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ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?
RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?
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Introducción La diabetes mellitus tipo 2 es una enfermedad de alta prevalencia y está asociada a mayor morbimortalidad. Debido al bajo porcentaje de compensación, se han buscado nuevas estrategias de tratamiento farmacológico, como los inhibidores del cotransportador sodio-glucosa tipo 2. Objetivo Describir la evolución de pacientes diabéticos tipo 2 insulino-requirentes tratados con empagliflozina en el Hospital Peñaflor, ubicado en el sector poniente de la Región Metropolitana, Chile. El objetivo primario fue evaluar la eficacia del medicamento respecto a hemoglobina glicosilada A1c. Los objetivos secundarios fueron registrar el logro de hemoglobina glicosilada A1c igual o menor a 7,5% según análisis de supervivencia. Luego, consignar el cambio en la velocidad de filtración glomerular y en la excreción urinaria de albúmina post tratamiento. Métodos Revisión de ficha clínica de todos los pacientes tratados con empagliflozina desde noviembre de 2019 a junio de 2023. Media de seguimiento de 19 (de 16,3 a 40) meses. Para comparación entre valores de hemoglobina glicosilada A1c según rangos de seguimiento, se utilizó prueba T de Student de términos pareados o prueba de Wilcoxon. Resultados Se estudió a 58 pacientes, 15 hombres y 43 mujeres (74,1%). Edad 58,5 ± 9,2 años, rango de 35 a 75 años. Hemoglobina glicosilada A1c basal de 10,3 ± 1,6% y 8,98% ± 2,2 en un rango de seguimiento de 18 a 24 meses post tratamiento, resultando en un descenso de 1,27% (p = 0,002; intervalo de confianza 95%: 0,5 a 2,03). El efecto adverso más frecuente fue infección del tracto urinario. Conclusiones Los pacientes diabéticos tipo 2 insulino-requirentes tratados con empagliflozina en el Hospital Peñaflor lograron un mejor control glicémico con pocos efectos adversos.
Background Type 2 diabetes mellitus is a highly prevalent disease and is associated with increased morbidity and mortality. Due to the low percentage of adequate glycemic control, new strategies for the treatment of type 2 diabetes mellitus have been sought, including sodium-glucose cotransporter type 2 inhibitorss. Objective To describe the evolution of patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital. The primary objective was to evaluate the efficacy of the medication regarding glycosylated hemoglobin A1c (HbA1c). The secondary objectives were: 1) achievement of HbA1c equal to or less than 7.5% according to survival analysis. 2) Change in glomerular filtration rate and urinary albumin excretion post treatment. Methods Review of clinical records of all patients treated with empagliflozin from November 2019 to June 2023. Average follow-up of 19 (16.3 to 40) months. To compare HbA1c values according to follow-up ranges, the paired T test or Wilcoxon test was used. Results We included 58 patients, 15 men and 43 women (74.1%), with an average age of 58.5 ± 9.2 years, ranging from 35 to 75 years. Baseline HbA1c of 10.3 ± 1.6% and 8.98% ± 2.2 in a follow-up of 18 to 24 months post-treatment, resulted in a decrease of 1.27% (p = 0.002; confidence interval 95%: 0.5 to 2.03). The most common adverse effect was urinary tract infection. Conclusions Patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital achieved better glycemic control with few adverse effects.
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OBJECTIVE To systematically review the pharmacoeconomic evaluation literature about proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors for the prevention of cardiovascular disease in patients with hypercholesterolemia， and to provide a reference for clinical treatment， health decision-making and future follow-up research. METHODS Retrieved from English and Chinese databases such as PubMed and CNKI， the pharmacoeconomic literature about PCSK9 inhibitors （evolocumab and alirocumab） for the prevention of cardiovascular disease in patients with hypercholesterolemia was collected from the establishment of the database to October 8， 2023. The quality of the included literature was assessed with Consolidated Health Economic Evaluation Reporting Standards 2022 （CHEERS 2022） scale. The descriptive analysis was performed for basic information， model structure， related parameters， sensitivity analysis and the results of included studies. RESULTS & CONCLUSIONS A total of 29 literature were included， with overall good quality. The evaluation mainly adopted the Markov model from the healthcare system， payer and societal perspective. The effectiveness and utility data mainly came from the previous studies； the direct cost was mainly considered with a discount rate of 1.5%-5.0% per year， while the willingness-to-pay threshold was often set at 1-3 times the gross domestic product per capita. Most health output indicators were measured in life years and quality-adjusted life years. The sensitivity analysis of most studies demonstrated the robustness and the main influential factor was the drug cost. Most Chinese studies showed that PCSK9 inhibitor was not cost-effective for the prevention of cardiovascular disease in patients with acute coronary syndrome， myocardial infarction and atherosclerotic cardiovascular disease. It was cost-effective to use PCSK9 inhibitors for the prevention of cardiovascular disease only in specific groups， such as patients with triple vessel disease， patients with newly diagnosed acute coronary syndrome and low-density lipoprotein cholesterol≥100 mg/dL. Future research should refer to the CHEERS 2022 scale to improve the design， and strive to select large-scale， high-quality data to enhance the quality of reports and the transparency of health decisions， so as to more accurately assess the cost-effectiveness of PCSK9 inhibitors.
