Serum free beta-HCG and alpha-fetoprotein levels in IVF, ICSI and frozen embryo transfer pregnancies in maternal mid-trimester serum screening for Down's syndrome.

BACKGROUND: The aim of this study was to compare the maternal mid-trimester free beta-HCG and alpha-fetoprotein (AFP) levels in pregnancies conceived by assisted reproduction technology and spontaneous pregnancies in Down's syndrome screening. The influence of the number of embryos transferred and the amount of gonadotrophins used on the marker levels was also evaluated. METHODS: The study population consisted of 58 IVF, 32 ICSI and 26 frozen embryo transfer (FET) singleton pregnancies. The levels of beta-HCG and AFP were compared with the control group of 6548 singleton spontaneous pregnancies. RESULTS: The false positive rate (FPR) in the Down's syndrome screening was 19% overall in assisted reproductive technology pregnancies, being highest (30.8%) in the FET group. The free beta-HCG multiples of the median (MoM) values were statistically significantly elevated only in the FET group (1.33 MoM; P = 0.012). A positive correlation between the number of embryos transferred and the marker levels was observed in the IVF group. No correlation was found between the amount of gonadotrophin medication used and the marker levels. CONCLUSIONS: The present data confirm that the overall FPR in the serum screening for Down's syndrome in assisted reproduction pregnancies is high, resulting in unnecessary invasive procedures.

Frequency and clinical outcome of potentially harmful drug metabolic interactions in patients hospitalized on internal and pulmonary medicine wards: focus on warfarin and cisapride.

Drug metabolic interactions present potential risks in patient care, but their frequency and relative importance as a clinical problem remains unclear. To assess the frequency and clinical outcome of potentially harmful drug metabolic interactions in hospitalized patients, the authors performed a survey of the medication data of patients treated on internal and pulmonary medicine wards in a university hospital. The database was searched for concomitantly administered drug pairs that would, according to Hansten and Horn's drug interaction database, carry a high risk for a clinically harmful metabolic drug interaction. Coadministrations involving warfarin or cisapride were subjected to further analysis regarding clinical outcome. A total of 142 patients were exposed to 150 interactions with potentially harmful clinical outcome, resulting in a frequency of 0.9% (95% CI 0.7% to 1.0%). Inhibition of warfarin metabolism by metronidazole produced significant overanticoagulation as evidenced by elevated international normalized ratio values, whereas inducers (rifampicin and phenobarbital) of warfarin metabolism significantly reduced the efficacy of warfarin. One case of minor bleeding and one case of clavicular vein thrombosis were detected as possible consequences of disturbed anticoagulation. The coadministration of cisapride and erythromycin significantly prolonged the corrected QT (QTc) interval and was associated with clinical symptoms of cardiac arrhythmias. Coadministration of cisapride with fluconazole or miconazole was not associated with prolongation of the QTc interval or cardiac sequelae. Evaluations of patient materials are needed to assess the clinical relevance of metabolic drug interactions.

Reminders of drug effects on laboratory test results.

Drug effects on laboratory test results are difficult to take into account without an online decision support system. In this study, drug effects on hormone test results were coded using a drug-laboratory effect (DLE) code. The criteria that trigger the reminders were defined. To issue reminders, it was necessary to write a computer program linking the DLE knowledge base with databases containing individual patient medication and laboratory test results. During the first 10 months, 11% of the results from hormone samples were accompanied by one or more DLE reminders. The most common drugs to trigger reminders were glucocorticoids, furosemide, and metoclopramide. Physicians facing the reminders completed a questionnaire on the usefulness of the reminders. All respondents considered them useful. In addition, DLE reminders had caused 74% of respondents to refrain from additional, usually performed examinations. In conclusion, drug effects on laboratory tests should always be considered when interpreting laboratory results. An online reminder system is useful in displaying potential drug effects alongside test results.

Imaging end-stage kidney disease in adults. Low-field MR imaging with magnetization transfer vs. ultrasonography.

PURPOSE: To 1) assess the potential of magnetization transfer (MT)-weighted MR imaging to improve the often poor visibility of native kidneys in patients with a renal transplant; and 2) compare low-field MR imaging and ultrasonography (US) for imaging these fibrotic kidney remnants. MATERIAL AND METHODS: Seventy-two native kidneys of 36 patients were prospectively evaluated with US and MR. In low-field (0.1 T) MR imaging, T1-, T2- and MT-weighted sequences were used. MT-weighted images were compared with T2-weighted images in their ability to delineate the kidneys from their surroundings whereas US and MR were compared for detection of renal cysts and possible solid tumors. RESULTS: MT-weighted images proved superior to conventional T2-weighted images in producing contrast between the kidney remnants and their fatty surroundings. Although US revealed a few small renal cysts that were not seen at MR images, no statistical difference was found between the two modalities in this respect. CONCLUSION: MT imaging, due to its unique protein-specific signal depression, offers significantly improved visualization and delineation of end-stage kidneys. US, because its better availability and cost-benefit ratio, remains the method-of-choice compared to low-field MR imaging in detecting cysts in multicystic kidneys. MR investigation is helpful in selected patients and may be used as an alternative.

