Treatment Considerations Research Articles

The effect of histone deacetylase inhibitors on the efficiency of the CRISPR/Cas9 system

The CRISPR/Cas9 technology is a prominent genome-editing tool capable of producing a double-strand break in the genome. However, the modification of hematopoietic stem cells via the homology-directed repair pathway is still inefficient. Therefore, we hypothesize that histone deacetylase inhibitors, such as valproic acid (VPA) and sodium butyrate (NaB), could enhance HDR efficiency by increasing the accessibility of the genome-editing machinery. To address the potential utilization of HDAC inhibitors therapeutically, we began by assessing the effect of VPA and NaB on two cell lines representative of the two hematopoietic stem cell lineages. No statistically significant effect on cell growth or viability was observed at concentrations as high as 5 mM. At a concentration as low as 0.005 mM NaB, an enhancement in CRISPR cutting efficiency was evidenced in both cell lines. This enhancement did not appear to be locus-specific. However, an enhancement in cutting efficiency following VPA treatment does appear to be. HDR efficiency was enhanced greater than two-fold with the use of 0.005 mM VPA. These results are promising and suggest the consideration of treatment with an HDAC inhibitor in CRISPR/Cas9 genome editing protocols.

Clinical impact of the type VI secretion system on clinical characteristics, virulence and prognosis of Acinetobacter baumannii during bloodstream infection

The type VI secretion system (T6SS) has been regarded as a late-model virulence factor widely distributed in Acinetobacter baumannii (A. baumannii). This study aimed to elucidate the clinical manifestations, the genetic background and microbiological characteristics of A. baumannii isolates causing bloodstream infection (BSI), and assessed the impact of T6SS carrying state on the clinical course. In this study, Clinical samples of A. baumannii causing BSI were collected from a teaching hospital in China from 2016 to 2020 and a retrospective cohort was conducted. Experimental strains were categorized into T6SS positive and negative groups through PCR targeting on hcp gene. The antimicrobials sensitivity test, virulence genes, biofilm formation ability, serum resistance of A. baumannii strains and Galleria mellonella infection model were investigated. Independent risk factors for T6SS+ A. baumannii BSI and Kaplan-Meier curve through follow-up survey were analyzed. A total of 182 A. baumannii strains were isolated from patients with BSI during 5 years and the medical records of all patients were retrospectively reviewed. The proportion of T6SS+ isolates was 62.64% (114/182), which exhibited significantly higher resistance rates of commonly used antibacterial drugs compared to T6SS- group. We found that T6SS+ A. baumannii strains had significantly weaker biofilm formation ability compared to T6SS- A. baumannii. Despite no difference in the positivity rate of tested virulence genes in two groups, T6SS+ strains exhibited higher resistance to the serum and increased virulence in vivo compared to T6SS- strains, indicating that T6SS is likely to enhance the survival and invasive capabilities of A. baumannii in vivo. Indwelling catheter, respiratory diseases, ICU history, white blood cell count and percentage of neutrophils increasing were independent risk factors for T6SS+ A. baumannii BSI. At last, the Kaplan-Meier curve confirmed a higher mortality rate associated with T6SS+ A. baumannii BSI, suggesting that the presence of T6SS may serve as a prognostic factor for mortality. In conclusion, our study revealed that T6SS+ A. baumannii exhibited distinct clinical features, characterized by high antimicrobial resistance and enhanced virulence, providing valuable insights for clinical treatment considerations.

Pathophysiology of Acute Coronary Syndromes-Diagnostic and Treatment Considerations.

Coronary artery disease and acute coronary syndromes are accountable for significant morbidity and mortality, despite the preventive measures and technological advancements in their management. Thus, it is mandatory to further explore the pathophysiology in order to provide tailored and more effective therapies, since acute coronary syndrome pathogenesis is more varied than previously assumed. It consists of plaque rupture, plaque erosion, and calcified nodules. The advancement of vascular imaging tools has been critical in this regard, redefining the epidemiology of each mechanism. When it comes to acute coronary syndrome management, the presence of ruptured plaques almost always necessitates emergent reperfusion, whereas the presence of plaque erosions may indicate the possibility of conservative management with potent antiplatelet and anti-atherosclerotic medications. Calcified nodules, on the other hand, are an uncommon phenomenon that has largely gone unexplored in terms of the best management plan. Future studies should further establish the importance of detecting the underlying mechanism and the role of various treatment plans in each of these distinct entities.

