Cost-Effectiveness Analysis of a Once-Daily Single-Inhaler Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease (COPD) Using the FULFIL Trial: A Spanish Perspective.

Purpose: To evaluate the cost-effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) vs twice-daily budesonide/formoterol (BUD/FOR) in patients with symptomatic chronic obstructive pulmonary disease (COPD) at risk of exacerbations, from the Spanish National Healthcare System perspective. Patients and Methods: The validated GALAXY-COPD model was used to simulate disease progression and predict healthcare costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) over a 3-year time horizon for a Spanish population. Patient characteristics from published literature were supplemented by data from FULFIL (NCT02345161), which compared FF/UMEC/VI vs BUD/FOR in patients with symptomatic COPD at risk of exacerbations. Treatment effects, extrapolated to 3 years, were based on Week 24 results in the FULFIL intent-to-treat population, including change in forced expiratory volume in 1 second, St. George's Respiratory Questionnaire score, and exacerbation rates. Treatment, exacerbations, and COPD management costs (2019€) were informed by Spanish public sources and published literature. A 3% discount rate for costs and benefits was applied. One-way sensitivity and scenario analyses, and probabilistic sensitivity analysis (PSA), were performed. Results: FF/UMEC/VI treatment led to fewer moderate and severe exacerbations (2.126 and 0.306, respectively) vs BUD/FOR (2.608 and 0.515, respectively), with a mean incremental cost of €69 and gain of 0.107 QALYs, which resulted in an ICER of €642 per QALY gained. In sensitivity analyses, the ICER was most sensitive to treatment effect variations in exacerbations and healthcare resource utilization/event costs. Overall, 95% of 1000 PSA simulations resulted in an ICER less than €11,000 per QALY gained for FF/UMEC/VI vs BUD/FOR, confirming robustness of the results. The probability of FF/UMEC/VI being cost-effective vs BUD/FOR was 100% at a willingness-to-pay threshold of €30,000 per QALY gained. Conclusion: At the accepted Spanish ICER threshold of €30,000, FF/UMEC/VI represents a cost-effective treatment option vs BUD/FOR in patients with symptomatic COPD at risk of exacerbations.

Accuracy of Currently Used Paper Burn Diagram vs a Three-Dimensional Computerized Model.

Burn units have historically used paper diagrams to estimate percent burn; however, unintentional errors can occur. The use of a computer program that incorporates wound mapping from photographs onto a three-dimensional (3D) human diagram could decrease subjectivity in preparing burn diagrams and subsequent calculations of TBSA burned. Analyses were done on 19 burned patients who had an estimated TBSA burned of ≥20%. The patients were admitted to Shriners Hospitals for Children or the University of Texas Medical Branch in Galveston, Texas, from July 2012 to September 2013 for treatment. Digital photographs were collected before the patient's first surgery. Using BurnCase 3D (RISC Software GmbH, Hagenberg, Austria), a burn mapping software, the user traced partial- and full-thickness burns from photographs. The program then superimposed tracings onto a 3D model and calculated percent burned. The results were compared with the Lund and Browder diagrams completed after the first operation. A two-tailed t-test was used to calculate statistical differences. For partial-thickness burns, burn sizes calculated using Lund and Browder diagrams were significantly larger than those calculated using BurnCase 3D (15% difference, P < .01). The opposite was found for full-thickness burns, with burn sizes being smaller when calculated using Lund and Browder diagrams (11% difference, P < .05). In conclusion, substantial differences exist in percent burn estimations derived from BurnCase 3D and paper diagrams. In our studied cohort, paper diagrams were associated with overestimation of partial-thickness burn size and underestimation of full-thickness burn size. Additional studies comparing BurnCase 3D with other commonly used methods are warranted.

