The effect of levetiracetam treatment on survival in patients with glioblastoma: a systematic review and meta-analysis.

BACKGROUND: Levetiracetam (LEV) is an anti-epileptic drug (AED) that sensitizes glioblastoma (GBM) to temozolomide (TMZ) chemotherapy by inhibiting O6-methylguanine-DNA methyltransferase (MGMT) expression. Adding LEV to the standard of care (SOC) for GBM may improve TMZ efficacy. This study aimed to pool the existing evidence in the literature to quantify LEV's effect on GBM survival and characterize its safety profile to determine whether incorporating LEV into the SOC is warranted. METHOD: A search of CINAHL, Embase, PubMed, and Web of Science from inception to May 2021 was performed to identify relevant articles. Hazard ratios (HR), median overall survival, and adverse events were pooled using random-effect models. Meta-regression, funnel plots, and the Newcastle-Ottawa Scale were utilized to identify sources of heterogeneity, bias, and statistical influence. RESULTS: From 20 included studies, 5804 GBM patients underwent meta-analysis, of which 1923 (33%) were treated with LEV. Administration of LEV did not significantly improve survival in the entire patient population (HR 0.89, p = 0.094). Significant heterogeneity was observed during pooling of HRs (I2 = 75%, p < 0.01). Meta-regression determined that LEV treatment effect decreased with greater rates of MGMT methylation (RC = 0.03, p = 0.02) and increased with greater proportions of female patients (RC = - 0.05, p = 0.002). Concurrent LEV with the SOC for GBM did not increase odds of adverse events relative to other AEDs. CONCLUSIONS: Levetiracetam treatment may not be effective for all GBM patients. Instead, LEV may be better suited for treating specific molecular profiles of GBM. Further studies are necessary to identify optimal GBM candidates for LEV.

Machine Learning Offers Exciting Potential for Predicting Postprocedural Outcomes: A Framework for Developing Random Forest Models in IR.

PURPOSE: To demonstrate that random forest models trained on a large national sample can accurately predict relevant outcomes and may ultimately contribute to future clinical decision support tools in IR. MATERIALS AND METHODS: Patient data from years 2012-2014 of the National Inpatient Sample were used to develop random forest machine learning models to predict iatrogenic pneumothorax after computed tomography-guided transthoracic biopsy (TTB), in-hospital mortality after transjugular intrahepatic portosystemic shunt (TIPS), and length of stay > 3 days after uterine artery embolization (UAE). Model performance was evaluated with area under the receiver operating characteristic curve (AUROC) and maximum F1 score. The threshold for AUROC significance was set at 0.75. RESULTS: AUROC was 0.913 for the TTB model, 0.788 for the TIPS model, and 0.879 for the UAE model. Maximum F1 score was 0.532 for the TTB model, 0.357 for the TIPS model, and 0.700 for the UAE model. The TTB model had the highest AUROC, while the UAE model had the highest F1 score. All models met the criteria for AUROC significance. CONCLUSIONS: This study demonstrates that machine learning models may suitably predict a variety of different clinically relevant outcomes, including procedure-specific complications, mortality, and length of stay. Performance of these models will improve as more high-quality IR data become available.

Analysis of 8q24.21 miRNA cluster expression and copy number variation in gastric cancer.

Aim: To analyze gene expression and copy number of five miRNAs (miR-1204, miR-1205, miR-1206, miR-1207 and miR-1208) localized in this chromosome region in gastric cancer (GC). Materials & methods: 65 paired neoplastic and non-neoplastic specimens collected from GC patients and 20 non-neoplastic gastric tissues from cancer-free individuals were included in this study. The expression levels of the five miRNAs were accessed by real time qPCR and were correlated. Results: MiR-1207-3p, miR-1205, miR-1207-5p and miR-1208 were upregulated in approximately 50% of GC tumors in relation to those of adjacent non-neoplastic tissues. MiR-1205 expression was associated with gain of gene copies and was upregulated in adjacent non-neoplastic samples relative to external controls. Conclusion: The coexpression of the 8q24 miRNAs indicated the role of miR-1205 in the initiation of gastric cancer development.

