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1.
Pediatr Pulmonol ; 59(2): 458-464, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38018665

RESUMO

INTRODUCTION: Cystic fibrosis (CF) is a genetic disorder that creates a multisystem pathology resulting in complex treatment regimens. In 2014, 43% of people with CF at an academic medical center experienced medication acquisition barriers. The creation of an integrated specialty pharmacy with an embedded CF team pharmacist was launched in 2016. In addition to filling specialty medications, this specialty pharmacy filled all patient medications through a service called total care pharmacy (TCP). This service was hypothesized to positively impact medication adherence. METHODS: Adherence analysis was performed by utilizing the proportion of days covered (PDC). PDC was analyzed during years 1, 2, and 3 of therapy. PDC was calculated for medications with at least three fills during each year. Patients with PDC less than 80% were considered nonadherent and underwent manual chart review to identify a documented reason for nonadherence. RESULTS: Patients in the first year of dornase alfa therapy had significantly higher adherence in the TCP cohort compared to non-TCP (81.3% PDC vs. 66.0%; p = .006), which was largely driven by adult patients (73.3% vs. 56.5% for pediatric). Analysis of other medications and groups did not yield statistically significant differences. Many patients who had been classified as nonadherent had valid clinical reasons that explained gaps in therapy. CONCLUSIONS: When filling medications at a specialty pharmacy integrated within the academic medication center, dornase alfa adherence was higher in the TCP group. Further studies comparing TCP with services offered by pharmacies external to the health system would better characterize the impact of TCP services.


Assuntos
Fibrose Cística , Assistência Farmacêutica , Farmácias , Adulto , Humanos , Criança , Fibrose Cística/tratamento farmacológico , Adesão à Medicação , Farmacêuticos , Estudos Retrospectivos
2.
Pediatr Pulmonol ; 59(3): 652-661, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38050809

RESUMO

INTRODUCTION: People with cystic fibrosis (pwCF) require a multidisciplinary care team due to disease complexity. The Cystic Fibrosis Foundation (CFF) notes that pharmacists are recommended, while other organizations consider pharmacists required. In 2016, the CFF initiated a grant program for CFF-accredited care centers and affiliate programs (CFF-ACCAP) to implement outpatient pharmacy services. The primary objective of this study was to compare surveys regarding pharmacy involvement in CFF-ACCAP pre- and post-grant implementation. METHODS: This was an IRB-approved, survey-based study. The surveys were distributed via the CF pharmacist-pharmacy technician and center director e-mail exchanges. RESULTS: There are currently 244 CFF-ACCAP and 158 pharmacists. Forty-two pharmacists completed the 2013 survey and 77 completed the 2023 survey. Practice site shifted from primarily the inpatient (58.5%) to outpatient settings (67.5%; p < .001). Most positions were created in the past 7 years (81%) with 50% currently or previously funded by the CFF grant program. CFF center director response decreased from 2013 to 2023 (106 vs. 48) but centers with a dedicated CF pharmacist increased from 2013 to 2023 (66%-86%; p = .014). In the 2023 survey, we received responses from 17 pharmacy technicians, who were newly included. Most of these technicians (64%) reported working in outpatient clinics. CONCLUSIONS: Since 2013, pharmacy presence has grown at CFF-ACCAP, partly due to the CFF grant program. Despite pharmacists not being required members of the multidisciplinary care team, their presence is notable in 65% of CFF-ACCAP centers, where they contribute significantly to improving the care provided for pwCF.


