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Objectives Twin pregnancies have a higher likelihood to experience spontaneous preterm birth (PTB). Those with imminent PTB need to be determined in order to undergo fetal lung maturation with glucocorticoids and therewith improve neonatal outcomes. The aim of this study was to assess the predictive value of the fetal fibronectin (fFN) test and the measurement of cervical length in twin pregnancies with symptoms of imminent PTB. Study design We performed an observational study on all twin pregnancies at the Medical University Vienna. Women were admitted to the hospital either due to symptoms of imminent PTB or due to a shortening of the cervical length before completed 34 weeks of gestational age. Logistic regression analysis was performed to assess the predictive value of the fFN test and cervical length on imminent preterm birth. Results The data of 82 women with twin pregnancies were eligible, of which 10 (12 %) had a positive, 45 (55 %) a negative, 21 (26 %) an unclear fFN result, and 6 (7 %) showed missing data. Cervical length ≤20 mm did not show any statistical significant prediction of PTB in our study cohort. After 7 days, 4/10 (40 %) pregnant women with positive fFN test gave birth, while 4/45 (9 %) women with a negative fFN test gave birth. Within 14 days after hospitalization, 6/10 (60 %) women with a positive fFN test gave birth, compared to 4/45 (9 %) with a negative fFN test. The positive fFN test was a statistically significant predictor of PTB within 7 days (p = 0.02) and 14 days (p = 0.004), respectively. Conclusion The fFN test has the potential to detect women with twin pregnancies, who are at risk of giving birth within the following days. Hence, the practice of hospitalizing women solely due to the shortening of the cervical length cannot be supported.

Background: Culture-proven sepsis is the gold standard in early-onset neonatal sepsis diagnosis. Infants born ≤29 weeks gestation after preterm rupture of membranes in the years 2009–2015 were included in a retrospective cohort study performed at a level III fetal-maternal unit. The study aimed to compare culture-proven sepsis, clinical sepsis and positive laboratory biomarkers ≤72 h as predictors of mortality before discharge and the combined outcome of mortality or severe short-term morbidity (severe cerebral morbidity, bronchopulmonary dysplasia and retinopathy). Results: Of the 354 patients included, culture-proven sepsis, clinical sepsis and laboratory biomarkers were positive in 2.3%, 8.5% and 9.6%, respectively. The mortality rate was 37.5% for patients with culture-proven sepsis (3/8), 33.3% for patients with clinical sepsis (10/30) and 8.8% for patients with positive laboratory biomarkers (3/34), respectively. Mortality or severe morbidity occurred in 75.0% of patients with culture-proven sepsis (6/8), 80.0% of patients with clinical sepsis (24/30) and 44.1% of patients with positive laboratory biomarkers (15/34), respectively. Conclusion: In preterm infants after preterm rupture of membranes, clinical sepsis was almost four times more common and at least equally valuable in predicting mortality and mortality or severe morbidity compared to culture-proven sepsis.

Evidence-based clinical guidelines positively effect physician decision-making. Actionable clinical guidelines that actively trigger alerts, reminders, and instructive texts will increase effectiveness. We applied Activiti, a Business Process Model and Notation language system to model a clinical guideline for the prevention of mother-to-child transmission of hepatitis B as a computerized clinical workflow. Furthermore, we implemented an interconnected Arden-Syntax-based medical rule engine, which is part of the ARDENSUITE software.

Background Chronic medical conditions such as opioid dependence require evidence-based treatment recommendations. However, pregnant women are underrepresented in clinical trials. We describe the first within-subject comparison of maternal and neonatal outcomes for methadone vs. buprenorphine exposed pregnancies. Though methadone is the established treatment of pregnant opioid dependent women, recent investigations have shown a trend for a milder neonatal abstinence syndrome (NAS) under buprenorphine. However, it is not only the choice of maintenance medication that determines the occurrence of NAS, other factors such as maternal metabolism, illicit substance abuse and nicotine consumption also influence its severity and duration and represent confounding factors in the assessment of randomized clinical trials.

Background: One third of all preterm births are due to preterm premature rupture of membranes (pPROM). An accurate prognostic evaluation after admission to the neonatal intensive care unit is necessary. Objective: The aim of this study was to identify prognostic factors within the first hour of life for mortality, short-term pulmonary morbidity, chronic lung disease (CLD) and severe cerebral morbidity in very low birth weight (VLBW) infants after pPROM. Methods: This retrospective study included 300 infants with pPROM who fit the study criteria and were derived from a cohort of 1,435 VLBW infants. A total of 17 obstetric and neonatal factors were evaluated by univariate and multivariate analysis. Results: Gestational age at birth and 5-min Apgar score correlated significantly with all 4 outcomes. The results of the first blood gas analysis correlated with 3 outcomes and the first mean arterial pressure with 2 outcomes. Anhydramnios and a lower number of courses of antenatal steroids correlated with higher mortality, and preterm labor correlated with CLD. The multivariate analysis revealed gestational age, 5-min Apgar score, the results of the first blood gas analysis, the first mean arterial pressure and anhydramnios to be significant predictors. The positive predictive value ranged from 20 to 81%, and the negative predictive value ranged from 79 to 92%. Conclusion: Gestational age at birth and parameters reflecting postnatal adaptation were the most precise factors for assessment of the prognosis of VLBW infants after pPROM within the first hour of life. Apart from anhydramnios, obstetric factors did not predict neonatal outcome. At 1 h of age, our models of perinatal risk factors were more effective in predicting a favorable outcome than an adverse outcome.

