Healthcare utilization after liver transplantation is highly variable among both centers and recipients.

The relationship between healthcare utilization before and after liver transplantation (LT), and its association with center characteristics, is incompletely understood. This was a retrospective cohort study of 34 402 adult LTs between 2002 and 2013 using Vizient inpatient claims data linked to the United Network for Organ Sharing (UNOS) database. Multivariable mixed-effects linear regression models evaluated the association between hospitalization 90 days pre-LT and the number of days alive and out of the hospital (DAOH) 1 year post-LT. Of those patients alive at LT discharge, 24.7% spent ≥30 days hospitalized during the first year. Hospitalization in the 90 days pre-LT was inversely associated with DAOH (ß = -3.4 DAOH/week hospitalized pre-LT; P = .002). Centers with >30% of their liver transplant recipients hospitalized ≥30 days in the first LT year were typically smaller volume and/or transplanting higher risk recipients (Model for End-Stage Liver Disease [MELD] score ≥35, inpatient or ventilated pre-LT). In conclusion, pre-LT hospitalization predicts 1-year post-LT hospitalization independent of MELD score at the patient-level, whereas center-specific post-LT healthcare utilization is associated with certain center behaviors and selection practices.

Rare clinically significant hepatic events and hepatitis B reactivation occur more frequently following rather than during direct-acting antiviral therapy for chronic hepatitis C: Data from a national US cohort.

Recently, cases of hepatitis B virus reactivation (HBVr) with direct-acting antiviral therapy (DAAs) for HCV have been reported. However, few data exist from large, Western cohorts. The study objectives were to evaluate the incidence of alanine aminotransferase (ALT) flares, clinically significant hepatic events, and HBVr among a national cohort of US veterans with prior exposure to HBV (anti-HBc+) treated with DAAs. We used a national administrative database to identify patients treated with DAAs from January 2014 through November 2016 and obtained clinical and demographic as well as HBV and HCV treatment data. HBVr was defined as an at least 1-log increase in HBV DNA titre. Among 17 779 anti-HBc+ patients, 17 400 were HIV- and 379 were HIV+. Among the HIV- patients, 17 266 (99%) were HBsAg- prior to DAA therapy and 134 were HBsAg+. Among HIV-, HBsAg- patients, ALT elevations greater than 10 times the upper limit of normal (ULN; ≥300 IU/mL) were rare and occurred more frequently after treatment completion: 31 cases (<0.1%) during vs 85 (0.6%) following treatment. Clinically significant hepatic events defined as ALT increases >100 IU/L with total bilirubin >2.5 mg/dL occurred in 39 cases (0.3%), most often following DAA completion (n = 35 cases, 3/35 in setting of HCV relapse). Among 31 patients with post-DAA hepatic events without HCV relapse, 10 (32%) were confirmed unrelated to HBVr by HBsAg and/or HBV DNA testing, 1 (3%) confirmed due to HBVr, and 20 (65%) did not have documented HBV-related testing. One additional case of HBsAg- to + seroreversion was identified. Among HBsAg+ DAA recipients, 2/97 (2%), both with cirrhosis, experienced ALT elevations ≥300 IU/mL in the setting of HBVr. In conclusion, clinically significant hepatic events and HBVr were rare and much more likely among HBsAg-positive individuals. Anti-HBc + patients should be monitored for ALT flares and HBVr during and possibly for up to 6 months post-DAA therapy.

Safety and efficacy of sofosbuvir-based direct-acting antiviral regimens for hepatitis C virus genotypes 1-4 and 6 in Myanmar: Real-world experience.

