The Management of Substance Use Disorders: Synopsis of the 2021 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

DESCRIPTION: In August 2021, leadership within the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline (CPG) for the management of substance use disorders (SUDs). This synopsis summarizes key recommendations. METHODS: In March 2020, the VA/DoD Evidence-Based Practice Work Group assembled a team to update the 2015 VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders that included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy CPGs. The guideline panel developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and distilled 35 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. This synopsis presents the recommendations that were believed to be the most clinically impactful. RECOMMENDATIONS: The scope of the CPG is broad; however, this synopsis focuses on key recommendations for the management of alcohol use disorder, use of buprenorphine in opioid use disorder, contingency management, and use of technology and telehealth to manage patients remotely.

Frailty and stroke thrombectomy outcomes-an observational cohort study.

INTRODUCTION: Mechanical thrombectomy (MT) can improve outcomes following ischaemic stroke. Patient selection for MT is predominantly based on physiological and imaging parameters. We assessed whether people living with pre-stroke frailty had differing outcomes following MT. METHODS: We included consecutive patients undergoing MT at a UK comprehensive stroke centre. We calculated a cumulative deficits frailty index to identify pre-stroke frailty in those patients presenting directly to the centre. Frailty was defined as an index score ≥ 0.24. We assessed univariable and multivariable association between pre-stroke frailty and stroke outcomes. Our primary outcomes were modified Rankin Scale (mRS) and mortality at 90 days. RESULTS: Of 175 patients who underwent MT (2014-2018), we identified frailty in 49 (28%). Frail and non-frail patients had similar rates of thrombolysis administration, successful recanalization and onset to recanalization times. Those with pre-stroke frailty had higher 24 hour National Institutes of Health Stroke Scale (12(IQR: 8-17) versus 3(IQR: 2-13); P = 0.001); were less likely to be independent (mRS 0-2: 18% versus 61%; P < 0.001) and more likely to die (47% versus 14%; P < 0.001) within 90 days. Adjusting for age, baseline NIHSS and thrombolysis, frailty remained a strong, independent predictor of poor clinical outcome at 90 days (Death OR: 3.12 (95% CI: 1.32-7.4); dependency OR: 3.04 (95%CI: 1.10-8.44). Age was no longer a predictor of outcome when adjusted for frailty. CONCLUSION: Pre-stroke frailty is prevalent in real-world patients eligible for MT and is an important predictor of poor outcomes. Routine assessment of pre-stroke frailty could help decision-making around patient selection for MT.

Loss of Meaning at Work Associated with Burnout Risk in Academic Medicine.

OBJECTIVES: Meaning at work has been proposed as one of the key drivers of professional burnout in healthcare, but few studies have simultaneously measured this relation. METHODS: In this cross-sectional analysis of 1637 individuals at the University of Arkansas for Medical Sciences, burnout was measured using the Copenhagen Burnout Inventory work-related subscale. RESULTS: Meaningful work was measured using items adapted from the Work as Meaning Inventory. The prevalence of work-related burnout increased with each level of diminished meaning at work. From the highest ("always") to the lowest ("never") level of meaning at work, the prevalence of burnout was: 13, 26, 57, 84, and 94%, respectively. CONCLUSIONS: Work-related burnout was inversely proportional to reported meaning at work in an academic medical center.

COVID-19 in a rural health system in New York - case series and an approach to management.

INTRODUCTION: Many rural hospitals and health systems in the USA lack sufficient resources to treat COVID-19. St Lawrence Health (SLH) developed a system for managing inpatient COVID-19 hospital admissions in St Lawrence County, an underserved rural county that is the largest county in New York State. METHODS: SLH used a hub-and-spoke system to route COVID-19 patients to its flagship hospital. It further assembled a small clinical team to manage admitted COVID-19 patients and to stay abreast of a quickly changing body of literature and standard of care. A review of clinical data was completed for patients who were treated by SLH's inpatient COVID-19 treatment team between 20 March and 22 May 2020. RESULTS: Twenty COVID-19 patients were identified. Sixteen patients (80%) met National Institutes of Health criteria for severe or critical disease. One patient died. No patients were transferred to other hospitals. CONCLUSION: During the first 2 months of the pandemic, the authors were able to manage hospitalized COVID-19 patients in their rural community. Development of similar treatment models in other rural areas should be considered.

