Oral sex is associated with reduced incidence of recurrent miscarriage.

A possible way of immunomodulation of the maternal immune system before pregnancy would be exposure to paternal antigens via seminal fluid to oral mucosa. We hypothesized that women with recurrent miscarriage have had less oral sex compared to women with uneventful pregnancy. In a matched case control study, 97 women with at least three unexplained consecutive miscarriages prior to the 20th week of gestation with the same partner were included. Cases were younger than 36 years at time of the third miscarriage. The control group included 137 matched women with an uneventful pregnancy. The association between oral sex and recurrent miscarriage was assessed with conditional logistic regression, odds ratios (ORs) were estimated. Missing data were imputed using Imputation by Chained Equations. In the matched analysis, 41 out of 72 women with recurrent miscarriage had have oral sex, whereas 70 out of 96 matched controls answered positive to this question (56.9% vs. 72.9%, OR 0.50 95%CI 0.25-0.97, p = 0.04). After imputation of missing exposure data (51.7%), the association became weaker (OR 0.67, 95%CI 0.36-1.24, p = 0.21). In conclusion, this study suggests a possible protective role of oral sex in the occurrence of recurrent miscarriage in a proportion of the cases. Future studies in women with recurrent miscarriage explained by immune abnormalities should reveal whether oral exposure to seminal plasma indeed modifies the maternal immune system, resulting in more live births.

Assessment of novel cardiovascular biomarkers in women with a history of recurrent miscarriage.

OBJECTIVES: A history of recurrent miscarriage is associated with future cardiovascular disease. The aim of this study was to determine novel cardiovascular biomarkers in women with a history of recurrent miscarriage as this might lead to a better understanding of the association. STUDY DESIGN: Women who visited the recurrent miscarriage clinic at Leiden University Medical Centre (between 2000 and 2010), and had three consecutive miscarriages ≤30 years were invited to participate in this follow-up study (between 2012 and 2014). The reference group consisted of women with at least one uncomplicated pregnancy and a history of no miscarriage, matched on zip code, age, and date of pregnancy. MAIN OUTCOME MEASURES: Cardiovascular biomarkers were determined, classified into; inflammation (HsCRP, lipoprotein-associated phospholipase A2), thrombosis (homocysteine, folate, anti-cardiolipin antibodies and anti-ß-2-glycoprotein antibodies), lipid metabolism (lipoprotein(a)), renal function (creatinine, microalbuminuria), myocardial damage (N-terminal pro-brain natriuretic peptide, high sensitive TroponineT) and multiple mechanisms (albumin, vitamin D). RESULTS: In both groups, 36 women were included. Women with recurrent miscarriage had a significantly higher median HsCRP (1.49 mg/L) compared to women with no miscarriage (1.01 mg/L, p = 0.03) and a significantly lower mean albumin (46.0 vs 47.6g/L, p = 0.004) and vitamin D (55.6 vs 75.4nmol/L, p = 0.007), respectively. Differences remained after adjustments for classic cardiovascular risk factors (BMI, smoking, diabetes mellitus, and hypertension). CONCLUSIONS: Our findings suggest a proinflammatory state in women with a history of recurrent miscarriage, which suggests a less optimal health, compared to women with no miscarriage. More research (observational and intervention) is warranted to investigate the association with vitamin D.

Anti-Emm in a pregnant patient--case report.

A 23-year-old primigravida of North African origin presented with a positive antibody screen at booking at 15 weeks of gestation. An antibody to a high-frequency antigen (HFA) of unknown identity was detected, which was reactive with the red blood cells of the father. This led to several challenges including antibody identification, clinical monitoring to detect signs of haemolytic disease of the foetus and newborn (HDFN) and compatible blood in case perinatal transfusion was needed. Anti-Emm was identified 2 months post-partum. This is the first published case which describes a pregnant patient with anti-Emm.

The emerging science of very early detection of disease outbreaks.

A surge of development of new public health surveillance systems designed to provide more timely detection of outbreaks suggests that public health has a new requirement: extreme timeliness of detection. The authors review previous work relevant to measuring timeliness and to defining timeliness requirements. Using signal detection theory and decision theory, the authors identify strategies to improve timeliness of detection and position ongoing system development within that framework.

A national agenda for public health informatics.

