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Care for people with cystic fibrosis (PWCF) is highly complex and requires a multidisciplinary approach where the pharmacist plays a vital role. The purpose of this manuscript is to serve as a guideline for pharmacists and pharmacy technicians who provide care for PWCF by providing background and current recommendations for the use of cystic fibrosis (CF)-specific medications in both the acute and ambulatory care settings. The article explores current literature surrounding the role of pharmacists and pharmacy technicians, proven pharmacy models to emulate, and pharmacokinetic idiosyncrasies unique to the CF population while also identifying areas of future research. Clinical recommendations for the use of CF-specific medications are broken down by organ system including mechanism of action, adverse events, dosages, and monitoring parameters. The article also includes quick reference tables essential to the acute and chronic medication therapy management of PWCF.
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Fibrosis Quística , Servicios Farmacéuticos , Fibrosis Quística/tratamiento farmacológico , Humanos , Administración del Tratamiento Farmacológico , Farmacéuticos , Técnicos de Farmacia , Rol ProfesionalRESUMEN
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder characterized by the loss of nigrostriatal dopaminergic neurons. Mounting evidence suggests that Nrf2 is a promising target for neuroprotective interventions in PD. However, electrophilic chemical properties of the canonical Nrf2-based drugs cause irreversible alkylation of cysteine residues on cellular proteins resulting in side effects. Bach1 is a known transcriptional repressor of the Nrf2 pathway. We report that Bach1 levels are up-regulated in PD postmortem brains and preclinical models. Bach1 knockout (KO) mice were protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity and associated oxidative damage and neuroinflammation. Functional genomic analysis demonstrated that the neuroprotective effects in Bach1 KO mice was due to up-regulation of Bach1-targeted pathways that are associated with both Nrf2-dependent antioxidant response element (ARE) and Nrf2-independent non-ARE genes. Using a proprietary translational technology platform, a drug library screen identified a substituted benzimidazole as a Bach1 inhibitor that was validated as a nonelectrophile. Oral administration of the Bach1 inhibitor attenuated MPTP neurotoxicity in pre- and posttreatment paradigms. Bach1 inhibitor-induced neuroprotection was associated with the up-regulation of Bach1-targeted pathways in concurrence with the results from Bach1 KO mice. Our results suggest that genetic deletion as well as pharmacologic inhibition of Bach1 by a nonelectrophilic inhibitor is a promising therapeutic approach for PD.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Neuroprotección , Enfermedad de Parkinson/terapia , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Anciano , Anciano de 80 o más Años , Animales , Elementos de Respuesta Antioxidante , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/antagonistas & inhibidores , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Masculino , Ratones , Ratones Noqueados , Enfermedad de Parkinson/metabolismo , RatasRESUMEN
BACKGROUND: Vancomycin is commonly used to treat acute cystic fibrosis (CF) exacerbations associated with methicillin-resistant Staphylococcus aureus (MRSA). Multiple studies have demonstrated pharmacokinetic differences of antimicrobials in the CF population. Very little data exist regarding pharmacokinetics postlung transplant, but 2 studies have noted changes in tobramycin pharmacokinetics. No such studies exist evaluating vancomycin in CF patients postlung transplant. METHODS: A retrospective cohort review of CF patients who underwent lung transplantation and received vancomycin pre- and posttransplant was conducted. CF patients who underwent transplant between 2007 and 2016 at 4 medical centers throughout the United States were included. The primary endpoint was the change in elimination rate constant. The secondary endpoints were subgroup analyses of patients grouped by age, time posttransplant, and number of nephrotoxic medications. RESULTS: A total of 25 patients were included, of which just under half were pediatric. Patients were significantly older and heavier posttransplant and had higher serum creatinine and number of nephrotoxic medications. The change in elimination rate constant from pre- to posttransplant was -0.50 hr-1 which was statistically significant (P < .001). This significant decrease was consistent among all subgroups of patients evaluated with the exception of pediatric patients. CONCLUSION: Vancomycin pharmacokinetics are significantly altered in CF patients in the posttransplant setting as evidenced by a decrease in elimination rate constant. This decrease may be related to a decrease in renal clearance and higher numbers of nephrotoxic medications posttransplant. Regardless, pretransplant vancomycin regimens may not predict appropriate posttransplant regimens.
