Contemporary management of pain in cirrhosis: Toward precision therapy for pain.

Chronic pain is highly prevalent in patients with cirrhosis and is associated with poor health-related quality of life and poor functional status. However, there is limited guidance on appropriate pain management in this population, and pharmacologic treatment can be harmful, leading to adverse outcomes, such as gastrointestinal bleeding, renal injury, falls, and hepatic encephalopathy. Chronic pain can be categorized mechanistically into three pain types: nociceptive, neuropathic, and nociplastic, each responsive to different therapies. By discussing the identification, etiology, and treatment of these three mechanistic pain descriptors with a focus on specific challenges in patients with cirrhosis, we provide a framework for better tailoring treatments, including nonpharmacologic therapies, to patients' needs.

Is Bioequivalence a Sufficient Measure of Equivalence?

This article reviews the U.S. Food and Drug Administration (FDA) regulation of generic medications-specifically, the use of bioequivalence to compare generic and brand prescriptions. New or "brand" drugs are subjected to extensive review by the FDA before they can be marketed to the public. Generics, which are posited to be identical to brands, are subject to a less extensive review process and must prove only that the generic is the "bioequivalent" (BE) of the brand drug. Generic medications are important because they comprise almost 80% of prescriptions filled in the United States and cost 80% to 85% less than brand drugs, playing a crucial role in patients' access to cost-effective treatments. However, there is dissension about whether they can be interchanged with brand drugs without any consequences for the patient, especially for Narrow Therapeutic Index (NTI) drugs, which have precise dosage requirements. The regulatory designation of bioequivalence also has implications for doctor-patient relationships, patient outcomes, and patient legal rights. This article aims to establish that there is insufficient evidence to conclude whether using bioequivalence is adequate to determine whether two drugs can be considered equivalent given the medical and legal implications that flow from deeming two drugs equivalent.

Medical malpractice claims in Hepatology: Rates, Reasons, and Results.

BACKGROUND: Clinicians are motivated to provide safe, high-quality care to patients with chronic liver disease. This includes the desire to avoid litigation. Data are limited regarding the actual sources of medicolegal risk in chronic liver disease. METHODS: We conducted a review of a national liability insurer (Candello) with an additional granular analysis of our institution's registry of liability claims. We included closed cases involving chronic liver disease-related encounters between 2012 and 2021. We determined rates of legal claims from a denominator of unique patients with cirrhosis or transplant care seen over the study period. RESULTS: Local database: We retrieved 39 claims of which 15 involved patients with non-cirrhotic chronic liver disease, 13 involved cirrhosis (0.06% incidence), and 11 involved patients who underwent transplantation (0.6% incidence). Most claims involved periprocedural complications. Others included adverse reactions to prophylactic plasma transfusion, medication-induced HE, and falls/fractures. NATIONAL DATABASE: We found 94 claims related to liver disease out of 102,575 (0.09%) total claims. Overall, 56% involved diagnosis-related issues (failure/delay in ordering a diagnostic test, failure to appreciate and reconcile a symptom/sign or result, or the misinterpretation of a diagnostic study). Miscommunication between providers and between providers and patients was implicated in 22% of cases. Patient behavior-related factors (nonadherence with scheduled appointments, treatments, or diagnostic testing) factored in 20% of cases. Selection or the management of therapy played a role in 7% of cases. Very rarely were cases associated with technical skill (4%), house staff supervision (3%), or weekend/holiday care (1%). Fifty-one (55%) claims involved HCC. CONCLUSION: We provide the rates and reasons for medical malpractice claims in hepatology.

Association between widespread pain and associated symptoms in patients with cirrhosis.

BACKGROUND: Chronic pain is common in cirrhosis; however, the mechanistic classifications are not well characterized. Nociplastic pain, for instance, is associated with comorbid nonpain symptoms and responds to different treatments than nociceptive pain. METHODS: We conducted a survey study in February 2022 of adult patients with cirrhosis at the University of Michigan (N = 238) to evaluate pain widespreadedness, associated nociplastic symptoms, and pain intensity. FINDINGS: Pain and pain widespreadedness were associated with mood and cognitive disturbance, fatigue, sleep difficulty, and physical and social functioning. Patient-reported Outcomes, such as body maps, can be useful to phenotype patients for pain mechanisms.

