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PubMed1995

Postmarketing surveillance with computer-based patient records.

Postmarketing Surveillance (PMS) concerns the investigation of side-effects of drugs after they are introduced into the market. Traditionally, data collection for PMS-studies has been paper-based. The increasing number of general practitioners (GP) that use Computer-Based Patient Records (CBPR) and the central role these general practitioners in the Netherlands play in the delivery of care makes the use of CBPRs as a resource of data for PMS studies possible. Analysis of the current available CBPRs, however, proved them insufficient for PMS studies, because too much data is available only in free text, and other necessary data for PMS is lacking. To make the CBPR suitable for PMS, we had to build a software-module that could be plugged into the computer system of the GP. The module checks the data immediately after they it has been entered into the system, and missing data is requested. Initial filed studies have shown that, with this module, the collection of PMS data is feasible.

Medical Records Systems, Computerized↗
PubMed2006

Multivariate curve resolution of time course microarray data.

BACKGROUND: Modeling of gene expression data from time course experiments often involves the use of linear models such as those obtained from principal component analysis (PCA), independent component analysis (ICA), or other methods. Such methods do not generally yield factors with a clear biological interpretation. Moreover, implicit assumptions about the measurement errors often limit the application of these methods to log-transformed data, destroying linear structure in the untransformed expression data. RESULTS: In this work, a method for the linear decomposition of gene expression data by multivariate curve resolution (MCR) is introduced. The MCR method is based on an alternating least-squares (ALS) algorithm implemented with a weighted least squares approach. The new method, MCR-WALS, extracts a small number of basis functions from untransformed microarray data using only non-negativity constraints. Measurement error information can be incorporated into the modeling process and missing data can be imputed. The utility of the method is demonstrated through its application to yeast cell cycle data. CONCLUSION: Profiles extracted by MCR-WALS exhibit a strong correlation with cell cycle-associated genes, but also suggest new insights into the regulation of those genes. The unique features of the MCR-WALS algorithm are its freedom from assumptions about the underlying linear model other than the non-negativity of gene expression, its ability to analyze non-log-transformed data, and its use of measurement error information to obtain a weighted model and accommodate missing measurements.

Algorithms↗
PubMed2005

Uncertainty method improved on best-worst case analysis in a binary meta-analysis.

BACKGROUND: Most systematic reviewers aim to perform an intention-to-treat meta-analysis, including all randomized participants from each trial. This is not straightforward in practice: reviewers must decide how to handle missing outcome data in the contributing trials. OBJECTIVE: To investigate methods of allowing for uncertainty due to missing data in a meta-analysis. STUDY DESIGN AND SETTING: The Cochrane Library was surveyed to assess current use of imputation methods. We developed a methodology for incorporating uncertainty, with weights assigned to trials based on uncertainty interval widths. The uncertainty interval for a trial incorporates both sampling error and the potential impact of missing data. We evaluated the performance of this method using simulated data. RESULTS: The survey showed that complete-case analysis is commonly considered alongside best-worst case analysis. Best-worst case analysis gives an interval for the treatment effect that includes all of the uncertainty due to missing data. Unless there are few missing data, this interval is very wide. Simulations show that the uncertainty method consistently has better power and narrower interval widths than best-worst case analysis. CONCLUSION: The uncertainty method performs consistently better than best-worst case imputation and should be considered along with complete-case analysis whenever missing data are a concern.

Antimalarials↗
PubMed2002

Sample entropy analysis of neonatal heart rate variability.

Abnormal heart rate characteristics of reduced variability and transient decelerations are present early in the course of neonatal sepsis. To investigate the dynamics, we calculated sample entropy, a similar but less biased measure than the popular approximate entropy. Both calculate the probability that epochs of window length m that are similar within a tolerance r remain similar at the next point. We studied 89 consecutive admissions to a tertiary care neonatal intensive care unit, among whom there were 21 episodes of sepsis, and we performed numerical simulations. We addressed the fundamental issues of optimal selection of m and r and the impact of missing data. The major findings are that entropy falls before clinical signs of neonatal sepsis and that missing points are well tolerated. The major mechanism, surprisingly, is unrelated to the regularity of the data: entropy estimates inevitably fall in any record with spikes. We propose more informed selection of parameters and reexamination of studies where approximate entropy was interpreted solely as a regularity measure.

