Gut and bladder fermentation syndromes: a narrative review.

We recently reported the first clinical case of bladder fermentation syndrome (BFS) or urinary auto-brewery syndrome, which caused the patient to fail abstinence monitoring. In BFS, ethanol is generated by Crabtree-positive fermenting yeast Candida glabrata in a patient with poorly controlled diabetes. One crucial characteristic of BFS is the absence of alcoholic intoxication, as the bladder lumen contains transitional epithelium with low ethanol permeability. In contrast, patients with gut fermentation syndrome (GFS) or auto-brewery syndrome can spontaneously develop symptoms of ethanol intoxication even without any alcohol ingestion because of alcoholic fermentation in the gut lumen. In abstinence monitoring, a constellation of laboratory findings with positive urinary glucose and ethanol, negative ethanol metabolites, and the presence of yeast in urinalysis should raise suspicion for BFS, whereas endogenous ethanol production needs to be shown by a carbohydrate challenge test for GFS diagnosis. GFS patients will also likely fail abstinence monitoring because of the positive ethanol blood testing. BFS and GFS are treated by yeast eradication of fermenting microorganisms with antifungals (or antibiotics for bacterial GFS cases) and modification of underlying conditions (diabetes for BFS and gut dysbiosis for GFS). The under-recognition of these rare medical conditions has led to not only harm but also adverse legal consequences for patients, such as driving under the influence (DUI). GFS patients may be at risk of various alcohol-related diseases.

Definition and measurement of alcohol-associated insight in early liver transplantation for acute alcohol-associated hepatitis: A systematic review.

BACKGROUND: Alcohol accounts for a large disease burden in hepatology and liver transplantation (LT) and across the globe. Clinical evaluations and decisions about LT candidacy are challenging because they rely on detailed psychosocial assessments and interpretations of psychiatric and substance use disorder data, which often must occur rapidly according to the acuity of end-stage liver disease. Such difficulties commonly occur during the process of candidate selection and liver allocation, particularly during early LT (eLT) in patients with acute alcohol-associated hepatitis (AAH). Patients with AAH commonly have very recent or active substance use, high short-term mortality, psychiatric comorbidities, and compressed evaluation and treatment timetables. LT clinicians report that patients' alcohol-associated insight (AAI) is among the most relevant psychosocial data in this population, yet no studies exist examining how LT teams define and use AAI in eLT or its effect on clinical outcomes. In April 2022, we searched Ovid MEDLINE, Elsevier Embase, EBSCOhost PsycInfo and CINAHL, and Wiley Cochrane Central Register of Controlled Trials for reports describing AAH populations who underwent eLT, which also described psychosocial evaluation parameters. The searches retrieved 1603 unique reports. After eligibility screening, 8 were included in the qualitative analysis. This systematic review reveals that AAI is a poorly defined construct that is not measured in a standardized way. Yet it is a commonly cited parameter in articles that describe the psychosocial evaluation and decision-making of patients undergoing eLT for AAH. This article also discusses the general challenges of assessing AAI during eLT for AAH, existing AAI definitions and rating scales, how AAI has been used to date in the broader hepatology and LT literature, and future areas for clinical and research progress.

Health-related quality of life and psychological indicators of thriving 15-19 years after heart or lung transplantation.

BACKGROUND: Survival into the second decade after cardiothoracic transplantation (CTX) is no longer uncommon. Few data exist on any health-related quality of life (HRQOL) impairments survivors face, or whether they may even experience positive psychological outcomes indicative of "thriving" (e.g., personal growth). We provide such data in a long-term survivor cohort. METHODS: Among 304 patients prospectively studied across the first 2 years post-CTX, we re-interviewed patients ≥15 years post-CTX. We (a) examined levels of HRQOL and positive psychological outcomes (posttraumatic growth related to CTX, purpose in life, life satisfaction) at follow-up, (b) evaluated change since transplant with mixed-effects models, and (c) identified psychosocial and clinical correlates of study outcomes with multivariable regression. RESULTS: Of 77 survivors, 64 (83%) were assessed (35 heart, 29 lung recipients; 15-19 years post-CTX). Physical HRQOL was poorer than the general population norm and earlier post-transplant levels (P's < .001). Mental HRQOL exceeded the norm (P < .001), with little temporal change (P = .070). Mean positive psychological outcome scores exceeded scales' midpoints at follow-up. Life satisfaction, assessed longitudinally, declined over time (P < .001) but remained similar to the norm at follow-up. Recent hospitalization and dyspnea increased patients' likelihood of poor physical HRQOL at follow-up (P's ≤ .022). Lower sense of mastery and poorer caregiver support lessened patients' likelihood of positive psychological outcomes (P's ≤ .049). Medical comorbidities and type of CTX were not associated with study outcomes at follow-up. CONCLUSIONS: Despite physical HRQOL impairment, long-term CTX survivors otherwise showed favorable outcomes. Clinical attention to correlates of HRQOL and positive psychological outcomes may help maximize survivors' well-being.

