Testing an Intervention to Improve Health Care Worker Well-Being During the COVID-19 Pandemic: A Cluster Randomized Clinical Trial.

Importance: Stress First Aid is an evidence-informed peer-to-peer support intervention to mitigate the effect of the COVID-19 pandemic on the well-being of health care workers (HCWs). Objective: To evaluate the effectiveness of a tailored peer-to-peer support intervention compared with usual care to support HCWs' well-being at hospitals and federally qualified health centers (FQHCs) during the COVID-19 pandemic. Design, Setting, and Participants: This cluster randomized clinical trial comprised 3 cohorts of HCWs who were enrolled from March 2021 through July 2022 at 28 hospitals and FQHCs in the US. Participating sites were matched as pairs by type, size, and COVID-19 burden and then randomized to the intervention arm or usual care arm (any programs already in place to support HCW well-being). The HCWs were surveyed before and after peer-to-peer support intervention implementation. Intention-to-treat (ITT) analysis was used to evaluate the intervention's effect on outcomes, including general psychological distress and posttraumatic stress disorder (PTSD). Intervention: The peer-to-peer support intervention was delivered to HCWs by site champions who received training and subsequently trained the HCWs at their site. Recipients of the intervention were taught to respond to their own and their peers' stress reactions. Main Outcomes and Measures: Primary outcomes were general psychological distress and PTSD. General psychological distress was measured with the Kessler 6 instrument, and PTSD was measured with the PTSD Checklist. Results: A total of 28 hospitals and FQHCs with 2077 HCWs participated. Both preintervention and postintervention surveys were completed by 2077 HCWs, for an overall response rate of 28% (41% at FQHCs and 26% at hospitals). A total of 862 individuals (696 females [80.7%]) were from sites that were randomly assigned to the intervention arm; the baseline mean (SD) psychological distress score was 5.86 (5.70) and the baseline mean (SD) PTSD score was 16.11 (16.07). A total of 1215 individuals (947 females [78.2%]) were from sites assigned to the usual care arm; the baseline mean (SD) psychological distress score was 5.98 (5.62) and the baseline mean (SD) PTSD score was 16.40 (16.43). Adherence to the intervention was 70% for FQHCs and 32% for hospitals. The ITT analyses revealed no overall treatment effect for psychological distress score (0.238 [95% CI, -0.310 to 0.785] points) or PTSD symptom score (0.189 [95% CI, -1.068 to 1.446] points). Post hoc analyses examined the heterogeneity of treatment effect by age group with consistent age effects observed across primary outcomes (psychological distress and PTSD). Among HCWs in FQHCs, there were significant and clinically meaningful treatment effects for HCWs 30 years or younger: a more than 4-point reduction for psychological distress (-4.552 [95% CI, -8.067 to -1.037]) and a nearly 7-point reduction for PTSD symptom scores (-6.771 [95% CI, -13.224 to -0.318]). Conclusions and Relevance: This trial found that this peer-to-peer support intervention did not improve well-being outcomes for HCWs overall but had a protective effect against general psychological distress and PTSD in HCWs aged 30 years or younger in FQHCs, which had higher intervention adherence. Incorporating this peer-to-peer support intervention into medical training, with ongoing support over time, may yield beneficial results in both standard care and during public health crises. Trial Registration: ClinicalTrials.gov Identifier: NCT04723576.

Adapting the Stress First Aid Model for Frontline Healthcare Workers during COVID-19.

The coronavirus pandemic has generated and continues to create unprecedented demands on our healthcare systems. Healthcare workers (HCWs) face physical and psychological stresses caring for critically ill patients, including experiencing anxiety, depression, and posttraumatic stress symptoms. Nurses and nursing staff disproportionately experienced COVID-19-related psychological distress due to their vital role in infection mitigation and direct patient care. Therefore, there is a critical need to understand the short- and long-term impact of COVID-19 stress exposures on nursing staff wellbeing and to assess the impact of wellbeing programs aimed at supporting HCWs. To that end, the current study aims to evaluate an evidence-informed peer support stress reduction model, Stress First Aid (SFA), implemented across units within a psychiatric hospital in the New York City area during the pandemic. To examine the effectiveness of SFA, we measured stress, burnout, coping self-efficacy, resilience, and workplace support through self-report surveys completed by nurses and nursing staff over twelve months. The implementation of SFA across units has the potential to provide the workplace-level and individual-level skills necessary to reduce stress and promote resilience, which can be utilized and applied during waves of respiratory illness acuity or any other healthcare-related stressors among this population.

