Posttransplant Metabolic Syndrome

Metabolic syndrome (MS) is a cluster of metabolic derangements associated with insulin resistance and an increased risk of cardiovascular mortality. MS has become a major health concern worldwide and is considered to be the etiology of the current epidemic of diabetes and cardiovascular disease. In addition to cardiovascular disease, the presence of MS is also closely associated with other comorbidities including nonalcoholic fatty liver disease (NAFLD). The prevalence of MS in patients with cirrhosis and end-stage liver disease is not well established and difficult to ascertain. Following liver transplant, the prevalence of MS is estimated to be 44–58%. The main factors associated with posttransplant MS are posttransplant diabetes, obesity, dyslipidemia, and hypertension. In addition to developing NAFLD, posttransplant MS is associated with increased cardiovascular mortality that is 2.5 times that of the age- and sex-matched individuals. Additionally, the presence of posttransplant MS has been associated with rapid progression to fibrosis in individuals transplanted for HCV cirrhosis. There is an urgent need for well-designed prospective studies to fully delineate the natural history and risk factors associated with posttransplant MS. Until then, early recognition, prevention, and treatment of its components are vital in improving outcomes in liver transplant recipients

Utility of Non-Invasive Testing for Fibrosis Assessment in Patients with End Stage Renal Disease

Background: Non-alcoholic fatty liver disease (NAFLD) risk factors including metabolic syndrome (MS) and its components obesity (BMI ≥ 30), diabetes mellitus (DM), hypertension (HTN), and dyslipidemia (DL), has an increased prevalence in end stage renal disease (ESRD). The goal of study was to assess utility of non-invasive testing (NIT) including transient elastography (TE) for liver stiffness (LS), controlled attenuated parameter (CAP) for steatosis, Fibrosis-4 (FIB-4), AST to platelet ratio (APRI) and NAFLD Fibrosis score (NFS), for assessment of NAFLD in patients with ESRD undergoing renal transplant (RT) evaluation. Methods: Demographic, clinical and laboratory data were collected within 12 weeks of TE. Primary outcomes were significant fibrosis (SF) and steatosis, defined by TE ≥ 9 kPa and CAP ≥ 263 dB/m, respectively. Univariate analysis was performed to identify factors associated with SF and steatosis. In those with available liver histology, utility of LS, FIB-4 and NFS to predict SF was assessed. Results: Total of 171 patients were evaluated. Mean age was 56 years, 65% male, 60% African American, 36% obese, 47% had DM, 96% had HTN, and 56% had DL. Median (IQR) LS was 6.5 kPa (4.7-8.9) with 21% having SF (\u3eF2). Mean CAP was 232 dB/m with 25% having steatosis. Those with SF were older (62 vs. 54 years; p=.005) and had higher NFS (0.138 vs. 0.560; p=0.021). Those with steatosis had obesity and DM without higher fibrosis. Those with liver histology (N=14), SF was associated with LS ≥ 9 kPa (p=.037) but not with APRI, FIB-4, or NFS. Conclusion: Amongst patients with ESRD being evaluated for RT, there was a high prevalence of LS. Normal liver enzymes, SF and steatosis were common, yet these were not detected by APRI or FIB-4. Patient’s who are at low risk for SF can be identified by NFS and TE with moderate negative predictive value and specificity

Symptom Domain Groups of the Patient-Reported Outcomes Measurement Information System Tools Independently Predict Hospitalizations and Re-hospitalizations in Cirrhosis