Variability in Opioid Equivalence Calculations.

OBJECTIVE: Equianalgesic conversion methods are commonly used to switch patients from one opioid to another due to suboptimal pain relief or adverse events. There is no universally accepted opioid conversion method, however, and there is often significant variability between conversion resources. As a result, patients are at risk for undertreated pain and serious adverse events. The purpose of this survey was to compare the equianalgesic conversion estimates between nurse practitioners, pharmacists, and physicians for commonly prescribed opioids. METHODS: A survey form was developed using Survey Monkey. Participation was solicited by providing a link to the survey via social media (e.g., Facebook, Twitter, LinkedIn, etc.) and emailing professional organizations for sharing with their members and followers. Data collected included demographics and estimated morphine equivalents (MEQs) of hydrocodone 80 mg, fentanyl transdermal patches 1,800 mcg (as 75 mcg/hour), methadone 40 mg, oxycodone 120 mg, and hydromorphone 48 mg. Participants were also asked to provide their choice of reference utilized to complete the conversions, including personal knowledge. Descriptive analyses were performed using measures of central tendency. Hypothesis testing was performed using Pearson's chi-squared and Fisher's Exact Test for categorical data and the Kruskal-Wallis equality of populations rank test for continuous data to assess differences between median opioid doses by professional groups. RESULTS: The total number of respondents included in the analysis was 319. Physicians, pharmacists, and nurse practitioners/physician assistants comprised 25.4%, 56.7%, and 16.3%, respectively, of respondents. The overall mean (± standard deviation) MEQ doses for fentanyl, hydrocodone, hydromorphone, methadone, and oxycodone were: 176 (±117) mg, 88 (±42) mg, 192 (±55) mg, 193 (±201) mg, and 173 (±39) mg, respectively. For fentanyl, the mean (±standard deviation) MEQ doses were 180 (±122) mg, 178 (±128) mg, and 157 (±68) mg, for physicians, pharmacists, and nurse practitioners/physician assistants, respectively. For all three groups of clinicians, the median MEQ dose for fentanyl was 150 mg. The mean (±standard deviation) MEQ doses of methadone for physicians, pharmacists, and nurse practitioners/physician assistants were: 214 (±142) mg, 171 (±107) mg, and 185 (±129) mg, respectively. The median MEQ dose for methadone was 160 mg for each of the clinician groups. CONCLUSIONS: As evidenced by large standard deviations, there was significant variation in mean opioid conversions to MEQ doses within each profession type, particularly for fentanyl and methadone. The median MEQ doses provided for opioid conversions were the same among each profession. No universal method exists that allows each of the five studied opioids to be accurately and consistently converted to another opioid (i.e., morphine).

Gross hematuria caused by nutcracker syndrome and segmental pseudoaneursym.

Nutcracker syndrome is a rare disorder characterized by extrinsic compression of left renal vein by the superior mesenteric artery and aorta. Prevalence of the disease is unknown, but presents most commonly with gross hematuria and flank pain. Diagnosis requires a high index of suspicion and treatment consists of a wide range of vascular surgical options with a more recent focus using an endovascular approach. We present a case of a 29-year-old female with continuous gross hematuria and flank pain from a segmental artery pseudoaneursym secondary to nutcracker and pelvic congestion syndrome.

PARP-1 regulates epithelial-mesenchymal transition (EMT) in prostate tumorigenesis.