Commercial provider staff experiences of the NHS low calorie diet programme pilot: a qualitative exploration of key barriers and facilitators.

BACKGROUND: The National Health Service Type 2 Diabetes Path to Remission programme in England (known as the NHS Low Calorie Diet programme when piloted) was established to support people living with excess weight and Type 2 Diabetes to lose weight and improve their glycaemic control. A mixed method evaluation was commissioned to provide an enhanced understanding of the long-term cost effectiveness of the pilot programme, its implementation, equity and transferability across broad and diverse populations. This study provided key insights on implementation and equity from the service providers' perspective. METHODS: Thirteen focus groups were conducted with commercial providers of the programme, during the initial pilot rollout. Participants were purposively sampled across all provider organisations and staff roles involved in implementing and delivering the programme. Normalisation Process Theory (NPT) was used to design the topic schedule, with the addition of topics on equity and person-centredness. Data were thematically analysed using NPT constructs with additional inductively created codes. Codes were summarised, and analytical themes generated. RESULTS: The programme was found to fulfil the requirements for normalisation from the providers' perspective. However, barriers were identified in engaging GP practices and receiving sufficient referrals, as well as supporting service users through challenges to remain compliant. There was variation in communication and training between provider sites. Areas for learning and improvement included adapting systems and processes and closing the gap where needs of service users are not fully met. CONCLUSIONS: The evaluation of the pilot programme demonstrated that it was workable when supported by effective primary care engagement, comprehensive training, and effective internal and external communication. However, limitations were identified in relation to programme specifications e.g. eligibility criteria, service specification and local commissioning decisions e.g. pattern of roll out, incentivisation of general practice. A person-centred approach to care is fundamental and should include cultural adaptation(s), and the assessment and signposting to additional support and services where required.

Evaluation of the Implementation of the NFFF Stress First Aid Intervention in Career Fire Departments: A Cluster Randomized Controlled Trial.

Firefighting is inherently dangerous, though recently concerns have shifted from traditional fireground injuries (burns and asphyxiation) to a focus on mental and behavioral health. Although firefighters are remarkably resilient, research suggests many suffer negative psychological consequences from repeated exposures to trauma. While the Stress First Aid (SFA) model has gained increased attention and adoption among fire departments as a model for behavioral health training, it has not been formally evaluated. This cluster randomized controlled trial used a crossover design comparing the immediate SFA group to delayed SFA control to test the impact of the SFA on firefighters' mental and behavioral health changes after 10-12 months (n = 400; Mage = 37.6, 4.8% women). A convenience sample of 79 firefighters (Mage = 41.4; 8.7% women) provided evaluations on one or more of the training modules. Participants reported satisfaction with all training components (Peer team training 97.6%, Online SFA 94.9%, Curbside Manner 88.4%, After Action Review 89.4%) and reported success in changing personnel's perception of their department's ability to respond to behavioral health issues (SFA M = 3.93, Control 3.50; t = 2.52, p = 0.042). Future work should focus on additional resources and training to augment existing efforts to help departments continue their efforts.

Demise of the USMLE Step-2 CS exam: Rationalizing a way forward.

The COVID-19 pandemic has compelled rethinking and changes in medical education, the most controversial perhaps being the cancelation of USMLE Step-2 Clinical Skills exam (Step-2 CS). What started in March of 2020 as suspension of this professional licensure exam, because of concerns about infection risk for examinees, standardized patients (SPs), and administrators, soon became permanent cancelation in January 2021. Expectedly, it triggered debate in medical education circles. Positively, however, the USMLE regulatory agencies (NBME and FSMB) saw an opportunity to innovate an exam tainted with perceptions of validity deficits, cost, examinee inconvenience, and worries about future pandemics; they therefore called for a public debate to fashion a way forward. We have approached the issue by defining Clinical Skills (CS), exploring its epistemology and historic evolution, including assessment modalities from Hippocratic times to the modern era. We defined CS as the art of medicine manifest in the physician-patient encounter as history taking (driven by communication skills and cultural competence) and physical examination. We classified CS components into knowledge and psychomotor skill domains, established their relative importance in the physician process (clinical reasoning) of diagnosis, thus establishing a theoretical framework for developing valid, reliable, feasible, fair, and verifiable CS assessment. Given the concerns for COVID-19 and future pandemics, we established that CS can largely be assessed remotely, and what could not, can be assessed locally (school/regional consortia level) as part of a USMLE-regulated/supervised assessment regimen with established national standards, thus maintaining USMLE's fiduciary responsibilities. We have suggested a national/regional program for faculty development in CS curriculum development, and assessment, including standard setting skills. This pool of expert faculty will form the nucleus of our proposed USMLE-regulated External Peer Review Initiative (EPRI). Finally, we suggest that CS evolves into an academic discipline/department of its own, rooted in scholarship.

