RESUMEN
BACKGROUND: The optimal antithrombotic regimen for patients with atrial fibrillation (AF) who had an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI) is not known. OBJECTIVES: The authors sought to determine which antithrombotic regimen best balances safety and efficacy. METHODS: AUGUSTUS, a multicenter 2 × 2 factorial design randomized trial compared apixaban with vitamin K antagonist (VKA) and aspirin with placebo in patients with AF with recent ACS and/or PCI treated with a P2Y12 inhibitor. We conducted a 4-way analysis comparing safety and efficacy outcomes in the 4 randomized groups. The primary outcome was a composite of all-cause death, major or clinically relevant nonmajor bleeding, or hospitalization for cardiovascular causes over 6-month follow-up. Secondary outcomes included individual components of the primary endpoint. RESULTS: A total of 4,614 patients were enrolled. All patients were treated with a P2Y12 inhibitor. The primary endpoint occurred in 21.9% of patients randomized to apixaban plus placebo, 27.3% randomized to apixaban plus aspirin, 28.0% randomized to VKA plus placebo, and 33.3% randomized to VKA plus aspirin. Rates of major or clinically relevant nonmajor bleeding and hospitalization for cardiovascular causes were lower with apixaban and placebo compared with the other 3 antithrombotic strategies. There was no difference between the 4 randomized groups with respect to all-cause death. CONCLUSIONS: In patients with AF and a recent ACS and/or PCI, an antithrombotic regimen that included a P2Y12 inhibitor and apixaban without aspirin resulted in a lower incidence of the composite of death, bleeding, or cardiovascular hospitalization than regimens including VKA, aspirin, or both. (An Open-label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; NCT02415400).
Asunto(s)
Síndrome Coronario Agudo , Aspirina , Fibrilación Atrial , Fibrinolíticos , Intervención Coronaria Percutánea , Pirazoles , Piridonas , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Intervención Coronaria Percutánea/métodos , Masculino , Femenino , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/complicaciones , Anciano , Aspirina/uso terapéutico , Persona de Mediana Edad , Pirazoles/uso terapéutico , Piridonas/uso terapéutico , Piridonas/efectos adversos , Piridonas/administración & dosificación , Fibrinolíticos/uso terapéutico , Vitamina K/antagonistas & inhibidores , Resultado del Tratamiento , Inhibidores del Factor Xa/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/epidemiologíaRESUMEN
BACKGROUND: Vitamin K antagonists (VKAs) are the recommended first-line treatment for left ventricular thrombus (LVT); however, direct oral anticoagulants (DOACs) have been considered an alternative therapy. OBJECTIVES: To evaluate the efficacy and safety of DOACs compared with VKAs therapy in patients with LVT. METHODS: PubMed, Embase, and Cochrane were systematically searched for randomized clinical trials or cohort studies that compared DOACs versus VKAs for LVT. Risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (95% CIs). Statistical significance was defined as p value < 0.05. RESULTS: A total of 4 randomized clinical trials and 29 cohort studies were included, with 4,450 patients assigned to either DOACs or VKAs. There was no significant difference between groups for stroke or systemic embolic (SSE) events (RR 0.84; 95% CI 0.65 to 1.07; p = 0.157), stroke (RR 0.73; 95% CI 0.48 to 1.11; p = 0.140), systemic embolic (SE) events (RR 0.69; 95% CI 0.40 to 1.17; p = 0.166), thrombus resolution (RR 1.05; 95% CI 0.99 to 1.11; p = 0.077), any bleeding (RR 0.78; 95% CI 0.60 to 1.00; p = 0.054), clinically relevant bleeding (RR 0.69; 95% CI 0.46 to 1.03; p = 0.066), minor bleeding (RR 0.73; 95% CI 0.43 to 1.23; p = 0.234), major bleeding (RR 0.87; 95% CI 0.42 to 1.80; p = 0.705), and all-cause mortality (RR 1.05; 95% CI 0.79 to 1.39; p = 0.752). Compared with VKAs, rivaroxaban significantly reduced SSE events (RR 0.35; 95% CI 0.16 to 0.91; p = 0.029) and SE events (RR 0.39; 95% CI 0.16 to 0.95; p = 0.037). CONCLUSIONS: DOACs had a similar rate of thromboembolic and hemorrhagic events, as well as thrombus resolution, compared to VKAs in the treatment of LVTs. Rivaroxaban therapy had a significant reduction in thromboembolic events, compared to VKAs.