We updated a previously published meta-analysis to evaluate bacterial vaginosis (BV) and intermediate vaginal flora as risk factors for adverse pregnancy outcome. Selection criteria were original, published, English-language reports of cohort studies or control groups of clinical trials including women

Introduction Clinical decision support systems (CDSSs) are being developed to assist physicians in processing extensive data and new knowledge based on recent scientific advances. Structured medical knowledge in the form of clinical alerts or reminder rules, decision trees or tables, clinical protocols or practice guidelines, score algorithms, and others, constitute the core of CDSSs. Several medical knowledge representation and guideline languages have been developed for the formal computerized definition of such knowledge. One of these languages is Arden Syntax for Medical Logic Systems, an International Health Level Seven (HL7) standard whose development started in 1989. Its latest version is 2.10, which was presented in 2014. In the present report we discuss Arden Syntax as a modern medical knowledge representation and processing language, and show that this language is not only well suited to define clinical alerts, reminders, and recommendations, but can also be used to implement and process computerized medical practice guidelines. Methods This section describes how contemporary software such as Java, server software, web-services, XML, is used to implement CDSSs based on Arden Syntax. Special emphasis is given to clinical decision support (CDS) that employs practice guidelines as its clinical knowledge base. Results Two guideline-based applications using Arden Syntax for medical knowledge representation and processing were developed. The first is a software platform for implementing practice guidelines from dermatology. This application employs fuzzy set theory and logic to represent linguistic and propositional uncertainty in medical data, knowledge, and conclusions. The second application implements a reminder system based on clinically published standard operating procedures in obstetrics to prevent deviations from state-of-the-art care. A to-do list with necessary actions specifically tailored to the gestational week/labor/delivery is generated. Discussion Today, with the latest versions of Arden Syntax and the application of contemporary software development methods, Arden Syntax has become a powerful and versatile medical knowledge representation and processing language, well suited to implement a large range of CDSSs, including clinical-practice-guideline-based CDSSs. Moreover, such CDS is provided and can be shared as a service by different medical institutions, redefining the sharing of medical knowledge. Arden Syntax is also highly flexible and provides developers the freedom to use up-to-date software design and programming patterns for external patient data access.

We performed a meta-analysis to evaluate bacterial vaginosis as a risk factor for preterm delivery.Selection criteria were (1). the data appeared in original, published English-language reports of prospective studies or control groups of clinical trials that included women at37 weeks of gestation with intact amniotic membranes, (2). all the women had to have been screened for bacterial vaginosis that was diagnosed by either clinical criteria or criteria that were based on Gram stain findings, and (3). the outcomes were preterm delivery, spontaneous abortion, maternal or neonatal infection, and perinatal death.Eighteen studies with results for 20,232 patients were included. Bacterial vaginosis increased the risk of preterm delivery2-fold (odds ratio, 2.19; 95% CI, 1.54-3.12). Higher risks were calculated for subgroups of studies that screened for bacterial vaginosis at16 weeks of gestation (odds ratio, 7.55; 95% CI, 1.80-31.65) or at20 weeks of gestation (odds ratio, 4.20; 95% CI, 2.11-8.39). Bacterial vaginosis also significantly increased the risk of spontaneous abortion (odds ratio, 9.91; 95% CI, 1.99-49.34) and maternal infection (odds ratio, 2.53; 95% CI, 1.26-5.08). No significant results were calculated for the outcome of neonatal infection or perinatal death.Bacterial vaginosis, early in pregnancy, is a strong risk factor for preterm delivery and spontaneous abortion.

To determine the value of cervicovaginal fetal fibronectin as a marker for preterm delivery, a previously published meta-analysis was updated.Selection criteria confined the analysis to English-language original reports of prospective studies including women at37 weeks' gestation with intact amniotic membranes. For the outcomes of delivery37 or34 weeks' gestation or delivery within 7, 14, or 21 days after fibronectin sampling, we calculated sensitivity and specificity rates for each study, for subgroups of studies, and for all studies combined.A total of 40 studies were included. Statistical heterogeneity was seen in the majority of calculations of combined results and a random-effects model was used in these cases. For the outcomes of delivery37 and34 weeks' gestation, overall sensitivity rates were 52% and 53%, and overall specificity rates were 85% and 89%, respectively. For the outcomes of delivery within 7, 14, and 21 days, we calculated sensitivity rates of 71%, 67%, and 59% and specificity rates of 89%, 89%, and 92%, respectively. For the subgroup of women with symptoms of preterm labour, sensitivity rates for delivery37 and34 weeks' gestation or delivery within 7, 14, and 21 days of 54%, 63%, 77%, 74%, and 70% and specificity rates of 85%, 86%, 87%, 87%, and 90% were calculated.Cervicovaginal fetal fibronectin is an effective short-term marker of preterm delivery, especially in women with symptoms of preterm labour. Because results appear to be heterogeneous in different studies, caution should be taken when they are applied to a specific population.

The purpose of this study was to evaluate the effectiveness of antibiotic treatment of bacterial vaginosis in pregnancy to reduce preterm delivery.We performed a meta-analysis of published, English-language, randomized, placebo-controlled clinical trials of antibiotic treatment of bacterial vaginosis in pregnant women with intact amniotic membranes at37 weeks of gestation. Primary outcomes included preterm delivery, perinatal or neonatal death, and neonatal morbidity.Ten studies with results for 3969 patients were included. In patients without preterm labor, antibiotic treatment did not significantly decrease preterm delivery at37 weeks of gestation, in all patients combined (odds ratio, 0.83; 95% CI, 0.57-1.21) nor in high-risk patients with a previous preterm delivery (odds ratio, 0.50; 95% CI, 0.22-1.12). In both groups, significant statistical heterogeneity was observed. A significant reduction in preterm delivery and no statistical heterogeneity were observed in 338 high-risk patients who received oral regimens with treatment durations ofor =7 days (odds ratio, 0.42; 95% CI, 0.27-0.67). Nonsignificant effects and no statistical heterogeneity were observed in low-risk patients (odds ratio, 0.94; 95% CI, 0.71-1.25) and with vaginal regimens (odds ratio, 1.25; 95% CI: 0.86-1.81). In one study antibiotic treatment in patients with preterm labor led to a nonsignificant decrease in the rate of preterm deliveries (odds ratio, 0.31; 95% CI, 0.03-3.24).The screening of pregnant women who have bacterial vaginosis and who have had a previous preterm delivery and treatment with an oral regimen of longer duration can be justified on the basis of current evidence. More studies are needed to confirm the effectiveness of this strategy, both in high-risk patients without preterm labor and in patients with preterm labor.

