Text mining for the Vaccine Adverse Event Reporting System: medical text classification using informative feature selection

Objective

The US Vaccine Adverse Event Reporting System (VAERS) collects spontaneous reports of adverse events following vaccination. Medical officers review the reports and often apply standardized case definitions, such as those developed by the Brighton Collaboration. Our objective was to demonstrate a multi-level text mining approach for automated text classification of VAERS reports that could potentially reduce human workload.

Design

We selected 6034 VAERS reports for H1N1 vaccine that were classified by medical officers as potentially positive (N_pos=237) or negative for anaphylaxis. We created a categorized corpus of text files that included the class label and the symptom text field of each report. A validation set of 1100 labeled text files was also used. Text mining techniques were applied to extract three feature sets for important keywords, low- and high-level patterns. A rule-based classifier processed the high-level feature representation, while several machine learning classifiers were trained for the remaining two feature representations.

Measurements

Classifiers'' performance was evaluated by macro-averaging recall, precision, and F-measure, and Friedman''s test; misclassification error rate analysis was also performed.

Results

Rule-based classifier, boosted trees, and weighted support vector machines performed well in terms of macro-recall, however at the expense of a higher mean misclassification error rate. The rule-based classifier performed very well in terms of average sensitivity and specificity (79.05% and 94.80%, respectively).

Conclusion

Our validated results showed the possibility of developing effective medical text classifiers for VAERS reports by combining text mining with informative feature selection; this strategy has the potential to reduce reviewer workload considerably.     

Concurrent administration of liposomal doxorubicin improves the survival of patients with invasive bladder cancer undergoing hypofractionated accelerated radiotherapy (HypoARC)

Cisplatin-based radio-chemotherapy is an effective alternative to cystectomy. The position of cisplatin has been challenged by novel drugs, while altered radiotherapy fractionation is also tested against conventional radiotherapy (RT). This study focuses on liposomal doxorubicin (LDox) in combination with an aggressive radiotherapy scheme (HypoARC). Eighty-two bladder cancer patients were treated with hypofractionated/accelerated RT (14 × 2.7 Gy to the pelvis and 15 × 3.4 Gy to the bladder, within 19 days), supported with amifostine (0–1,000 mg sc.). Forty-one out of 82 patients received concurrently LDox (20 mg/m2 for 3 bi-weekly cycles). LDox was free of haematological toxicity, erythordysestesia grade 1 being the only side effect noted in 5/41 patients. Although the incidence of early toxicities did not increase with LDox, delays of radiotherapy were increased (P = 0.16). Amifostine significantly protected patients against toxicities and delays. There were no severe late complications recorded. Complete response rate was similar in both groups (85.4 vs. 87.8%). The 3-year local relapse-free survival was better in patients receiving LDox, but at a non-statistical level (64 vs. 47%; P = 0.59). The 3-year survival rate was significantly improved in T2-4 stage patients receiving LDox (72.1 vs. 58.7%; P = 0.04). Multivariate analysis did not identify any independent prognostic variables of relapse or death events. LDox is a well-tolerated drug during pelvic radiotherapy. Although its efficacy in terms of bladder tumour control rates could not be substantiated due to the high efficacy of the HypoARC regimen applied, survival was improved suggesting either a spatial co-operation or a radio-sensitization of pelvic in-field subclinical disease.     

Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study

In spite the close association of the triple-negative breast cancer immunophenotype with hereditary breast cancers and the BRCA1 pathway, there is a lack of population studies that determine the frequency of BRCA1 mutations among triple-negative breast cancer patients. To address this, we have screened a large sample of 403 women diagnosed with triple-negative invasive breast cancer, independently of their age or family history, for germline BRCA1 mutations. Median age at diagnosis was 50 years (range 20-83). The overall prevalence of triple-negative cases among the initial patient group with invasive breast cancer was 8%. BRCA1 was screened by direct DNA sequencing in all patients, including all exons where a mutation was previously found in the Greek population (exons 5, 11, 12, 16, 20, 21, 22, 23, 24-77% of the BRCA1 coding region), including diagnostic PCRs to detect the three Greek founder large genomic rearrangements. Sixty-five deleterious BRCA1 mutations were identified among the 403 triple-negative breast cancer patients (16%). Median age of onset for mutation carriers was 39 years. Among a total of 106 women with early-onset triple-negative breast cancer (<40 years), 38 (36%) had a BRCA1 mutation, while 27% of women with triple-negative breast cancer diagnosed before 50 years (56/208) had a BRCA1 mutation. A mutation was found in 48% (50/105) of the triple-negative breast cancer patients with family history of breast or ovarian cancer. It is noteworthy, however, that of the 65 carriers, 15 (23%) had no reported family history of related cancers. All but one of the carriers had grade III tumors (98%). These results indicate that women with early-onset triple-negative breast cancer, and ideally all triple-negative breast cancer patients, are candidates for BRCA1 genetic testing even in the absence of a family history of breast or ovarian cancer.     