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The FMS-like tyrosine kinase 3 (FLT3) gene mutation is the most common genetic mutation in acute myeloid leukemia (AML) and is associated with poor prognosis. Various targeted inhibitors have been developed for FLT3 mutations and have shown promising clinical efficacy. However, the emergence of resistance poses new challenges for targeted therapy in AML. This article provides an overview of the pathological and prognostic role of FLT3 mutations in AML, the current research progress on commonly used FLT3 inhibitors (type I and type II), the mechanisms of FLT3 inhibitor resistance, and strategies for overcoming resistance.
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Receptor-interacting serine/threonine-protein kinase 3(RIPK3),a member of the RIP kinase family,plays an important role in cell death,especially in necroptosis. In addition,RIPK3 is also involved in apoptosis and pyroptosis,suggesting that RIPK3 may be the intersection of multiple cell death and it possesses the potential to be a target for precise regulation of cell death. According to the kinase binding mode,current RIPK3 inhibitors can be classified into type ,type Ⅱ and other types. This review summarizes the research progress in the role of RIPK3 in cell death and its inhibitors,which is of great significance in seeking drugs for the treatment of injury-related diseases.
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ObjectiveTo investigate whether anti-PD-1 monoclonal antibody can improve the efficacy and safety of cryoablation combined with lenvatinib in the treatment of unresectable hepatocellular carcinoma （HCC）. MethodsA retrospective analysis was performed for 232 patients with unresectable HCC who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2018 to December 2022， among whom 128 received cryoablation combined with lenvatinib （double combination） and 104 received cryoablation combined with lenvatinib and anti-PD-1 monoclonal antibody （triple combination）. Propensity score matching was performed at a ratio of 1∶1， and finally there were 86 patients in each group. The two groups were evaluated in terms of objective response rate （ORR）， disease control rate （DCR）， overall survival （OS）， progression-free survival （PFS）， and adverse events （AEs）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Survival curves were plotted， and the Kaplan-Meier method was used to calculate the survival rate of patients in both groups， while the log-rank test was used for comparison between the two groups. The Cox regression model was used to calculate hazard ratio （HR） and 95% confidence interval （CI） and perform the univariate and multivariate analyses of influencing factors for prognosis. ResultsThe median follow-up time was 28 months， and there were 33 deaths （38.0%） in the triple combination group and 40 deaths （46.0%） in the double combination group. Compared with the double combination group， the triple combination group had significantly higher ORR （35.6% vs 14.5%， P=0.008） and DCR （86.1% vs 64.1%， P=0.003）. OS and PFS in the triple combination group were significantly higher than those in the double combination group （P=0.045 and 0.026）. The univariate and multivariate Cox proportional-hazards regression model analyses showed that treatment regimen （HR=0.60， P=0.038） and alpha-fetoprotein level （HR=2.37， P=0.001） were independent risk factors for OS， and treatment regimen （HR=0.65， P=0.025）， diabetes mellitus （HR=1.94， P=0.005）， whether or not to have received local treatment （HR=0.63， P=0.014）， and distant metastasis （HR=0.58， P=0.009） were independent risk factors for PFS. There was no significant difference in the incidence rate of AEs between the two groups （P>0.05）. ConclusionFor patients with unresectable HCC， the triple combination of cryoablation， lenvatinib， and anti-PD-1 monoclonal antibody significantly improves the treatment outcome and survival of patients compared with the double combination of cryoablation and lenvatinib， without increasing AEs， which provides a clinical basis for optimizing the treatment regimen for unresectable HCC.
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Neurotrophic receptor kinase (NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors, and tropomyosin receptor kinase (TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these fusions. Currently, two generations TRK inhibitors have been developed. The representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target mutations. However, xDFG (TRKAG667C/A/S, homologous TRKCG696C/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib, and overcoming these resistances represents a major unmet clinical need. In this review, we summarize the acquired resistance mechanism of the first- and second-generation TRK inhibitors, and firstly put forward the emerging selective type II TRK inhibitors to overcome xDFG mutations mediated resistance. Additionally, we concluded our perspectives on new challenges and future directions in this field.
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Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.