In den letzten zehn Jahren wurden verschiedene chirurgische Techniken zur Behandlung der altersabhangigen Makuladegeneration (AMD) eingefuhrt. Trotz vielversprechender Ergebnisse konnte sich bis heute keine dieser operativen Behandlungsformen als Standardtherapie etablieren. In der Literatur sind zumeist kleine Fallserien beschrieben, die nur einen begrenzten Einblick uber die Wirksamkeit der submakularen Chirurgie zulassen. Es wurde ein systematischer Review der Literatur der Jahre 1992 bis 2001 mit der Suchmaschine MEDLINE durchgefuhrt. Nur wissenschaftliche Arbeiten in deutscher oder englischer Sprache uber die Behandlung von AMD, in denen die Ergebnisse einer chirurgischen Intervention beschrieben wurden, wurden inkludiert. Um die Wirksamkeit der verschiedenen operativen Therapien vergleichen zu konnen, wurden die eingeschlossenen Studien vier vordefinierten Therapiegruppen zugewiesen. Als Outcome-Parameter wurden Visusverbesserung oder -Verschlechterung nach der Operation definiert. Die Einschlusskriterien wurden von 61 Studien erfullt. Die beschriebenen operativen Eingriffe waren Extraktion von subretinalen Neovaskularisationen (CNV) (43%), Makulatranslokation (25%), Transplantation von Pigmentepithelzellen (10%) und Entfernung subretinaler Blutungen (23%). Achtunddreisig Prozent (0–87%) aller Falle zeigten eine Visusverbesserung und 26% (0–90%) eine Verschlechterung. Die submakulare Chirurgie ist eine innovative und viel versprechende Behandlungsform der exsudativen altersabhangigen Makuladegeneration. Es bedarf jedoch noch weiterer randomisierter Studien, um eindeutige Schlussfolgerungen ziehen und generelle Therapieempfehlungen aussprechen zu konnen. Different surgical procedures for the treatment of age-related macular degeneration (AMD) were introduced in the last ten years. Although promising results have been reported, none of these surgical techniques can be recommended as a standard procedure. Most studies are reporting the results of small case series, thus giving only little insight into the effectiveness of submacular surgery. We performed a systematic review using a MEDLINE search for the years 1992 to 2001. Only original English- or German-language studies evaluating surgical interventions in AMD were assigned to one of four groups of surgical treatments. The main outcomes were improve-ment or deterioration of visual acuity (VA) after surgery. Sixty-one studies met the inclusion criteria. The surgical procedures performed were removal of subfovcal choroidal neovascularization (CNV) (43%), macular translocation (25%), transplantation of pigment epithelium (10%) and removal of subretinal hemorrhage (23%). Thirty-eight percent (range 0–87%) of all cases showed an improvement of VA and 26% (range 0–90%) a deterioration. Submacular surgery appears to be an innovative and promising method for the treatment of exsudative age-related macular degeneration (AMD). More randomized clinical studies are needed to draw unbiased conclusions and to allow for standard recommendations.

Aim Type of delivery onset is not currently evaluated for its predictive impact. This study explored whether the type of preterm delivery onset was an antenatal predictor for post-natal mortality in preterm infants

To evaluate the performance of CADIAG-II/RHEUMA as consultant in the primary evaluation of patients visiting a rheumatological outpatient clinic, a CADIAG-II/RHEUMA consultation was done for 54 patients and the list of generated diagnostic hypotheses was compared to each clinical discharge diagnosis. For 26 of a total of 126 rheumatological discharge diagnoses, no matching CADIAG-II/RHEUMA diagnosis was available. 94% of all other discharge diagnoses were found in the list of CADIAG-II/RHEUMA hypotheses, 82% among the first third of the list of hypotheses and 48% among the first five hypotheses. We identified the following factors limiting the ability of CADIAG-II/RHEUMA to generate a comprehensive and correctly ranked list of diagnostic hypotheses: (1) a large percentage of patients with early stages of not clearly identified rheumatological conditions; (2) the limited number of CADIAG-II/RHEUMA diagnoses compared to the large number of known rheumatological conditions; (3) the fact that rheumato-logical diseases are rarely characterized by a single pathognomonic feature but are usually diagnosed by combinations of rather unspecific findings.

Objective. Accurately predicting the onset of delivery continues to be problematic notwithstanding the clinical relevance of this capability, especially with regard to the elective induction of labor. While the assessment of the cervix according to Bishop, to date, constitutes the single generally recognized method, the determination of fetal fibronectin (FFN) cervicovaginal secretions promises greater precision in this context. Design. English-language medical literature was analyzed using the search parameter ‘fetal fibronectin’, ‘term delivery’, ‘induction of labor’, ‘labor’, and ‘birth’, respectively. All those original reports examining cervicovaginal FFN that were originally published in English and followed a prospective design were subsequently included in the study at hand. These reports were evaluated in regard to their findings on the predictive value of FFN for spontaneous delivery and induction of labor. Results. A total of eight reports were included in the present study: five of these, covering a total of 480 patients, discussed the relationship between FFN and the spontaneous onset of labor; the other three addressed the subject of FFN and the induction of labor (300 patients). All reports clearly related the presence of FFN in cervicovaginal secretions to the imminent onset of delivery; three studies, furthermore, demonstrated a correlation with the spontaneous onset of labor, with a sensitivity greater than 90%. In case of the studies concerning induction of labor, a positive FFN result was accompanied by a significantly shorter interval until delivery than a negative FFN result. Conclusion. Determining the presence of FFN in cervicovaginal secretions promises to provide an indicator relating to the prediction of term labor, as well as to the prediction of successful labor induction.

