Recent advances in the investigation of fusion RNAs and their role in molecular pathology of cancer.

Gene fusions have had a significant role in the development of various types of cancer, oftentimes involved in oncogenic activities through dysregulation of gene expression or signalling pathways. Some cancer-associated chromosomal translocations can undergo backsplicing, resulting in fusion-circular RNAs, a more stable isoform immune to RNase degradation. This stability makes fusion circular RNAs a promising diagnostic biomarker for cancer. While the detection of linear fusion RNAs and their function in certain cancers have been described in literature, fusion circular RNAs lag behind due to their low abundance in cancer cells. This review highlights current literature on the role of linear and circular fusion transcripts in cancer, tools currently available for detecting of these chimeric RNAs and their function and how they play a role in tumorigenesis.

Real-world evidence from the first online healthcare analytics platform-Livingstone. Validation of its descriptive epidemiology module.

Incidence and prevalence are key epidemiological determinants characterizing the quantum of a disease. We compared incidence and prevalence estimates derived automatically from the first ever online, essentially real-time, healthcare analytics platform-Livingstone-against findings from comparable peer-reviewed studies in order to validate the descriptive epidemiology module. The source of routine NHS data for Livingstone was the Clinical Practice Research Datalink (CPRD). After applying a general search strategy looking for any disease or condition, 76 relevant studies were first retrieved, of which 10 met pre-specified inclusion and exclusion criteria. Findings reported in these studies were compared with estimates produced automatically by Livingstone. The published reports described elements of the epidemiology of 14 diseases or conditions. Lin's concordance correlation coefficient (CCC) was used to evaluate the concordance between findings from Livingstone and those detailed in the published studies. The concordance of incidence values in the final year reported by each study versus Livingstone was 0.96 (95% CI: 0.89-0.98), whilst for all annual incidence values the concordance was 0.93 (0.91-0.94). For prevalence, concordance for the final annual prevalence reported in each study versus Livingstone was 1.00 (0.99-1.00) and for all reported annual prevalence values, the concordance was 0.93 (0.90-0.95). The concordance between Livingstone and the latest published findings was near perfect for prevalence and substantial for incidence. For the first time, it is now possible to automatically generate reliable descriptive epidemiology from routine health records, and in near-real time. Livingstone provides the first mechanism to rapidly generate standardised, descriptive epidemiology for all clinical events from real world data.

A treatment prediction strategy for overactive bladder using a machine learning algorithm that utilized data from the FAITH study.

AIMS: To use machine learning algorithms to develop a model to accurately predict treatment responses to mirabegron or antimuscarinic agents in patients with overactive bladder (OAB), using real-world data from the FAITH registry (NCT03572231). METHODS: The FAITH registry data included patients who had been diagnosed with OAB symptoms for at least 3 months and were due to initiate monotherapy with mirabegron or any antimuscarinic. For the development of the machine learning model, data from patients were included if they had completed the 183-day study period, had data for all timepoints and had completed the overactive bladder symptom scores (OABSS) at baseline and end of study. The primary outcome of the study was a composite outcome combining efficacy, persistence, and safety outcomes. Treatment was deemed "more effective" if the composite outcome criteria for "successful," "no treatment change," and "safe" were met, otherwise treatment was deemed "less effective." To explore the composite algorithm, a total of 14 clinical risk factors were included in the initial data set and a 10-fold cross-validation procedure was performed. A range of machine learning models were evaluated to determine the most effective algorithm. RESULTS: In total, data from 396 patients were included (266 [67.2%] treated with mirabegron and 130 [32.8%] treated with an antimuscarinic). Of these, 138 (34.8%) were in the "more effective" group and 258 (65.2%) were in the "less effective" group. The groups were comparable in terms of their characteristic distributions across patient age, sex, body mass index, and Charlson Comorbidity Index. Of the six models initially selected and tested, the decision tree (C5.0) model was chosen for further optimization, and the receiver operating characteristic of the final optimized model had an area under the curve result of 0.70 (95% confidence interval: 0.54-0.85) when 15 was used for the min n parameter. CONCLUSIONS: This study successfully created a simple, rapid, and easy-to-use interface that could be further refined to produce a valuable educational or clinical decision-making aid.

Construct validity and reproducibility of the Prescription Opioid Misuse And Abuse Questionnaire (POMAQ).