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Anticoagulantes , Ventrículos Cardíacos , Trombosis , Vitamina K , Humanos , Vitamina K/antagonistas & inhibidores , Anticoagulantes/uso terapéutico , Trombosis/tratamiento farmacológico , Ventrículos Cardíacos/efectos de los fármacos , Administración Oral , Hemorragia/inducido químicamente , Cardiopatías/tratamiento farmacológico , Resultado del Tratamiento , Accidente Cerebrovascular/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: We aimed to evaluate the safety and efficacy of antithrombotic strategies by age in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention in AUGUSTUS. METHODS: Patients were stratified into 3 age groups: <65, 65-74, and ≥75 years. Outcomes of interest were major or clinically relevant non-major bleeding, major bleeding, death or rehospitalization, and ischemic events. Treatment effects of apixaban vs. vitamin K antagonist (VKA) and aspirin vs. placebo were assessed across age groups using Cox models. RESULTS: Of 4614 patients, 1267 (27.5%) were <65, 1802 (39.0%) were 65-74, and 1545 (33.5%) were ≥75 years. Apixaban was associated with lower rates of major or clinically relevant non-major bleeding than VKA (<65: HR 0.69 [0.47-1.00]; 65-74: HR 0.57 [0.43-0.75]; ≥75: HR 0.81 [0.63-1.04]). Death or hospitalization occurred less often with apixaban, regardless of age. No differences were observed in rates of ischemic events between apixaban and VKA according to age. Aspirin was associated with higher rates of bleeding than placebo (<65: HR 1.67 [1.15-2.43]; 65-74: HR 2.32 [1.73-3.10]; ≥75: HR 1.69 [1.31-2.19]). Rates of death or rehospitalization and ischemic events were similar among patients receiving aspirin or placebo across age groups. CONCLUSIONS: Apixaban was associated with greater absolute reduction in bleeding than VKA in older age groups, reflecting their higher hemorrhagic risk. Aspirin increased bleeding in all age groups vs. placebo. Our findings support the use of apixaban plus a purinergic receptor P2Y12(P2Y12) inhibitor without aspirin in patients with atrial fibrillation and recent acute coronary syndrome/percutaneous coronary intervention, regardless of age.
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Síndrome Coronario Agudo , Aspirina , Fibrilación Atrial , Fibrinolíticos , Hemorragia , Intervención Coronaria Percutánea , Pirazoles , Piridonas , Humanos , Anciano , Piridonas/uso terapéutico , Piridonas/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Masculino , Femenino , Aspirina/uso terapéutico , Aspirina/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Síndrome Coronario Agudo/tratamiento farmacológico , Factores de Edad , Hemorragia/inducido químicamente , Persona de Mediana Edad , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Vitamina K/antagonistas & inhibidores , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Anciano de 80 o más AñosRESUMEN
The worldwide market for vegetable and fruit juices stands as a thriving sector with projected revenues reaching to $81.4 billion by 2024 and an anticipated annual growth rate of 5.27% until 2028. Juices offer a convenient means of consuming bioactive compounds and essential nutrients crucial for human health. However, conventional thermal treatments employed in the juice and beverage industry to inactivate spoilage and pathogenic microorganisms, as well as endogenous enzymes, can lead to the degradation of bioactive compounds and vitamins. In response, non-thermal technologies have emerged as promising alternatives to traditional heat processing, with pulsed electric field (PEF) technology standing out as an innovative and sustainable choice. In this context, this comprehensive review investigated the impact of PEF on the microbiological, physicochemical, functional, nutritional, and sensory qualities of vegetable and fruit juices. PEF induces electroporation phenomena in cell membranes, resulting in reversible or irreversible changes. Consequently, a detailed examination of the effects of PEF process variables on juice properties is essential. Monitoring factors such as electric field strength, frequency, pulse width, total treatment time, and specific energy is important to ensure the production of a safe and chemically/kinetically stable product. PEF technology proves effective in microbial and enzymatic inactivation within vegetable and fruit juices, mitigating factors contributing to deterioration while maintaining the physicochemical characteristics of these products. Furthermore, PEF treatment does not compromise the content of substances with functional, nutritional, and sensory properties, such as phenolic compounds and vitamins. When compared to alternative processing methods, such as mild thermal treatments and other non-thermal technologies, PEF treatment consistently demonstrates comparable outcomes in terms of physicochemical attributes, functional properties, nutritional quality, and overall safety.
