Cost-Effectiveness of Pembrolizumab as an Adjuvant Treatment in Colombia for Melanoma Patients with Lymph Node Involvement After Complete Resection.

INTRODUCTION: The KEYNOTE-054 trial found that adjuvant treatment with pembrolizumab improved recurrence-free survival versus placebo in completely resected high-risk stage III melanoma patients. We assessed the cost-effectiveness of adjuvant pembrolizumab in Colombia compared with watchful waiting, a widely used strategy despite the high risk of recurrence with surgery alone. METHODS: A four-health state [recurrence-free (RF), locoregional recurrence (LR), distant metastases (DM), and death) Markov model was developed to assess the lifetime medical costs and outcomes (3% annual discount), along with cost-effectiveness ratios (ICERs). The transitions from the RF and LR states were modeled using KEYNOTE-054 data, and those from the DM state were modeled using data from the KEYNOTE-006 trial and a network meta-analysis of advanced treatments received after adjuvant pembrolizumab and watchful waiting. The health state utilities were derived from KEYNOTE-054 Euro-QoL data and literature. Costs are expressed in 2021 Colombian pesos (COP). RESULTS: Over a 46-year time horizon, patients on adjuvant pembrolizumab and watchful waiting were estimated to gain 9.69 and 7.56 quality-adjusted life-years (QALYs), 10.83 and 8.65 life-years (LYs), and incur costs of COP 663,595,726 and COP 563,237,206, respectively. The proportion of LYs spent in RF state was 84.63% for pembrolizumab and 72.13% for watchful waiting, yielding lower subsequent treatment, disease management, and terminal care costs for pembrolizumab. Adjuvant pembrolizumab improved survival by 2.18 LYs and 2.13 QALYs versus watchful waiting. The ICER per QALY was COP 47,081,917, primarily driven by recurrence rates and advanced melanoma treatments. The deterministic sensitivity analysis results were robust and consistent across various reasonable inputs and alternative scenarios. At a willingness-to-pay threshold of COP 69,150,201 per QALY, the probability of pembrolizumab being cost-effective was 65.70%. CONCLUSION: Pembrolizumab is cost-effective as an adjuvant treatment compared to watchful waiting among patients with high-risk stage III melanoma after complete resection in Colombia.

Cost-Effectiveness of Pembrolizumab Regimens for the First-Line Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma in Argentina.

INTRODUCTION: The phase III KEYNOTE-048 trial showed that the programmed death receptor 1 (PD-1) inhibitor pembrolizumab, in the combined positive score (CPS) ≥ 1 population and combined with platinum + 5-fluorouracil in the total population, improves survival over cetuximab + platinum + 5-fluorouracil in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). We evaluated the cost-effectiveness of pembrolizumab as monotherapy in the CPS ≥ 1 population or combined with platinum + 5-fluorouracil in the total population versus cetuximab + platinum + 5-fluorouracil from the social security perspective in Argentina. METHODS: A partitioned survival model projected costs and outcomes over 20 years with 3% annual discounting. Health state occupancy was modeled using KEYNOTE-048 Kaplan-Meier curves until the final analysis data cutoff, followed by parametric extrapolations guided by statistical criteria. Costs for initial and subsequent treatments, disease and adverse events management, and terminal care were included (AR $74.00 = 1 USD). Time-on-treatment and EuroQol five-dimension scores were taken from KEYNOTE-048. Utilities were derived using an Argentina-specific algorithm. RESULTS: With pembrolizumab monotherapy, patients accrued 1.1040 additional life-years and 0.8768 additional quality-adjusted life-years (QALYs), for incremental cost-effectiveness ratios (ICERs) of AR $135,801/life-year and AR $170,985/QALY gained over cetuximab + platinum + 5-fluorouracil. Additional life-years and QALYs gained with pembrolizumab combination therapy versus cetuximab + platinum + 5-fluorouracil were 1.3296 and 1.0536, respectively (ICERs of AR $680,143/life-year and AR $858,306/QALY). Considering a threshold of AR $1,676,122/QALY gained, pembrolizumab monotherapy and combination therapy had an 88.0% and a 77.1% probability of being cost-effective, respectively. CONCLUSION: Pembrolizumab either as monotherapy or in combination with chemotherapy offers substantial survival gains for patients with R/M HNSCC at small additional costs, making it a cost-effective treatment versus cetuximab + platinum + 5-FU in Argentina.