Background Patient-Reported Outcomes Measurement Information System (PROMIS) tools can identify health-related quality of life (HRQOL) domains that could differentially affect disease progression. Cirrhotics are highly prone to hospitalizations and re-hospitalizations, but the current clinical prognostic models may be insufficient, and thus studying the contribution of individual HRQOL domains could improve prognostication. Aim Analyze the impact of individual HRQOL PROMIS domains in predicting time to all non-elective hospitalizations and re-hospitalizations in cirrhosis. Methods Outpatient cirrhotics were administered PROMIS computerized tools. The first non-elective hospitalization and subsequent re-hospitalizations after enrollment were recorded. Individual PROMIS domains significantly contributing toward these outcomes were generated using principal component analysis. Factor analysis revealed three major PROMIS domain groups: daily function (fatigue, physical function, social roles/activities and sleep issues), mood (anxiety, anger, and depression), and pain (pain behavior/impact) accounted for 77% of the variability. Cox proportional hazards regression modeling was used for these groups to evaluate time to first hospitalization and re-hospitalization. Results A total of 286 patients [57 years, MELD 13, 67% men, 40% hepatic encephalopathy (HE)] were enrolled. Patients were followed at 6-month (mth) intervals for a median of 38 mths (IQR 22–47), during which 31% were hospitalized [median IQR mths 12.5 (3–27)] and 12% were re-hospitalized [10.5 mths (3–28)]. Time to first hospitalization was predicted by HE, HR 1.5 (CI 1.01–2.5, p = 0.04) and daily function PROMIS group HR 1.4 (CI 1.1–1.8, p = 0.01), independently. In contrast, the pain PROMIS group were predictive of the time to re-hospitalization HR 1.6 (CI 1.1–2.3, p = 0.03) as was HE, HR 2.1 (CI 1.1–4.3, p = 0.03). Conclusions Daily function and pain HRQOL domain groups using PROMIS tools independently predict hospitalizations and re-hospitalizations in cirrhotic patients

On the Challenges of Identifying Benthic Dominance on Anthropocene Coral Reefs

The concept of dominance is frequently used to describe changes in rapidly reconfiguring ecosystems, but the definition of dominance can vary widely among studies. Using coral reefs as a model, we use extensive benthic composition data to explore how variability in applying dominance concepts can shape perceptions. We reveal that coral dominance is sensitive to the exclusion of key algal groups and the categorization of other benthic groups, with ramifications for detecting an ecosystem phase shift. For example, ignoring algal turf inflates the dominance of hard and soft corals in the benthic habitats underpinning reef ecosystems. We need a consensus on how dominance concepts are applied so that we can build a more comprehensive understanding of ecosystem shifts across a broad range of aquatic and terrestrial settings. For reefs, we highlight the benefits of comprehensive and inclusive surveys for evaluating and managing the altered ecosystem states that are emerging in the Anthropocene

Homelessness predicts attrition but not alcohol abstinence in outpatients experiencing co-occurring alcohol dependence and serious mental illness.

BACKGROUND: Adults experiencing homelessness and serious mental illnesses (SMI) are at an increased risk of poor mental health and treatment outcomes compared with stably housed adults with SMI. The additional issue of alcohol misuse further complicates the difficulties of those living with homelessness and SMI. In this secondary data analysis, the authors investigated the impact of homelessness on attrition and alcohol use in a contingency management (CM) intervention that rewarded alcohol abstinence in outpatients with SMI. METHODS: The associations between housing status and attrition and alcohol abstinence during treatment, as assessed by ethyl glucuronide (EtG) urine tests, were evaluated in 79 adults diagnosed with alcohol dependence and SMI. RESULTS: Thirty-nine percent (n = 31) of participants reported being homeless at baseline. Individuals who were homeless were more likely to drop out of CM (n = 10, 62.5%) than those who were housed (n = 4, 16.7%), χ CONCLUSIONS: Individuals experiencing homelessness and co-occurring alcohol dependence and SMI receiving CM had higher rates of attrition, relative to those who were housed. Homelessness was not associated with differences in biologically assessed alcohol abstinence

Prevalence and Correlates of Cannabis Use in Outpatients with Serious Mental Illness Receiving Treatment for Alcohol Use Disorders.

