[Is cobalamin measurement overprescribed by physicians? Results of an eight-year single academic centre survey]. / Les internistes français abusent-ils du dosage de la vitaminémie B12 ?

INTRODUCTION: Cobalamin (Cb) blood level is widely measured among inpatients, while relevant indications for ordering this assay in clinical practice are limited and tended to decline in the recent years. We evaluated retrospectively, in a single academic centre, changes in volume of Cb measurement in an eight-year period. RESULTS: The annual number of Cb assays has doubled between 2005 and 2012, from 3049 to 6158, in the medical departments of our hospital. The proportion of patients in which Cb was measured increased to 84% in the same period. The increase was of 36% in the internal medicine department. In this department, 30% of the 1753 patients admitted in 2012 had Cb measurement. CONCLUSION: The significant changes in the volume of Cb assay in recent years are not justified by any new scientific data about new indications for ordering Cb measurement. It seems necessary to establish robust national and international guidelines for inpatient Cb measurement.

Long-term effects of a multifaceted intervention to encourage the choice of the oral route for proton pump inhibitors: an interrupted time-series analysis.

PROBLEM: Drugs are often given intravenously even when the patient is able to swallow and when an oral form would be more cost-effective. DESIGN: Evaluation of the impact of a multifaceted intervention on the early switch from intravenous to oral administration of proton pump inhibitors (PPI) in a hospital setting. The interrupted time series of intravenous PPI consumption was analysed. BACKGROUND AND SETTING: At a French University Hospital, the Drug Committee, composed of multidisciplinary pharmacy and medical staff, addressed the issue of increasing consumption of intravenous PPI drugs (May 2003). STRATEGY FOR CHANGE: Letters to department heads, academic analyses from members of the Drug Committee, paper reminders at the point of care and audit-feedbacks by pharmacists. Monitoring of consumption and repeated reminder letters were planned. EFFECT OF CHANGE: The consumption of PPI was stable before the first intervention (mean level: 954 units/month). An immediate decrease occurred after the first Drug Committee letter (30% relative reduction, 95% CI -16% to -46%; p<0.001) with a significant trend change during the first multifaceted intervention (-24 units/month, 95% CI -42 to -7; p = 0.007). After the end of the outreach visits (July 2004), the consumptions increased (+32 units/month, 95% CI: 14 to 50, p<0.001). The second intervention had no significant impact. LESSONS LEARNT: A complex intervention (audit, feedbacks, outreach visits) had an effect on practice. It was not sustained even after a less resource-intensive intervention. Other types of interventions are needed that could be continuously implemented to improve ordering practices long term.

A comparative analysis of four clinical guidelines for hypertension management.

We compared the structure and content of guidelines for hypertension management across countries to gain an understanding of where differences between them originate from. Four guidelines published between 2003 and 2006 were selected. Two were issued by national agencies in the United Kingdom and France, and two were issued by working groups or national medical societies in the United States and in Europe. The structure of guidelines, the content of each section and their underlying bibliographic references were compared between authoring bodies. If differences were found between guidelines in terms of content, we analysed the rationales. The guidelines were sufficiently similar in structure, showing common sections such as lifestyle interventions, cardiovascular risk assessment and drug therapies. However, contentwise, major differences were observed across the four hypertension guidelines in virtually every section of the document. The definition of hypertension was consistent, whereas the grade stratification was not. Information concerning the blood pressure self-measurement, the estimation of cardiovascular risk and the antihypertensive drugs proposed for initial treatment also varied. Most of the differences were present in both guidelines and their rationales, but some were only found in the guidelines. The bibliographic references for the rationales differed significantly, with only 1.2, 2.2 and 8.8% of the total number of references were common to four, three and two authoring bodies, accounting for the variability. We conclude that improving the selection process of bibliographic references and the extraction process of guidelines from the rationales might be the first step to harmonize guidelines' development.

From paper-based to electronic guidelines: application to French guidelines.

In order to develop an internet-based decision support system, making available for French general practitioners several prevention guidelines is was necessary to implement paper based guideline. We propose a framework allowing to transform paper based practice guideline into their electronic form. Three different problems were identified: computability (e.g. determinism of the eCPG), logic (e.g. ambiguities when combining Booleans operators) and external validity (i.e. stability of decision for variations around thresholds and proportion of subjects classified in the various terminal nodes). The last problem concerned documentation of evidence: the level of evidence was associated only with the terminal decision node and not with the pathway through the decision tree. We concluded that computerisation of guidelines is not possible without expertise or authors advice. To improve computability it is necessary to provide authors with a framework that checks ambiguities, and logical errors.

Logistic regression model: an assessment of variability of predictions.