We performed a meta-analysis to determine the value of cervicovaginal fetal fibronectin as a marker for preterm delivery.Selection criteria confined the analysis to original, English-language reports of prospective studies including women at37 weeks' gestation with intact amniotic membranes. For the outcomes of delivery at37 or34 weeks' gestation or delivery within 7, 14, 21, or 28 days after fibronectin sampling, we calculated sensitivity and specificity rates for each study, for subgroups of studies, and for all studies combined.A total of 27 studies met our inclusion criteria. For the outcomes of delivery at37 and34 weeks' gestation, overall sensitivity rates were 56% and 61% and overall specificity rates were 84% and 83%, respectively. For the outcomes of delivery within 7, 14, 21, and 28 days, we calculated sensitivity rates of 76%, 68%, 61%, and 43% and specificity rates of 88%, 89%, 91%, and 93%, respectively. For the subgroup of patients with symptoms of preterm labor, sensitivity rates for delivery within 7, 14, 21, and 28 days of 89%, 78%, 76%, and 71% and specificity rates of 86%, 86%, 88%, and 83%, respectively, were calculated.Among patients with symptoms of preterm labor, cervicovaginal fetal fibronectin appears to be among the most effective predictors of preterm delivery.

Despite scientific advances, efforts to prevent preterm birth can be disappointing. Obstetric care must focus on strategies to improve the outcome of preterm infants. The major goal is to delay preterm birth long enough to allow the transfer of women about to deliver preterm to a facility with a neonatal intensive care unit and to administer corticosteroids to enhance fetal lung maturation. A prerequisite for the success of this strategy is the reliable identification of women who will give birth preterm. Although symptoms of preterm labour strongly suggest preterm birth, contractions-even if combined with cervical effacement and dilation-do not reliably predict preterm birth. The diagnosis of true preterm labour that will eventually lead to preterm birth has been facilitated by the use of transvaginal cervical ultrasonography and by the detection of fetal fibronectin (FFN) in cervicovaginal secretions. The main clinical value of these tests is that preterm birth is very unlikely if the results of both tests are negative. This may help to avoid unnecessary transfer, hospitalisation and treatment of women with false preterm labour. The detection of phosphorylated insulin-like growth factor binding protein-1 in cervicovaginal secretions, or elevated levels of inflammatory markers, like interleukin-6, interleukin-8 and tumour necrosis factor-alpha (TNF-alpha), also predict preterm birth in symptomatic women. These markers, however, are not routinely used to predict preterm birth in women with symptoms of preterm labour.

In addition to primary predictors of preterm birth which are used to estimate the baseline risk of preterm birth, secondary predictors (based on examinations done during the current pregnancy) allow a more accurate assessment of the risk of preterm birth in individual women. Screening for early signs of spontaneous preterm labour has always been an important topic in obstetric care. During the last two decades, the detection of fetal fibronectin (FFN) from cervicovaginal secretions and cervical shortening diagnosed by transvaginal ultrasonography have emerged as the major secondary predictors of preterm birth. Both markers have been extensively studied and consistently shown to be strong short term predictors of preterm birth across a wide range of gestational ages. Other secondary predictors that confirm the role of intrauterine infection in the pathogenesis of preterm birth are bacterial vaginosis (BV) and elevated levels of interleukin (IL)-6, IL-8, ferritin and granulocyte colony-stimulating factor. Apart from BV, inflammatory markers are still not routinely used. The sensitivity of single markers in predicting preterm birth is only moderate and serial examinations of markers, combinations of different markers and multiple marker tests have been studied, with limited results. Studies of interventions in order to prevent preterm birth have also yielded mixed benefits, as a consequence of which the use of these markers to screen low risk pregnancies is generally not recommended. Currently, secondary predictors of preterm birth are used mainly to design new intervention studies tailored to specific high risk populations and to avoid unnecessary interventions in the management of high risk women.

Objective To estimate the effect of prophylactic antibiotics on neonatal mortality and morbidity in patients with preterm labor, based on a meta-analysis of seven published randomized clinical trials. Data Sources We searched 18 medical data bases, including MEDLINE from 1964 and EMBASE from 1974, to identify all literature included under preterm or premature labor and antibiotics. We scanned all abstracts from the computer printouts, the retrieved full-text reports, the references from each retrieved report, and review articles to determine whether studies met our inclusion criteria. Methods of Study Selection The following criteria were used to select studies for inclusion: article—original published report written in English; study design—randomized controlled trial; population—patients with preterm labor, defined as labor before 37 weeks' gestation; intervention—antibiotic treatment; and one or more of the following outcomes—neonatal mortality, sepsis, pneumonia, respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. Tabulation, Integration, and Results We analyzed study patients and methods, and abstracted quantitative outcome data. For each outcome, both odds ratio (OR) and 95% confidence interval (CI) were calculated. Seven trials, published between 1989 and 1995 included a total of 795 patients. Adjunctive antibiotic therapy appeared to reduce the risk of pneumonia (OR 0.45, 95% CI 0.12–1.72) and necrotizing enterocolitis (OR 0.38, 95% CI 0.14–1.08) and to increase the risk of neonatal mortality (OR 3.25, 95% CI 0.93–11.38), but it had no effect on neonatal sepsis (OR 0.98, 95% CI 0.34–2.83), respiratory distress syndrome (OR 0.93, 95% CI 0.54–1.87), and intraventricular hemorrhage (OR 1.01, 95% CI 0.20–5.10). None of the effects observed reached a significance level of P Conclusion The results of this meta-analysis do not support the routine use of adjunctive antibiotic treatment in patients with preterm labor diagnosed on the basis of subjective uterine contractions and the resulting cervical changes.