The Combined Roles of Race/Ethnicity and Substance Use in Predicting Likelihood of Kidney Transplantation.

BACKGROUND: Racial/ethnic minorities face known disparities in likelihood of kidney transplantation. These disparities may be exacerbated when coupled with ongoing substance use, a factor also reducing likelihood of transplantation. We examined whether race/ethnicity in combination with ongoing substance use predicted incidence of transplantation. METHODS: Patients were enrolled between March 2010 and October 2012 at the time of transplant evaluation. Substance use data were retrieved from transplant evaluations. Following descriptive analyses, the primary multivariable analyses evaluated whether, relative to the referent group (White patients with no substance use), racial/ethnic minority patients using any substances at the time of evaluation were less likely to receive transplants by the end of study follow-up (August 2020). RESULTS: Among 1152 patients, 69% were non-Hispanic White, 23% non-Hispanic Black, and 8% Other racial/ethnic minorities. White, Black, and Other patients differed in percentages of current tobacco smoking (15%, 26%, and 18%, respectively; P = 0.002) and illicit substance use (3%, 8%, and 9%; P < 0.001) but not heavy alcohol consumption (2%, 4%, and 1%; P = 0.346). Black and Other minority patients using substances were each less likely to receive transplants than the referent group (hazard ratios ≤0.45, P ≤ 0.021). Neither White patients using substances nor racial/ethnic minority nonusers differed from the referent group in transplant rates. Additional analyses indicated that these effects reflected differences in waitlisting rates; once waitlisted, study groups did not differ in transplant rates. CONCLUSIONS: The combination of minority race/ethnicity and substance use may lead to unique disparities in likelihood of transplantation. To facilitate equity, strategies should be considered to remove any barriers to referral for and receipt of substance use care in racial/ethnic minorities.

Barriers to the management of alcohol use disorder and alcohol-associated liver disease: strategies to implement integrated care models.

Despite its increased recognition as a major public health issue, alcohol use disorder is mostly underdiagnosed and undertreated. The undertreatment and underdiagnosis of alcohol use disorder is most concerning in the management of patients with alcohol-associated liver disease, which is one of the main medical consequences of chronic and excessive alcohol use. Dual pathology (alcohol use disorder and alcohol-associated liver disease) requires multidisciplinary care involving hepatologists and addiction specialists. Such integrated care models are widely accepted as optimal care for treating comorbid medical and mental health conditions. However, the implementation of such models in clinical practice is challenging and often represents the exception, rather than the rule, in managing patients with alcohol use disorder and alcohol-associated liver disease. Barriers at the patient, clinician, and system levels are encountered in treating patients with alcohol use disorder and alcohol-associated liver disease. In this Viewpoint, we synthesise the emerging literature on the potential barriers encountered in caring for patients with alcohol-associated liver disease and alcohol use disorder and focus on how integrated models of care could overcome these barriers. We provide our perspective on why these barriers exist and propose strategies to overcome them.

Transplant-related trauma, personal growth and alcohol use outcomes in a cohort of patients receiving transplants for alcohol associated liver disease.

