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PubMed2004

Application of data mining techniques to healthcare data.

A high-level introduction to data mining as it relates to surveillance of healthcare data is presented. Data mining is compared with traditional statistics, some advantages of automated data systems are identified, and some data mining strategies and algorithms are described. A concrete example illustrates steps involved in the data mining process, and three successful data mining applications in the healthcare arena are described.

Databases, Factual↗
PubMed2005

Mining coherent dense subgraphs across massive biological networks for functional discovery.

MOTIVATION: The rapid accumulation of biological network data translates into an urgent need for computational methods for graph pattern mining. One important problem is to identify recurrent patterns across multiple networks to discover biological modules. However, existing algorithms for frequent pattern mining become very costly in time and space as the pattern sizes and network numbers increase. Currently, no efficient algorithm is available for mining recurrent patterns across large collections of genome-wide networks. RESULTS: We developed a novel algorithm, CODENSE, to efficiently mine frequent coherent dense subgraphs across large numbers of massive graphs. Compared with previous methods, our approach is scalable in the number and size of the input graphs and adjustable in terms of exact or approximate pattern mining. Applying CODENSE to 39 co-expression networks derived from microarray datasets, we discovered a large number of functionally homogeneous clusters and made functional predictions for 169 uncharacterized yeast genes. AVAILABILITY: http://zhoulab.usc.edu/CODENSE/

Algorithms↗
PubMed2005

Evaluation of late functional results of patients treated with free muscle flaps for heel defects caused by land-mine explosions.

BACKGROUND: High-energy land-mine explosions cause extensive soft-tissue and bone defects in the heel area, which mostly require free flap coverage. In this article, the authors present the long-term functional outcomes of 72 patients who had free muscle flap reconstructions for composite heel defects caused by land-mine explosions. METHODS: The composite heel defects of 72 male patients caused by land-mine explosions were reconstructed by means of free muscle flaps. The mean follow-up was 6.5 years (range, 1 to 12 years). Each patient completed a questionnaire rating his level of satisfaction. Dynamic foot pressure distribution testing, three-dimensional motion analysis, and dynamic electromyography were performed for all patients. The data were compared with the control group of 20 volunteers. Statistical analysis was performed by Kruskal-Wallis, Mann-Whitney U, and Wilcoxon tests. RESULTS: Dynamic pressure distribution tests revealed significantly higher pressure and load in the injured feet of the patients (p < 0.05). Three-dimensional motion analysis showed restricted range of motion at the ankle joints of the injured extremity (p < 0.05). Seventeen patients were able to stand as long as the control group; the mean standing time for the others was 2.85 hours per day (range, 36 minutes to 5.32 hours). Many of the patients (71 percent) declared their satisfaction of having their own feet instead of prostheses. CONCLUSIONS: This is the longest series documenting the long-term functional results of patients injured by land mines who were treated with free muscle flaps. Reconstructive options should be preferred to amputation procedures in extensive tissue loss caused by land-mine explosion where possible.

Adult↗
PubMed2006

Mining statistically significant associations for exploratory analysis of human sleep data.

We introduce a specialized association rule mining technique that can extract patterns from complex sleep data comprising polysomnographic recordings, clinical summaries, and sleep questionnaire responses. The rules mined can describe associations among temporally annotated events and questionnaire or summary data; e.g., the likelihood that an occurrence of a rapid eye movement (REM) sleep stage during the second 100 sleep epochs of the night is associated with moderate caffeine intake. We use chi2 analysis to ensure statistical significance of the mined rules at the level P < 0.05. Our results, obtained by mining sleep-related data from 242 human subjects, reveal clinically interesting associations among the polysomnographic and summary variables. Our experience suggests that association mining may also be useful for selection of variables prior to using logistic regression.

Algorithms↗
PubMed2006

Herbivory mitigation through increased water-use efficiency in a leaf-mining moth-apple tree relationship.

Herbivory alters plant gas exchange but the effects depend on the type of leaf damage. In contrast to ectophagous insects, leaf miners, by living inside the leaf tissues, do not affect the integrity of the leaf surface. Thus, the effect of leaf miners on CO2 uptake and water-use efficiency by leaves remains unclear. We explored the impacts of the leaf-mining moth Phyllonorycter blancardella (Lepidoptera: Gracillariidae) on light responses of the apple leaf gas exchanges to determine the balance between the negative effects of reduced photosynthesis and potential positive impacts of increased water-use efficiency (WUE). Gas exchange in intact and mined leaf tissues was measured using an infrared gas analyser. The maximal assimilation rate was slightly reduced but the light response of net photosynthesis was not affected in mined leaf tissues. The transpiration rate was far more affected than the assimilation rate in the mine integument as a result of stomatal closure from moderate to high irradiance level. The WUE was about 200% higher in the mined leaf tissues than in intact leaf portions. Our results illustrate a novel mechanism by which plants might minimize losses from herbivore attacks; via trade-offs between the negative impacts on photosynthesis and the positive effects of increased WUE.

