Cystic Fibrosis Foundation Pulmonary Guidelines. Use of Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy in Patients with Cystic Fibrosis.

RATIONALE: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators are a new class of medications targeting the underlying defect in CF. Ivacaftor (IVA) and IVA combined with lumacaftor (LUM; IVA/LUM) have been approved by the U.S. Food and Drug Administration (FDA) for use in patients with CF. However, the FDA label for these medications encompasses patient groups that were not studied as part of the drug approval process. CF clinicians, patients, and their families have recognized a need for recommendations to guide the use of these medications. OBJECTIVE: Develop evidence-based guidelines for CFTR modulator therapy in patients with CF. METHODS: A multidisciplinary committee of CF caregivers and patient representatives was assembled. A methodologist, an epidemiologist, a medical librarian, and a biostatistician were recruited to assist with the literature search, evidence grading, and generation of recommendations. The committee developed clinical questions using the Patient-Intervention-Comparison-Outcome format. A systematic review was conducted to find relevant publications. The evidence was then evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach, and recommendations were made based on this analysis. RESULTS: For adults and children aged 6 years and older with CF due to gating mutations other than G551D or R117H, the guideline panel made a conditional recommendation for treatment with IVA. For those with the R117H mutation, the guideline panel made a conditional recommendation for treatment with IVA for 1) adults aged 18 years or older, and 2) children aged 6-17 years with a forced expiratory volume in 1 second (FEV1) less than 90% predicted. For those with the R117H mutation, the guideline panel made a conditional recommendation against treatment with IVA for 1) children aged 12-17 years with an FEV1 greater than 90% predicted, and 2) children less than 6 years of age. Among those with two copies of F508del, the guideline panel made a strong recommendation for treatment with IVA/LUM for adults and children aged 12 years and older with an FEV1 less than 90% predicted; and made a conditional recommendation for treatment with IVA/LUM for 1) adults and children aged 12 years or older with an FEV1 greater than 90% predicted, and 2) children aged 6-11 years. CONCLUSIONS: Using the GRADE approach, we have made recommendations for the use of CFTR modulators in patients with CF. These recommendations will be of help to CF clinicians, patients, and their families in guiding decisions regarding use of these medications.

Vancomycin Dosing and Monitoring in the Treatment of Cystic Fibrosis: Results of a National Practice Survey.

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.

Tobramycin and Beta-Lactam Antibiotic Use in Cystic Fibrosis Exacerbations: A Pharmacist Approach.

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.

Use and perception of herbal and dietary supplements in the Hutterites of South Dakota.

BACKGROUND: South Dakota is home to 6,000 Hutterites, the largest population of Hutterites in the United States. Observation of frequent supplement use by this population prompted the current survey based study. Use of supplements is on the rise with around 53 percent of Americans reporting at least one herbal and dietary supplement (HDS). Use and perception of HDS has not previously been evaluated in the Hutterite population. METHODS: Participants were 18 years of age and older and had to be present at the time of survey administration. Surveys were administered before and after an educational presentation at five colonies to volunteer participants. Survey data was analyzed using descriptive analysis and chi-square tests. RESULTS: One-hundred and six surveys were completed with 81.1 percent being female. Approximately 78 percent reported using at least one type of HDS, with an average of 2.7 (SD = 1.4) supplements per person. Women were more likely to report supplement use than men. Hutterites reported they felt HDS were safer than prescription medications. Education was effective on some aspects such as telling their doctor if they are taking HDS. CONCLUSIONS: Some study limitations included small sample size, possible lack of survey understanding, and the limited number of male participants. The frequency of HDS use in South Dakota Hutterites appears to be very high. Baseline knowledge on the safety and regulation of HDS reveals that education of this population is needed. Further investigation of HDS use in Hutterites is warranted.