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Jugos de Frutas y Vegetales , Verduras , Humanos , Vitaminas , Vitamina A , Vitamina K , TecnologíaRESUMEN
FUNDAMENTOS: A prevenção de acidente vascular encefálico é uma das prioridades no tratamento da fibrilação atrial (FA). Devido ao alto custo dos anticoagulantes diretos, os antagonistas da vitamina K (AVK) representam importante estratégia terapêutica oferecida pelo SUS aos pacientes com FA no Brasil. Entretanto, os preditores de desfechos clínicos relevantes foram pouco estudados no mundo real. O objetivo do estudo foi identificar a incidência e os preditores independentes de morte cardiovascular, eventos tromboembólicos, sangramento maior e não-maior clinicamente relevante, em pacientes com FA tratados com AVK. MÉTODOS: Coorte prospectiva de pacientes com FA recebendo ≥1 ano de varfarina ou femprocumona, incluídos em 2017/2018 e seguidos até 2019. Foram classificados como FA valvar ou não valvar de acordo com as diretrizes vigentes à época. Os desfechos clínicos foram morte cardiovascular, eventos tromboembólicos, sangramento maior e não maior clinicamente relevante, separadamente e como desfecho composto, e adjudicados de forma independente. Foram coletados o tempo na faixa terapêutica (TFT), os escores CHADS2, CHA2DS2-VASc, HAS-BLED e SAMe-TT2R2. RESULTADOS: Foram incluídos 1.350 pacientes, com idade média de 69,2 (±11,8) anos e 53,6% do sexo feminino, e seguimento de 17 (15-19) meses. A mediana do TFT foi 65%. Prevalência de comorbidades foi elevada e 38,4% apresentavam doença reumática. Incidência anual de eventos tromboembólicos e morte cardiovascular foi 4,4% e preditores foram tromboembolismo prévio (HR 2,12 [IC95% 1,22-3,67], TFT <50% (HR 1,98 [IC95% 1,16-3,37]) e taxa de filtração glomerular (TFG) <45mL/min/1,73m2 (HR 2,76 [IC95% 4,82-1,58]). Sangramento maior e não-maior clinicamente relevante foram 3,24%/ano (IC95% 2,47-4,14), e preditores foram sangramento prévio (HR 2,60 [IC95% 1,47- 4,61]) e prótese valvar mecânica (HR 1,91 [IC95% 1,15-3,15]). A incidência do desfecho composto por eventos tromboembólicos e hemorrágicos foi 8,7%/ano e preditores foram sangramento prévio (HR 1,70 [IC95% 1,07-2,70]), TFT <41% (HR 1,79 [IC95% 1,11-2,86]) e átrio esquerdo >44mm (HR 1,97 [IC95% 3,26-1,19]). A incidência anual de eventos aumentou gradualmente de acordo com pontuações mais altas dos escores de risco CHADS2, CHA2DS2-VASc e HAS-BLED. Os valores de TFT foram significativamente menores entre os pacientes com ≥3 pontos no escore SAMe-TT2R2. CONCLUSÕES: Tromboembolismo ou sangramento prévios, TFG e TFT reduzidos, prótese valvar mecânica, e átrio esquerdo aumentado foram preditores de desfechos clínicos em pacientes com FA tratados com AVK.
Asunto(s)
Fibrilación Atrial , Vitamina K , Accidente Cerebrovascular/prevención & control , AnticoagulantesAsunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Charlatanería , Humanos , Vitaminas , Brasil , Vitamina A , Vitamina K , Nutrientes , TecnologíaRESUMEN
BACKGROUND: In patients with atrial fibrillation (AF) and normal or slightly impaired renal function, the use of direct oral anticoagulants (DOACs) is preferable to vitamin K antagonists (VKAs). However, in patients undergoing hemodialysis, the efficacy, and safety of DOACs compared with VKAs are still unknown. PURPOSE: To review current evidence about the safety and efficacy of DOACs compared to VKAs, in patients with AF and chronic kidney disease under hemodialysis. METHODS: We systematically searched PubMed, Scopus, and Cochrane databases for RCTs comparing DOACs with VKAs for anticoagulation in patients with AF on dialysis therapy. Outcomes of interest were: (1) stroke; (2) major bleeding; (3) cardiovascular mortality; and (4) all-cause mortality. Statistical analysis was performed using RevMan 5.1.7 and heterogeneity was assessed by I2 statistics. RESULTS: Three randomized controlled trials were included, comprising a total of 383 patients. Of these, 218 received DOACs (130 received apixaban; 88 received rivaroxaban), and 165 were treated with VKAs (116 received warfarin; 49 received phenprocoumon). The incidence of stroke was significantly lower in patients treated with DOACs (4.7%) compared with those using VKAs (9.5%) (RR 0.42; 95% CI 0.18-0.97; p = 0.04; I2 = 0%). However, the difference was not statistically significant in the case of ischemic stroke specifically (RR 0.42; 95% CI 0.17-1.04; p = 0.06; I2 = 0%). As for the major bleeding outcome, the DOAC group (11%) had fewer events than the VKA group (13.9%) but without statistical significance (RR 0.75; 95% CI 0.45-1.28; p = 0.29; I2 = 0%). There was no significant difference between groups regarding cardiovascular mortality (RR 1.23; 95% CI 0.66-2.29; p = 0.52; I2 = 13%) and all-cause mortality (RR 0.98; 95% CI 0.77-1.24; p = 0.84; I2 = 16%). CONCLUSION: This meta-analysis suggests that in patients with AF on dialysis, the use of DOACs was associated with a significant reduction in stroke, and a numerical trend of less incidence of major bleeding compared with VKAs, but in this case with no statistical significance. Results may be limited by a small sample size or insufficient statistical power.