Risk prediction models available for cardiovascular prevention are statistical or based on machine learning methods. This paper investigates whether the logistic regression method can be considered as reference for validation of other methods. In order to test the stability of the predictions using this method, we performed two types of analyses on 50 random training and test samples drawn from the same database. In first analyses three models were obtained by forced entry of different sets of four variables. In second analyses, models were built with increasing number of predictive variables. The predictive performance was assessed by the area under the ROC curve. Although across-samples variability is low for a given model, it is large enough to lead to wrong conclusions when comparing different prediction methods. We also suggest that a low events-per-variable ratio alters the stability of a model's coefficients but does not affect the variability of prediction performance.

Quantitation of human immunodeficiency virus type 1 (HIV-1) RNA in cell-free cervicovaginal secretions: comparison of reverse transcription-PCR amplification (AMPLICOR HIV-A MONITOR 1.5) with enhanced-sensitivity branched-DNA assay (Quantiplex 3.0).

Two commercially available hypersensitive assays for human immunodeficiency virus type 1 (HIV-1) RNA quantitation, AMPLICOR HIV-1 Monitor Test 1.5 and Quantiplex HIV RNA 3.0, were compared to detect and quantify HIV-1 RNA in the cell-free fraction of cervicovaginal secretions collected by vaginal washing. Three panel specimens were used: pooled cervicovaginal secretions spiked with HIV-1 subtype A or HIV-1 subtype B and cervicovaginal lavages from HIV-positive and HIV-negative women. Compared to the AMPLICOR HIV-1 Monitor Test 1.5 assay, the Quantiplex HIV-1 3.0 assay yielded higher estimates of HIV-1 RNA concentrations in several tested samples spiked with HIV-1 RNA subtype A, as well as subtype B, particularly samples containing low amounts of HIV-1 RNA. The sensitivity and specificity of the AMPLICOR HIV-1 Monitor Test 1.5 assay were 93 and 100%, respectively; the sensitivity and specificity of the Quantiplex HIV RNA 3.0 assay were 97 and 50%, respectively. In conclusion, in quantifying HIV-1 RNA in cervicovaginal secretions, the Quantiplex HIV RNA 3.0 may lack specificity, and the AMPLICOR HIV-1 Monitor Test 1.5 assay, although highly specific, may lack sensitivity.

Identification of patients at high cardiovascular risk: a critical appraisal of applicability of statistical risk prediction models.

Assessment of cardiovascular risk is widely proposed as a basis for taking management decisions about patients presenting with hypertension or hypercholesterolemia. Our aim was to critically assess the use of risk equations derived from epidemiological studies for the purpose of identifying high-risk patients. Risk equations were retrieved from the MEDLINE database and then applied to a data set of 118 patients. This data set was an evaluation study of the clinical value of the World Health Organization 1993 hypertension guidelines for the decision to treat mild hypertensive patients. We calculated agreement: 1) between equations and 2) between equations and the decision to treat taken by the physician. Most models were not applicable to our population, mainly because the original population had a narrow age range or comprised only males. Between-model agreement was better for the lower and upper risk quintiles than for the three other risk quintiles (0.58, 0.33, 0.34, 0.45, 0.70, from the lower to the upper risk quintile). When using an arbitrary threshold for defining high-risk patients (i.e. > 2% per year), we observed a huge variation of the proportion of patients classified at high risk (from 0 to 17%). There was a poor agreement between risk models and the decision to treat taken by the physician. These results suggest that risk-based guidelines should be validated before their diffusion.

Modeling uncertainty in computerized guidelines using fuzzy logic.

Computerized Clinical Practice Guidelines (CPGs) improve quality of care by assisting physicians in their decision making. A number of problems emerges since patients with close characteristics are given contradictory recommendations. In this article, we propose to use fuzzy logic to model uncertainty due to the use of thresholds in CPGs. A fuzzy classification procedure has been developed that provides for each message of the CPG, a strength of recommendation that rates the appropriateness of the recommendation for the patient under consideration. This work is done in the context of a CPG for the diagnosis and the management of hypertension, published in 1997 by the French agency ANAES. A population of 82 patients with mild to moderate hypertension was selected and the results of the classification system were compared to whose given by a classical decision tree. Observed agreement is 86.6% and the variability of recommendations for patients with close characteristics is reduced.

[Information technologies: new partners in treating diabetes]. / Les techniques de l'information: de nouveaux partenaires pour soigner le diabétique.

The management of chronic diseases such as diabetes is becoming a crucial issue in developed countries. Innovative communication technologies should now be included as new partners in the health care system. These technologies can help both in managing patients and measuring quality of care. Internet-based health promotion programs may improve compliance with treatment. Decision systems are available on the Net to help patients monitoring their diet and insulin doses. The use of electronic medical record shared on Internet may help both physicians and patients to monitor on the long term the effect of interventions. It is now time to perform appropriate trials to determine, beside other interventions, the precise role of innovative communication technologies in diabetes management.

