The development and implementation of a guideline-based clinical decision support system to improve empirical antibiotic prescribing.

BACKGROUND: To describe and evaluate a clinical decision support system (CDSS) for empirical antibiotic therapy using a systematic framework. METHODS: A reporting framework for behavior change intervention implementation was used, which includes several domains: development, evaluation and implementation. Within the development domain a description is given of the engagement of stakeholders, a rationale for how the CDSS may influence antibiotic prescribing and a detailed outline of how the system was developed. Within the evaluation domain a technical validation is performed and the interaction between potential users and the CDSS is analyzed. Within the domain of implementation a description is given on how the CDSS was tested in the real world and the strategies that were used for implementation and adoption of the CDSS. RESULTS: Development: a CDSS was developed, with the involvement of stakeholders, to assist empirical antibiotic prescribing by physicians. EVALUATION: Technical problems were determined during the validation process and corrected in a new CDSS version. A usability study was performed to assess problems in the system-user interaction. IMPLEMENTATION: In 114 patients the antibiotic advice that was generated by the CDSS was followed. For 54 patients the recommendations were not adhered to. CONCLUSIONS: This study describes the development and validation of a CDSS for empirical antibiotic therapy and shows the usefulness of the systematic framework for reporting CDSS interventions. In addition it shows that CDSS recommendations are not always adhered to which is associated with incorrect use of the system.

A clinical decision support system algorithm for intravenous to oral antibiotic switch therapy: validity, clinical relevance and usefulness in a three-step evaluation study.

Objectives: To evaluate a clinical decision support system (CDSS) based on consensus-based intravenous to oral switch criteria, which identifies intravenous to oral switch candidates. Methods: A three-step evaluation study of a stand-alone CDSS with electronic health record interoperability was performed at the Erasmus University Medical Centre in the Netherlands. During the first step, we performed a technical validation. During the second step, we determined the sensitivity, specificity, negative predictive value and positive predictive value in a retrospective cohort of all hospitalized adult patients starting at least one therapeutic antibacterial drug between 1 and 16 May 2013. ICU, paediatric and psychiatric wards were excluded. During the last step the clinical relevance and usefulness was prospectively assessed by reports to infectious disease specialists. An alert was considered clinically relevant if antibiotics could be discontinued or switched to oral therapy at the time of the alert. Results: During the first step, one technical error was found. The second step yielded a positive predictive value of 76.6% and a negative predictive value of 99.1%. The third step showed that alerts were clinically relevant in 53.5% of patients. For 43.4% it had already been decided to discontinue or switch the intravenous antibiotics by the treating physician. In 10.1%, the alert resulted in advice to change antibiotic policy and was considered useful. Conclusions: This prospective cohort study shows that the alerts were clinically relevant in >50% (n = 449) and useful in 10% (n = 85). The CDSS needs to be evaluated in hospitals with varying activity of infectious disease consultancy services as this probably influences usefulness.

The added value of cardiac index and pulse pressure variation monitoring to mean arterial pressure-guided volume therapy in moderate-risk abdominal surgery (COGUIDE): a pragmatic multicentre randomised controlled trial.

There is disagreement regarding the benefits of goal-directed therapy in moderate-risk abdominal surgery. Therefore, we tested the hypothesis that the addition of non-invasive cardiac index and pulse pressure variation monitoring to mean arterial pressure-based goal-directed therapy would reduce the incidence of postoperative complications in patients having moderate-risk abdominal surgery. In this pragmatic multicentre randomised controlled trial, we randomly allocated 244 patients by envelope drawing in a 1:1 fashion, stratified per centre. All patients had mean arterial pressure, cardiac index and pulse pressure variation measured continuously. In one group, healthcare professionals were blinded to cardiac index and pulse pressure variation values and were asked to guide haemodynamic therapy only based on mean arterial pressure (control group). In the second group, cardiac index and pulse pressure variation values were displayed and kept within target ranges following a pre-defined algorithm (CI-PPV group). The primary endpoint was the incidence of postoperative complications within 30 days. One hundred and seventy-five patients were eligible for final analysis. Overall complication rates were similar (42/94 (44.7%) vs. 38/81 (46.9%) in the control and CI-PPV groups, respectively; p = 0.95). The CI-PPV group had lower mean (SD) pulse pressure variation values (9.5 (2.0)% vs. 11.9 (4.6)%; p = 0.003) and higher mean (SD) cardiac indices (2.76 (0.62) l min-1 .m-2 vs. 2.53 (0.66) l min-1 .m-2 ; p = 0.004) than the control group. In moderate-risk abdominal surgery, we observed no additional value of cardiac index and pulse pressure variation-guided haemodynamic therapy to mean arterial pressure-guided volume therapy with regard to postoperative complications.

Point prevalence of appropriate antimicrobial therapy in a Dutch university hospital.

