***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 Heart failure is a major cause of mortality and morbidity . As mortality rates are high , it is important that patients seen by general practitioners with symptoms suggestive of heart failure are identified quickly and treated appropriately . Identifying patients with heart failure or deciding which patients need further tests is a challenge . All patients with suspected heart failure should be diagnosed using objective tests such as echocardiography , but it is expensive , often delayed , and limited by the significant skill shortage of trained echocardiographers . Alternative approaches for diagnosing heart failure are currently limited . Clinical decision tools that combine clinical signs , symptoms or patient characteristics are design ed to be used to support clinical decision-making and vali date d according to strict method ological procedures . The REFER Study aims to determine the accuracy and cost-effectiveness of our previously derived novel , simple clinical decision rule , a natriuretic peptide assay , or their combination , in the triage for referral for echocardiography of symptomatic adult patients who present in general practice with symptoms suggestive of heart failure . Methods / design This is a prospect i ve , Phase II observational , diagnostic validation study of a clinical decision rule , natriuretic peptides or their combination , for diagnosing heart failure in primary care . Consecutive adult primary care patients 55 years of age or over presenting to their general practitioner with a chief complaint of recent new onset shortness of breath , lethargy or peripheral ankle oedema of over 48 hours duration , with no obvious recurrent , acute or self-limiting cause will be enrolled . Our reference st and ard is based upon a three step expert specialist consensus using echocardiography and clinical variables and tests . Discussion Our clinical decision rule offers a potential solution to the diagnostic challenge of providing a timely and accurate diagnosis of heart failure in primary care . Study results will provide an evidence -base from which to develop heart failure care pathway recommendations and may be useful in st and ardising care . If demonstrated to be effective , the clinical decision rule will be of interest to research ers , policy makers and general practitioners worldwide . Trial registration IS RCT Background — Early diagnosis of nonacute heart failure is crucial because prompt initiation of evidence -based treatment can prevent or slow down further progression . To diagnose new-onset heart failure in primary care is challenging . Methods and Results — This is a cross-sectional diagnostic accuracy study with external validation . Seven hundred twenty-one consecutive patients suspected of new-onset heart failure underwent st and ardized diagnostic work-up including chest x-ray , spirometry , ECG , N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) measurement , and echocardiography in specially equipped outpatient diagnostic heart failure clinics . The presence of heart failure was determined by an outcome panel using the initial clinical data and 6-month follow-up data , blinded to biomarker data . Of the 721 patients , 207 ( 28.7 % ) had heart failure . The combination of 3 items from history ( age , coronary artery disease , and loop diuretic use ) plus 6 from physical examination ( pulse rate and regularity , displaced apex beat , rales , heart murmur , and increased jugular vein pressure ) showed independent diagnostic value ( c-statistic 0.83 ) . NT-proBNP was the most powerful supplementary diagnostic test , increasing the c-statistic to 0.86 and result ing in net reclassification improvement of 69 % ( P<0.0001 ) . A simplified diagnostic rule was applied to 2 external validation data sets , result ing in c- statistics of 0.95 and 0.88 , confirming the results . Conclusions — In this study , we estimated the quantitative diagnostic contribution of elements of the history and physical examination in the diagnosis of heart failure in primary care out patients , which may help to improve clinical decision making . The largest additional quantitative diagnostic contribution to those elements was provided by measurement of NT-proBNP . For daily practice , a diagnostic rule was derived that may be useful to quantify the probability of heart failure in patients with new symptoms suggestive of heart failure Objective To identify existing prediction models for the risk of development of type 2 diabetes and to externally vali date them in a large independent cohort . Data sources Systematic search of English , German , and Dutch literature in PubMed until February 2011 to identify prediction models for diabetes . Design Performance of the models was assessed in terms of discrimination ( C statistic ) and calibration ( calibration plots and Hosmer-Lemeshow test).The validation study was a prospect i ve cohort study , with a case cohort study in a r and om subcohort . Setting Models were applied to the Dutch cohort of the European Prospect i ve Investigation into Cancer and Nutrition cohort study ( EPIC-NL ) . Participants 38 379 people aged 20 - 70 with no diabetes at baseline , 2506 of whom made up the r and om subcohort . Outcome measure Incident type 2 diabetes . Results The review identified 16 studies containing 25 prediction models . We considered 12 models as basic because they were based on variables that can be assessed non-invasively and 13 models as extended because they additionally included conventional biomarkers such as glucose concentration . During a median follow-up of 10.2 years there were 924 cases in the full EPIC-NL cohort and 79 in the r and om subcohort . The C statistic for the basic models ranged from 0.74 ( 95 % confidence interval 0.73 to 0.75 ) to 0.84 ( 0.82 to 0.85 ) for risk at 7.5 years . For prediction models including biomarkers the C statistic ranged from 0.81 ( 0.80 to 0.83 ) to 0.93 ( 0.92 to 0.94 ) . Most prediction models overestimated the observed risk of diabetes , particularly at higher observed risks . After adjustment for differences in incidence of diabetes , calibration improved considerably . Conclusions Most basic prediction models can identify people at high risk of developing diabetes in a time frame of five to 10 years . Models including biomarkers classified cases slightly better than basic ones . Most models overestimated the actual risk of diabetes . Existing prediction models therefore perform well to identify those at high risk , but can not sufficiently quantify actual risk of future diabetes AIMS To survey a r and om sample of primary care physicians across six European countries regarding their perceptions of diagnostic and prescribing issues in heart failure , and to consider factors that might be associated with physician under-performance . METHODS AND RESULTS Qualitative , postal question naire-based , vali date d survey in the native tongue of a r and om sample of 200 primary care physicians in each of five European countries ( France , Germany , Italy , The Netherl and s and Spain ) and of 250 U.K. primary care physicians . Respondents provided : details of practice characteristics ; the usual way a diagnosis of heart failure was established ; access to investigations ; names of drugs prescribed in heart failure , with estimates of the proportion of patients supplied with particular classes ; and physician attitudes regarding the evidence base ( in terms of benefits and risks ) for treatments used . Outcomes were physician perceptions and attitudes about heart failure diagnosis and treatment . Adjusted response rates varied from 17 % ( France ) to 56 % ( Britain ) . Primary care physicians underestimate the prevalence of heart failure . Most patients are diagnosed on symptoms and signs alone , with only 32 % having further investigations or referral . Although most primary care physicians stated they prescribe ACE inhibitors in heart failure , this was for only 47 - 62 % of patients , and at doses below those identified as effective in trials . Most prescribing doctors ( 91 % ) believe there is strong evidence of reduced mortality in heart failure patients using ACE inhibitors , but 51 % also consider ACE inhibitors have substantial risks with their use . CONCLUSION Limitations of the data include the general problem of question naires , whether responses accord with actual clinical practice , and , specific to these data , the low response rate in some countries ( although the study does provide information from nearly 300 r and omly selected primary care physicians across Europe ) . New preliminary insights include exposition of the ' low tech ' approach to heart failure diagnosis across Europe : doctors report the use of symptoms and signs alone ; the lack of direct ( open ) access to objective investigations , such as echocardiography , which almost guarantees that misdiagnoses will occur ; and the under-utilization and under-dosing with ACE inhibitors . The main factor influencing under-use would appear to be the exaggerated perceptions of treatment risk amongst primary care physicians that dominate the widespread and accurate knowledge of treatment benefits Background Symptoms of breathlessness , fatigue , and ankle swelling are common in general practice but