OBJECTIVE: We performed a metaanalysis of seven published randomized clinical trials to estimate more precisely the effect of prophylactic antibiotics on neonatal mortality, clinical sepsis of the neonate, respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. STUDY DESIGN: To evaluate the effect of antibiotic treatment unaffected by other forms of treatment such as tocolytics or corticosteroids, investigations in which these additional measures were used were not included. We analyzed study patients and methods and abstracted quantitative outcome data. For each outcome both odds ratios and 95% confidence intervals were calculated. RESULTS: Among the 657 patients from seven trials published between 1989 and 1994, antibiotic therapy significantly reduced the risk of neonatal sepsis by 68% (odds ratio 0.32, 95% confidence interval 0.16 to 0.65, p = 0.001) and that of intraventricular hemorrhage by 50% (odds ratio 0.50, 95% confidence interval 0.28 to 0.89, p = 0019). In contrast, no significant effect of antibiotics on overall neonatal mortality (odds ratio 0.92, 95% confidence interval 0.46 to 1.81), respiratory distress syndrome (odds ratio 0.84, 95% confidence interval 0.58 to 1.22), or necrotizing enterocolitis (odds ratio 1.27, 95% confidence interval 0.61 to 2.62) was found. CONCLUSION: This metaanalysis supports an improvement of neonatal morbidity in mothers with preterm premature rupture of membranes treated prenatally with different antibiotic regimens. (AM J OBSTET GYNECOL 1996;174:589-97.)

Identify factors for discrimination of “high” and “low risk” small for gestational age infants. Singleton infants born small for gestational age with a birthweight

Cadiag -2/ Rheuma is a medical expert system developed to assist in the differential diagnosis of rheumatic diseases. Based on fuzzy set theory and fuzzy logic, it supports the formalization of vague and uncertain medical information (i.e., medical entities and relationships between them) and draws justifiable conclusions from these imprecise data. Given a patient's finding patter, Cadiag -2 provides confirmed and excluded diagnoses, diagnostic hypotheses, and suggestions for further examinations. The knowledge base of Cadiag -2 has been designed to contain simple finding/disease relationships as well as diagnostic rules of high complexity to confirm or hypothesize disease. We shall present results obtained with 300 clinical cases from a hospital for rheumatic diseases. Different rules for the diagnosis of rheumatoid arthritis based upon classification criteria issued by the American Rheumatism Association were tested against each other. That diagnostic rule which had shown the best results was then further improved by a rheumatology expert, which finally yielded a sensitivity of 83.3% and a specificity of 95.3%.

In vitro fertilisation (IVF) pregnancies are at increased risk for adverse perinatal outcome including very low birth weight infants. The purpose of this study was to find out whether the perinatal outcome of preterm infants1500 g after IVF is different from those in naturally conceived pregnancies.This retrospective cohort study included preterm infants1500 g born between 1999 and 2007 in a tertiary perinatal referral centre. All analyses were made separately for singletons and multiples, divided into infants1000 g and 1000-1499 g. The primary study outcomes were infant mortality, short term pulmonary morbidity and cerebral morbidity. The secondary study outcomes were small for gestational age, Apgar score at 5 min, the results of the first venous blood gas analysis of the preterm infant, and the first mean arterial blood pressure after neonatal intensive care unit admission. Logistic regression analysis was done to assess the impact of IVF compared to other maternal and infant factors.1423 patients (195 IVF and 1228 non-IVF patients) were included in this study. The incidence of preterm labour was significantly higher in multiples after IVF than in spontaneously conceived multiples. In the IVF group, there were significantly more multiples. Mortality, pulmonary morbidity and cerebral morbidity did not differ among patients after IVF and naturally conceived patients. Also, there were no significant differences for the secondary outcomes, except for a significantly higher initial pH value in multiples after IVF between 1000-1499 g.IVF treatment was not associated with adverse outcome in very low birth weight infants. IVF, preterm birth, VLBW, singletons, multiples, outcome.

In this chapter, the most relevant maternal diseases with possible adverse effects on pregnancy are briefly reviewed. The choice of maternal disorders covered in this chapter reflects the chances that they may be encountered in daily practice and that they may exhibit prominent features on fetal MR examinations. The topics covered in this chapter are: hypertensive disease, diabetes mellitus, thromboembolic disease, Rhesus alloimmunization, intrauterine infection, syphilis, Listeria monocytogenes infection, rubella, Parvovirus B19 infection, Cytomegalovirus infection, Varicella-zoster virus infection, and toxoplasmosis. Genetic diseases will be covered in a specific chapter of this volume and (with the exception of inherited thrombophilias) are not reviewed in this chapter.

The aim of this meta-analysis was to summarize and to discuss the results of the four main submacular surgical procedures for age-related macular degeneration (AMD) as reported in the literature through 2004 and to compare them to the Submacular Surgery Trials (SST) data. The existing data in the literature on submacular surgery for AMD from 1992 to 2004 were evaluated. The main outcomes were proportion of patients with two or more lines of improvement in visual acuity (VA) and proportion with two or more lines of deterioration in VA after surgery. Eighty-eight studies including 1,915 cases met the inclusion criteria. Estimates for the treatment outcome within the four groups of treatment based on a logistic regression model gave comparable results for removal of choroidal neovascularization (CNV) (improvement of VA 28%, deterioration of VA 25%), macular translocation (improvement of VA 31%, deteriora-tion of VA 27%), and for transplantation of pigment epithelium (improvement of VA 22%, deterioration of VA 21%). Estimates for removal of subretinal hemorrhage were significantly different (improvement of VA 62%, deterioration of VA 13%). Selected case series showed superior results of VA compared to the SST. The question of whether this is due to selection bias that seems inevitable when dealing with medium-sized nonrandomized case series or due to better results in single centers cannot be answered. In our opinion there still seem to be indications for submacular surgery such as in patients with AMD with low preoperative VA due to large hemorrhagic or fibrotic membranes or nonresponders to photodynamic therapy (PDT).