Entropy↗
PubMed2004

Pharmacotherapy for social phobia.

BACKGROUND: Social phobia (SP), or social anxiety disorder, is a prevalent and disabling disorder. There is growing evidence that SP is mediated by specific neurobiological factors, and increased interest in the use of medication in its treatment. OBJECTIVES: To assess the effects of pharmacotherapy for Social Phobia, and to determine whether particular classes of medication are more effective and/or acceptable than others in its treatment. SEARCH STRATEGY: Studies of the pharmacotherapy of SP were identified using literature searches of the Cochrane Depression, Anxiety & Neurosis Group (CCDAN) specialised register, the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 1, 2004), MEDLINE (1966 to 2003) and PsycLit (1966 to 2003). In addition, published and unpublished RCTs were requested from SP researchers and pharmaceutical companies and additional studies of any language were sought in reference lists of retrieved articles. SELECTION CRITERIA: All RCTs of the pharmacotherapy of SP were considered for the review. DATA COLLECTION AND ANALYSIS: The quality of selected RCTs was independently assessed by 2 raters on the CCDAN Quality Rating Scale, with the same raters collating data on treatment response and SP symptom ratings. Investigators were contacted to obtain missing data. Summary statistics were stratified by medication class (SSRIs - selective serotonin reuptake inhibitors; MAOIs - Monoamine oxidase inhibitors; RIMAs - reversible inhibitors of monoamine oxidase A), from which dichotomous and continuous measures were calculated, heterogeneity was assessed, and subgroup/sensitivity analyses undertaken. MAIN RESULTS: 36 RCTs of a range of medications were included in the analysis (4268 participants), of which 26 were short-term (14 weeks or less). A funnel plot provided evidence of publication bias. Summary statistics for responder status (assessed using the Clinical Global Impressions scale change item (CGI-C)) from 25 short-term comparisons demonstrated superiority of various medication agents over placebo (relative risk of non-response (RR) = 0.63; 95% CI = 0.55, 0.72; random effects model). Response to treatment by serotonin reuptake inhibitors (N = 11; RR = 0.67; 95% CI = 0.59, 0.76), MAOIs (N = 3; RR = 0.43; 95% CI = 0.24, 0.76) and RIMAs (N = 6; RR = 0.74; 95% CI = 0.59, 0.91) supported the value of these agents. However, the SSRIs were significantly more effective than the RIMAs (Deeks' stratified test of heterogeneity (Deeks 2001): Qb = 29.82; p < 0.00001). Summary statistics for SP symptoms from 16 comparisons using the Liebowitz Social Anxiety Scale (LSAS) showed a statistically significant difference between medication and placebo (weighed mean difference = -15.56, 95%CI = -17.95, -13.16), with this effect once again most evident for the SSRIs. Medication was also significantly superior to placebo in reducing SP symptom clusters, comorbid depressive symptoms, and associated disability. The value of long-term medication treatment in treatment responders was supported by 3 comparisons from maintenance studies (relative risk of non-response = 0.58; 95% CI = 0.39, 0.85) and 5 comparisons from relapse prevention studies (relative risk of relapse = 0.33; 95% CI = 0.22, 0.49). REVIEWERS' CONCLUSIONS: This review provides evidence that medication can be effective in treating SP over the short term, with the strongest evidence of treatment efficacy observed amongst the SSRIs. Furthermore, the data support continued pharmacotherapy in medication responders over the longer-term. Nevertheless, the possibility of publication has to be acknowledged. Additional issues for future research include the use of medication in children and adolescents with SP, and in SP with comorbid psychiatric disorders.

Humans↗
PubMed2003

Inhaled long acting beta agonists for stable chronic asthma.