Poly (ADP-ribose) polymerase (PARP) is involved in key cellular processes such as DNA replication and repair, gene transcription, cell proliferation and apoptosis. The role of PARP-1 in prostate cancer development and progression is not fully understood. The present study investigated the function of PARP-1 in prostate growth and tumorigenesis in vivo. Functional inactivation of PARP-1 by gene-targeted deletion led to a significant reduction in the prostate gland size in young PARP-1-/- mice (6 weeks) compared with wild-type (WT) littermates. To determine the effect of PARP-1 functional loss on prostate cancer onset, PARP-1-/- mice were crossed with the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Pathological assessment of prostate tumors revealed that TRAMP+/-, PARP-1-/- mice exhibited higher grade prostate tumors compared with TRAMP+/- PARP-1+/+ (16-28 weeks) that was associated with a significantly increased proliferative index and decreased apoptosis among the epithelial cells in TRAMP+/- PARP-1-/- prostate tumors. Furthermore tumors harboring PARP-1 loss, exhibited a downregulation of nuclear androgen receptor. Impairing PARP-1 led to increased levels of transforming growth factor-ß (TGF-ß) and Smads that correlated with induction of epithelial-mesenchymal transition (EMT), as established by loss of E-cadherin and ß-catenin and upregulation of N-cadherin and ZEB-1. Our findings suggest that impaired PARP-1 function promotes prostate tumorigenesis in vivo via TGF-ß-induced EMT. Defining the EMT control by PARP-1 during prostate cancer progression is of translational significance for optimizing PARP-1 therapeutic targeting and predicting response in metastatic castration-resistant prostate cancer.

Identifying Risk Factors for Cardiovascular Events Among Active-Duty Service Members and Veterans Prescribed Nonsteroidal Anti-Inflammatory Drugs (NSAIDs).

Background: Oral NSAIDs are widely used analgesic medications for the treatment of musculoskeletal and inflammatory conditions. NSAIDs are associated with adverse effects that arise from COX enzyme inhibition including cardiovascular events. The combined role of patient and prescription factors associated with NSAID use on cardiovascular risk is not well characterized. Objective: The purpose of this study is to identify the risk factors with cardiovascular events among NSAID users. Methods: This study is a retrospective, nested case-control study, within the DAVINCI database, among active-duty service members and veterans with at least one NSAID pharmacy claim between fiscal year (FY) 2015-FY2020. Inclusion criteria individuals ≥18 years of age received a prescription NSAID for ≥7-day supply and a duration ≥1 month overall. Cases experienced nonfatal myocardial infarction, nonfatal stroke, or new onset heart failure. Ten controls were selected per case. Risk factors were identified through logistic regression modeling. Results: The risk factors with strongest association to the primary outcome included age starting at 45 up to 75 and older, the first 90 days of NSAID exposure, cerebrovascular disease, cardiomyopathy, and history of myocardial infarction. Cox-selectivity and dose did not appear to be clinically significant in their association with cardiovascular events. Conclusion: The results of this study indicate that age, initial NSAID exposure, and comorbidities are more predictive than NSAID-specific factors such as COX-selectivity and dose. The results provide the framework for development of a risk score to improve prediction of NSAID-associated cardiovascular events.

What's new in NSAID pharmacotherapy: oral agents to injectables.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) represent a critically important class of medications useful in numerous musculoskeletal and inflammatory diseases. The focus of NSAID use has recently centered on gastrointestinal (GI) side effects and potential cardiovascular toxicity. Innovative new oral and intra-articular pharmaceutically engineered dosage forms are examined. We review recently developed intravenous NSAIDs and their potential advantages over oral products in the perioperative setting. DESIGN: Databases searched included PubMed, Google Scholar, Ovid, and Athens. We contacted key U.S. and Japanese manufactures who are developing new and innovative NSAID technologies for inclusion in this overview. Early attempts at mitigating GI toxicity with oral agents combined with gastroprotective additives are outlined. RESULTS: Contemporary technologies coupled with uniquely advanced pharmaceutical manipulations to improve safety and efficacy are discussed including combined vasodilating agent naproxcinod as the prototypical cyclooxygenase-inhibiting nitric oxide (NO) donor; hydrogen sulfide-releasing compounds to protect GI mucosa; glycoscience technologies combining the intra-articular hyaluronic acid SI-613 combined with NSAIDs; and nano-formulated SoluMatrix submicron technologies that include diclofenac, indomethacin, naproxen, and meloxicam. CONCLUSIONS: New NSAIDs under development are intended to address GI and cardiovascular pitfalls inherent to current therapy options across the entire NSAID drug class. NO or hydrogen sulfide donating drugs, new reliable injectables for perioperative and inpatient use, novel intra-articular extended-release NSAIDs combined with IAHA, and nano-formulations of submicron NSAIDs featuring delivery of decreased doses without diminished efficacy promise to afford innovative technologies that likely will be the future of NSAID therapy.