Assuntos
Fibrose Cística , Assistência Farmacêutica , Humanos , Fibrose Cística/tratamento farmacológico , Papel Profissional , Inquéritos e Questionários , Instituições de Assistência Ambulatorial
3.
Am J Pharm Educ ; 87(2): ajpe8954, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35351797

RESUMO

Objective. To assess the impact of the COVID-19 pandemic on pharmacy residency application/interview processes, match rate, and factors influencing match rankings at a single college of pharmacyMethods. In spring of 2020 and 2021, an anonymous survey of fourth-year pharmacy school (P4) residency applicants at one college of pharmacy was administered. Survey responses were compared to explore trends in showcase participation, number/type/geographic dispersion of applications submitted, interview invitations, grade point average (GPA), research experience, and match rate. A thematic analysis evaluated common factors influencing match rankings.Results. Responses were collected from 75 of 99 (75.8% response rate) residency-seeking students in 2020 and 79 of 94 (84.0% response rate) in 2021. Students in 2021 reported applying to a higher median number of programs, with no significant differences in mean reported number of interview invitations or match rate. The virtual American Society of Health-System Pharmacists (ASHP) Midyear Showcase led to a median reported savings of $1000 with no significant impact on perceived value. Virtual interviews led to a median reported savings of $430. Thematic analysis revealed feel/culture, location, and learning experience options as the most prevalent deciding factors for match rankings in both years.Conclusion. The pandemic led to an increase in the number of residency applications per student and yielded a net cost savings. There were no differences in number of interviews offered, match rate, or in deciding factors influencing match rankings. As the pandemic evolves, schools should maintain a flexible and dynamic approach to support students.


Assuntos
COVID-19 , Educação em Farmácia , Internato e Residência , Residências em Farmácia , Estudantes de Farmácia , Humanos , Pandemias , COVID-19/epidemiologia , Inquéritos e Questionários
4.
Ann Pharmacother ; 46(1): 137-40, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22215685

RESUMO

Aluminum toxicity has been described in patients of all ages who are receiving a variety of therapies, including dialysis, phosphate-binding medications, and parenteral nutrition (PN). Neonates are at an increased risk of aluminum toxicity because of anatomic, physiologic, and nutrition-related factors not present in other populations. In 2004, the Food and Drug Administration recommended restricting daily aluminum administration to 5 µg/kg/day and now requires that additives used to compound PN have the maximum aluminum content at expiration listed on the product label. Although the pharmacist can work to decrease aluminum toxicity in this population, it remains difficult to reach this threshold.


Assuntos
Alumínio/toxicidade , Qualidade de Produtos para o Consumidor , Rotulagem de Medicamentos , Soluções de Nutrição Parenteral/química , Soluções de Nutrição Parenteral/normas , Nutrição Parenteral/normas , Alumínio/análise , Rotulagem de Medicamentos/legislação & jurisprudência , Humanos , Recém-Nascido , Estados Unidos , United States Food and Drug Administration
5.
Curr Opin Pediatr ; 23(5): 541-4, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21799412

RESUMO

PURPOSE OF REVIEW: In 2010, the Food and Drug Administration required manufacturers of pancreatic enzymes replacement therapy (PERT) to have approval for marketing, rescinding the distribution of PERT that had been available for decades without definitive studies of efficacy and safety. Therefore, many patients on PERT had to change preparation in the last year and be placed on new formulations of PERT or switched to a new branded product altogether. This review summarizes the clinical data on these new products and reviews their general use. RECENT FINDINGS: The three new commercially available PERTs all demonstrated similar (as good as or slightly improved) abilities to increase the absorption of fat and nitrogen compared with previous PERT preparations. All preparations tests demonstrated superiority over placebo-controlled portions of the clinical trials. Side-effects seem to be no different compared with placebo. Additional PERTs are being evaluated including a nonporcine preparation which may be available in the future. SUMMARY: These new preparations, Creon, Zenpep, and Pancreaze, demonstrated improvement in the absorption of fat and nitrogen in patients with pancreatic insufficiency related to cystic fibrosis. Some patient variability to response continues, so clinicians need to continue to titrate dose and preparations based on weight gain and patient response.