Time in Bed, Sleeping Difficulties, and Nutrition in Pregnant New Zealand Women.

We consider the relationship between time in bed (TIB) and sleeping difficulties with demographic variables and nutrient intakes in the second (T2) and third (T3) trimester of pregnancy. Data were acquired from a volunteer sample of New Zealand pregnant women. In T2 and T3, questionnaires were administered, diets were obtained from one 24 h recall and three weighed food records, and physical activity was measured with the use of three 24 h diaries. In total, 370 women had complete information in T2 and 310 in T3. In both trimesters, TIB was associated with welfare or disability status, marital status and age. In T2, TIB was associated with work, childcare, education and pre-pregnancy alcohol consumption. There were fewer significant lifestyle covariates in T3. In both trimesters, TIB declined with increasing dietary intake, especially water, protein, biotin, potassium, magnesium, calcium, phosphorus and manganese. Adjusted for weight of dietary intake and welfare/disability, TIB declined with increasing nutrient density of B vitamins, saturated fats, potassium, fructose and lactose; and TIB increased with carbohydrate, sucrose and vitamin E. Subjective sleeping difficulties increased with the week of gestation, morning sickness severity, anxiety, dairy and saturated fat intake, and they decreased with fruit, vegetable and monounsaturated fat intake. The study highlights the changing influence of covariates throughout the pregnancy and corroborates several published findings on the relationship of diet and sleep.

Helping the Helpers: Adaptation and Evaluation of Stress First Aid for Healthcare Workers in the Veterans Health Administration During the COVID-19 Pandemic.

BACKGROUND: Early interventions are needed to support the behavioral health of healthcare staff in the context of the COVID-19 pandemic. Stress First Aid (SFA) is a self-care and peer support model for reducing burnout and stress that is designed for use in high-stress occupations. METHODS: We conducted a mixed-methods evaluation of an SFA program in the Veterans Health Administration (VHA). This brief, multi-session, didactic program was adapted for hospital workgroups. Program attendees completed a survey assessing implementation outcomes, burnout, stress, mood, and SFA skills at the beginning (N = 246) and end (n = 94) of the SFA program and a subgroup (n = 11) completed qualitative feedback interviews. FINDINGS: Program acceptability, appropriateness, and feasibility were rated highly. From pre- to post-SFA, the impact of the pandemic on stress and anxiety, as well as proficiency in supporting peers increased. Qualitative findings suggest the program provided a shared language to discuss stress, normalized stress reactions, met a need for stress management tools, and helped staff feel valued, empowered, connected with each other. Staff reported being more aware of their stress, but SFA was insufficient to address many of the systemic sources of burnout and stress. CONCLUSIONS AND APPLICATIONS TO PRACTICE: While the SFA program was well received, the impact of brief programs is likely to be modest when implemented in the middle of an ongoing pandemic and when burnout arises from chiefly from systemic sources. Lessons learned during the program implementation that may guide future efforts are discussed.

We need to build the evidence: A systematic review of psychological first aid on mental health and well-being.

Ensuring effective mental health and psychosocial support is crucial following exposure to a potentially traumatic event and can have long-term consequences for individuals, families, and communities. Psychological first aid (PFA) has become a widespread intervention of choice following exposure to conflict or disaster; however, its impact is unknown. This systematic review assessed PFA efficacy in improving the mental health and psychosocial well-being of individuals exposed to potentially traumatic events. We searched PubMed, PsycINFO, PTSDpubs, and EMBASE for peer reviewed studies evaluating programmatic outcomes of PFA, or an adapted intervention, published in English before March 9, 2021. Studies evaluating training outcomes or program feasibility were excluded. The primary outcomes were reported measures of participant mental health and psychosocial well-being, with narrative results presented for each. The Cochrane Risk of Bias tool was applied. Of 9,048 potentially eligible citations, 12 studies with a total of 1,437 participants met the inclusion criteria. Only one study was a randomized controlled trial. The findings from all studies suggest a positive impact of PFA, with most reporting reduced symptoms of anxiety, depression, posttraumatic stress, and distress, as well as improved ratings of mood, the experience of safety, connectedness, and a sense of control, among youth and adults. Risk of bias was generally high. Inconsistent intervention components, insufficient evaluation methodologies, and a high risk of bias within the reviewed studies present challenges in assessing PFA efficacy, and an imbalance between popular support for PFA and scant evidence of outcome data exists. Further research is needed to justify the proliferation of PFA.