BACKGROUND: Asthma is a common respiratory disease among both adults and children and short acting inhaled beta-2 agonists are used widely for 'reliever' bronchodilator therapy. Long acting beta-2 agonists were introduced as prospective 'symptom controllers' in addition to inhaled corticosteroid 'preventer' therapy (ICS). OBJECTIVES: This review aimed to determine the benefit or detriment on the primary outcome of asthma control with the regular use of long acting inhaled beta-2 agonists compared with placebo. SEARCH STRATEGY: We carried out searches using the Cochrane Airways Group trial register, most recently in October 2002. We searched bibliographies of identified RCTs for additional relevant RCTs and contacted authors of identified RCTs for other published and unpublished studies. SELECTION CRITERIA: All randomised studies of at least two weeks duration, comparing a long acting inhaled beta-agonist given twice daily with a placebo, in chronic asthma. DATA COLLECTION AND ANALYSIS: Two reviewers performed data extraction and study quality assessment independently. We contacted authors of studies for missing data. MAIN RESULTS: Eighty five studies met the inclusion criteria, 56 parallel group and 29 cross over design. Salmeterol xinafoate was used as long acting agent in 60 studies and formoterol fumarate in 25. The treatment period was two to four weeks in 32 studies, and 12 to 52 weeks in 53 studies. 34 study groups used concurrent inhaled corticosteroid treatment, 21 studies did not permit their use and 35 permitted either inhaled corticosteroid or cromones. There were significant advantages to long acting beta-2 agonist treatment compared to placebo for a variety of measurements of airway calibre including morning peak expiratory flow (PEF) (weighted mean difference (WMD) 26.78 L/min 95%CI 20.36 to 33.20), evening PEF (WMD 19.17 L/min 95%CI 11.63 to 26.73). They were associated with significantly fewer symptoms, less use of rescue medication and higher quality of life scores. The risk of exacerbation was lower in adults using regular inhaled corticosteroids. REVIEWER'S CONCLUSIONS: Long acting beta-2 agonists are effective in the control of chronic asthma, and the evidence supports their use in addition to inhaled corticosteroids, as emphasised in current guidelines. Further research is needed on their use in children under 12 and in mild asthmatics not taking ICS.

Adrenergic beta-Agonists↗
PubMed2004

Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma.

BACKGROUND: Granulopoiesis-stimulating factors (G-CSF and GM-CSF) are being used to prevent febrile neutropenia and infections in the treatment of patients with malignant lymphoma. The question whether G-CSF and GM-CSF improve dose-intensity, tumour response and overall survival in this patient population has not been answered yet. Since the results from single studies are inconclusive a systematic review was required. OBJECTIVES: To undertake a systematic review in patients with malignant lymphoma to determine the effectiveness of G-CSF and GM-CSF to prevent neutropenia, febrile neutropenia, infection, improve quality of life, adherence to the treatment protocol, tumour response, freedom from treatment failure (FFTF), overall survival (OS) and to assess adverse events of G-CSF and GM-CSF. SEARCH STRATEGY: Medline, Embase, CancerLit, the Cochrane Library and smaller databases, Internet-databases of ongoing trials, conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology were searched. We included full-text and abstract publications as well as unpublished data. SELECTION CRITERIA: Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus placebo/no prophylaxis in adult patients with malignant lymphoma undergoing chemotherapy were included in this review. Both study arms had to receive identical chemotherapy and supportive care. DATA COLLECTION AND ANALYSIS: Eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data. MAIN RESULTS: We included 12 eligible studies with 1.823 randomised patients. Compared with no prophylaxis, G-/GM-CSF significantly reduced the relative risk for severe neutropenia (RR 0.67 [95% CI 0.60-0.73]), febrile neutropenia (RR 0.74 [95% CI 0.62-0.89]) and infection (RR 0.74 [95% CI 0.64-0.85]). There was no evidence for G-/GM-CSF to decrease the number of patients who required iv antibiotics (RR 0.82 [95%CI 0.57-1.18]), to reduce infection related mortality (RR 1.37 [95% CI 0.66-2.82]), or to improve complete tumour response (RR 1.02 [95% CI 0.94-1.11]), FFTF (HR 1.11 [95% CI 0.91-1.35]) and OS (HR 1.00 [95% CI 0.86-1.16]). One study evaluated quality of life parameters and did not find differences between the groups. REVIEWER'S CONCLUSIONS: G-CSF and GM-CSF, when given prophylactically in patients with malignant lymphoma undergoing conventional chemotherapy, reduce the risk of neutropenia, febrile neutropenia and infection. However, based on the currently available randomised trials in this clinical setting, there is no evidence for G-/GM-CSF to provide a significant advantage in terms of complete tumour response, FFTF and OS.

Antineoplastic Agents↗
PubMed2004

Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma.