Asunto(s)
Fibrilación Atrial , Fallo Renal Crónico , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Diálisis Renal/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Anticoagulantes/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Fallo Renal Crónico/complicaciones , Fibrinolíticos/uso terapéutico , Vitamina K , Administración OralRESUMEN
OBJECTIVE: It is well known that female infertility is multifactorial. Therefore, we aimed to compare the effects of thyroid dysfunction, vitamin deficiency, and microelement deficiency in fertile and infertile patients. MATERIALS AND METHODS: Between May 1st, 2017, and April 1st, 2019, we conducted a retrospective case-control study with of 380 infertile and 346 pregnant patients (who normally fertile and able to conceive spontaneously). The fertile patients were selected among those who got pregnant spontaneously without treatment, had a term birth, and did not have systemic or obstetric diseases. The levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), anti-thyroid peroxidase (anti-TPO), vitamin D, vitamin B12, folic acid, ferritin, and zinc of both groups were compared. RESULTS: There was no difference between patients in the infertile and pregnant groups in terms of low normal and high serum T3 and T4 levels (p = 0.938; p > 0.05) respectively, nor in terms of normal and high anti-TPO levels (p = 0.182; p > 0.05) respectively. There was no significant difference regarding patients with low, insufficient, and sufficient vitamin D levels in the infertile and pregnant groups (p = 0.160; p >0.05) respectively. The levels of folic acid, ferritin, and zinc of the infertile group were significantly lower than those of the pregnant group. CONCLUSION: The serum levels of folic acid, ferritin, and zinc in infertile patients presenting to our outpatient clinic were lower than those o the fertile patients.
OBJETIVO: Sabe-se que a infertilidade feminina é multifatorial. Portanto, nosso objetivo foi comparar os efeitos da disfunção tireoidiana, deficiência de vitaminas e deficiência de microelementos em pacientes férteis e inférteis. MATERIAIS E MéTODOS: Entre 1° de maio de 2017 e 1° de abril de 2019, realizamos um estudo retrospectivo caso-controle com 380 pacientes inférteis e 346 grávidas (normalmente férteis e capazes de conceber espontaneamente). As pacientes férteis foram selecionadas entre aquelas que engravidaram espontaneamente sem tratamento, tiveram parto a termo e não apresentavam doenças sistêmicas ou obstétricas. Os níveis de hormônio estimulante da tireoide (TSH), triiodotironina (T3), tiroxina (T4), antitireoide peroxidase (anti-TPO), vitamina D, vitamina B12, ácido fólico, ferritina e zinco de ambos os grupos foram comparados. RESULTADOS: Não houve diferença entre as pacientes dos grupos inférteis e gestantes em relação aos níveis altos de sérumT3 e T4 normais baixos e altos (p = 0,938; p > 0,05), respectivamente nem aos níveis normais e altos de anti-TPO (p = 0,182; p > 0,05), respectivamente. Não houve diferença significativa em relação aos pacientes com níveis baixos, insuficientes e suficientes de vitamina D nos grupos inférteis e gestantes (p = 0,160; p > 0,05), respectivamente. Os níveis de ácido fólico, ferritina e zinco do grupo infértil foram significativamente menores do que os do grupo grávida. CONCLUSãO: Os níveis de sérum de ácido fólico, ferritina e zinco nas pacientes inférteis atendidas em nosso ambulatório foram menores do que nas pacientes férteis.