Giant Liver Infections: Cryptogenic Liver Abscess Secondary to Bacteroides Fragilis.

Hepatic abscesses are a seldom finding although they are the most common type of intraabdominal abscess. We find that this localized collection of pus can be a result of bacteria, ameba, or fungi. This study will mainly focus on the first type, the pyogenic liver abscess (PLA), in which management is predicated on size of abscess. There is no standard definition as to what constitutes a small or large hepatic abscess. Here, we present a case of a 10 cm PLA found in the right lobe of the liver. We aimed to discuss the relevant epidemiology, pathophysiology, clinical manifestations, and management of PLAs.

The Burden of Cold Agglutinin Disease on Patients' Daily Life: Web-Based Cross-sectional Survey of 50 American Patients.

BACKGROUND: Cold agglutinin disease (CAD) is a rare disorder, affecting 15% of patients with autoimmune hemolytic anemia. Few studies have assessed CAD symptoms and their impact on daily life, but these studies did not address the patients' perspectives. OBJECTIVE: The aims of this study were to increase the knowledge about CAD through a patient-centric survey and to gain a better understanding of the burden of this disease. METHODS: We conducted an internet-based survey in September 2020 among American patients registered on the CAD Unraveled website and members of the Cold Agglutinin Disease Foundation. RESULTS: A total of 50 respondents were included in this study. Totally, 90% (45/50) of the patients reported having experienced fatigue. Fatigue was mainly reported on a daily basis, and approximately one-third of these patients (13/45, 29%) said that their fatigue was constant throughout the day. It has also been shown that CAD has a great impact on patients' physical well-being, emotional well-being, social life, and household finances. The disease varies over time, with or without symptoms. A total of 88% (44/50) of the patients reported previous episodes of the increased intensity or sensitivity of their CAD symptoms, with a mean of 4.5 (SD 5.4) episodes reported during the past year. More than half of the patients (27/50, 54%) considered their disease to be moderate or severe, and 42% (21/50) of the study group reported that their symptoms had worsened since the time of diagnosis. CONCLUSIONS: Our study has provided new data on CAD symptoms, particularly data on the importance and type of fatigue and the fluctuation of CAD symptoms.

Protecting the mental and physical well-being of frontline health care workers during COVID-19: Study protocol of a cluster randomized controlled trial.

INTRODUCTION: The COVID-19 pandemic has placed health care workers at unprecedented risk of stress, burnout, and moral injury. This paper describes the design of an ongoing cluster randomized controlled trial to compare the effectiveness of Stress First Aid (SFA) to Usual Care (UC) in protecting the well-being of frontline health care workers. METHODS: We plan to recruit a diverse set of hospitals and health centers (eight matched pairs of hospitals and six pairs of centers), with a goal of approximately 50 HCW per health center and 170 per hospital. Participating sites in each pair are randomly assigned to SFA or UC (i.e., whatever psychosocial support is currently being received by HCW). Each site identified a leader to provide organizational support of the study; SFA sites also identified at least one champion to be trained in the intervention. Using a "train the trainer" model, champions in turn trained their peers in selected HCW teams or units to implement SFA over an eight-week period. We surveyed HCW before and after the implementation period. The primary outcomes are posttraumatic stress disorder and general psychological distress; secondary outcomes include depression and anxiety symptoms, sleep problems, social functioning problems, burnout, moral distress, and resilience. In addition, through in-depth qualitative interviews with leaders, champions, and HCW, we assessed the implementation of SFA, including acceptability, feasibility, and uptake. DISCUSSION: Results from this study will provide initial evidence for the application of SFA to support HCW well-being during a pandemic. TRIAL REGISTRATION: (Clinicaltrials.govNCT04723576).

Stress, PTSD, and COVID-19: the Utility of Disaster Mental Health Interventions During the COVID-19 Pandemic.