Animals↗
PubMed2000

Membrane redistribution of the Escherichia coli MinD protein induced by MinE.

Escherichia coli cells contain potential division sites at midcell and adjacent to the cell poles. Selection of the correct division site at midcell is controlled by three proteins: MinC, MinD, and MinE. It has previously been shown (D. Raskin and P. de Boer, Cell 91:685-694, 1997) that MinE-Gfp localizes to the midcell site in an MinD-dependent manner. We use here Gfp-MinD to show that MinD associates with the membrane around the entire periphery of the cell in the absence of the other Min proteins and that MinE is capable of altering the membrane distribution pattern of Gfp-MinD. Studies with the isolated N-terminal and C-terminal MinE domains indicated different roles for the two MinE domains in the redistribution of membrane-associated MinD.

Adenosine Triphosphatases↗
PubMed2005

Analysis of MinD mutations reveals residues required for MinE stimulation of the MinD ATPase and residues required for MinC interaction.

The MinD ATPase is critical to the oscillation of the Min proteins, which limits formation of the Z ring to midcell. In the presence of ATP, MinD binds to the membrane and recruits MinC, forming a complex that can destabilize the cytokinetic Z ring. MinE, which is also recruited to the membrane by MinD, displaces MinC and stimulates the MinD ATPase, resulting in the oscillation of the Min proteins. In this study we have investigated the role of lysine 11, present in the deviant Walker A motif of MinD, and the three residues in helix 7 (E146, S148, and D152) that interact electrostatically with lysine 11. Lysine 11 is required for interaction of MinD with the membrane, MinC, MinE, and itself. In contrast, the three residues in helix 7 that interact with lysine 11 are not required for binding to the membrane or activation of MinC. They are also not required for MinE binding; however, they are required for MinE to stimulate the MinD ATPase. Interestingly, the D152A mutant self-interacts, binds to the membrane, and recruits MinC and MinE in the presence of ADP as well as ATP. This mutant provides evidence that dimerization of MinD is sufficient for MinD to bind the membrane and recruit its partners.

Adenosine Diphosphate↗
PubMed2005

Potential utility of data-mining algorithms for early detection of potentially fatal/disabling adverse drug reactions: a retrospective evaluation.

The objective of this study was to apply 2 data-mining algorithms to a drug safety database to determine if these methods would have flagged potentially fatal/disabling adverse drug reactions that triggered black box warnings/drug withdrawals in advance of initial identification via "traditional" methods. Relevant drug-event combinations were identified from a journal publication. Data-mining algorithms using commonly cited disproportionality thresholds were then applied to the US Food and Drug Administration database. Seventy drug-event combinations were considered sufficiently specific for retrospective data mining. In a minority of instances, potential signals of disproportionate reporting were provided clearly in advance of initial identification via traditional pharmacovigilance methods. Data-mining algorithms have the potential to improve pharmacovigilance screening; however, for the majority of drug-event combinations, there was no substantial benefit of either over traditional methods. They should be considered as potential supplements to, and not substitutes for, traditional pharmacovigilance strategies. More research and experience will be needed to optimize deployment of data-mining algorithms in pharmacovigilance.

Adverse Drug Reaction Reporting Systems↗
PubMed1995

Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP.