Patterns and Economic Burden of Hospitalizations and Exacerbations Among Patients Diagnosed with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare and fatal restrictive respiratory disease under the idiopathic lung disease (ILD) class. IPF is a form of chronic, progressive fibrosing interstitial pneumonia and has more scarring, less inflammation, and poorer prognosis than most other ILD forms. Exacerbation of IPF is rapid, with unpredictable deterioration of lung function, and is associated with short-term mortality. The American Thoracic Society (ATS) evidence-based guidelines for diagnosis and management of IPF reports that the incidence of acute exacerbations is between 5%-10%. Limited real-world evidence has been identified in the United States that assesses patterns of hospitalization, exacerbation of IPF, and the associated economic burden. OBJECTIVES: To (a) characterize patients newly diagnosed with IPF and (b) examine incidence rates and costs of all-cause hospitalizations, IPF-related hospitalizations, and exacerbations. METHODS: A retrospective analysis was performed with a national commercial claims database from calendar years 2006 to 2011. Newly diagnosed IPF patients were identified with either ≥ 2 claims for idiopathic fibrosing alveolitis (IFA) or ≥ 1 claim for IFA and ≥ 1 claim for postinflammatory pulmonary fibrosis and a lung biopsy or thoracic high-resolution computed tomography within 90 days of the first claim for IFA (index date). IPF-related hospitalizations and possible IPF exacerbations were defined based on diagnoses recorded on event claims. Frequency, incidence rate, duration of events, and associated costs from the third-party payer's perspective were estimated. RESULTS: Among 1,735 identified IPF patients, 38.6% had at least 1 all-cause hospitalization; 10.8% had IPF-related hospitalizations; 4.6% had suspected IPF exacerbations leading to hospitalization; and 72.1% had suspected IPF exacerbations leading to urgent outpatient visits during the 1-year post-index period. Incident rates for these 4 events were 83 (95% CI = 79-88), 17 (95% CI = 14-19), 7 (95% CI = 6-9), and 277 (95% CI = 269-286) per 100 person-years, respectively. Average costs per event were $13,987 (SD = $41,988), $16,812 (SD = $66,399), $14,731 (SD = $85,468), and $444 (SD = $1,481), respectively. CONCLUSIONS: Hospitalizations and possible exacerbations among patients with IPF were costly. Appropriate management of IPF needs to be considered to help slow IPF disease progression. DISCLOSURES: Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) provided funding for this study. Yu and Devercelli are currently salaried employees of BIPI. Wu, Chuang, Wang, Pan, and Benjamin are currently employees of Evidera, which provides consulting and other research services to pharmaceutical, device, government, and nongovernment organizations. In their salaried positions, they work with a variety of companies and organizations and are precluded from receiving payment or honoraria directly from these organizations for services rendered. Evidera received funding from BIPI to conduct the analysis. Coultas was previously a paid consultant of BIPI. The contents do not represent the views of the Department of Veterans Affairs or the U.S. government. This manuscript does not contain clinical studies or patient data. The authors have full control of all primary data, and they agree to allow the journal to review their data if requested. All authors meet the criteria for authorship as recommended by the International Committee of Medical Journal Editors, and they are fully responsible for all content and editorial decisions and were involved at all stages of manuscript development. The manuscript was drafted by Benjamin, Wu, and Yu and revised by Wang, Pan, Yu, Coultas, and Devercelli. The study was designed by Yu, Wu, Chuang, Wang, Benjamin, and Coultas. Statistical analysis was conducted by Wu, Chuang, and Wang. Senior review was provided by Coultas and Devercelli.

Using a 3D tool to document and determine graft loss: A mini-review and case report.

In severe burns, accurate determination of burn wound size and areas of debridement and graft loss is challenging. In this case report, we describe the use of 3D wound measurement software (BurnCase 3D, RISC Software GmbH, Hagenberg, Austria) in a 29-year-old patient with burns covering 92% of the total body surface area. BurnCase 3D was used to assess burn and monitor all surgical interventions. The software allowed us to calculate areas of graft loss and graft take throughout the acute hospitalization (until 90% of the wounds were covered with homografts). It also enabled preoperative planning for wound coverage and blood loss. Thus, BurnCase 3D appears to be a useful tool for accurate determination of burn wound areas and preoperative planning. However, whether the benefit of more efficient preoperative planning overcomes the disadvantage of the additional time needed to document the wound using the software needs to be evaluated further.

