***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: Background — Oral anticoagulation ( OAC ) therapy is effective in atrial fibrillation but requires vigilance to maintain the international normalized ratio in the therapeutic range . This report examines how differences in time in therapeutic range ( TTR ) between centers and between countries affect the outcomes of OAC therapy . Methods and Results — In a posthoc analysis , the TTRs of patients on OAC in a r and omized trial of OAC versus clopidogrel plus aspirin  ( Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events [ ACTIVE W ] ) were used to calculate the mean TTR  for each of 526 centers and 15 countries . Proportional-hazards analysis , with and without adjustment for baseline variables , was performed , with patients stratified by TTR quartile and country . A wide variation in TTRs was found between centers , with mean TTRs for centers in the 4 quartiles of 44 % , 60 % , 69 % , and 78 % . For patients at centers below the median TTR ( 65 % ) , no treatment benefit was demonstrated as measured by relative risk for vascular events of clopidogrel plus aspirin versus OAC ( relative risk , 0.93 ; 95 % confidence interval , 0.70 to 1.24 ; P=0.61 ) . However , for patients at centers with a TTR above the study median , OAC had a marked benefit , reducing vascular events by > 2-fold ( relative risk , 2.14 ; 95 % confidence interval , 1.61 to 2.85 ; P<0.0001 ) . Mean TTR also varied between countries from 46 % to 78 % ; relative risk ( clopidogrel plus aspirin versus OAC ) varied from 0.6 to 3.6 ( a 5-fold difference ) . A population -average model predicted that a TTR of 58 % would be needed to be confident that patients would benefit from being on OAC . Conclusions — A wide variation exists in international normalized ratio control , as measured by TTR , between clinical centers and between countries , which has a major impact on the treatment benefit of OAC therapy . For centers and countries , a target threshold TTR exists ( estimated between 58 % and 65 % ) below which there appears to be little benefit of OAC over antiplatelet therapy Three dosage-prediction methods for initial in-hospital stabilization of warfarin therapy were evaluated . Adult in patients who had received warfarin sodium 10 mg daily for less than three days were eligible for the study . After receiving their third warfarin dose , patients were r and omly assigned to have their warfarin dosages adjusted using one of three dosage-prediction methods : by analog computer ( n = 31 ) , linear regression ( n = 22 ) , or empiric dosing by the physician ( n = 34 ) . A prothrombin time ( PT ) ratio ( patient PT divided by control PT ) between 1.3 and 2.5 was considered to be in the therapeutic range . For patients who achieved a stable PT ratio ( defined as a PT ratio between 1.3 and 2.5 that varied by less than 0.05 on two consecutive days or by less than 0.1 on three consecutive days without a dosage change ) before discharge , the number of days ( time to stabilization ) from administration of the first warfarin dose to achievement of the warfarin dosage that produced a stable PT ratio ( stabilization dosage ) was compared . A total of 54 patients met the study criteria for a  stable PT ratio before hospital discharge ( analog computer , n = 20 ; linear regression , n = 15 ; empiric dosing , n = 19 ) . The mean times to stabilization were 6.8 days in the analog-computer group , 7.3 days in the linear-regression group , and 8.4 days in the empiric-dosing group ; these times were not significantly different . All 20 stabilized patients in the analog-computer group achieved a stable PT ratio by the fourth dosage prediction . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND There is increased pressure on primary care physicians to monitor oral anticoagulation . OBJECTIVE To test the null hypothesis that oral anticoagulation care can be provided at least as well in primary care through a nurse-led clinic , involving near-patient testing and computerized decision support software , compared with routine hospital management based on a variety of clinical outcome measures . METHODS A r and omized , controlled trial in 12 primary care practice s in Birmingham , Engl and ( 9 intervention and 3 control ) . Two control population s were used :  patients individually r and omly allocated as controls in the intervention practice s ( intra practice controls ) and all patients in control practice s ( inter practice controls ) . Intervention practice s ' patients were r and omized to the intervention ( practice -based anticoagulation clinic ) or control ( hospital clinic ) group . The main outcome measure was therapeutic control of the international normalized ratio . RESULTS Three hundred sixty-seven patients were recruited ( 122 intervention patients , 102 intra practice control patients , and 143 inter practice control patients ) . St and ard measures of control of the international normalized ratio ( point prevalence ) showed no significant difference between the intervention and control groups . Data on proportion of time spent in the international normalized ratio range showed significant improvement for patients in the intervention group ( paired t test , P = .008 ) . CONCLUSIONS Nurse-led anticoagulation clinics can be implemented in novice primary care setting s by means of computerized decision support software and near-patient testing . Care given by this model is at least as good as routine hospital follow-up . The model is generalizable to primary health care centers operating in developed health care systems AIMS In Belgium , general practitioners ( GPs ) mainly manage oral anticoagulation therapy . To improve the quality of oral anticoagulation management by GPs and to compare different models and interventions , a r and omized clinical trial was performed . METHODS AND RESULTS Stratified r and omization divided 66 GP- practice s into four groups . A 6-month retrospective analysis assessed the baseline quality . In the prospect i ve study , each group received education on oral anticoagulation , anticoagulation files , and patient information booklets ( groups A , B , C , and D ) . Group B additionally received feedback every 2 months on their anticoagulation performance ; group C determined the international normalized ratio ( INR ) with a CoaguChek device in the doctor 's office or at the patient 's home ; and group D received Dawn AC computer assisted advice for adapting oral anticoagulation . For the different groups , the time spent in target INR range ( Rosendaal 's method ) and adverse events related to anticoagulation were determined and compared with the same quality indicators at baseline . There was a significant increase in per cent of time within 0.5 INR from target , from 49.5 % at baseline to 60 % after implementing the different interventions . However , neither the per cent in target range nor the event rates differed among the four groups . CONCLUSION The interventions significantly improved the quality of management of oral anticoagulation by Belgian GPs , mainly as a result of an education and support programme This study was undertaken to determine if a computerized pharmacokinetic program for adjusting theophylline infusion rates could attain a goal serum theophylline level more accurately than physician‐derived adjustments and what clinical impact this would have . Thirty‐five patients with diagnoses of asthma or chronic obstructive pulmonary disease were r and omized to a control group ( empiric ) or experimental group ( kinetic ) after initial theophylline levels were drawn from each group . After second levels were drawn , patients in the kinetic group had their infusion rates adjusted by the computerized pharmacokinetic program to achieve a level of 15 mg/L , whereas patients in the empiric group had their infusions adjusted empirically by the primary care physicians to achieve a serum theophylline level of 15 mg/L. A final theophylline level was obtained just before the infusion was discontinued . The kinetic group was closer to the goal level of 15 mg/L than the empiric group , but this was not statistically significant ( 14.8 ± 4.4 versus 12.6 ± 4.1 ; p > 0.05 ) . The total number of days that patients were receiving intravenous theophylline was slightly longer for the kinetic group ( 4.1 ± 3.3 versus 3.2 ± 1.5 ; p > 0.05 ) as was the total number of hospital days , but neither of these were statistically significant ( 11.4 ± 21.6 versus 8.8 ± 15.4 days ; p > 0.05 ) . There were no differences between the two groups in the number of subtherapeutic or toxic levels , and there were no significant differences in arterial blood gas measurements . We were unable to show in this study any clinical advantage to adjusting the dosage of a theophylline infusion by a computerized pharmacokinetic program compared with adjustments made empirically by a physician AIMS --To compare the effectiveness of three computerised systems that are currently used for assisting warfarin control in out patients with the customary dosing method used by experienced medical staff . METHODS --A pilot r and omised study of three systems with a follow up independently r and omised study of two of these was made on 186 patients receiving long term treatment or who had recently started warfarin treatment and had been discharged from hospital . RESULTS --All three computerised systems seemed to give satisfactory control compared with the traditional dosing method . For patients receiving more intensive treatment with an assigned target range of 3.0 - 4.5 computerised dosage programs achieved significantly better