Assuntos
Amilases/uso terapêutico , Terapia de Reposição de Enzimas , Insuficiência Pancreática Exócrina/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Lipase/uso terapêutico , Pancrelipase/uso terapêutico , Peptídeo Hidrolases/uso terapêutico , Fibrose Cística/complicações , Aprovação de Drogas , Insuficiência Pancreática Exócrina/etiologia , Humanos , Estados Unidos , United States Food and Drug Administration
6.
J Pediatr Pharmacol Ther ; 26(5): 427-436, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239393

RESUMO

The management of pediatric patients with asthma continues to be a major health issue. For many patients, traditional therapies have been very effective, but for a large number of patients asthma remains poorly controlled. This leads to significant morbidity and impairment to quality of life. Recently, several new biologics, as well as new dosage forms of combination inhaled drugs, have been made available for use adding to the armamentarium of therapy for specific asthma phenotypes. Biologics have shown promise in the more difficult to manage asthma patient. Approved in children, omalizumab, an anti-immunoglobulin E (anti-IgE) antibody, has been available for several years. New agents, like mepolizumab and benralizumab, directed against interleukin (IL) 5, have indications for children >6 and >12 years of age, respectively. Dupilumab, an IL-4- and IL-13-directed antibody, has been studied as well in eosinophilic asthma, with positive results. A thorough understanding of the clinical data of these agents is key, as they may greatly improve the quality of life in children with difficult-to-manage asthma.

7.
Pediatr Pulmonol ; 56(8): 2546-2552, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33913624

RESUMO

The development of modulator therapy has, for the first time, allowed direct targeting of the underlying cause of cystic fibrosis (CF), the cystic fibrosis transmembrane conductance regulator (CFTR). Patients treated with CFTR modulators have improvement in lung function and decreased rates of pulmonary exacerbations. In 2019, elexacaftor/tezacaftor/ivacaftor was approved for use in the United States, opening these therapies to 90% of patients with CF. Intolerable adverse drug reactions to CFTR modulators results in discontinuation of therapy, which can be devastating to our patients. We describe our approach to two cases, not previously reported, of rash to elexacaftor/tezacaftor/ivacaftor in patients with a previous history of cutaneous adverse reactions to dual modulator therapy that had been addressed by desensitization. Case 1 was able to tolerate elexacaftor/tezacaftor/ivacaftor after desensitization to the triple combination therapy, while in Case 2 tolerance was obtained by treating through the reaction. The loss of tolerance in these patients was unexpected, and may be a common finding in patients with history of cutaneous adverse reactions to these drugs. We hope reporting our experience, including our desensitization protocol, may benefit CF patients for whom these drug reactions may be limiting access to powerful disease altering therapies.


Assuntos
Aminofenóis , Regulador de Condutância Transmembrana em Fibrose Cística , Aminofenóis/efeitos adversos , Benzodioxóis/uso terapêutico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Combinação de Medicamentos , Humanos , Mutação
8.
J Pediatr Pharmacol Ther ; 26(7): 746-752, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34588940

RESUMO

OBJECTIVE: Vancomycin dosing requirements to achieve a target area under curve/minimum inhibitory concentration (AUC/MIC) of 400 to 600 mg•hr/L have not been established in pediatrics. Dose modeling studies and recent guidelines suggest dosing higher than historical recommendations. This study examines dosing requirements to achieve target AUC/MIC in human pediatric patients. METHODS: This retrospective study includes 77 patients, aged 1 month to 18 years, at a single center, who received at least 2 days of intravenous vancomycin with a pharmacokinetic monitoring note and calculated AUC/MIC. Dosing to achieve target AUC/MIC was evaluated by age and indication. Nephrotoxicity was also assessed. RESULTS: The mean dose required to achieve target AUC/MIC for all patients was 67.7 mg/kg/day. Adjusting for age, the mean dose required to achieve target AUC/MIC of 400 to 600 mg•hr/L was found to be statistically significantly different among 3 age cohorts: 1 month to 5 years, 6 to 12 years, and 13 to 18 years [F(2,74) = 15.32, p < 0.001], with mean requirements of 79 ± 14.1, 65.6 ± 21.1, and 53.9 ± 17.1 mg/kg/day, respectively. Dosing requirements were also found to be statistically significantly different across indications [F(6,70) = 4.84, p < 0.001]. Acute kidney injury was identified in 5 patients (6.5%). CONCLUSIONS: The vancomycin dose required to achieve target AUC/MIC in pediatrics was significantly higher in younger pediatric patients and ranged from 53.9 to 79 mg/kg/day, confirming recent guideline recommendations. Doses can be further adjusted for indication. Nephrotoxicity rates remain low compared with historical rates with single trough monitoring.