Treatment considerations in total anomalous pulmonary venous connection

Background Total anomalous pulmonary venous connection (TAPVC) is a rare cyanotic abnormality that accounts for about 1%–3% of congenital heart disease malformations. TAPVC is a condition in which there is no direct connection between all four pulmonary veins and the left atrium but makes abnormal connections to the right atrium or systemic venous system. TAPVC caused a high mortality rate of 80% in the first year of life, and 50% of them die within 3 months after birth without intervention. Objectives The aim of this review is to elucidate the various treatment considerations of TAPVC. Methods A literature search was conducted on PubMed, ScienceDirect and Google Scholar using various combinations of keywords related to treatment of TAPVC. The citations from all selected articles were reviewed for additional studies. Results and Conclusion TAPVC intervention, including medical and surgical, is tailored to each type of TAPVC. Catheter-based interventions are frequently used to temporize neonates and provide time to optimize patients medically prior to definite repair. Corrective surgery is required for all patients with this condition. Several latest catheter-based or surgical intervention technique modifications have also been reported.

Clinical treatment considerations in the intensity-modulated radiotherapy era for parotid lymph node metastasis in patients with nasopharyngeal carcinoma

PurposeNo specific irradiation guidelines have been proposed for parotid lymph node (PLN) metastasis in patients with nasopharyngeal carcinoma (NPC). This study aimed to explore the dose prescription and target delineation for PLN metastasis in patients with NPC. MethodsWith the NPC database from a big-data platform, 10,685 patients with primarily diagnosed, non-distant metastatic, histologically proven NPC and treated with intensity modulated radiotherapy (IMRT) at our center from 2008 to 2019 were reviewed and those with PLN metastasis were enrolled in this study. Dosimetry parameters were collected from the dose-volume histograms (DVH). The primary endpoint was overall survival (OS). Least absolute shrinkage and selection operator regression (LASSO) was operated for variable selection. Multivariate Cox regression analysis was applied to identify the independent prognostic factors. ResultsPLN metastases were identified in 275/10685 (2.5%) patients. Of 367 positive PLN, 199 were in superficial intra-parotid, followed by 70 in deep intra-parotid, 54 in subparotid and 44 in subcutaneous pre-auricular. Better survival outcome was observed in PLN-radical IMRT group, compared with PLN-sparing group. In 190 patients received PLN-radical IMRT, multivariate analysis revealed that D95% of level VIII > 55 Gy was an independent beneficial prognostic factor for overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and parotid relapse-free survival (PRFS). ConclusionBased on the distribution pattern of PLN metastasis in NPC and the result of dose-finding study, involving the ipsilateral level VIII into low-risk clinical target volume (CTV2) is recommended for NPC with PLN metastasis.

Impact of aging on treatment considerations for multiple sclerosis patients.

With a rapidly aging global population and improvement of outcomes with newer multiple sclerosis (MS)-specific disease-modifying therapies (DMTs), the epidemiology of MS has shifted to an older than previously described population, with a peak prevalence of the disease seen in the 55-65 years age group. Changes in the pathophysiology of MS appear to be age-dependent. Several studies have identified a consistent phase of disability worsening around the fifth decade of life. The latter appears to be independent of prior disease duration and inflammatory activity and concomitant to pathological changes from acute focal active demyelination to chronic smoldering plaques, slow-expanding lesions, and compartmentalized inflammation within the central nervous system (CNS). On the other hand, decreased CNS tissue reserve and poorer remyelinating capacity with aging lead to loss of relapse recovery potential. Aging with MS may imply longer exposure to DMTs, although treatment efficacy in patients >55 years has not been evaluated in pivotal randomized controlled trials and appears to decrease with age. Older individuals are more prone to adverse effects of DMTs, an important aspect of treatment individualization. Aging with MS also implies a higher global burden of comorbid illnesses that contribute to overall impairments and represent a crucial confounder in interpreting clinical worsening. Discontinuation of DMTs after age 55, when no evidence of clinical or radiological activity is detected, is currently under the spotlight. In this review, we will discuss the impact of aging on MS pathobiology, the effect of comorbidities and other confounders on clinical worsening, and focus on current therapeutic considerations in this age group.