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ABSTRACT Purpose: To evaluate early changes after the first antivascular endothelial growth factor injection for macular edema secondary to diabetic retinopathy and retinal vein occlusion and the relationship between longterm outcomes. Methods: The study enrolled patients who received anti-vascular endothelial growth factor injections for treatment-naive macular edema due to retinal vein occlusion and diabetic retinopathy. The central macular thickness was measured at baseline, post-injection day 1, week 2, and month 1, and at the last visit using spectral-domain optical coherence tomography. A good response was defined as a central macular thickness reduction of ≥10% on post-injection day 1. Patients were reassessed at the last visit with regard to treatment response on post-injection day 1 based on the favorable anatomic outcome defined as a central macular thickness <350 µm. Results: In total, 26 (44.8%) patients had macular edema-retinal vein occlusion and 32 (55.2%) had macular edema-diabetic retinopathy. The mean follow-up time was 24.0 (SD 8.5) months. A statistically significant decrease in the central macular thickness was observed in both patients with macular edema-retinal vein occlusion and macular edema-diabetic retinopathy after antivascular endothelial growth factor injection therapy (p<0.001 for both). All patients with macular edema-retinal vein occlusion were good responders at post-injection day 1. All nongood responders at post-injection day 1 belong to the macular edema-diabetic retinopathy group (n=16.50%). The rate of hyperreflective spots was higher in nongood responders than in good responders of the macular edema-diabetic retinopathy group (p=0.03). Of 42 (2.4%) total good responders, one had a central macular thickness >350 µm, whereas 5 (31.2%) of 16 total nongood responders had a central macular thickness >350 µm at the last visit (p=0.003). Conclusion: The longterm anatomical outcomes of macular edema secondary to retinal vein occlusion and diabetic retinopathy may be predicted by treatment response 1 day after antivascular endothelial growth factor injection.
RESUMO Objetivo: Avaliar as alterações precoces após a primeira injeção de anticorpos antifator de crescimento endotelial vascular (anti-VEGF) em casos de edema macular secundário à retinopatia diabética e oclusão da veia da retina e a relação entre essas alterações e o resultado a longo prazo. Métodos: Foram incluídos no estudo pacientes que receberam uma injeção de antifator de crescimento endotelial vascular para edema macular, virgem de tratamento e devido à oclusão da veia retiniana ou a retinopatia diabética. A espessura macular central foi medida no início do tratamento e no 1º dia, 2ª semana e 1º mês após a injeção, bem como na última visita, através de tomografia de coerência óptica de domínio espectral. Definiu-se uma "boa resposta" como uma redução ≥10% na espessura macular central no 1º dia após a injeção. Os pacientes foram reavaliados na última visita com relação à resposta ao tratamento no 1º dia após a injeção, com base em um resultado anatômico favorável, definido como uma espessura macular central <350 µm. Resultado: Foram registrados 26 (44,8%) pacientes com edema macular e oclusão da veia da retina e 32 (55,2%) com edema macular e retinopatia diabética. O tempo médio de acompanhamento foi de 24,0 meses (desvio-padrão de 8,5 meses). Foi observada uma diminuição estatisticamente significativa da espessura macular central após o tratamento antifator de crescimento endotelial vascular tanto em pacientes com edema macular e oclusão da veia retiniana quanto naqueles com edema macular e retinopatia diabética (p<0,001 para ambos). Todos os pacientes com edema macular e oclusão da veia retiniana responderam bem no 1º dia pós-injeção. Todos os que responderam mal no 1º dia pós-injeção pertenciam ao grupo com edema macular e retinopatia diabética (n=16,50%). A presença de manchas hiperrefletivas foi maior nos pacientes que responderam mal do que naqueles que tiveram boa resposta no grupo com edema macular e retinopatia diabética (p=0,03). Um dos 42 (2,4%) pacientes com boa resposta total teve espessura macular central >350 um, enquanto 5 (31,2%) do total de 16 pacientes com resposta ruim apresentaram espessura macular central >350 µm na última visita (p=0,003). Conclusão: O resultado anatômico de longo prazo do edema macular secundário à oclusão da veia retiniana e à retinopatia diabética pode ser previsto pela resposta ao tratamento no 1º dia após a injeção de antifator de crescimento endotelial vascular.
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Abstract Background The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. Methods Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. Results In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). Conclusion In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort. .
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ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.
RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.
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ABSTRACT Purpose: Intravitreal antiangiogenic therapy is currently the most invasive ophthalmic procedure performed worldwide. This study aimed to describe the clinical and epidemiological profile of patients undergoing intravitreal antiangiogenic therapy in a tertiary referral hospital in Brazil. Methods: This cross-sectional, retrospective, and observational study analyzed medical records of patients who received intravitreal injections of antiangiogenic agents for the treatment of retinal diseases at the ophthalmology outpatient clinic in the Hospital das Clínicas at Unicamp between January and December 2020. Results: The study included 429 patients and 514 eyes. The study population was predominantly male (51.28%), white (80.89%), between 50 and 80 years old (mean age, 60.92 years), had complete or incomplete first-grade education (56.88%), and did not belong to the Regional Health Department of which Campinas is a part (78.55%). Bevacizumab was the most commonly used intravitreal injectable medicine (79.38%), pro re nata was the most commonly used treatment regimen (90.27%), and macular edema was the most prevalent pathology indicative of treatment (60.12%), with diabetes etiology accounting for 48.25%. The average number of injections per patient was 3.83, with the macular neovascularization group and the pro re nata group having the highest and lowest with five and three injections, respectively. Treatment adherence was associated with the patient's pathology, and the macular edema (52.24%) and macular neovascularization (49.48%) groups had the lowest adherence rates. Conclusions: This study evaluated the epidemiological and clinical profile of patients undergoing antiangiogenic therapy in a high-complexity public hospital, which is fundamental for a better understanding of the demand for ophthalmic reference service in Brazil, and the analysis of functional results and user adherence profile promotes optimization of indications and leverages the benefits of intravitreal therapy.