Purpose of review: In the context of an ongoing, highly uncertain pandemic, disaster mental health measures can increase community capacity for resilience and well-being, support formal mental health treatment, and help address the risk for mental health reactions in high-stress occupations. The purpose of this review is to summarize the literature on disaster mental health interventions that have been helpful both prior to and during the pandemic in a broad range of applications, including for use with high-stress occupations in an effort to mitigate risk for post-traumatic stress disorder (PTSD) and other mental health sequelae. Recent findings: Evidence-based and evidence-informed disaster mental health interventions, frameworks, and treatments have been studied in pilot studies, non-randomized trials, and randomized clinical trials prior to and in the context of the current COVID-19 pandemic. The studies have demonstrated feasibility and acceptability of these modalities and improved perceived support, as well as significant reductions in distress, and mental health symptoms such as depression, anxiety, and PTSD. Summary: A disaster mental health approach to the COVID-19 pandemic can generate opportunities for prevention and support at multiple levels with timely interventions tailored for different concerns, cultures, and available resources.

Five Essential Elements of Immediate and Mid-Term Mass Trauma Intervention: Empirical Evidence.

Given the devastation caused by disasters and mass violence, it is critical that intervention policy be based on the most updated research findings. However, to date, no evidence-based consensus has been reached supporting a clear set of recommendations for intervention during the immediate and the mid-term post mass trauma phases. Because it is unlikely that there will be evidence in the near or mid-term future from clinical trials that cover the diversity of disaster and mass violence circumstances, we assembled a worldwide panel of experts on the study and treatment of those exposed to disaster and mass violence to extrapolate from related fields of research, and to gain consensus on intervention principles. We identified five empirically supported intervention principles that should be used to guide and inform intervention and prevention efforts at the early to mid-term stages. These are promoting: 1) a sense of safety, 2) calming, 3) a sense of self- and community efficacy, 4) connectedness, and 5) hope.

Maternal alcohol intakes before and during pregnancy: Impact on the mother and infant outcome to 18 months.

AIM: To investigate maternal alcohol intakes before and during pregnancy, their impact on mothers and infants to 18 months. METHOD: Prospective study of 504 New Zealand volunteers visited in months 4 and 7 of pregnancy, measurements taken, lifestyle details recorded including alcohol intake before and during pregnancy. Eighteen months after birth, 370 infants were measured, and infant development recorded. RESULTS: Nineteen per cent of mothers never drank, 53% stopped when they knew they were pregnant, 29% continued to drink. Twenty-two per cent of drinkers binge drank (over 50 g alcohol per session) before pregnancy and 10% during pregnancy. Daily drinking was associated with increased obesity in mothers. Alcohol consumption before or during pregnancy was not associated with infant motor development, had a slight negative effect on growth, and a significant association with vocal ability to 18 months. Energy intake appeared to partially moderate this effect. CONCLUSION: Maternal alcohol consumption exceeding 50 g per session both before and during pregnancy was associated with decreasing vocal ability in the 18-month old infant.

An Open Label Pilot Study of a Brief Psychosocial Intervention for Disaster and Trauma Survivors.

BACKGROUND: In the aftermath of disaster, a large proportion of people will develop psychosocial difficulties that impair recovery, but for which presentations do not meet threshold criteria for disorder. Although these adjustment problems can cause high distress and impairment, and often have a trajectory towards mental health disorder, few evidence-based interventions are available to facilitate recovery. OBJECTIVE: This paper describes the development and pilot testing of an internationally developed, brief, and scalable psychosocial intervention that targets distress and poor adjustment following disaster and trauma. METHOD: The Skills fOr Life Adjustment and Resilience (SOLAR) program was developed by an international collaboration of trauma and disaster mental health experts through an iterative expert consensus process. The resulting five session, skills-based intervention, deliverable by community-based or frontline health or disaster workers with little or no formal mental health training (known as coaches), was piloted with 15 Australian bushfire survivors using a pre-post with follow up, mixed-methods design study. RESULTS: Findings from this pilot demonstrated that the SOLAR program was safe and feasible for non-mental health frontline workers (coaches) to deliver locally after two days of training. Participants' attendance rates and feedback about the program indicated that the program was acceptable. Pre-post quantitative analysis demonstrated reductions in psychological distress, posttraumatic stress symptoms, and impairment. CONCLUSIONS: This study provides preliminary evidence that the delivery of the SOLAR program after disaster by trained, frontline workers with little or no mental health experience is feasible, acceptable, safe, and beneficial in reducing psychological symptoms and impairment among disaster survivors. Randomized controlled trials of the SOLAR program are required to advance evidence of its efficacy.

PTSD as a Public Mental Health Priority.