Cost-Effectiveness of Pembrolizumab for the Adjuvant Treatment of Melanoma Patients with Lymph Node Involvement Who Have Undergone Complete Resection in Argentina.

INTRODUCTION: The KEYNOTE-054 trial demonstrated that adjuvant pembrolizumab improves recurrence-free survival in completely resected stage III melanoma versus watchful waiting (hazard ratio [HR] = 0.57; 98.4% confidence interval [CI], 0.43-0.74). We evaluated the cost-effectiveness of pembrolizumab in Argentina, where watchful waiting is still widely used among these patients despite the high risk of recurrence with surgery alone. METHODS: A four-health state model was used (recurrence-free, locoregional recurrence [LR], distant metastases [DM], death). Lifetime medical costs to payers (72.08 Argentine pesos [AR$] = 1.00 U.S. dollar [USD]) and outcomes (3% annual discount) were assessed, together with incremental cost-effectiveness ratios (ICERs). First and LR→DM recurrences were modeled using KEYNOTE-054 and real-world data, respectively. No benefits of adjuvant treatment were assumed post-progression. Pre-DM and post-DM mortality was based on KEYNOTE-054 and on a network meta-analysis of advanced treatments expected in each arm, respectively. Utilities were derived from KEYNOTE-054 Euro-QoL data using an Argentinian algorithm, and from the literature. Public ex-factory drug prices were used. RESULTS: Patients in the pembrolizumab and the watchful waiting arms accrued 8.78 and 5.83 quality-adjusted life-years (QALYs), 9.91 and 6.98 life-years, and costs of AR$12,698,595 (176,174 USD) and AR$11,967,717 (166,034 USD), respectively. The proportion of life-years accrued that were recurrence-free was 80.8% and 56.9% in the pembrolizumab and the watchful waiting arms, respectively. Pembrolizumab patients gained 2.94 life-years and 2.96 QALYs versus watchful waiting; the ICER per QALY was AR$247,094 (3428 USD). Recurrence rates and advanced melanoma treatments were the key drivers of the ICER. At a threshold of AR$1,445,325 (29,935 USD) per QALY, pembrolizumab had an 83.5% probability of being cost-effective versus watchful waiting. CONCLUSIONS: Adjuvant pembrolizumab after complete resection of melanoma with node involvement is highly cost-effective relative to watchful waiting in Argentina, across disease stage subgroups and BRAF mutational status. This strongly supports its coverage and reimbursement across the entire health system.

The Value of Diagnostic Information in Personalised Healthcare: A Comprehensive Concept to Facilitate Bringing This Technology into Healthcare Systems.

Health systems around the world seek to address patients' unmet health needs for a range of acute and chronic diseases. Simultaneously, governments strive to keep healthcare spending sustainable, while providing equal access to high-quality care. This has fuelled debate around what constitutes a valuable healthcare intervention in a health system and the corollary consideration of what governments are willing to pay for a certain health intervention. Until recently, the value of information in general, and the value of diagnostic information (VODI) specifically, was not part of the discussion.However, investment in diagnostic information can be a key development as information may guide more effective and efficient healthcare and help maintain an affordable health system. This paper therefore explores ways to best define, evaluate, and reward the value created from diagnostics in healthcare and how to include these value considerations in decision-making processes for diagnostics. The authors ultimately call for a holistic VODI framework that accounts for the full range of potential benefits of diagnostic testing, beyond the traditional clinical and health economic domains, and that is essential to recognise, measure, and fully leverage the benefits of diagnostics for patients, health systems, and society.

The Value of Companion Diagnostics: Overcoming Access Barriers to Transform Personalised Health Care into an Affordable Reality in Europe.

Personalised health care is an evolution, moving away from a disease-focused model of care, translating scientific and technological advances into benefits for patients, and placing them at the centre of the patients' health and care. Companion diagnostics emerge as a very specific and special group of in vitro diagnostics among the different technologies shaping the personalised health care spectrum. Companion diagnostics provide highly valuable information, allowing patients, health practitioners and payers to decide with a higher level of certainty on the potential benefits of a treatment or care pathway. Decreasing uncertainty may result in a more efficient selection of treatments and care, targeted at subpopulations that are most likely to benefit. Companion diagnostics account for a minimal portion of the already small expenditure on in vitro diagnostics (far less than 1% of total health care expenditure), and yet they provide the means to limit inefficient use of health care resources while optimising patient outcomes. It is clear that equal access to personalised health care is still an issue across the EU. One of the most common perceived barriers is affordability. The investment in companion diagnostics can provide long-term value for patients and health care systems, shifting resources to areas of need. Health systems do not fully recognise yet the value that companion diagnostics bring to make personalised health care more affordable across the EU. This inhibits patient access to personalised treatments and care, preventing improved outcomes. In many countries, market access frameworks for diagnostic tests are fragmented and not aligned with specific funding and reimbursement mechanisms, discouraging the use of these tests. Emerging evidence shows that patients are missing out on the appropriate tests and treatments while a reduction in the inefficient use of health care resources is not realised. This article outlines some of these market access barriers for companion diagnostics in the EU, including reimbursement challenges specific to some member states (Germany, the UK, and France). Furthermore, proposals addressing barriers and increasing timely patient access to companion diagnostics in the EU are presented.