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OBJECTIVES: Vancomycin is commonly used in patients with cystic fibrosis (CF) to treat acute pulmonary exacerbations, but few guidelines exist to help dose and monitor patients. The objective of this study was to assess vancomycin use and monitoring strategies at Cystic Fibrosis Foundation (CFF)-accredited centers in hopes of developing and implementing vancomycin dosing and monitoring standards. METHODS: An anonymous national cross-sectional survey of pharmacists affiliated with CFF-accredited pediatric and/or adult centers was performed by using Surveymonkey.com. The survey consisted of 3 sections: (1) CF Center Demographic Information (10 questions); 2) vancomycin use in pediatric CF patients (31 questions); and 3) vancomycin use in adult CF patients (29 questions); it was administered from March 9, 2015, to April 13, 2015. RESULTS: The survey was completed by 31/69 (45%) pharmacists and 28 (90.3%) reported using vancomycin in the pediatric population. The most common initial starting dose for pediatric patients was 15 mg/kg/dose (57.1%) and every 6 hours was the most common dosing frequency (67.9%). The most common monitoring strategy was collection of a trough concentration (92.9%) with 57.7% of pharmacist targeting a range of 15 to 20 mg/L. The most common initial starting vancomycin dose in adults with CF was 15 mg/kg/dose (61.5%), and initial frequency of every 8 hours (73.1%). The most common monitoring strategy was a trough concentration (96.2%) with 83.3% of pharmacists reporting a goal trough range of 15 to 20 mg/L. CONCLUSIONS: The most common vancomycin dosing reported was 15 to 20 mg/kg/dose every 6 hours (pediatric) and 15 to 20 mg/kg/dose every 8 to 12 hours (adults). Serum concentrations measured to meet monitoring parameters of trough concentrations of 15 to 20 mg/L, or area under the curve to minimum inhibitory concentration ratio > 400, were the same in both pediatric and adult patients.
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BACKGROUND: Advances in cardiac operations over the last few decades, including corrective operations in early life, have dramatically increased the survival of children with congenital heart disease. However, postoperative care has been associated with neurologic complications, with seizures being the most common manifestation. The primary objective of this study is to describe the outcomes in pediatric patients who received an antiepileptic drug (AED) post-cardiac surgery. METHOD: A retrospective cohort study was performed in all patients less than 18 years of age who received an AED in the cardiovascular intensive care unit at Texas Children's Hospital from June 2002 until June 2012. Cardiac surgical patients initiated on phenobarbital, phenytoin, and levetiracetam were queried. Patients were excluded if the AED was not initiated on the admission for surgery. Patients who received 1 AED were compared to patients who received 2 AED, and differences in outcomes examined between the 3 AEDs used were evaluated. RESULTS: A total of 37 patients met the study criteria. Patients were initiated on an AED a median of 4 days following surgery and became seizure free a median of 1 day after initiation, with 65% remaining seizure free after the first dose. Half of all patients required 2 AEDs for seizure control, with a higher proportion of adolescents requiring 2 AEDs (p = 0.04). No differences were found when comparing the collected outcomes between phenobarbital, fosphenytoin, or levetiracetam. CONCLUSION: No adverse events were reported with the AEDs reviewed. Further work is necessary to evaluate long-term neurodevelopmental outcomes in this population and whether outcomes are a result of the AED or of other clinical sequelae.
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OBJECTIVES: Survey suggests that recommended doses and dosage regimens for antipseudomonal antibiotics for the treatment of acute pulmonary exacerbations in cystic fibrosis (CF) patients are not used, and one way to address these disparities is the involvement of pharmacists who are dedicated to CF. This is the first survey specifically designed for pharmacists at Cystic Fibrosis Foundation (CFF)-accredited centers to identify how tobramycin and antipseudomonal beta-lactams are being used. The purpose of this survey is to quantify this information and to promote future study to allow for implementation of tobramycin and beta-lactam dosage and monitoring standardization. METHODS: An anonymous national cross-sectional survey of pharmacists that are affliated with CFF-accredited programs was performed using Qualtrics.com. RESULTS: The survey had a 48.5% response rate. Most pediatric pharmacists (78.6%) report using extended-interval tobramycin dosage. The most common reported starting dosage was 10 mg/kg every 24 hours; most centers aim for a maximum serum concentration (Cmax) between 20 and 40 mg/L (78.6%). A total of 26 adult pharmacists reported using extended-interval dosage (96%), using an initial dosage of 10 mg/kg/day. The most common parameters used to adjust dosage were Cmax and area under the curve (AUC; 31%); the Cmax goal was 20 to 40 mg/L (84.2%). Most respondents (79%) report using beta-lactams in combination with tobramycin. Extended-infusion and continuous-infusion beta-lactams were used more in adults than pediatric patients. CONCLUSIONS: Most CF pharmacists report using extended-interval tobramycin. With the information from this survey, the establishment of future consensus recommendations by pharmacists for optimal and consistent tobramycin and antipseudomonal beta-lactam dosage and monitoring strategies needs to be considered.