Venous thromboembolism characteristics, treatment and outcomes in young adults: findings from the Registro Informatizado de Enfermedad TromboEmbólica registry

BackgroundVenous thromboembolism (VTE) is rare in patients aged <21 years. Young adults aged 18 to 21 years are frequently included in adult VTE studies, whereas pediatric VTE studies include patients aged up to either 18 or 21 years. The clinical characteristics of young adult patients with VTE have not been well defined. ObjectivesWe aimed to highlight any unique characteristics or treatment considerations that may apply to young adult patients with VTE. MethodsData from the prospective, international Registro Informatizado de Enfermedad TromboEmbólica registry were used. Patients were stratified into subcohorts according to age. The clinical characteristics, risk factors, management, and outcomes of young adult patients with VTE were compared with those of adolescents aged 12 to 18 years and adults aged >21 years. ResultsOf 104 253 Registro Informatizado de Enfermedad TromboEmbólica patients enrolled until August 2022, 234 were adolescents and 884 were young adults. Less cases of pulmonary embolism were reported in adolescents (P < .001). Estrogen use was a common risk factor, more prevalent in adolescents and young adults (P < .001), whereas active cancer and immobilization were uncommon in both. Most patients were initially treated with low-molecular–weight heparin. VTE recurrence, major bleeding, and all-cause mortality rates were comparably low among adolescents and young adults. None of the patients aged <21 years died from VTE recurrence. ConclusionYoung adults have some distinctive VTE risk factors. While VTE presentation may be similar among young adults and older patients, the outcomes of patients aged <21 years are more favorable.

Irritable bowel syndrome – controversies in diagnosis and management

ABSTRACT Introduction The irritable bowel syndrome (IBS) is the best-recognized disorder of gut brain interactions (DGBI). However, it is controversial if the Rome IV criteria iteration for IBS diagnosis is fit for purpose. Areas covered This review critically evaluates Rome IV criteria for diagnosis of IBS and addresses clinical considerations in IBS treatment and management, including dietary factors, biomarkers, disease mimics, symptom severity, and subtypes. The role of diet in IBS is critically reviewed along with the influence of the microbiota, including small intestinal bacterial overgrowth. Expert opinion Emerging data suggest the Rome IV criteria are more suitable for identifying severe IBS and least useful for sub-diagnostic patients who are still likely to benefit from IBS treatment. Despite convincing evidence that IBS symptoms are diet-driven and often postprandial, a relationship to eating is not a Rome IV diagnostic criterion. Few IBS biomarkers have been identified, suggesting the syndrome is too heterogeneous to be measured by a single marker, and combined biomarker, clinical, dietary, and microbial profiling may be needed for objective characterization. With many organic diseases mimicking and overlapping with IBS, it’s important clinicians are knowledgable about this to mitigate the risk of missing comorbid organic intestinal disease and to optimally treat IBS symptoms.

Assessment and management of chronic kidney disease in people living with obesity

Obesity and chronic kidney disease (CKD) are common and frequently coexisting medical conditions. Already well known to be a risk factor for type 2 diabetes mellitus (T2DM), ischaemic heart disease, stroke, hypertension, malignancy and premature death, obesity also predisposes to CKD. Elevated weight leads to declining renal function through several mechanisms, including established pathways via metabolic syndrome, hypertension and T2DM, but also through relatively recently understood glomerulosclerosis, directly related to obesity. Compared with non-obese comparators, people living with obesity and established CKD develop faster decline in glomerular filtration, progression to end-stage renal disease (ESRD) and death. Importantly, treatment of obesity can influence these crucial renal outcomes and significantly improve quality of life. Declining renal function also impacts the medical and surgical treatment options available to treat patients with overweight and obesity. In this article, we briefly outline the epidemiology of obesity and renal disease and review the pathological interactions between these diseases before focusing on considerations for assessment and evidence-based treatments for obesity and renal disease.

Treatment of older patients with multiple sclerosis: Results of an International Delphi Survey.