The effect of lower body burns on physical function.

OBJECTIVE: To attenuate burn-induced catabolism, patients are often enrolled in a resistance exercise program as part of their physical rehabilitation. This study assessed how lower body burn locations affected strength and cardiopulmonary function. METHODS: Children enrolled in an exercise study between 2003 and 2013, were 7-18 years of age, and burned ≥30% of their total body surface area were included. Analysis of variance was used to model the relationship of lower body strength (PTW) and cardiopulmonary function (VO2peak) due to burns which traverse the subject's lower body joints. RESULTS: There was a significant relationship between PTW and burns at the hip and toe joints, showing a 26 N m/kg (p=0.010) and 33 N m/kg (p=0.013) decrease in peak torque, respectively. Burns at the hip joint corresponded to a significant decrease in VO2peak by 4.9 ml kg(-1) min(-1) (p=0.010) in peak cardiopulmonary function. CONCLUSION: Physical function and performance are detrimentally affected by burns that traverse specific lower body joints. The most significant relationship on exercise performance was that of hip joint burns as it affected both strength and cardiopulmonary measurements. Ultimately, burns at hip and toe joints need to be considered when interpreting exercise test results involving the lower body.

High tidal volume decreases adult respiratory distress syndrome, atelectasis, and ventilator days compared with low tidal volume in pediatric burned patients with inhalation injury.

BACKGROUND: Inhalation injury, which is among the causes of acute lung injury and acute respiratory distress syndrome (ARDS), continues to represent a significant source of mortality in burned patients. Inhalation injury often requires mechanical ventilation, but the ideal tidal volume strategy is not clearly defined in burned pediatric patients. The aim of this study was to determine the effects of low and high tidal volume on the number of ventilator days, ventilation pressures, and incidence of atelectasis, pneumonia, and ARDS in pediatric burned patients with inhalation injury within 1 year post burn injury. METHODS: From 1986 to 2014, inhalation injury was diagnosed by bronchoscopy in pediatric burned patients (n = 932). Patients were divided into 3 groups: unventilated (n = 241), high tidal volume (HTV, 15 ± 3 mL/kg, n = 190), and low tidal volume (LTV, 9 ± 3 mL/kg, n = 501). RESULTS: High tidal volume was associated with significantly decreased ventilator days (p < 0.005) and maximum positive end expiratory pressure (p < 0.0001) and significantly increased maximum peak inspiratory pressure (p < 0.02) and plateau pressure (p < 0.02) compared with those in patients with LTV. The incidence of atelectasis (p < 0.0001) and ARDS (p < 0.02) was significantly decreased with HTV compared with LTV. However, the incidence of pneumothorax was significantly increased in the HTV group compared with the LTV group (p < 0.03). CONCLUSIONS: High tidal volume significantly decreases ventilator days and the incidence of both atelectasis and ARDS compared with low tidal volume in pediatric burned patients with inhalation injury. Therefore, the use of HTV may interrupt sequences leading to lung injury in our patient population.

Healthcare resource utilization among patients diagnosed with idiopathic pulmonary fibrosis in the United States.