PURPOSE OF REVIEW: This article reviews recent evidence related to public health epidemiology and intervention for traumatic stress and PTSD. Recent evidence is presented regarding incidence of traumatic stress worldwide, as well as most frequent types of traumas, indicators of the public health burden of PTSD, and prevalence, predictors, and correlates of PTSD. Public health perspectives on intervention and treatment are delineated, and innovations in both psychosocial and psychopharmacological interventions are highlighted. RECENT FINDINGS: PTSD has been associated with substantial medical and economic burden. Recent public health preventive innovations include integrated medical/behavioral health care, acute CBT and attention interventions, modifications to CBT protocols, use of novel and augmentative psychopharmacological agents, and use of technology. Recent research regarding the scope and impact of traumatic stress, as well as prevention strategies for PTSD, have resulted in an improved understanding of its impact and more effective public health interventions.

Complementary feature selection from alternative splicing events and gene expression for phenotype prediction.

MOTIVATION: A central task of bioinformatics is to develop sensitive and specific means of providing medical prognoses from biomarker patterns. Common methods to predict phenotypes in RNA-Seq datasets utilize machine learning algorithms trained via gene expression. Isoforms, however, generated from alternative splicing, may provide a novel and complementary set of transcripts for phenotype prediction. In contrast to gene expression, the number of isoforms increases significantly due to numerous alternative splicing patterns, resulting in a prioritization problem for many machine learning algorithms. This study identifies the empirically optimal methods of transcript quantification, feature engineering and filtering steps using phenotype prediction accuracy as a metric. At the same time, the complementary nature of gene and isoform data is analyzed and the feasibility of identifying isoforms as biomarker candidates is examined. RESULTS: Isoform features are complementary to gene features, providing non-redundant information and enhanced predictive power when prioritized and filtered. A univariate filtering algorithm, which selects up to the N highest ranking features for phenotype prediction is described and evaluated in this study. An empirical comparison of pipelines for isoform quantification is reported by performing cross-validation prediction tests with datasets from human non-small cell lung cancer (NSCLC) patients, human patients with chronic obstructive pulmonary disease (COPD) and amyotrophic lateral sclerosis (ALS) transgenic mice, each including samples of diseased and non-diseased phenotypes. AVAILABILITY AND IMPLEMENTATION: https://github.com/clabuzze/Phenotype-Prediction-Pipeline.git CONTACT: clabuzze@iastate.edu, antoniom@bc.edu, watsondk@musc.edu, andersonpe2@cofc.edu.

Multivariate models from RNA-Seq SNVs yield candidate molecular targets for biomarker discovery: SNV-DA.

BACKGROUND: It has recently been shown that significant and accurate single nucleotide variants (SNVs) can be reliably called from RNA-Seq data. These may provide another source of features for multivariate predictive modeling of disease phenotype for the prioritization of candidate biomarkers. The continuous nature of SNV allele fraction features allows the concurrent investigation of several genomic phenomena, including allele specific expression, clonal expansion and/or deletion, and copy number variation. RESULTS: The proposed software pipeline and package, SNV Discriminant Analysis (SNV-DA), was applied on two RNA-Seq datasets with varying sample sizes sequenced at different depths: a dataset containing primary tumors from twenty patients with different disease outcomes in lung adenocarcinoma and a larger dataset of primary tumors representing two major breast cancer subtypes, estrogen receptor positive and triple negative. Predictive models were generated using the machine learning algorithm, sparse projections to latent structures discriminant analysis. Training sets composed of RNA-Seq SNV features limited to genomic regions of origin (e.g. exonic or intronic) and/or RNA-editing sites were shown to produce models with accurate predictive performances, were discriminant towards true label groupings, and were able to produce SNV rankings significantly different from than univariate tests. Furthermore, the utility of the proposed methodology is supported by its comparable performance to traditional models as well as the enrichment of selected SNVs located in genes previously associated with cancer and genes showing allele-specific expression. As proof of concept, we highlight the discovery of a previously unannotated intergenic locus that is associated with epigenetic regulatory marks in cancer and whose significant allele-specific expression is correlated with ER+ status; hereafter named ER+ associated hotspot (ERPAHS). CONCLUSION: The use of models from RNA-Seq SNVs to identify and prioritize candidate molecular targets for biomarker discovery is supported by the ability of the proposed method to produce significantly accurate predictive models that are discriminant towards true label groupings. Importantly, the proposed methodology allows investigation of mutations outside of exonic regions and identification of interesting expressed loci not included in traditional gene annotations. An implementation of the proposed methodology is provided that allows the user to specify SNV filtering criteria and cross-validation design during model creation and evaluation.