***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: Emerging health problems require rapid advice . We describe the development and pilot testing of a systematic , transparent approach used by the World Health Organization ( WHO ) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A ( H5N1 ) virus infection . We first search ed for systematic review s of r and omized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection , including case reports and animal and in vitro studies . A panel of clinical experts , clinicians with experience in treating patients with H5N1 , influenza research ers , and method ologists was convened for a two-day meeting . Panel members review ed the evidence prior to the meeting and agreed on the process . It took one month to put together a team to prepare the evidence profiles ( i.e. , summaries of the evidence on important clinical and policy questions ) , and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting . A draft manuscript for publication was prepared within 10 days following the panel meeting . Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines . The process could be improved by shortening the time required to commission evidence profiles . Further development is needed to facilitate stakeholder involvement , and evaluate and ensure the guideline 's usefulness STUDY OBJECTIVE We report on the incremental costs associated with improvements in health-related quality of life ( HRQL ) following 6 months of respiratory rehabilitation compared with conventional community care . DESIGN Prospect i ve r and omized controlled trial of rehabilitation . SETTING A respiratory rehabilitation unit . PARTICIPANTS Eighty-four subjects who completed the rehabilitation trial . INTERVENTION Two months of inpatient rehabilitation followed by 4 months of outpatient supervision . MEASUREMENTS AND RESULTS All costs ( hospitalization , medical care , medications , home care , assistive devices , transportation ) were included . Simultaneous allocation was used to determine capital and direct and indirect hospitalization costs . The incremental cost of achieving improvements beyond the minimal clinical ly important difference in dyspnea , emotional function , and mastery was $ 11,597 ( Canadian ) . More than 90 % of this cost was attributable to the inpatient phase of the program . Of the nonphysician health-care professionals , nursing was identified as the largest cost center , followed by physical therapy and occupational therapy . The number of subjects needed to be treated ( NNT ) to improve one subject was 4.1 for dyspnea , 4.4 for fatigue , 3.3 for emotion , and 2.5 for mastery . CONCLUSION Cost estimates of various approaches to rehabilitation should be combined with valid , reliable , and responsive measures of outcome to enable cost-effectiveness measures to be reported . Comparison studies with the same method are necessary to determine whether the improvements in HRQL that follow inpatient rehabilitation are cheap or expensive . Such information will be important in identifying the extent to which alternative approaches to rehabilitation can influence re source allocation . A consideration of cost-effectiveness from the perspective of NNT may be useful in the evaluation of health-care programs The aim of this paper is to assess the health economic consequences of substituting ipratropium with the new , once-daily bronchodilator tiotropium in patients with a diagnosis of chronic obstructive pulmonary disease ( COPD ) . This prospect i ve cost-effectiveness analysis was performed alongside two 1‐yr r and omised , double-blind clinical trials in the Netherl and s and Belgium . Patients had a diagnosis of COPD and a forced expiratory volume in one second ( FEV1 ) ≤65 % predicted normal . Patients were r and omised to tiotropium ( 18 µg once daily ) or ipratropium ( 2 puffs of 20 µg administered four times daily ) in a ratio of 2:1 . The mean number of exacerbations was reduced from 1.01 in the ipratropium group ( n=175 ) to 0.74 in the tiotropium group ( n=344 ) . The percentages of patients with a relevant improvement on the St. George 's Respiratory Question naire ( SGRQ ) were 34.6 % and 51.2 % respectively . Compared to ipratropium , the number of hospital admissions , hospital days and unscheduled visits to healthcare providers was reduced by 46 % , 42 % and 36 % respectively . Mean annual healthcare costs including the acquisition cost of the study drugs were 1721 ( sem 160 ) in the tiotropium group and 1,541 ( SEM 163 ) in the ipratropium group ( difference 180 ) . Incremental cost-effectiveness ratios were 667 per exacerbation avoided and 1084 per patient with a relevant improvement on the SGRQ . Substituting tiotropium for ipratropium in chronic obstructive pulmonary disease patients offers improved health outcomes and is associated with increased costs of 180 per patient per year BACKGROUND Valproate is widely accepted as a drug of first choice for patients with generalised onset seizures , and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify .  Lamotrigine and topiramate are also thought to possess broad spectrum activity . The SANAD study aim ed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify . METHODS SANAD was an unblinded r and omised controlled trial in hospital-based outpatient clinics in the UK . Arm B of the study recruited 716 patients for whom valproate was considered to be st and ard treatment . Patients were r and omly assigned to valproate , lamotrigine , or topiramate between Jan 12 , 1999 , and Aug 31 , 2004 , and follow-up data were obtained up to Jan 13 , 2006 . Primary outcomes were time to treatment failure , and time to 1-year remission , and analysis was by both intention to treat and per protocol . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N38354748 . FINDINGS For time to treatment failure , valproate was significantly better than topiramate ( hazard ratio 1.57 [ 95 % CI 1.19 - 2.08 ] ) , but there was no significant difference between valproate and lamotrigine ( 1.25 [ 0.94 - 1.68 ] ) . For patients with an idiopathic generalised epilepsy , valproate was significantly better than both lamotrigine ( 1.55 [ 1.07 - 2.24 ] and topiramate ( 1.89 [ 1.32 - 2.70 ] ) . For time to 12-month remission  valproate was significantly better than lamotrigine overall ( 0.76 [ 0.62 - 0.94 ] ) , and for the subgroup with an idiopathic generalised epilepsy 0.68 ( 0.53 - 0.89 ) . But there was no significant difference between valproate and topiramate in either the analysis overall or for the subgroup with an idiopathic generalised epilepsy . INTERPRETATION Valproate is better tolerated than topiramate and more efficacious than lamotrigine , and should remain the drug of first choice for many patients with generalised and unclassified epilepsies . However , because of known potential adverse effects of valproate during pregnancy , the benefits for seizure control in women of childbearing years should be considered 
    Output:
    
At present , disaggregated re source utilization accompanied by some cost information seems to be the most promising approach .
The method for assigning values to costs , including external or indirect cost ( such as time off work ) , can have a significant impact on the outcome of any economic evaluation .