El tratamiento antibiótico dos veces por día es tan eficaz como la dosificación más frecuente en la faringitis aguda estreptocóccica / Antibiotic treatment twice a day is as effective as more frequent dosing in acute streptococcal pharyngitis

A partir de la descripción de un caso clínico sobre la necesidad de administrar un tratamiento antibiótico a una niña con faringitis aguda estreptocóccica, se plantea la posible diferencia de eficacia entre dosis administradas cada seis u ocho horas, comparadas con la administración cada 12 o 24 horas. Se concluye que la indicación de penicilina o amoxicilina oral cada doce horas tiene eficacia similar a la indicación cada seis u ocho, para producir la resolución clínica y bacteriológica de la faringitis estreptocóccica en niños, con las ventajas de una mayor probabilidad de adherencia al tratamiento en la población infantil. No se evidenció el mismo efecto en el caso de la dosis única de penicilina, que disminuye su eficacia, sin embargo la amoxicilina así podría indicarse en una dosis única diaria.

El tratamiento antibiótico dos veces por día es tan eficaz como la dosificación más frecuente en la faringitis aguda estreptocóccica / Antibiotic treatment twice a day is as effective as more frequent dosing in acute streptococcal pharyngitis

A partir de la descripción de un caso clínico sobre la necesidad de administrar un tratamiento antibiótico a una niña con faringitis aguda estreptocóccica, se plantea la posible diferencia de eficacia entre dosis administradas cada seis u ocho horas, comparadas con la administración cada 12 o 24 horas. Se concluye que la indicación de penicilina o amoxicilina oral cada doce horas tiene eficacia similar a la indicación cada seis u ocho, para producir la resolución clínica y bacteriológica de la faringitis estreptocóccica en niños, con las ventajas de una mayor probabilidad de adherencia al tratamiento en la población infantil. No se evidenció el mismo efecto en el caso de la dosis única de penicilina, que disminuye su eficacia, sin embargo la amoxicilina así podría indicarse en una dosis única diaria.(AU)

Rol de la glucosamina en el tratamiento de la osteoartritis / Role of glucosamine in the treatment of osteoarthritis

La osteoartritis es una enfermedad degenerativa del cartílago que produce disminución del espacio articular y cambios en el hueso subyacente. Se postula que la administración de glucosamina exógena estimularía la síntesis de matriz cartilaginosa y protegería el hueso. A pesar de esto, no hay evidencia sólida para sostener el uso de glucosamina en la osteoartritis leve.

Rol de la glucosamina en el tratamiento de la osteoartritis / Role of glucosamine in the treatment of osteoarthritis

La osteoartritis es una enfermedad degenerativa del cartílago que produce disminución del espacio articular y cambios en el hueso subyacente. Se postula que la administración de glucosamina exógena estimularía la síntesis de matriz cartilaginosa y protegería el hueso. A pesar de esto, no hay evidencia sólida para sostener el uso de glucosamina en la osteoartritis leve.(AU)

Evaluación de tecnología sanitaria: informe de respuesta rápida colecistectomía laparoscópica ambulatoria / Health technology assessment: rapid response report laparoscopic laparoscopic cholecystectomy

