A decade of change: The evolution of pharmacy services at U.S. cystic fibrosis centers.

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.

Assessment of long-term medication adherence with cystic fibrosis: An integrated approach.

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.

A Survey of Pandemic Impacts on Pharmacy Residency Applications, Interviews, and Selection Factors.

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.

Optimization of Vancomycin Dosing to Achieve Target Area Under the Curve in Pediatrics.

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.

The Role of Biologics in the Management of Asthma in the Pediatric Patient.

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.

Comparison of the predictive value of area under the curve versus maximum serum concentration of intravenous tobramycin in cystic fibrosis patients treated for an acute pulmonary exacerbation.

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.

CFTR modulator drug desensitization: Preserving the hope of long term improvement.

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.

Incidence of nephrotoxicity with prolonged aminoglycoside exposure in patients with cystic fibrosis.

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.

Characterization of Admission Medication Reconciliations Performed by Pharmacists in a Pediatric Institution: Resource Allocation.

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.

Amikacin target achievement in adult cystic fibrosis patients utilizing Monte Carlo simulation.

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.

Pharmacokinetic and Pharmacodynamic Analyses of Ceftaroline in Adults with Cystic Fibrosis.

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.

Medication preparation in pediatric emergencies: comparison of a web-based, standard-dose, bar code-enabled system and a traditional approach.

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.

A Filtration System That Greatly Reduces Aluminum in Calcium Gluconate Injection, USP Used to Prepare Parenteral Nutrition Solutions.

OBJECTIVE: The study objective was to reduce aluminum (Al) in Calcium Gluconate Injection, US Pharmacopeia (USP) used in the preparation of parenteral nutrition (PN) solutions. METHODS: A flow-through filter containing an immobilized chelator that complexes Al from Calcium Gluconate Injection, USP as it flows through the filter was designed, refined by design modifications, and extensively tested. When a small-volume parenteral vial containing 100 mL of Calcium Gluconate Injection, USP is connected on the inlet side of the filter, and the outlet side is connected to an evacuated receiving vial, the filtered solution is drawn into the receiving vial. This constitutes a complete system to remove Al from Calcium Gluconate Injection, USP. RESULTS: The extent of Al removal is flow rate dependent. At a flow rate of 1 mL/min approximately 85% of the Al was removed from calcium gluconate solution. PN solutions have been reported to deliver 15 to 23 mcg/kg/day Al to neonates. Given that Calcium Gluconate Injection, USP provides 85% of the Al in neonatal PN solutions, removal of 85% of the Al from this source was calculated to reduce Al delivered to most neonates to <5 mcg/kg/day. CONCLUSIONS: A point-of-use, self-contained, single-use, disposable, Al-complexing filter has been created. It was calculated to reduce Al delivered in PN solutions by 72%, resulting in daily Al delivery below the level that results in Al accumulation associated with central nervous system and bone toxicity to all but the smallest (<1 kg) infants.

Impact of azithromycin treatment on macrophage gene expression in subjects with cystic fibrosis.

BACKGROUND: Azithromycin treatment improves clinical parameters in patients with CF, and alters macrophage activation from a pro-inflammatory (M1) phenotype to a pro-fibrotic, alternatively activated (M2) phenotype. The transcriptional profile of cells from patients receiving azithromycin is unknown. METHODS: Gene expression in association with macrophage polarization, inflammation, and tissue remodeling was assessed from sputum samples collected from patients with CF. Transcriptional profiles and clinical characteristics, including azithromycin therapy, were compared. RESULTS: Expression of NOS2 and TNFα was decreased in subjects receiving azithromycin, whereas expression of M2-associated genes was unaffected. Principal component analysis revealed gene expression profiles consistent with M1- (MMP9, NOS2, and TLR4) or M2-polarization (CCL18, fibronectin, and MR1) in select subject groups. These expression signatures did not significantly correlate with clinical characteristics. CONCLUSIONS: Pro-inflammatory gene expression was low in subjects receiving AZM. Genes were stratified into groupings characteristic of M1- or M2-polarization, suggesting that overall polarization status is distinct among patient groups.

Severe Malaria Complicated by G6PD Deficiency in a Pediatric Tanzanian Immigrant.