People over age 50-55 have historically been excluded from randomized clinical trials for multiple sclerosis (MS). However, more than half of those living with an MS diagnosis are over 55. Explore the unique considerations of treating older people with MS (PwMS) using an iterative and structured Delphi-based assessment to gather expert opinions. Eight MS neurologists with an interest in older PwMS developed a 2-round survey. Survey respondents were qualified neurologists with ≥3 years' experience, personally responsible for treatment decisions, and treating ≥20 patients per month, of whom ≥10% were ≥50 years old. Consensus was defined as ≥75% agreement on questions with categorical responses or as a mean score ≥4 on questions with numerical responses. In Survey 1, 224 neurologists responded; 180 of these completed Survey 2. Limited consensus was reached with varying levels of agreement on several topics including identification and assessment of older patients; factors relating to treatment decisions including immunosenescence and comorbidities; considerations for high-efficacy treatments; de-escalation or discontinuation of treatment; effects of COVID-19; and unmet needs for treating this population. The results of this Delphi process highlight the need for targeted studies to create guidance for the care of older PwMS.

Reducing Cardiopulmonary Risk and Exacerbations in COPD.

New updates in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report include major changes to initial disease assessment and pharmacologic therapy, highlighting the clinical relevance of exacerbations. The updated GOLD 2023 algorithms offer a shorter path to consideration of triple therapy, including both initial and follow-up treatment. Most mild- or moderate-severity chronic obstructive pulmonary disease (COPD) exacerbations can be successfully managed in outpatient settings; primary care clinicians have many opportunities to identify, diagnose, and treat patients with COPD earlier to reduce lung damage and disease progression. COPD and cardiovascular disease share common mechanisms and risk factors that influence COPD management.

Gene Therapy as a Promising Approach for the Underlying Causes of Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a range of developmental disorders characterized by impaired traits associated with three distinct domains: communication, social interaction, and stereotypic repetitive behavior. Although its etiology depends on various components, current research mainly focuses on the genetic factors that contribute to the development of ASD and its effects. A big treatment consideration is gene therapy, which has disease-modifying potential. This article provides an insight into the foundation of ASD and the leading gene therapies that aim to rescue impaired neurological behavior. It will discuss how certain genetic factors can have large contributions to ASD development and how scientists can go about targeting these for potential remedy.

Central Auditory Processing Dysfunction in Service Members and Veterans: Treatment Considerations and Strategies.

Military risk factors such as blast exposure, noise exposure, head trauma, and neurotoxin exposure place Service members and Veterans at risk for deficits associated with auditory processing dysfunction. However, there is no clinical guidance specific to the treatment of auditory processing deficits in this unique population. We provide an overview of available treatments and their limited supporting evidence for use in adults, emphasizing the need for multidisciplinary case management and interdisciplinary research to support evidence-based solutions. We explored relevant literature to inform the treatment of auditory processing dysfunction in adults, with emphasis on findings involving active or former military personnel. We were able to identify a limited number of studies, pertaining primarily to the treatment of auditory processing deficits through the use of assistive technologies and training strategies. We assessed the current state of the science for knowledge gaps that warrant additional study. Auditory processing deficits often co-occur with other military injuries and may pose significant risk in military operational and occupational settings. Research is needed to advance clinical diagnostic and rehabilitative capabilities, guide treatment planning, support effective multidisciplinary management, and inform fitness-for-duty standards. We emphasize the need for an inclusive approach to the assessment and treatment of auditory processing concerns in Service members and Veterans and for evidence-based solutions to address complex military risk factors and injuries.

PS09 The raising of Lazarus: re-engagement of adults with atopic dermatitis following the advent of novel effective therapies

Abstract Atopic dermatitis (AD) has a devastating impact on quality of life, and persistent AD affects at least 7% of adults. Until recently, options for severe AD beyond topical therapies were limited to phototherapy and conventional immunosuppressive systemic drugs. With the advent of highly effective targeted treatments such as dupilumab and Janus kinase inhibitors (JAKi), patients with AD who had been lost to follow-up in dermatology are now returning en masse for consideration of biologic treatment or JAKi. The aim of this study was to analyse qualitatively the recapture of adults with severe AD who had previously been lost to follow-up because of disillusionment with suboptimal therapies and care. Semi-structured interviews were performed with 12 adults with severe AD to discuss their pathway to return to dermatology. Thematic analysis divided concepts into two categories: experiences of losing contact with dermatology and experiences of re-engagement with dermatology. Themes related to leaving dermatology care included the ineffectiveness of older treatments, toxicity of older treatments, attendance futility, dermatologist fatigue and ‘fizzling out’. ‘The ciclosporin would work for a few weeks but then I would have a flare, and my kidneys nearly gave out’; ‘I could tell the dermatologist was sick of looking at me. Back then I thought I was the problem, but now I think he was embarrassed because he couldn’t help me’; ‘I never decided I was going to stop going, it just ended up fizzling out and never going back.’ Themes related to re-engaging with dermatology care included social media influence, novelty, exasperation with quality of life and the life-changing improvements seen with novel treatments. ‘I saw someone on Facebook showing pictures after a few weeks on the injection and I went straight to my GP for a referral back to the dermatologist’; ‘After 60 years with eczema I just wanted to try something new, even if it killed me!’; ‘A few days after starting the tablets I left like Lazarus, it was like standing up out of a wheelchair for the first time in my life.’ This study highlights the reasons why adults with AD left dermatology services, explains why they re-engaged and deeply explores the transformative effect that novel treatments have had on the AD landscape. As adults with AD continue to return to dermatology care, the implications of increasing patient numbers needing biologic and JAKi therapy should be factored into healthcare and finance planning.

