Daptomycin Pharmacokinetics in Adolescents Undergoing Hemodialysis and Peritoneal Dialysis: A Case Series With Pharmacokinetic Modeling.

BACKGROUND: Children who undergo hemodialysis (HD) and peritoneal dialysis are at increased risk of infection. Daptomcyin is used to treat resistant infections; however, the pharmacokinetics of daptomycin in pediatric and adolescent dialysis patients remain unknown. METHODS: We report the safety and pharmacokinetics of a single intravenous 5 mg/kg dose of daptomycin for 6 individuals age 12 to 17 years old who underwent HD or continuous cycling peritoneal dialysis (CCPD). Daptomycin concentrations from all samples were determined by high-performance liquid chromatography. A non-compartmental analysis was performed to compare the pharmacokinetic parameters among HD and CCPD patients. A population pharmacokinetic model was developed to describe the concentration-time profiles of daptomycin in plasma, urine, and dialysis effluent. Monte Carlo simulations were performed to assess the pharmacodynamic outcomes. RESULTS: All subjects tolerated the single dose of daptomycin. During HD, significant drug removal was observed, compared with CCPD (26% vs 5% of total dose). A low daptomycin renal clearance (<12% of total clearance) with moderate variability (40.5%) was observed among subjects with residual renal function. An anuric and obese subject who received CCPD treatment appeared to have >80% higher daptomycin area under the plasma concentration-time curve than the other CCPD subjects. Dosing regimens that achieved predefined pharmacodynamic targets were reported. CONCLUSIONS: Daptomycin clearance was faster in 12- to 17-year-old patients receiving HD than CCPD. Administration of daptomycin immediately after HD reduces drug loss. The CCPD treatment, anuria, and obesity may increase the risk for drug accumulation. Our pharmacokinetic model can be further used to optimize dosing regimens of daptomycin in this population.

Reduction of post-surgical scarring with the use of ablative fractional CO2 lasers: A pilot study using a porcine model.

BACKGROUND AND OBJECTIVE: Wound healing inevitably leads to scarring, which leads to functional and cosmetic defects. It is the goal of this study to investigate the immediate use of ablative fractional CO2 lasers to reduce post-operative scarring secondary to surgical wounds. STUDY DESIGN/MATERIALS AND METHODS: In this prospective controlled study, 20 surgical incisions were created on each of three pigs. Fifteen of the incisions were treated with an ablative fractional CO2 laser at one of three laser settings. The remaining five incisions served as a control. Punch biopsies were taken post-operatively over time. Digital photographs were taken of each incisional scar at each time period. Blinded evaluators used a previously verified scoring system to score photographs of the incisional scars taken at the 6 month time period. RESULTS: With regards to the comparison between the three individual laser treatment groups and the control, there were no statistically significant effects for treatment (P = 0.40), time (P = 0.48), or for the interaction of time and treatment (P = 0.57). With regards to the visual assessment tool, there were no statistically significant differences between treatments for Overall Appearance (P = 0.21) or for Total Score (P = 0.24). CONCLUSIONS: In the limited setting of this pilot study, treatment of surgical incisions with ablative fractional CO2 lasers does not significantly lessen scar formation. In addition, photographic analysis was not able to demonstrate a significant difference. Future studies on this topic will need a larger sample size to better answer whether a statistically significant difference may exist. Lasers Surg. Med. 49:122-128, 2017. © 2016 Wiley Periodicals, Inc.

Vancomycin Dosing and Pharmacokinetics in Postoperative Pediatric Cardiothoracic Surgery Patients.

OBJECTIVES: This study compared vancomycin trough concentrations and pharmacokinetic parameters in pediatric cardiothoracic surgery (CTS) patients versus those in controls receiving 20 mg/kg/dose, intravenously, every 8 hours. METHODS: A retrospective study was conducted in children <18 years of age, following CTS, versus an age-and sex-matched control group. The primary objective was to determine differences in trough concentrations between groups. Secondary objectives included comparisons of pharmacokinetics between groups and development of vancomycin-associated acute kidney injury (AKI), defined as a doubling in serum creatinine from baseline. Also dosing projections were developed to target an area-under-the-curve-to-minimum inhibitory concentration (AUC:MIC) ratio of ≥400. RESULTS: Twenty-seven patients in each group were evaluated. Mean trough concentrations were significantly different between groups (CTS: 18.4 mg/L; control: 8.8 mg/L; p < 0.01). Vancomycin-associated acute kidney injury AKI was significantly higher in the CTS group than in controls (25.9% versus 0%, respectively, p<0.01). There were significant differences in vancomycin elimination rates, with a high degree of variability, but no statistical differences in other parameters. Based on dosing projections, CTS patients would require 21 to 88 mg/kg/day, with a dosage interval determined by the child's glomerular filtration rate to achieve the target AUC:MIC ≥400. CONCLUSIONS: Vancomycin dosage of 20 mg/kg/dose intravenously every 8 hours achieved significantly higher trough concentrations in CTS patients than in controls. Pharmacokinetic parameters were highly variable in CTS patients, indicating more individualization of dosage is needed. A future prospective study is needed to determine whether the revised dosage projections achieve the AUC:MIC target and to determine whether these regimens are associated with less vancomycin-associated AKI.

Treatment of cranial synostosis: the directive growth approach.

Reconstruction for single sutural synostosis typically involves cranial reshaping to correct for compensatory growth changes. Current remodeling techniques involve obliteration of both pathologic and normal sutures. Presented here is a case report describing a new approach to the treatment of single cranial synostosis. The concept involves excision of the offending suture and transient plating of the remaining functional sutures. Compensatory sutures are then allowed to direct the growth forces to the area of the synostosis, leading to the reversal of the compensatory shape deformity. This more natural approach leaves functioning sutures intact and allows for their active participation in the reshaping process.

