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Biomedical subjects

Stephen M Downs

Publications and source records attributed to Stephen M Downs.

35 records · Page 2Linked to original sources

Child Health Improvement through Computer Automation: the CHICA system.

Clinical guidelines are prevalent but frequently not used. Computer reminder systems can improve adherence to guidelines but have not been widely adopted. We present a computer-based decision support system that combines these elements: 1) pediatric preventive care guidelines encoded in Arden Syntax; 2) a dynamic, scannable paper user interface; and 3) a HL7-compliant interface to existing electronic medical record systems. The result is a system that both delivers "just in time" patient-relevant guidelines to physicians during the clinical encounter and accurately captures structured data from all who interact with the system. The system performs these tasks while remaining sensitive to the workflow constraints of a busy outpatient pediatric practice.

Algorithms↗

Physiological changes in oocyte-cumulus cell complexes from diabetic mice that potentially influence meiotic regulation.

We have previously shown that the type I diabetic condition significantly alters meiotic regulation in mouse oocytes. In the present study, possible physiological deficiencies underlying such meiotic dysfunction were examined in oocyte-cumulus cell complexes (OCC) from type I diabetic mice. Whereas the diabetic condition did not affect glycolysis or the tricarboxylic acid cycle, the increased flux of glucose through the pentose phosphate pathway in response to FSH treatment was suppressed. De novo purine synthesis was also compromised, and ATP levels were reduced in freshly isolated OCC. Additionally, diabetes resulted in a reduction in FSH-mediated cAMP synthesis. The responsiveness of the oocyte to cAMP was also affected; fewer oocytes were induced to resume maturation after a stimulatory pulse with cAMP analogs. Meiotic induction triggered by FSH was significantly reduced, but that stimulated by phorbol ester or epidermal growth factor was affected to a much lesser extent. In addition to metabolic deficiencies, the cell-cell communication between the oocyte and the cumulus cells was reduced in diabetic mice as determined by coupling assays. Thus, numerous physiological parameters are affected by type I diabetes, and these changes may collectively contribute to altered meiotic regulation.

Animals↗

Oral erythromycin prophylaxis vs watchful waiting in caring for newborns exposed to Chlamydia trachomatis.

BACKGROUND: Chlamydia trachomatis exposure at birth may cause conjunctivitis or pneumonia. Until recently, a course of oral erythromycin prophylaxis was recommended for C trachomatis-exposed neonates. However, recognition of an association between erythromycin and pyloric stenosis prompted a change to a watchful waiting recommendation under which only infants who develop symptomatic C trachomatis infection are treated with oral erythromycin. OBJECTIVE: To compare erythromycin prophylaxis with watchful waiting for a hypothetical cohort of 100 000 neonates exposed to C trachomatis. METHODS: In a decision tree, potential outcomes were C trachomatis conjunctivitis, C trachomatis pneumonia (which could require inpatient or outpatient therapy), no clinical disease, and pyloric stenosis. Published data were reviewed to derive probability point estimates and ranges. Estimated charges served as outcome measures. RESULTS: Watchful waiting is less expensive than erythromycin prophylaxis ($15.1 million vs $28.3 million); prophylaxis prevents 5986 cases of C trachomatis pneumonia, including 1197 hospital admissions, but causes 3284 pyloric stenosis cases. (For every 30 infants given oral erythromycin prophylaxis, one additional case of pyloric stenosis would be expected to occur, and approximately 1.8 cases of C trachomatis pneumonia would be prevented.) In sensitivity analyses, if more than 3.4% of exposed neonates are hospitalized for C trachomatis pneumonia, prophylaxis becomes favored. CONCLUSIONS: This study supports the watchful waiting recommendation for asymptomatic C trachomatis-exposed neonates. However, there are wide plausible ranges for pyloric stenosis risk after erythromycin administration and for the incidence of C trachomatis pneumonia severe enough to require hospitalization; under some combinations of these rates, prophylaxis could be favored.

Anti-Bacterial Agents↗

Glutamine and the maintenance of meiotic arrest in mouse oocytes: influence of culture medium, glucose, and cumulus cells.