Antimicrobial stewardship teams have been shown to increase appropriate empirical antibiotic therapy and reduce medical errors and costs in targeted populations, but the effect in non-targeted populations is still unclear. The aim of this study was to determine the prevalence of inappropriate antibiotic use in a large university hospital and identify areas in which antimicrobial stewardship will be the most effective. In a point prevalence survey we assessed the appropriateness of antibiotic therapy using an electronic surveillance system in combination with a standardized method for duration of therapy, dosage, dosage interval, route of administration, and choice of antibiotic drug. Patients using at least one antibiotic drug were included. Among 996 patients admitted in the surveyed wards, 337 patients (33.8 %) used one or more antibiotic drugs. Two hundred and twenty-one patients (22.2 %) used antibiotic medication therapeutically, with a total of 307 antibiotic prescriptions. Antibiotic therapy was deemed inappropriate in 90 (29.3 %) of these prescribed antibiotics, with an unjustified prescription as the most common reason for an inappropriate prescription. Use of fluoroquinolones and amoxicillin/clavulanic acid and a presumed diagnosis of fever of unknown origin, urinary tract infection, and respiratory tract infection were associated with inappropriate antibiotic therapy. Our study provides insight into the (in)appropriateness of antibiotic prescriptions in a tertiary care center in the Netherlands and identifies areas for improvement. The use of an electronic surveillance system for this point prevalence study is easy and may serve as a baseline measurement for the future effect of antibiotic stewardship.

The influence of anaesthetic drugs on the lower oesophageal sphincter in propofol/nitrous oxide anaesthetized dogs. Pressure profilometry in an animal model.

The lower oesophageal sphincter (LES) is the main barrier against gastro-oesophageal reflux. Various anaesthetic drugs have been reported to affect the LES pressure. In this study, the effects of cisapride, atropine, suxamethonium, vecuronium and pancuronium on the LES pressure of six mongrel dogs anaesthetized with propofol and nitrous oxide were investigated. By means of eight-channel pressure profilometry the LES pressure was measured in consecutive sessions before and after administration of each drug. Compared to basal values, atropine and suxamethonium significantly decreased LES pressure, pressure vector volume and sphincter length. Cisapride significantly increased all sphincter parameters, vecuronium significantly increased LES pressure and pressure vector volume while pancuronium had no significant effects. A significant decrease of the LES pressure and pressure vector volume was observed when nitrous oxide was omitted from the ventilation mixture. Three-dimensional imaging showed an asymmetric shape of the LES pressure which resulted from radial differences of the LES pressure. The results from this study show that both the anaesthetic animal model and the eight-channel pressure profilometry are useful procedures in studying the effects on sphincter function of different drugs during anaesthesia.

Treatment of faecal incontinence in a child with sacral agenesis: the use of biofeedback training.

The case of a 14-year-old girl is presented who was born with sacral agenesis and severe, chronic constipation not responding to laxative treatment. Biofeedback was employed in the treatment of the constipation and soiling. After six treatment sessions over four months, the constipation and soiling ceased and there was no relapse during follow-up of 12 months. Although this child had an absence of S3-S5 and the coccyx, with possible innervation abnormalities, this case illustrates that biofeedback training might be a useful adjunct to existing therapies.

Manometry, profilometry, and endosonography: normal physiology and anatomy of the anal canal in healthy children.

Normal and manometric and profilometric values and normal endosonographic features of the anal canal are required for evaluation of pathological conditions such as slow-transit constipation, anorectal outlet obstruction, and Hirschsprung's disease, status after surgery for imperforate anus, and other anal abnormalities. Anorectal manometry, profilometry (rapid-pull-through, three-dimensional, eight-channel radial manometry), and endosonography were carried out in 13 healthy children. A significant correlation was demonstrated between conventional manometric and profilometric maximal squeeze pressure of the external anal sphincter (EAS). However, the maximal and resting tone of the sphincter complex in profilometry was twice as high as in manometry due to reflexive contraction of a pelvic floor muscle, probably the EAS. With profilometry a positive correlation was found between age and sphincter length. Endosonographically assessed thickness of the EAS, puborectal muscle, and levator ani complex showed a significant correlation with age. However, no correlation was demonstrated between age and internal anal sphincter thickness. Thus, the development of the essential structures of the anal canal in children is age dependent. In addition, these measurements of normal physiology and anatomy of the anal canal provide the basis for detecting pathological conditions of the anorectal region in children.

Expression of phosphinothricin acetyltransferase from the root specific par promoter in transgenic tobacco plants is sufficient for herbicide tolerance.

The pat gene, coding for phosphinothricin acetyltransferase (PAT) from Streptomyces viridochromogenes, was cloned behind the par promoter of the hemoglobin gene from Parasponia andersonii, Introduction into tobacco (Nicotiana tabacum) resulted in predominantly root specific PAT expression. Application of 5 l/ha BASTA(®) (herbicidal component: phosphinothricin) did not effect growth morphology and vigor of the plants. After application of 20 l/ha BASTA(®) the plants showed herbicide damage. Nevertheless, they all recovered by forming new undamaged leaves and resumed full growth despite virtually non-detectable expression of the PAT enzyme in the leaves.

The lower esophageal sphincter shown by a computerized representation.