Maternal midtrimester serum AFP and free beta-hCG levels in in vitro fertilization twin pregnancies.

We aimed to compare the levels of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG) levels as multiples of the median (MoM) values between spontaneous and in vitro fertilized (IVF) twin pregnancies. The control group of spontaneous singleton pregnancies was used for calculating the gestational age specific median levels of the values. Within a cohort of 19 310 pregnancies, 145 twin pregnancies were identified. The data were collected from Down syndrome (DS) screening programmes in four University catchment areas in Finland between 1994-98. Maternal midtrimester serum marker levels were measured across gestational weeks 14-18. There were no fetal chromosome anomalies in either of the twin groups or the singleton group. Serum AFP of 145 and beta-hCG values of 39 spontaneous twin pregnancies were compared to the values of 6548 singleton pregnancies. In IVF twins 30 AFP and 29 beta-hCG values were compared to the levels of the control group. Both AFP and beta-hCG values were twice as high in the spontaneous twin pregnancies (medians 2.18 and 1.83 MoM respectively) as in the singleton group (medians 1.00 and 1.00 MoM respectively). In IVF twin pregnancies beta-hCG levels were higher (median 2.20 MoM) than in spontaneous twins (p=0.08), whereas no significant difference was found in AFP levels (2.30 MoM). In conclusion, the higher levels of beta-hCG levels in IVF twin pregnancies should be considered in DS screening to avoid high false positive rates.

TEAC-Health--research-based recommendations for European certification of health telematics services.

Health Telematics services are now a major part of health care delivery, and of citizens' health behaviour, and will rapidly develop further in scope and significance. However, despite their pivotal position in care and treatment, they are unregulated--unlike all other aspects of health care services. This anomaly is potentially putting the citizen at risk, and also underpinning good clinical practice as clinicians are uncertain of the integrity of specific health telematics tools. The TEAC-Health project, funded by the European Commission, has studied the issues, and produced evidence-based recommendations.

Considerations on the quality of medical software and information services.

Fast developments in information and communication technology have made it possible to develop new services for citizens. One of the most interesting areas is health care. Medical knowledge is usually valid all over the world that makes the market global. Information services and decision support software are becoming important tools for medical professionals but also ordinary citizens are interested in health related information. It has been estimated that by the year 2010 the turnover of health care telematics industry may be close to that of the drug industry today. The nature of this global information industry is very different from any industry in history. Since there are no frontiers, no clear products and no shops in the information market, it is difficult to develop any effective legislation. However, the history of medicine has shown that health care sector cannot be free from regulation without risking citizens' health. The huge commercial potential of the Internet has already been used to promote products and services that have no proven effect on health and that may sometimes be even dangerous. In this paper we discuss the needs and possibilities to assess the quality of medical decision support software and information services. For brevity the terms medical software and medical knowledge are used, but the issues also relate to informatics systems used by any health professional, and to computerised systems used to schedule care or to organise record systems.

Methodology for security development of an electronic prescription system.

Data security is an essential requirement in all health care applications. Developers of medical information systems should utilize the existing security development and evaluation methods to foresee as many of the technical and human factors that may endanger data security as possible and apply appropriate precautions. Modern smart card technology facilitates the building of robust security framework for interorganizational shared care systems. In this article, we describe the way we utilized the existing security evaluation criteria in developing the security concept of our electronic prescription system.

Effects of ramipril on the hormone concentrations in serum of hypertensive patients.

The effects of the angiotensin-converting enzyme inhibitor ramipril on thirteen endocrinological tests were evaluated. These tests comprised serum follitropin, lutropin, prolactin, thyrotropin, free thyroxine, total thyroxine, free triiodothyronine, parathyrin, cortisol, testosterone, sex hormone binding globulin, androstenedione and dehydroepiandrosterone sulphate. Eleven hypertensive outpatients, 9 men and 2 women, treated at the department of internal medicine in Turku University Central Hospital, received 5 mg of ramipril once a day for the study period of four weeks. The above mentioned endocrinological tests were performed before and at the end of the ramipril treatment. Ramipril decreased the value of free thyroxine statistically significantly, p = 0.011, from the mean value of 17.1 pmol/l to the mean value of 16.0 pmol/l when measured with Amerlex-MAB* free thyroxine kit. The mean within-subject difference was -1.10 pmol/l with a 95% confidence interval of -1.87 - -0.33 pmol/l. With the AutoDELFIA free thyroxine kit and with the reference method dialysis+RIA no effect was detected. Other endocrinological tests examined were not affected by ramipril. Since the decreasing effect of ramipril on free thyroxine was detected only with Amerlex-MAB* but neither with AutoDELFIA nor with dialysis+RIA, the effect was concluded to be analytical. The underlying mechanism and the component ultimately interfering with the analysis is unknown.