PURPOSE: We report the results of a prospective trial in which patients with relapsing non-Hodgkin's lymphomas were sequentially treated with two regimens (mesna, ifosfamide, mitoxantrone, and etoposide [MINE], and etoposide, methylprednisolone, cytarabine, and cisplatin [ESHAP]) if they had no history of disease resistance to these drugs. PATIENTS AND METHODS: Ninety-two patients received MINE (mesna 4 g/m2, ifosfamide 4 g/m2, mitoxantrone 8 mg/m2, and etoposide 195 mg/m2) for a maximum of six courses followed by ESHAP (etoposide 240 mg/m2, methylprednisone 500 mg/d, high-dose cytarabine 2 g/m2, and cisplatin 100 mg/m2) for three courses to consolidate complete response (CR) or for a maximum of six cycles after a partial response (PR) or no response to MINE. Pretreatment serum levels of lactate dehydrogenase (LDH) and beta 2-microglobulin (beta 2M) were documented in 80 of 92 patients. RESULTS: The response rate to MINE-ESHAP was 69% (48% CRs and 21% PRs), with a median survival time of 24 months and median time to treatment failure of 12 months. The median time to treatment failure according to histology was as follows: low-grade histologies, 16 months; low-grade transformed to intermediate-grade, 8 months; and intermediate-grade, 5 months. The most serious complication was myelosuppression, which resulted in two deaths due to neutropenic sepsis. A risk factor model based on beta 2M and LDH levels before salvage treatment showed three categories of risk, with 36-month survival rates as follows: low (beta 2M < 3 mg/dL and LDH normal), 61%; intermediate (beta 2M > or = 3 mg/dL or LDH above normal), 23%; and high (beta 2M > or = 3 mg/dL and LDH above normal), 0%. CONCLUSION: MINE-ESHAP is an effective salvage strategy for patients with recurrent lymphoma. Toxicity was acceptable. Factors that determine prognostic categories at relapse merit further study.

Adult↗
PubMed2004

Application of an empiric Bayesian data mining algorithm to reports of pancreatitis associated with atypical antipsychotics.

STUDY OBJECTIVE: To compare the results from one frequently cited data mining algorithm with those from a study, which was published in a peer-reviewed journal, that examined the association of pancreatitis with selected atypical antipsychotics observed by traditional rule-based methods of signal detection. DESIGN: Retrospective pharmacovigilance study. INTERVENTION: The widely studied data mining algorithm known as the Multi-item Gamma Poisson Shrinker (MGPS) was applied to adverse-event reports from the United States Food and Drug Administration's Adverse Event Reporting System database through the first quarter of 2003 for clozapine, olanzapine, and risperidone to determine if a significant signal of pancreatitis would have been generated by this method in advance of their review or the addition of these events to the respective product labels. MEASUREMENTS AND MAIN RESULTS: Data mining was performed by using nine preferred terms relevant to drug-induced pancreatitis from the Medical Dictionary for Regulatory Activities (MedDRA). Results from a previous study on the antipsychotics were reviewed and analyzed. Physicians' Desk References (PDRs) starting from 1994 were manually reviewed to determine the first year that pancreatitis was listed as an adverse event in the product label for each antipsychotic. This information was used as a surrogate marker of the timing of initial signal detection by traditional criteria. Pancreatitis was listed as an adverse event in a PDR for all three atypical antipsychotics. Despite the presence of up to 88 reports/drug-event combination in the Food and Drug Administration's Adverse Event Reporting System database, the MGPS failed to generate a signal of disproportional reporting of pancreatitis associated with the three antipsychotics despite the signaling of these drug-event combinations by traditional rule-based methods, as reflected in product labeling and/or the literature. These discordant findings illustrate key principles in the application of data mining algorithms to drug safety surveillance. CONCLUSION: The optimal place of data mining algorithms in the pharmacovigilance tool kit remains to be determined, requires consideration of numerous factors that may affect their performance, and is highly situation dependent.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Perspectives on the use of data mining in pharmaco-vigilance.

In the last 5 years, regulatory agencies and drug monitoring centres have been developing computerised data-mining methods to better identify reporting relationships in spontaneous reporting databases that could signal possible adverse drug reactions. At present, there are no guidelines or standards for the use of these methods in routine pharmaco-vigilance. In 2003, a group of statisticians, pharmaco-epidemiologists and pharmaco-vigilance professionals from the pharmaceutical industry and the US FDA formed the Pharmaceutical Research and Manufacturers of America-FDA Collaborative Working Group on Safety Evaluation Tools to review best practices for the use of these methods.In this paper, we provide an overview of: (i) the statistical and operational attributes of several currently used methods and their strengths and limitations; (ii) information about the characteristics of various postmarketing safety databases with which these tools can be deployed; (iii) analytical considerations for using safety data-mining methods and interpreting the results; and (iv) points to consider in integration of safety data mining with traditional pharmaco-vigilance methods. Perspectives from both the FDA and the industry are provided. Data mining is a potentially useful adjunct to traditional pharmaco-vigilance methods. The results of data mining should be viewed as hypothesis generating and should be evaluated in the context of other relevant data. The availability of a publicly accessible global safety database, which is updated on a frequent basis, would further enhance detection and communication about safety issues.

Adverse Drug Reaction Reporting Systems↗
PubMed2004

Antipersonnel mine injuries in Southern Croatia.

