más del 50% fallecen en las primeras 24 horas. El trauma torácico penetrante con compromiso de los grandes vasos es un problema quirúrgico dado a su severidad y la asociación con lesiones a órganos adyacentes. El objetivo de este artículo es presentar la experiencia en el manejo quirúrgico de las lesiones del opérculo torácico con la creación de un algoritmo de manejo quirúrgico en seis pasos prácticos de seguir basados en la clasificación de la AAST. que incluye los principios básicos del control de daños. La esternotomía mediana de resucitación junto con la colocación de un balón de resucitación de oclusión aortica (Resuscitative Endovascular Balloon Occlusion of the Aorta - REBOA) en zona 1 permiten un control primario de la hemorragia y mejoran la sobrevida de los pacientes con trauma del opérculo torácico e inestabilidad hemodinámica.

Primary repair: damage control surgery in esophageal trauma.

Esophageal trauma is a rare but life-threatening event associated with high morbidity and mortality. An inadvertent esophageal perforation can rapidly contaminate the neck, mediastinum, pleural space, or abdominal cavity, resulting in sepsis or septic shock. Higher complications and mortality rates are commonly associated with adjacent organ injuries and/or delays in diagnosis or definitive management. This article aims to delineate the experience obtained by the Trauma and Emergency Surgery Group (CTE) of Cali, Colombia, on the surgical management of esophageal trauma following damage control principles. Esophageal injuries should always be suspected in thoracoabdominal or cervical trauma when the trajectory or mechanism suggests so. Hemodynamically stable patients should be radiologically evaluated before a surgical correction, ideally with computed tomography of the neck, chest, and abdomen. While hemodynamically unstable patients should be immediately transferred to the operating room for direct surgical control. A primary repair is the surgical management of choice in all esophageal injuries, along with endoscopic nasogastric tube placement and immediate postoperative care in the intensive care unit. We propose an easy-to-follow surgical management algorithm that sticks to the philosophy of "Less is Better" by avoiding esophagostomas.

El trauma esofágico es un evento poco frecuente pero potencialmente mortal. Una perforación esofágica inadvertida puede ocasionar la rápida contaminación del cuello, el mediastino, el espacio pleural o la cavidad abdominal, lo cual puede resultar en sepsis o choque séptico. Las complicaciones y la mortalidad aumentan con el retraso en el diagnóstico o manejo definitivo, y la presencia de lesiones asociadas. El objetivo del presente artículo es describir la experiencia adquirida por el grupo de cirugía de Trauma y Emergencias (CTE) de Cali, Colombia en el manejo del trauma de esófago de acuerdo con los principios de la cirugía de control de daños. Las lesiones esofágicas deben sospecharse en todo trauma toraco-abdominal o cervical en el que el mecanismo o la trayectoria de la lesión lo sugieran. El paciente hemodinámicamente estable se debe estudiar con imágenes diagnósticas antes de la corrección quirúrgica del defecto, idealmente por medio de tomografía computarizada del cuello, tórax y abdomen con contraste endovenoso. Mientras que en el paciente hemodinámicamente inestable se debe explorar y controlar la lesión. El reparo primario es el manejo quirúrgico de elección, con la previa colocación de una sonda nasogástrica y el seguimiento postoperatorio estricto en la unidad de cuidado intensivo. Se propone un algoritmo de manejo quirúrgico que resulta fácil de seguir y adopta la premisa "Menos es Mejor" evitando realizar derivaciones esofágicas.

Costoefectividad del régimen combinado de mirabegron/solifenacina en el tratamiento del síndrome de vejiga hiperactiva en Colombia / Cost-effectiveness of the Combined Regimen of Mirabegron/Solifenacin in the Treatment of Overactive Bladder Syndrome in Colombia

