Decreasing Opioid Use in Pediatric Lower Extremity Trauma: A Quality Improvement Project.

INTRODUCTION: Perioperative anxiety increases postoperative pain and the risk of complications in hospitalized children. Nonpharmacologic pain resources provided by Certified Child Life Specialists (CCLS) are a viable adjunct for pain management. METHOD: A routine CCLS consult was implemented for patients admitted to the orthopedic service with traumatic lower extremity injuries requiring surgery. A retrospective chart review compared patients who did not receive a CCLS consult. Daily pain rating scores, total doses of opioid and nonopioid pain medication, number of physical therapy attempts, length of stay, and demographics were compared for both groups. RESULTS: A clinically significant improvement was seen for decreased pain rating scores and opioid use after a routine CCLS consult was implemented. DISCUSSION: Adopting a routine CCLS consult for children with unplanned admissions because of trauma reduces the number of opioids used, provides children with pain management resources, and promotes coping skills that may be used in the future.

Pharmacodynamic Response of the MET/HGF Receptor to Small-Molecule Tyrosine Kinase Inhibitors Examined with Validated, Fit-for-Clinic Immunoassays.

PURPOSE: Rational development of targeted MET inhibitors for cancer treatment requires a quantitative understanding of target pharmacodynamics, including molecular target engagement, mechanism of action, and duration of effect. EXPERIMENTAL DESIGN: Sandwich immunoassays and specimen handling procedures were developed and validated for quantifying full-length MET and its key phosphospecies (pMET) in core tumor biopsies. MET was captured using an antibody to the extracellular domain and then probed using antibodies to its C-terminus (full-length) and epitopes containing pY1234/1235, pY1235, and pY1356. Using pMET:MET ratios as assay endpoints, MET inhibitor pharmacodynamics were characterized in MET-amplified and -compensated (VEGFR blockade) models. RESULTS: By limiting cold ischemia time to less than two minutes, the pharmacodynamic effects of the MET inhibitors PHA665752 and PF02341066 (crizotinib) were quantifiable using core needle biopsies of human gastric carcinoma xenografts (GTL-16 and SNU5). One dose decreased pY1234/1235 MET:MET, pY1235-MET:MET, and pY1356-MET:MET ratios by 60% to 80% within 4 hours, but this effect was not fully sustained despite continued daily dosing. VEGFR blockade by pazopanib increased pY1235-MET:MET and pY1356-MET:MET ratios, which was reversed by tivantinib. Full-length MET was quantifiable in 5 of 5 core needle samples obtained from a resected hereditary papillary renal carcinoma, but the levels of pMET species were near the assay lower limit of quantitation. CONCLUSIONS: These validated immunoassays for pharmacodynamic biomarkers of MET signaling are suitable for studying MET responses in amplified cancers as well as compensatory responses to VEGFR blockade. Incorporating pharmacodynamic biomarker studies into clinical trials of MET inhibitors could provide critical proof of mechanism and proof of concept for the field. Clin Cancer Res; 22(14); 3683-94. ©2016 AACR.

Impact of nonadherence to antiepileptic drugs on health care utilization and costs: findings from the RANSOM study.