The American Medical Informatics Association 2001 Spring Congress brought together the public health and informatics communities to develop a national agenda for public health informatics. Discussions on funding and governance; architecture and infrastructure; standards and vocabulary; research, evaluation, and best practices; privacy, confidentiality, and security; and training and workforce resulted in 74 recommendations with two key themes: (1) all stakeholders need to be engaged in coordinated activities related to public health information architecture, standards, confidentiality, best practices, and research and (2) informatics training is needed throughout the public health workforce. Implementation of this consensus agenda will help promote progress in the application of information technology to improve public health.

Accuracy of ICD-9-coded chief complaints and diagnoses for the detection of acute respiratory illness.

ICD-9-coded chief complaints and diagnoses are a routinely collected source of data with potential for use in public health surveillance. We constructed two detectors of acute respiratory illness: one based on ICD-9-coded chief complaints and one based on ICD-9-coded diagnoses. We measured the classification performance of these detectors against the human classification of cases based on review of emergency department reports. Using ICD-9-coded chief complaints, the sensitivity of detection of acute respiratory illness was 0.44 and its specificity was 0.97. The sensitivity and specificity using ICD-9-coded diagnoses were no different. These properties of excellent specificity and moderate sensitivity, coupled with the earliness and electronic availability of such data, support the use of detectors based on ICD-9 coding of emergency department chief complaints in public health surveillance.

Value of ICD-9 coded chief complaints for detection of epidemics.

To assess the value of ICD-9 coded chief complaints for early detection of epidemics, we measured sensitivity, positive predictive value, and timeliness of Influenza detection using a respiratory set (RS) of ICD-9 codes and an Influenza set (IS). We also measured inherent timeliness of these data using the cross-correlation function. We found that, for a one-year period, the detectors had sensitivity of 100% (1/1 epidemic) and positive predictive values of 50% (1/2) for RS and 25% (1/4) for IS. The timeliness of detection using ICD-9 coded chief complaints was one week earlier than the detection using Pneumonia and Influenza deaths (the gold standard). The inherent timeliness of ICD-9 data measured by the cross-correlation function was two weeks earlier than the gold standard.

The use of an explanation algorithm in a clinical event monitor.

Clinical event monitors (CEMs) seek to improve patient care and reduce its cost by prompting clinicians to take actions that have these effects. To persuade clinicians to act, CEMs have used prewritten-text explanations. However, we encountered limitations of prewritten-text explanations in our CEM. Therefore, we decided to implement an advanced method for explanation (Suermondt's method for belief-network explanation). This method is promising, but whether it is generally applicable to all of clinical event monitoring and whether it is as efficacious as prewritten-text explanations remain areas for future research.

A feasibility study of two methods for end-user configuration of a clinical event monitor.

We developed and evaluated a feature that allows users to control what types of clinical information are delivered to them. Using a paper or web-based configuration form, users turn individual alerts and sets of results on or off, and set how they are delivered. We used usage rates to evaluate this feature. Of 16 residents who had received clinical information from our clinical event monitor, 4 (25%) made at least one change (range 10-25). Of 41 interns, 5 (12.2%) made at least one change (range 5-91). The difference was borderline significant (p < 0.1). 5/7 web users changed preferences through a dial-up connection from home. More users used the web-based preference form than the paper form. This difference may be due to the better accessibility of the web-based form. A survey established that this feature was not as highly utilized as anticipated partly because the initial (default) preference setting was acceptable and partly because the users were too busy to customize their alert settings. We conclude that user configuration of a system that delivers information using a web-based preference form is feasible and may become important as the volume of information and number of available communication channels increase.

Design of a clinical notification system.

We describe the requirements and design of an enterprise-wide notification system. From published descriptions of notification schemes, our own experience, and use cases provided by diverse users in our institution, we developed a set of functional requirements. The resulting design supports multiple communication channels, third party mappings (algorithms) from message to recipient and/or channel of delivery, and escalation algorithms. A requirement for multiple message formats is addressed by a document specification. We implemented this system in Java as a CORBA object. This paper describes the design and current implementation of our notification system.

[Interpretation of pair diagnosis with the Giessen test. An algorithm and a computer program to determine types]. / Zur Interpretation der Paardiagnostik mit dem Giessen-Test. Ein Algorithmus samt Auswertungsprogramm für die Bestimmung des Typus.

