***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The present study focused on patients with cystic fibrosis ( CF ) , who were on maintenance therapy with recombinant human deoxyribonuclease ( rhDNase )  , with the aim of comparing efficacy and possible side effects of nebulisation of rhDNase when taken before bedtime with efficacy and side effects when taken after waking up . A r and omised , double-blind , double-dummy , crossover study group was used . The inclusion criteria were as follows : 1 ) CF , 2 ) stable clinical condition and 3 ) rhDNase maintenance therapy .  Patients in group I inhaled rhDNase before bedtime and a placebo after waking up in weeks 1–2 . The protocol was reversed during weeks 3–4 . Group II patients performed the reverse of this sequence . Patients continued with their daily routine sputum expectoration . The primary end-point was classified as the maximal instantaneous forced flow when 25 % of the forced vital capacity remained to be exhaled ( MEF25 % ) . Pulmonary functions tests were performed on days 0 , 7 , 14 , 21 and 28 . At 1 , 2 , 3 and 4 weeks arterial oxygen saturation and cough frequency were measured during the night . A total of 24 patients completed the study . The mean ( range ) age of the patients was 13 ( 6–19 ) yrs . MEF25 % , taken to be the primary end-point , did not show a significant difference between nebulisation of rhDNase before bedtime compared with when taken after waking up . Nocturnal cough , oxygen saturation , and other secondary end-points were not significantly different between the two study periods . In conclusion , the present study found that it is equally effective and safe to nebulise recombinant human deoxyribonuclease before bedtime compared with when performed after waking up in children with cystic fibrosis , who are on maintenance treatment with recombinant human deoxyribonuclease Objective . Although dornase alfa is a widely used , aerosolized , mucolytic agent in patients with cystic fibrosis ( CF ) , its efficacy in relation to the timing of physiotherapy has not been tested . We sought to determine whether dornase alfa is more efficacious when it is administered 30 minutes before versus 30 minutes after physiotherapy/positive expiratory pressure ( PEP ) therapy in clinical ly stable children . Methods . Using a crossover , r and omized , double-blind , and placebo-controlled trial , we undertook a 6-week study of the efficacy of dornase alfa in relation to the timing of physiotherapy at home . There were 2 treatment orders . Dornase alfa before + placebo after physiotherapy/PEP for 2 weeks was followed by a 2-week washout and then the reverse order placebo before and dornase alfa after physiotherapy/PEP for the final 2 weeks . The second treatment order reversed the placebo and dornase alfa therapy for the first and last 2-week blocks . The main outcome measures used included the change in predicted percentage of forced expiratory volume in 1 second ( FEV1 ) , a composite quality of well-being score ( QWB ) , and a measure of aerobic fitness ( maximal oxygen consumption , [ VO2max ] ) , determined using shuttle testing . Results . Fifty-two patients who had CF ( 27 female ) with mild to moderate suppurative lung disease , were a mean ± SD age of 10.7 ± 3.2 years , had Shwachman scores of 86 ± 11.8 , had predicted FEV1 of 83 % ± 18 % , had quality of well-being score of 0.76 ± 0.08 , and had VO2max of 42.6 ± 6.3 ml/kg per min were enrolled . Fifty patients completed the study . Intention-to-treat analysis was used . Nonsignificant mean ( 95 % confidence interval ) differences in FEV1 ( 0.02 L [ −0.05 to 0.10 ] ) , VO2max ( −0.75 ml/kg per min [ −1.85 to 0.35 ] ) , and QWB ( 0.005 [ −0.94 to 0.0028 ] ) for dornase alfa after physiotherapy/PEP were detected . A post hoc analysis showed that patients who were colonized persistently with Pseudomonas aeruginosa had a significantly greater improvement in FEV1 ( 0.12 L [ 0.23 to 0.01 ] vs −0.04 L [ 0.05 to −0.13 ] ) when dornase alfa was administered after physiotherapy/PEP . Conclusions . Dornase alfa is equally efficacious when delivered before or after physiotherapy/PEP in patients with CF . Patients who are colonized persistently with P aeruginosa may derive more improvement in FEV1 when dornase alfa is delivered after physiotherapy/PEP The goal of this study was to evaluate the safety and efficacy of recombinant human DNase ( rhDNase ) in hospitalized patients with cystic fibrosis ( CF ) experiencing