9.
Pediatr Pulmonol ; 56(10): 3209-3216, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34241975

RESUMO

OBJECTIVES: The primary objective of this study was to compare the therapeutic predictive value of area under the curve (AUC24 ) versus maximum concentration (Cmax ) in cystic fibrosis (CF) patients receiving intravenous (IV) tobramycin for a Pseudomonas aeruginosa (PsA) acute pulmonary exacerbation (APE). Acute kidney injury (AKI) incidence and the relationship between time undetectable and efficacy were also assessed. METHODS: A retrospective review was conducted in patients aged at least 1 month with a diagnosis of CF receiving IV tobramycin for treatment of a PsA APE and admitted to the University of Kentucky between August 2015 and August 2019. Patients were excluded if they had no growth of PsA on sputum culture or if two postdose tobramycin levels were not obtained following a dose adjustment of ≥20%. RESULTS: A total of 44 pediatric and 107 adult patient encounters met inclusion criteria. In patients with therapeutic success (n = 91), 75.8% had an AUC24 ≥80% and 80.3% had a Cmax ≥8 times the highest PsA minimal inhibitory concentration. There was a significant correlation between AUC24 and Cmax (r[149] = 0.727; p < 0.001). AKI incidence was significantly higher in patients receiving IV tobramycin dosed multiple times daily versus at least every 24 h (χ2 [1, 151] = 3.9; p = 0.047). CONCLUSIONS: The results of this study indicate that both AUC24 and Cmax serve as relatively accurate predictors of tobramycin efficacy. Additionally, given the significant increase in incidence of AKI, multidaily dosing of IV tobramycin should be avoided in pediatric and adult patients with CF.


Assuntos
Fibrose Cística , Infecções por Pseudomonas , Adulto , Antibacterianos/uso terapêutico , Criança , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Estudos Retrospectivos , Tobramicina
10.
Am J Respir Crit Care Med ; 180(9): 802-8, 2009 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-19729669

RESUMO

The natural history of cystic fibrosis lung disease is one of chronic progression with intermittent episodes of acute worsening of symptoms frequently called acute pulmonary exacerbations These exacerbations typically warrant medical intervention. It is important that appropriate therapies are recommended on the basis of available evidence of efficacy and safety. The Cystic Fibrosis Foundation therefore established a committee to define the key questions related to pulmonary exacerbations, review the clinical evidence using an evidence-based methodology, and provide recommendations to clinicians. It is hoped that these guidelines will be helpful to clinicians in the treatment of individuals with cystic fibrosis.


Assuntos
Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Fibrose Cística/terapia , Terapia Respiratória/métodos , Aminoglicosídeos/uso terapêutico , Fibrose Cística/tratamento farmacológico , Sinergismo Farmacológico , Humanos , beta-Lactamas/uso terapêutico
11.
J Pediatr Pharmacol Ther ; 25(2): 139-148, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32071589

RESUMO

BACKGROUND: Compared with adults, children may be at greater risk of medication errors and potential adverse effects. The American Academy of Pediatrics recommends developing mechanisms for proactively identifying patients at risk for medication-related adverse events and failed reconciliation. This study's primary purpose was to evaluate pediatric patients admitted to identify risk factors requiring pharmacist intervention during medication reconciliation (MedRec). METHODS: This prospective study included pediatric patients admitted during the study time frame until the target population of 500 patient encounters was achieved. During each admission, pharmacy staff completed a medication history, after which a pediatric pharmacist completed a MedRec, as is standard hospital practice. The primary outcome was identification of factors for high-risk transitions of care during pediatric admissions based on the need for pharmacist interventions during the MedRec process. RESULTS: In total, 331 interventions were made for 127 patients (median 2; range, 1-12). Of the 331 interventions, 196 (59.2%) were classified as being of moderate or significant severity. Although patients with at least 2 home medications were significantly more likely to require any intervention (p < 0.0001), patients with 5 or more home medications were more likely to have a significant intervention. CONCLUSION: Identifying patients with home medications could allow for focused efforts to intervene. Also, patients admitted to the PICU or those with cardiology- or endocrinology-related diagnoses should be prioritized for MedRec process, because of the likelihood of requiring multiple home medications. This strategy should be tailored to individual pediatric institutions based on internal quality control assessments and available resources.