Models to predict cardiovascular risk: comparison of CART, multilayer perceptron and logistic regression.

The estimate of a multivariate risk is now required in guidelines for cardiovascular prevention. Limitations of existing statistical risk models lead to explore machine-learning methods. This study evaluates the implementation and performance of a decision tree (CART) and a multilayer perceptron (MLP) to predict cardiovascular risk from real data. The study population was randomly splitted in a learning set (n = 10,296) and a test set (n = 5,148). CART and the MLP were implemented at their best performance on the learning set and applied on the test set and compared to a logistic model. Implementation, explicative and discriminative performance criteria are considered, based on ROC analysis. Areas under ROC curves and their 95% confidence interval are 0.78 (0.75-0.81), 0.78 (0.75-0.80) and 0.76 (0.73-0.79) respectively for logistic regression, MLP and CART. Given their implementation and explicative characteristics, these methods can complement existing statistical models and contribute to the interpretation of risk.

[Cardiovascular risk and management of patients with hypertension]. / Risque cardiovasculaire et prise en charge individualisée de l'hypertendu.

Whereas cardiovascular diseases remain a priority amongst preventable diseases and that their risk factors, especially hypertension, remain inadequately controlled, new tools, such as the cardiovascular risk, would allow better targeting of treatment on high risk patients. All the evidence is in favour of prevention based on the estimation of the risk, but this article summarises the problems which this strategy continues to pose. In particular, necessity of validation at several levels of the equation or equations used (exactitude of the estimated risk, its accuracy and transportability); influence of the mode of presentation of the risk on the perception and decision of the physician and patient; practical application of the strategy; choice of decisional threshold respecting the requirements of different age groups, and presentation to physicians (recommendations and/or computerisation?).

Decision aids for triage of patients with chest pain: a systematic review of field evaluation studies.

We performed an overview of published controlled trials to assess the overall effectiveness of decision aids directed at improving triage of patients with acute chest pain. Searches of the Medline database identified 11 randomized or quasi-randomized controlled trials testing various decision aids: risk stratification system (n = 6), practice guidelines (n = 3), and formalized protocols of care (n = 2). Sensitivity, specificity of the decision aid and length of stay (LOS) in the intensive care unit (ICU) were the main outcomes. Decision aids slightly modified sensitivity and specificity (available in 5 studies), but sensitivity was already high in reference groups. Among the 9 studies providing information on LOS, 7 showed a statistically significant difference favoring the decision aid. The level of evidence concerning the efficacy of decision aids in this domain is relatively low. Larger and appropriately designed clinical trials are required to show an impact on acute cardiac ischaemia complications and mortality.

Decision aids for triage of patients with chest pain: a systematic review of field evaluation studies.

We performed an overview of published controlled trials to assess the overall effectiveness of decision aids directed at improving triage of patients with acute chest pain. Searches of the Medline database identified 11 randomized or quasi-randomized controlled trials testing various decision aids: risk stratification system (n = 6), practice guidelines (n = 3), and formalized protocols of care (n = 2). Sensitivity, specificity of the decision aid and length of stay (LOS) in the intensive care unit (ICU) were the main outcomes. Decision aids slightly modified sensitivity and specificity (available in 5 studies), but sensitivity was already high in reference groups. Among the 9 studies providing information on LOS, 7 showed a statistically significant difference favoring the decision aid. The level of evidence concerning the efficacy of decision aids in this domain is relatively low. Larger and appropriately designed clinical trials are required to show an impact on acute cardiac ischaemia complications and mortality.

A critical appraisal of the use of Internet for calculating cardiovascular risk.

This paper aims to retrieve and evaluate the quality of the Internet sites providing information on cardiovascular risk. We searched web pages related to risk prediction using six search engines. Sites proposing a cardiovascular risk prediction were selected for evaluation. The quality of each site was checked against criteria testing the validity, type and potential usefulness of information for physicians or patients. Search engines retrieved about 50 10(6) web pages. Eight sites were included. Only 2 of them provided calculation of cardiovascular risk based on Framingham equation. The others proposed algorithms, guidelines, or general information on cardiovascular health. Most sites lacked details to ensure quality of information. Present search engines are inefficient to retrieve precise and valid information. Facing the inflation of medical information, a systematic approach to validate the quality of a site is mandatory. Application of Evidence Based Medicine concepts gives a solution for evaluation of internet-based medical information.

[Arterial hypertension and cerebrovascular accident: the need for improved prevention strategies]. / Pression artérielle et accident vasculaire cérébral: nécessité d'améliorer les stratégies de prévention.