RESUMO Objetivo: A terapia antiangiogênica intravítrea revolucionou o tratamento de inúmeras patologias de relevância global, sendo atualmente o procedimento oftalmológico invasivo mais realizado no mundo. Objetiva-se no presente estudo descrever o perfil clínico e epidemiológico dos pacientes submetidos a terapia intravítrea com antiangiogênicos em hospital terciário de referência no Brasil. Métodos: Trata-se de um estudo transversal, retrospectivo e observacional que foi realizado através da análise de prontuários de pacientes submetidos a injeção intravítrea de antiangiogênicos para tratamento de doenças retinianas no ambulatório de oftalmologia do Hospital das Clínicas da Unicamp no período de janeiro a dezembro de 2020. Resultados: O estudo analisou 429 pacientes e 514 olhos. A maioria pertencia ao sexo masculino (51,28%), raça branca (80,89%), possuía entre 50-80 anos com idade média de 60,92 anos e escolaridade de 1º grau completo ou incompleto (56,88%) e não pertenciam (78,55%) a área de abrangência do Departamento Regional de Saúde do qual Campinas faz parte. O fármaco mais utilizado nas injeções intravítreas foi o bevacizumabe (79,38%), o principal regime de tratamento foi o pro re nata (90,27%) e a principal grupo de patologia indicativa de tratamento foi o edema macular (60,12%), sendo 48,25% desses de etiologia diabética. A média de injeções foi de 3,83/paciente, sendo o grupo de neovascularização macular o de maior mediana com 5 injeções/paciente e o esquema pro re nata o regime de tratamento com menor mediana, 3 injeções/paciente. A adesão ao tratamento associou-se a patologia do paciente, sendo as menores taxas de adesão as dos grupos com edema macular (52,24%) e neovascularização macular (49,48%). Conclusões: O presente estudo avaliou o perfil epidemiológico e clínico dos pacientes submetidos a terapia antiangiogênica em hospital público de alta complexidade, o que é fundamental para melhor conhecimento da demanda de serviço oftalmológico de referência no Brasil e possibilita, a partir da análise dos resultados funcionais e perfil de adesão dos usuários, otimizar as indicações e alavancar os benefícios de terapia intravítrea.
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ABSTRACT Background: Proton pump inhibitors (PPIs) are widely prescribed worldwide, often resulting in their overuse. Consequently, it is essential to identify the likely causes of this overuse to facilitate their appropriate prescription. Objective: This study aims to assess physician prescribing patterns, their knowledge of PPIs, and factors affecting their knowledge. Methods: An online survey was conducted among Latin American and Spanish physicians, collecting the following data: professional information, patterns of PPI usage, familiarity with published evidence, and the management approach in three hypothetical case-scenarios. Participant knowledge was categorized as sufficient or insufficient based on the results of the case scenarios. Subsequently, subgroup analysis was performed based on physician training level, years in practice, specialty, and time since the last PPI literature review. Results: A total of 371 physicians participated in the survey. Thirty-eight percent frequently prescribe PPIs, primarily for prophylactic purposes (57.9%). Eighty percent were unfamiliar with PPI deprescribing strategies, and 54.4% rarely reviewed the ongoing indication of patients taking a PPI. Sixty-four percent demonstrated sufficient knowledge in the case-scenarios. A significant association was observed between specialty type (medical vs surgical: 69.4% vs 46.8%, P<0.001), the timing of the PPI indication literature review (<5 years vs >5 years: 71.4% vs 58.7%, P=0.010), and sufficient knowledge. Conclusion: While most participants prescribed PPIs regularly and for prophylaxis purposes, the majority were unfamiliar with deprescribing strategies and rarely reviewed ongoing indications. Sufficient knowledge is correlated with recent literature reviews and medical specialty affiliation.