PURPOSE: To study the impact of nonadherence to antiepileptic drugs (AEDs) on health care utilization and direct medical costs in a Medicaid population. METHODS: A retrospective cohort design was employed using state Medicaid claims data from Florida, Iowa, and New Jersey during the period from January 1997 to June 2006. Patients aged >or=18 years with one or more neurologist visit with an epilepsy diagnosis and two or more pharmacy claims for AEDs were included. Medication possession ratio (MPR) was used to evaluate AED adherence with MPR >or= 0.80 considered adherent and <0.80 considered nonadherent. The association of nonadherence with utilization outcomes [hospitalizations, inpatient days, emergency department (ED), and outpatient visits] was assessed with univariate and multivariate Poisson regressions. Quarterly per-patient inpatient, outpatient, ED, and pharmacy costs were calculated across nonadherent and adherent quarters for the younger than 65 population (under-65) and cost differences were computed. Adjusted incremental costs of nonadherence were estimated with multivariate Tobit regression models. RESULTS: A total of 33,658 patients were included (28,470 under-65), together contributing 388,564 treated quarters (26% nonadherent). In multivariate analyses, AED nonadherence was associated with significantly higher incidence of hospitalizations [incident rate ratio (IRR) = 1.39, 95% confidence interval (CI) = 1.37-1.41], inpatient days (IRR = 1.76, 95% CI = 1.75-1.78), and ED visits (IRR = 1.19, 95% CI = 1.18-1.21). Nonadherence was associated with cost increases related to serious outcomes, including inpatient ($4,320 additional cost per quarter, 95% CI = $4,077-$4,564) and ED services ($303 additional cost per quarter, 95% CI = $273-$334), but lower costs for outpatient and pharmacy services, likely because of nonadherent behavior. DISCUSSION: Nonadherence to AEDs appears to be associated with serious outcomes, as evidenced by increased utilization and costs of inpatient and ED services.

Costs, quality of life and treatment compliance associated with antibiotic therapies in patients with cystic fibrosis: a review of the literature.

BACKGROUND: Cystic fibrosis is the most common incurable hereditary disease in the US. Persistent respiratory infection is the leading cause of morbidity and mortality in cystic fibrosis patients. OBJECTIVE: This study aimed to review the literature on economic and quality of life outcomes and treatment compliance associated with antibiotic therapies for cystic fibrosis patients. METHODS: A systematic literature review was conducted using keyword searches of the MEDLINE database and selected conference abstracts. The review covered studies published between January 1990 and May 2007. RESULTS/CONCLUSIONS: Evidence suggests that inhaled tobramycin, a key chronic suppressive therapy, can reduce other healthcare costs. The main determinants of the cost of care include disease severity and respiratory infection. Costs vary widely by country. There is evidence that inhaled tobramycin and oral azithromycin improve quality of life and that treatment setting and patient convenience may also impact on quality of life. Antibiotic treatment compliance varied significantly and depended on the method of measurement, with more subjective measures tending to be higher. This review concludes by offering directions for future research.

Costs associated with intravenous chemotherapy administration in patients with small cell lung cancer: a retrospective claims database analysis.

OBJECTIVES: With new oral chemotherapy drugs emerging, it is useful to understand the costs associated with traditional intravenous (IV) therapy. This study aims to assess costs associated with IV chemotherapy in patients with small cell lung cancer (SCLC) from the perspective of large employer-payers. STUDY DESIGN: Descriptive retrospective claims database analysis. METHODS: Using medical claims data from 5.5 million beneficiaries between 01/01/1998 and 01/31/2006, we identified patients with lung cancer (ICD-9 codes 162.3-162.9, 176.4, or 197.0) who received IV chemotherapy. A case-finding SCLC algorithm was then applied which selected patients who were treated with chemotherapies commonly used in SCLC (cisplatin/etoposide, cisplatin/irinotecan, carboplatin/etoposide, topotecan, or cyclophosphamide/doxorubicin/vincristine) and then excluded those who had treatments or procedures indicative of non-small cell lung cancer (NSCLC) (positron emission tomography [PET] scan imaging, lung surgery, common NSCLC chemotherapies). Average total costs paid per day of IV chemotherapy administration were computed, along with separate costs for IV chemotherapy drugs, IV chemotherapy administration procedures, and other drugs and services received on IV visit days. Costs were also estimated per course of treatment based on the assumption of four chemotherapy cycles per course with three visits per cycle. RESULTS: Among 8010 patients with a lung cancer diagnosis, 802 were identified as SCLC. In the SCLC subset, the average total daily cost was $787 ($9449/course), with $395 ($4742/course; 50.2%) attributable to IV chemotherapy drugs, $93 ($1112/course; 11.8%) to IV chemotherapy administration, and $300 ($3595/course; 38.0%) to other drugs and services. CONCLUSIONS: The proposed algorithm identified about 10% of patients with lung cancer receiving IV chemotherapy as likely SCLC cases. Future studies should validate this algorithm with medical records data. IV chemotherapy administration and other visit-related drugs and services represented about half of the total cost per IV visit day, with the remainder attributable to direct costs for IV chemotherapy drugs.