It is well demonstrated that the antihypertensive treatment is effective, particularly for the primary prevention of stroke. However, benefits of treatment are rather small in certain groups of patients. The explicit assessment of absolute cardiovascular risks and likely treatment benefits in patients with hypertension can usefully guide treatment decisions and provide a more rational basis for initiating therapy than blood pressure levels alone. This approach highlights the generally greater cardiovascular risk and potential treatment benefits in older compared with younger hypertensive patients. Some specific questions remain still unanswered. Evidence is accumulating concerning protective effect of antihypertensive treatment against dementia. Trials are in progress to investigate the effect of treatment on stroke incidence in hypertensive patients over the age of 80 years. Finally, despite the worldwide use of calcium antagonists and converting enzyme inhibitors, solid evidence of their safety and efficacy compared with the references drugs (beta-blockers and diuretics) is still lacking.

An overview of the effect of computer-assisted management of anticoagulant therapy on the quality of anticoagulation.

Risks and benefits of anticoagulant therapy depend directly of the quality of anticoagulation. We carried out a meta-analysis of published randomized trials to assess the overall effectiveness of computer-assisted prescription systems on the quality of anticoagulation. Randomized controlled trials were identified through electronic searches of the Medline database (1966-1997) and systematic analyses of the references of articles. Two investigators selected relevant papers and summarized data from the studies. The outcome variable was the proportion of days within the target range of anticoagulation. A pooled estimate of the common odds ratio of being in the target range and its confidence interval was obtained by the Mantel-Haenszel method. Nine trials having included 1336 patients were identified. Computer systems were based on a pharmacokinetic-pharmacodynamic model and a bayesian prediction method. Most of them concerned the oral anticoagulant warfarin. The global odds ratio of being in the target range was 1.29 [95% CI: 1.17-1.49], thus meaning that the use of a computer for anticoagulation optimization increased by 29% the proportion of visits where patients were appropriately treated. The proportion of clinical events was too low for allowing a summary analysis, but major hemorrhages tended to be less frequent among patients of the computer groups than among patients of the control groups (2.0 versus 3.9%). Evidence from randomized controlled trials supports the effectiveness of computer-aided anticoagulant prescription. Widespread use of these systems in ambulatory care could increase the benefit/risk ratio of anticoagulant treatment at a low cost.

Implementation of a fuzzy prototype-based machine learning method to predict myocardial infarction from coronary angiography.

Formal knowledge on the predictive value of morphological angiographic factors is lacking to estimate the risk of myocardial infarction. This article presents a computer system for predicting the incidence of myocardial infarction from angiographic morphological descriptions of coronary lesions. The system includes two phases. The learning phase consists in extracting from a large database of described stenoses two classes represented by one or several fuzzy prototypes. One class corresponds to stenoses leading to infarction and the other to stenoses not leading to that event. The evaluation phase consists in classifying a stenosis according to its morphological characteristics in one of these two classes. The learning method is based on a fuzzy supervised Machine Learning algorithm that combines some aspects of the K-nearest neighbours clustering approach with a defined measure of similarity, and a prototype induction function from the most similar stenoses, taking into account their degree of typicality. The current results of the evaluation phase to correctly predicted X% stenoses for their risk of myocardial infarction. This article emphasizes the feasibility of the approach, however, the learning phase relies on some heuristics that should be validated to get a formal evaluation of the system.

Computer-adjusted dosage of anticoagulant therapy improves the quality of anticoagulation.

OBJECTIVE: Risks and benefits of anticoagulant therapy depend directly of the quality of anticoagulation. We performed a meta-analysis of published randomized trials to assess the overall effectiveness of computer-based prescription systems on the quality of anticoagulation. DESIGN: Randomized controlled trials were identified through electronic searches of the Medline database (1966-1997) and systematic analyses of the references of articles. Two investigators selected relevant papers and summarized data from the studies. METHODS: The outcome variable was the proportion of days within the target range of anticoagulation. A pooled estimate of the common odds ratio of being in the target range and its confidence interval was obtained by the Mantel-Haenszel method. RESULTS: Seven trials having included 1217 patients were identified. Computer systems were based on a pharmacokinetic-pharmacodynamic model and a bayesian prediction method. Most of them concerned the oral anticoagulant warfarin. The global odds ratio of being in the target range was 1.58 [95% CI: 1.34-1.86], thus meaning that the use of a computer for anticoagulation optimization increased by 58% the proportion of visits where patients were appropriately treated. The proportion of clinical events was too low for allowing a summary analysis. CONCLUSION: Evidence from randomized controlled trials supports the effectiveness of computer-aided anticoagulant prescription. Diffusion of these systems in ambulatory care could increase the benefit/risk ratio of anticoagulant treatment at a low cost.