The selection of culture media and supplements therein has a tremendous impact on the regulation of oocyte maturation in vitro. In the present study, we have evaluated how altering the levels of glutamine in the presence or absence of glucose affects meiotic arrest in cumulus cell-enclosed oocytes (CEO) and denuded oocytes (DO) when cultured in either the simple medium M16 or the more complex Eagle's minimum essential medium (MEM). We have also tested the effectiveness of follicle-stimulating hormone (FSH) in triggering germinal vesicle breakdown (GVB) and purine de novo synthesis in differing MEM culture conditions. When DO were cultured 17-18 hr in hypoxanthine (HX)- or dbcAMP-supplemented M16 medium, neither glucose nor glutamine had any effect on oocyte maturation, with dbcAMP the more effective inhibitor. In the absence of glutamine, cumulus cells promoted meiotic resumption, since significantly lower levels of meiotic arrest were maintained in CEO than in DO by either HX or dbcAMP, but addition of the amino acid dose-dependently decreased the maturation percentage in CEO below that observed in DO. In MEM, glutamine and glucose again had little effect on the maturation of DO, although the percentage of maturing DO in HX-supplemented medium was about 20% lower than that in M16 medium. In the absence of glucose, high levels of maturation were observed in CEO in glutamine-free medium that were dose-dependently lowered by the amino acid. However, when glucose was present, CEO were as effectively arrested as DO when glutamine was absent, with no further effect of the amino acid. This inhibitory action of glucose was dependent on the essential amino acids present in MEM. The effects of glutamine were not due to changes in metabolic coupling between the oocyte and cumulus cells. Measurement of purine de novo synthesis indicated that the maintenance of meiotic arrest as well as FSH induction of meiotic resumption were associated with increases in purine synthesis. We conclude that glucose and glutamine act cooperatively to promote the synthesis of new purine compounds within the somatic compartment and that the timing and duration of such synthesis determines whether meiotic resumption will be suppressed or promoted.

Animals↗

A randomized trial of three videos that differ in the framing of information about mammography in women 40 to 49 years old.

OBJECTIVE: To assess the effect of providing structured information about the benefits and harms of mammography in differing frames on women's perceptions of screening. DESIGN: Randomized control trial. SETTING: General internal medicine academic practice. PARTICIPANTS: One hundred seventy-nine women aged 35 through 49. INTERVENTION: Women received 1 of 3 5-minute videos about the benefits and harms of screening mammography in women aged 40 to 49. These videos differed only in the way the probabilities of potential outcomes were framed (positive, neutral, or negative). MEASUREMENTS AND MAIN RESULTS: We measured the change in accurate responses to questions about potential benefits and harms of mammography, and the change in the proportion of participants who perceived that the benefits of mammography were more important than the harms. Before seeing the videos, women's knowledge about the benefits and harms of mammography was inaccurate (82% responded incorrectly to all 3 knowledge questions). After seeing the videos, the proportion that answered correctly increased by 52%, 43%, and 30% for the 3 knowledge questions, respectively, but there were no differences between video frames. At baseline, most women thought the benefits of mammography outweighed the harms (79% positive frame, 80% neutral frame, and 85% negative frame). After the videos, these proportions were similar among the 3 groups (84%, 81%, 83%, P =.93). CONCLUSIONS: Women improved the accuracy of their responses to questions about the benefits and harms of mammography after seeing the videos, but this change was not affected by the framing of information. Women strongly perceived that the benefits of mammography outweighed the harms, and providing accurate information had no effect on these perceptions, regardless of how it was framed.

Adult↗

Using adaptive turnaround documents to electronically acquire structured data in clinical settings.

We developed adaptive turnaround documents (ATDs) to address longstanding challenges inherent in acquiring structured data at the point of care. These computer-generated paper forms both request and receive patient tailored information specifically for electronic storage. In our pilot, we evaluated the usability, accuracy, and user acceptance of an ATD designed to enrich a pediatric preventative care decision support system. The system had an overall digit recognition rate of 98.6% (95% CI: 98.3 to 98.9) and a marksense accuracy of 99.2% (95% CI: 99.1 to 99.3). More importantly, the system reliably extracted all data from 56.6% (95% CI: 53.3 to 59.9) of our pilot forms without the need for a verification step. These results translate to a minimal workflow burden to end users. This suggests that ATDs can serve as an inexpensive, workflow-sensitive means of structured data acquisition in the clinical setting.

Ambulatory Care Information Systems↗

A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes.

