The biochemistry of oocyte maturation.
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Animals↗
Biomedical subjects
S M Downs
Publications and source records attributed to S M Downs.
Protein kinase C and meiotic regulation in isolated mouse oocytes.
In this study, the possible role of protein kinase C (PKC) in mediating both positive and negative actions on meiotic maturation in isolated mouse oocytes has been examined. When cumulus cell-enclosed oocytes (CEO) were cultured for 17-18 hr in a medium containing 4 mM hypoxanthine (HX) to maintain meiotic arrest, each of the five different activators and five different antagonists of PKC stimulated germinal vesicle breakdown (GVB) in a dose-dependent fashion. One of the activators, phorbol-12-myristate 13-acetate (PMA), also triggered GVB in CEO arrested with isobutylmethylxanthine or guanosine, but not in those arrested with dibutyryl cyclic AMP. When denuded oocytes (DO) were cultured for 3hr in inhibitor-free medium, all PKC activators suppressed maturation (<10% GVB compared to 94% in controls), while the effect of PKC antagonists was negligible. Four of the five antagonists reversed the meiosis-arresting action of HX in DO. PMA transiently arrested the spontaneous maturation of both CEO and DO, with greater potency in DO. The stimulatory action of PMA in HX-arrested oocytes was dependent on cumulus cells, because meiotic induction occurred in CEO but not DO. PKC activators also preferentially stimulated cumulus expansion when compared to antagonists. A cell-cell coupling assay determined that the action of PMA on oocyte maturation was not due to a loss of metabolic coupling between the oocyte and cumulus oophorus. Finally, Western analysis demonstrated the presence of PKCs alpha, beta1, delta, and eta in both cumulus cells and oocytes, but only PKC epsilon was detected in the cumulus cells. It is concluded that direct activation of PKC in the oocyte suppresses maturation, while stimulation within cumulus cells generates a positive trigger that leads to meiotic resumption.
Animals↗
Pediatric injury prevention counseling: an observational study of process and content.
OBJECTIVES: To describe routine injury prevention counseling; to observe how three visit components - printed prompts, parent remarks, and parent behaviors - affect such counseling; to describe the process and content of discussions about car seats as an example of routine injury prevention. METHODS: A total of 128 well-child visits of children under 7 months of age to a university pediatric clinic were videotaped (76% of eligible visits). RESULTS: Three injury topics were mentioned, on an average, per visit. Parents or caregivers rarely introduced injury topics (5%). Physicians frequently introduced those topics listed on age-specific prompting sheets (73%). Car seat counseling typically began with a physician's question (82%). Most asked simply about ownership or use (93%). Few addressed difficult issues, such as consistency of use (11%). CONCLUSIONS: Physicians bring up the injury topics that are prompted. However, most discussion is superficial. Printed prompts that address counseling process as well as content might be beneficial.
Age Factors↗
A gap-junction-mediated signal, rather than an external paracrine factor, predominates during meiotic induction in isolated mouse oocytes.