acute pulmonary exacerbations . Eighty patients with documented CF were enrolled at 11 CF centers when admitted for antibiotic therapy . Patients were at least 5 yr old with a forced vital capacity ( FVC ) > or = 35 % of predicted and an oxygen saturation > or = 90 % on a fraction of inspired oxygen ( FIO2 ) < 0.5 . Patients were r and omized to receive rhDNase 2.5 mg in 2.5 ml excipient twice a day ( n = 43 ) or 2.5 ml excipient alone twice daily ( n = 37 ) along with conventional treatment for exacerbations . Administration of rhDNase was not associated with acute adverse events or deaths , and no patients experienced allergic or anaphylactic reactions . Although forced expiratory volume in one second ( FEV1 ) and FVC improved in both treatment groups during the double-blind period , there were no statistically significant differences in the mean change from baseline in FEV1 or FVC between the two groups . rhDNase therapy is safe and well tolerated in CF patients with acute exacerbations requiring hospitalization , but the study did not demonstrate a statistically significant therapeutic effect of rhDNase when added to a regimen of antibiotics and chest physical therapy Recombinant human deoxyribonuclease I ( dornase alfa ) is currently used as an inhaled mucoactive agent in the treatment of cystic fibrosis . In a r and omized , placebo-controlled , double-blind clinical study in 100 infants , we investigated whether the therapeutic use of dornase alfa can be extended to ventilated , fluid-restricted children to reduce reintubation rate , ventilation duration , pediatric intensive care unit ( PICU ) stay , and ventilation complications . While reintubation rates were similar for dornase alfa 7 % vs. placebo 9 % ( odds ratio , 0.77 ; confidence interval , 0.11 - 4.9 ) , the incidence of atelectasis ( 6 vs. 17 , respectively ; P-value 0.051 ) , median ventilation time ( 2.2 vs. 3.4 days , respectively ; P-value 0.043 ) , median length of PICU stay ( 7 vs. 8 days , respectively ; P-value 0.051 ) , and mean costs ( 4,830 vs. 6,320 , respectively ) were lower in the dornase alfa group . No adverse effects were observed , even in critically ill patients . We found that dornase alfa was beneficial and safe . Our findings also indicate that dornase alfa is possibly of value from the first day of mechanical ventilation onward , particularly when longer ventilation ( > 3 days ) is expected in fluid-restricted children after cardiac surgery OBJECTIVE To assess the feasibility of measuring short-term effects of inhaled recombinant human deoxyribonuclease ( rhDNase , Pulmozyme on lung function , pulse oximetry and symptom scores in infants and toddlers with stable cystic fibrosis . DESIGN open-label r and omized placebo controlled cross-over pilot study . PATIENTS AND METHODS We treated nine CF patients ( 0.7 - 1.9 years ) with nebulised rhDNase ( 2.5 mg ) and NaCl 0.9 % ( 10 ml ) via jet nebulizer cross-over once daily during 2-week treatment blocks . Measurements were performed at baseline and after treatment blocks and consisted of lung function tests ( plethysmography and tidal rapid thoraco-abdominal compression technique ) , overnight pulse oximetry , and daily symptom scores . RESULTS DNase treatment and the different assessment s were well tolerated by all children and their parents . Lung function showed increased airway patency after treatment with rhDNase ( P < 0.001 ) , but not after NaCl 0.9 % . Overnight pulse oximetry and daily symptom scores did not change during the study period . CONCLUSIONS This pilot study indicates that objective assessment of the effects of rhDNase is feasible in infants with CF who have little or no respiratory symptoms . Our results warrant a larger r and omized placebo-controlled trial Economic evaluations of pharmaceuticals are increasingly being conducted in conjunction with r and omized phase III clinical trials to meet the dem and for pharmacoeconomic data when new products are launched . While the need for such data is often global , the trials in which relevant information may be collected are often conducted in only one or a limited number of countries . A critical issue is how data from pivotal clinical trials in one setting can serve as the basis for pharmacoeconomic evaluations in others . We address this issue and report on four economic evaluations that we undertook in conjunction with a recent U.S. phase III clinical trial of recombinant human deoxyribonuclease ( rhDNase ) , which