Cyclic adenosine monophosphate (cAMP) has been implicated as an important regulator of meiotic maturation in mammalian oocytes. A decrease in cAMP, brought about by the action of cAMP phosphodiesterase (PDE), is thought to initiate germinal vesicle breakdown (GVB) by the inactivation of cAMP-dependent protein kinase. However, the product of PDE activity, 5'-AMP, is a potent activator of an important regulatory enzyme, AMP-activated protein kinase (AMPK). The aim of this study was to evaluate a possible role for AMPK in meiotic induction, using oocytes obtained from eCG-primed, immature mice. Alpha-1 and -2 isoforms of the catalytic subunit of AMPK were detected in both oocytes and cumulus cells. When 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICA riboside), an activator of AMPK, was tested on denuded oocytes (DO) and cumulus cell-enclosed oocytes (CEO) maintained in meiotic arrest by dbcAMP or hypoxanthine, GVB was dose-dependently induced. Meiotic induction by AICA riboside in dbcAMP-supplemented medium was initiated within 3 h in DO and 4 h in CEO and was accompanied by increased AMPK activity in the oocyte. AICA riboside also triggered GVB when meiotic arrest was maintained with hypoxanthine, 8-AHA-cAMP, guanosine, or milrinone, but was ineffective in olomoucine- or roscovitine-arrested oocytes, indicating that it acts upstream of maturation-promoting factor. Adenosine monophosphate dose-dependently stimulated GVB in DO when meiotic arrest was maintained with dbcAMP or hypoxanthine. This effect was not mimicked by other monophosphate or adenosine nucleotides and was not affected by inhibitors of ectophosphatases. Combined treatment with adenosine and deoxycoformycin, an adenosine deaminase inhibitor, stimulated GVB in dbcAMP-arrested CEO, suggesting AMPK activation due to AMP accumulation. It is concluded that phosphodiesterase-generated AMP may serve as a transducer of the meiotic induction process through activation of AMPK.

AMP-Activated Protein Kinases↗

Pyruvate utilization by mouse oocytes is influenced by meiotic status and the cumulus oophorus.

In this study, the effects of meiotic status on the energy substrate dynamics of mouse oocyte-cumulus cell complexes (OCCs) and denuded oocytes (DOs) have been examined. In the first series of experiments, OCCs from PMSG-primed, immature mice were cultured in minimum essential medium in 8-microl microdrops under a variety of conditions, and the medium and oocytes were sampled for pyruvate and glucose concentration and for meiotic status. Oocytes in control medium underwent germinal vesicle breakdown within 3 hr and the OCCs displayed a time-dependent increase in pyruvate consumption, but the glucose concentration changed very little. Treatment with IBMX or dbcAMP, which maintained complete meiotic arrest, suppressed pyruvate consumption, but slightly more glucose was consumed than in controls. Hypoxanthine (HX) allowed up to 10% of the oocytes to resume maturation, and pyruvate and glucose consumption resembled that of control OCCs. FSH added to HX-containing medium stimulated significant glucose consumption and pyruvate production. In general, a reciprocal relationship was observed between glucose and pyruvate consumption. When the energy substrate dynamics were compared with meiotic status of the oocytes, pyruvate consumption was associated with the maturation process. Although HX maintained oocytes in the germinal vesicle stage, the meiotic arrest was "leaky," allowing increased pyruvate consumption. Additional experiments showed that DOs at either the prophase I or metaphase II stages consumed less pyruvate than oocytes actively engaged in meiotic maturation. DOs oxidized significantly more pyruvate than OCCs, and glycolytic metabolism of glucose lowered the oxidation rate in OCCs. Furthermore, while 5-6.2 times more pyruvate was consumed by OCCs than by DOs in the absence of glucose, oxidation did not mediate the meiosis-inducing effect of pyruvate, since less of this substrate was oxidized by OCCs than by DOs. We conclude that meiotically active oocytes have a greater requirement for pyruvate than prophase I- or metaphase II-arrested oocytes and that meiotic status can influence the metabolism not only of oocytes, but also of the OCCs.

1-Methyl-3-isobutylxanthine↗

Reducing the caesarean delivery risk in elective inductions of labour: a decision analysis.