Management of anaemia: a critical and systematic review of the cost effectiveness of erythropoiesis-stimulating agents.

Erythropoiesis-stimulating agents (ESAs) are genetically engineered forms of erythropoietin that are used in the treatment of anaemia. Their successful use in the treatment of anaemia associated with renal disease, cancer and other diseases, as well as the development of multiple agents, has increased the visibility of these agents in the clinical and health economics literature. The circumstances under which the use of ESAs is cost effective, or indeed, whether it is cost effective, is of central concern for clinicians and payers who must make informed decisions regarding the management of these costly resources. Much of the recent literature on ESAs in the treatment of anaemia associated with chronic kidney disease and cancer, the two major therapeutic areas for ESA treatment, has focused on comparisons between individual ESAs, particularly epoetin alfa and darbepoetin alfa. While there have been some studies of cost effectiveness, many studies in these treatment areas have employed a cost-minimization approach and have relied on published prices rather than actual market prices. In general, this review of the literature suggests a cost advantage for epoetin alfa relative to darbepoetin alfa in the treatment of anaemia in renal and oncology indications. For other indications in which the literature is less developed, such as anaemia induced by antiviral therapy and blood management in surgery, small prospective studies or decision-analytic models comparing ESA therapy and standard care have been most common. Few conclusions can be drawn about the overall and relative costs or cost effectiveness of ESAs in these treatment areas. With the recent concerns about the safety of ESAs, especially when used outside the approved product labelling, future evaluations of epoetin alfa and darbepoetin alfa should factor their safety profiles into estimates of cost effectiveness. Moreover, additional studies are needed to evaluate whether the treatment of anaemia with ESAs is cost effective compared with no treatment or minimal blood transfusions, and whether the cost effectiveness of ESAs would be improved if ESA doses and durations were reduced. With the introduction of new longer-acting ESAs, such as the continuous erythropoietin receptor activator, the relative cost effectiveness among the different ESAs will continue to be an important question for public and private payers, policy makers and clinicians who must consider the emergence of new data and changing dosing patterns when making decisions about the use of these important but costly agents.

The economic consequences of generic substitution for antiepileptic drugs in a public payer setting: the case of lamotrigine.

Generic substitution of antiepileptic drugs (AEDs) may increase pharmacy utilization, thus counterbalancing per-pill savings. The purpose of our study was to analyze the economic impact of government-mandated switching from branded to generic lamotrigine. Patients in a Canadian public pharmacy claims database using branded lamotrigine (Lamictal GlaxoSmithKline, UK) in 2002 converted to generic lamotrigine in 2003 and were observed from July 2002 to March 2006. Patients used branded lamotrigine for >or=90 days pre-generic entry and had >or=1 claim for generic lamotrigine post-generic entry. For the generic period, observed per-patient monthly drug costs were calculated as the sum of costs for lamotrigine, other AEDs, and non-AEDs. Expected per-patient drug costs were estimated assuming lamotrigine dose and other prescription drug utilization in the generic period were identical to those observed during the brand period. Differences between observed and expected costs were compared. Among 1,142 branded lamotrigine users, overall average monthly drug costs per person were expected to decrease by $30.55 due to lower pill costs. Instead, they fell by $11.98 from the brand to the generic periods (p < 0.001). Because of dosage changes, lamotrigine costs decreased by $29.92 instead of the anticipated $33.87 (p < 0.001). Increased pharmacy utilization caused other AED costs to rise by $6.29 versus the expected $0.36 (p < 0.001), while non-AED drug cost increased by $11.64 rather than by $2.95 (p < 0.001). We concluded that conversion to generic lamotrigine resulted in lower than expected cost savings. Further research is necessary to determine whether this is due to reduced effectiveness and/or tolerability. Payers may weigh smaller-than-expected cost reductions against a possible decrease in effectiveness to assess the relevance of mandatory generic switching of lamotrigine.