BACKGROUND: Liver transplantation (LT) is stressful experience which can cause psychological trauma but also positive growth. We examined the prevalence of transplant related post-traumatic stress disorder symptoms (PTSD) and post-traumatic growth (PTG) in a cohort of alcohol-associated liver disease (ALD) LT recipients. We also examined whether PTG or PTSD symptoms were associated with post-LT alcohol use. METHODS: Cross sectional survey of 51 ALD LT recipients one-year post-LT assessed PTSD symptoms, PTG, stress, self-efficacy, social support, and alcohol use. RESULTS: 18% endorsed symptoms of PTSD; 59% endorsed high PTG. PTSD symptoms and PTG were not associated. 18% drank alcohol; 10% returned to health harmful use. Neither PTSD symptoms nor PTG were associated with alcohol use. Less self-efficacy to abstain and thoughts of drinking were associated with alcohol use. CONCLUSIONS: A substantial percentage of ALD LT patients had transplant-related PTSD symptoms and high PTG. Alcohol use was not associated with PTSD symptoms or PTG. Lower self-efficacy to abstain from alcohol use may provide a valuable clinical measure to assess risk for post-LT use. Clinical screening for PTSD would be beneficial as effective treatments for PTSD exist. Whether PTG can be facilitated in transplant recipients would be a valuable future line of inquiry.

Alcohol and other substance use after liver transplant.

In this article we tackle the controversial subject of alcohol and other substance use following liver transplantation (LT). Most of the literature on and importance of this topic pertains not to recreational use of alcohol or substances but to patients who have alcohol or substance use disorders (AUDs/SUDs). To understand these behaviors after such a lifesaving and resource-intensive procedure as LT necessitates an understanding of these disorders as chronic medical diseases. It also requires an awareness that management of these disorders begins before transplant, so we will briefly touch on considerations to prepare patients for the transplantation. Additionally, we review not only the rates of alcohol and substance use post-LT but strategies clinicians could adopt to identify and manage these events post-LT. Thus, we will summarize approaches for monitoring use and a range of therapeutic treatment options, including pharmacotherapy, to employ once use is discovered. While clinical gastroenterologists may be the primary clinicians responsible for the care of LT recipients, we emphasize a multidisciplinary team approach which, especially for the behavioral health components of the treatment, is likely to be the most successful. This article concludes with a summary of recommendations for clinicians working with these patients and possible future directions for both clinical care and research. While the bulk of the literature is on LT in the context of AUD, we review the smaller body of literature available on non-alcohol substance use.

Impact of a Mobile Health Intervention on Long-term Nonadherence After Lung Transplantation: Follow-up After a Randomized Controlled Trial.

BACKGROUND: In a randomized controlled trial, lung transplant recipients (LTRs) using a mobile health intervention, Pocket Personal Assistant for Tracking Health (Pocket PATH), showed better adherence to the medical regimen than LTRs receiving usual care during the first year posttransplant. We examined whether these effects were maintained beyond the end of the trial and evaluated other potential risk factors for long-term nonadherence. METHODS: Adherence in 8 areas was evaluated at follow-up in separate LTR and family caregiver (collateral) assessments. Pocket PATH and usual care groups' nonadherence rates were compared; multivariable regression analyses then examined and controlled for other patient characteristics' associations with nonadherence. RESULTS: One hundred five LTRs (75% of survivors) were assessed (M = 3.9 years posttransplant, SD = 0.8). Nonadherence rates in the past month were 23%-81% for self-care and lifestyle requirements (diet, exercise, blood pressure monitoring, spirometry), 13%-23% for immunosuppressants and other medications, and 4% for tobacco use, with 31% clinic appointment nonadherence in the past year. In multivariable analysis, the Pocket PATH group showed lower risk of nonadherence to lifestyle requirements (diet/exercise) than the usual care group (P < 0.05). Younger age and factors during the first year posttransplant (acute graft rejection, chronically elevated anxiety, less time rehospitalized, nonadherence at the final randomized controlled trial assessment) were each associated with nonadherence in at least 1 area at follow-up (P < 0.05). CONCLUSIONS: Pocket PATH did not have sustained impact on most areas of the regimen, although we identified other risk factors for long-term nonadherence. Future work should explore strategies to facilitate sustained effects of mobile health interventions.

The Approach to the Psychosocial Evaluation of Cardiac Transplant and Mechanical Circulatory Support Candidates.