Objetivo Evaluar la costoefectividad incremental del régimen combinado de mirabegron/solifenacina en comparación con el uso temprano de toxina botulínica, desde la perspectiva del sistema de salud colombiano, para el tratamiento de adultos con vejiga hiperactiva. Métodos Se empleó un modelo de Markov en que se comparan dos secuencias de tratamiento, una con y otra sin mirabegron/solifenacina, para evaluar la costoefectividad en un horizonte temporal de cinco años. Debido a la perspectiva de análisis, sólo se tuvieron en cuenta los costos médicos directos. La eficacia del tratamiento evaluado y su comparador fue medida en términos de la reducción de episodios diarios de incontinencia y de la frecuencia de micciones. Los costos fueron expresados en pesos colombianos de 2019, y se aplicó una tasa de descuento de 5% tanto para desenlaces como para costos. Resultados Para el caso base, el costo del tratamiento en la secuencia que incluye mirabegron/solifenacina fue mayor, pero generó un mayor número de años de vida ajustados por calidad, y así e obtuvo una razón de costoefectividad incremental de $13.637,184 si se considera el desenlace de reducción de episodios diarios de incontinencia de 50%, y de $29.313,848 si se considera el del 100%. Conclusiones De acuerdo con los resultados de esta evaluación, para un horizonte de análisis de cinco años, la secuencia de tratamiento con mirabegron/solifenacina es una alternativa costoefectiva, si se considera un umbral de disposición a pagar de tres veces el producto interno bruto (PIB) per cápita.

Aim To evaluate the incremental cost-effectiveness of the combined regimen of mirabegron/solifenacin compared with the early use of botulinum toxin, from the perspective of the Colombian health system, for the treatment of adults with overactive bladder. Methods A Markov model comparing two treatment sequences, one with and one without mirabegron/solifenacin, was used to assess cost-effectiveness over a five-year period. Due to the perspective of the analysis, only direct medical costs were considered. The efficacy of the evaluated treatment and its comparator was measured in terms of the reduction in the daily incontinence episodes and the frequency of micturition. The costs were expressed in Colombian pesos of 2019, and a discount rate of 5% was applied for both outcomes and costs. Results For the base case, the cost of the treatment in the sequence that includes mirabegron/solifenacin was higher, but it generated a greater number of quality-adjusted years of life, thus obtaining an incremental cost-effectiveness ratio of $13,637,184 when considering the outcome of 50% of reduction in the daily incontinence episodes, and $29,313,848 when considering 100%. Conclusions According to the results of the present assessment, for a five-year period of analysi, the mirabegron/solifenacin treatment sequence is a cost-effective alternative when considering a threshold of willingness to pay three times the per capita gross domestic product (GDP).

Cost-Effectiveness of the Dabrafenib Schedule in Combination With Trametinib Compared With Other Targeted Therapies, Immunotherapy, and Dacarbazine for the Treatment of Unresectable or Metastatic Melanoma With BRAFV600 Mutation in Colombia.

OBJECTIVES: Advanced melanoma accounts for 4% of malignant skin tumors, and approximately 80% of deaths are attributed to it. The most frequent mutation of the RAF gene is BRAFV600, which has been associated with a worse prognosis. The objective of the research was to evaluate the cost-effectiveness of the combined regimen of dabrafenib plus trametinib (D + T) compared with other targeted therapies, immunotherapy, and dacarbazine for the treatment of unresectable/metastatic melanoma with BRAFV600 mutation from the perspective of the Colombian health system. METHODS: A partitioned survival model with 3 states (progression-free survival, progression, and death) was used to evaluate the cost-effectiveness for a time horizon of 20 years. Owing to the perspective of the analysis, only direct medical costs were taken into account. The efficacy of the evaluated treatment and the comparators were measured in terms of overall survival and progression-free survival. All costs were expressed in Colombian pesos as of 2018, and outcomes and costs were discounted at 5% annually. Two analysis scenarios were considered, one in which only monitoring and follow-up costs were included in the progression phase and another in which costs of acquisition of possible treatment sequences were also included. RESULTS: In the first scenario (without postprogression medication costs), the combined D + T regimen was a dominant alternative to vemurafenib + cobimetinib but was not a cost-effective option compared with vemurafenib, nivolumab, ipilimumab, nivolumab + ipilimumab, pembrolizumab, and dacarbazine. In the second scenario (with drug costs in postprogression), D + T was dominant compared with vemurafenib + cobimetinib and cost-effective compared with nivolumab and pembrolizumab. Compared with other schemes, the incremental cost-effectiveness ratio was above the threshold of 3 gross domestic product per capita. Probabilistic sensitivity analyses showed that a willingness-to-pay threshold of Col$56 484 300 (US$19 108) per quality-adjusted life-year would not be reached at the current price of schema in Colombia. CONCLUSIONS: The combined scheme could be a cost-effective and even a cost-saving alternative to vemurafenib + cobimetinib, nivolumab, and pembrolizumab if the costs associated with the use of other medications are taken into account after progression to the first line of treatment. Compared with the other comparators, it produces a greater number of quality-adjusted life-years, but the incremental cost-effectiveness ratio is above that of the willingness to pay.

