RESUMEN
PURPOSE: To describe a pharmacist-managed virtual consult service practice model for rheumatology patients and evaluate its initial impact on compliance with institutional critical care guidelines for biologic response modifiers (BRMs). SUMMARY: Pharmacologic care of patients with rheumatologic conditions often revolves around the use of BRMs. While these drugs are generally well tolerated, nearly all of them carry risks for serious adverse events. The severity of these possible problems necessitates a thorough initial and ongoing clinical workup. Based on results of a needs assessment, a virtual consult service was introduced at the University of Illinois Hospital and Health Sciences System (UI Health) in August 2018 to integrate clinical, specialty pharmacy, and therapeutic infusion services for proactive medication and safety management of patients with rheumatologic conditions requiring treatment with BRMs. The consult service was managed by an embedded clinical pharmacist and a postgraduate year 1 specialty pharmacy resident, who evaluated each request for therapy appropriateness prior to submission for insurance approval. CONCLUSION: Forty-one percent of the pharmacy benefit consult orders required a pharmacist intervention prior to referral to the specialty pharmacy. All consults (100%) adhered to the safety management guidelines for BRMs after review by the pharmacist. The pharmacist-managed virtual consult service is a novel practice model in specialty pharmacy that permits pharmacists to manage multiple patients simultaneously, virtually, and with optimal impact on medication selection and management at or before the point of prescribing.
Asunto(s)
Artritis Reumatoide , Preparaciones Farmacéuticas , Servicio de Farmacia en Hospital , Humanos , Farmacéuticos , Derivación y ConsultaRESUMEN
Synovial macrophages are crucial in the development of joint inflammation and bone damage; however, the pathways that control macrophage remodeling in inflammatory M1 cells or bone-eroding osteoclasts are not fully understood. We determined that elevated IL-7R/CD127 expression is the hallmark of rheumatoid arthritis (RA) M1 macrophages and that these cells are highly responsive to interleukin-7 (IL-7)-driven osteoclastogenesis. We established that lipopolysaccharide (LPS), interferon-γ (IFNγ), and tumor necrosis factor-α (TNFα), the classic M1 macrophage mediators, enhance IL-7R expression in RA and murine macrophages. The local expression of IL-7 provokes arthritis, predominantly through escalating the number of F480+iNOS+ cells rather than CD3+ T cells. Ectopic LPS injection stabilizes IL-7-induced arthritis by increasing myeloid IL-7R expression, in part via IFNγ induction. Hence, in RAG-/- mice, IL-7-mediated arthritis is suppressed because of the reduction in myeloid IL-7R expression due to the lack of IFNγ. Moreover, the amelioration of IL-7-induced arthritis by anti-TNF therapy is due to a decrease in the number of cells in the unique F480+iNOS+IL-7R+CCL5+ subset, with no impact on the F480+Arginase+ cell or CD3+ T cell frequency. Consistent with the preclinical findings, the findings of a phase 4 study performed with RA patients following 6 months of anti-TNF therapy revealed that IL-7R expression was reduced without affecting the levels of IL-7. This study shifts the paradigm by discovering that IL-7-induced arthritis is dependent on F480+iNOS+IL-7R+CCL5+ cell function, which activates TH-1 cells to amplify myeloid IL-7R expression and disease severity.
Asunto(s)
Artritis Reumatoide/patología , Interleucina-7/metabolismo , Macrófagos/patología , Animales , Células de la Médula Ósea/metabolismo , Diferenciación Celular , Humanos , Interferón gamma/metabolismo , Lipopolisacáridos , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Células Mieloides/metabolismo , Osteoclastos/metabolismo , Receptores de Interleucina-7/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Decades of research have been devoted to developing effective, safe, and convenient anticoagulant agents. In recent years, much emphasis has been placed on the development of direct thrombin inhibitors (DTIs) that offer benefits over agents like heparin and warfarin including the inhibition of both circulating and clot-bound thrombin; a more predictable anticoagulant response, because they do not bind to plasma proteins and are not neutralized by platelet factor 4; lack of required cofactors, such as antithrombin or heparin cofactor II; inhibiting thrombin-induced platelet aggregation; and absence of induction of immune-mediated thrombocytopenia. Various injectable DTIs are currently available and used for many indications. In addition, research is now focusing on oral DTIs that seem promising and offer various advantages, such as oral administration, predictable pharmacokinetics and pharmacodynamics, a broad therapeutic window, no routine monitoring, no significant drug interactions, and fixed-dose administration.