Treatment Considerations for Indigenous/First Nations Adopted Young Adults Placed with Dominant Culture Families

This article reviews the history, cultural features and issues that therapists and researchers need to be aware of in working with and for Indigenous adoptees. It discusses areas to cover in assessment, including awareness of the ubiquity of dissociation in this population, both culturally normal and trauma induced dissociation. Finally, it offers suggestions for interventions drawing from cultural ceremonies, arts/crafts and other traditions, as well as psychotherapeutic interventions based on building a trusting relationship, ego state therapy and Eye Movement Desensitization and Reprocessing.

Head Kinematics, Blood Biomarkers, and Histology in Large Animal Models of Traumatic Brain Injury and Hemorrhagic Shock.

Traumatic brain injury (TBI) and severe blood loss resulting in hemorrhagic shock (HS) are each leading causes of mortality and morbidity worldwide, and present additional treatment considerations when they are comorbid (TBI+HS) as a result of competing pathophysiological responses. The current study rigorously quantified injury biomechanics with high precision sensors and examined whether blood-based surrogate markers were altered in general trauma as well as post-neurotrauma. Eighty-nine sexually mature male and female Yucatan swine were subjected to a closed-head TBI+HS (40% of circulating blood volume; n = 68), HS only (n = 9), or sham trauma (n = 12). Markers of systemic (e.g., glucose, lactate) and neural functioning were obtained at baseline, and at 35 and 295 min post-trauma. Opposite and approximately twofold differences existed for both magnitude (device > head) and duration (head > device) of quantified injury biomechanics. Circulating levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase L1 (UCH-L1) demonstrated differential sensitivity for both general trauma (HS) and neurotrauma (TBI+HS) relative to shams in a temporally dynamic fashion. GFAP and NfL were both strongly associated with changes in systemic markers during general trauma and exhibited consistent time-dependent changes in individual sham animals. Finally, circulating GFAP was associated with histopathological markers of diffuse axonal injury and blood-brain barrier breach, as well as variations in device kinematics following TBI+HS. Current findings therefore highlight the need to directly quantify injury biomechanics with head mounted sensors and suggest that GFAP, NfL, and UCH-L1 are sensitive to multiple forms of trauma rather than having a single pathological indication (e.g., GFAP = astrogliosis).

Artificial Intelligence for Automated DWI/FLAIR Mismatch Assessment on Magnetic Resonance Imaging in Stroke: A Systematic Review.

We conducted this Systematic Review to create an overview of the currently existing Artificial Intelligence (AI) methods for Magnetic Resonance Diffusion-Weighted Imaging (DWI)/Fluid-Attenuated Inversion Recovery (FLAIR)-mismatch assessment and to determine how well DWI/FLAIR mismatch algorithms perform compared to domain experts. We searched PubMed Medline, Ovid Embase, Scopus, Web of Science, Cochrane, and IEEE Xplore literature databases for relevant studies published between 1 January 2017 and 20 November 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We assessed the included studies using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Five studies fit the scope of this review. The area under the curve ranged from 0.74 to 0.90. The sensitivity and specificity ranged from 0.70 to 0.85 and 0.74 to 0.84, respectively. Negative predictive value, positive predictive value, and accuracy ranged from 0.55 to 0.82, 0.74 to 0.91, and 0.73 to 0.83, respectively. In a binary classification of ±4.5 h from stroke onset, the surveyed AI methods performed equivalent to or even better than domain experts. However, using the relation between time since stroke onset (TSS) and increasing visibility of FLAIR hyperintensity lesions is not recommended for the determination of TSS within the first 4.5 h. An AI algorithm on DWI/FLAIR mismatch assessment focused on treatment eligibility, outcome prediction, and consideration of patient-specific data could potentially increase the proportion of stroke patients with unknown onset who could be treated with thrombolysis.