RESUMO Contexto: Os inibidores da bomba de prótons (IBPs) são amplamente prescritos em todo o mundo, muitas vezes resultando em seu uso excessivo. Consequentemente, é essencial identificar as prováveis causas desse uso excessivo para facilitar sua prescrição adequada. Objetivo: Este estudo tem como objetivo avaliar o padrão de prescrição dos médicos, seu conhecimento sobre IBPs e fatores que afetam seu conhecimento. Métodos: Uma pesquisa on-line foi conduzida entre médicos latino-americanos e espanhóis, coletando os seguintes dados: informações profissionais, padrões de uso de IBP, familiaridade com evidências publicadas e abordagem de manejo em três casos-cenários hipotéticos. O conhecimento dos participantes foi categorizado em suficiente ou insuficiente com base nos resultados dos cenários de caso. Posteriormente, a análise de subgrupos foi realizada com base no nível de formação do médico, anos de prática, especialidade e tempo desde a última revisão da literatura dos IBPs. Resultados: Um total de 371 médicos participaram da pesquisa. Trinta e oito por cento prescrevem frequentemente IBP, principalmente para fins profiláticos (57,9%). Oitenta por cento não estavam familiarizados com as estratégias de prescrição de IBP, e 54,4% raramente revisaram a indicação contínua de pacientes em uso de IBP. Sessenta e quatro por cento demonstraram conhecimento suficiente nos cenários-caso. Observou-se associação significativa entre o tipo de especialidade (médica vs cirúrgica: 69,4% vs 46,8%, P<0,001), o momento da revisão da literatura de indicação do IBP (<5 anos vs >5 anos: 71,4% vs 58,7%, P=0,010) e conhecimento suficiente. Conclusão: Embora a maioria dos participantes prescrevesse IBPs regularmente e para fins de profilaxia, no entanto, não estava familiarizada com estratégias de prescrição e raramente revisava as indicações em andamento. O conhecimento suficiente está correlacionado com revisões recentes da literatura e afiliação à especialidade médica.
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ABSTRACT Introduction Instruments to manage adverse effects of endocrine therapy with Aromatase inhibitors (AI) may improve adherence and persistence to treatment and Health-Related Quality of Life (HRQL). The 31-item Cervantes Scale (CS-31) is an HRQL questionnaire with particularities of the perimenopausal and postmenopausal period that could be an appropriate instrument to assess HRQL in Breast Cancer (BC) survivors. Objective This study aimed to perform additional validation of the CS-31 for BC survivors undergoing adjuvant endocrine therapy. Methods This prospective study was performed at three time points named T0, T1, and T2: initial, intermediate, and final follow-up period, respectively, totaling 24 months of follow-up. At each time point, the participants completed the CS-31, Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F), and Hospital Anxiety and Depression Scale (HADS). The internal consistency, construct validity, responsiveness analyses, and known-group validity of CS-31 were evaluated. Results This study included 89 postmenopausal women diagnosed with hormone receptor-positive early BC in adjuvant endocrine therapy with AI. The internal consistency was good (Cronbach's alpha = 0.89). Construct validity received a positive rating, with 100% of results consistent with prior hypotheses. A prospective improvement in HRQL was identified for the CS-31 Global Score and FACIT-F Total Score and for most of their domains. Furthermore, women with anxiety and depression by HADS presented worse HRQL by CS-31. Conclusion The authors identified that the CS-31 seems to be appropriate for use in oncology medical routine and may help to monitor adverse effects and HRQL of BC survivors during adjuvant endocrine therapy.
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RESUMEN Introducción: el modelo SMART-REACH predice el riesgo de eventos cardiovasculares recurrentes. Objetivos: los objetivos de este estudio fueron: a) evaluar el riesgo residual en una población en prevención secundaria y niveles de colesterol asociado a lipoproteínas de baja densidad (C-LDL) fuera de meta; b) mediante un modelo de simulación, determinar el impacto de optimizar las terapias hipolipemiantes en términos de reducción del riesgo residual. Material y métodos: estudio transversal, descriptivo y multicéntrico. Se incluyeron consecutivamente pacientes con antecedentes cardiovasculares y un C-LDL mayor o igual que 55 mg/dL. El riesgo de eventos recurrentes (infarto agudo de miocardio, accidente cerebrovascular o muerte vascular) a 10 años y a lo largo de la vida se estimó utilizando el modelo SMART-REACH. Mediante una simulación, se optimizó el tratamiento hipolipemiante de cada paciente (utilizando estatinas, ezetimibe o inhibidores de proproteína convertasa subtilisina kexina tipo 9 [iPCSK9]), se estimó el descenso del C-LDL, se verificó el alcance del objetivo lipídico y se calculó la reducción del riesgo cardiovascular y el número necesario a tratar (NNT) correspondiente. Resultados: se incluyeron 187 pacientes (edad media 67,9 ± 9,3 años, 72,7% hombres). Los riesgos residuales calculados a 10 años y a lo largo de la vida fueron 37,1 ± 14,7% y 60,3 ± 10,7%, respectivamente. Globalmente, se pudo optimizar una sola estrategia farmacológica con estatinas, ezetimibe o un iPCSK9 en el 38,5%, el 11,5% y el 5,5% de la población, respectivamente. La optimización basada en dos tratamientos se realizó en el 27,5% (estatinas + ezetimibe), el 7,7% (estatinas + iPCSK9) y el 1,1% (ezetimibe + iPCSK9) de los casos. En 15 pacientes se optimizó el tratamiento considerando los tres fármacos. El 53,9% y el 62,9% de las acciones para optimizar el tratamiento mostraron un NNT menor que 30 para evitar un evento a 10 años o a lo largo de la vida, respectivamente. Conclusión: en este estudio, los pacientes con antecedentes cardiovasculares que no alcanzan la meta de C-LDL mostraron un riesgo residual considerable. La simulación mostró un importante margen para optimizar el tratamiento, con un impacto notable en el riesgo residual.