Healthcare provider and medical cannabis patient communication regarding referral and medication substitution: the Canadian context.

BACKGROUND: Patients use medical cannabis for a wide array of illnesses and symptoms, and many substitute cannabis for pharmaceuticals. This substitution often occurs without physician oversight, raising patient safety concerns. We aimed to characterize substitution and doctor-patient communication patterns in Canada, where there is a mature market and national regulatory system for medical cannabis. METHODS: We conducted an anonymous, cross-sectional online survey in May 2021 for seven days with adult Canadian federally-authorized medical cannabis patients (N = 2697) registered with two global cannabis companies to evaluate patient perceptions of Primary Care Provider (PCP) knowledge of medical cannabis and communication regarding medical cannabis with PCPs, including PCP authorization of licensure and substitution of cannabis for other medications. RESULTS: Most participants (62.7%, n = 1390) obtained medical cannabis authorization from their PCP. Of those who spoke with their PCP about medical cannabis (82.2%, n = 2217), 38.6% (n = 857) reported that their PCP had "very good" or "excellent" knowledge of medical cannabis and, on average, were moderately confident in their PCP's ability to integrate medical cannabis into treatment. Participants generally reported higher ratings for secondary care providers, with 82.8% (n = 808) of participants rating their secondary care provider's knowledge about medical cannabis as "very good" or "excellent." Overall, 47.1% (n = 1269) of participants reported substituting cannabis for pharmaceuticals or other substances (e.g., alcohol, tobacco/nicotine). Of these, 31.3% (n = 397) reported a delay in informing their PCP of up to 6 months or more, and 34.8% (n = 441) reported that their PCP was still not aware of their substitution. Older, female participants had higher odds of disclosing cannabis substitution to their PCPs. CONCLUSION: Most of the surveyed Canadian medical cannabis patients considered their PCPs knowledgeable about cannabis and were confident in their PCPs' ability to integrate cannabis into treatment plans. However, many surveyed patients substituted cannabis for other medications without consulting their PCPs. These results suggest a lack of integration between mainstream healthcare and medical cannabis that may be improved through physician education and clinical experience.

The Impact of an Educational Video on Clinical Trial Enrollment and Knowledge in Ethnic Minorities: A Randomized Control Trial.

Introduction: Innovative methods to increase awareness about clinical trials and address barriers associated with low participation among racial/ethnic minorities are desperately needed. African Americans comprise 5% of all clinical trial participants, and Hispanics make up 1%. Use of multimedia educational material has shown promise as an effective strategy to increase minority clinical trial enrollment. However, this approach has not been broadly implemented. We tested the effect of a video educational program on clinical trial knowledge and enrollment in a sample of oncology outpatients. Methods: A randomized controlled trial was conducted with 63 oncology patients without previous history of clinical trial participation. Participants were randomly assigned to the intervention, to watch a clinical trial educational video in the office, or to the control group which did not receive in-office education. The Clinical Trial Knowledge survey was administered before the intervention and 1 week after the intervention. Participation in clinical trials was assessed 1-year post study participation. Results for white participants and ethnic minorities were compared. Ethnicity was self-reported through the electronic health record and confirmed by self-reporting on questionnaire. Results: Sixty-three participants were recruited in this study. At 1-year follow-up, 3 participants enrolled in clinical trials in the study group which had received office-based video intervention and 2 participants enrolled in the control group (Z = 0.39, p = 0.69). These results were not statistically significant. Impact of the intervention by ethnicity could not be assessed due to low total clinical trial enrollment. The video intervention did not change knowledge, attitudes, or barriers as measured by the Clinical Trial Knowledge Survey. Minority participants did report significantly more negative beliefs and barriers to participation than white participants. Conclusions: Increasing awareness and knowledge about clinical trials in underrepresented communities is an important step to providing opportunities for participation. Future studies should focus on how to address the negative expectations of clinical trials and the greater information needs in minority populations. Tailored or personalized messaging may address negative perceptions of clinical trial participation.