Hemodynamically unstable non-compressible penetrating torso trauma: a practical surgical approach.

Penetrating torso trauma is the second leading cause of death following head injury. Traffic accidents, falls and overall blunt trauma are the most common mechanism of injuries in developed countries; whereas, penetrating trauma which includes gunshot and stabs wounds is more prevalent in developing countries due to ongoing violence and social unrest. Penetrating chest and abdominal trauma have high mortality rates at the scene of the incident when important structures such as the heart, great vessels, or liver are involved. Current controversies surround the optimal surgical approach of these cases including the use of an endovascular device such as the Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) and the timing of additional imaging aids. This article aims to shed light on this subject based on the experience earned during the past 30 years in trauma critical care management of the severely injured patient. We have found that prioritizing the fact that the patient is hemodynamically unstable and obtaining early open or endovascular occlusion of the aorta to gain ground on avoiding the development of the lethal diamond is of utmost importance. Damage control surgery starts with choosing the right surgery of the right cavity in the right patient. For this purpose, we present a practical and simple guide on how to perform the surgical approach to penetrating torso trauma in a hemodynamically unstable patient.

El trauma penetrante del torso representa la segunda causa de muerte de origen traumático después del trauma craneoencefálico. En países desarrollados existe mayor prevalencia de trauma cerrado, asociado principalmente a accidentes de tránsito o caídas de grandes alturas. Mientas, que en países en vía de desarrollo el trauma penetrante es más prevalente con heridas por arma de fuego o por arma blanca asociado a la violencia y las desigualdades sociales. El trauma penetrante torácico y abdominal pueden presentar altas tasas de mortalidad en la escena del trauma si se comprometen estructuras importantes como el corazón, los grandes vasos o el hígado. Actualmente, existen controversias sobre el adecuado abordaje quirúrgico con la implementación o no de dispositivos endovasculares como el balón de resucitación endovascular de oclusión aórtica (Resuscitative Endovascular Balloon Oclussion of the Aorta - REBOA) y la realización de ayudas imagenológicas. El objetivo de este artículo es presentar el conocimiento sobre este tema, basado en la experiencia adquirida durante los últimos 30 años con el manejo del trauma, cirugía general y cuidado crítico. Sostenemos que en un paciente hemodinámicamente inestable se debe realizar una temprana oclusión aórtica endovascular o abierta con el objetivo de evitar el desarrollo o propagación del rombo de la muerte. Con este propósito, presentamos una guía práctica y sencilla sobre el abordaje quirúrgico del paciente hemodinámicamente inestable con trauma penetrante del torso.

Damage control in penetrating cardiac trauma.

Definitive management of hemodynamically stable patients with penetrating cardiac injuries remains controversial between those who propose aggressive invasive care versus those who opt for a less invasive or non-operative approach. This controversy even extends to cases of hemodynamically unstable patients in which damage control surgery is thought to be useful and effective. The aim of this article is to delineate our experience in the surgical management of penetrating cardiac injuries via the creation of a clear and practical algorithm that includes basic principles of damage control surgery. We recommend that all patients with precordial penetrating injuries undergo trans-thoracic ultrasound screening as an integral component of their initial evaluation. In those patients who arrive hemodynamically stable but have a positive ultrasound, a pericardial window with lavage and drainage should follow. We want to emphasize the importance of the pericardial lavage and drainage in the surgical management algorithm of these patients. Before this concept, all positive pericardial windows ended up in an open chest exploration. With the coming of the pericardial lavage and drainage procedure, the reported literature and our experience have shown that 25% of positive pericardial windows do not benefit and/or require further invasive procedures. However, in hemodynamically unstable patients, damage control surgery may still be required to control ongoing bleeding. For this purpose, we propose a surgical management algorithm that includes all of these essential clinical aspects in the care of these patients.