BACKGROUND: Granulopoiesis-stimulating factors, such as granulocyte-colony-stimulating factor (G-CSF) and granulocyte-macrophage-colony-stimulating factor (GM-CSF), are being used to prevent febrile neutropenia and infection in patients undergoing treatment for malignant lymphoma. The question of whether G-CSF and GM-CSF improve dose intensity, tumour response, and overall survival in this patient population has not been answered yet. Since the results from single studies are inconclusive, a systematic review was undertaken. OBJECTIVES: To determine the effectiveness of G-CSF and GM-CSF in patients with malignant lymphoma with respect to preventing neutropenia, febrile neutropenia and infection; improving quality of life, adherence to treatment protocol, tumour response, freedom from treatment failure (FFTF) and overall survival (OS); and adverse effects. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, CancerLit, and other relevant literature databases; internet databases of ongoing trials; and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 - 2003). We included full-text and abstract publications as well as unpublished data. SELECTION CRITERIA: Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus placebo/no prophylaxis in adult patients with malignant lymphoma undergoing chemotherapy were included for review. Both study arms had to receive identical chemotherapy and supportive care. DATA COLLECTION AND ANALYSIS: Trial eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data. MAIN RESULTS: We included 12 eligible randomised controlled trials with 1823 patients. Compared with no prophylaxis, both G-CSF and GM-CSF significantly reduced the relative risk (RR) for severe neutropenia (RR 0.67; 95% confidence interval (CI) 0.60 to 0.73), febrile neutropenia (RR 0.74; 95% CI 0.62 to 0.89) and infection (RR 0.74; 95% CI 0.64 to 0.85). There was no evidence that either G-CSF or GM-CSF reduced the number of patients requiring intravenous antibiotics (RR 0.82; 95%CI 0.57 to 1.18); lowered infection related mortality (RR 1.37; 95% CI 0.66 to 2.82); or improved complete tumour response (RR 1.02; 95% CI 0.94 to 1.11), FFTF (hazard ratio 1.11; 95% CI 0.91 to 1.35) and OS (hazard ratio 1.00; 95% CI 0.86 to 1.16). One study evaluated quality of life parameters and found no differences between the treatment groups. REVIEWERS' CONCLUSIONS: G-CSF and GM-CSF, when used as a prophylaxis in patients with malignant lymphoma undergoing conventional chemotherapy, reduce the risk of neutropenia, febrile neutropenia and infection. However, based on the randomised trials currently available, there is no evidence that either G-CSF or GM-CSF provide a significant advantage in terms of complete tumour response, FFTF or OS.

Antineoplastic Agents↗
PubMed2002

Regular treatment with long acting beta agonists versus daily regular treatment with short acting beta agonists in adults and children with stable asthma.

BACKGROUND: Selective beta-adrenergic agonists for use in asthma are: short acting (2-6 hours) and long acting (>12 hours). There has been little controversy about using short acting beta-agonists intermittently, but long acting beta-agonists are used regularly, and their regular use has been controversial. OBJECTIVES: To determine the benefit or detriment of treatment with regular short- or long acting inhaled beta-agonists in chronic asthma. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group register. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTs were contacted for other published and unpublished studies. SELECTION CRITERIA: All randomised studies of at least two weeks duration, comparing a long acting inhaled beta-agonist given twice daily with any short acting inhaled beta-agonist of equivalent bronchodilator effectiveness given regularly in chronic asthma. DATA COLLECTION AND ANALYSIS: Two reviewers performed data extraction and study quality assessment independently. Authors of studies were contacted for missing data. MAIN RESULTS: 31 studies met the inclusion criteria, 24 of parallel group and 7 cross over design. Salmeterol xinafoate was used as long acting agent in 22 studies and formoterol fumarate in 9. Salbutamol was the short acting agent used in 27 studies and terbutaline in 5. The treatment period was over 2 weeks in 29 studies, and at least 12 weeks in 20. 25 studies permitted a variety of co-intervention treatments, usually inhaled corticosteroid or cromones. One study did not permit inhaled corticosteroid. Long acting beta-agonists were significantly better than short acting for a variety of lung function measurements including morning PEF (Weighted Mean Difference (WMD) 33 l/min 95% CI 25, 42) or evening PEF (WMD 26 l/min 95% CI 18, 33); and had significantly lower scores for day and night time asthma symptom scores and percentage of days and nights without symptoms. They were also associated with a significantly lower use of rescue medication both during the day and night. Risk of exacerbations was not different between the two types of agent, but most studies were of short duration which limits the power to test for such differences. REVIEWER'S CONCLUSIONS: Long acting inhaled beta-agonists have advantages across a wide range of physiological and clinical outcomes for regular treatment.