ABSTRACT Background: The SMART-REACH model predicts the risk or recurrent cardiovascular events. Objectives: The objectives of this study were: a) to evaluate the residual cardiovascular risk in a secondary prevention population with LDL-C levels above the recommended goal, using a simulation model; and b) to determine the impact of optimizing lipid-lowering therapies in terms of residual cardiovascular risk reduction. Methods: We conducted a cross-sectional, descriptive and multicenter study. Patient with a history of cardiovascular disease and a LDL-C ≥55 mg/dL were consecutively included. The 10-year and lifetime risk of recurrent events (myocardial infarction, stroke, or vascular death) were estimated using the SMART-REACH model. By means of a simulation, lipid-lowering treatment was optimized for each patient [using statins, ezetimibe and/or PCSK9 (PCSK9) inhibitors], with estimation of LDL-C reduction, checking if lipid-lowering goal was achieved and calculating the reduction in cardiovascular risk and the corresponding number needed to treat (NNT). Results: The cohort was made up of 187 patients; mean age was 67.9 ± 9.3 years and 72.7% were men. The calculated 10-year and lifetime residual risks were 37.1 ± 14.7% and 60.3 ± 10.7%, respectively. Overall, treatment was optimized with a single pharmacological strategy with statins, ezetimibe or PCSK9 inhibitor in 38.5%, 11.5% and 5.5% of the population, respectively. Optimization based on two treatments was performed in 27.5% (statins + ezetimibe), 7.7% (statins + PCSK9 inhibitor) and 1.1% (ezetimibe + PCSK9 inhibitor) of the cases. In 15 patients, treatment was optimized when the three drugs (statins + ezetimibe + PCSK9 inhibitor) were considered. Overall, 53.9% and 62.9% of the actions implemented to optimize treatment showed a 10-year or lifetime NNT < 30 to prevent an event, respectively. Conclusion: In this study, patients with a history of cardiovascular disease who do not reach LDL-C goal showed significant residual cardiovascular risk. The simulation model showed a significant margin for optimizing treatment, with a marked reduction in residual cardiovascular risk.
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Abstract Avoidant or Restrictive Food Intake Disorder (ARFID) is an eating disorder (ED) not common in adults. In this article we present a clinical case of ARFID in a 37-year-old male patient treated in an ED center in Medellin, Colombia; displaying anxious symptoms that began a year earlier and concomitant weight loss, following a traumatic event causing an overall impairment with that patient. Several medical evaluations/examinations looking for organic causes, were excluded. Interventions were implemented by a psychiatry, a psychotherapist using cognitive-behavior therapy (CBT), and a nutritionist, all in face-to-face modality, which were carried out weekly for the first three months, then biweekly and subsequently quarterly. each lasting approximately 40-60 minutes. After the set of pharmacological interventions and psychotherapy, a great improvement in the functionality of the patient was observed. Improvement was found with respect to eating in public, food variation and panic attacks. In the absence of guidelines, it is important to use standardized and replicable treatments in this population.
Resumen El trastorno evitativo restrictivo de la ingesta (TERIA) es un trastorno alimentario (TCA) raro en adultos. Se presenta el caso de un hombre de 37 años con TERIA y trastorno de pánico atendido en un centro para TCA en Medellín, Colombia, quien presentó un año de síntomas ansiosos y pérdida de peso después de evento traumático, generando disfuncionalidad. Fue evaluada y excluida organicidad. Se realizaron intervenciones por parte de psiquiatría, psicoterapia con enfoque cognitivo conductual y nutrición, todas en modalidad presencial, las cuales se realizaron semanalmente los primeros tres meses, luego quincenalmente y posteriormente trimestralmente. Cada una con una duración de 40-60 minutos aproximadamente por sesión. Posterior al conjunto de intervenciones farmacológicas y psicoterapia, se observó una gran mejoría la funcionalidad del paciente, se encontró mejoría con respecto a comer en público, variación en los alimentos y ataques de panico. Ante la ausencia de guías de manejo de TERIA en adultos es relevante realizar tratamientos estandarizados que puedan ser replicados.