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Infertilidad Femenina , Vitaminas , Embarazo , Humanos , Femenino , Estudios Retrospectivos , Estudios de Casos y Controles , Hormonas Tiroideas , Vitamina D , Vitamina A , Vitamina K , Ácido Fólico , Ferritinas , ZincRESUMEN
Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to manufacture daily-use articles. Exposure to these compounds is related to many pathologies of public health importance, such as infertility. Using a protector compound against the reproductive toxicological effects of bisphenols is of scientific interest. Melatonin and vitamins have been tested, but the results are not conclusive. To this end, this systematic review and meta-analysis compared the response of reproductive variables to melatonin and vitamin administration as protectors against damage caused by bisphenols. We search for controlled studies of male rats exposed to bisphenols to induce alterations in reproduction, with at least one intervention group receiving melatonin or vitamins (B, C, or E). Also, molecular docking simulations were performed between the androgen (AR) and estrogen receptors (ER), melatonin, and vitamins. About 1234 records were initially found; finally, 13 studies were qualified for review and meta-analysis. Melatonin plus bisphenol improves sperm concentration and viability of sperm and increases testosterone serum levels compared with control groups; however, groups receiving vitamins plus bisphenols had lower sperm concentration, total testis weight, and testosterone serum levels than the control. In the docking analysis, vitamin E had the highest negative MolDock score, representing the best binding affinity with AR and ER, compared with other vitamins and melatonin in the docking. Our findings suggest that vitamins could act as an endocrine disruptor, and melatonin is most effective in protecting against the toxic effects of bisphenols.
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Disruptores Endocrinos , Melatonina , Masculino , Ratas , Animales , Melatonina/farmacología , Vitaminas , Simulación del Acoplamiento Molecular , Semen/metabolismo , Compuestos de Bencidrilo/toxicidad , Compuestos de Bencidrilo/química , Reproducción , Receptores de Estrógenos , Vitamina A , Vitamina K , Testosterona/metabolismo , Disruptores Endocrinos/toxicidad , Disruptores Endocrinos/químicaRESUMEN
Autism spectrum disorder (ASD) is characterized by early-appearing social communication deficits, with genetic and environmental factors potentially playing a role in its etiology, which remains largely unknown. During pregnancy, certain deficiencies in critical nutrients are mainly associated with central nervous system impairment. The vitamin B9 (folate) is primarily related to one-carbon and methionine metabolism, participating in methyl donor generation. In addition, supplementation with folic acid (FA) is recommended by the World Health Organization (WHO) in the first three gestational months to prevent neural tube defects. Vitamin B12 is related to folate regeneration, converting it into an active form. Deficiencies in this vitamin have a negative impact on cognitive function and brain development since it is involved in myelin synthesis. Vitamin D is intimately associated with Ca2+ levels, acting in bone development and calcium-dependent signaling. This vitamin is associated with ASD at several levels since it has a relation with ASD genes and oxidative stress environment. This review carries the recent literature about the role of folate, vitamin B12, and vitamin D in ASD. In addition, we discuss the possible impact of nutrient deficiency or hypersupplementation during fetal development. On the other hand, we explore the biases of vitamin supplementation studies such as the loss of participants in retrospective studies, as well as multiple variants that are not considered in the conclusion, like dietary intake or auto-medication during pregnancy. In this regard, we aim to contribute to the discussion about the role of vitamins in ASD currency, but also in pregnancy and fetal development as well. Furthermore, stress during pregnancy can be an ASD predisposition, with cortisol as a regulator. In this view, we propose that cortisol is the bridge of susceptibility between vitamin disorders and ASD prevalence.
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Trastorno del Espectro Autista , Vitaminas , Embarazo , Femenino , Humanos , Vitaminas/uso terapéutico , Trastorno del Espectro Autista/tratamiento farmacológico , Estudios Retrospectivos , Hidrocortisona , Ácido Fólico/uso terapéutico , Vitamina B 12 , Vitamina A , Vitamina K , Vitamina DRESUMEN
La intoxicación humana por rodenticidas anticoagulantes de acción prolongada, conocidos como superwarfarinas, provoca coagulopatía de prolongado manejo. Presentamos el caso de un hombre de 42 años que ingirió una dosis tóxica de rodenticida en un intento suicida, evolucionando con epistaxis, INR de 11,6 y necesidad de hospitalización. Durante 7 días se realizaron controles seriados de pruebas de coagulación, con optimización de diferentes dosis de suplementación de Vitamina K. El caso destaca la potencia y vida media prolongada (aproximadamente 6 semanas) de este tipo de anticoagulantes, hecho que requiere un control clínico regular y una adherencia al tratamiento satisfactoria.