Repeat transurethral manipulation of bulbar urethral strictures is associated with increased stricture complexity and prolonged disease duration.

PURPOSE: We examined the association of previous transurethral manipulation with stricture complexity and disease duration among men referred for bulbar urethral reconstruction. MATERIALS AND METHODS: We retrospectively reviewed the records of 340 consecutive urethroplasties performed by a single surgeon between July 2007 and October 2010. Only men treated with initial open surgery for bulbar strictures were included in analysis, thus excluding those with hypospadias, lichen sclerosus, pelvic radiation, prior urethroplasty, incomplete data, or pure penile or posterior urethral stenosis. Cases were divided into 2 groups based on the history of transurethral treatment for urethral stricture before urethroplasty, including group 1-0 or 1 and group 2-2 or greater treatments. RESULTS: Of 101 patients with bulbar urethral stricture and all data available 50 and 51 underwent 0 to 1 and 2 or greater previous transurethral treatments, respectively. Repeat transurethral manipulation was strongly associated with longer strictures and the need for complex reconstruction. Repeat transurethral manipulation of bulbar urethral strictures was also associated with an eightfold increase in disease duration between stricture diagnosis and curative urethroplasty. CONCLUSIONS: Repeat transurethral manipulation of bulbar strictures is associated with increased stricture complexity and a marked delay to curative urethroplasty.

NMP-22, urinary cytology, and cystoscopy: a 1 year comparison study.

INTRODUCTION: Bladder cancer diagnosis and surveillance is costly and frequent. Urinary cytology is used with cystoscopy in the diagnosis and surveillance of bladder cancer with little evidence to support this practice. Nuclear Matrix Protein-22 (NMP-22) is a marker of urothelial cell death and is elevated in the urine of patients with bladder cancer. Our study compares the performance of NMP-22, urinary cytology and office cystoscopy when utilized in a Veteran Affairs urology practice for 1 year. MATERIALS AND METHODS: A total of 391 consecutive office cystoscopy procedures performed over 1 year were included in the study. NMP-22 and cytology were performed on the urine specimens of patients presenting for cystoscopy. Tumor resection/bladder biopsy was performed when cystoscopy, NMP-22 or urinary cytology were abnormal. RESULTS: Cystoscopy, NMP-22, and urinary cytology data were available in 351 encounters and 69 tumor resections were performed. Urothelial carcinoma bladder (UCB) was identified in 37 bladder specimens. NMP-22, urinary cytology and cystoscopy demonstrated sensitivity and specificity of (51%/96%), (35%/97%), and (92%/88%), respectively. NMP-22 cost $8,750 in the study group and urinary cytology cost $52,500 in the same group. CONCLUSIONS: This study demonstrates cystoscopy was the most sensitive test in the diagnosis of UCB. NMP-22 had a higher sensitivity than urinary cytology and similar specificity to cytology. Additional urinary marker testing has a limited role in the management of bladder cancer in the office setting. When adjunct testing is desired in the diagnosis and surveillance of bladder cancer, NMP-22 is a cost effective alternative to urinary cytology.

A review of the safety of buprenorphine in special populations.