deciding which patients are likely to have heart failure is challenging . Aim To evaluate the performance of a clinical decision rule ( CDR ) , with or without N-Terminal pro-B type natriuretic peptide ( NT-proBNP ) assay , for identifying heart failure . Design and setting Prospect i ve , observational , diagnostic validation study of patients aged > 55 years , presenting with shortness of breath , lethargy , or ankle oedema , from 28 general practice s in Engl and . Method The outcome was test performance of the CDR and natriuretic peptide test  in determining a diagnosis of heart failure . The reference st and ard was an expert consensus panel of three cardiologists . Results Three hundred and four participants were recruited , with 104 ( 34.2 % ; 95 % confidence interval [ CI ] = 28.9 to 39.8 ) having a confirmed diagnosis of heart failure . The CDR+NT-proBNP had a sensitivity of 90.4 % ( 95 % CI = 83.0 to 95.3 ) and specificity 45.5 % ( 95 % CI = 38.5 to 52.7 ) . NT-proBNP level alone with a cut-off < 400 pg/ml had sensitivity 76.9 % ( 95 % CI = 67.6 to 84.6 ) and specificity 91.5 % ( 95 % CI = 86.7 to 95.0 ) . At the lower cut-off of NT-proBNP < 125 pg/ml , sensitivity was 94.2 % ( 95 % CI = 87.9 to 97.9 ) and specificity 49.0 % ( 95 % CI = 41.9 to 56.1 ) . Conclusion At the low threshold of NT-proBNP < 125 pg/ml , natriuretic peptide testing alone was better than a vali date d CDR+NT-proBNP in determining which patients presenting with symptoms went on to have a diagnosis of heart failure . The higher NT-proBNP threshold of 400 pg/ml may mean more than one in five patients with heart failure are not appropriately referred . Guideline natriuretic peptide thresholds may need to be revised BACKGROUND Diagnosing suspected left ventricular systolic dysfunction ( LVSD ) in the community is a challenge for GPs . We developed and vali date d a clinical prediction rule ( CPR ) for LVSD based on history , examination and electrocardiogram ( ECG ) . METHODS Prospect i ve cohort studies of 458 symptomatic patients ( derivation cohort ) and 535 patients ( validation cohort ) in 26 general practice s in Tayside and Fife , Scotl and . All patients underwent a structured clinical examination and ECG and the ' reference st and ard ' investigation of echocardiography to establish the presence of LVSD . RESULTS Four elements from the clinical history and examination were all independently associated with LVSD -- male sex [ adjusted odds ratio ( OR ) 2.5 ; 95 % CI 1.1 , 5.0 ] , presence of orthopnoea ( OR 5.4 ; 1.9 , 13.8 ) history of myocardial infa rct ion ( OR 5.6 ; 2.3 , 13.6 ) and elevated jugular venous pulsations ( OR 15.1 ; 4.6 , 49.3 ) . Addition of ECG ( OR 20.6 ; 2.7 , 158.6 ) provides important diagnostic information in terms of probability of LVSD . A CPR based on the presence or absence of these five elements will generate probabilities ranging from 1 % to 97 % for LVSD when applied to an individual patient . In the validation cohort , the model under-predicted the probability of LVSD , particularly at lower levels of expected risk , reflecting differences in the risk-factor profiles of the derivation and validation cohorts . CONCLUSIONS The derived CPR provides quantitative estimates of post-test probability for LVSD . This rule requires further validation in other population s and setting s because of the difficulties encountered in the validation cohort AIMS Diagnosis of heart failure in primary care is often inaccurate , and access to and use of echocardiography is suboptimal . This study aim ed to develop and provisionally vali date a clinical prediction rule to optimize referral for echocardiography of people identified in primary care with suspected heart failure . METHODS AND RESULTS A systematic review identified studies of diagnosis of heart failure set in primary care . The individual patient data for five of these studies were obtained . Logistic regression models to predict heart failure were developed on one of the data sets and vali date d on the others using area under the receiver operating characteristic curve ( AUROC ) , and goodness-of-fit calibration plots . A model based upon four simple clinical features ( Male , history of myocardial Infa rct ion , Crepitations , Edema : MICE ) and natriuretic peptide had good validity when applied to other data sets , with AUROCs between 0.84 and 0.93 , and reasonable calibration . The rule performed well across the data sets , with sensitivity between 81 % and 96 % and specificity between  
    Output:
    
This review demonstrates that there are a number of clinical prediction rules relevant to the diagnosis of chronic heart failure in the literature .