Associations of Cerebrovascular Metabolism Genotypes With Neuropsychiatric Symptoms and Age at Onset of Alzheimer's Disease Dementia

Objective: To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer’s disease dementia (AD) onset and with neuropsychiatric symptoms according to each dementia stage. Methods: Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE) haplotypes, angiotensin-converting enzyme gene (ACE) variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR) variants rs11669576 and rs5930, cholesteryl ester transfer protein gene (CETP) variants I422V and TaqIB, and liver X receptor beta gene (NR1H2) polymorphism rs2695121. Results: Considering 201 patients, only APOE-ɛ4 carriers had earlier dementia onset in multiple correlations, as well as less apathy, more delusions, and more aberrant motor behavior. Both ACE polymorphisms were associated with less intense frontally mediated behaviors. Regarding LDLR variants, carriers of the A allele of rs11669576 had less anxiety and more aberrant motor behavior, whereas carriers of the A allele of rs5930 had less delusions, less anxiety, more apathy, and more irritability. CETP variants that included G alleles of I422V and TaqIB were mostly associated with less intense frontally mediated behaviors, while severely impaired carriers of the T allele of rs2695121 had more anxiety and more aberrant motor behavior. Conclusion: Though only APOE haplotypes affected AD onset, cerebrovascular metabolism genotypes were associated with differences in several neuropsychiatric manifestations of AD.

Investigating Longitudinal Tobacco Use Information from Social History and Clinical Notes in the Electronic Health Record.

The electronic health record (EHR) provides an opportunity for improved use of clinical documentation including leveraging tobacco use information by clinicians and researchers. In this study, we investigated the content, consistency, and completeness of tobacco use data from structured and unstructured sources in the EHR. A natural language process (NLP) pipeline was utilized to extract details about tobacco use from clinical notes and free-text tobacco use comments within the social history module of an EHR system. We analyzed the consistency of tobacco use information within clinical notes, comments, and available structured fields for tobacco use. Our results indicate that structured fields for tobacco use alone may not be able to provide complete tobacco use information. While there was better consistency for some elements (e.g., status and type), inconsistencies were found particularly for temporal information. Further work is needed to improve tobacco use information integration from different parts of the EHR.

Towards the Standardized Documentation of E-Cigarette Use in the Electronic Health Record for Population Health Surveillance and Research.

The debate regarding potential negative health effects of electronic nicotine delivery systems (ENDS), which include electronic cigarettes, has received much recent attention. Currently, it is unknown whether ENDS pose a real health risk to users or those passively exposed to their vapor. With the increased use of these devices, the goal of this study was to examine if and how their use is being documented in the electronic health record (EHR) and the associated implications for clinical research. Analysis of five years of progress notes and tobacco use comments revealed that ENDS use is documented at an increasing rate with variable associated information, most often consisting of the status, purpose, and side effects of ENDS use. These results highlight that improved and consistent EHR discrete data entry for ENDS with associated clinical standards for documentation and representation of potential exposures are needed for enabling effective population health surveillance and research.

Contrasts Between Patients With Lewy Body Dementia Syndromes and APOE-ε3/ε3 Patients With Late-onset Alzheimer Disease Dementia.

INTRODUCTION: Neuropsychiatric and epidemiological patterns may compensate for insufficient specificity of diagnostic criteria of Lewy body dementia (LBD) syndromes in differential analysis with Alzheimer disease (AD) dementia. We aimed to compare and distinguish demographic and neuropsychiatric features between LBD and APOE-ε3/ε3 late-onset AD. METHODS: A total of 39 consecutive patients with Parkinson disease dementia or dementia with Lewy bodies were matched with 39 APOE-ε3/ε3 patients with late-onset AD according to sex and Mini-Mental State Examination scores, and evaluated for education, age at disease onset, lifetime sanitary conditions, anthropometric measures, alcohol use, smoking, history of head trauma or bacterial infections, family history of neurodegenerative diseases, caregiver burden, functional independence, cognitive decline, neuropsychiatric symptoms, and pharmacological treatment. RESULTS: Family history of parkinsonism and worse motor performance were more prevalent in Parkinson disease dementia, also impacting sleep satisfaction and physical self-maintenance. Patients with AD had higher systolic blood pressure, were more independent, and had better performance in visuospatial tasks and calculations, whereas patients with LBD were more oriented and previously lived longer in rural areas without sanitation. Among neuropsychiatric symptoms, hallucinations, apathy, dysphoria, anxiety, and aberrant motor behavior were the most significant for discrimination amidst dementia diagnoses. CONCLUSIONS: Functional performance, visuospatial skills, and behavioral symptoms are helpful for differential diagnoses between LBD and AD. Cerebrovascular risk might be more important for AD pathogenesis, whereas environmental factors might impact development of LBD.

Analyzing Operative Note Structure in Development of a Section Header Resource.

Operative notes contain essential details of surgical procedures and are an important form of clinical documentation. Sections within operative notes segment provide high level note structure. We evaluated the HL7 Implementation Guide for Clinical Document Architecture Release 2.0 Operative Note Draft Standard for Trial Use (HL7-ON DSTU) Release 1 as well as Logical Observation Identifiers Names and Codes (LOINC®) section names on 384 unique section headers from 362,311 operative notes. Overall, HL7-ON DSTU alone and HL7-ON DSTU with LOINC® section headers covered 66% and 79% of sections headers (93% and 98% of header instances), respectively. Section headers contained large numbers of synonyms, formatting variation, and variation of word forms, as well as smaller numbers of compound sections and issues with mismatches in header granularity. Robust operative note section mapping is important for clinical note interoperability and effective use of operative notes by natural language processing systems. The resulting operative note section resource is made publicly available.