PURPOSE OF REVIEW: We update evidence underlying the recommendations of a 2018 multi-society consensus report regarding the psychosocial evaluation of individuals for cardiothoracic transplantation and mechanical circulatory support (MCS). In the present review, we focus on heart transplantation and MCS. RECENT FINDINGS: Expert opinion and new evidence support the inclusion of ten core content areas in the psychosocial evaluation. Prospective data indicate that psychosocial factors can predict post-transplantation/post-implantation outcomes. Such factors include treatment adherence history, mental health and substance use history, cognitive impairment, knowledge about treatment options, and social factors such as socioeconomic status. For other factors (e.g., coping, social support), new evidence is weaker because it derives largely from cross-sectional studies. Concerning evaluation process issues, expert opinion remains consistent with consensus recommendations, but there is a dearth of empirical evidence. The psychosocial evaluation can identify factors relevant for candidacy for heart transplantation and MCS implantation. It enables the provision of interventions to improve patients' viability as candidates, and facilitates care planning.

Posttransplant Medical Adherence: What Have We Learned and Can We Do Better?

PURPOSE OF REVIEW: Non-adherence to the medical regimen after kidney transplantation can contribute to poor clinical outcomes, and strategies to maximize adherence are sought by care providers and patients alike. We assessed recent evidence on prevalence, risk factors, and clinical outcomes associated with non-adherence to the medical regimen after kidney transplantation. We summarized recent clinical trials testing interventions to improve adherence and generated recommendations for future research and clinical practice. RECENT FINDINGS: A large evidence base documents rates of non-adherence to each of the multiple components of the regimen, including medication-taking, lifestyle activities, clinical care requirements, and substance use restrictions. Some risk factors for non-adherence are well known but the full range of risk factors remains unclear. Non-adherence to immunosuppressants and to other components of the regimen increases morbidity and mortality risks. Recent interventions, including education and counseling; electronic health strategies; and medication dose modifications, show promise for reducing immunosuppressant non-adherence. However, most of these interventions would be difficult to deploy in everyday clinical practice. Systematic dissemination of efficacious interventions into clinical practice has not been undertaken. SUMMARY: Rates and risk factors for non-adherence to the medical regimen have been examined and there is evidence that non-adherence may be ameliorated by a range of interventions. Although gaps in the evidence base remain, it would be timely to devote greater efforts to dissemination of findings. Thus, efforts are needed to assist transplant programs in using existing evidence to better identify patients who are non-adherent and to design and implement strategies to reduce or prevent non-adherence.

The 2018 ISHLT/APM/AST/ICCAC/STSW Recommendations for the Psychosocial Evaluation of Adult Cardiothoracic Transplant Candidates and Candidates for Long-term Mechanical Circulatory Support.

The psychosocial evaluation is well-recognized as an important component of the multifaceted assessment process to determine candidacy for heart transplantation, lung transplantation, and long-term mechanical circulatory support (MCS). However, there is no consensus-based set of recommendations for either the full range of psychosocial domains to be assessed during the evaluation, or the set of processes and procedures to be used to conduct the evaluation, report its findings, and monitor patients' receipt of and response to interventions for any problems identified. This document provides recommendations on both evaluation content and process. It represents a collaborative effort of the International Society for Heart and Lung Transplantation (ISHLT) and the Academy of Psychosomatic Medicine, American Society of Transplantation, International Consortium of Circulatory Assist Clinicians, and Society for Transplant Social Workers. The Nursing, Health Science and Allied Health Council of the ISHLT organized a Writing Committee composed of international experts representing the ISHLT and the collaborating societies. This Committee synthesized expert opinion and conducted a comprehensive literature review to support the psychosocial evaluation content and process recommendations that were developed. The recommendations are intended to dovetail with current ISHLT guidelines and consensus statements for the selection of candidates for cardiothoracic transplantation and MCS implantation. Moreover, the recommendations are designed to promote consistency across programs in the performance of the psychosocial evaluation by proposing a core set of content domains and processes that can be expanded as needed to meet programs' unique needs and goals.

The 2018 ISHLT/APM/AST/ICCAC/STSW recommendations for the psychosocial evaluation of adult cardiothoracic transplant candidates and candidates for long-term mechanical circulatory support.