This study was carried out to compare the possible role of a secreted paracrine factor versus that of a gap-junction-transmitted signal in mediating meiotic induction in isolated mouse oocytes from PMSG-primed, immature mice. In the first set of experiments, oocyte-cumulus cell complexes (OCC) were pretreated for 3 h with 2 mM dbcAMP or FSH, washed, and the oocytes then cultured for 17-18 h in 40 microl drops containing either 300 microM dbcAMP or 4 mM hypoxanthine (HX). Each set of pretreated oocytes was cultured under three different conditions: (1) intact cumulus-cell-enclosed oocytes (CEO); (2) denuded oocytes (DO), cultured alone after removal of cumulus cells; and (3) co-cultured cumulus cells and oocytes (CC/DO), where the cumulus cells were removed in the same drop with a mouth-operated pipette and cultured alongside the oocytes. When pretreated with high dbcAMP or FSH, maturation was stimulated in CEO when cultured in either inhibitor (by 41.4-53.7%). Pretreatment failed to affect the maturation rate in DO. DO maturation was not altered appreciably by co-cultured cumulus cells when arrest was maintained with dbcAMP. However, an increase in maturation of 21-23% was observed in CC/DO in the HX-containing cultures that was not dependent on prior treatment with a meiosis-inducing stimulus. When DO were co-cultured with intact, FSH-treated OCC, there was no evidence of a positive factor secreted by the stimulated complexes, despite the fact that oocytes within the OCC were induced to resume maturation. In a second series of experiments the gap junction inhibitor, 18alpha-glycyrrhetinic acid (GA), was utilised. An initial experiment determined that GA dose-dependently blocked OCC metabolic coupling (0.2% coupling at 10 microM compared with 13.6% in controls). When HX-arrested CEO and DO were cultured for 17-18 h in medium containing increasing concentrations of GA, meiotic maturation was induced in CEO but not DO, suggesting that the cumulus cells provided a positive stimulus in the absence of functional gap junctional communication. No effect of GA was seen in dbcAMP-arrested oocytes. A kinetics experiment showed that when CEO were cultured in dbcAMP +/- FSH, meiotic induction was initiated after 3 h and germinal vesicle breakdown reached 60% by 6 h. When GA was added to the cultures at different times after the initiation of culture (0, 2, 3, 4 and 5 h), meiotic induction was immediately blocked. In addition, measurement of OCC coupling revealed that no reduction in coupling occurred during this induction period in the absence of GA. It is concluded that cumulus cells can secrete a positive factor, but that this is normally overridden by inhibitory influences transmitted through the gap junction pathway in intact complexes. Furthermore, upon exposure of complexes to a meiosis-inducing stimulus, a positive gap-junction-mediated signal now predominates to trigger germinal vesicle breakdown, and this signal is utilised throughout the induction period.
Animals↗
Meiosis-activating sterol and the maturation of isolated mouse oocytes.
This study was carried out to examine the effects of the meiosis-activating C(29) sterol, 4,4-dimethyl-5 alpha-cholesta-8,14, 24-trien-3 beta-ol (FF-MAS), on mouse oocyte maturation in vitro. Cumulus cell-enclosed oocytes (CEO) and denuded oocytes (DO) from hormonally primed, immature mice were cultured 17-18 h in minimum essential medium (MEM) containing 4 mM hypoxanthine plus increasing concentrations of FF-MAS. The sterol induced maturation in DO with an optimal concentration of 3 microg/ml but was without effect in CEO, even at concentrations as high as 10 microg/ml. Some stimulation of maturation in hypoxanthine-arrested CEO was observed when MEM was replaced by MEMalpha. Interestingly, the sterol suppressed the maturation of hypoxanthine-arrested CEO in MEM upon removal of glucose from the medium. FF-MAS also failed to induce maturation in DO when meiotic arrest was maintained with dibutyryl cAMP (dbcAMP). The rate of maturation in FF-MAS-stimulated, hypoxanthine-arrested DO was slow, as more than 6 h of culture elapsed before significant meiotic induction was observed, and this response required the continued presence of the sterol. Although the oocyte took up radiolabeled lanosterol, such accumulation was restricted by the presence of cumulus cells. In addition, lanosterol failed to augment FSH-induced maturation and was even inhibitory at a high concentration. Moreover, the downstream metabolite, cholesterol, augmented the inhibitory action of dbcAMP on maturation in both CEO and DO. Two inhibitors of 14 alpha-demethylase, ketoconazole, and 14 alpha-ethyl-5 alpha-cholest-7-ene-3 beta, 15 alpha-diol that can suppress FF-MAS production from lanosterol failed to block consistently FSH-induced maturation. These results confirm the stimulatory action of FF-MAS on hypoxanthine-arrested DO but do not support a universal meiosis-inducing function for this sterol.
Animals↗
A cost-effectiveness analysis of newborn hearing screening strategies.