Visualization of clinical data with neural networks, case study: polycystic ovary syndrome.

In medicine, the use of neural networks has concentrated mainly on classification problems. Clinicians are often interested in knowing what a patient's status is compared with other similar cases. Compared with biostatistics neural networks have one major drawback: the reliability of the classification is difficult to express. Therefore, clear visualization of the measurements can be more helpful than the calculated probability of a disease. The self-organizing map is the most widely used neural network for data visualization. Although, visualization can be attached to almost any feed-forward network as well. In this paper, we describe a topology-preserving feed-forward network and compare it with the self-organizing map. The two neural network models are used in a case study on the diagnosis of polycystic ovary syndrome, which is a common female endocrine disorder characterized by menstrual abnormalities, hirsutism and infertility.

A PC program for automatic analysis of NMR spectrum series.

31P nuclear magnetic resonance (NMR) spectroscopy enables us to study intracellular energy metabolism noninvasively. The present work concerns the analysis of a series of 31P NMR spectra on human muscle during exercise. The spectra contain signals corresponding to certain metabolites in the sample and the aim is to identify and quantify these signals. We have written a PC program to perform this task automatically. With the program the results can be achieved substantially faster compared to operating with the spectrometer software. The methods implemented in the program and the functions of the program itself are described. Although we have focused on the 31P NMR spectrum series, the program can also be applied to other liquid state NMR spectra.

A medication database--a tool for detecting drug interactions in hospital.

OBJECTIVE: Drug interactions may lead to life-threatening injuries. More often, however, they lead to slow recovery, induce slight symptoms or result only in potential injury. Therefore, clinicians are not always aware of using potentially interacting drug combinations. An on-line alarming system of potential drug interactions was developed in Turku University Central Hospital. In the present study, we utilised the system to find out the incidence and nature of potential drug interactions occurring in a representative hospital patient population. METHODS: Computerised anatomical therapeutic chemical (ATC)-coded patient medication data of 2547 patients, treated in two internal medicine wards, were combined with an ATC-coded rule base of drug interactions. All potential drug interactions in the study population were searched for. RESULTS: A total of 326 potentially serious drug interactions were detected in the study population. The number of patients in this group was 173, i.e. 6.8% of all patients had one or several drug combinations which might have led to serious clinical consequences. Concomitant use of calcium and fluoroquinolones (decreased absorption) was the most common mistake (66 prescriptions). CONCLUSIONS: Potentially inappropriate drug combinations seem to occur frequently. Structured and coded medication data can be utilised efficiently to detect potential drug interactions in hospital. Computerised online monitoring and automatic alarming of potentially hazardous drug combinations might help clinicians to prescribe more safely, but further development of the system is needed to avoid unnecessary alarms.

Computerized monitoring of potentially interfering medication in thyroid function diagnostics.

OBJECTIVE: Many drugs are known to affect the results of laboratory tests. This may cause problems in the interpretation of clinical laboratory data and lead to wrong diagnoses, unnecessary further tests and additional costs. A computerized monitoring system of potential drug effects on laboratory tests was developed in Turku University Central Hospital. In the present study the incidence and nature of potentially interfering drug effects in thyroid function diagnostics was examined in order to ease the clinical implementation of the system. METHODS: Computerized medication data of 754 hospital in-patients whose thyroid function was tested were combined with a knowledge base of drug effects on laboratory tests. All medications that potentially affected the levels of serum thyrotropin or free thyroxin in study patients were detected. RESULTS: 40% (292 of 735) of the patients tested for thyrotropin and 32% (107 of 333) of the patients tested for free thyroxin received potentially interfering medication during the tests. The most common potentially interfering medication was acetylsalicylic acid, but the daily dose was usually low, 100 mg. CONCLUSIONS: The coincidence of potentially interfering medication and thyroid function tests was substantial. On-line hints of drug effects on thyroid function tests might offer valuable decision support to clinicians, but further development of the system is needed to regulate the prevalence of warnings into a clinically optimal level.

Why certification of medical software would be useful?