Focusing on the locus of the breakdown for treatment of anomia: a pilot study

ABSTRACT The primary goal of this study was to evaluate the treatment effects of semantic feature analysis (SFA) and phonological components analysis (PCA) on word retrieval processing in persons with aphasia (PWAs). After identifying the locus of the breakdown in lexical retrieval processing, 15 monolingual native Persian speakers with aphasia were divided into two groups. After three naming trials, participants with dominant semantic deficits received SFA, and participants with primary phonological deficits were provided with PCA three times a week for eight weeks. Both approaches improved participants’ naming and performance on language tests, including spontaneous speech, repetition, comprehension, and semantic processing. However, the correct naming of treated and untreated items was higher in mild-to-moderate participants, with mostly circumlocution and semantic paraphasias in the SFA group. The same holds for mild-to-moderate participants with mostly phonemic paraphasia who received PCA therapy. Moreover, the results showed that participants’ baseline naming performance and semantic abilities could be associated with the treatment outcomes. Although limited by a lack of a control group, this study provided evidence supporting the possible benefits of focusing on the locus of the breakdown for treating anomia through SFA and PCA approaches, specifically in participants with mild to moderate aphasia. However, for those with severe aphasia, the treatment choice may not be as straightforward because several variables are likely to contribute to this population’s word-finding difficulties. Replication with larger, well-stratified samples, use of a within-subjects alternating treatment design and consideration of treatments’ long-term effects are required to better ascertain the effects of focusing on the locus of breakdown for treatment of anomia.

Update to Management of Acute Scaphoid Fractures.

The scaphoid is the most commonly fractured carpal bone. With high clinical suspicion and negative radiographs, expedient evaluation by CT or MRI has been recommended. When treating nondisplaced or minimally displaced scaphoid waist and distal pole fractures, immobilization below the elbow without inclusion of the thumb is an option. Comparatively, early surgical intervention for nondisplaced or minimally displaced scaphoid waist fractures allows for quicker return of function, but with increased risk of surgical complications and no long-term outcomes differences compared with cast immobilization. For most patients with such fractures, consideration for aggressive conservative treatment involving 6 weeks of immobilization with CT assessment to guide the need for continued casting, surgical intervention, or mobilization is advocated. Determination of union is best done with a CT scan at 6 weeks and at least 50% continuous trabecular bridging across the fracture site deemed sufficient to begin mobilization. Nonsurgical and surgical management of scaphoid fractures requires a thorough understanding of fracture location, fracture characteristics, and patient-specific factors to provide the best healing opportunity of this notoriously difficult fracture and return the patient to full function.

Predicting Reasons for Drinking in a Dually-Diagnosed Sample with PTSD and Substance Use Disorders

Objective: Using the negative reinforcement and common factors frameworks, this work assessed whether and how anxiety sensitivity, distress tolerance, and impulsivity relate to reasons for drinking (RFD) in a residential treatment sample with co-occurring alcohol use disorder and posttraumatic stress disorder (AUD-PTSD). Demographic differences were also examined. Method: Participants were 75 (52.0% male, 78.7% white) adults at a residential substance use treatment facility who met criteria for AUD-PTSD with 98.67% meeting criteria for one or more substance use disorders in addition to AUD. Participants completed measures of anxiety sensitivity, distress tolerance, impulsivity, RFD, and AUD-PTSD symptoms. Univariate and multivariate linear regression was used with and without controlling for demographic variables (i.e., age, race, and sex). Results: The positive and negative urgency facets of impulsivity were positively related to both negative affect and cue/craving response RFD with relations maintained after controlling for demographic variables and including PTSD symptom severity (βs .30−.51). There were no significant relations between impulsivity and social RFD. No facets of anxiety sensitivity or distress tolerance were significantly related to RFD domains. Conclusions: Findings suggest that the urgency facets of impulsivity are crucial in understanding negative affect and cue/craving RFD. However, anxiety sensitivity and distress tolerance are not related to RFD in this dually diagnosed AUD-PTSD sample. Treatment considerations and future directions are discussed.