CONTEXT: Congenital hearing loss affects between 1 and 3 out of every 1,000 children. Screening of all neonates has been made possible by the development of portable automated devices. Universal screening is a 2-stage screening process using automated transient-evoked otoacoustic emissions, followed when indicated by automated auditory brain response testing. Targeted screening reserves the 2-stage screening process for those infants at risk for congenital hearing loss. OBJECTIVE: To compare the expected costs and benefits of targeted screening with universal screening for the detection of significant bilateral congenital hearing loss. DESIGN: Cost-effectiveness analysis from the health care system perspective. including costs directly related to screening and initial follow-up evaluation. MAIN OUTCOME MEASURES: Number of cases identified, number of false positives, and cost per case. RESULTS: For every 100,000 newborns screened, universal screening detects 86 of 110 cases of congenital hearing loss, at a cost of $11,650 per case identified. Targeted screening identifies 51 of 110 cases, at $3,120 per case identified. Universal screening produces 320 false-positive results, 304 more than targeted screening. Switching to universal screening from targeted screening would cost an additional $23, 930 for each extra case detected. CONCLUSIONS: Universal screening detects more cases of congenital hearing loss, at the expense of both greater cost and more false-positive screening results. Little is known about the negative impact of false-positive screening and about the benefits of early intervention for congenital hearing loss. Those who advocate adoption of universal screening should be aware not only of the direct costs of universal screening, but of the indirect costs and strategies to increase the benefits of screening.
Cost-Benefit Analysis↗
Adenosine blocks hormone-induced meiotic maturation by suppressing purine de novo synthesis.
We have examined adenosine (Ado) suppression of FSH-induced germinal vesicle breakdown (GVB) and its relationship to purine de novo synthesis. Oocyte-cumulus cell complexes (OCC) from PMSG-primed, immature mice were cultured 17-18 hr in medium containing 4 mM hypoxanthine (HX) or 300 microM dibutyryl cAMP (dbcAMP) to maintain meiotic arrest, and FSH was added to stimulate meiotic maturation. In the absence of FSH, Ado (1-250 microM) had no effect in dbcAMP-arrested oocytes but dose-dependently suppressed maturation in HX-treated oocytes. FSH-induced maturation was prevented by Ado, though more effectively in dbcAMP-supplemented cultures. Ado affected the magnitude, but not the kinetics pattern, of the response to FSH. Inosine also blocked meiotic induction, but only in dbcAMP-arrested oocytes. Purine de novo synthesis was nearly doubled in OCC by FSH treatment, and this response was completely prevented by Ado. FSH had no effect on HX salvage, although Ado reduced this activity by 98%. Inosine effects on metabolism were intermediate between the control and Ado groups. Experiments with radiolabeled energy substrates showed that Ado suppressed FSH activation of the pentose phosphate pathway but did not prevent significant activation of glycolysis or oxidation of pyruvate. Finally, in cultured follicles from primed mice, hCG-induced maturation was blocked by Ado as effectively as by the purine de novo synthesis inhibitor, azaserine. It is concluded that Ado has an inhibitory action on hormone-induced maturation that is due, at least in part, to suppression of glucose metabolism, leading to compromised purine de novo synthesis.
Adenosine↗
Energy substrates and the completion of spontaneous meiotic maturation.
