RESUMEN
OBJECTIVES: Current aim of rheumatoid arthritis (RA) treatment is to achieve remission in as many patients as possible. Rates of remission and clinical outcomes after treatment with abatacept in biologic-naive rheumatoid arthritis (RA) patients with early disease and an inadequate response to methotrexate (MTX) versus patients with ≥ 10 years of disease were assessed. METHODS: Data from two trials assessing the efficacy of abatacept in MTX inadequate responders were pooled for this exploratory post hoc analysis. Patients with disease duration of ≤ 2 years at baseline (early disease), originally assigned to an abatacept approximately 10 mg/kg treatment arm and entered into a long-term extension (LTE), were compared with patients with ≥ 10 years of disease (long-standing RA). Remission, DAS28-CRP, ACR 70 responses and the Routine Assessment of Patient Index Data 3 (RAPID3), improvement in physical function as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI). RESULTS: Twenty-three percent of these patients (n=108) had early disease. A higher percentage of patients with early disease achieved DAS28-CRP remission versus patients with long-standing disease (35.2% vs. 19.4% at year 1, p<0.01; 46.0% vs. 30.9% at year 3, p<0.05). In addition, a higher percentage of the subgroup with early RA achieved ACR70 responses. More patients with early RA had a meaningful improvement in their HAQ-DI (75.2% vs. 60.4%; p<0.05) and RAPID3 scores at one year (mean changes from baseline of -9.6 vs. -8.1; p=0.009). CONCLUSIONS: These data provide additional support for the possible use of abatacept in biologic-naive patients who have had inadequate response to MTX, earlier in their disease course.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Inmunoconjugados/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Abatacept , Adulto , Anciano , Evaluación de la Discapacidad , Método Doble Ciego , Femenino , Humanos , Estudios Longitudinales , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Inducción de Remisión , Factores de Tiempo , Resultado del TratamientoRESUMEN
Emerging evidence indicates that medically recalcitrant sinusitis may be associated with a prolonged and excessive state of inflammation rather than a simple bacterial infection. Corticosteroids have been anecdotally reported to be helpful in treating patients with sinusitis; however, there are no scientific studies documenting the safety and efficacy of corticosteroid therapy in sinusitis. To resolve the controversy over whether corticosteroids promote or inhibit the resolution of sinusitis, we present a prospective study of 80 rabbits with surgically introduced pseudomonal sinusitis that were then treated in one of four arms: control, ceftazidime, methylprednisolone, and ceftazidime with methylprednisolone. Sinus cavities were then evaluated after 5, 14, 21, and 28 days of treatment both by histologic inflammation grading and bacterial quantification. Results showed a significant decrease in bacterial loads in both the antibiotic and antibiotic with steroid arms over control animals, although no difference was seen between the two. Histologic grading showed a similar trend, although statistical significance was not obtained. Overall, this study demonstrated no clear advantage of steroids in the treatment of sinus infections using this model. At the same point, no significant reduction in the effectiveness of antibiotic therapy was seen with concurrent steroid use. A number of limitations of the animal model are noted and the need for human studies in this area is discussed.
Asunto(s)
Antiinflamatorios/uso terapéutico , Ceftazidima/administración & dosificación , Metilprednisolona/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Animales , Antiinflamatorios/administración & dosificación , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Masculino , Metilprednisolona/administración & dosificación , Infecciones por Pseudomonas/inmunología , Infecciones por Pseudomonas/patología , Conejos , Distribución Aleatoria , Sinusitis/inmunología , Sinusitis/patología , Resultado del TratamientoRESUMEN
OBJECTIVES: To determine the effectiveness of bilateral submandibular and parotid duct ligation on children with severe neuromuscular impairment and chronic aspiration of salivary secretions and to identify any predictable anatomical connections between the submandibular duct and sublingual glands. DESIGN: Case series; retrospective anatomical study of adult cadaveric submandibular gland specimens. SETTING: Academic tertiary referral medical center. PATIENTS: Five children with severe neuromuscular impairment and recurrent aspiration pneumonitis. INTERVENTION: The children underwent bilateral submandibular and parotid duct ligation. The oral cavities of 8 cadavers were dissected to identify anatomical connections between the submandibular duct and sublingual glands. MAIN OUTCOME MEASURES: Incidence of postoperative aspiration pneumonitis; gross anatomical connections between the submandibular duct and sublingual gland in cadaveric specimens. RESULTS: No postoperative airway obstruction, infection, or xerostomia was noted, and technetium scanning confirmed control of salivary secretions from major salivary glands. Caregivers noted diminished salivary secretions and no aspiration pneumonia. CONCLUSIONS: This new, simple intraoral procedure controls aspiration pneumonitis with minimal surgical dissection and has less morbidity than procedures involving major salivary gland excision. Ranula formation, a common complication of submandibular duct transposition, is unlikely in this procedure because the sublingual ducts are not interrupted.