Tongue strength,dysphagia questionnaire,pharyngeal secretions and FEES findings in dysphagia management in amyotrophic lateral sclerosis

ObjectiveDysphagia is common in Amyotrophic lateral sclerosis (ALS). ALS shows significant phenotypic variability. It is characterized by progressive weakness and/or spasticity of muscles. Dysphagia symptoms vary. Aspiration is often silent and cognitive dysfunction is common. The purpose of the study was to evaluate tongue strength measurements, dysphagia questionnaire, the presence of pharyngeal secretions, and FEES findings in dysphagia management in ALS.MethodsTwenty-five patients completed the Eating Assessment Tool-10 (EAT-10), had their Maximum Isometric Tongue Pressure (MITP), and endurance measured and underwent Flexible Endoscopic Evaluation of Swallowing (FEES) providing 31 examinations.ResultsOut of 25 patients, 76% were self-reported as dysphagic (EAT-10≥3) with a mean EAT-10 at 14.95 (±7.96). ALS patients had significantly decreased tongue strength (mean MITPanterior: 31.69 ± 17.32kPa). Comparing examinations of dysphagic and non-dysphagic status the mean MITPa of non-dysphagic was significantly greater (52.33 ± 10.97 kPa versus 20.6 ± 12.67 kPa), p<0.001. FEES detected aspiration in 10 out of 31 examinations [Penetration Aspiration Scale(PAS) ≥6]. Aspirator status examinations showed statistically significantly worse cough (p = 0.001), tongue strength (p = 0.001) and endurance (p = 0.003), pharyngeal secretions (p<0.001), velopharyngeal sufficiency (p = 0.006), pharyngeal squeeze (p = 0.009), vocal cords’ movements (p = 0.001), pharyngeal pooling (p<0.001), EAT-10 (p = 0.001) and bulbar subscale of ALS Functioning Rating Scale-Revised (b-ALSFRS-R) scores (p = 0.014) compared to non-aspirator status. Correlation analysis indicated that the feeding status had strong statistically significant correlations with the EAT-10 score (rho = ?0.816), anterior tongue strength (rho = 0.735), secretions (rho = ?0.811), pharyngeal pooling (rho = ?0.712) and PAS (rho = ?0.676) at FEES, and b-ALSFRS-R score (rho = 0.791), all p<0.001. The EAT-10 had strong statistically significant correlations with the MITPa (r = ?0.794, p<0.001), secretions (rho = 0.668, p<0.001), and b-ALSFRS-R score (rho = -0.766, p = 0.001). The FEES findings had strong statistically significant correlations with the anterior tongue strength (pooling: rho = ?0.784), and secretions (PAS: rho = 0.723; pooling: rho = 0.671), all p<0.001. For the questionnaire, tongue strength and pharyngeal secretions, ROC analysis assessed cut-off points and discriminating ability to predict aspiration status (Area Under the Curve: 0.838; 0.845 and 0.93, respectively). EAT-10 with a cut-off at 8 was able to predict aspirator status with a sensitivity of 100% and a specificity of 42.9% (negative predictive value-NPV = 100%). A cut-off value of 22KPa for the MITPa discriminated aspirator status (sensitivity = 80%, specificity = 89.5%, NPV = 89.5%). The quantity of secretions observed upon endoscopy with a cut-off value at 1 was able to predict aspirator status (sensitivity = 90%, specificity = 80%, NPV = 94.1%).ConclusionReduced tongue strength, questionnaire-reported symptoms, pharyngeal secretions, and FESS findings can guide identification of patients with ALS at risk of inefficient and unsafe swallowing.     