Adrenergic beta-Agonists↗
PubMed2006

Purine antagonists for chronic lymphocytic leukaemia.

BACKGROUND: Recent trials suggest improved response rates for purine antagonists compared to alkylator-based regimens in the treatment of B-CLL. However, none was able to show a survival advantage. OBJECTIVES: To determine if there is any advantage of purine antagonists compared to alkylating agents (alone or in combination) in the treatment of patients with previously untreated B-CLL. SEARCH STRATEGY: Medical databases (Cochrane Library, MEDLINE, EMBASE), conference proceedings and internet-based trial registers were searched electronically and/or by hand (1990-2003). All references were checked for further trial information. We also contacted experts in the field and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials comparing purine antagonists as single agents with alkylator-based regimens in patients with previously untreated B-CLL were included. We included full-text and abstract publications as well as unpublished data. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were done in duplicate by two independent reviewers. Missing data were obtained from original authors. Endpoints included overall survival, overall response rate, rate of complete remissions, progression-free survival, treatment-related morbidity and mortality. MAIN RESULTS: Five trials with 1838 randomised patients were included. There is some evidence for improved overall survival after treatment with purine antagonists compared to alkylators, but statistical significance was not reached (HR 0.89 [95% CI 0.78-1.01], 4 trials, n=1638). However, the relative risk for achieving an overall response (RR 1.22 [95% CI 1.13-1.31], 5 trials, n=1751) and complete remission (RR 1.94 [95% CI 1.65-2.28], 5 trials, n=1751) was significantly higher, resulting in a longer progression-free survival (HR 0.70 [95% CI 0.61-0.82], 4 trials, n=1638). Incidence of grade III/IV infections was significantly higher in patients receiving treatment with purine antagonists (RR 1.83 [95% 1.30-2.58], 4 trials, n=1620). There was no significant difference concerning the relative risk for grade III/IV neutropenia (RR 1.14 [95% CI 0.98-1.34], 4 trials, n=1620) and therapy-related mortality (RR 0.94 [95% CI 0.45-1.95]). Overall incidence of hemolytic anemia was low, but significantly increased in the purine antagonist group (RR 3.36 [95% CI 1.27-8.91], 3 trials, n=1258). AUTHORS' CONCLUSIONS: Despite significantly increased overall response and complete remission rates and longer progression-free survival with first-line treatment of B-CLL patients with single-agent purine antagonists, we were not able to detect a statistically significant improvement of overall survival compared to alkylator-based regimens. Furthermore, the use of purine antagonists also augments the risk for grade III/IV infections and hemolytic anemia.

Antineoplastic Agents↗
PubMed1977

Cytogenetic effects of inhaled ozone in man.

Peripheral blood samples were collected from 30 normal male volunteers before and at intervals after inhaling 0.4 ppm ozone for 4 h. Data from 4 of the subjects were excluded from the analysis because of missing data points. The blood samples were cultured for 48 h, slides made and stained with a uniform Giemsa stain, and 100 metaphase spreads per subject per treatment scored for chromosome aberrations. Cells with suspected aberrations were photographed, destained, restained with a banding procedure and rephotographed to identify the specific chromosomes and regions involved. Pre-exposure, immediate post-exposure, 3 days post-exposure, 2 weeks post-exposure and 4 weeks post-exposure means for the percentage of cells with 46 chromosomes were 93.0, 93.6, 91.7, 94.5 and 94.2, respectively; in the same order, the mean number of cells with chromatid and/or chromosome breaks per order, the mean number of cells with chromatid and/or chromosome breaks per 100 cells was 0.96, 0.85, 1.00, 0.88 and 0.81 respectively, and for chromatid and/or chromosome gaps per 100 cells: 1.35, 0.96, 1.35, 0.81 and 0.77, respectively. The means for each of these parameters as well as the mean frequencies of complex aberrations are not statistically significantly different between blood sampling times. The distribution of aberrations by chromosome and light and dark bands is not significantly influenced by ozone exposure. These data indicate no apparent detectable human cytogenetic effect due to exposure to ozone under the conditions of this experiment.