OBJECTIVES: In this retrospective study, antipersonnel mine casualties in Southern Croatia from 1991 to 1995 are analyzed and treatment options are discussed. METHODS: Mechanism, degree of injury according to Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS), as well as surgical treatment were analyzed. RESULTS: Of a 2,693 war trauma population, 422 (15.67%) patients sustained antipersonnel mine injuries, 241 (57.11%) from pressure mines and 181 (42.89%) from fragmentation mines. Military personnel were injured in 329 cases, civilians in 60 cases, and children in 33 cases. AIS was 3.01 +/- 0.56 and ISS was 17.92 +/- 6.59. Of 39 fatalities (9.24%) with a mean age of 27.98 +/- 1.70 years, 34 were soldiers, 4 were civilians, and 1 was a child. AIS was 5.35 +/- 0.39 and ISS was 54.94 +/- 2.36. CONCLUSION: Fatalities and morbidity arising from antipersonnel mines can be reduced by the provision of appropriate surgical and evacuation facilities at the actual battlefield.

Adolescent↗
PubMed2004

Mine clearance injuries in South Croatia.

OBJECTIVE: The purpose of this retrospective study was to describe and analyze casualties in mine-clearance operations in South Croatia from 1991 to 1995. During the war in Croatia, the laying of mines by both sides was largely unplanned, without mapping or documentation, making demining, an already expensive, complicated task, even more dangerous. METHODS: The study comprised all those injured in mine-clearance operations treated at Clinical Hospital Split. The type of mines used, the mechanism of the incident, and the location and severity of injury according to the Abbreviated Injury Scale and the Injury Severity Score were analyzed. RESULTS: In a 5-year period, 160 pyrotechnicians of the Croatian Army performed demining in Southern Croatia. In 29 incidents, 53 deminers were injured. The degree of injury according to the Abbreviated Injury Scale was 2.85 +/- 0.6 and Injury Severity Score grade was 19.68 +/- 8.57. Two of the injured died. CONCLUSION: To find and remove approximately 2 million mines laid in Croatia will take at least 10 years and 2,000 to 3,000 specialized personnel. Unfortunately, the results of the study demonstrate that a significant number of deminers will suffer grave injuries or die in the process.

Blast Injuries↗
PubMed2004

Predicting survival causes after out of hospital cardiac arrest using data mining method.

BACKGROUND: The prognosis of life for patients with heart failure remains poor. By using data mining methods, the purpose of this study was to evaluate the most important criteria for predicting patient survival and to profile patients to estimate their survival chances together with the most appropriate technique for health care. METHODS: Five hundred and thirty three patients who had suffered from cardiac arrest were included in the analysis. We performed classical statistical analysis and data mining analysis using mainly Bayesian networks. RESULTS: The mean age of the 533 patients was 63 (+/- 17) and the sample was composed of 390 (73 %) men and 143 (27 %) women. Cardiac arrest was observed at home for 411 (77 %) patients, in a public place for 62 (12 %) patients and on a public highway for 60 (11 %) patients. The belief network of the variables showed that the probability of remaining alive after heart failure is directly associated to five variables: age, sex, the initial cardiac rhythm, the origin of the heart failure and specialized resuscitation techniques employed. CONCLUSIONS: Data mining methods could help clinicians to predict the survival of patients and then adapt their practices accordingly. This work could be carried out for each medical procedure or medical problem and it would become possible to build a decision tree rapidly with the data of a service or a physician. The comparison between classic analysis and data mining analysis showed us the contribution of the data mining method for sorting variables and quickly conclude on the importance or the impact of the data and variables on the criterion of the study. The main limit of the method is knowledge acquisition and the necessity to gather sufficient data to produce a relevant model.

Bayes Theorem↗
PubMed2005

[MINE regimen for patients with relapsed or chemo-resistant invasive non-Hodgkin's lymphoma].