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OBJECTIVES: The presence of methicillin-resistant Staphylococcus aureus (MRSA) in cystic fibrosis (CF) patients' sputa is associated with a decline in pulmonary function and increased mortality. Vancomycin is the preferred treatment for MRSA pneumonia in children. No published studies have evaluated the vancomycin dose needed to achieve goal vancomycin trough concentrations (VTCs; 15-20 mg/L) in pediatric patients with CF. The primary objective is to determine whether a vancomycin dosage of 60 mg/kg/day achieves a goal VTC in pediatric CF patients. Secondary objectives include determining the average dosage required to reach a goal VTC and the impact of achieving a goal VTC on estimated glomerular filtration rate (eGFR) and pulmonary function. METHODS: A retrospective review of pediatric patients with CF who received vancomycin was conducted. RESULTS: A total of 90 vancomycin treatment courses were analyzed. Standard vancomycin dosing (60 mg/kg/day) achieved goal VTC in 11 courses (12.2%). The mean dosage required to achieve a goal VTC for all courses was 70.6 ± 16.7 mg/kg/day. Patients who achieved goal VTCs were more often older, weighed more, and had higher serum creatinine concentrations at therapy initiation. On average, a dosage of 70.6 mg/kg/day was required to achieve a goal VTC. Despite dosages up to 120 mg/kg/day, no significant changes in renal function occurred. Achieving a goal VTC had no significant impact on eGFR or pulmonary function during therapy. CONCLUSIONS: Vancomycin dosing of 60 mg/kg/day does not reliably achieve a VTC of 15 to 20 mg/L in pediatric CF patients. Younger CF patients may require higher vancomycin doses.
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OBJECTIVE: This study aimed to establish the potential for significant energy reduction in hospitals in the United States by providing evidence of Scandinavian operational precedents with high Interior Environmental Quality (IEQ) and substantially lower energy profiles than comparable U.S. facilities. These facilities set important precedents for design teams seeking operational examples for achieving aggressive energy and interior environmental quality goals. This examination of operational hospitals is intended to offer hospital owners, designers, and building managers a strong case and concrete framework for strategies to achieve exceptionally high performing buildings. BACKGROUND: Energy efficient hospitals have the potential to significantly impact the U.S.'s overall energy profile, and key stakeholders in the hospital industry need specific, operationally grounded precedents in order to successfully implement informed energy reduction strategies. This study is an outgrowth of previous research evaluating high quality, low energy hospitals that serve as examples for new high performance hospital design, construction, and operation. Through extensive interviews, numerous site visits, the development of case studies, and data collection, this team has established thorough qualitative and quantitative analyses of several contemporary hospitals in Scandinavia and the Pacific Northwest. Many Scandinavian hospitals demonstrate a low energy profile, and when analyzed in comparison with U.S. hospitals, such Scandinavian precedents help define the framework required to make significant changes in the U.S. hospital building industry. METHODS: Eight hospitals, four Scandinavian and four Pacific Northwest, were quantitatively compared using the Environmental Protection Agency's Portfolio Manager, allowing researchers to answer specific questions about the impact of energy source and architectural and mechanical strategies on energy efficiency in operational hospitals. RESULTS: Specific architectural, mechanical, and plant systems make these Scandinavian hospitals more energy efficient than their Pacific Northwest counterparts. More importantly, synergistic systems integration allows for their significant reductions in energy consumption. CONCLUSIONS: This quantitative comparison of operational Scandinavian and Pacific Northwest hospitals resulted in compelling evidence of the potential for deep energy savings in the U.S., and allowed researchers to outline specific strategies for achieving such reductions.