Human intoxication by long-acting anticoagulant rodenticides, known as superwarfarins, causes coagulopathy that is difficult to manage. We present the case of a 42-year-old man who ingested a toxic dose of rodenticide in a suicide attempt, evolving with epistaxis, INR of 11.6, and needing hospitalization. For seven days, serial controls of coagulation tests were carried out, with optimization of different doses of Vitamin K supplementation. The case highlights this type of anticoagulant's potency and prolonged half-life (approximately six weeks), which requires regular clinical control and satisfactory treatment adherence.
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Humanos , Masculino , Adulto , Rodenticidas/envenenamiento , Intento de Suicidio , Anticoagulantes/envenenamiento , Vitamina K/uso terapéutico , 4-Hidroxicumarinas/envenenamientoAsunto(s)
Humanos , Recién Nacido , Vitamina K , Recien Nacido Prematuro , Dolor/tratamiento farmacológicoRESUMEN
Abstract Introduction Plasma transfusion is a common therapeutic strategy used to lower international normalized ratio (INR) values in the non-emergent setting. However, due to lack of evidence of its efficacy, standardized guidelines for this practice have not been well established. Methods This retrospective observational cohort study analyzed 276 inpatient encounters that involved plasma transfusions focusing on change in INR values from pre- to post-transfusion, with respect to the following predictor variables: vitamin K co-administration, number of plasma units transfused, order indication and body mass index (BMI). Results The overall average change in the INR was 1.35. Patients who received vitamin K showed an average change of 2.51, while patients that did not receive vitamin K demonstrated an average change of 0.70. Increased numbers of plasma units transfused showed benefit up to three-unit orders. Greater decreases in the INR were observed for patients requiring plasma for anticoagulation reversal or active bleeding. There was no significant difference in the change in INR based on the BMI. By multivariate and regression analyses, the stepwise addition of each successive predictor variable demonstrated an increase in the shared variance in the outcome of the post-transfusion INR: the pre-transfusion INR and vitamin K co-administration alone was not significant (p= 0.45); the additional number of plasma units transfused was significant (R² = 0.13, p < 0.001), and; the subsequent additional plasma order indications (R² = 0.19, p < 0.001) and BMI (R² = 0.18, p < 0.001) were increasingly significant. Conclusion Taking into consideration the combination of multiple predictive factors may aid in a more efficient use of plasma products.
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Humanos , Plasma , Vitamina K , Valor Predictivo de las Pruebas , Relación Normalizada InternacionalRESUMEN
Micronutrients are essential dietary components that regulate many biologic functions, including the immune response, and are required in small amounts (typically milligrams or less) in humans. Examples of micronutrients known to affect immune function include several trace minerals (such as zinc and selenium) as well as vitamins (including vitamins A and D). Deficiencies of specific micronutrients are associated with an increased risk of infection in infants in the NICU. Identifying micronutrient supplementation strategies during this period may result in low-cost interventions to reduce the burden of neonatal infectious disease. Many replacement trials thus far demonstrate conflicting results about whether micronutrient supplementation decreases the incidence or severity of sepsis in the neonatal period. The baseline incidence of micronutrient deficiency is important to consider but is often unknown as clinical assessment of micronutrient status occurs infrequently. Future research is needed to clarify the clinical scenarios in which optimizing micronutrient status in term and preterm infants may prevent infection or improve outcomes in those patients who become infected.