Asunto(s)
Neumonía por Aspiración/cirugía , Conductos Salivales/cirugía , Sialorrea/cirugía , Adolescente , Adulto , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Lactante , Ligadura , Masculino , Glándula Parótida/cirugía , Complicaciones Posoperatorias/etiología , Glándula Submandibular/cirugía , Resultado del TratamientoRESUMEN
Pharmacists have an integral role in the care of ICU patients, including those with infections. Antibiotics continue to be among the most widely prescribed drugs in the ICU environment. This article focuses on the impact pharmacists have on the care and economics for the critically ill infected patient and on mechanisms used in hospitals to control antibiotic misuse. Numerous studies point to inappropriate antibiotic use and resultant selection pressure on antimicrobial resistance. The critical care pharmacist can impact this prescribing by assuring optimal pharmacotherapy specific for the organism and associated disease. Furthermore, policies have been implemented to modify antibiotic use, including formulary manipulations, antibiotic stop order forms, care plans, antibiotic cycling, oral switching, and computer-assisted antimicrobial therapy. Future research is needed to determine the optimal method for preventing resistance. However, a multidisciplinary approach to rational antimicrobial use is suggested.
Asunto(s)
Farmacorresistencia Microbiana , Farmacias , Medicina Preventiva , Antibacterianos/uso terapéutico , Costos de los Medicamentos , Humanos , Unidades de Cuidados Intensivos , Farmacología Clínica/métodosRESUMEN
This study was conducted to assess the pulmonary extraction of dobutamine. Eleven patients admitted to the general surgical intensive care unit, with varying diagnoses requiring dobutamine as part of their therapeutic intervention, were included. A single simultaneous sample was drawn, at the clinically required rate of infusion, from the radial and pulmonary artery catheter sites. Total dobutamine clearance was determined using the pulmonary artery (pre-lung) sample. The mean +/- SD total dobutamine clearance was 82 +/- 67 mL.kg-1.min-1 a value which is larger than the average cardiac output of plasma of 56 +/- 20 mL.kg-1.min-1. The mean percent pulmonary extraction fraction of dobutamine was 3.6% +/- 22.5% (range -34-52), a value within the 9% coefficient of variability (CV) of the assay. However, five patients had pulmonary extraction greater than the CV of the assay. Of these five patients, three had "negative" extraction values, and two had "positive" extraction values. There was no relationship between the percent pulmonary extraction of dobutamine and the rate or duration of dobutamine infusion before sampling. The results show that the extraction of dobutamine by the lungs is minimal.
Asunto(s)
Enfermedad Crítica , Dobutamina/farmacocinética , Pulmón/metabolismo , Procedimientos Quirúrgicos Operativos , Adulto , Anciano , Anciano de 80 o más Años , Infecciones Bacterianas/sangre , Infecciones Bacterianas/metabolismo , Gasto Cardíaco , Cuidados Críticos , Dobutamina/administración & dosificación , Dobutamina/sangre , Femenino , Humanos , Infusiones Intravenosas , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Arteria Pulmonar , Arteria Radial , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/metabolismo , Choque Séptico/sangre , Choque Séptico/metabolismoRESUMEN
OBJECTIVE: To delineate the variability in the pharmacokinetics of dobutamine over time in an unstable critically ill adult surgical patient population concurrently receiving therapeutic interventions to optimize oxygen delivery and consumption variables. DESIGN: Prospective study. SETTING: University hospital adult surgical intensive care unit. PATIENTS: Sixteen hemodynamically unstable adults (aged 18 to 84 yrs) requiring dobutamine for inotropic support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Samples for dobutamine serum concentration determination were collected at selected times during therapy, following at least 30 mins of a constant infusion rate and measured using high-performance liquid chromatography. Clearance and changes in clearance were calculated. A first-order pharmacokinetic model was validated by lack of dependence of dose on clearance and an established graphical method. Mean +/- SD infusion rate of dobutamine was 8.2 +/- 5.7 micrograms/kg/min (range 1.7 to 22.3), which resulted in a mean serum concentration of 214 +/- 183 ng/mL (range 15 to 759). The correlation between infusion rate and steady-state dobutamine concentration was r2 = .67. Variability in steady-state dobutamine concentration at various infusion rates was large. Clearance at initial pharmacokinetic analysis averaged 58.4 +/- 33.3 mL/kg/min (range 19 to 120). The percent change in calculated clearance varies from a 72% decrease to an 88% increase, with the greatest variability in clearance occurring during the first 24 hrs of therapy. There was little correlation between initial dobutamine clearance and weight (r2 = .10), net cumulative fluid balance before initiation of dobutamine (r2 < .01), age (r2 = .20), and estimated creatinine clearance (r2 = .09). CONCLUSIONS: Dobutamine pharmacokinetics in adult critically ill patients is best described by a first-order model. Pathophysiologic factors may have an effect on the pharmacokinetics of dobutamine which appears to change over time. Both inter- and intrapatient variability in infusion rate administered and resultant serum concentrations were wide, suggesting that infusion rate should be guided by clinical end points rather than by predetermined values.
Asunto(s)
Enfermedad Crítica , Dobutamina/farmacocinética , Procedimientos Quirúrgicos Operativos , Adolescente , Adulto , Anciano , Análisis de Varianza , Cromatografía Líquida de Alta Presión/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Dobutamina/administración & dosificación , Dobutamina/sangre , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Consumo de Oxígeno/efectos de los fármacos , Estudios Prospectivos , Factores de TiempoRESUMEN
Direct care providers in home healthcare demonstrate strong support for the patient's right to self-determination. The increasing use of home healthcare, the higher the acuity of patients receiving care in the home, and the collaborative relationship between care providers and patients dictate that professionals in the home care practice arena possess a high comfort level with the patient's right to self-determination. This study was conducted to validate this hypothesis.