Approximately 1,500 cases of malaria are diagnosed in the United States each year. Most cases are travelers and immigrants returning from parts of the world where malaria transmission occurs. Malaria is the most frequent cause of systemic febrile illness without localizing symptoms in travelers returning from the developing world, so vigilance by providers is needed when evaluating patients returning from areas in which malaria is endemic. Despite the availability of effective treatment, malaria still accounts for more than 1 million deaths per year worldwide, with rates being disproportionately high in young children under the age of 5. We present the case of a 4-year-old refugee who emigrated from Tanzania with severe malaria due to dual infections of Plasmodium falciparum and P. ovale, whose treatment course was complicated by quinidine gluconate cardiotoxicity and glucose-6-phosphate dehydrogenase deficiency.

Design and physicochemical characterization of advanced spray-dried tacrolimus multifunctional particles for inhalation.

The aim of this study was to design, develop, and optimize respirable tacrolimus microparticles and nanoparticles and multifunctional tacrolimus lung surfactant mimic particles for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced at different pump rates by advanced spray-drying particle engineering design from organic solution in closed mode. In addition, multifunctional tacrolimus lung surfactant mimic dry powder particles were prepared by co-dissolving tacrolimus and lung surfactant mimic phospholipids in methanol, followed by advanced co-spray-drying particle engineering design technology in closed mode. The lung surfactant mimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-[phosphor-rac-1-glycerol]. Laser diffraction particle sizing indicated that the particle size distributions were suitable for pulmonary delivery, whereas scanning electron microscopy imaging indicated that these particles had both optimal particle morphology and surface morphology. Increasing the pump rate percent of tacrolimus solution resulted in a larger particle size. X-ray powder diffraction patterns and differential scanning calorimetry thermograms indicated that spray drying produced particles with higher amounts of amorphous phase. X-ray powder diffraction and differential scanning calorimetry also confirmed the preservation of the phospholipid bilayer structure in the solid state for all engineered respirable particles. Furthermore, it was observed in hot-stage micrographs that raw tacrolimus displayed a liquid crystal transition following the main phase transition, which is consistent with its interfacial properties. Water vapor uptake and lyotropic phase transitions in the solid state at varying levels of relative humidity were determined by gravimetric vapor sorption technique. Water content in the various powders was very low and well within the levels necessary for dry powder inhalation, as quantified by Karl Fisher coulometric titration. Conclusively, advanced spray-drying particle engineering design from organic solution in closed mode was successfully used to design and optimize solid-state particles in the respirable size range necessary for targeted pulmonary delivery, particularly for the deep lung. These particles were dry, stable, and had optimal properties for dry powder inhalation as a novel pulmonary nanomedicine.

Aluminum toxicity in neonatal parenteral nutrition: what can we do?

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.

Economic impact of tobramycin in patients with cystic fibrosis in a managed care population.

OBJECTIVE: Guidelines recommend chronic use of tobramycin solution for inhalation (TSI) for cystic fibrosis (CF) patients with moderate-to-severe lung disease and persistent airway Pseudomonas aeruginosa. This study evaluated the economic impact of TSI in managed care CF patients. METHODS: Patients (0-64 years) with ≥2 CF medical claims between 01/01/04-03/31/09 were identified. For TSI users, the index date was the first TSI claim in the period; for non-users, a pseudo-index date was determined and randomly assigned by simulating the distribution of index dates of TSI users. Maximum sample size was obtained for patients with ≥3 months pre- and ≥12 months post-index eligibility. Users were categorized by number of TSI prescriptions filled during 12-month post-index period as low (1 fill), medium (2-3 fills) and high adherence (≥4 fills). Differences in per member per month (PMPM) costs pre-index to post-index were analyzed using paired t-tests. RESULTS: A total of 388 TSI users (mean age 19 years, 48% female) and 444 non-users (mean age 30 years, 54% female) met study criteria. In users, total and CF-related PMPM costs decreased $959 (17%) and $113 (3%), respectively, after starting TSI. Among TSI users, CF-related inpatient PMPM costs decreased by $1171 (49%; p=0.01), while CF-related prescription PMPM costs increased by $992 (p<0.01). CF-related inpatient PMPM costs decreased by $381 (38%; p=0.16) for low and $1425 (50%; p=0.21) for medium users and decreased by $1829 (51%; p=0.02) for high users. LIMITATIONS: Limitations include use of administrative claims data, small sample size due to disease rarity, random assignment of pseudo-index date to non-users and differences in baseline characteristics between TSI users and non-users. CONCLUSION: All-cause and CF-related PMPM medical costs significantly decreased after TSI initiation. Among TSI users, total healthcare costs decreased, although not significantly, due to PMPM increases in prescription costs. A trend towards greater decrease in inpatient PMPM costs was observed with increasing TSI adherence.

Pancreatic enzyme supplementation.

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.