Human drugs and medical devices have to be approved by the health authorities before they can enter the market. For medical software this is not needed. The main argument to resist all attempts to regulate medical software has been that it is impossible to guarantee that software is error-free. This is true of all software. However, in medical software the correctness of medical knowledge is at least as important as the correctness of the code itself. The medical contents of the software could usually be evaluated but the end-users do not have the time or possibilities to do so. The Internet makes it possible to provide commercial services designed by non-professionals. For health care, there are already several commercial services on the net. Since there is no quality assurance or regulation of medical software anyone can sell medical software on the net. Even if physicians were cautious enough not to use untested software, there is a possibility that patients do. In Finland, where over 10% of the population is using the Internet at least weekly, the problem is real. It is impossible to remove poor services from the net and therefore, it is essential to guide the users to use high quality services. The paper discusses different aspects of evaluation of medical software.

Approaches for certification of electronic prescription software.

The proper management of drug treatment is essential, since adverse drug reactions are common reasons of hospitalisations. Expenditure on drug therapy has also been growing faster than any other aspect of health care in many countries. Savings and quality improvements in drug treatment could be achieved with computerised prescribing. In this paper, the architecture of an electronic prescription system is described in the light of software certification and registration. An electronic prescription system is an example of a system supporting shared care and therefore it should be person based, integrated, secure and confidential and data should be shared among health care institutions. The system architecture shares the idea of a virtual patient record and a smart card will be used as a key to prescription data located on the network. The certification and registration of medical software is a difficult and costly procedure. Ensuring the quality of software can be based on; certification of development process, voluntary evaluation, and post-market surveillance. Voluntary evaluation practice would be a precious tool for both the customers and software developers, and it would also be an invaluable source of information in terms of developing new software.

Linking patient medication data with laboratory information system.

Dozens of new drugs are taken into clinical use each year. Even if the clinicians were able to learn the most important therapeutic effects of the drugs they prescribe, they would still be unable to remember all of their minor effects. After storing patient related medication data on computerized patient records it is possible to build decision support modules which automatically remind of possible drug influences on laboratory tests and cause alarms or alerts of drug interactions. Medication profiles coded using the Anatomical Therapeutic Chemical-code (ATC-code) constitutes a valuable part of an Electronic Patient Record (EPR). In this paper, we describe the benefits of our system. By building links to commercially available drug and laboratory databases we can automatically inform clinicians on clinically relevant drug influences on laboratory test results.

Serum phospholipase A2 in patients with multiple organ failure.

Multiple organ failure (MOF) is the most common cause of death in the surgical intensive care unit. We studied the relation of MOF to changes in the concentration of group II phospholipase A2 (PLA2) in serum. Altogether, 215 surgical intensive care patients with multiple injuries, diffuse peritonitis, or sepsis and control patients, who were at a high risk for postoperative sepsis after various surgical interventions, were included in the present prospective study. The clinical performance of the MOF score and the concentrations of group II PLA2 and C-reactive protein (CRP) in serum were studied using receiver operating characteristic (ROC) curves. The group II PLA2 level was considerably above normal in all groups of patients during the first week of observation. There was a highly significant difference in group II PLA2 levels between patients with severe infections (peritonitis and sepsis) and the other patients studied (multiple injuries and elective surgery) (ROC 0.931, P < 0.0001). The concentration of group II PLA2 had a significant positive correlation to the CRP level and body temperature, which indicates that group II PLA2 is an acute phase reactant and that the determination of group II PLA2 is a useful measurement to diagnose severe infections. It was concluded that the concentration of group II PLA2 in serum effectively predicts lethal MOF in patients with multiple injuries after the second day (ROC 0.739, P < 0.01) and in patients with diffuse peritonitis after the fourth day (ROC 0.750, P < 0.02).

Artificial neural networks for decision support in clinical medicine.

Connectionist models such as neural networks are alternatives to linear, parametric statistical methods. Neural networks are computer-based pattern recognition methods with loose similarities with the nervous system. Individual variables of the network, usually called 'neurones', can receive inhibitory and excitatory inputs from other neurones. The networks can define relationships among input data that are not apparent when using other approaches, and they can use these relationships to improve accuracy. Thus, neural nets have substantial power to recognize patterns even in complex datasets. Neural network methodology has outperformed classical statistical methods in cases where the input variables are interrelated. Because clinical measurements usually derive from multiple interrelated systems it is evident that neural networks might be more accurate than classical methods in multivariate analysis of clinical data. This paper reviews the use of neural networks in medical decision support. A short introduction to the basics of neural networks is given, and some practical issues in applying the networks are highlighted. The current use of neural networks in image analysis, signal processing and laboratory medicine is reviewed. It is concluded that neural networks have an important role in image analysis and in signal processing. However, further studies are needed to determine the value of neural networks in the analysis of laboratory data.