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Conservación de los Recursos Energéticos/estadística & datos numéricos , Suministros de Energía Eléctrica/estadística & datos numéricos , Ambiente de Instituciones de Salud/estadística & datos numéricos , Arquitectura y Construcción de Hospitales/estadística & datos numéricos , Noroeste de Estados Unidos , Países Escandinavos y Nórdicos , Estados Unidos , United States Environmental Protection AgencyRESUMEN
BACKGROUND: Potassium supplementation is a common practice in critically ill children, especially those with heart disease. Intravenous potassium supplementation is the standard route of administration in most intensive care units. Although the enteral route is safer and thus may be a reasonable alternative, data on the efficacy of enteral potassium administration are lacking. METHODS: A change of practice to encourage use of enteral potassium was instituted in the cardiac intensive care unit at Texas Children's Hospital, and a review of this practice change was undertaken. The primary outcome of interest was the comparable efficacy of enteral and intravenous potassium administration. Patient demographic data, including urine output, diuretic use, route of potassium administration, and adverse events were documented and analyzed. RESULTS: Seventy-six patients met inclusion criteria and received 399 bolus doses of potassium (166 intravenous and 233 enteral). No patients became hyperkalemic after either route of administration. The increase in serum potassium was similar in both groups of patients. Side effects of the two routes of administration were not different. CONCLUSIONS: The efficacy of enteral potassium is comparable to intravenous potassium for potassium replacement in pediatric patients after congenital heart surgery.
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Nutrición Enteral/normas , Cardiopatías/cirugía , Unidades de Cuidado Intensivo Pediátrico , Potasio/administración & dosificación , Suplementos Dietéticos , Humanos , Pautas de la Práctica en Medicina , Texas , Resultado del TratamientoRESUMEN
We performed a retrospective case-cohort study of 50 obese pediatric patients aged 2 to 18 years who received scheduled gentamicin therapy, with serum peak and trough concentrations measured. Obese pediatric patients had significantly higher gentamicin serum peak and trough concentrations despite receiving significantly lower mg/kg of actual body weight doses of gentamicin.
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Antibacterianos/farmacocinética , Gentamicinas/farmacocinética , Obesidad/complicaciones , Suero/química , Adolescente , Antibacterianos/administración & dosificación , Niño , Preescolar , Estudios de Cohortes , Femenino , Gentamicinas/administración & dosificación , Humanos , Masculino , Obesidad/metabolismo , Estudios RetrospectivosRESUMEN
STUDY OBJECTIVE: To estimate an appropriate once-daily gentamicin dose and dosing interval for non-critical care pediatric patients older than 3 months of age without cystic fibrosis. DESIGN: Pharmacokinetic analysis of data from a retrospective medical record review. SETTING: Large academic children's hospital. PATIENTS: One hundred fourteen non-critical care pediatric patients older than 3 months of age without cystic fibrosis who received multiple-daily dosing regimens of gentamicin between September 2007 and April 2008. MEASUREMENTS AND MAIN RESULTS: Patient-specific pharmacokinetic parameters were calculated using drug concentrations obtained at steady state. Once-daily doses were extrapolated for each patient to achieve goal peak and trough concentrations. Using the average of these doses and the patient-specific pharmacokinetic parameters, theoretical once-daily peak and trough concentrations were calculated for each patient. Patient characteristics were analyzed to determine differences between patients who did and those who did not achieve adequate peak concentrations. Mean +/- SD pharmacokinetic parameters were as follows: elimination rate constant 0.32 +/- 0.06 hour(-1), half-life 2.28 +/- 0.54 hours, and volume of distribution 0.24 +/- 0.08 L/kg. The only patient demographic characteristic found to have a significant effect on the extrapolated peak concentration was age. The following age-specific once-daily doses were calculated: 3 months to less than 2 years, 9.5 mg/kg; 2 years to less than 8 years, 8.5 mg/kg; and 8-18 years, 7 mg/kg. CONCLUSION: Age was the primary factor in determining the once-daily dose of gentamicin in our pediatric population. Further prospective research is necessary to determine the safety and efficacy of these age-based, once-daily doses for gentamicin.