12.
Pediatr Pulmonol ; 55(12): 3384-3390, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32910553

RESUMO

Cystic fibrosis (CF) patients, with Pseudomonas aeruginosa infection, often require repeated aminoglycoside courses for the management of acute pulmonary exacerbations (APEs). Acute kidney injury (AKI) due to aminoglycosides has been reported; little data exist regarding long-term nephrotoxicity with repeated exposure. The objective of this study was to describe the incidence of acute and chronic nephrotoxicity due to cumulative intravenous (IV) aminoglycoside exposure. This is a retrospective, observational study of pediatric and adult CF patients admitted to an academic medical center between January 1, 2006 and October 1, 2018 for APE management. Patients were eligible for inclusion if they received at least five courses of an IV aminoglycoside for at least 7 days each. Cumulative weight-based aminoglycoside dose was reported in milligrams per kilogram. For each admission, baseline and highest serum creatinine were collected to assess the incidence of AKI. The baseline and final estimated glomerular filtration rate (eGFR) were calculated to assess long-term effects on renal function. Sixty-six patients, representing greater than 700 courses, were included in the final analysis. The median cumulative weight-based aminoglycoside dose was 1183 mg/kg of tobramycin or tobramycin equivalent. Twenty percent of courses resulted in AKI; 86% were Stage 1. A repeated measure multivariate model showed colistin, piperacillin/tazobactam, vancomycin, and age were significant AKI risk factors. There was no correlation between cumulative aminoglycoside dose and change in eGFR. AKI from IV aminoglycoside exposure occurred in 20% of courses. Cumulative exposure to IV aminoglycosides in APE management was not correlated with long-term renal dysfunction.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Fibrose Cística/tratamento farmacológico , Infecções por Pseudomonas/tratamento farmacológico , Tobramicina/efeitos adversos , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Colistina/uso terapêutico , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Combinação Piperacilina e Tazobactam/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Vancomicina/uso terapêutico , Adulto Jovem
13.
Pediatr Pulmonol ; 54(1): 33-39, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30507069

RESUMO

AIM: Pseudomonas aeruginosa (PsA) is a common pathogen in cystic fibrosis (CF). Management of an acute pulmonary exacerbation (APE) caused by PsA is dual anti-pseudomonal antibiotics, a beta-lactam plus aminoglycoside. Aminoglycoside dosing in CF differs from the general population due to altered pharmacokinetics. The primary objective of this study was to utilize pharmacokinetic data from adult CF patients that received amikacin to determine the probability of target attainment for APEs caused by PsA. METHODS: This was a single-center, non-randomized, retrospective cohort study of patients >18 years with CF that received intravenous amikacin between January 2010 and July 2016. Amikacin dose, frequency, and serum concentrations were used to calculate pharmacokinetic parameters assuming a one-compartment model. Monte Carlo simulation was conducted with MIC values from CF patients with a PsA positive sputum culture between January 2014 and September 2016 to predict concentration-time profiles for different doses of amikacin. RESULTS: This study included pharmacokinetic parameters for 14 amikacin courses administered to six unique patients. The average empiric dose of amikacin was 24.3 ± 14.6 mg/kg, achieving a peak:MIC ratio ≥8 at a rate of 37% (median 5.87; IQR 3.05-10.96). A dose of 45 mg/kg/day was needed to achieve target peak:MIC ratios 90% of the time for a PsA MIC of 8 mg/L. CONCLUSION: Our data suggests it may not be clinically feasible to utilize amikacin for PsA isolates with a MIC of 16 mg/L. Current guideline dosing recommendations of amikacin 30-35 mg/kg/day are only adequate for PsA with a MIC ≤4 mg/L.