El objetivo de esta revisión consiste en determinar la seguridad de la colecistectomía laparoscópica ambulatoria comparada con la de corta estancia (o estadía noctura), así como su efectividad. La evidencia encontrada indica que la colecistectomía laparoscópica ambulatoria es una práctica segura y efectiva siempre y cuando se realice en pacientes seleccionados. Esta selección se basa en su estado de salud previo a la cirugía y su capacidad de soportar el stress impuesto por la misma, su proximidad al centro hospitalario, su capacidad de comprender los signos de alarma relacionados a posibles complicaciones post-quirúrgicas, la presencia de un adulto responsable que pueda acompañar al paciente al menos 24 horas luego de la cirugía, y, de acuerdo a nuestro medio, que el ambiente al que retorne el paciente que es operado en forma ambulatoria cuente con los requerimientos mínimos de seguridad. Además, el sistema de salud debe estar preparado para el manejo de las eventuales re-internaciones de estos pacientes. Otro requisito es la idoneidad del equipo quirúrgico, que debe tener experiencia en cirugía laparoscópica biliar. Los pacientes que fueron excluídos y a los que no podría extrapolarse esta evidencia son los que habían tenido una cirugía abdominal superior previa, los que tienen sospecha de litiasis coledociana y los que presentan colecistitis aguda. La evidencia encontrada indica que la colecistectomía laparoscópica ambulatoria es una práctica segura y efectiva siempre y cuando se realice en pacientes con litiasis biliar no complicada, seleccionados en base a su estado de salud previo (ASA I y II), accesibilidad al hospital, nivel de comprensión de los signos de alarma postquirúrgicos, acceso a un adulto acompañante responsable luego de la cirugía, ambiente domiciliario adecuado para el retorno del paciente y sistema de salud preparado con protocolos orales de analgesia y antiemesis, además de un sistema de manejo de las eventuales reinternaciones y un equipo quirúrgico con adecuada capacitación en cirugía laparoscópica biliar.

Evaluación de Tecnología Sanitaria: límite máximo recomendable de cafeína contenida en las bebidas energizantes / Health Technology Assessment: recommended maximum limit of caffeine contained in energy drinks

Objetivo: Conocer la evidencia científica y las recomendaciones de organismos expertos en el tema sobre el límite máximo recomendable de cafeína en las bebidas energizantes. Metodología: Se realizó una búsqueda en las bases de datos bibliográficas (Medline, Cochrane, Tripdatabase, LILACS), en buscadores genéricos de Internet como Google, agencias de evaluación de tecnologías sanitarias y agencias nacionales e internacionales reguladoras de alimentos y medicamentos. Conclusiones: La evidencia encontrada en estudios primarios sobre la seguridad de la cafeína contenida en las bebidas energizantes ha sido de baja calidad, con eventos adversos surgidos principalmente de reportes aislados de casos u opiniones de expertos, por lo que no es posible recomendar con precisión un límite de seguridad para el contenido de cafeína en estas bebidas. Los límites recomendados por las diferentes agencias reguladoras varían entre 32­35 mg/100 mL, aunque algunas requieren el rotulado de "alto contendido de cafeína" cuando éste supera los 15­ 18mg/100 mL. Otras agencias fijan además un límite mínimo de cafeína (25 mg/100mL) para considerarse bebida energizante. La mayoría de las recomendaciones derivadas de las agencias reguladoras también se basa en evidencia de baja calidad. Los datos encontrados sugieren una interacción entre la cafeína y el alcohol, que podría depender de la dosis, en relación a una menor percepción de la intoxicación alcohólica por los tomadores de bebidas energizantes, con un patrón de co­consumo entre los jóvenes, tanto en estudios locales como internacionales. No se ha encontrado suficiente evidencia para recomendar un límite máximo de cafeína en las bebidas energizantes

Lista de cotejo para el control de salud de niños en edad escolar / Check-list for health control in primary school children

Se presenta una sencilla y corta lista de cotejo basada en la evidencia para facilitar el control de salud de los niños en edad escolar y que incluye maniobras de rastreo, consejería e inmunizaciones.

Lista de cotejo para el control de salud de niños en edad preescolar / Check-list for health control in preschool children

Se presenta una sencilla y corta lista de cotejo basada en la evidencia para facilitar el control de salud de los niños enedad escolar y que incluye maniobras de rastreo, consejería e inmunizaciones. La lista puede ser reproducida citandola fuente.

Calambres nocturnos en embarazadas / Nocturnal leg cramps in pregnant women

Se evalúa la evidencia acerca de los posibles tratamientos para los calambres en embarazadas de más de 20 semanas de edad gestacional. La mejor evidencia de eficacia disponible se relaciona a la suplementación de magnesio, ya sea en forma de lactato o citrato, a una dosis de 5 mmoles a la mañana y 10 mmoles a la tarde. La evidencia sobre la suplementación de calcio, cloruro de sodio y multivitamínicos es débil por lo que no son recomendables. Los expertos recomiendan ejercicios y masajes en las piernas, aunque carecemos de evidencia para demostrar su eficacia.