The willed body donor interview project: medical student and donor expectations.

The Anatomical Donations Program at the University of Michigan Medical School (UMMS) has begun a multiphase project wherein interviews of donors will be recorded and later shown to medical students who participate in the anatomical dissection course. The first phase of this project included surveys of both current UMMS medical students and donors concerning their perceptions of such a program. A five-question survey administered via Qualtrics software was electronically mailed to all current medical students at UMMS, and a survey was mailed to registered and potential donors requesting information from the UMMS on anatomical donations. A total of 224 medical student responses (response rate 33%) and 54 donor responses (response rate 27%) were received. Seventy-four percent of students and 81% of donors reported they would participate in this program if it existed. Students and donors supported the implementation of this program for varying reasons, though many felt strongly they would not want to participate in a donor interview program. These qualitative results support those of previous studies that show a majority of students desire a closer personal relationship with the donor, and these are the first results to be reported on donor perceptions of a donor interview program. Although many students and donors are in favor of instituting this program, others feel strongly that such an experience could be traumatic. The causes of these differing reactions need to be further explored, and the opinions of those who object to this study will be respected by maintaining voluntary participation in future phases of this study.

Neural response to errors in combat-exposed returning veterans with and without post-traumatic stress disorder: a preliminary event-related potential study.

Post-traumatic stress disorder (PTSD) is characterized by sustained anxiety, hypervigilance for potential threat, and hyperarousal. These symptoms may enhance self-perception of one's actions, particularly the detection of errors, which may threaten safety. The error-related negativity (ERN) is an electrocortical response to the commission of errors, and previous studies have shown that other anxiety disorders associated with exaggerated anxiety and enhanced action monitoring exhibit an enhanced ERN. However, little is known about how traumatic experience and PTSD would affect the ERN. To address this gap, we measured the ERN in returning Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans with combat-related PTSD (PTSD group), combat-exposed OEF/OIF veterans without PTSD [combat-exposed control (CEC) group], and non-traumatized healthy participants [healthy control (HC) group]. Event-related potential and behavioral measures were recorded while 16 PTSD patients, 18 CEC, and 16 HC participants completed an arrow version of the flanker task. No difference in the magnitude of the ERN was observed between the PTSD and HC groups; however, in comparison with the PTSD and HC groups, the CEC group displayed a blunted ERN response. These findings suggest that (1) combat trauma itself does not affect the ERN response; (2) PTSD is not associated with an abnormal ERN response; and (3) an attenuated ERN in those previously exposed to combat trauma but who have not developed PTSD may reflect resilience to the disorder, less motivation to do the task, or a decrease in the significance or meaningfulness of 'errors,' which could be related to combat experience.

Danger and disease: electrocortical responses to threat- and disgust-eliciting images.

Previous research suggests facilitated processing of evolutionarily significant stimuli (e.g., depictions of erotica, mutilation, threat), as reflected by augmented event-related potentials (ERPs), including the early posterior negativity (EPN) and late positive potential (LPP). Evolutionary models suggest that images that evoke disgust should be high in motivational salience, but evidence that the EPN and LPP are enhanced by disgusting images is lacking. Prior studies have employed only a small number of disgusting images that were limited in the types of content depicted. In the current study, participants viewed larger sets of disgusting, threatening, and neutral images with more varied content while electroencephalography (EEG) was recorded. Results showed that disgusting and threatening images elicited equivalent LPPs, which were both significantly increased relative to LPPs elicited by neutral images. EPN amplitudes were augmented for both disgusting and threatening relative to neutral images, though significantly more for disgust. These findings offer initial evidence that the EPN and the LPP are sensitive to disgust-eliciting pictures and that these pictures may receive processing that is at least on par with that of threatening images. Limitations of the current study and implications for future research are discussed.