Despite scientific advances, efforts to prevent preterm birth can be disappointing. Obstetric care must focus on strategies to improve the outcome of preterm infants. The major goal is to delay preterm birth long enough to allow the transfer of women about to deliver preterm to a facility with a neonatal intensive care unit and to administer corticosteroids to enhance fetal lung maturation. A prerequisite for the success of this strategy is the reliable identification of women who will give birth preterm. Although symptoms of preterm labour strongly suggest preterm birth, contractions-even if combined with cervical effacement and dilation-do not reliably predict preterm birth. The diagnosis of true preterm labour that will eventually lead to preterm birth has been facilitated by the use of transvaginal cervical ultrasonography and by the detection of fetal fibronectin (FFN) in cervicovaginal secretions. The main clinical value of these tests is that preterm birth is very unlikely if the results of both tests are negative. This may help to avoid unnecessary transfer, hospitalisation and treatment of women with false preterm labour. The detection of phosphorylated insulin-like growth factor binding protein-1 in cervicovaginal secretions, or elevated levels of inflammatory markers, like interleukin-6, interleukin-8 and tumour necrosis factor-alpha (TNF-alpha), also predict preterm birth in symptomatic women. These markers, however, are not routinely used to predict preterm birth in women with symptoms of preterm labour.

In addition to primary predictors of preterm birth which are used to estimate the baseline risk of preterm birth, secondary predictors (based on examinations done during the current pregnancy) allow a more accurate assessment of the risk of preterm birth in individual women. Screening for early signs of spontaneous preterm labour has always been an important topic in obstetric care. During the last two decades, the detection of fetal fibronectin (FFN) from cervicovaginal secretions and cervical shortening diagnosed by transvaginal ultrasonography have emerged as the major secondary predictors of preterm birth. Both markers have been extensively studied and consistently shown to be strong short term predictors of preterm birth across a wide range of gestational ages. Other secondary predictors that confirm the role of intrauterine infection in the pathogenesis of preterm birth are bacterial vaginosis (BV) and elevated levels of interleukin (IL)-6, IL-8, ferritin and granulocyte colony-stimulating factor. Apart from BV, inflammatory markers are still not routinely used. The sensitivity of single markers in predicting preterm birth is only moderate and serial examinations of markers, combinations of different markers and multiple marker tests have been studied, with limited results. Studies of interventions in order to prevent preterm birth have also yielded mixed benefits, as a consequence of which the use of these markers to screen low risk pregnancies is generally not recommended. Currently, secondary predictors of preterm birth are used mainly to design new intervention studies tailored to specific high risk populations and to avoid unnecessary interventions in the management of high risk women.

Background: Age-related macular degeneration (AMD) is the leading cause of legal blindness in people 50 years of age or older in the developed world. The treatment of AMD is still controversial and the search for a standard therapy for all forms of choroidal neovascularization (CNV) is on-going. Few randomized clinical trials are available regarding the surgical treatment of AMD. We performed a systematic review to determine the effectiveness of subretinal surgery for AMD and to summarize the reported results.

This paper describes the fuzzy knowledge representation framework of the medical computer consultation system MedFrame/CADIAG-IV as well as the specific knowledge acquisition techniques that have been developed to support the definition of knowledge concepts and inference rules. As in its predecessor system CADIAG-II, fuzzy medical knowledge bases are used to model the uncertainty and the vagueness of medical concepts and fuzzy logic reasoning mechanisms provide the basic inference processes. The elicitation and acquisition of medical knowledge from domain experts has often been described as the most difficult and time-consuming task in knowledge-based system development in medicine. It comes as no surprise that this is even more so when unfamiliar representations like fuzzy membership functions are to be acquired. From previous projects we have learned that a user-centered approach is mandatory in complex and ill-defined knowledge domains such as internal medicine. This paper describes the knowledge acquisition framework that has been developed in order to make easier and more accessible the three main tasks of: (a) defining medical concepts; (b) providing appropriate interpretations for patient data; and (c) constructing inferential knowledge in a fuzzy knowledge representation framework. Special emphasis is laid on the motivations for some system design and data modeling decisions. The theoretical framework has been implemented in a software package, the Knowledge Base Builder Toolkit. The conception and the design of this system reflect the need for a user-centered, intuitive, and easy-to-handle tool. First results gained from pilot studies have shown that our approach can be successfully implemented in the context of a complex fuzzy theoretical framework. As a result, this critical aspect of knowledge-based system development can be accomplished more easily.

OBJECTIVE: To review the efficacy of drug therapy for urinary urge incontinence by examining the published literature. METHODS OF STUDY SELECTION: In October 1999, we searched the medical databases MEDLINE, EMBASE, and Cochrane Controlled Trials Register to identify prospective randomized, double-blind, placebo-controlled clinical trials in the English literature evaluating drug therapy (except hormonal therapy) of urinary urge incontinence. Trials were categorized by type of drug and outcome variables. TABULATION, INTEGRATION, AND RESULTS: Forty-seven trials were identified. Twenty-four, 12, and 11 trials evaluated anticholinergic drugs, drugs with anticholinergic and calcium antagonistic properties, and alternative regimens, respectively. Data regarding treatment effects of anticholinergic drugs are consistent with a high therapeutic efficacy and characteristic side effects. Therapeutic efficacy and side effect patterns of terodiline, an agent with anticholinergic and calcium antagonistic properties, were comparable to those of anticholinergic agents. Terodiline, however, has been withdrawn from the market because of its association with cardiac arrhythmia. Of the investigated alternative drug regimens, the papaverine-like smooth muscle relaxant flavoxate was reported to be ineffective. Studies investigating the dopamine agonist bromocryptine, the α-adrenoceptor blocker prazosin, or the γ-aminobutyric acid receptor agonist baclofen showed subjective and/or objective improvement of symptoms without reaching statistical significance, whereas the tricyclic antidepressant doxepin, the neurotoxin capsaicin, and the prostaglandin synthase inhibitor flurbiprofen led to statistically significant subjective and/or objective improvement of symptoms. No data for subjective and/or objective improvement of symptoms could be extracted from the studies using the anticholinergic and calcium antagonistic agent propiverine and the calcium antagonist thiphenamil. CONCLUSION: Published trials support anticholinergic drugs as efficacious therapy for urinary urge incontinence, with predictable side effects. At present, these agents represent the pharmacological treatment of choice for this condition. The potential value of selected alternative drugs is underscored by the available data.