OBJECTIVES: Few studies have characterized healthcare resource utilization among patients with idiopathic pulmonary fibrosis. The objective of this study is to assess healthcare resource utilization among patients with idiopathic pulmonary fibrosis as compared to members without this condition. METHODS: Patients newly diagnosed with idiopathic pulmonary fibrosis were identified from a national administrative claims database (2006-2011) as having ≥ 2 claims with idiopathic fibrosing alveolitis, or ≥ 1 claim with idiopathic fibrosing alveolitis and ≥ 1 claim with post-inflammatory pulmonary fibrosis (earliest claim with idiopathic fibrosing alveolitis denoted the index date), a procedure of lung biopsy or high-resolution computed tomography within ± 90 days of the index date, 12-month pre-index continuous enrollment, plus ≥ 2 confirmatory idiopathic fibrosing alveolitis diagnoses after the procedure. For each idiopathic pulmonary fibrosis patient, three members without the condition were matched by age/gender/region/payer type. Demographic/clinical characteristics were measured during the 1-year pre-index period. Healthcare resource utilization was assessed by quarter during 1-year pre- and post-index periods. Generalized estimating equation models controlling for patient characteristics were constructed to estimate adjusted post-index healthcare resource utilization. RESULTS: In total, 1735 patients with idiopathic pulmonary fibrosis and 5205 without (mean age = 71.5 years; 46.1% female) were included. Adjusted results revealed idiopathic pulmonary fibrosis patients were more likely to use healthcare resources than members without the condition 1-year post-index (number of hospitalizations, emergency room visits, and outpatients visits: 0.63 vs 0.31, 0.62 vs 0.48, and 5.7 vs 3.1 per person-year, respectively). CONCLUSIONS: Healthcare resource utilization is considerably higher among patients with idiopathic pulmonary fibrosis than members without the condition. Effective treatments for patients with idiopathic pulmonary fibrosis are needed to help reduce burden of healthcare resource use.

Clinical effectiveness of liraglutide across body mass index in patients with type 2 diabetes in the United States: a retrospective cohort study.

INTRODUCTION: Clinical trials have shown that liraglutide effectively lowers glycated hemoglobin A1c (A1C) levels in adult patients with type 2 diabetes (T2D). However, no studies have evaluated the effectiveness of liraglutide by body mass index (BMI) in the United States (US) in clinical practice. This study examined liraglutide's clinical effectiveness to lower A1C and body weight after 6 months in T2D patients stratified by baseline BMI. METHODS: This was a retrospective cohort study using the General Electric Centricity electronic medical records database. Adult patients with T2D (≥18 years and BMI≥ 25 kg/m(2)) and A1C >7% at baseline who started liraglutide between January 1, 2010 and January 31, 2013 and who did not use insulin or a glucagon-like peptide-1 analog 12 months before initiating liraglutide (N = 3,005) were selected. Changes from baseline, stratified by BMI, in A1C, body weight, A1C <7% goal attainment, and incidence of severe hypoglycemia at 6-month follow-up were examined. RESULTS: After 6 months, A1C levels decreased on average by 0.95%, 1.02%, 0.99%, and 0.84% for BMI categories 25.0-29.9 (n = 333), 30.0-34.9 (n = 793), 35.0-39.9 (n = 821), and ≥40.0 kg/m(2) (n = 1,058), respectively (P = 0.30). The proportions of patients achieving A1C <7% at 6 months were 38.2%, 37.0%, 40.9%, and 41.0% (P = 0.54). The absolute body weight decreased by 1.5 to 4.0 kg across BMI and the rate of severe hypoglycemia (0.2%) was low. CONCLUSION: Patients with T2D experienced statistically significant decreases in A1C and body weight after initiating liraglutide regardless of their BMI. Liraglutide reduced A1C equally well across baseline BMI in clinical practice in the US.

Impact of stress-induced diabetes on outcomes in severely burned children.

BACKGROUND: Post-burn hyperglycemia leads to graft failure, multiple organ failure, and death. A hyperinsulinemic-euglycemic clamp is used to keep serum glucose between 60 and 110 mg/dL. Because of frequent hypoglycemic episodes, a less-stringent sliding scale insulin protocol is used to maintain serum glucose levels between 80 and 160 mg/dL after elevations >180 mg/dL. STUDY DESIGN: We randomized pediatric patients with massive burns into 2 groups, patients receiving sliding scale insulin to lower blood glucose levels (n = 145) and those receiving no insulin (n = 98), to determine the differences in morbidity and mortality. Patients 0 to 18 years old with burns covering ≥ 30% of the total body surface area and not randomized to receive anabolic agents were included in this study. End points included glucose levels, infections, resting energy expenditure, lean body mass, bone mineral content, fat mass, muscle strength, and serum inflammatory cytokines, hormones, and liver enzymes. RESULTS: Maximal glucose levels occurred within 6 days of burn injury. Blood glucose levels were age dependent, with older children requiring more insulin (p < 0.05). Daily maximum and daily minimum, but not 6 am, glucose levels were significantly different based on treatment group (p < 0.05). Insulin significantly increased resting energy expenditure and improved bone mineral content (p < 0.05). Each additional wound infection increased incidence of hyperglycemia (p = 0.004). There was no mortality in patients not receiving insulin, only in patients who received insulin (p < 0.004). Muscle strength was increased in patients receiving insulin (p < 0.05). CONCLUSIONS: Burn-induced hyperglycemia develops in a subset of severely burned children. Length of stay was reduced in the no insulin group, and there were no deaths in this group. Administration of insulin positively impacted bone mineral content and muscle strength, but increased resting energy expenditure, hypoglycemic episodes, and mortality. New glucose-lowering strategies might be needed.

