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Biomedical subjects

Martina Mueller

Publications and source records attributed to Martina Mueller.

12 recordsLinked to original sources
PubMed2006

Parameter selection for and implementation of a web-based decision-support tool to predict extubation outcome in premature infants.

BACKGROUND: Approximately 30% of intubated preterm infants with respiratory distress syndrome (RDS) will fail attempted extubation, requiring reintubation and mechanical ventilation. Although ventilator technology and monitoring of premature infants have improved over time, optimal extubation remains challenging. Furthermore, extubation decisions for premature infants require complex informational processing, techniques implicitly learned through clinical practice. Computer-aided decision-support tools would benefit inexperienced clinicians, especially during peak neonatal intensive care unit (NICU) census. METHODS: A five-step procedure was developed to identify predictive variables. Clinical expert (CE) thought processes comprised one model. Variables from that model were used to develop two mathematical models for the decision-support tool: an artificial neural network (ANN) and a multivariate logistic regression model (MLR). The ranking of the variables in the three models was compared using the Wilcoxon Signed Rank Test. The best performing model was used in a web-based decision-support tool with a user interface implemented in Hypertext Markup Language (HTML) and the mathematical model employing the ANN. RESULTS: CEs identified 51 potentially predictive variables for extubation decisions for an infant on mechanical ventilation. Comparisons of the three models showed a significant difference between the ANN and the CE (p = 0.0006). Of the original 51 potentially predictive variables, the 13 most predictive variables were used to develop an ANN as a web-based decision-tool. The ANN processes user-provided data and returns the prediction 0-1 score and a novelty index. The user then selects the most appropriate threshold for categorizing the prediction as a success or failure. Furthermore, the novelty index, indicating the similarity of the test case to the training case, allows the user to assess the confidence level of the prediction with regard to how much the new data differ from the data originally used for the development of the prediction tool. CONCLUSION: State-of-the-art, machine-learning methods can be employed for the development of sophisticated tools to aid clinicians' decisions. We identified numerous variables considered relevant for extubation decisions for mechanically ventilated premature infants with RDS. We then developed a web-based decision-support tool for clinicians which can be made widely available and potentially improve patient care world wide.

Birth Weight↗
PubMed2006

Continuation electroconvulsive therapy vs pharmacotherapy for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE).

BACKGROUND: Although electroconvulsive therapy (ECT) has been shown to be extremely effective for the acute treatment of major depression, it has never been systematically assessed as a strategy for relapse prevention. OBJECTIVE: To evaluate the comparative efficacy of continuation ECT (C-ECT) and the combination of lithium carbonate plus nortriptyline hydrochloride (C-Pharm) in the prevention of depressive relapse. DESIGN: Multisite, randomized, parallel design, 6-month trial performed from 1997 to 2004. SETTING: Five academic medical centers and their outpatient psychiatry clinics. PATIENTS: Two hundred one patients with Structured Clinical Interview for DSM-IV-diagnosed unipolar depression who had remitted with a course of bilateral ECT. INTERVENTIONS: Random assignment to 2 treatment groups receiving either C-ECT (10 treatments) or C-Pharm for 6 months. MAIN OUTCOME MEASURE: Relapse of depression, compared between the C-ECT and C-Pharm groups. RESULTS: In the C-ECT group, 37.1% experienced disease relapse, 46.1% continued to have disease remission at the study end, and 16.8% dropped out of the study. In the C-Pharm group, 31.6% experienced disease relapse, 46.3% continued to have disease remission, and 22.1% dropped out of the study. Both Kaplan-Meier and Cox proportional hazards regression analyses indicated no statistically significant differences in overall survival curves and time to relapse for the groups. Mean +/- SD time to relapse for the C-ECT group was 9.1 +/- 7.0 weeks compared with 6.7 +/- 4.6 weeks for the C-Pharm group (P = .13). Both groups had relapse proportions significantly lower than a historical placebo control from a similarly designed study. CONCLUSIONS: Both C-ECT and C-Pharm were shown to be superior to a historical placebo control, but both had limited efficacy, with more than half of patients either experiencing disease relapse or dropping out of the study. Even more effective strategies for relapse prevention in mood disorders are urgently needed.

Adolescent↗
PubMed2006

Pitfalls of neonatal screening for very-long-chain acyl-CoA dehydrogenase deficiency using tandem mass spectrometry.

Neonatal screening programs for very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) have recently been implemented. We report 2 newborns with elevated C14:1-carnitine levels on day 3 of life and normal levels on days 5 to 7. Enzyme and molecular analyses confirmed VLCADD in the first patient and heterozygosity in the second patient. We conclude that the diagnosis of VLCADD can be missed by acylcarnitine analysis during anabolic conditions. An increased C14:1-carnitine level can also occur in heterozygous individuals. Elevated C14:1-carnitine level on neonatal screening warrants further diagnostic workup even if a repeat sample demonstrates normal acylcarnitine levels.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed2006

Patterns of psychotropic medication use among patients with severe depression referred for electroconvulsive therapy: data from the Consortium for Research on Electroconvulsive Therapy.