Introduction: People with serious mental illness (SMI) use cannabis more than any other illicit drug. Cannabis use is associated with increased psychotic symptoms and is highly comorbid with alcohol use disorders (AUDs). Despite the national trend toward decriminalization, little is known about the prevalence, correlates, and impact of cannabis use on those with SMI receiving treatment for substance use disorders, a group at high risk for the negative effects of cannabis use. Methods: In this secondary data analysis, cannabis use prevalence, correlates, and impact on treatment outcomes were examined in 121 adults with cooccurring SMI and AUDs receiving outpatient addiction treatment in a randomized trial of contingency management (CM) for alcohol. Prevalence and frequency of cannabis use were calculated across the 7-month study period using self-report and urine tests. Cannabis users were compared with nonusers by SMI diagnosis, psychiatric symptoms, medical problems, legal problems, and HIV-risk behavior. The relationship between cannabis use and longest duration of alcohol abstinence in participants randomized to CM (n=40) was assessed. Results: Fifty-seven (47%) of participants submitted at least one cannabis-positive urine sample during the study. Out of the 2834 total samples submitted, 751 (27%) were positive for cannabis. Cannabis users were 2.2 times more likely to submit an alcohol-positive sample, and 2.5 times more likely to submit a cocaine-positive sample at baseline, relative to noncannabis users (p=0.01). Cannabis users were more likely to engage in risky sexual behavior (p=0.01) and to report being homeless (p=0.03) than nonusers. When controlling for pretreatment alcohol use, the relationship between comorbid cannabis use and alcohol abstinence during CM was not significant (p=0.77). Conclusion: Rates of comorbid cannabis use were high in this sample of adults with SMI and AUDs. Cannabis use was correlated with recent alcohol and cocaine use, risky sexual behavior, and homelessness, but not with alcohol abstinence during CM

Interaction between pre-treatment drug use and heterogeneity of psychiatric diagnosis predicts outcomes in outpatients with co-occurring disorders.

We examined whether the interaction of baseline stimulant use, assessed by urine drug tests, and type of serious mental illness (SMI) diagnosis predicted stimulant use in a trial of contingency management (CM). The interaction between baseline stimulant use and SMI diagnoses was significant in the overall sample (p=0.002) when controlling for the main effects of treatment condition, baseline stimulant use, and SMI diagnosis. Similar results were also found within the CM sample. Individuals with bipolar disorder were more or less likely, depending on their baseline stimulant-drug test results, to use stimulants during treatment compared to those with other SMI diagnoses

A Randomized Controlled Trial of Ethyl Glucuronide-Based Contingency Management for Outpatients With Co-Occurring Alcohol Use Disorders and Serious Mental Illness.

OBJECTIVE: The authors examined whether a contingency management intervention using the ethyl glucuronide (EtG) alcohol biomarker resulted in increased alcohol abstinence in outpatients with co-occurring serious mental illnesses. Secondary objectives were to determine whether contingency management was associated with changes in heavy drinking, treatment attendance, drug use, cigarette smoking, psychiatric symptoms, and HIV-risk behavior. METHOD: Seventy-nine (37% female, 44% nonwhite) outpatients with serious mental illness and alcohol dependence receiving treatment as usual completed a 4-week observation period and were randomly assigned to 12 weeks of contingency management for EtG-negative urine samples and addiction treatment attendance, or reinforcement only for study participation. Contingency management included the variable magnitude of reinforcement prize draw procedure contingent on EtG-negative samples (/mL) three times a week and weekly gift cards for outpatient treatment attendance. Urine EtG, drug test, and self-report outcomes were assessed during the 12-week intervention and 3-month follow-up periods. RESULTS: Contingency management participants were 3.1 times (95% CI=2.2-4.5) more likely to submit an EtG-negative urine test during the 12-week intervention period, attaining nearly 1.5 weeks of additional alcohol abstinence compared with controls. Contingency management participants had significantly lower mean EtG levels, reported less drinking and fewer heavy drinking episodes, and were more likely to submit stimulant-negative urine and smoking-negative breath samples, compared with controls. Differences in self-reported alcohol use were maintained at the 3-month follow-up. CONCLUSIONS: This is the first randomized trial utilizing an accurate and validated biomarker (EtG) to demonstrate the efficacy of contingency management for alcohol dependence in outpatients with serious mental illness