is used to improve pulmonary function in patients with cystic fibrosis ( CF ) . The objective of these evaluations was to estimate the potential impact of  rhDNase therapy in France , Germany , Italy , and the United Kingdom on the direct costs of medical care for the treatment of respiratory tract infections ( RTIs ) in patients with CF . Analyses of economic impact were undertaken both with and without adjustment for differences in practice patterns between the United States and the countries of interest . Our findings suggest that rhDNase therapy may reduce the cost of RTI-related care by between US$ 600 and US$ 1,100 over a 24-week period ; the cost of rhDNase is not included in these figures , as a price was unavailable when our analyses were undertaken . Despite method ologic challenges , economic evaluations that meet the information needs of decision makers in diverse countries can nonetheless be undertaken in conjunction with phase III clinical trials Accumulation of viscous sputum enhances lung damage in patients with cystic fibrosis . High contents of DNA , released by leucocytes , are the major cause of the high viscosity of this sputum . Recombinant human DNase I ( rhDNase ) decreases viscoelastic properties of sputum in cystic fibrosis and improves lung function . We have investigated the effect of rhDNase over a period of 6 weeks , 2.5 mg once daily , on lung function and quality of life in 12 adult patients with cystic fibrosis . Significant improvements in FEV1 , IVC and daily peak flow values were measured . Airway resistance and FVC did not improve significantly . The cause of the improvements found is probably due to recruitment of previously , due to mucus plugging , unventilated lung areas . In addition , the awareness of symptoms related to sputum retention improved , although subjective parameters on general well-being and physical condition remained unchanged Cystic fibrosis ( CF ) is the most frequent lethal autosomal recessive disease among Caucasians . In more than 90 % of all patients the pulmonary involvement is the life-limiting factor . In the lung , the production of viscous sputum is a main and early clinical feature of CF . To help clear the lungs from this material mucolytic active drugs were used . Recombinant human DNase ( rhDNase ) w1x and hypertonic ( 5.85 % ) saline ( HS ) w2x both were mucolytic active and improved FEV1 in the same range in patients with CF . Besides this similarity there are differences such as the modulation of rheological parameters and costs . To determine whether these treatments can replace each other , we compared effect and acceptance in the same group of patients Recombinant human deoxyribonuclease ( rhDNase ) has been shown to improve lung function and reduce the number of pulmonary exacerbations in patients with cystic fibrosis ( CF ) , but its long-term effect on airway inflammation remains unknown . In this study , we used bronchoalveolar lavage ( BAL ) to investigate the long-term effect of rhDNase on inflammation in patients with CF having mild lung disease . A total of 105 patients with CF ( > or = 5 years of age ) having normal lung function were r and omized to receive rhDNase ( 2.5 mg/day ) or no rhDNase .  Patients with a normal percentage of neutrophils in BAL fluid at baseline were not r and omized and served as the control group . The percentage of neutrophils in the pooled BAL sample was similar in both r and omized groups at baseline . A significant increase in neutrophils was observed over the 3-year study period in both untreated patients and control subjects , whereas neutrophils remained unchanged in patients treated with rhDNase .  Elastase activities and interleukin-8 concentrations also increased in untreated patients and remained stable in patients on rhDNase . We conclude that in patients with CF , an increase in neutrophilic airway inflammation is found that is positively influenced by rhDNase treatment OBJECTIVES This study compared the relative cost-effectiveness of daily recombinant human deoxyribonuclease ( rhDNase ) , with alternate day 
    Output:
    
The number of deaths was not significant between treatment groups .
Therapy over a two-year period ( based on one trial ) significantly improved FEV(1 ) in children and there was a non-significant reduction in the risk of infective exacerbations .
Voice alteration and rash appear to be the only adverse events reported with increased frequency in r and omised controlled trials