Assuntos
Amicacina/farmacocinética , Antibacterianos/farmacocinética , Fibrose Cística/tratamento farmacológico , Fibrose Cística/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Adulto , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Estudos Retrospectivos , Adulto Jovem
14.
Pharmacotherapy ; 27(4): 519-25, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17381378

RESUMO

STUDY OBJECTIVE: To describe the dose-concentration relationship of a continuous intravenous infusion of valproic acid (VPA) in pediatric patients when a dosing protocol is used. DESIGN: Retrospective and concurrent chart review. SETTING: Tertiary care, 473-bed, academic medical center with a 120-bed, dedicated children's hospital. PATIENTS: Twenty-six pediatric patients (< 18 yrs old) who received VPA according to the protocol for continuous intravenous infusions between January 1, 2004, and March 31, 2006, identified by using a pharmacy order-entry system. MEASUREMENTS AND MAIN RESULTS: Patient demographics, VPA treatment regimens, clinical responses, and safety data were recorded and analyzed. Median patient age was 8.5 years (range 1.4-16 yrs). Approximately two thirds received VPA for seizures, and one third for migraines. Patients were given a mean +/- SD VPA loading dose of 28.5 +/- 5.2 mg/kg followed by a continuous infusion rate of 1 +/- 0.2 mg/kg/hour. Mean +/- SD serum concentration measured 4.5 +/- 1.6 hours after the loading dose was 83.3 +/- 22.8 microg/ml. Steady-state concentration at 23.3 +/- 3.0 hours after the start of the continuous infusion was 80.0 +/- 26.0 microg/ml. Postload and steady-state serum concentrations were within the target concentration of 50-100 microg/ml in 77% and 69% of patients, respectively. On further analysis, when the target range was expanded to 50-125 microg/ml (125 microg/ml was deemed acceptable if no adverse effects were noted), 89% and 92% of patients, respectively, had postload and steady-state VPA serum concentrations within this range. The response rate was excellent, with nearly 85% of patients achieving a complete or partial response to therapy. Adverse effects were generally mild and uncommon. CONCLUSIONS: The continuous-infusion protocol permitted rapid intravenous loading of VPA in pediatric patients while minimizing adverse events and achieving concentrations in the upper region of the therapeutic range.


Assuntos
Revisão de Uso de Medicamentos/estatística & dados numéricos , Prontuários Médicos/estatística & dados numéricos , Ácido Valproico/uso terapêutico , Administração Oral , Adolescente , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Frutose/administração & dosagem , Frutose/análogos & derivados , Frutose/uso terapêutico , Alucinações/induzido quimicamente , Humanos , Hiperamonemia/etiologia , Infusões Intravenosas/métodos , Masculino , Taxa de Depuração Metabólica , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Fenobarbital/administração & dosagem , Fenobarbital/uso terapêutico , Fenitoína/administração & dosagem , Fenitoína/uso terapêutico , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/tratamento farmacológico , Topiramato , Resultado do Tratamento , Ácido Valproico/administração & dosagem , Ácido Valproico/farmacocinética
15.
Ann Pharmacother ; 41(3): 481-4, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17327291