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Recien Nacido Prematuro , Micronutrientes , Recién Nacido , Lactante , Humanos , Vitaminas , Vitamina A , Vitamina KRESUMEN
BACKGROUND & AIMS: We aimed to estimate the prevalence of the inadequate intake and status of magnesium, zinc, and vitamins A, C, E, and D and identify factors associated with micronutrient deficiency in serum/plasma among residents of São Paulo, Brazil. METHODS: Data from 824 individuals aged ≥14 years were obtained from the 2015 ISA-Nutrition, a population-based, cross-sectional survey. Dietary and supplement intakes were assessed using two 24-h dietary recalls, and the micronutrient inadequacies were estimated using the National Cancer Institute method. Micronutrient status was measured in serum or plasma, and deficiency was established according to the lower limit of the reference values. Receiver operating characteristic curve analysis was used to identify the effect of intake on the micronutrient status in serum/plasma. Logistic regression analysis was applied to assess the association between micronutrient status and individual characteristics. RESULTS: More than 80% of the population had an inadequate dietary intake of magnesium, vitamin E, and vitamin D. Males had a high prevalence of inadequate dietary intake of vitamin A and zinc. A high-to-moderate prevalence of inadequate vitamin C intake was observed. Vitamin D was the only nutrient with a deficient status comparable to its dietary inadequacy. The other nutrients demonstrated a lower deficiency prevalence compared to dietary inadequacy, and vitamin A demonstrated the lowest prevalence of deficiency in plasma. Generally, dietary intake showed a non-notable association with micronutrient deficiency in serum/plasma. Individuals with fasting glucose concentrations ≥100 mg/dL and those using diuretic drugs had a higher risk of serum magnesium deficiency. Those using lipid-lowering drugs and those with high plasma adiponectin concentrations had a higher risk of serum zinc deficiency. Individuals who smoked and those with hypertension showed a higher risk of plasma vitamin C deficiency. Individuals with average leptin concentrations had a higher risk of plasma vitamin E deficiency. Finally, those with sufficient leisure-time physical activity had a lower risk of serum vitamin D deficiency. CONCLUSIONS: Residents of the urban areas of São Paulo demonstrated substantially inadequate intakes of most of the assessed micronutrients; however, micronutrient deficiency in serum/plasma was not associated with dietary inadequacy, and it usually demonstrated a lower prevalence than dietary indicators. Thus, using micronutrient intake to determine the serum/plasma profile should be done with caution. The status of the micronutrients varied according to individual characteristics, indicating the interplay of complex mechanisms underlying micronutrient balance.
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Desnutrición , Micronutrientes , Oligoelementos , Vitaminas , Humanos , Masculino , Brasil/epidemiología , Estudios Transversales , Magnesio , Micronutrientes/deficiencia , Oligoelementos/deficiencia , Vitamina A , Vitamina D , Vitamina K , Zinc , Desnutrición/epidemiología , DietaRESUMEN
Restoration of the international normalized ratio (INR) to values <1.5 is commonly targeted to achieve hemostasis in patients with major bleeding or undergoing urgent surgery who are treated using vitamin K antagonists (VKAs). However, the relationship between corrected INR and vitamin K-dependent factor (VKDF) levels for hemostasis is uncertain. We aim to examine the impact of 4-factor prothrombin complex concentrate (4F-PCC) or plasma on INR correction and VKDF restoration and evaluate the relationship between INR values and VKDF levels in patients with acute major bleeding or patients requiring an urgent surgical procedure. Adult patients treated with VKA with an elevated INR (≥2.0 within 3 hours before study treatment) who received 4F-PCC or plasma after major bleeding or before an urgent surgery or invasive procedure were included in this retrospective analysis of data from 2 prospective phase 3b randomized controlled trials. Of the 370 patients included in this analysis, 185 received 4F-PCC, and 185 received plasma. In the 4F-PCC group, 159 of 185 (85.9%) had an INR ≤1.5 at 30 minutes after the end of infusion compared with only 72 of 184 (39.1%) in the plasma group. After 4F-PCC treatment, all VKDF levels exceeded 50% activity regardless of the postinfusion INR value. However, after plasma administration, mean activity levels for factors II and X were <50% at all time points assessed within 3 hours after starting the infusion, regardless of the postinfusion INR value. This retrospective analysis demonstrated that treatment with 4F-PCC among patients treated with VKA rapidly restores VKDFs to hemostatic levels irrespective of the postinfusion INR value, whereas treatment with plasma does not.
Asunto(s)
Factor IX , Vitamina K , Adulto , Humanos , Relación Normalizada Internacional , Estudios Prospectivos , Estudios Retrospectivos , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Fibrinolíticos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Direct oral anticoagulants have been an increasingly used class of drugs in the setting of nonvalvular atrial fibrillation, defying vitamin K antagonists' monopoly when it comes to anticoagulation due to its several limitations. Direct oral anticoagulants (DOACs) have entered the market as a noninferior and safer option in comparison with vitamin K antagonists, as their respective phase III clinical trials proved. The aim of this article was to update and summarize data on their clinical pharmacology and to review real-world data to know their comparative effectiveness and safety. We performed a systematic review using PubMed, Google Scholar, Embase, and Web of Science as search engines. Regarding pharmacodynamics, there were no substantial changes reported from their original profile. There were many advances in the knowledge about clinical pharmacokinetics of DOACs that have had a direct impact on their clinical use, mainly related to drug-drug interactions. In a real-world setting, DOACs have shown to be noninferior in preventing thromboembolic events compared to vitamin K antagonists. In regards to safety, DOACs have shown a lower bleeding risk relative to warfarin. Comparison between DOACs has demonstrated rivaroxaban to have the highest bleeding risk. Overall, the evidence gathered showed few changes from the original data presented in phase III clinical trials, concluding that their real-world use coincides greatly with them.