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Objetivo: Estimar o custo da sequência de tratamento considerando as terapias com niraparibe e bevacizumabe, respectivamente, como terapias de manutenção de 1L e 2L para pacientes com câncer de ovário (CO) epitelial com deficiência de recombinação homóloga (HRD) e BRCA selvagem (BRCAwt) em um horizonte temporal de cinco anos, sob a perspectiva do sistema de saúde suplementar brasileiro. Métodos: Foi desenvolvido um modelo de sobrevida particionado com três transições de estados de saúde, considerando os seguintes regimes em 1L e 2L, respectivamente: carboplatina + paclitaxel seguido de terapia de manutenção com niraparibe; carboplatina + gencitabina + bevacizumabe seguido pela continuação de bevacizumabe. As posologias em bula e as curvas de sobrevida livre de progressão dos respectivos estudos pivotais em cada uma das linhas terapêuticas foram utilizadas na análise, e o custo de tratamento foi calculado a partir da lista oficial de preços de medicamentos da CMED de abril de 2023. Resultados: O custo em 1L e 2L foi de BRL 868.830 e BRL 403.407, totalizando BRL 1.272.237 em um horizonte temporal de cinco anos, com 2,28 e 0,52 anos de vida livre de progressão, respectivamente, na 1L e 2L, com o total de 2,8 anos. Conclusões: O resultado da análise de custo de sequência de tratamento de câncer de ovário HRD/BRCAwt apresentou um custo total estimado de BRL 1.272.237, com 2,8 anos de vida livre de progressão. Essa análise contribui no entendimento dos custos e da eficácia esperada com o uso da terapia de manutenção de niraparibe em 1L e bevacizumabe em 2L em um horizonte temporal de cinco anos.
Objective: To estimate the cost of the treatment sequence, considering the maintenance therapies niraparib and bevacizumab, respectively, as maintenance therapies in 1L and 2L for patients with epithelial ovarian cancer with homologous recombination deficiency (HRD) and BRCA wild-type (BRCAwt) over a 5-year time horizon from the perspective of the Brazilian supplementary health system. Methods: A partitioned survival model was developed with three health state transitions, considering the following regimens in the 1L and 2L, respectively: carboplatin + paclitaxel followed by maintenance therapy with niraparib; carboplatin + gemcitabine + bevacizumab followed by the continuation of bevacizumab. The product's label and progression-free survival curves from the respective pivotal studies in each of the therapeutic lines were used in the analysis and the cost of treatment was calculated using as a reference the official CMED drug price list from April 2023. Results: The cost in 1L and 2L was BRL 868,830 and BRL 403,407, totaling BRL 1,272,237 over a 5-year period, with 2.28 and 0.52 years of progression-free survival, respectively in 1L and 2L, with a total of 2.8 years. Conclusions: The result of the analysis of the cost of the treatment sequence of ovarian cancer HRD/BRCAwt presented an estimated total cost of 1,272,237 with 2.8 year of progression-free survival. This analysis contributes to understand the expected cost and effectiveness with the use of maintenance therapy niraparib in 1L and bevacizumab in 2L over a 5-year time horizon.
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Neoplasias Ovarianas , Custos e Análise de Custo , Saúde Suplementar , Inibidores de Poli(ADP-Ribose) PolimerasesRESUMO
Introduction: Laryngopharyngeal reflux (LPR) manifests with a constellation of common throat symptoms and inconclusive signs on laryngoscopic exam. It is a diagnosis, often made clinically, that can lead to prescriptions of proton pump inhibitors that are unnecessary and potentially harmful. Glottic insufficiency (GI) and the accompanying hyperfunctional laryngeal behaviors can also present with similar, common throat complaints that may or may not include a qualitative change to the voice. Methods: This is a reflection article. It is written to summarize, explain, and support with evidence the opinion of the author on the topic of how symptoms of voice disorders can easily be mistaken for symptoms of LPR. The offered reflection is based on his experience, research and the available literature. Reflection: This article intends to explore the similarities between GI and LPR, how to ultimately differentiate them and how to approach treatment with a broader differential diagnosis. Conclusion: LPR and GI can present with identical, vague throat, and voice symptoms. Empiric medication trials, behavioral interventions and objective laryngovideostroboscopy, impedance-based reflux, and esophageal motility testing may all be needed, sometimes in a trial and error fashion, to correctly diagnose and treat a patient's symptoms.
Introducción: El reflujo laríngeo-faríngeo (LPR, por sus siglas en inglés) se manifiesta con una serie de síntomas comunes en la garganta y signos no concluyentes en el examen larinoscópico. Es un diagnóstico que a menudo se realiza clínicamente y que puede llevar a la prescripción de inhibidores de la bomba de protones que son innecesarios y potencialmente perjudiciales. La insuficiencia glótica (IG) y los comportamientos laríngeos hiperfuncionales que la acompañan también pueden presentar síntomas de garganta comunes similares, que pueden o no incluir un cambio cualitativo en la voz. Métodos: Este es un artículo de reflexión. Está escrito para resumir, explicar y respaldar con evidencia la opinión del autor sobre cómo los síntomas de los trastornos de la voz pueden confundirse fácilmente con los síntomas del LPR. La reflexión ofrecida se basa en su experiencia, investigación y la literatura disponible. Reflexión: Este artículo tiene la intención de explorar las similitudes entre la IG y el LPR, cómo diferenciarlos finalmente y cómo abordar el tratamiento con un diagnóstico diferencial más amplio. Conclusión: El LPR y la IG pueden presentar síntomas idénticos y vagos en la garganta y la voz. Puede ser necesario realizar ensayos de medicación empírica, intervenciones conductuales y pruebas objetivas de laringovideostroboscopia, reflujo basado en impedancia y motilidad esofágica, a veces de manera experimental, para diagnosticar y tratar correctamente los síntomas de un paciente.