RESUMO

OBJECTIVE: To review the literature concerning the use of hypertonic saline (HS) in patients with cystic fibrosis and explain the rationale for its use. DATA SOURCES: A MEDLINE search was conducted through February 2007. Search terms included hypertonic saline, mucociliary clearance, cystic fibrosis, and human DNASE 1 protein. Additional data were identified through subsequent bibliographic reviews. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated. Pertinent studies using HS in patients with cystic fibrosis were included in the analysis. DATA SYNTHESIS: Cystic fibrosis is caused by a deficiency in the cystic fibrosis transmembrane regulator gene, resulting in reduced chloride secretion and excessive sodium absorption. The most significant changes are seen in the airway lumen of the lungs. HS has been shown to improve mucociliary clearance versus placebo. A short-term efficacy trial showed a modest and variable increase in forced expiratory volume in 1 second (FEV(1)) over a 2 week period (15.0 +/- 16.0% from baseline vs 2.8 +/- 13.1% with HS 6% and NaCl 0.9%, respectively; p = 0.004). A long-term efficacy trial of either HS 7% or NaCl 0.9% twice daily for 48 weeks has shown a modest sustained improvement in FEV(1) and a significantly increased exacerbation-free survival rate (76% vs 62% for HS 7% and NaCl 0.9%, respectively; p = 0.03). CONCLUSIONS: HS preceded by a bronchodilator is an inexpensive, safe, effective additional therapy in cystic fibrosis patients with stable lung function. Its use has been associated with a modest improvement in lung function and reduced frequency of pulmonary exacerbations.


Assuntos
Fibrose Cística/tratamento farmacológico , Solução Salina Hipertônica/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Solução Salina Hipertônica/efeitos adversos
16.
Ann Pharmacother ; 41(9): 1361-7, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17652124

RESUMO

BACKGROUND: Limited data exist concerning characteristics of community-acquired Staphylococcus aureus infections (CA-SAI) in central and eastern Kentucky. OBJECTIVE: To describe the incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections from January 1, 2004 through December 31, 2005, compare the number of CA-MRSA infections between years, and contrast treatment interventions and antibiotic susceptibility patterns of CA-SAI. METHODS: A concurrent and retrospective study was conducted in 125 patients less than 18 years of age with CA-SAI admitted to the hospital/clinic based on criteria from the Centers for Disease Control and Prevention. Data on demographics, length of stay, antibiotic therapy, and antibiotic susceptibilities were collected. RESULTS: Seventy patients were included for analysis (CA-MRSA, n = 51; community-acquired methicillin-susceptible S. aureus [CA-MSSA], n = 19). No statistically significant differences were noted between the number of CA-MRSA infections and the total CA-SAI (9/15 in 2004 vs 42/55 in 2005; p = 0.15). Approximately 75% of patients with CA-SAI were admitted to the hospital with no significant difference in length of stay. Ninety percent of CA-SAI were skin and soft tissue infections. There was a significant difference between groups with cutaneous abscesses (CA-MRSA, n = 37 vs CA-MSSA, n = 6; p = 0.002). Greater than 95% of all isolates were susceptible to vancomycin and trimethoprim/sulfamethoxazole. Half of CA-MRSA patients received inappropriate antibiotic therapy with beta-lactam antibiotics or clindamycin without confirmatory disk diffusion test. Twenty-five (49%) patients with CA-MRSA received surgical debridement (S/D) and/or incision and drainage (I/D) with concomitant antibiotic therapy. Four patients with CA-MRSA were rehospitalized for subsequent infections; all 4 received appropriate antibiotic therapy. CONCLUSIONS: A noticeable increase in CA-MRSA infections with cutaneous abscess between 2004 and 2005 was noted. In patients receiving inappropriate antibiotic therapy, treatment success was attributed to concomitant S/D and I/D. Further analysis should focus on the impact of antibiotic therapy alone or in combination with S/D and I/D on the incidence of subsequent CA-MRSA infections.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecções Estafilocócicas/epidemiologia , Adolescente , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Kentucky/epidemiologia , Masculino , Resistência a Meticilina , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/terapia , Staphylococcus aureus/efeitos dos fármacos
18.
Pharmacotherapy ; 36(1): 13-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26748559