An algorithm is given in order to quantify the similarity of a couple's test profile in the Giessen-Test as concerns that 16 typical test profiles discovered by Brähler and Brähler (1993). The German Giessen-Test is a personality-inventory based on psychoanalysis. The Euklidian distance was chosen as a measuring unit. The identification of that typical test profile to which any couple belongs succeeds very easily, a task which is otherwise only possible with difficulty. However, any allocation is merely for reasons of description, not based on statistical decisions. As a special service, the respective computer programme is placed at everyone's disposal.

The Parents as Teachers program: results from two demonstrations.

The Parents as Teachers (PAT) program is a parent-education program that includes home visiting and is designed to begin prenatally or at birth. Through home visits, visitors called parent educators help parents to strengthen their parenting skills and knowledge of child development and to prepare young children for school. This article describes the PAT program and reports the results of evaluations of two randomized trials of PAT: (1) the Northern California (Salinas Valley) Parents as Teachers Demonstration, which served primarily Latino parents in the Salinas Valley of California's Monterey County; and (2) the Teen Parents as Teachers Demonstration, which served adolescent parents in four counties in Southern California. The two evaluations revealed small and inconsistent positive effects on parent knowledge, attitudes, and behavior, and no gains in child development or health, when analyses compared the experimental and control groups overall. However, subgroup analyses in the Salinas Valley program indicated that children in primarily Spanish-speaking Latino families benefitted more than either non-Latino or English-speaking Latino families, with significant gains in cognitive, communication, social, and self-help development. Subgroup analyses in the Teen PAT Demonstration indicated that families that received both PAT services and comprehensive case management services designed to help mothers improve their life course benefitted most. Subgroup analyses in the Salinas Valley study suggested that children in families that received more intensive services benefitted more than children whose families received less intensive services. Results from that study suggested that home visits produced about a one-month developmental advantage per 10 visits for participating children.

In vitro pharmacology of cryptophycin 52 (LY355703) in human tumor cell lines.

PURPOSE: Cryptophycin 52 (LY355703) is a new member of the cryptophycin family of antitumor agents that is currently undergoing clinical evaluation for cancer chemotherapy. The mechanism of action of the cryptophycin class of compounds is associated with an action on microtubules. This report details the pharmacological profile of this new clinical compound in a panel of human tumor cell lines. METHODS: Antiproliferative effects of cryptophycin 52 were measured indirectly by detection of the metabolic reduction of alamarBlue. Cytoxicity was assessed by enzymatic dye activation (calcein AM) combined with dye exclusion (ethidium homodimer) and by clonogenicity assay. Cell cycle effects were evaluated using flow cytometry and fluorescence microscopy. RESULTS: Both antiproliferative and cytotoxic effects of cryptophycin 52 were concentration- and time-dependent. IC50 values for antiproliferative activity in both solid and hematologic tumor cell lines were in the low picomolar range, and without exception, were significantly below values for the antimitotic agents paclitaxel and vinblastine. Flow cytometry and microscopic examination of tumor cells treated with cryptophycin 52 indicated that they accumulated in the mitotic phase of the cell cycle. Cryptophycin 52 was tested for its sensitivity to multidrug-resistance in several paired cell lines in which a sensitive parental line was matched with a multidrug-resistant derivative line. The resistant lines have been shown to over express Pgp and/or MRP multidrug-resistance transport factors. Compared to other antimitotic agents (paclitaxel, vinblastine, vincristine), the potency of cryptophycin 52 was shown to be minimally affected in multidrug-resistant cells compared to their sensitive parental lines. CONCLUSION: Cryptophycin 52 has potent antimitotic, antiproliferative and cytotoxic activity in in vitro human tumor cell models. It is significantly more potent and less sensitive to multidrug resistance mechanisms than other antimitotic antitumor agents currently used in cancer therapy. These characteristics may translate into therapeutic advantages for the clinical use of cryptophycin 52 in cancer chemotherapy.

Optimal use of communication channels in clinical event monitoring.