This study was carried out to examine how different combinations of pyruvate and glucose affect spontaneous meiotic maturation of cumulus-cell-enclosed mouse oocytes (CEO) to metaphase II (MII). Most experiments used an open system in which oocytes were cultured in 1 ml medium in plastic tubes. Initial experiments examined the dose response effects of pyruvate or glucose alone in the presence or absence of 2 mM glutamine. When medium lacked both pyruvate and glucose, more than 91% of the oocytes died in glutamine-free medium during 15 h of culture; viability was restored with the addition of glutamine, but only 11% of the CEO reached MII. In the absence of glutamine, 62-68% of oocytes completed maturation in 0.23-2.3 mM pyruvate, while 44-60% MII was observed in 0.55-27.8 mM glucose. The addition of glutamine to these cultures had a general suppressive effect on the completion of maturation. When glucose was added to pyruvate-containing cultures, the combination of 1 mM pyruvate/5.5 mM glucose was most effective in supporting maturation (about 90% MII), with little effect of glutamine. No further increase in maturation was observed when glucose was increased five-fold (to 27.8 mM). The positive effect of glucose was in part attributed to stimulation of glycolysis and increased production of pyruvate, since a reduced culture volume (8 microl), which allows the accumulation of secreted pyruvate, improved maturation in glucose-containing, but not pyruvate-containing, medium, and FSH, which stimulates glycolysis, increased progression to MII in glucose-containing, but not pyruvate-containing, medium. Yet these results also suggest that glucose has a beneficial effect on maturation apart from simple provision of pyruvate. The pyruvate effect was directly on the oocyte, because denuded oocytes responded more effectively than CEO to this energy substrate. The highest percentage of MII oocytes (96-97%) occurred in microdrop cultures containing glucose but lacking glutamine. These results indicate that glutamine supports oocyte viability but is not an adequate energy source for the completion of spontaneous meiotic maturation and may be detrimental. In addition, while pyruvate and glucose alone can each support meiotic progression of CEO to MII, optimal maturation requires the provision of both substrates to the culture medium when a large volume (1 ml) is used. It is concluded that careful attention to specific energy substrate supplementation and culture volume is important to optimise spontaneous meiotic maturation in vitro.
Animals↗
Parents' utilities for outcomes of occult bacteremia.
OBJECTIVE: To describe parents' values for outcomes of occult bacteremia using utility assessment, a quantitative method that incorporates risk preference. DESIGN: Computer-based utility assessment interview. SETTING: Urban children's hospital pediatric emergency department with 50 000 visits annually. PARTICIPANTS: Convenience sample of parents presenting with a child between 3 and 36 months. MAIN OUTCOME MEASURE: Parents' utility values for 8 outcomes from treatment of occult bacteremia: blood drawing, localized infection, hospitalization for antibiotics, meningitis with recovery, meningitis resulting in deafness, minor brain damage, severe brain damage, and death. RESULTS: Ninety-four subjects successfully completed the interview. Mean utilities were 0.9974 for blood drawing, 0.9941 for local infection, 0.9921 for hospitalization, 0.9768 for meningitis with recovery, 0.8611 for deafness, 0.7393 for minor brain damage, 0.3903 for severe brain damage, and 0.0177 for death. All values were significantly different from those that immediately preceded and succeeded (P<.0001), except for local infection vs hospitalization (P = .14). Median utilities for blood drawn, local infection, and hospitalization were 1. There were no significant differences among utilities of parents who presented with a febrile child (temperature > or =39 degrees C), or an afebrile child (temperature <39 degrees C). There were also no significant differences among utilities regardless of whether parents had children with prior experience with the outcomes. CONCLUSIONS: Assessment of utilities for outcomes of occult bacteremia yielded extremely high mean and median values for outcomes without permanent sequelae. This suggests that parents presenting to an emergency department may rationally prefer painful transient experiences, including venipuncture, for their children rather than risk even rare chances of severe outcomes.
Adult↗
Mining association rules from a pediatric primary care decision support system.
The purpose of this study was to apply an unsupervised data mining algorithm to a database containing data collected at the point of care for clinical decision support. The data set was taken from the Child Health Improvement Program (CHIP), a preventive services tracking and reminder system in use at the University of North Carolina. The database contains over 30,000 visits. We used a previously described pattern discovery algorithm to extract 2nd and 3rd order association rules from the data and reviewed the literature two see if the associations had been described before. The algorithm discovered 16 2nd order associations and 103 3rd order associations. The 3rd order associations contained no new information. The 2nd order associations demonstrated a covariance among a range of health risk behaviors. Additionally, the algorithm discovered that both tobacco smoke exposure and chronic cardiopulmonary disease are associated with failure on developmental screens. These relationships have been described before and have been attributed to underlying poverty. The work demonstrates the ability of unsupervised data mining by rule association on sparse clinical data to discover clinically important associations. However, many associations may be previously known or explained by confounding variables.
Algorithms↗
Comparing user acceptance of a computer system in two pediatric offices: a qualitative study.