Asunto(s)
Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Trombina/antagonistas & inhibidores , Anticoagulantes/administración & dosificación , Arginina/análogos & derivados , Fibrilación Atrial/complicaciones , Bencimidazoles/administración & dosificación , Bencimidazoles/farmacología , Bencimidazoles/uso terapéutico , Dabigatrán , Fibrinolíticos/administración & dosificación , Fibrinolíticos/farmacología , Semivida , Hirudinas/administración & dosificación , Hirudinas/farmacología , Humanos , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/farmacología , Ácidos Pipecólicos/administración & dosificación , Ácidos Pipecólicos/farmacología , Piridinas/administración & dosificación , Piridinas/farmacología , Piridinas/uso terapéutico , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , SulfonamidasRESUMEN
Decades of research have been devoted to developing effective, safe, and convenient anticoagulant agents. In recent years, much emphasis has been placed on the development of direct thrombin inhibitors (DTIs) that offer benefits over agents like heparin and warfarin including the inhibition of both circulating and clot-bound thrombin; a more predictable anticoagulant response, because they do not bind to plasma proteins and are not neutralized by platelet factor 4; lack of required cofactors, such as antithrombin or heparin cofactor II; inhibiting thrombin-induced platelet aggregation; and absence of induction of immune-mediated thrombocytopenia. Various injectable DTIs are currently available and used for many indications. In addition, research is now focusing on oral DTIs that seem promising and offer various advantages, such as oral administration, predictable pharmacokinetics and pharmacodynamics, a broad therapeutic window, no routine monitoring, no significant drug interactions, and fixed-dose administration.
Asunto(s)
Anticoagulantes/farmacología , Antitrombinas/farmacología , Administración Oral , Anticoagulantes/uso terapéutico , Antitrombinas/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Humanos , Infusiones Intravenosas , Inyecciones Subcutáneas , Dosis Máxima Tolerada , Sensibilidad y EspecificidadRESUMEN
For over 50 years, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to traditional agents such as unfractionated heparin and oral vitamin K antagonists such as warfarin. These traditional agents are fraught with limitations that complicate their clinical use. A variety of novel anticoagulants with improved pharmacologic and clinical profiles have recently been introduced or are in development, offering benefits over traditional therapies. Specifically, progress has been made in the development of low-molecular-weight heparins, factor Xa inhibitors, and direct thrombin inhibitors. Because of their convenience and ease of use, some of these novel compounds are competing with the traditional anticoagulants and are needed additions to the antithrombotic arsenal.
Asunto(s)
Anticoagulantes/uso terapéutico , Antitrombina III/uso terapéutico , Antitrombinas/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Trombosis/tratamiento farmacológico , Anticoagulantes/farmacología , Antitrombina III/farmacología , Antitrombinas/farmacología , Heparina de Bajo-Peso-Molecular/farmacología , HumanosRESUMEN
STUDY OBJECTIVE: To evaluate dosing requirements and monitoring patterns of low-molecular-weight heparin (LMWH) when used in high-risk pregnancy. DESIGN: Retrospective, observational, cohort study. SETTING: University-affiliated medical center. PATIENTS: Forty-nine women treated with LMWH between 2001 and 2005 for either prophylaxis or treatment of venous thromboembolism during pregnancy and monitored with antifactor Xa activity. MEASUREMENTS AND MAIN RESULTS: Data were obtained on 53 pregnancies in the 49 women. The primary outcome was change in dosing requirements of LMWH throughout pregnancy as determined by the corresponding antifactor Xa activity peak levels. Mean starting doses of twice-daily enoxaparin and doses most proximate to delivery were 39.2 mg (range 30-60 mg) and 55.0 mg (range 30-100 mg, p=0.06), respectively, for the prophylaxis group and 83.0 mg (range 30-180 mg) and 85.7 mg (range 30-160 mg, p=0.41), respectively, for the therapeutic group. Weight-based mean starting doses and doses most proximate to delivery were 0.46 and 0.62 mg/kg (p=0.03), respectively, for the prophylaxis group and 0.90 and 0.87 mg/kg (p=0.29), respectively, for the therapeutic group. Dose changes were required in 9 (69%) of 13 pregnancies and 21 (55%) of 38 pregnancies (data from two of the 40 pregnancies were excluded-one in a patient receiving dalteparin, and one in a patient with mitral valve replacement who had higher antifactor Xa goals) in the prophylaxis and therapeutic groups, respectively, to achieve target antifactor Xa activity. The weight-based prophylactic dose was consistently 0.6 mg/kg in all three trimesters, achieving a mean ± SD target antifactor Xa activity of 0.39 ± 0.18 units/ml, whereas the therapeutic dose was 0.9 mg/kg to maintain antifactor Xa activity of 0.71 ± 0.22 units/ml. CONCLUSION: Dose changes for LMWH throughout pregnancy as guided by antifactor Xa activity were common. A significant increase in the LMWH dose requirements in the prophylactic group suggests that more frequent monitoring of antifactor Xa activity may be appropriate in pregnant patients to maintain target anticoagulant levels.