control ; the medical staff undertreated such patients almost 50 % of the time . CONCLUSION --Computer based programs can assist outpatient anticoagulant control with warfarin during both early and long term treatment . For most patients the control achieved is as good as that obtained by the customary method of dosing , by experienced clinic doctors , although the latter tend to be too conservative when dosing patients within the intense target range of 3.0 to 4.5 International Normalised Ratio ( INR ) . The computers were significantly more successful in this higher range Abstract In 42 patients requiring digitalis , and r and omly divided into two groups , the performance of a computer program using patient size and renal function to compute digoxin dosage was compared to that of unaided physician judgment . Serum digoxin concentrations were measured repeatedly . Efficacy was measured by changes in the manifestations of heart failure , and toxicity by electrocardiographic criteria . For each patient , physicians specified a desired serum digoxin concentration and predicted this concentration at each visit . For one group , the computer program suggested the dosage needed to achieve the desired digoxin concentration . Efficacy was the same in both groups , and there was no toxicity . Although the computer slightly outperformed the physicians , prediction and achievement errors were unacceptably large . Hence , much between-patient variability in serum digoxin concentrations remains unexplained after adjustments for dose , body size and renal function . This argues for measurement of digoxin With increasing work-loads in anticoagulant clinics different methods of service delivery need evaluation . The quality of anticoagulant control achieved by a  nurse-practitioner  using a computer decision-support system ( CDSS ) was compared with that achieved by trainee doctors without CDSS . Eighty-one out- patients ( group A , therapeutic range 2 - 3 ) and 96 out- patients ( group B , therapeutic range 3 - 4.5 ) were r and omized to management by a nurse-practitioner or by trainee doctors ( clinicians ) . Thirty-seven patients in group A and 50 patients in group B were r and omized to be managed by the nurse-practitioner .  In group A , patients in the nurse-practitioner group spent a longer time in the therapeutic range than those in the clinician group ( 60.7 % compared with 51.6 % ) . Dose suggestion acceptance in the nurse-practitioner group ( 88 % ) was higher compared with agreement between the CDSS and the clinicians ( 60 % ) . In group B , patients in the clinician group spent a slightly longer time in the therapeutic range ( 70 % compared with 67.6 % ) . Acceptance of dose suggestion was lower in the nurse-practitioner group ( 67 % ) compared with agreement between the CDSS and the clinicians ( 73 % ) . In conclusion , the CDSS can improve the quality of control of warfarin therapy by a nurse-practitioner over that by trainee doctors for the therapeutic range 2 - 3 . Similar quality of control is achieved for the therapeutic range 3 - 4.5 . The CDSS may be used by nurse-practitioners to achieve safe and effective anticoagulation in hospital-based or out-reach anticoagulant clinics OBJECTIVES A clinical trial , " Belgian Improvement Study on Oral Anticoagulation Therapy ( BISOAT ) , " significantly improved the quality after implementing four different quality -improving interventions in four r and omly divided groups of general practitioners ( GPs ) . The quality -improving interventions consisted of multifaceted education with or without feedback reports on their performance , international normalized ratio ( INR ) testing by the GP with a CoaguChek device or computer-assisted advice for adapting oral anticoagulation therapy . The quality improvement in INR control versus baseline was similar in the four groups . The aim of the current study was to calculate the cost-effectiveness and influencing factors of the four quality -improving interventions compared with usual care . METHODS  Activity-based costing techniques with question naires were used to determine the global costs per patient per month in the different intervention groups . Effectiveness data were obtained from the BISOAT study . Cost-effectiveness was expressed as cost per additional day within a 0.5 range from INR target . RESULTS The one-time cost of  multif 
    Output:
    
In meta- analysis , CCDSSs for vitamin K antagonist dosing significantly improved time in therapeutic range .
Conclusions CCDSSs have potential for improving process of care for therapeutic drug monitoring and dosing , specifically insulin and vitamin K antagonist dosing .
However , studies were small and generally of modest quality , and effects on patient outcomes were uncertain , with no convincing benefit in the largest studies .