Development of a challenge assessment tool for high-functioning children with an acquired brain injury.

PURPOSE: To develop a performance-based challenge assessment to evaluate gross motor abilities of high-functioning youth with an acquired brain injury (ABI). METHODS: Potential items were identified from the literature. A panel of 4 expert physical therapists selected items on the basis of 3 criteria: safety to test, feasibility to administer, and importance to perform. Item reduction was completed using ratings from a physical therapist web survey. The Acquired Brain Injury-Challenge Assessment (ABI-CA) was created and pilot tested with youth with an ABI. RESULTS: Seventy-eight items were identified and reduced to 47 items following expert panel discussion. Web-survey item reduction by 75 pediatric physical therapists yielded a 24-item ABI-CA that was administered to 6 youth with an ABI, aged 8 to 17 years. The ABI-CA mean score was 50.7/81.0 (SD = 17.4). CONCLUSION: The ABI-CA was feasible to administer and demonstrated gross motor activity challenges beyond the Gross Motor Function Measure. Response option refinement and measure validation are required prior to clinical/research use.

Triazole inhibitors of Cryptosporidium parvum inosine 5'-monophosphate dehydrogenase.

Cryptosporidium parvum is an important human pathogen and potential bioterrorism agent. This protozoan parasite cannot salvage guanine or guanosine and therefore relies on inosine 5'-monophosphate dehydrogenase (IMPDH) for biosynthesis of guanine nucleotides and hence for survival. Because C. parvum IMPDH is highly divergent from the host counterpart, selective inhibitors could potentially be used to treat cryptosporidiosis with minimal effects on its mammalian host. A series of 1,2,3-triazole containing ether CpIMPDH inhibitors are described. A structure-activity relationship study revealed that a small alkyl group on the alpha-position of the ether was required, with the (R)-enantiomer significantly more active than the (S)-enantiomer. Electron-withdrawing groups in the 3- and/or 4-positions of the pendent phenyl ring were best, and conversion of the quinoline containing inhibitors to quinoline-N-oxides retained inhibitory activity both in the presence and absence of bovine serum albumin. The 1,2,3-triazole CpIMPDH inhibitors provide new tools for elucidating the role of IMPDH in C. parvum and may serve as potential therapeutics for treating cryptosporidiosis.

Targeting a prokaryotic protein in a eukaryotic pathogen: identification of lead compounds against cryptosporidiosis.

Cryptosporidium parvum is an important human pathogen and potential bioterrorism agent. No vaccines exist against C. parvum, the drugs currently approved to treat cryptosporidiosis are ineffective, and drug discovery is challenging because the parasite cannot be maintained continuously in cell culture. Mining the sequence of the C. parvum genome has revealed that the only route to guanine nucleotides is via inosine-5'-monophosphate dehydrogenase (IMPDH). Moreover, phylogenetic analysis suggests that the IMPDH gene was obtained from bacteria by lateral gene transfer. Here we exploit the unexpected evolutionary divergence of parasite and host enzymes by designing a high-throughput screen to target the most diverged portion of the IMPDH active site. We have identified four parasite-selective IMPDH inhibitors that display antiparasitic activity with greater potency than paromomycin, the current gold standard for anticryptosporidial activity.