Rates of opioid misuse and opioid use disorder have been increasing in recent years. Buprenorphine has emerged as an appealing medication for its use not only as treatment for opioid use disorder, but also as an opioid for chronic pain that has a ceiling effect on risks associated with opioid therapy. As other opioid prescribing decreases, buprenorphine prescribing continues to increase. As a result, it is imperative to understand the safety and efficacy of its use in special populations. This review article will explore the safety and efficacy of buprenorphine when used in subjects with hepatic and renal impairment, the elderly, and pregnant women. While manufacturer labeling for buprenorphine products may caution against their use in these populations, further examination of available data indicates that buprenorphine can be used safely and effectively for both chronic pain and/or opioid use disorder in all four of these populations.

Psychometric Properties of the Copenhagen Burnout Inventory in an Academic Healthcare Institution Sample in the U.S.

The Copenhagen Burnout Inventory (CBI) has demonstrated good psychometric properties among respondents in many different countries, but minimal research exists using the CBI in a U.S.-based sample. The current study represents a secondary analysis of existing CBI data from 1,679 academic health center employees at one mid-size teaching hospital in the southeastern region of the U.S. Analyses assessed CBI scale reliability, confirmatory factorial validity, discriminant validity against a measure of meaningful work, and test invariance for professional role sub-groups (physicians, nurses/physician assistants, and other hospital staff), gender groups, and different age groups. Results provided evidence for good reliability and discriminant validity as well as construct validity supporting the CBI proposed three-factor structure. Configural and metric variance equivalence were demonstrated across the range of employee types, and across age and gender groups. Scalar invariance equivalence was not established, suggesting further research may be needed to support group mean comparisons using the CBI.

Pain Management and Opioid Therapy: Persistent Knowledge Gaps Among Primary Care Providers.

INTRODUCTION: Given the opioid epidemic in the US, it is vital that clinicians who prescribe opioids for pain management to do so in an evidence-based manner, eg considering all pharmacologic and non-pharmacologic options, assessing risk of opioid use disorder prior to initiating opioids. Continuing education regarding the evidence-based prescribing of opioids is now required for US healthcare providers who prescribe opioids. A "blueprint" of the content to be included in continuing education programs was developed by the US Food and Drug Administration and updated in 2018. METHODS: To understand the baseline knowledge and confidence of healthcare professionals in prescribing opioids for pain management, we posed 27 unique knowledge-based questions and 1 confidence question to clinician participants before or during 2 continuing educational programs that were based respectively on the 2016 and 2018 FDA Risk Evaluation and Mitigation Strategy (REMS) educational blueprints for pain management. RESULTS: Overall, 5571 clinicians completed these programs, including 1925 physicians (1516 [79%] identifying as primary care), 1181 physician assistants, 737 advanced practice nurses, 719 nurses, and 479 pharmacists. Responses to pretest questions in both programs indicated profound and persistent gaps in knowledge, particularly in definitions and mechanisms of pain, general principles of pharmacologic analgesic therapy, and specific aspects of opioid analgesic therapy and addiction. Participants in both programs also expressed limited confidence in their abilities to incorporate patient engagement techniques into pain management or develop a treatment plan for a patient with chronic pain. DISCUSSION: These data support an ongoing need for comprehensive clinician-based education as outlined in the FDA REMS educational blueprint, especially given recent data of escalating overdose deaths during the COVID-19 pandemic.

Empowering Medical Students to Respond to Discriminatory Comments from Patients: A Just-in-Time Training Method.