El manejo definitivo de los pacientes hemodinámicamente estables con heridas cardíacas penetrantes continúa siendo controversial con abordajes invasivos versus manejos conservadores. Estas posiciones contrarias se extienden hasta aquellos casos de pacientes hemodinámicamente inestables donde se ha descrito y considerado la cirugía de control de daños como un procedimiento útil y efectivo. El objetivo de este artículo es presentar la experiencia en el manejo quirúrgico de heridas cardíacas penetrantes con la creación de un algoritmo práctico que incluye los principios básicos del control de daños. Se recomienda que a todos los pacientes con heridas precordiales penetrantes se les debe realizar un ultrasonido torácico como componente integral de la evaluación inicial. Aquellos que presenten un ultrasonido torácico positivo y se encuentren hemodinámicamente estables se les debe realizar una ventana pericárdica con posterior lavado. Se ha demostrado que el 25% de las ventanas pericárdicas positivas no se benefician ni requieren de posteriores abordajes quirúrgicos invasivos. Antes de este concepto, todos los pacientes con ventana pericárdica positiva terminaban en una exploración abierta del tórax y del pericárdico.Los pacientes hemodinámicamente inestables requieren de una cirugía de control de daños para un adecuado y oportuno control del sangrado. Con este propósito, se propone un algoritmo de manejo quirúrgico que incluye todos estos aspectos esenciales en el abordaje de este grupo de pacientes.

Damage control in penetrating duodenal trauma: less is better - the sequel.

The overall incidence of duodenal injuries in severely injured trauma patients is between 0.2 to 0.6% and the overall prevalence in those suffering from abdominal trauma is 3 to 5%. Approximately 80% of these cases are secondary to penetrating trauma, commonly associated with vascular and adjacent organ injuries. Therefore, defining the best surgical treatment algorithm remains controversial. Mild to moderate duodenal trauma is currently managed via primary repair and simple surgical techniques. However, severe injuries have required complex surgical techniques without significant favorable outcomes and a consequential increase in mortality rates. This article aims to delineate the experience in the surgical management of penetrating duodenal injuries via the creation of a practical and effective algorithm that includes basic principles of damage control surgery that sticks to the philosophy of "Less is Better". Surgical management of all penetrating duodenal trauma should always default when possible to primary repair. When confronted with a complex duodenal injury, hemodynamic instability, and/or significant associated injuries, the default should be damage control surgery. Definitive reconstructive surgery should be postponed until the patient has been adequately resuscitated and the diamond of death has been corrected.

El trauma de duodeno comúnmente se produce por un trauma penetrante que puede asociarse a lesiones vasculares y de órganos adyacentes. En el manejo quirúrgico se recomienda realizar un reparo primario o el empleo de técnicas quirúrgicas simples. Sin embargo, el abordaje de lesiones severas del duodeno es un tema controversial. Anteriormente, se han descrito técnicas como la exclusión pilórica o la pancreatoduodenectomía con resultados no concluyentes. El presente artículo presenta una propuesta del manejo de control de daños del trauma penetrante de duodeno, a través, de un algoritmo de cinco pasos. Este algoritmo plantea una solución para el cirujano cuando no es posible realizar el reparo primario. El control de daños del duodeno y su reconstrucción depende de una toma de decisiones respecto a la porción del duodeno lesionada y el compromiso sobre el complejo pancreatoduodenal. Se recomiendan medidas rápidas para contener el daño y se proponen vías de reconstrucción duodenal diferente a las clásicamente descritas. Igualmente, la probabilidad de complicaciones como fistula duodenales es considerable, por lo que proponemos, que el manejo de este tipo de fistulas de alto gasto se aborde por medio de una laparostomía retroperitoneal (lumbotomía). El abordaje del trauma penetrante de duodeno se puede realizar a través del principio "menos es mejor".

Damage control surgical management of combined small and large bowel injuries in penetrating trauma: Are ostomies still pertinent?