Most studies of trends in antidepressant pharmacotherapy have focused on relatively mildly ill, nonpyschotic outpatients. In this report, we provide detailed information on psychotropic use among patients with unipolar depression participating in a large, multisite electroconculsive therapy (ECT) study. Adequacy of antidepressant medication trials was assessed with the Antidepressant Treatment History Form. Among patients with nonpsychotic depression, 27% (60/220) had not had an adequate trial of an antidepressant before ECT, and 63% (139/220) had had at least one inadequate trial. Surprisingly, 33% (79/243) of nonpsychotic patients had been prescribed an antipsychotic. Among patients with psychotic depression, 95% (101/106) had not been given an adequate combination of an antidepressant and antipsychotic agent, mostly due to low doses of the latter class. Among all patients in the trial, 61% (213/352) had been prescribed at least one benzodiazepine, and only 7% (24/352) had been given a lithium augmentation trial. Use of hypnotic agents and anticonvulsants was common. In conclusion, patients with severe depression referred for ECT with a unipolar depressive episode have high rates of psychotropic usage, much of which is inadequate.

Adolescent↗
PubMed2006

Neonatal screening for very long-chain acyl-coA dehydrogenase deficiency: enzymatic and molecular evaluation of neonates with elevated C14:1-carnitine levels.

OBJECTIVE: Neonatal screening programs for very long-chain acyl-coenzyme A dehydrogenase deficiency have been implemented recently in various countries. Mildly elevated C14:1-carnitine on day 3 of life strongly suggests very long-chain acyl-coenzyme A dehydrogenase deficiency. DESIGN: We characterized 11 neonates with elevated C14:1-carnitine by enzyme and molecular analyses. Palmitoyl-coenzyme A oxidation was measured in lymphocytes. Sequencing of all 20 exons of the VLCAD gene was performed from genomic DNA. RESULTS: Palmitoyl-coenzyme A oxidation revealed significantly decreased residual activities consistent with very long-chain acyl-coenzyme A dehydrogenase deficiency in 7 neonates. In 2 individuals, residual activities of 48% and 44%, respectively, suggested heterozygosity. Two disease-causing mutations were detected in 6 of 7 neonates with very long-chain acyl-coenzyme A dehydrogenase deficiency; in the remaining 1 patient, only 1 mutation was identified. Of 2 individuals with residual activities consistent with heterozygosity, 1 was heterozygous for a VLCAD mutation. The other child and both individuals with normal palmitoyl-coenzyme A oxidation had normal genotypes. CONCLUSIONS: In 4 of 11 neonates identified with elevated C14:1-carnitine, very long-chain acyl-coenzyme A dehydrogenase deficiency was excluded. A C14:1-carnitine level > 1 micromol/L strongly suggests very long-chain acyl-coenzyme A dehydrogenase deficiency, whereas concentrations < or = 1 micromol/L do not allow a clear discrimination among affected patients, carriers, and healthy individuals. Further diagnostic evaluation, including enzyme and molecular analyses, is essential to identify very long-chain acyl-coenzyme A dehydrogenase deficiency correctly.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed2005

p73 induces apoptosis by different mechanisms.

p73, like its homologue, the tumor suppressor p53, is able to induce apoptosis in several cell types. This property is important for the involvement of p73 in cancer development and therapy. However, in contrast with p53, the TAp73 gene has two distinct promoters coding for two protein isoforms with opposite effects: while the transactivation proficient TAp73 shows pro-apoptotic effects, the amino-terminal-deleted DeltaNp73 has an anti-apoptotic function. Indeed, the relative expression of these two proteins is related to the prognosis of several cancers. Here we discuss recent developments in the control of p73-induced apoptosis. First, TAp73 induces ER stress via the direct transactivation of Scotin. Second, TAp73 induces the mitochondrial pathway by directly transactivating both Bax and the BH3 only protein PUMA promoters. While the first transactivation is weak, and not sufficient to trigger apoptosis (at least in the in vitro cellular models so far evaluated), the induction of PUMA is strong and lethal. Third, the promoter of the death receptor CD95 contains a p53 responsive element and preliminary experiments suggest that TAp73 also activates the death receptor pathway. In addition, TAp73 is able to transactivate its own second promoter, thus inducing the expression of the anti-apoptotic DeltaNp73 isoform. Therefore, the balance between TAp73 and DeltaNp73 finely regulates cellular sensitivity to death.

Animals↗
PubMed2005

Relief of expressed suicidal intent by ECT: a consortium for research in ECT study.