The psychosocial evaluation is well-recognized as an important component of the multifaceted assessment process to determine candidacy for heart transplantation, lung transplantation, and long-term mechanical circulatory support (MCS). However, there is no consensus-based set of recommendations for either the full range of psychosocial domains to be assessed during the evaluation, or the set of processes and procedures to be used to conduct the evaluation, report its findings, and monitor patients' receipt of and response to interventions for any problems identified. This document provides recommendations on both evaluation content and process. It represents a collaborative effort of the International Society for Heart and Lung Transplantation (ISHLT) and the Academy of Psychosomatic Medicine, American Society of Transplantation, International Consortium of Circulatory Assist Clinicians, and Society for Transplant Social Workers. The Nursing, Health Science and Allied Health Council of the ISHLT organized a Writing Committee composed of international experts representing the ISHLT and the collaborating societies. This Committee synthesized expert opinion and conducted a comprehensive literature review to support the psychosocial evaluation content and process recommendations that were developed. The recommendations are intended to dovetail with current ISHLT guidelines and consensus statements for the selection of candidates for cardiothoracic transplantation and MCS implantation. Moreover, the recommendations are designed to promote consistency across programs in the performance of the psychosocial evaluation by proposing a core set of content domains and processes that can be expanded as needed to meet programs' unique needs and goals.

Fatigue, Pain, and Other Physical Symptoms of Living Liver Donors in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study.

Little is known about living liver donors' perceptions of their physical well-being following the procedure. We collected data on donor fatigue, pain, and other relevant physical outcomes as part of the prospective, multicenter Adult-to-Adult Living Donor Liver Transplantation Cohort Study consortium. A total of 271 (91%) of 297 eligible donors were interviewed at least once before donation and 3, 6, 12, and 24 months after donation using validated measures when available. Repeated measures regression models were used to identify potential predictors of worse physical outcomes. We found that donors reported more fatigue immediately after surgery that improved by 2 years after donation, but not to predonation levels. A similar pattern was seen across a number of other physical outcomes. Abdominal or back pain and interference from their pain were rated relatively low on average at all study points. However, 21% of donors did report clinically significant pain at some point during postdonation study follow-up. Across multiple outcomes, female donors, donors whose recipients died, donors with longer hospital stays after surgery, and those whose families discouraged donation were at risk for worse physical well-being outcomes. In conclusion, although not readily modifiable, we have identified risk factors that may help identify donors at risk for worse physical outcomes for targeted intervention. Liver Transplantation 00 000-000 2018 AASLD.

Prevalence and Predictors of Patient-Reported Long-term Mental and Physical Health After Donation in the Adult-to-Adult Living-Donor Liver Transplantation Cohort Study.

BACKGROUND: Prospective and longitudinal studies have examined liver donors' medical outcomes beyond the first 1 to 2 years postdonation. There is no analogous longitudinal evidence on long-term psychosocial outcomes, including patient-reported clinically significant mental health problems and perceptions of physical well-being. We examined prevalence, descriptive characteristics, and predictors of diagnosable mental health conditions and self-reported physical health problems, including fatigue and pain, in the long-term years after liver donation. METHODS: Donors from 9 centers who initially completed telephone interviews at 3 to 10 years postdonation (mean, 5.8 years; SD, 1.9) were reinterviewed annually for 2 years using validated measures. Outcomes were examined descriptively. Repeated-measures regression analyses evaluated potential predictors and correlates of outcomes. RESULTS: Of 517 donors initially interviewed (66% of those eligible), 424 (82%) were reassessed at least once. Prevalence rates of major depression and clinically significant pain were similar to general population norms; average fatigue levels were better than norms. All prevalence rates showed little temporal change. Anxiety and alcohol use disorder rates exceeded normative rates at 1 or more assessments. Longer postdonation hospitalization, female sex, higher body mass index, concerns about donation-related health effects, and burdensome donation-related financial costs were associated with increased risk for most outcomes (P's < 0.05). Men were at higher risk for alcohol use disorder (P < 0.001). CONCLUSIONS: Anxiety and alcohol use disorders were more common than would be expected; they may warrant increased research attention and clinical surveillance. Surveillance for long-term problems in the areas assessed may be optimized by targeting donors at higher risk based on identified predictors and correlates.