BACKGROUND & OBJECTIVE: Treatment of relapsed or refractory non-Hodgkin's lymphoma (NHL) remains problematic with no standard salvage chemotherapy regimen. This study was to evaluate the efficacy of MINE (mitoxantrone, mesna/ifosfamide and etoposide) regimen on relapsed or refractory NHL, and observe its toxicity. METHODS: Records of 38 patients with relapsed or refractory invasive NHL, treated with MINE regimen from Jan. 2001 to Jun. 2003, were reviewed. All patients had received at least 1 type of chemotherapy regimen (median, 2 types; range, 1-4 types) with a median of 6 chemotherapy cycles (range, 2-12 cycles). The patients received a median of 4 cycles (range, 2-6 cycles) of MINE regimen. RESULTS: The treatment outcome and adverse events of all patients were assessable. The overall response rate was 47.4%, with a complete response (CR) rate of 15.8%. The response rates were 57.7% in the 26 patients with B-cell lymphoma and 25.0% in the 12 patients with T-cell lymphoma. The 1- and 2-year survival rates were 34.2% and 7.9%, respectively. The major adverse event was myelosuppression: the prevalence of grade III-IV neutropenia was 39.5%, and that of grade III-IV thrombocytopenia was 13.1%. One patient suffered grade III liver toxicity. CONCLUSIONS: MINE regimen was effective for patients with relapsed or refractory invasive NHL, and its toxicity is well tolerated, but the response term is relatively short. Further clinical study on the application of MINE regimen is warranted.

Adolescent↗
PubMed2001

Molecular characterization of Acidithiobacillus ferrooxidans and A. thiooxidans strains isolated from mine wastes in Brazil.

Nineteen strains of Acidithiobacillus ferrooxidans and Acidithiobacillus thiooxidans, including 12 strains isolated from coal, copper, gold and uranium mines in Brazil, strains isolated from similar sources in other countries and the type strains of the two species were characterized together with the type strain of A. caldus by using a combination of molecular systematic methods, namely ribotyping, BOX- and ERIC-PCR and DNA-DNA hybridization assays. Data derived from the molecular fingerprinting analyses showed that the tested strains encompassed a high degree of genetic variability. Two of the Brazilian A. ferrooxidans organisms (strains SSP and PCE) isolated from acid coal mine waste and uranium mine effluent, respectively, and A. thiooxidans strain DAMS, isolated from uranium mine effluent, were the most genetically divergent organisms. The DNA-DNA hybridization data did not support the allocation of Acidithiobacillus strain SSP to the A. ferrooxidans genomic species, as it shared only just over 40% DNA relatedness with the type strain of the species. Acidithiobacillus strain SSP was not clearly related to A. ferrooxidans in the 16S rDNA tree.

Brazil↗
PubMed1996

Two case reports of neurological disease in coal mine preparation plant workers.

Of 60 cases of neurotoxicity related to occupational exposures of workers at plants producing acrylamide monomers, cases involving neurotoxicity related to jobs using polymers with acrylamide monomer contamination have not been widely reported. In 1992, two patients were referred to the Division of Occupational and Environmental Health, Department of Family and Community Health, Marshall University School of Medicine, in Huntington, West Virginia for evaluation. The patients had worked in different coal preparation plants in southern West Virginia for over 10 years and had exposure to an acrylamide polymer flocculent contaminated with acrylamide monomer. Both patients had no instruction on proper use of, or the dangers of, acrylamide and were not given adequate safety equipment. Patient A developed Parkinsonism and Patient B peripheral neuropathies with a neurogenic bladder. These two case reports highlight the need to reemphasize the basic tenets of occupational health and safety. Many chemicals are being introduced into mining operations and awareness of potential toxic exposures and new diseases not previously reported in the mining industry must become part of the surveillance system by mine management and labor safety committees. Further studies on the extent of acrylamide neurotoxicity in the mining industry is encouraged.

Acrylamides↗
PubMed1985

A case-control study of stomach cancer in a coal mining region of Pennsylvania.

Historically coal mining populations have been reported to have elevated stomach cancer incidence rates. To identify which factors might be associated with cases who reside in these high risk areas, and specifically if particulate exposures from coal mining and coal utilization are associated with risk, a mining area of western Pennsylvania was defined for a retrospective case-control study. One hundred seventy-eight resident cases, identified from certificates of death, were compared to three controls: digestive cancer deaths, arteriosclerotic heart disease deaths, and neighborhood (living) controls. Controls were matched to each case on age, race, sex, and residence. Interviews were conducted during 1981 and 1982. Excess risks were shown for foreign born and eastern Europeans. Coal mining was not shown to be a risk factor for males, while an association was seen for female cases whose husbands were miners. Farming was a risk factor for males and females. Marked decreased risks were shown for gas heating and cooking fuels, with elevated risks for coal, wood and oil heating fuels, and wood cooking fuel. These findings are associated with lower socioeconomic status, and suggest environmental exposures or lifestyles that are directly and indirectly related to these risks factors. The marked inverse relationship between stomach cancer and use of gas heating and cooking fuel may be of important etiologic significance, especially in association with dietary changes. Further evaluation of prior use of various types of heating and cooking fuels needs to be considered especially using incident rather than case deaths.

Adult↗