Adult↗
PubMed2004

A prospective multicenter randomized trial of tension-free vaginal tape and colposuspension for primary urodynamic stress incontinence: two-year follow-up.

OBJECTIVE: This study was undertaken to compare tension-free vaginal tape (TVT) with colposuspension as the primary treatment for stress incontinence. STUDY DESIGN: The trial was conducted in gynecology or urology departments in 14 centers in the United Kingdom and Ireland. Three hundred forty-four women with urodynamic stress incontinence were randomly assigned to groups: 175 to TVT and 169 to colposuspension. Patients were assessed using the Short Form-36 health status questionnaire, the Bristol Female Lower Urinary Tract Symptoms questionnaire, clinical examination, and a 1-hour perineal pad test. Unpaired and paired data were analyzed with the Wilcoxon rank sum and matched pairs tests, respectively, and proportions were compared with the Fisher exact test. RESULTS: When data were analyzed on an intention-to-treat basis, assuming patients with missing data to be treatment failures, 63% of the TVT group and 51% of the colposuspension group were objectively cured at 2 years (odds ratio 1.67, 95% CI 1.09-2.58). CONCLUSION: The TVT procedure appears to be as effective as colposuspension for the treatment of urodynamic stress incontinence at 2 years.

Female↗
PubMed2005

Early age at menarche and allostatic load: data from the Third National Health and Nutrition Examination Survey.

PURPOSE: To examine whether there is an association between early age at menarche and allostatic load-a measure of cumulative biologic risk-using data from the Third National Health and Nutrition Examination Survey (NHANES III). METHODS: A total of 2470 (weighted N=25,544,838) women aged between 17 and 30 years with interview and examination data who did not report oral contraceptive use before menarche and were not missing data on the exposure or outcome were included. Early menarche was defined as menarche at age 10 or younger. The allostatic load score was the sum of the number of 11 components for which an individual had a value within the high-risk range. RESULTS: The prevalence of early menarche was 7%. Although the overall allostatic load scores were low when compared with older adults, the mean allostatic load score was higher among those with menarche at ages 10 or younger compared with those with later ages at menarche (1.99 vs. 1.33). After adjusting for age, race/ethnicity, level of education, household poverty income ratio, smoking, and depression history, women with high allostatic load scores had more than 2 times the odds as those with low scores of experiencing menarche at age 10 or earlier (OR=2.18; 95% CI, 1.29-3.68). CONCLUSIONS: This study is the first to report and examine the relationship between age at menarche and allostatic load. Future studies involving prospective measurement of allostatic load biomarkers may prove essential for disentangling the association between allostatic load and early age at menarche.

Adolescent↗
PubMed2003

A note on estimation of dynamics of multiple gene expression based on singular value decomposition.

Recently, data on multiple gene expression at sequential time points were analyzed, using singular value decomposition (SVD) as a means to capture dominant trends, called characteristic modes, followed by fitting of a linear discrete-time dynamical system in which the expression values at a given time point are linear combinations of the values at a previous time point. We attempt to address several aspects of the method. To obtain the model we formulate a non-linear optimization problem and present how to solve it numerically using standard MATLAB procedures. We use publicly available data to test the approach. For reader's convenience, we provide a straightforward, ready-to-use, procedure in MATLAB, which employs its standard features to analyze data of this kind. Then, we investigate the sensitivity of the method to missing measurements and its possibilities to reconstruct missing data. Also, we discuss the possible consequences of data regularization, called sometimes 'polishing', on the outcome of analysis, especially when model is to be used for prediction purposes. Summarizing we point out that approximation of multiple gene expression data preceded by SVD provides some insight into the dynamics but may also lead to unexpected difficulties, like overfitting problems.

Algorithms↗
PubMed1998

How well do birth certificates describe the pregnancies they report? The Washington State experience with low-risk pregnancies.