OBJECTIVE: The Prescription Opioid Misuse and Abuse Questionnaire was developed to identify prescription opioid abuse and misuse among patients with chronic pain, however, evidence of construct validity and reproducibility is needed. METHODS: Chronic pain patients were recruited from five Department of Defense Military Health System clinics across the United States. Construct validity was examined using subjective clinician-reported and patient-reported measures as well as objective information (e.g. hair/urine drug screens and electronic medical records). Test-retest reliability was assessed across 2 timepoints among a subgroup of patients with stable chronic pain. RESULTS: Of 3,263 screened patients, 938 (28.7%) met eligibility and were enrolled; 809 (86.2%) completed the Prescription Opioid Misuse and Abuse Questionnaire. Construct validity was supported by comparison to other validated questionnaires and hair and urine screens which yielded high agreements with patient reports on the Prescription Opioid Misuse and Abuse Questionnaire. Electronic medical record data supported patients' Prescription Opioid Misuse and Abuse Questionnaire responses regarding physician and emergency room visits and opioid refills. The Prescription Opioid Misuse and Abuse Questionnaire had excellent test-retest reliability; the percentage agreement between the two Prescription Opioid Misuse and Abuse Questionnaire administrations was high (>90%) for most questions. DISCUSSION: Results suggest that the Prescription Opioid Misuse and Abuse Questionnaire is a valid and reproducible tool that can be used to assess the presence of prescription opioid misuse and abuse among patients with chronic pain.

Insight into chronic pain in the United States: descriptive results from the Prescription Opioid Misuse and Abuse Questionnaire (POMAQ) validation study.

OBJECTIVE: A chronic pain patient sample living in the United States who participated in a cross-sectional study to evaluate the validity and reproducibility of the Prescription Opioid Misuse and Abuse Questionnaire is characterized. METHODS: Patients with chronic pain identified through electronic medical records as refilling at least one opioid prescription within the prior 3 months were recruited from five United States Department of Defense Military Health System clinics. Patients completed the Prescription Opioid Misuse and Abuse Questionnaire, Brief Pain Inventory-Short Form, Medical Outcomes Study: 36-item Short Form, and sociodemographic questions online. Clinical characteristics and electronic medical records for 1 year prior to consent were collected. RESULTS: 809 (86.2%) participants completed the Prescription Opioid Misuse and Abuse Questionnaire. Mean (± standard deviation) age was 55.4 ± 12.7 years; the majority female (55.5%) and white (74.8%). Mean duration of chronic pain was 14.7 ± 10.5 years; the most common pain conditions were lower back pain (76.6%), neck or shoulder pain (60.3%), and osteoarthritis (38.7%). The most commonly prescribed opioids were oxycodone (35.7%), tramadol (34.5%), and hydrocodone (26.9%); 54.8% took one opioid, 44.9% took 2 or more opioids. DISCUSSION: Participants' health status was poor; pain severity and interference were moderate. Electronic medical record data revealed high healthcare resource utilization. This chronic pain population was severely impacted by their pain condition(s).

An Interdisciplinary Examination of Stress and Injury Occurrence in Athletes.

This paper adopts a novel, interdisciplinary approach to explore the relationship between stress-related psychosocial factors, physiological markers and occurrence of injury in athletes using a repeated measures prospective design. At four data collection time-points, across 1-year of a total 2-year data collection period, athletes completed measures of major life events, the reinforcement sensitivity theory personality questionnaire, muscle stiffness, heart rate variability and postural stability, and reported any injuries they had sustained since the last data collection. Two Bayesian networks were used to examine the relationships between variables and model the changes between data collection points in the study. Findings revealed muscle stiffness to have the strongest relationship with injury occurrence, with high levels of stiffness increasing the probability of sustaining an injury. Negative life events did not increase the probability of injury occurrence at any single time-point; however, when examining changes between time points, increases in negative life events did increase the probability of injury. In addition, the combination of increases in negative life events and muscle stiffness resulted in the greatest probability of sustaining an injury. Findings demonstrated the importance of both an interdisciplinary approach and a repeated measures design to furthering our understanding of the relationship between stress-related markers and injury occurrence.

Relationship Between Force Production During Isometric Squats and Knee Flexion Angles During Landing.

Decreased knee flexion angles during landing are associated with increased anterior cruciate ligament loading. The underlying mechanisms associated with decreased self-selected knee flexion angles during landing are still unclear. The purpose of this study was to establish the relationship between the peak force production at various knee flexion angles (35, 55, 70, and 90°) during isometric squats and the actual knee flexion angles that occur during landing in both men and women. A total of 18 men and 18 women recreational/collegiate athletes performed 4 isometric squats at various knee flexion angles while vertical ground reaction forces were recorded. Participants also performed a jump-landing-jump task while lower extremity kinematics were collected. For women, significant correlations were found between the peak force production at 55 and 70° of knee flexion during isometric squats and the knee flexion angle at initial contact of landing. There were also significant correlations between the peak force production at 55, 70, and 90° of knee flexion during isometric squats and the peak knee flexion angle during landing. These correlations tended to be stronger during isometric squats at greater knee flexion compared with smaller knee flexion. No significant correlations were found for men. Posture-specific strength may play an important role in determining self-selected knee flexion angles during landing for women.

Leveraging the military health system as a laboratory for health care reform.

The Patient Protection and Affordable Care Act recently passed into law is poised to profoundly affect the provision of medical care in the United States. In today's environment, the foundation for most ongoing comparative effectiveness research is financial claims data. However, there is an alternative that possesses much richer data. That alternative, uniquely positioned to serve as a test system for national health reform efforts, is the Department of Defense Military Health System. This article describes how to leverage the Military Health System and provide effective solutions to current health care reform challenges in the United States.