RESUMO

STUDY OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of ceftaroline in adults with cystic fibrosis (CF). DESIGN: Open-label, single-center, prospective study. SETTING: University-affiliated teaching institution. PATIENTS: Eight patients with a diagnosis of CF and a history of methicillin-resistant Staphylococcus aureus who were treated with ceftaroline between November 2013 and September 2014. INTERVENTION: All patients received at least three doses of intravenous ceftaroline 600 mg every 12 hours, administered as a 60-minute infusion, to achieve steady-state concentrations before blood sample collection. After an interim analysis of the first four patients' pharmacokinetic data, the remaining four patients received a change in dosage of ceftaroline to 600 mg every 8 hours. MEASUREMENTS AND MAIN RESULTS: Patients' blood samples were collected at two time points, 2 and 6 hours after infusion initiation, after administration of at least three doses of ceftaroline. Serum ceftaroline concentrations were determined by using a validated mass spectrometry, with a lower limit of detection of 20 ng/ml. These ceftaroline concentrations were used to estimate patient-specific pharmacokinetic parameters, and 10,000-patient Monte Carlo simulations were performed to determine the pharmacodynamic probability of target attainment (PTA) for ceftaroline in adults with CF. A PTA of 90% or higher for the desired pharmacodynamic target was considered adequate. The PTA for 60% or higher of the dosing interval during which free (unbound) drug concentrations exceed the minimum inhibitory concentration (%fT > MIC) was simulated for various MICs. Compared with values previously reported in other populations, the volume of distribution was increased in the study patients, and the estimated half-life was shorter. Monte Carlo simulations revealed that a dose of ceftaroline 600 mg every 8 hours, infused over 60 minutes, maintained a higher than 90% PTA for %fT > MIC of 60% or higher for an MIC at the susceptibility breakpoint of 1 mg/L. CONCLUSION: The pharmacokinetics of ceftaroline is altered in adults with CF, which suggests the need for modified dosing in this patient population to achieve adequate %fT > MIC. A dosage of intravenous ceftaroline 600 mg every 8 hours administered as a 60-minute infusion should be considered to achieve 60% fT > MIC.


Assuntos
Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Fibrose Cística/complicações , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antibacterianos/uso terapêutico , Cefalosporinas/administração & dosagem , Cefalosporinas/sangue , Cefalosporinas/uso terapêutico , Fibrose Cística/metabolismo , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem , Ceftarolina
19.
Pharmacotherapy ; 22(3 Pt 2): 80S-85S, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11898885

RESUMO

Aerosolized drug delivery has been used for over 50 years, but its quality and scope continue to increase. Three factors affect this form of drug delivery: the nebulizer, the compressor, and the actual drug preparation. As technology and knowledge improve, this delivery system also improves. Patients with cystic fibrosis, in particular, can benefit significantly from this form of therapy.


Assuntos
Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos , Nebulizadores e Vaporizadores , Administração por Inalação , Aerossóis , Fatores Etários , Aminoglicosídeos/administração & dosagem , Aminoglicosídeos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Química Farmacêutica/métodos , Fibrose Cística/tratamento farmacológico , Formas de Dosagem , Relação Dose-Resposta a Droga , Humanos , Tobramicina/administração & dosagem , Tobramicina/uso terapêutico
20.
J Pediatr Pharmacol Ther ; 19(3): 174-81, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25309147

RESUMO

OBJECTIVES: Increased acuity within the pediatric emergency department increases the risk of medication-related adverse events, despite the availability of validated dosing references. The eBroselow system is a standardized, web-based, bar code-enabled dosing system that eliminates the need for mathematic calculations. This study was designed to assess the accuracy of the eBroselow system and the time needed to prepare medications during pediatric simulated resuscitations compared with standard dosing references. METHODS: This is a two-treatment, two-period crossover trial in which 13 nurses from the adult emergency department who had had pediatric advanced life support training within the previous 3 years, carried out medication dosing during pediatric code simulations. Nurses were randomized to the eBroselow system or to traditional dosing references during period one and transitioned to the opposite treatment group during period two. RESULTS: Use of the eBroselow system resulted in a 24.6% increase in the accuracy of prepared medications, with a complete elimination of clinically significant errors (those ≥20% deviation from the recommended dose). In addition, on average, medications were prepared 8 minutes faster with the eBroselow system versus standard dosing references. CONCLUSIONS: Use of the eBroselow system, a standardized, bar code-based, electronic medication dosing reference, increased the accuracy of medication doses prepared during pediatric code simulations by nearly 25%, with no errors being considered clinically significant.

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