To determine whether the vaginal delivery rate is increased in nulliparous women who have positive fetal fibronectin (fFN) testing before elective induction of labour, we performed a decision analysis that tested three options: (1) spontaneous labour; (2) testing nulliparous candidates for elective induction of labour at 39 weeks gestation with fFN and inducing labour if fFN positive (women who are fFN negative are managed expectantly); (3) elective induction of labour for women who are at least 39 weeks. We found that spontaneous labour had a vaginal delivery rate of 90, elective induction 79 and fFN screening 83. At baseline, a mother must be willing to take an additional 7 risk of caesarean delivery to warrant fFN testing or an additional 11 risk of caesarean delivery to warrant elective induction. We conclude that spontaneous labour has the highest vaginal delivery rates. An fFN test in a nulliparous woman may help to raise her likelihood of a vaginal delivery in an elective induction.

Cesarean Section↗

Altered meiotic regulation in oocytes from diabetic mice.

In the present study, we have utilized a streptozotocin-induced diabetic mouse model to examine how the diabetic condition and different glucose concentrations affect several parameters of reproductive physiology. We report that oocyte maturation is altered under all experimental conditions examined. In cumulus cell-enclosed oocytes (CEO) from diabetic mice, spontaneous maturation was accelerated but the FSH-mediated delay of spontaneous maturation was suppressed. Higher glucose levels in the culture medium suppressed spontaneous maturation but did not influence the transient arrest mediated by FSH. Meiotic arrest in CEO by hypoxanthine and dibutyryl cAMP (dbcAMP) was less effective at higher glucose concentrations. In addition, both FSH-induced maturation in vitro and hCG-induced maturation in vivo were reduced by the diabetic condition. The ovulation rate was lowered by about 50% in diabetic mice and fewer ovulated ova had reached metaphase II. Despite the decreased number of ova at metaphase II, in vitro cultures showed the oocytes were capable of completing meiotic maturation at control levels. Insulin treatment reversed the detrimental effects of diabetes on meiotic induction, ovulation, and completion of meiotic maturation. Cultures of pronuclear-staged embryos confirmed a negative effect of diabetes and hyperglycemia on development to the blastocyst stage. These data suggest that defects in meiotic regulation brought about by the diabetic condition are due to decreased communication between the somatic and germ cell compartments, and it is concluded that such conditions may contribute to postfertilization developmental abnormalities.

Animals↗

A modern optical character recognition system in a real world clinical setting: some accuracy and feasibility observations.

Advances in optical character recognition (OCR) software and computer hardware have stimulated a reevaluation of the technology and its ability to capture structured clinical data from preexisting paper forms. In our pilot evaluation, we measured the accuracy and feasibility of capturing vitals data from a pediatric encounter form that has been in use for over twenty years. We found that the software had a digit recognition rate of 92.4% (95% confidence interval: 91.6 to 93.2) overall. More importantly, this system was approximately three times as fast as our existing method of data entry. These preliminary results suggest that with further refinements in the approach and additional development, we may be able to incorporate OCR as another method for capturing structured clinical data.

Electronic Data Processing↗

Expected value prioritization of prompts and reminders.

Computer-based prompting and reminder systems have been shown to be highly effective in increasing rates of preventive services delivery. However, there are many more recommended preventive services than can be practically included in a typical clinic visit. Therefore prioritization of preventive services prompts is necessary. We describe two approaches to prioritizing preventive services prompts based on expected value decision making. One method involves a static, global prioritization across all preventive services and has been used in a production system for almost 7 years. The second method uses influence diagrams to prioritize prompts dynamically, based on individual patient data. The latter approach is still under development. Both methods are labor intensive and require a combination of epidemiologic data and expert judgment. Compromises in strictly normative process were necessary to achieve user satisfaction.

Artificial Intelligence↗

A spatial analysis of obesogenic environments for children.

In this study, we use spatial analysis techniques to explore environmental and social predictors of obesity in children. We constructed a merged database, incorporating clinical data from an electronic medical record system, the Regenstrief Medical Record System (RMRS) and societal & environmental data from a geographical information system, the Social Assets and Vulnerabilities Indicators (SAVI) Project. We used the RMRS to identify cohorts of children that were normal weight, overweight, or obese. The RMRS records were geocoded and merged into the SAVI database. Using the merged databases, we analyzed the relationships between markers of socioeconomic status and obesity outcomes in children. Our preliminary analyses show that markers of low socioeconomic status at the census tract level correlate with both overweight and obese outcomes in our study population. Utilization of geographic information systems (GIS) for the study of health epidemiology is discussed.

Adolescent↗

Telephonic case-finding of major depression in a Medicaid chronic disease management program for diabetes and heart failure.