OBJECTIVES: Birth certificates are a major source of population-based data on maternal and perinatal health, but their value depends on the accuracy of the data. This study assesses the validity of information recorded on the birth certificates for women in Washington State who were considered to be low risk at entry into care. METHODS: Birth certificates were matched to data abstracted from prenatal and intrapartum clinic and hospital records of a sample of 1937 Washington State obstetrical patients who were considered to be low risk at the beginning of their pregnancies. Accuracy of a variety of pregnancy characteristics (e.g., complications, procedures) on the birth certificate was analyzed using percentage agreement and sensitivity with record abstracts as the "gold standard." Next, we weighted the data from each source to produce estimates of pregnancy characteristics in the population. We compared these estimates from the two data sources to see whether they provide similar pictures of this subpopulation. RESULTS: Missing data for specific items on the birth certificates ranged from 0% to 24%. The birth certificate accurately captured gravidity and parity, but was less likely to report prenatal and intrapartum complications. The population estimates of the two data sources were significantly different. CONCLUSIONS: Because birth certificates significantly underestimated the complications of pregnancies, number of interventions, number of procedures, and prenatal visits, use of these data for health policy development or resource allocation should be tempered with caution.

Adult↗
PubMed2006

Relevance feedback for CBIR: a new approach based on probabilistic feature weighting with positive and negative examples.

In content-based image retrieval, understanding the user's needs is a challenging task that requires integrating him in the process of retrieval. Relevance feedback (RF) has proven to be an effective tool for taking the user's judgement into account. In this paper, we present a new RF framework based on a feature selection algorithm that nicely combines the advantages of a probabilistic formulation with those of using both the positive example (PE) and the negative example (NE). Through interaction with the user, our algorithm learns the importance he assigns to image features, and then applies the results obtained to define similarity measures that correspond better to his judgement. The use of the NE allows images undesired by the user to be discarded, thereby improving retrieval accuracy. As for the probabilistic formulation of the problem, it presents a multitude of advantages and opens the door to more modeling possibilities that achieve a good feature selection. It makes it possible to cluster the query data into classes, choose the probability law that best models each class, model missing data, and support queries with multiple PE and/or NE classes. The basic principle of our algorithm is to assign more importance to features with a high likelihood and those which distinguish well between PE classes and NE classes. The proposed algorithm was validated separately and in image retrieval context, and the experiments show that it performs a good feature selection and contributes to improving retrieval effectiveness.

Algorithms↗
PubMed2000

Research ethics: ethical issues of data reporting and the quest for authenticity.

The search for truth and its unbiased reporting are ultimate goals of conducting scientific research. Ideally, the reporting of research data ought to be an objective task. In practice, however, it is fraught with numerous statistical and ethical pitfalls, seldom addressed in formal emergency medicine training. The lure of academic celebrity and related influences may persuade researchers to report results in ways that make data appear more interesting, or worthy of publication. Several examples of potentially misleading data reporting are illustrated, including using inappropriate statistical tests, neglecting negative results, omitting missing data points, failing to report actual numbers of eligible subjects, using inappropriate graph labels or terminology, data dredging, and others. Although potentially inaccurate or inflated methods of data reporting may not constitute overt scientific misconduct, the intentional misrepresentation of data is a form of fraud or deception. Publicly funded academic inquiry is a privilege and honor enjoyed by a trusted few. Regardless of outcome, every effort should be made to report data in the most scientifically accurate method. To this end, the Society for Academic Emergency Medicine Code of Conduct and American College of Emergency Physicians Code of Ethics provide important guidance toward the accurate, compassionate, competent, impartial, and honest conduct of scientific research. Accuracy and authenticity in data reporting are first and foremost a matter of individual integrity, and are crucial to the preservation of academic credibility, the protection of future patients, and the public's trust in the medical research enterprise.

Emergency Medicine↗
PubMed2005

Helical cone beam CT with an asymmetrical detector.

If a multislice or other area detector is shifted to one side to cover a larger field of view, then the data are truncated on one side. We propose a method to restore the missing data in helical cone-beam acquisitions that uses measured data on the longer side of the asymmetric detector array. The method is based on the idea of complementary rays, which is well known in fan beam geometry; in this paper we extend this concept to the cone-beam case. Different cases of complementary data coverage and dependence on the helical pitch are considered. The proposed method is used in our prototype 16-row CT scanner with an asymmetric detector and a 700 mm field of view. For evaluation we used scanned body phantom data and computer-simulated data. To simulate asymmetric truncation, the full, symmetric datasets were truncated by dropping either 22.5% or 45% from one side of the detector. Reconstructed images from the prototype scanner with the asymmetrical detector show excellent image quality in the extended field of view. The proposed method allows flexible helical pitch selection and can be used with overscan, short-scan, and super-short-scan reconstructions.

Algorithms↗