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Fibrilación Atrial , Farmacología Clínica , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/tratamiento farmacológico , Accidente Cerebrovascular/prevención & control , Administración Oral , Anticoagulantes/uso terapéutico , Rivaroxabán/uso terapéutico , Resultado del Tratamiento , Vitamina K , Dabigatrán/uso terapéuticoAsunto(s)
Recien Nacido Prematuro , Vitamina K , Recién Nacido , Humanos , Dolor/tratamiento farmacológicoRESUMEN
OBJECTIVE: To study the efficacy of 3 different vitamin K birth prophylaxis regimens in infants born premature. STUDY DESIGN: This was an open-label, parallel-group, randomized clinical trial conducted in a tertiary neonatal care unit in India. Infants born very preterm (≤32 weeks) and/or with very low birth weight (≤1500 g) were included. In each arm, 25 babies were enrolled. Babies were randomized to receive 1.0 mg, 0.5 mg, or 0.3 mg intramuscular (IM) vitamin K1 at birth. Protein induced by vitamin K absence - II (PIVKA-II) levels were assessed at birth, and on days 5 and 28, along with the frequency of death, bleeding manifestations, intraventricular hemorrhage, necrotizing enterocolitis, bilirubin levels, and duration of phototherapy. The primary outcome was comparison of PIVKA-II levels on day 5 of life. RESULTS: All the 3 regimens resulted in similar proportion of vitamin K subclinical sufficiency (PIVKA-II < 0.028 AU/mL) infants on day 5 (1 mg - 100%; 0.5 mg - 91.7%; 0.3 mg - 91.7%, P = .347), with no significant difference in median (IQR) PIVKA-II levels (AU/mL): 1 mg 0.006 (0.004, 0.009); 0.5 mg 0.008 (0.004, 0.009); 0.3 mg 0.006 (0.003, 0.009), P = .301. However, on day 28, there was a significant decrease in the proportion of vitamin K-sufficient infants in the 0.3-mg IM group (72.7%) compared with the 1.0-mg (100%) or 0.5-mg (91.3) groups. The 1.0-mg group had significantly greater bilirubin levels and duration of phototherapy. None of the other clinical outcomes were statistically different. CONCLUSIONS: Both 1-mg and 0.5-mg IM vitamin K birth prophylaxis resulted in high sufficiency on follow-up, compared with 0.3 mg. The current recommendation of 0.5-1 mg IM vitamin K birth prophylaxis for infants born preterm, needs to be continued. TRIAL REGISTRATION: CTRI/2022/02/040396.
Asunto(s)
Protrombina , Vitamina K , Recién Nacido , Lactante , Humanos , Precursores de Proteínas/metabolismo , Vitamina K 1/uso terapéutico , Vitaminas , BilirrubinaRESUMEN
Sodium dehydroacetate (Na-DHA) is widely used as an antibacterial and preservative additive in food and cosmetics. Previously, we reported that repeated oral administration of Na-DHA induces coagulation disorders, and inhibited liver vitamin K epoxide reductase complex subunit 1 (VKORC1) and VKORC1-like protein 1 (VKORC1L1) in rats. However, the effects of Na-DHA on coagulation factors in rat hepatocytes and the mechanism of VKORC1 and VKORC1L1 signaling in that process are unclear. Here, we constructed stable Vkorc1 and Vkorc1l1 overexpressing cell lines using lentiviruses and transfected small interfering RNAs into buffalo rat liver BRL3A cells for Vkorc1 and Vkorc1l1 overexpression and silencing, respectively. After treatment with 5 mmol/L Na-DHA for 24 h, VKORC1 and VKORC1L1 expression levels were detected by real-time PCR and western blotting. Vitamin K (VK) and factor IX (FIX) contents were detected using enzyme linked immunosorbent assays. We observed that Na-DHA inhibited VKORC1 and VKORC1L1 expression levels and reduced VK and FIX levels in rat hepatocytes. Overexpression or silencing of Vkorc1 and Vkorc1l1 increased or decreased, respectively, the production and secretion of VK and FIX in rat hepatocytes, and alleviated or aggravated the inhibitory effects of Na-DHA on VKORC1 and VKORC1L1 expression levels. Taken together, the results indicated that both VKORC1 and VKORC1L1 signaling play regulatory roles in the effects of Na-DHA on coagulation factors in rat hepatocytes.