OBJECTIVE: Major depression is common in low-income and chronically ill persons and is a barrier for effective chronic disease care. We evaluated a Medicaid-sponsored strategy for detecting depressive symptoms in adults with diabetes or congestive heart failure. METHODS: Using a two-item screening tool, 890 adults enrolled in the Indiana Chronic Disease Management Program were assessed by telephone for depressive symptoms between December 2003 and March 2004. A subset of 386 participants also completed the eight-item Patient Health Questionnaire (PHQ-8) depression measure. Antidepressant use was examined using pharmacy claims. RESULTS: Depressed mood or anhedonia was reported by 51% of participants. About one in four participants had a PHQ-8 score indicating a high risk for major depression (score >or=10). The two-item screen was 96% sensitive [95% confidence interval (CI), 89-99%] and 60% specific (95% CI, 54-65%) for identifying members at high risk for depression by the full PHQ-8 instrument. Only half of participants with high-risk PHQ-8 scores had a pharmacy claim indicating that an antidepressant medication was filled within 120 days of the depression screening. CONCLUSIONS: A two-stage, telephonic approach involving the PHQ-8 instrument for Medicaid members with either depressed mood or anhedonia could identify two clinically depressed persons for every nine members screened.

Antidepressive Agents↗

A simple, flexible and scalable approach for generating tailored questionnaires and health education messages.

Tailored health information is important for generating patient-specific recommendations in clinical decision support systems and for crafting health education materials that are specifically customized to a patient. Many previous attempts to generate tailored information require complex representations, lack general applicability, and are inflexible to content alterations. In this article, we describe a simple, yet flexible approach for tailoring health communication. This generalized and scalable approach relies on a flexible state representation of each individual and an expandable rule drafting and processing engine. It utilizes a relational database schema and a simple table structure to maintain each individual's past and current health information. Content for tailored communication is represented in a single table which stores predefined logic describing the rules for selecting content applicable to specific individuals. The flexibility, scalability, and simplicity of this approach are demonstrated by describing two diverse projects. One project has provided patient-tailored decision support for physicians for over 82,000 patient encounters and the other generates tailored health questions and messages for patients through a tool developed in less than 4 months.

Decision Support Systems, Clinical↗

What adolescents with type I diabetes and their parents want from testing technology: a qualitative study.

The presence of diabetes in an adolescent can significantly affect his/her normal development. Mobile technology may offer the ability to lessen this negative impact. We wished to learn from adolescents with diabetes and their parents how monitoring systems that incorporated mobile communication technology could potentially help to reduce hassles associated with testing, improve compliance, and ease adolescent-parent conflict about testing behavior. We recruited adolescents between the ages of 13 and 18 years, living with type 1 diabetes mellitus and their parents for focus groups. Qualitative analysis of the focus group data followed a set procedure. From the discussions, the following themes were identified: issues with blood glucose monitoring and desired technology. Elements of desired technology included hardware requirements, software requirements, communication, and miscellaneous requirements. The reported needs of this end-user group can help others to leverage maximally the capabilities of new and existing technology to care for children managing chronic disease.

Adolescent↗

Variations in risk attitude across race, gender, and education.

BACKGROUND: Significant disparities in health care utilization exist across gender and race. Little is known about the patient-specific factors that may contribute to this variation. This study examined variations in risk attitude across major sociodemographic groups. METHODS: A survey elicited utility measures for health states under risk-insensitive and risk-sensitive conditions (time tradeoff and standard gamble methods, respectively). Risk attitude was modeled assuming constant proportional risk posture, thus the utility function used was a power function. A multivariable linear regression model was used to examine the relationship between risk attitude and sociodemographic factors. RESULTS: Of the 62 study subjects, the mean age was 47.6 years, 47% were female, and 33% were African American. Overall, 37% of respondents were decidedly risk averse, 37% moderately risk averse, 15% moderately risk seeking, and 11% decidedly risk seeking. Significant predictors of increasing risk aversion in multivariate modeling were white race (P < 0.01) and lower education (P < 0.05). Women also tended to be more risk averse (P = 0.07). CONCLUSIONS: This study found significant differences in risk attitude across race and educational status, with a smaller difference across gender. Further research is needed to validate these findings and clarify their contribution to racial and gender variations in health care utilization and their future role in decision and cost-effectiveness analyses.

Adult↗