We argue that the optimal use of communication channels in clinical event monitors is an important design consideration for these systems. We review the state-of-the-art in selection of communication channels, including our current approach--allowing users to choose the communication channel by which the event monitor sends each notification. We describe a new approach that we are in the process of developing. In this new approach, we view event monitoring as the decision of whether and how to send new patient data to a clinician and apply the principle of maximum expected utility to this decision problem. Our initial experience with this approach suggests that notifying clinicians of normal patient data may be of high utility. We also found that methods for explanation in uncertain reasoning may be necessary in this approach.

Mobile workers in healthcare and their information needs: are 2-way pagers the answer?

The ability to have access to information relevant to patient care is essential within the healthcare environment. To meet the information needs of its workers, healthcare information systems must fulfill a variety of functional requirements. One of these requirements is to define how workers will interact with the system to gain the information they need. Currently, most healthcare information systems rely on users querying the system via a fixed terminal for the information they desire; a method that is inefficient because there is no guarantee the information will be available at the time of their query and it interrupts their work flow. In general, clinical event monitors--systems whose efficacy relies on the delivery of time-critical information--have used e-mail and numeric pagers as their methods to deliver information. Each of these methods, however, still requires the user to perform additional steps, i.e., log into an information system in order to attain the information about which the system is alerting them. In this paper we describe the integration and use of 2-way alphanumeric pagers in CLEM, the UPMC Health System's Clinical Event Monitor, and how the use of these pagers addresses the information needs of mobile workers in healthcare.

Preferences of interns and residents for E-mail, paging, or traditional methods for the delivery of different types of clinical information.

We elicited from medical house staff their preferences for e-mail and alphanumeric pager as communication channels for the delivery of 18 different types of clinical information about their inpatients. For each type, we calculated the proportion of users who preferred delivery by e-mail, pager, both, or neither (usual delivery). For 14/18 (78%) types, more users preferred delivery by pager than by the other options. For 2/18 (11%) types, e-mail was preferred. For 2/18 (11%) types, more users preferred redundant delivery using both channels. For no types did more users prefer neither, meaning that the information would be delivered by traditional channels, if any. We conclude that medical house staff in the inpatient setting prefer to receive many types of clinical information by pager. The reason may be that they otherwise would have to query clinical information systems for these data, which is wasteful of their time and introduces delays into the process of care. Additionally, we found significant inter-user variability, suggesting that it may be useful for the notification services of an enterprise to employ user profiles for the delivery of clinical information.

Representing and developing temporally abstracted knowledge as a means towards facilitating time modeling in medical decision-support systems.

The utilization of the appropriate level of temporal abstraction is an important aspect of time modeling. We discuss some aspects of the relation of temporal abstraction to important knowledge engineering parameters such as model correctness, ease of model specification, knowledge availability, query completeness, inference tractability, and semantic clarity. We propose that versatile and efficient time-modeling formalisms should encompass ways to represent and reason at more than one level of abstraction, and we discuss such a hybrid formalism. Although many research efforts have concentrated on the automation of specific temporal abstractions, much research needs to be done in understanding and developing provably optimal abstractions. We provide an initial framework for studying this problem in a manner that is independent of the particular problem domain and knowledge representation, and suggest several research challenges that appear worth pursuing.

Accuracy of data in computer-based patient records.

Data in computer-based patient records (CPRs) have many uses beyond their primary role in patient care, including research and health-system management. Although the accuracy of CPR data directly affects these applications, there has been only sporadic interest in, and no previous review of, data accuracy in CPRs. This paper reviews the published studies of data accuracy in CPRs. These studies report highly variable levels of accuracy. This variability stems from differences in study design, in types of data studied, and in the CPRs themselves. These differences confound interpretation of this literature. We conclude that our knowledge of data accuracy in CPRs is not commensurate with its importance and further studies are needed. We propose methodological guidelines for studying accuracy that address shortcomings of the current literature. As CPR data are used increasingly for research, methods used in research databases to continuously monitor and improve accuracy should be applied to CPRs.

Clinical event monitoring at the University of Pittsburgh.

Although the literature on event monitoring is extensive, it does not cover all issues that we encountered while developing an event monitor at our institution. We had to resolve issues related to event detection, scalability, what topics were suitable for asynchronous decision support, and overlap of efforts of other groups at the institution attempting to improve quality and lower cost of care. In this paper, we describe our experience deploying CLEM, the clinical event monitor at the University of Pittsburgh with emphasis on these topics.