The purpose of this qualitative study was to examine user acceptance of a clinical computer system in two pediatric practices in the southeast. Data were gathered through interviews with practice and IS staff, observations in the clinical area, and review of system implementation records. Five months after implementation, Practice A continued to use the system but Practice B had quit using it because it was unacceptable to the users. The results are presented here, in relation to a conceptual framework, which was originally developed to describe the process of successful implementation of research findings into practice. Five main themes were identified relative to the differences in user acceptance at the two practices: 1) Benefits versus expense of system use varied, 2) Organizational cultures differed, 3) IS staff's relationship with practices differed, 4) Post-implementation experiences differed, and 5) Transfer of technology from the academic center to private practice proved challenging in Practice B. The findings indicate a need for the development and validation of tools to measure healthcare organizational climate and readiness for change.
Ambulatory Care Facilities↗
Cost-effectiveness of transesophageal echocardiography to determine the duration of therapy for intravascular catheter-associated Staphylococcus aureus bacteremia.
BACKGROUND: The appropriate duration of therapy for catheter-associated Staphylococcus aureus bacteremia is controversial. Conventional practice dictates that all patients receive prolonged courses of intravenous antibiotics. Some clinicians recommend abbreviated therapeutic courses, but an alternate approach involves prospectively identifying patients for whom abbreviated therapy is appropriate. OBJECTIVE: To determine the cost-effectiveness of transesophageal echocardiography (TEE) in establishing duration of therapy for catheter-associated S. aureus bacteremia. DESIGN: Cost-effectiveness analysis. DATA SOURCES: MEDLINE search of literature; clinical data from patients with S. aureus bacteremia (n = 196) and patients with endocarditis (n = 60); and costs obtained from the study institution, regional home health agency, and national estimates of professional and technical fees. TARGET POPULATION: Patients with catheter-associated S. aureus bacteremia on native heart valves without intravenous drug use or clinically apparent metastatic infection, immunosuppression, or indwelling prosthetic devices. TIME HORIZON: Patient lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Antibiotic treatment based on TEE results compared with 2- or 4-week empirical therapy. OUTCOME MEASURES: Quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: Compared with empirical short-course therapy, the TEE strategy cost $4938 per quality-adjusted life-year (QALY) gained. The effectiveness of the TEE strategy and the effectiveness of the long-course strategy were sufficiently similar that the additional cost of empirical long-course therapy ($1,667,971 per QALY) was higher than that which society usually considers cost-effective. RESULTS OF SENSITIVITY ANALYSES: In a four-way sensitivity analysis (endocarditis prevalence, TEE cost, short-course relapse rate, and TEE specificity), compared with empirical short-course therapy, the TEE strategy results ranged from cost savings to $155,624 per QALY. CONCLUSION: Within the limitations of existing empirical data, this study suggests that for patients with clinically uncomplicated catheter-associated S. aureus bacteremia, the use of TEE to determine therapy duration is a cost-effective alternative to 2- or 4-week empirical therapy.
Anti-Bacterial Agents↗
Uptake and metabolism of adenosine mediate a meiosis-arresting action on mouse oocytes.