The clinical application of manometry of the lower esophageal sphincter (LES) remains controversial. This is because of the large variability in recorded lower esophageal sphincter pressure (LESP). In this paper a computerized method providing a three-dimensional image of the LES is described. In 12 healthy subjects end-expiratory rapid pull-through LESP recordings were performed for 1 h, using a perfused 8-channel probe. A cylindric model of the sphincter was calculated by means of a graphics program. The graphic representation of the LES demonstrated a circular pressure zone that was affected by the gastric migrating motility complex. This pressure zone was located proximal to a persistent indentation in the posterior and right posterolateral direction. Three-dimensional visualization of the LES provides additional information that cannot be obtained by the usually used techniques of analysis of sphincter manometry.

"Sensitive tests" are poor predictors of the decline in forced expiratory volume in one second in middle-aged smokers.

In 1978, we studied 3 groups of steelworkers 45 to 55 yr of age who were all smokers: "obstructive" smokers (OS) with a FEV1/VC less than 66.6% (59.8% in average) (n = 37), smokers with "small airways disease" (SAD) and an abnormal closing capacity and/or slope of phase III (delta N2) but normal FEV1/VC (n = 32), and "resistant" smokers (RS) with normal functional indices (n = 36). Smokers with SAD had a lower (p less than 0.05) FEV1/VC (71.7%) than did RS (74.9%). We studied again 6 yr later about 85% of survivors in each group. Analysis of variance showed that FEV1 decreased significantly (p less than 0.001) only in OS (from 2.67 to 2.46 L). In RS and smokers with SAD, FEV1 declined from 3.34 to 3.26 L and from 2.95 to 2.85 L, respectively (p greater than 0.05). In all 3 groups, delta N2 increased (p less than 0.001) from 0.77 to 1.30% N2/L in RS, 1.41 to 2.43% N2/L in smokers with SAD, and 2.22 to 4.20% N2/L in OS. A multivariate analysis showed that the initial N2 explained about 30% (p less than 0.001) of the decline in FEV1 in OS, but only 10% (p less than 0.001) in the 3 groups together. In fact, the link between delta N2 and fall in FEV1 was restricted to OS. Closing volume and maximal expiratory flow rates were not related to decline in FEV1. The link between uneveness of ventilation and subsequent loss of FEV1 is of physiopathologic interest.(ABSTRACT TRUNCATED AT 250 WORDS)

The normal pediatric Frank orthogonal electrocardiogram: variations according to age and sex.

Quantitative computerized analysis of QRS and ST-T parameters of the Frank orthogonal electrocardiogram and vectorcardiogram was undertaken in a large series of 1317 normal infants, children and adolescents stratified according to age and sex. This study confirms the influence of these two constitutional variables, age and sex, over the normal VCG in the whole time span between birth and late adolescence. As children mature, the mid-portion of the spatial QRS loop shifts leftward and posteriorly with relatively little change in the initial and terminal vectors. The spatial T loop shifts anteriorly but at a different rate in males and in females. Unidirectional changes in many amplitude parameters are observed until age 19 in males whereas in females these changes stop earlier or even show a reverse trend around puberty, leading to more important differences between adolescent males and females. Sex-related differences are the most marked for parameters representing the repolarization process. Infants under six months of age form a distinct group with larger dispersions and more disparate variations in the values of vectorcardiographic parameters than in older children. In the newborn period larger sample size might be necessary in order to reduce the normal ranges of vectorcardiographic parameters.

The normal pediatric Frank orthogonal electrocardiogram: influence of weight, height and chest circumference.

The influence of body weight, height and chest circumference on the pediatric Frank vectorcardiogram (VCG) was investigated in a population of 1317 normal infants, children and adolescents. Simple linear regression analysis showed that 94, 96 and 57 VCG variables were significantly correlated with weight, height and chest circumference, respectively. These numbers were reduced to 10, 18 and 6 VCG variables after a stepwise multiple correlation analysis. The relationship between the VCG and the somatic variables was also studied in ten different age/sex subgroups. Simple regression analysis showed a residual significant correlation between the VCG and all three somatic variables in each group. The multiple correlation analysis allowed us to define a minimum set of VCG variables, from one to six, which could explain all the variation produced by the somatic variables. The coefficient of multiple correlation between VCG and weight was the highest in babies 0 to 6 months old (R = 0.73). For height, the strongest correlation was found in females two to five years old (R = 0.76). In subjects older than two years of age, the correlation between chest circumference and VCG (R = 0.30 to 0.69) was weaker than between VCG and pediatric VCG after stratification for age and sex, especially in the youngest groups.

Helium-neon laser stabilized on iodine: design and performance.

A helium-neon laser operating at 633 nm was frequency stabilized on a hyperfine component of (127)I(2) with saturated absorption. The stability achieved was 2.5 x 10(-12) at an averaging time of 400 sec. The frequency was reproducible to 5 x 10(-11).

Variable interference reflectors with independently settable wavelength and reflectance.

This paper describes the principles and design of interference reflectors whose reflectance at any desired wavelength can be adjusted continuously over a wide range of reflectances and wavelengths by two independent calibrated adjustments. Some calculated and experimental results are given for reflectors with a reflectance range of 0-90% suitable for interference microscopy, 80-100% for laser research, and 0-2% for low loss attenuators.