Desired professional development pathways for clinical pharmacists.

The 2012 American College of Clinical Pharmacy (ACCP) Certification Affairs Committee was charged with developing guidelines for the desired professional development pathways for clinical pharmacists. This document summarizes recommendations for postgraduate education and training for graduates of U.S. schools and colleges of pharmacy and describes the preferred pathways for achieving, demonstrating, and maintaining competence as clinical pharmacists. After initial licensure within the state or jurisdiction in which the pharmacist intends to practice, completion of an accredited PGY1 pharmacy residency is recommended to further develop the knowledge and skills needed to optimize medication therapy outcomes. An accredited PGY2 pharmacy residency should be completed if a pharmacist wishes to seek employment in a specific therapeutic area or practice setting, if such a residency exists. Clinical pharmacists intending to conduct advanced research that is competitive for federal funding are encouraged to complete a fellowship or graduate education. Initial certification by the Board of Pharmacy Specialties (BPS) or other appropriate sponsoring organizations should be completed in the desired primary therapeutic area or practice setting within 2 years after accepting a position within the desired specific therapeutic area or practice setting. Clinical pharmacists subsequently will need to meet the requirements to maintain pharmacist licensure and board certification. Traineeships, practice-based activities, and certificate programs can be used to obtain additional knowledge and skills that support professional growth. Pharmacists are strongly encouraged to adopt a lifelong, systematic process for professional development and work with ACCP and other professional organizations to facilitate the development and implementation of innovative strategies to assess core practice competencies.

Collaboration between a college of pharmacy and a for-profit health system at an academic medical center.

PURPOSE: The genesis and growth of a successful 14-year partnership between the University of Oklahoma (OU) college of pharmacy and the OU Medical Center (OUMC) department of pharmacy are described. SUMMARY: Pursuant to a 1998 joint operating agreement, the medical center and pharmacy school have achieved a high degree of collaboration on a wide range of educational and clinical initiatives. The close relationship has conferred a number of benefits on both institutions, including (1) expanded experiential education opportunities for pharmacy students, (2) joint faculty and staff funding arrangements that have facilitated the development and accreditation of OU pharmacy residency programs, and (3) patient care initiatives that have increased awareness of pharmacists' important contributions in areas such as venous thromboembolism prophylaxis, antibiotic stewardship, and core measures compliance. In addition to the formal integration of the college of pharmacy into the OUMC organizational structure, ongoing teamwork by clinicians and administrators at the two institutions has strengthened the 14-year partnership while helping to identify creative solutions to evolving communications, technology, and reimbursement challenges. Potential growth opportunities include the expansion of pharmacy services into additional service areas and greater involvement by OU pharmacy school faculty in the training of medical, nursing, and allied health professionals. CONCLUSION: A large for-profit academic medical center and a college of pharmacy developed a successful collaboration that is mutually beneficial and provides increased clinical, educational, and scholarly opportunities, advancing the mission of both institutions.

A new method for estimation of involved BSAs for obese and normal-weight patients with burn injury.

An accurate measurement of BSA involved in patients injured by burns is critical in determining initial fluid requirements, nutritional needs, and criteria for tertiary center admissions. The rule of nines and the Lund-Browder chart are commonly used to calculate the BSA involved. However, their accuracy in all patient populations, namely obese patients, remains to be proven. Detailed BSA measurements were obtained from 163 adult patients according to linear formulas defined previously for individual body segments. Patients were then grouped based on body mass index (BMI). The contribution of individual body segments to the TBSA was determined based on BMI, and the validity of existing measurement tools was examined. Significant errors were found when comparing all groups with the rule of nines, which overestimated the contribution of the head and arms to the TBSA while underestimating the trunk and legs for all BMI groups. A new rule is proposed to minimize error, assigning 5% of the TBSA to the head and 15% of the TBSA to the arms across all BMI groups, while alternating the contribution of the trunk/legs as follows: normal-weight 35/45%, obese 40/40%, and morbidly obese 45/35%. Current modalities used to determine BSA burned are subject to significant errors, which are magnified as BMI increases. This new method provides increased accuracy in estimating the BSA involved in patients with burn injury regardless of BMI.

Interpatient and intrapatient variability in phenytoin protein binding.

The authors retrospectively assessed the relation between total and free serum concentrations and serum albumin in a sample of hospitalized patients to evaluate how well free serum concentrations can be estimated from total phenytoin serum concentrations. The authors also assessed the interpatient and intrapatient variability of the phenytoin free fraction. Paired serum samples of total and free phenytoin serum concentrations and serum albumin were obtained from 48 hospitalized patients (28 males, 20 females; mean age, 51 y; range, 13-90 y). Concomitant medications were recorded. Phenytoin free fraction and adjusted total phenytoin serum concentrations (adjusted for serum albumin) were calculated. One hundred sixty-three samples were obtained (mean, 3.4 samples per patient; range, 1-16 samples); 28 patients had more than one pair of samples obtained. Mean phenytoin free fraction was 15% +/- 7% (range, 4%-61%) for the 163 samples. The variability for the total, free, and free fractions were 65%, 75.9%, and 45.8%, respectively. There was significant variability in the phenytoin free fraction within individual patients who had more than one pair of serum concentrations obtained. The intraindividual coefficient of variation in phenytoin free fraction was 85% +/- 21.3% (range, 2%-94%). Despite strong overall correlation between the total phenytoin serum and free serum concentrations, there is excessive variability in phenytoin protein binding. Correction for serum albumin was not useful in this patient group. Because of significant interpatient and intrapatient variability in phenytoin serum concentrations, monitoring of total serum concentrations is unreliable and free phenytoin serum concentrations should be considered for monitoring in hospitalized patients.