As part of a plan to promote semi-automatic knowledge acquisition for the medical consultant system CADIAG-II/RHEUMA, this study sought to explore and cope with the variability of results that may be anticipated when performing knowledge acquisition with patient data from different patient settings. Patient data were drawn both from a published study for the classification of rheumatoid arthritis (RA) and from a large database of rheumatological patient charts developed for the CADIAG-II/RHEUMA system. An analysis of the relationships between RA and selected CADIAG-II/RHEUMA symptoms was done using two models. In one of them, we controlled for the differences in baseline frequencies of symptoms and diseases in the two study populations as an important factor influencing the results of the calculations. Other factors that were identified included inconsistent definitions of symptoms and diseases, and the different composition of study groups in the two study populations. By eliminating differences in baseline frequencies as the most important bias, the results obtained from the two different knowledge sources became more consistent. All remaining inconsistencies and uncertainties about the contribution and relative importance of the factors were formalized using fuzzy intervals.

The purpose of this study was to investigate the placental passage of granulocyte-macrophage colony-stimulating factor in a placental perfusion model ex vivo.In an open system, 11 placentas were perfused on both the maternal and the fetal side immediately after delivery. Granulocyte-macrophage colony-stimulating factor was added to the maternal perfusion medium in concentrations from 10-55 micrograms/mL. Maternal and fetal samples were taken, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was measured by enzyme-linked immunosorbent assay.Accumulation of granulocyte-macrophage colony-stimulating factor in the fetal circuit averaged 2.42% of the concentration added initially to the arterial portion of the maternal circuit.There is only low transfer of GM-CSF across the fetal membranes. This finding is particularly remarkable in view of recently published results suggesting that administration of recombinant granulocyte growth factors to pregnant women with imminent preterm delivery helps prevent neonatal sepsis.

OBJECTIVE: This study was performed to investigate whether the demonstrated beneficial effects of antibiotics on maternal and neonatal morbidity are altered when glucocorticoids are part of the treatment of preterm premature rupture of membranes. STUDY DESIGN: We performed a metaanalysis of five published, randomized trials of antibiotic treatment in preterm premature rupture of membranes in which glucocorticoids were used as additional treatments and compared the results with those of a previously published metaanalysis of antibiotic treatment in preterm premature rupture of membranes, which excluded studies with concomitant glucocorticoids. Primary outcomes included chorioamnionitis, postpartum endometritis, neonatal sepsis, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal mortality. A logistic regression analysis was performed to test whether glucocorticoids significantly influenced the effect of antibiotic treatment. RESULTS: Among the 509 patients from five trials on antibiotic and glucocorticoid treatment published between 1986 and 1993 antibiotic therapy did not show any significant effect on any of the outcomes analyzed. In contrast, antibiotic therapy without concomitant use of glucocorticoids significantly reduced the odds of chorioamnionitis, postpartum endometritis, neonatal sepsis, and intraventricular hemorrhage by 62%, 50%, 68%, and 50%, respectively. The logistic regression analysis showed that glucocorticoids significantly diminished the effect of antibiotic treatment on chorioamnionitis and neonatal sepsis. CONCLUSION: Glucocorticoids appear to diminish the beneficial effects of antibiotics in the treatment of preterm premature rupture of membranes. A careful selection of patients who are likely to benefit from both therapies is therefore recommended. (Am J Obstet Gynecol 1998;178:899-908.)

We performed a representative survey to determine the level of knowledge of 1,010 Austrian adolescents aged 14 to 24 years about selected facts relating to the recent massive news coverage of the increase in the risk of venous thromboembolism in users of third-generation oral contraceptives and to assess the contraceptive behavior of this population. The overall use rate of oral contraceptives and condoms had increased significantly between 1991 and 1996. Sixty-six percent of the adolescents surveyed stated not having heard or read any media reports on oral contraceptives. Only 8% of those who had knew that most reports focused on the pill as a possible cause of venous thromboembolism, whereas the majority of respondents indicated that the media conveyed doubts regarding the health safety of oral contraceptives in general. Nearly half of adolescents were unable to define what a thrombosis was. Thus, although the mass media play an important role in transmitting medical information, the dissemination of practical, accurate advice on the risks of a drug and competent patient counseling is reserved for the health care professionals.

In 1987, the American Rheumatism Association issued a set of criteria for the classification of rheumatoid arthritis (RA) to provide a uniform definition of RA patients. Fuzzy set theory and fuzzy logic were used to transform this set of criteria into a diagnostic tool that offers diagnoses at different levels of confidence: a definite level, which was consistent with the original criteria definition, as well as several possible and superdefinite levels. Two fuzzy models and a reference model which provided results at a definite level only were applied to 292 clinical cases from a hospital for rheumatic diseases. At the definite level, all models yielded a sensitivity rate of 72.6% and a specificity rate of 87.0%. Sensitivity and specificity rates at the possible levels ranged from 73.3% to 85.6% and from 83.6% to 87.0%. At the superdefinite levels, sensitivity rates ranged from 39.0% to 63.7% and specificity rates from 90.4% to 95.2%. Fuzzy techniques were helpful to add flexibility to preexisting diagnostic criteria in order to obtain diagnoses at the desired level of confidence.

