Three-year cost-effectiveness model for non-animal stabilized hyaluronic acid and dextranomer copolymer compared with sacral nerve stimulation after conservative therapy for the management of fecal incontinence.

BACKGROUND: Two new therapies for fecal incontinence (FI) are now available: non-animal stabilized hyaluronic acid and dextranomer copolymer (NASHA/Dx) and sacral nerve stimulation (SNS). PURPOSE: This study aimed to determine the cost-effectiveness of NASHA/Dx compared with SNS and conservative therapy (CT) for the treatment of FI after CT failure. METHODS: Decision tree models with Markov subbranches were developed to compare all direct costs and outcomes during a 3-year period from the viewpoint of the US third-party payer. Costs (in 2013 US dollars) of devices, medical and surgical care, and hospitalization were included. Outcomes included quality-adjusted life-years (QALYs) and incontinence-free days (IFDs). Both costs and outcomes were discounted at an annual rate of 3%. The incremental cost-effectiveness ratio was calculated for each outcome. One-way and probabilistic sensitivity analyses were performed to examine robustness of results and model stability. A budget impact analysis was also undertaken to estimate the potential cost and savings of NASHA/Dx for a payer with 1,000,000 covered lives. RESULTS: For the 3-year cost-effectiveness models, the expected cost was $9053 for CT, $14,962 for NASHA/Dx, and $33,201 for SNS. The numbers of QALYs were 1.769, 1.929, and 2.004, respectively. The numbers of IFDs were 128.8, 267.6, and 514.8, respectively. The incremental cost-effectiveness ratios per additional IFD gained were $42.60 for NASHA/Dx vs CT, $73.76 for SNS vs NASHA/Dx, and $62.55 for SNS vs CT. The incremental costs per QALY gained were $37,036 for NASHA/Dx vs CT, $244,509 for SNS vs NASHA/Dx, and $103,066 for SNS vs CT. The budget impact analysis evaluated the financial effect on the health care system of the use of NASHA/Dx and SNS. For the scenarios evaluated, when all of the patients receive NASHA/Dx, the net annual effect to the health care payer budget ranged from $571,455 to $2,857,275. When all of the patients receive SNS, the net annual effect to the health care payer budget ranged from $1,959,323 to $9,796,613. CONCLUSION: Both NASHA/Dx and SNS have produced significant improvements in FI symptoms for affected patients. NASHA/Dx is a cost-effective and more efficient use of resources for the treatment of FI when compared with SNS. The budget impact analysis suggests that although reimbursement for NASHA/Dx treatment initially adds costs to the health care system, it is significantly less expensive than SNS for patients who are candidates for either treatment.

Mutation-specific antibodies for the detection of EGFR mutations in non-small-cell lung cancer.

PURPOSE: Activating mutations within the tyrosine kinase domain of epidermal growth factor receptor (EGFR) are found in approximately 10% to 20% of non-small-cell lung cancer (NSCLC) patients and are associated with response to EGFR inhibitors. The most common NSCLC-associated EGFR mutations are deletions in exon 19 and L858R mutation in exon 21, together accounting for 90% of EGFR mutations. To develop a simple, sensitive, and reliable clinical assay for the identification of EGFR mutations in NSCLC patients, we generated mutation-specific rabbit monoclonal antibodies against each of these two most common EGFR mutations and aimed to evaluate the detection of EGFR mutations in NSCLC patients by immunohistochemistry. EXPERIMENTAL DESIGN: We tested mutation-specific antibodies by Western blot, immunofluorescence, and immunohistochemistry. In addition, we stained 40 EGFR genotyped NSCLC tumor samples by immunohistochemistry with these antibodies. Finally, with a panel of four antibodies, we screened a large set of NSCLC patient samples with unknown genotype and confirmed the immunohistochemistry results by DNA sequencing. RESULTS: These two antibodies specifically detect the corresponding mutant form of EGFR by Western blotting, immunofluorescence, and immunohistochemistry. Screening a panel of 340 paraffin-embedded NSCLC tumor samples with these antibodies showed that the sensitivity of the immunohistochemistry assay is 92%, with a specificity of 99% as compared with direct and mass spectrometry-based DNA sequencing. CONCLUSIONS: This simple assay for detection of EGFR mutations in diagnostic human tissues provides a rapid, sensitive, specific, and cost-effective method to identify lung cancer patients responsive to EGFR-based therapies.

Arrhythmias in patients receiving enzyme replacement therapy for infantile Pompe disease.

PURPOSE: Enzyme replacement therapy in infants with Pompe disease prolongs survival, decreases cardiomegaly, and improves muscle function. Because ectopy has been previously described in these patients, we sought to determine the prevalence and types of arrhythmias. METHODS: Thirty-eight children with infantile Pompe disease received enzyme replacement therapy in two open-label, multicenter, international, clinical trials. Data were reviewed on a retrospective basis. The corrected QT interval, ejection fraction, and indexed left ventricular mass were measured on a scheduled basis from electrocardiograms and echocardiograms. Arrhythmias were identified and characterized from electrocardiograms, ambulatory electrocardiograms, and point-of-care monitoring. Electrocardiogram and echocardiogram measurements were compared in children with and without arrhythmias. RESULTS: Seven children (18%) experienced arrhythmias. The QT interval, ejection fraction, indexed left ventricular mass, and rate of reduction of indexed left ventricular mass were not statistically different in those seven versus the other 31 children. Two children with life-threatening arrhythmias had among the highest combined baseline maximum indexed left ventricular mass and QT interval. Their arrhythmias occurred during severe metabolic stress from noncardiac illness. CONCLUSIONS: There was a high incidence of arrhythmias in our cohort. The relationship of arrhythmias with enzyme replacement therapy, myocardial fibrosis, or simply longer survival is unknown. Therefore, further characterization of specific arrhythmia risk factors and continued vigilance regarding screening for arrhythmias in children receiving enzyme replacement therapy is warranted.