Examining the use, contents, and quality of free-text tobacco use documentation in the Electronic Health Record.

Recent initiatives have emphasized the potential role of Electronic Health Record (EHR) systems for improving tobacco use assessment and cessation. In support of these efforts, the goal of the present study was to examine tobacco use documentation in the EHR with an emphasis on free-text. Three coding schemes were developed and applied to analyze 525 tobacco use entries, including structured fields and a free-text comment field, from the social history module of an EHR system to characterize: (1) potential reasons for using free-text, (2) contents within the free-text, and (3) data quality issues. Free-text was most commonly used due to limitations for describing tobacco use amount (23.2%), frequency (26.9%), and start or quit dates (28.2%) as well as secondhand smoke exposure (17.9%) using a variety of words and phrases. The collective results provide insights for informing system enhancements, user training, natural language processing, and standards for tobacco use documentation.

Characterizing the use and contents of free-text family history comments in the Electronic Health Record.

The detailed collection of family history information is becoming increasingly important for patient care and biomedical research. Recent reports have highlighted the need for efforts to better understand collection and use of this information in resources such as the Electronic Health Record (EHR). This two-part study involved characterizing the use and contents of free-text comments within the family history section of an EHR. Based on a manual review of a subset of 11,456 cancer-related family history entries, 20 "reasons for use" were identified and the distribution across these reasons determined. A semi-automated analysis of the 3,358 unique comments associated with these entries was then performed to identify and quantify key categories of information. Implications of this study include guiding efforts for the improved use, collection, and subsequent analysis of family history information in the EHR.

Social and behavioral history information in public health datasets.

Social and behavioral history is increasingly recognized as integral for understanding important determinants of disease and critical for patient care, research, clinical guidelines, and public health policies. Social and behavioral history information in the public health domain, specifically large public health surveys, has not been well described. In this study, a content analysis was performed and information model constructed and contrasted with clinically-based models for each of three widely used public health surveys: BRFSS (Behavioral Risk Factor Surveillance System), NHANES (National Health and Nutrition Examination Survey), and NHIS (National Health Interview Survey). Survey items were predominantly related to alcohol use, drug use, occupation, and tobacco use. Although the clinical social history information model was similar, public health social history demonstrated additional complexity in coding temporality, degree of exposure, and certainty. Our results give insight into ongoing efforts to integrate clinical and public health information resources for improving and measuring health.

APO A-V-1131T-->C polymorphism frequency and its association with morbidity in a Brazilian elderly population.

Identification of genetic polymorphisms as risk factors for complex diseases affecting older people can be relevant for their prevention, diagnosis and management. The -1131T-->C polymorphism of the apolipoprotein A-V gene (APO A-V) is tightly linked to lipid metabolism and has been associated with increased triglyceride levels and familial dyslipidemia. The aims of this study were to analyze the allele and genotype frequencies of this polymorphism in a Brazilian elderly population and to investigate any association between the polymorphism and major morbidities affecting elderly people. This polymorphism was investigated in 371 individuals, aged 66-97 years, in a Brazilian Elderly Longitudinal Population Study. Major morbidities investigated were: cerebrovascular diseases (CVD); myocardial infarction (MI); type 2 diabetes; hypertension; obesity; dementia; depression; and neoplasia. DNA was isolated and amplified by PCR and its products were digested with restriction enzyme Tru1I. T and C allele frequencies were 0.842 and 0.158, respectively. Our population showed allele frequencies that were similar to European and Afro-American and different from Asiatic populations. Genotype distributions were not within Hardy-Weinberg equilibrium only for the obesity subject sample. On the other hand, a significant association between the C allele and obesity in the presence of CVDxdepression interaction was observed. Logistic analysis showed no association of the polymorphism with each morbidity group. Therefore, the C allele in elderly Brazilian subjects may represent a risk factor for these morbidity interactions, which may lead to better comprehension of their pathophysiology.

Approach to mobile information and communication for health care.

Evidence suggests that inadequate access to information and ineffective communication are proximal causes of errors and other adverse events in-patient care. Within the context of reducing these proximal causes of errors, we explore the use of novel information-based approaches to improve information access and communication in health care settings. This paper describes the approaches for and the design of extensions to a clinical information system used to improve information access and communication at the point of care using information-based handheld wireless applications. These extensions include clinical and information resources, event monitoring, and a virtual whiteboard (VWB).