Since the 1960s, several knowledge-based systems for computer-assisted diagnosis in radiology have been developed. The great majority of these tools has been implemented as off-line systems. This requires interaction with the system solely for the purpose of consultation and therefore interrupts the radiologist's work flow. This and inadequate man-machine interfaces may have inhibited the routine clinical use of such systems. The goal of this paper is to describe the current research toward the development of the on-line expert system Cadiag-4/Rheuma-Radio. The underlying fundamentals of the system design, including client/server architecture, communication interfaces, and fuzzy set theory and fuzzy logic as methods for knowledge representation and interference, are presented.In radiology today, computers are routinely used to acquire radiological images in hospital and radiology information systems (HIS/RIS) and picture archiving and communication systems (PACS). In our approach, we make use of pre-existent sources of information to build an expert system that minimizes the interaction between radiologists and the computer. To handle uncertainty and vagueness of medical knowledge, fuzzy set theory and fuzzy logic are used. Given data of a specific case, a deductive inference procedure combines the observed radiological signs, establishes confirmed and excluded diagnoses as well as diagnostic hypotheses, and provides explanations for these conclusions. Furthermore, proposals for confirmation or exclusion of diagnostic hypotheses are offered.For evaluation purposes, an early prototype of Cadiag-4/Rheuma-Radio was tested on radiological disorders of the hip joint related to rheumatological diseases. Twenty radiological cases were used as test cases, reaching a diagnostic accuracy of about 80%.The first results are acceptable and encourage further work to cover the whole area of rheumatologically relevant radiological signs and diagnoses. Furthermore, research into the development of user-oriented data acquisition tools will be carried out.

The mechanism of human labor is a complex issue. A series of partly still unknown processes of hormonal, neural, biochemical and biophysical nature lead to the dramatic changes of uterine physiology at the end of pregnancy. The uterus can be separated in two parts: the corpus, mainly containing myometrium, and the cervix consisting of connective tissue. During pregnancy the myometrium is quiescent and the cervix firm and closed, prerequisites for an undisturbed growth of the embryo, During labor the myometrium has to contract regularly while the cervix needs to lose its strength allowing the passage of the fetus through the lower uterine segment. This change in the roles of the corpus and cervix is a gradual process throughout the last part of pregnancy until the onset of spontaneous labor. Many factors have been thought to be involved, however there is as yet no final theory to explain the onset of human labor (Fig. 1) [1,2]. One of the candidates as a trigger hormone for the initiation of labor is oxytocin. The concentration of oxytocin in the maternal plasma gradually rises throughout pregnancy [3]. However there is no dramatic rise before the onset of labor. This has continuously been used as an argument against the involvement of oxytocin as a trigger for human labor. It is however well known from clinical work that apart from the concentration of a hormone in the peripheral circulation, another important parameter of its action is the sensitivity of the end organ. We have therefore conducted studies to measure oxytocin sensitivity during the last days before the onset of spontaneous labor, while measuring oxytocin plasma levels at the same time [4]. Fig. 2 shows that there is a clear rise in uterine sensitivity to oxytocin during the last few days

Cadiag-2/Rheuma is a medical expert system assisting in the differential diagnosis of rheumatic diseases. The aim of this study was to establish a set of criteria for diagnosing definite rheumatoid arthritis (RA) that provides optimal accuracy and to implement this set of criteria as an IF- THEN rule for application in Cadiag-2/RHEUMA. First, two different sets of criteria for the classification of definite RA described in medical literature were implemented and their respective diagnostic accuracies were evaluated with 154 patients suffering from RA and 154 control subjects. Second, that set of criteria which had performed best became the starting point for establishing an improved set of diagnostic criteria that eventually reached an accuracy of 88.7% (81.8% sensitivity and 95.5% specificity). This improvement was possible by combining literature definition of RA with specific clinical experience of a rheumatology expert.

To evaluate the performance of CADIAG-II/RHEUMA as consultant in the primary evaluation of patients visiting a rheumatological outpatient clinic, a CADIAG-II/RHEUMA consultation was done for 54 patients and the list of generated diagnostic hypotheses was compared to each clinical discharge diagnosis. For 26 of a total of 126 rheumatological discharge diagnoses, no matching CADIAG-II/RHEUMA diagnosis was available. 94% of all other discharge diagnoses were found in the list of CADIAG-II/RHEUMA hypotheses, 82% among the first third of the list of hypotheses and 48% among the first five hypotheses. We identified the following factors limiting the ability of CADIAG-II/RHEUMA to generate a comprehensive and correctly ranked list of diagnostic hypotheses: (1) a large percentage of patients with early stages of not clearly identified rheumatological conditions; (2) the limited number of CADIAG-II/RHEUMA diagnoses compared to the large number of known rheumatological conditions; (3) the fact that rheumatological diseases are rarely characterized by a single pathognomonic feature but are usually diagnosed by combinations of rather unspecific findings.

Objective To determine more precisely the effect of prophylactic low dose aspirin on intrauterine growth retardation and perinatal mortality. Design Meta-analysis of 13 published randomised clinical trials. Methods We searched 18 medical databases, including MEDLINE since 1964 and EMBASE since 1974, review articles and the references from each retrieved report to identify all studies evaluating the effect of aspirin in pregnancy and including both intrauterine growth retardation and perinatal mortality as outcome measures. Results Among 13,234 women from 13 studies between 1985 and 1994, aspirin showed a significant reduction in intrauterine growth retardation (IUGR) (OR 0.82; 95% CI 0.72–0.93; P= 0.003) and a nonsignificant reduction in perinatal mortality (OR 0.84; 95% CI 0.66–1.08; P= 0.18). Subgroup analyses revealed that aspirin was effective at lower doses between 50 and 80 mg/day (IUGR: OR 0.87; 95% CI 0.76–0.99; mortality: OR 0.90, 95% CI 0.70–1.16), but that the preventive effect was greater at higher doses between 100 and 150 mg/day (IUGR: OR 0.36, 95% CI 0.22–0.59; mortality: OR 0.40, 95% CI 0.16–0.97) and among women entered before the 17th week of gestation (IUGR: OR 0.35, 95% CI 0.21–0.58; mortality: OR 0.43, 95% CI 0.17–1.06). We did not identify any specific subgroup of women most likely to benefit from aspirin treatment. Conclusion The results of this meta-analysis showed that early aspirin treatment reduced the risk of intrauterine growth retardation. Low dose aspirin should not be used routinely in pregnant women until those most likely to benefit from aspirin treatment have been clearly identified.