Hollow viscus injuries represent a significant portion of overall lesions sustained during penetrating trauma. Currently, isolated small or large bowel injuries are commonly managed via primary anastomosis in patients undergoing definitive laparotomy or deferred anastomosis in patients requiring damage control surgery. The traditional surgical dogma of ostomy has proven to be unnecessary and, in many instances, actually increases morbidity. The aim of this article is to delineate the experience obtained in the management of combined hollow viscus injuries of patients suffering from penetrating trauma. We sought out to determine if primary and/or deferred bowel injury repair via anastomosis is the preferred surgical course in patients suffering from combined small and large bowel penetrating injuries. Our experience shows that more than 90% of all combined penetrating bowel injuries can be managed via primary or deferred anastomosis, even in the most severe cases requiring the application of damage control principles. Applying this strategy, the overall need for an ostomy (primary or deferred) could be reduced to less than 10%.

El trauma de las vísceras huecas representa una gran proporción de las lesiones asociadas al trauma penetrante. Actualmente, las lesiones aisladas de intestino delgado o colon se manejan a través de anastomosis primaria en pacientes sometidos a laparotomía definitiva o anastomosis diferida en pacientes que requieran cirugía de control de daños. El dogma quirúrgico tradicional de la ostomía se ha probado que es innecesario y en muchos casos puede aumentar la morbilidad. El objetivo de este artículo es describir la experiencia obtenida en el manejo de lesiones combinadas de vísceras huecas de pacientes con trauma penetrante. Se determinó que el manejo primario o diferido del intestino a través de anastomosis es el abordaje quirúrgico preferido en pacientes que presentan lesiones penetrantes combinadas de intestino delgado y colon. Se ha reportado que el 90% de lesiones combinadas penetrantes intestinales pueden ser manejadas a través de anastomosis primaria o diferida incluso en los casos más severos requieren la aplicación de los principios de control de daños. Aplicando esta estrategia, la tasa general para ostomía (primaria o diferida) puede ser reducida a menos del 10%.

Damage control in penetrating duodenal trauma: less is better - the sequel / El control de daños en trauma penetrante de duodeno: "Menos es Mejor

Abstract The overall incidence of duodenal injuries in severely injured trauma patients is between 0.2 to 0.6% and the overall prevalence in those suffering from abdominal trauma is 3 to 5%. Approximately 80% of these cases are secondary to penetrating trauma, commonly associated with vascular and adjacent organ injuries. Therefore, defining the best surgical treatment algorithm remains controversial. Mild to moderate duodenal trauma is currently managed via primary repair and simple surgical techniques. However, severe injuries have required complex surgical techniques without significant favorable outcomes and a consequential increase in mortality rates. This article aims to delineate the experience in the surgical management of penetrating duodenal injuries via the creation of a practical and effective algorithm that includes basic principles of damage control surgery that sticks to the philosophy of "Less is Better". Surgical management of all penetrating duodenal trauma should always default when possible to primary repair. When confronted with a complex duodenal injury, hemodynamic instability, and/or significant associated injuries, the default should be damage control surgery. Definitive reconstructive surgery should be postponed until the patient has been adequately resuscitated and the diamond of death has been corrected.

Resumen El trauma de duodeno comúnmente se produce por un trauma penetrante que puede asociarse a lesiones vasculares y de órganos adyacentes. En el manejo quirúrgico se recomienda realizar un reparo primario o el empleo de técnicas quirúrgicas simples. Sin embargo, el abordaje de lesiones severas del duodeno es un tema controversial. Anteriormente, se han descrito técnicas como la exclusión pilórica o la pancreatoduodenectomía con resultados no concluyentes. El presente artículo presenta una propuesta del manejo de control de daños del trauma penetrante de duodeno, a través, de un algoritmo de cinco pasos. Este algoritmo plantea una solución para el cirujano cuando no es posible realizar el reparo primario. El control de daños del duodeno y su reconstrucción depende de una toma de decisiones respecto a la porción del duodeno lesionada y el compromiso sobre el complejo pancreatoduodenal. Se recomiendan medidas rápidas para contener el daño y se proponen vías de reconstrucción duodenal diferente a las clásicamente descritas. Igualmente, la probabilidad de complicaciones como fistula duodenales es considerable, por lo que proponemos, que el manejo de este tipo de fistulas de alto gasto se aborde por medio de una laparostomía retroperitoneal (lumbotomía). El abordaje del trauma penetrante de duodeno se puede realizar a través del principio "menos es mejor".