This study was carried out to evaluate the possible role of adenosine uptake and metabolism in mediating the inhibitory actions of this nucleoside on spontaneous mouse oocyte maturation. Uridine blocked 3H-adenosine uptake by oocyte-cumulus cell complexes (OCCs) and cumulus cell-enclosed oocytes (CEOs) by 82-85%, whereas uptake by denuded oocytes (DOs) was suppressed by 97%. Uridine had no effect on germinal vesicle breakdown (GVB) in CEOs when meiotic arrest was maintained with hypoxanthine or hypoxanthine plus adenosine but reversed the combined inhibitory action of these purines in DOs. Five of six adenosine analogs that bind to purinoceptors demonstrated meiosis-arresting activity but not in relation to their relative affinities for inhibitory or stimulatory adenosine receptors and only at high concentrations. Moreover, in DOs, uridine reversed the inhibitory effect of 2-chloroadenosine and 5'-N-ethylcarboxamidoadenosine, two receptor agonists that are poor substrates for adenosine-metabolizing enzymes. Results of experiments with adenosine kinase inhibitors showed that methylmercaptopurine riboside (MMPR) and tubercidin, but not 5'-amino-5'-deoxyadenosine, reversed meiotic arrest maintained by hypoxanthine +/- adenosine, but this required an additional inhibitory action on de novo purine synthesis. Inhibition of de novo purine synthesis alone was not sufficient because azaserine failed to reverse meiotic arrest. MMPR was a very potent meiosis-inducing agent, completely reversing meiotic arrest in CEOs and DOs in the presence of a variety of meiotic inhibitors. The adenosine deaminase inhibitor deoxycoformycin had opposite effects on oocyte maturation depending on the presence or absence of adenosine: the inhibitory action of hypoxanthine alone was bolstered, but the meiosis-arresting action of adenosine was reversed. These data therefore indicate that at low adenosine concentrations phosphorylation predominates, but at higher adenosine concentrations deaminated products contribute to the meiotic inhibition. This idea was borne out by the ability of inosine to mimic the synergistic interaction of adenosine with hypoxanthine. The action of adenosine is not due to deamination to inosine and conversion to nucleotides through the hypoxanthine salvage pathway because adenosine-mediated inhibition was not compromised in oocytes from mutant mice unable to salvage hypoxanthine.
Adenosine↗
Metabolism of radiolabeled glucose by mouse oocytes and oocyte-cumulus cell complexes.
This study was carried out to examine the metabolism of [1-14C]-, [6-14C]-, and [5-3H]glucose by oocyte-cumulus cell complexes (OCC) and denuded oocytes (DO) and to test the hypothesis that metabolism of glucose through the pentose phosphate pathway is associated with meiotic induction. OCC or DO were cultured in hanging drops suspended from the cap of a microfuge tube, with NaOH serving as a trap to collect released 3H2O or 14CO2. Preliminary experiments established that this culture system supports both spontaneous and ligand-induced meiotic maturation. An initial time course experiment (1.5-6 h) showed that hypoxanthine-treated OCC from eCG-primed animals metabolized glucose principally via glycolysis, with an increase to 2.7-fold in response to FSH. Though more [1-14C]glucose was oxidized than [6-14C]glucose, its metabolism was about two orders of magnitude less than that of [5-3H]glucose. Also, FSH significantly increased oxidation of [1-14C]glucose but not [6-14C]glucose, indicating a preferential activation of the pentose phosphate pathway. Pyrroline carboxylate, an activator of the pentose phosphate pathway, increased the activity of this pathway to over 2-fold but failed to affect glucose oxidation through the tricarboxylic acid cycle. Glycolytic metabolism was increased by 25%. The addition of pyruvate to pyruvate-free medium resulted in significant reduction in the metabolism of all three glucose analogues. In OCC retrieved from hCG-injected, primed mice and cultured under hormone-free conditions, metabolic responses were similar to those in FSH-treated complexes cultured in hypoxanthine. DO metabolized glucose, but at a much reduced rate when compared to OCC. Pyruvate reduced the consumption of all three glucose analogues by DO. Pyrroline carboxylate reduced [5-3H]glucose metabolism by DO but had little effect on [1-14C]- and [6-14C]glucose oxidation. These data demonstrate metabolism of glucose by both DO and OCC, but reveal that cumulus cells are more active than the oocyte in this regard. In addition, induction of maturation by FSH, hCG, or pyrroline carboxylate was accompanied by a significant increase in the oxidation of [1-14C]glucose but not [6-14C]glucose by OCC, supporting a proposed role for the pentose phosphate pathway in meiotic induction.
Animals↗
Technical report: urinary tract infections in febrile infants and young children. The Urinary Tract Subcommittee of the American Academy of Pediatrics Committee on Quality Improvement.
