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Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel

by Ashley M. Brooks, Andrea Vornoli, Ramesh C. Kovi, Thai Vu T. Ton, Miaofei Xu, Ahmed Mashal, Eva Tibaldi, Federica Gnudi, Jian-Liang Li, Robert C. Sills, John R. Bucher, Daniele Mandrioli, Fiorella Belpoggi, Arun R. Pandiri

The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.

Cost of inaction: a framework to estimate the economic cost of missing a patient with tuberculosis in the Indian context

Por: Brooks · M. B. · Pingali · V. · Nicholson · T. · Keshavjee · S.
Objectives

To estimate the economic impact of failure to find and treat tuberculosis disease and prevent tuberculosis infection from progressing to active disease.

Design

Estimating the economic cost of not finding and treating a patient suffering from tuberculosis.

Setting

Estimation methodology is developed in the Indian context, as informed by local costs and reported tuberculosis epidemiology.

Participants

No individual participants were included.

Primary and secondary outcome measures

The primary outcome measure is the total cost of patients with drug-susceptible and drug-resistant tuberculosis who are and are not found and treated by tuberculosis programmes, including costs for medications, lost productivity, healthcare services and furthered transmission. We calculate the economic burdens by varying the number of individuals a person sick with tuberculosis infects (10 or 15 people) and the risk of progression to tuberculosis disease if infected (5 or 8%). The secondary outcome measure is the amount saved by finding a patient early or who would not have otherwise been found. All costs are presented in US dollars (exchange rate: 72 Indian rupees/1 US$).

Results

By finding and treating a patient early before furthered transmission occurs—or stopping progression of tuberculosis infection to tuberculosis disease with preventive therapy—the Indian health system can save US$5502 to US$15 825 and US$5846 to US$25 575, for each individual with drug-susceptible and drug-resistant tuberculosis, respectively, across scenarios.

Conclusions

These estimates provide crude, lower bounds for the potential costs of not appropriately diagnosing and treating a single patient with active tuberculosis in a timely manner, or preventing a patient with tuberculosis infection from progressing to active disease. The actual financial burden on society is far higher than estimated using this simple, short-term cost-effective analyses. Our results highlight the limitations of tuberculosis costing models to date, and demonstrate the importance of accounting for airborne transmission of tuberculosis.

Effect of the Nurse Work Environment on Older Hispanic Surgical Patient Readmissions

imageBackground Readmissions following hospitalization for common surgical procedures are prevalent among older adults and are disproportionally experienced by Hispanic patients. One potential explanation for these disparities is that Hispanic patients may receive care in hospitals with lower-quality nursing care. Objectives The objective of this study was to evaluate the relationship between the hospital-level work environment of nurses and hospital readmissions among older Hispanic patients. Methods Using linked data sources from 2014 to 2016, we conducted a cross-sectional analysis of 522 hospitals and 732,035 general, orthopedic, and vascular surgical patients (80,978 Hispanic patients and 651,057 non-Hispanic White patients) in four states. Multivariable logistic regression models were employed to determine the relationship between the work environment and older Hispanic patient readmissions at multiple time periods (7, 30, and 90 days). Results In final adjusted models that included an interaction between work environment and ethnicity, an increase in the quality of the work environment resulted in a decrease in the odds of readmission that was greater for older Hispanic surgical patients at all time periods. Specifically, an increase in three of the five work environment subscales (Nurse Participation in Hospital Affairs, Nursing Foundations for Quality of Care, and Staffing and Resource Adequacy) was associated with a reduction in the odds of readmission that was greater for Hispanic patients than their non-Hispanic White counterparts. Discussion System-level investments in the work environment may reduce Hispanic patient readmission disparities. This study’s findings may be used to inform the development of targeted interventions to prevent hospital readmissions for Hispanic patients.

Cut‐off scores of the Depression Anxiety Stress Scale‐8: Implications for improving the management of chronic pain

Abstract

Aim

Mental distress, non-specific symptoms of depression and anxiety, is common in chronic pelvic pain (CPP). It contributes to poor recovery. Women's health nurses operate in multidisciplinary teams to facilitate the assessment and treatment of CPP. However, valid cut-off points for identifying highly distressed patients are lacking, entailing a gap in CPP management.

Design

This instrumental cross-sectional study identified a statistically derived cut-off score for the Depression Anxiety Stress Scale-8 (DASS-8) among 214 Australian women with CPP (mean age = 33.3, SD = 12.4, range = 13–71 years).

Methods

Receiver operator characteristic curve, decision trees and K-means clustering techniques were used to examine the predictive capacity of the DASS-8 for psychiatric comorbidity, pain severity, any medication intake, analgesic intake and sexual abuse. The study is prepared according to the STROBE checklist.

Results

Cut-off points resulting from the analysis were ordered ascendingly. The median (13.0) was chosen as an optimal cut-off score for predicting key outcomes. Women with DASS-8 scores below 15.5 had higher analgesic intake.

Conclusion

CPP women with a DASS-8 score above 13.0 express greater pain severity, psychiatric comorbidity and polypharmacy. Thus, they may be a specific target for nursing interventions dedicated to alleviating pain through the management of associated co-morbidities.

Implications for patient care

At a cut-off point of 13.0, the DASS-8 may be a practical instrument for recommending a thorough clinician-based examination for psychiatric comorbidity to facilitate adequate CPP management. It may be useful for evaluating patients' response to nursing pain management efforts. Replications of the study in different populations/countries are warranted.

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