Mark Montgomery

Cost of care for individuals with cystic fibrosis: a regression approach to determining the impact of recombinant human DNase.

We estimated direct medical costs of care and important determinants of the costs in patients with cystic fibrosis (CF), including therapy with recombinant human DNase (rhDNase). Costs were estimated with resource use data from the Epidemiologic Study of Cystic Fibrosis. Ordinary least squares regression was used to determine the effect of clinical and demographic variables on individual cost of care. The estimated cost of caring for 303 patients in Alberta was

Dornase alfa for cystic fibrosis

2,279,801 in 1996. The mean cost of care was

Longer term effects of closed repair of pectus excavatum on cardiopulmonary status

7524 (range

Guidance for considering ethical, legal, and social issues in health technology assessment: Application to genetic screening

386–92,376)/patient. Regression results indicated that age and forced expiratory volume predicted had a negative association with costs. Being female, receiving rhDNase, and having Pseudomonas aeruginosa or Burkholderia cepacia were all associated with high costs. Our estimates indicated large interindividual variation in cost of care for patients with CF.

Pulmonary surfactant dysfunction in pediatric cystic fibrosis: Mechanisms and reversal with a lipid-sequestering drug

BACKGROUNDnDornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review.nnnOBJECTIVESnTo determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use.nnnSEARCH METHODSnWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Groups Cystic Fibrosis Register: 30 November 2015.Clinicaltrials.gov was also searched to identify unpublished or ongoing trials. Date of most recent search: 28 November 2015.nnnSELECTION CRITERIAnAll randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance.nnnDATA COLLECTION AND ANALYSISnAuthors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction.nnnMAIN RESULTSnThe searches identified 54 trials, of which 19 (including a total of 2565 participants) met our inclusion criteria. Three additional papers examined the healthcare cost from one of the clinical trials. Fifteen trials compared dornase alfa to placebo or no dornase alfa treatment (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa with hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years.Compared to placebo, forced expiratory volume at one second improved in the intervention groups, with significant differences at one, three, six months and two years. There was also a significant improvement in lung clearance index at one month. There was a decrease in pulmonary exacerbations compared to placebo in trials of longer duration. The quality of the evidence from placebo-controlled trials was moderate to high for outcomes of lung function and pulmonary exacerbations. Limited, low quality evidence was available for changes in quality of life from baseline. One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.The results for trials comparing dornase alfa to other medications that improve airway clearance (hypertonic saline or mannitol) were mixed, with one trial showing a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline, and three trials finding no difference between medications. In the only trial to assess the combination of dornase alfa with another medication compared to dornase alone, there was no benefit seen with the combination of dornase alfa and mannitol. Evidence of dornase alfa compared to other medications was limited and the open-label design of the trials may have induced bias, therefore the quality of the evidence was judged to be low.Dornase alfa did not cause significantly more adverse effects, except voice alteration and rash.nnnAUTHORS CONCLUSIONSnThere is evidence to show that, compared with placebo, therapy with dornase alfa improves lung function in people with cystic fibrosis in trials lasting one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to hyperosmolar agents in improving lung function.

Cardiopulmonary effects of closed repair of pectus excavatum

BACKGROUNDnThe Nuss repair is done for correction of moderate to severe pectus excavatum (PE). The long term cardiopulmonary and psychosocial effects of repair are uncertain. The objective of this study was to compare cardiopulmonary function and subjective evaluation of appearance and exercise tolerance pre-bar insertion with post-bar removal.nnnMETHODSnAll patients underwent preoperative and post-bar (3 month) removal evaluation with complete pulmonary function tests, exercise stress testing, echocardiogram, and self-rated appearance and exercise tolerance scoring. The protocol was approved by the regional ethics board, and all families gave informed consent.nnnRESULTSnSixty-seven patients underwent pre and post testing. Preoperative CT index was 4.4 ± 1.3. Cardiopulmonary outcomes, standardized for height and weight, showed significant improvements in FEV-1 as (pre) 81.1 ± 17.0 vs post 89.8 ± 20.5*, FVC: 91.2 ± 18.6 vs 98.9 ± 22.9*, O2 pulse: 75.8 ± 14.4 vs 80.5 ± 18.3* (each as % predicted). Both the self-ratings of appearance (2.5 ± 0.8 vs 4.4 ± 0.5) and ability to exercise (3.3 ± 0.7 vs 4.3 ± 0.6, scale 1-5) increased significantly. (All data: mean ± St Dev, *p<0.05) CONCLUSIONS: Closed repair of PE results in improvements in pulmonary and aerobic exercise function and perceived appearance and exercise tolerance. Our data suggest that the impact on appearance and self-perceived well being is greater than the physical effect.

Histamine challenge in young children using computerized lung sounds analysis.

OBJECTIVES AND METHODSnMany authors have argued that ethical, legal, and social issues (ELSIs) should be explicitly integrated into health technology assessment (HTA), yet doing so poses challenges. This discussion may be particularly salient for technologies viewed as ethically complex, such as genetic screening. Here we provide a brief overview of contemporary discussions of the issues from the HTA literature. We then describe key existing policy evaluation frameworks in the fields of disease screening and public health genomics. Finally, we map the insights from the HTA literature to the policy evaluation frameworks, with discussion of the implications for HTA in genetic screening.nnnRESULTS AND CONCLUSIONSnA critical discussion in the HTA literature considers the definition of ELSIs in HTA, highlighting the importance of thinking beyond ELSIs as impacts of technology. Existing HTA guidance on integrating ELSIs relates to three broad approaches: literature synthesis, involvement of experts, and consideration of stakeholder values. The thirteen key policy evaluation frameworks relating to disease screening and public health genomics identified a range of ELSIs relevant to genetic screening. Beyond straightforward impacts of screening, these ELSIs require consideration of factors such as the social and political context surrounding policy decisions. The three broad approaches to addressing ELSIs described above are apparent in the screening/genomics literatures. In integrating these findings we suggest that the method chosen for addressing ELSIs in HTA for genetic screening may determine which ELSIs are prioritized; and that an important challenge is the lack of guidance for evaluating such methods.

Midterm evaluation of cardiopulmonary effects of closed repair for pectus excavatum

BACKGROUNDnAirway surfactant is impaired in cystic fibrosis (CF) and associated with declines in pulmonary function. We hypothesized that surfactant dysfunction in CF is due to an excess of cholesterol with an interaction with oxidation.nnnMETHODSnSurfactant was extracted from bronchial lavage fluid from children with CF and surface tension, and lipid content, inflammatory cells and microbial flora were determined. Dysfunctional surfactant samples were re-tested with a lipid-sequestering agent, methyl-β-cyclodextrin (MβCD).nnnRESULTSnCF surfactant samples were unable to sustain a normal low surface tension. MβCD restored surfactant function in a majority of samples.Mechanistic studies showed that the dysfunction was due to a combination of elevated cholesterol and an interaction with oxidized phospholipids and their pro-inflammatory hydrolysis products.nnnCONCLUSIONnWe confirm that CF patients have impaired airway surfactant function which could be restored with MβCD. These findings have implications for improving lung function and mitigating inflammation in patients with CF.