OVERVIEW: The Urinary Tract Subcommittee of the American Academy of Pediatrics Committee on Quality Improvement has analyzed alternative strategies for the diagnosis and management of urinary tract infection (UTI) in children. The target population is limited to children between 2 months and 2 years of age who are examined because of fever without an obvious cause. Diagnosis and management of UTI in this group are especially challenging for these three reasons: 1) the manifestation of UTI tends to be nonspecific, and cases may be missed easily; 2) clean voided midstream urine specimens rarely can be obtained, leaving only urine collection methods that are invasive (transurethral catheterization or bladder tap) or result in nonspecific test results (bag urine); and 3) a substantial number of infants with UTI also may have structural or functional abnormalities of the urinary tract that put them at risk for ongoing renal damage, hypertension, and end-stage renal disease (ESRD). METHODS: To examine alternative management strategies for UTI in infants, a conceptual model of the steps in diagnosis and management of UTI was developed. The model was expanded into a decision tree. Probabilities for branch points in the decision tree were obtained by review of the literature on childhood UTI. Data were extracted on standardized forms. Cost data were obtained by literature review and from hospital billing data. The data were collated into evidence tables. Analysis of the decision tree was used to produce risk tables and incremental cost-effectiveness ratios for alternative strategies. RESULTS: Based on the results of this analysis and, when necessary, consensus opinion, the Committee developed recommendations for the management of UTI in this population. This document provides the evidence the Subcommittee used in the development of its recommendations. CONCLUSIONS: The Subcommittee agreed that the objective of the practice parameter would be to minimize the risk of chronic renal damage within reasonable economic constraints. Steps involved in achieving these objectives are: 1) identifying UTI; 2) short-term treatment of UTI; and 3) evaluation for urinary tract abnormalities.
Child, Preschool↗
Diagnostic testing strategies in childhood urinary tract infections.
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Child↗
A systematic review of vision screening tests for the detection of amblyopia.
OBJECTIVE: To review the test characteristics and the quality of evidence regarding available screening tests for the detection of amblyopia in preschool-aged children to help primary care practitioners select a screening strategy. DESIGN: Systematic review of published studies. DATA SOURCES: The MEDLINE database was searched from 1966 through January 1999 using a broad and inclusive strategy. A total of 9551 citations were identified. STUDY SELECTION: All studies that compared the results of commercially available screening tests in preschool-aged children to ophthalmologic examination. DATA EXTRACTION: The setting of the study, the age of the population, the type of screening test, criteria for a positive screen, criteria for the ophthalmologic examination, test characteristics, and measures of reliability were abstracted by 2 reviewers for each selected study. DATA SYNTHESIS: Four eligible articles were identified that studied the test characteristics of 3 screening tests. None of these studies were performed in a primary care setting. Each study used different criteria for failure of the ophthalmologic examination. None of the studies measured observer or test reliability. CONCLUSIONS: Few high-quality data exist regarding the performance of preschool vision screening. Important future work should include the development of a consensus gold standard ophthalmologic examination and evaluation of screening tests in the primary care setting.
Amblyopia↗
Scoring performance on computer-based patient simulations: beyond value of information.
As computer based clinical case simulations become increasingly popular for training and evaluating clinicians, approaches are needed to evaluate a trainee's or examinee's solution of the simulated cases. In 1997 we developed a decision analytic approach to scoring performance on computerized patient case simulations, using expected value of information (VOI) to generate a score each time the user requested clinical information from the simulation. Although this measure has many desirable characteristics, we found that the VOI was zero for the majority of information requests. We enhanced our original algorithm to measure potential decrements in expected utility that could result from using results of information requests that have zero VOI. Like the original algorithm, the new approach uses decision models, represented as influence diagrams, to represent the diagnostic problem. The process of solving computer based patient simulations involves repeated cycles of requesting and receiving these data from the simulations. Each time the user requests clinical data from the simulation, the influence diagram is evaluated to determine the expected VOI of the requested clinical datum. The VOI is non-zero only it the requested datum has the potential to change the leading diagnosis. The VOI is zero when the data item requested does not map to any node in the influence diagram or when the item maps to a node but does not change the leading diagnosis regardless of it's value. Our new algorithm generates a score for each of these situations by modeling what would happen to the expected utility of the model if the user changes the leading diagnosis based on the results. The resulting algorithm produces a non-zero score for all information requests. The score is the VOI when the VOI is non-zero It is a negative number when the VOI is zero.
Algorithms↗