OBJECTIVE: This study assessed the incidence, severity, and course of expressed suicidal intent in depressed patients who were treated with ECT. The data are from the first phase of an ongoing, collaborative multicenter study, the overall aim of which was to compare continuation ECT with pharmacotherapy in the prevention of relapse after a successful course of ECT. METHOD: Suicidal intent, as expressed by patients during an interview, was scored at baseline and before each ECT session with item 3 on the 24-item Hamilton Depression Rating Scale in 444 patients with unipolar depression. RESULTS: One hundred thirty-one patients (29.5%) reported suicidal thoughts and acts (score of 3 or 4) at baseline. Scores decreased to 0 after 1 week (three ECT sessions) in 38.2% of the patients, after 2 weeks (six ECT sessions) in 61.1%, and in 80.9% at the end of the course of treatment. CONCLUSIONS: Expressed suicidal intent in depressed patients was rapidly relieved with ECT. Evidence-based treatment algorithms for major depressive mood disorders should include dichotomization according to suicide risk, as assessed by interview. For patients at risk, ECT should be considered earlier than at its conventional "last resort" position.

Adult↗
PubMed2004

Relationship between somatization and remission with ECT.

Patients treated with electroconvulsive therapy (ECT) were divided into those with less severe depression and those with more severe depression. In the less severely depressed group, high somatic anxiety and hypochondriasis predicted a low likelihood of sustained remission with ECT. In the more severely depressed group, these traits were not predictive of ECT outcome.

Adult↗
PubMed2004

Predicting extubation outcome in preterm newborns: a comparison of neural networks with clinical expertise and statistical modeling.

Even though ventilator technology and monitoring of premature infants has improved immensely over the past decades, there are still no standards for weaning and determining optimal extubation time for those infants. Approximately 30% of intubated preterm infants will fail attempted extubation, requiring reintubation and resuming of mechanical ventilation. A machine-learning approach using artificial neural networks (ANNs) to aid in extubation decision making is hereby proposed. Using expert opinion, 51 variables were identified as being relevant for the decision of whether to extubate an infant who is on mechanical ventilation. The data on 183 premature infants, born between 1999 and 2002, were collected by review of medical charts. The ANN extubation model was compared with alternative statistical modeling using multivariate logistic regression and also with the clinician's own predictive insight using sensitivity analysis and receiver operating characteristic curves. The optimal ANN model used 13 parameters and achieved an area under the receiver operating characteristic curve of 0.87 (out-of-sample validation), comparing favorably with multivariate logistic regression. It also compared well with the clinician's expertise, which raises the possibility of being useful as an automated alert tool. Because an ANN learns directly from previous data obtained in the institution where it is to be used, this makes it particularly amenable for application to evidence-based medicine. Given the variety of practices and equipment being used in different hospitals, this may be particularly relevant in the context of caring for preterm newborns who are on mechanical ventilation.

Decision Making↗
PubMed2004

Speed of response and remission in major depressive disorder with acute electroconvulsive therapy (ECT): a Consortium for Research in ECT (CORE) report.

BACKGROUND: Remission of illness in patients with major depressive disorder (MDD) is achieved in less than half of patients initially treated with medication. Electroconvulsive therapy (ECT) is another treatment option. We report the speed of response and remission rates in a cohort of depressed patients who received a course of acute-phase ECT in the initial phase of an ongoing multicenter randomized trial of continuation ECT versus pharmacotherapy. METHOD: Patients with MDD according to DSM-IV criteria received bilateral ECT 3 times weekly. Prior to each treatment, a 24-item Hamilton Rating Scale for Depression (HAM-D-24) score was obtained by a clinical rater. Sustained response was defined as a > or = 50% reduction in baseline HAM-D-24 score for at least 2 and all subsequent measurement occasions. Remission was defined as HAM-D-24 scores of < or = 10 for at least the last 2 consecutive assessments. Data were collected from May 1997 through November 2000. RESULTS: Of the 253 patients who entered the study, 86% (N = 217) completed the acute course of ECT. Sustained response occurred in 79% of the sample, and remission occurred in 75% of the sample (N = 253); 34% (85/253) of patients achieved remission at or before ECT #6 (week 2), and 65% (164/253) achieved remission at or before ECT #10 (weeks 3-4). Over half (54%; 136/253) had an initial first response by ECT #3 (end of week 1). CONCLUSION: ECT was associated with rapid response and remission in a high percentage of patients. ECT warrants early consideration in treatment algorithms for patients with MDD.

Adult↗
PubMed2003

Web-based prediction of extubation outcome in premature infants on mechanical ventilation using an artificial neural network.

The web-based implementation of a decision-support tool for the prediction of extubation outcome in mechanically ventilated premature infants enables the integration of advanced and computationally intensive modeling approaches with easy-usage, no maintenance requirements and wide availability. Accordingly, the artificial neural network predictive tool developed provides decision-support in determining whether to extubate a premature infant to clinicians in NICUs anywhere with access to the Internet.

Decision Making, Computer-Assisted↗