This article was migrated. The article was marked as recommended. Physicians in training may experience harassment and discrimination from supervisors, consultants, colleagues, or patients and families. Instances of discrimination towards students may impact students' self-esteem, self-efficacy, and ultimately performance. In this particular time, many institutions are looking to enhance their curriculum regarding bias. More tools are needed to help students feel empowered to respond professionally when they encounter challenging situations. This study was designed to assess the impact of a training intervention in addressing biased patient statements. The training was strategically placed prior to clinical interactions. The authors' intention was to present discriminatory statements by patients as one of the many difficult clinical situations that students are being trained to navigate. The authors developed a clinical rubric for decision-making in flowchart style to mimic the decision trees used in diagnostic or treatment decisions. They then created a workshop to help learners use the flowsheet. The workshop was delivered to third-year medical students as part of "Junior Bootcamp," a day-long session of events to orient students to the clinical experiences of the M3 year. The workshop was delivered in the summer of 2019. Respondents indicated that they were more likely to be able to appropriately respond to discriminatory comments after completing the workshop. They also felt that they were more likely to be able to engage in respectful dialogue with a patient and to debrief with a faculty member. Fewer participants felt that they were likely to use the flowchart. Findings indicate that the workshop was useful to participants. It may be especially useful to educators dealing with the COVID pandemic because it is scalable and easily delivered remotely. Further studies are needed to determine if introducing this topic in the clinical years of medical school leads to improved skill in addressing instances of bias that come from patients and families.

Nonsteroidal Antiinflammatory Drugs for Acute and Chronic Pain.

Understanding nonsteroidal antiinflammatory drug (NSAID) use and impact on common rheumatic and arthritic conditions is critical to reconciling their appropriate use with their potentially serious adverse effects. NSAIDs have a profound impact on the treatment of connective tissue disorders because of their ability to address the underlying cause with specific benefits of decreasing stiffness and inflammation, and improving mobility. NSAID use is twice as common as opioid use, and inappropriate use of NSAIDs is widespread. NSAID use should be monitored and the impact understood to mitigate the risks. NSAID discontinuation should be evidence based and individualized to specific requirements.

A review of the role of benzene metabolites and mechanisms in malignant transformation: summative evidence for a lack of research in nonmyelogenous cancer types.

The aromatic hydrocarbon benzene is a well-recognised haematotoxin and carcinogen associated with malignancy in occupational environments. Primary benzene metabolites phenol, catechol, and hydroquinone are implicated in the progression from cytotoxicity to carcinogenicity, and malignant transformation in myelogenous cell lineage is hypothesised to encompass a complex multistep process involving gene mutations in cell signalling and mitosis, oncogene activation, downregulated immune-mediated tumour surveillance, anti-apoptotic activities, and genetic susceptibility. Several mechanisms of carcinogenicity are proposed but none are accepted widely as causative. Involvement of covariables such as duration and frequency of benzene exposure, metabolite concentration, and degree of biological interactions provides a theoretical framework for a multiple mechanistic model to explain cytotoxic-malignant transformation. Despite significant research in myeloid leukaemias, limited biological and epidemiological studies on benzene and its metabolites in nonhaematopoietic malignancies suggests more research is needed to determine its role in contributing to other cancer types.

Common elements in opioid use disorder guidelines for buprenorphine prescribing.

OBJECTIVES: This study sought to formulate a consolidation of guidelines representing best practices related to office-based opioid treatment (OBOT) of opioid use disorder (OUD) using buprenorphine. It also demonstrates how a set of evidence-based guidelines may be linked with claims data to leverage analytic techniques that drive cost-effective, positive health outcomes. STUDY DESIGN: Literature review of US and international guidelines for OBOT using buprenorphine for OUD. METHODS: The study conducted a review of currently available US and several international guidelines from 2009 to 2018 published on OUD and the use of buprenorphine in OBOT. Guidelines were consolidated based on common elements. The process of correlating common elements with available commercial and state Medicaid claims data is described, including which elements are amenable to analysis along with relative complexity. RESULTS: Seven guidelines met inclusion criteria and are presented as 3 tables, organized by clinical themes and phase of care related to OBOT use of buprenorphine for OUD. Themes included establishing care, monitoring treatment stability and engagement, and nonpharmacologic treatment to improve outcomes. Areas of agreement and divergence between guidelines are highlighted. Specific components are identified as they relate to metrics of interest to public and private payers. CONCLUSIONS: Among US and international guidelines for treatment of OUD, common themes are readily identified and may indicate agreement in regard to interventions. Linking pharmacy and medical billing claims data to evidence-supported best practices provides public and private payers the ability to track individual patients, facilitate high-quality care, and monitor outcomes.