Stress generation in mandibular anterior teeth restored with different types of post-and-core at various levels of ferrule

Statement of problem

Pertinent evidence regarding the mechanical integrity of mandibular anterior teeth restored with a post-and-core is limited.

Treatment of invasive bladder cancer with conformal hypofractionated accelerated radiotherapy and amifostine (HypoARC)

IntroductionRadiotherapy (RT) for bladder cancer is as an effective alternative of cystectomy. Although rapid cancer clonogen repopulation contributes to radio-resistance, accelerated RT schemes based on ≤2 Gy fractions have failed to improve results. We suggest that accelerated hypofractionation (HypoARC) may be more effective, as it targets both tumors with increased clonogenic activity and tumors with low radio-sensitivity.Patients and methodsEighty-two bladder cancer patients were treated with concomitant-boost conformal RT (14 × 2.7 Gy to the pelvis and 15 × 3.4 Gy to the bladder, within 19 days). Patients received a daily dose of 0/500/750/1,000 mg of amifostine using a dose-individualization algorithm (15.8%, 8.5%, 19.5%, and 56.1% of patients respectively).ResultsEarly frequency grade 2–3, dysuria grade 1–2, diarrhea grade 2, and proctitis grade 2 appeared in 10.9%, 15.8%, 8.5%, and 13.4% of patients, respectively. The incidence of late sequelae was low (1.2% grade 2 frequency, 2.4% grade 2–3 dysuria, 2.4% grade 2–3 hematuria, 2.4% grade 2–3 incontinence). Patients receiving 1,000 mg of amifostine experienced significantly lower toxicities. The complete response rate, 3-year local control and disease specific survival rates were 86.6%, 56%, and 63%, respectively.ConclusionsHypoARC is linked with low early and late radiation toxicity, which is further reduced with the administration of high dose daily amifostine. The control and survival rates compare favorably with previously published data.     

Predictive Modeling for Pharmaceutical Processes Using Kriging and Response Surface

Powder feeding is a fundamental unit operation in the pharmaceutical industry. For the cases in which first-principle process models are unknown, such as when new powder mixture feeding operations are being evaluated, or no longer accurately describe current operating behavior, surrogate model-based approaches can be employed in order to quantify input–output behavior. In this work, two such metamodeling techniques—kriging and response surface methods—are used to predict a loss-in-weight feeder unit’s flow variability in terms of unit flowability and feed rate. Based on a comparison of predicted with experimental values, an iteratively constructed kriging model is found to more accurately capture the feeder system behavior compared with the response surface methodology. Although feeders are used as a case study in this paper, the kriging methodology is general to address other processes where first-principle models are not available.     

Combined use of 99mTc-sestamibi and 99mTc-V-DMSA in the assessment of chemotherapy effectiveness in patients with multiple myeloma.

This study determined the role of the combined use of (99m)Tc-sestamibi and (99m)Tc-pentavalent dimercaptosuccinic acid (V-DMSA) scintigraphy in evaluating the effectiveness of chemotherapy in patients with multiple myeloma. METHODS: In 20 patients with multiple myeloma who had received or were receiving chemotherapy, (99m)Tc-sestamibi and (99m)Tc-V-DMSA scanning was performed to evaluate the effectiveness of chemotherapy. RESULTS: In group A (11 patients with active disease), 42 (99m)Tc-sestamibi-positive lesions were found. Thirty-seven of those lesions were also positive for (99m)Tc-V-DMSA uptake, as were 16 additional lesions (nonactive) (NAL). Thus, in group A, the total number of positive lesions (TPL) detected was 58 and the NAL/TPL ratio was 16:58. In group B (9 patients in remission), 5 (99m)Tc-sestamibi-positive lesions were found. A further 22 lesions were also positive for (99m)Tc-V-DMSA uptake. Thus, in group B, the NAL/TPL ratio was 22:27. Therefore, the NAL/TPL ratios considered to represent effectively treated lesions were 27.6% and 81.5% for groups A and B, respectively. CONCLUSION: Combined use of the 2 agents allows the effectiveness of chemotherapy to be evaluated through a comparison of NAL and TPL multiple myeloma lesions even in the absence of a baseline study.