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Introducción: Las colinesterasas son enzimas que se encargan de hidrolizar la acetilcolina en ácido acético y colina, poniéndole fin a la transmisión nerviosa a lo largo de la sinapsis de las uniones neuromusculares. La medición de la actividad de la colinesterasa sérica constituye un indicador del efecto causado por la exposición prolongada a los organofosforados. Objetivo: Determinar los niveles de colinesterasa sérica y factores relacionados con la exposición a organofosforados en agricultores de la vereda de Páramo Lagunas de San Pablo de Borbur, Boyacá, Colombia. Metodología: Estudio prospectivo, de corte transversal, con una muestra de 57 trabajadores. A cada individuo se le aplicó una encuesta de datos sociodemográficos y factores laborales, posteriormente se les tomó una muestra de sangre venosa en ayuno de 8-12 horas; con el fin de determinar las concentraciones de colinesterasa sérica (kit Colinesterasa Butiriltiocolina Biosystems®) con el equipo automatizado de química clínica A-15 de Biosystems®. Resultados: El rango de edad de los participantes estuvo entre los 22 y 64 aflos, el 72 % de los individuos pertenecía al sexo masculino. El 3,5 % (2 varones) presentó valores inferiores al intervalo biológico de referencia (IBR), el 88 % de las personas afirmó realizar tareas con plaguicidas y el 54 % afirmó no utilizar los elementos de protección personal (EPP) al trabajar con estas sustancias. Conclusiones: Se evidenció la falta de escolaridad y la ausencia del acompaflamiento técnico en esta zona, lo que induce a que estos agricultores realicen procesos agrícolas relacionados con la aplicación de plaguicidas sin el adecuado conocimiento y sin la utilización adecuada de EPP.
Introduction: Cholinesterases are enzymes responsible for hydrolyzing acetylcholine in acetic acid and choline, which ends nerve transmission along the synapse of neuromuscular junctions. Measurement of serum cholinesterase activity acts as an indicator of the effect caused by prolonged exposure to organophosphates and carbamates Objective: To determine serum cholinesterase levels and factors related to exposure to organophosphates in farmers from the county of Páramo Lagunas in San Pablo de Borbur, Boyacá, Colombia. Methodology: Prospective, cross-sectional study, with a sample of 57 agricultural workers, a survey of sociodemographic data and labor factors was applied to each individual and a venous blood sample was taken in an 8-12 hour fasting, Serum cholinesterase concentrations were determined (Biosystems® Butyrylthiocholine Cholinesterase kit), by means of the Biosystems® A-15 automated clinical chemistry kit. Results: The age range of the participants was between 22 and 64 years old, 72% of the individuals belonged to the male sex. 3.5% (2 male individuals) presented values lower than the biological reference interval (BRI); 88% of the people affirmed to carry out tasks with pesticides and 54% of them affirmed not to use personal protective equipment (PPE) when working with these substances. Conclusions: The lack of schooling was evidenced in most of the farmers, as well as the absence of technical support to this area, which induces these farmers to carry out agricultural processes such as pesticide application, without adequate knowledge and without the proper use of PPE.
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Background: Chronic myeloid leukemia (CML) is relatively rare in pediatric and adolescent age groups. The purpose of this study was to evaluate the clinical, hematopathological, and biochemical parameters of CML in pediatric and adolescent age groups, along with an assessment of the treatment response with first-line tyrosine kinase inhibitors (TKI) and its correlation with the prognostic scoring systems of adults. Materials and Methods: A retrospective study of 44 Breakpoint Cluster Region-Abelson leukemia virus (BCR-ABL1)-positive pediatric and adolescent CML cases registered at our hospital was done. The clinical and laboratory parameters were evaluated using hospital software. The treatment response was monitored and scoring was performed using mathematical calculations. Results: The mean age was 11.6 (±4.7) years. The median hemoglobin was 8.4 g/dL and 63.6% of the cases showed white blood cell (WBC) counts >250,000/?L. The average follow-up was 21 months. A total of 97.7 and 78.1% cases achieved complete hematological response (CHR) and molecular response, respectively, during the treatment course. The maximum number of patients had low Sokal and European treatment and Outcomes Study (EUTOS) scores. Seventy-five per cent of the cases achieved CHR at 3 months, while 73.6 and 78.6% CML-Chronic phase (CP) cases with low Sokal and EUTOS scores achieved CHR at 3 months, respectively. Conclusion: This study revealed that the CML cases in pediatric and adolescent age groups are normally present with higher WBC counts at the time of diagnosis. The association of the prognostic scoring system with treatment response was statistically insignificant. However, a larger cohort study is needed to determine the treatment response of TKI in children and adolescent CML and its correlation with the prognostic scoring systems.