This open-label, clinical experience investigated the safety and efficacy of direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy in Myanmar; 344 patients completed treatment between June 2015 and May 2016. Patients with HCV genotypes 1-4 and 6 received one of four treatments: (i) Peg-interferon (PEG-IFN)+sofosbuvir (SOF)+ribavirin (RBV) for 12 weeks, (ii) SOF+RBV for 24 weeks, (iii) ledipasvir (LDV)+SOF for 12 weeks or (iv) daclatasvir (DCV)+SOF+RBV for 12 or 24 weeks. Genotype 3 was most common (n=133, 38.7%), followed by genotype 6 (n=122, 35.5%) and genotype 1 (n=86, 25%). Overall, 91% of patients achieved sustained virologic response (SVR); 99% in group 1, (n=148/149), 90% in group 2 (n=95/106), 78% in group 3 (n=65/83) and 100% in group 4 (n=6/6). In group 3, SVR rates were 96.8% in genotype 1 (n=30/31) and 64.1% in genotype 6 (n=25/39). Multivariable regression analysis identified advanced fibrosis (F3-4) (OR=.16 CI: 0.05-0.57, P=.005), genotype 6 (OR=.35, CI: 0.16-0.79, P=.012) and diabetes (OR=.29, CI: 0.12-0.71, P=.007) as negative independent predictors of response. Adverse events were mild with all-oral therapy. CONCLUSION: DAA therapy ±PEG-IFN achieved high SVR rates. Genotype 6 patients had a low SVR to 12 weeks of LDV and SOF raising the need for other regimens, RBV or longer treatment duration in this population.

Factors Associated With Major Adverse Cardiovascular Events After Liver Transplantation Among a National Sample.

Assessment of major adverse cardiovascular events (MACE) after liver transplantation (LT) has been limited by the lack of a multicenter study with detailed clinical information. An integrated database linking information from the University HealthSystem Consortium and the Organ Procurement and Transplant Network was analyzed using multivariate Poisson regression to assess factors associated with 30- and 90-day MACE after LT (February 2002 to December 2012). MACE was defined as myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), cardiac arrest, pulmonary embolism, and/or stroke. Of 32 810 recipients, MACE hospitalizations occurred in 8% and 11% of patients at 30 and 90 days, respectively. Recipients with MACE were older and more likely to have a history of nonalcoholic steatohepatitis (NASH), alcoholic cirrhosis, MI, HF, stroke, AF and pulmonary and chronic renal disease than those without MACE. In multivariable analysis, age >65 years (incidence rate ratio [IRR] 2.8, 95% confidence interval [95% CI] 1.8-4.4), alcoholic cirrhosis (IRR 1.6, 95% CI 1.2-2.2), NASH (IRR 1.6, 95% CI 1.1-2.4), pre-LT creatinine (IRR 1.1, 95% CI 1.04-1.2), baseline AF (IRR 6.9, 95% CI 5.0-9.6) and stroke (IRR 6.3, 95% CI 1.6-25.4) were independently associated with MACE. MACE was associated with lower 1-year survival after LT (79% vs. 88%, p < 0.0001). In a national database, MACE occurred in 11% of LT recipients and had a negative impact on survival. Pre-LT AF and stroke substantially increase the risk of MACE, highlighting potentially high-risk LT candidates.

Psychometric properties of the PROMIS short form measures in a U.S. cohort of 961 patients with chronic hepatitis C prescribed direct acting antiviral therapy.

BACKGROUND: To better understand symptoms experienced by patients infected with chronic hepatitis C virus (HCV), valid and reliable patient-reported outcome (PRO) measures are needed. AIM: To assess the reliability and validity of 10 patient-reported outcomes measurement information system (PROMIS) measures and the Headache Impact Test-6 (HIT-6) in a large national sample of patients with HCV. METHODS: Pre-treatment data from 961 patients with HCV starting direct acting antiviral therapy at 11 U.S. liver centers were analyzed. Internal reliability was evaluated using Cronbach's alpha coefficient; frequency distributions were examined for floor and ceiling effects; structural validity was investigated via item-response-theory models; convergent validity was evaluated using correlations with theoretically-similar items from the HCV-PRO and memorial symptom assessment scale (MSAS); and known-groups validity was investigated by observing PRO differences by liver disease status and number of comorbidities. RESULTS: The HIT-6 and the majority of the PROMIS measures yielded excellent reliability (alphas ≥ 0.87). Ceiling effects were infrequent ( < 4%), while 30%-59% of patients reported no symptoms (floor effects). The data supported structural validity of the HIT-6 and most PROMIS measures. The PROMIS measures showed moderate to strong correlations with theoretically-similar items from the HCV-PRO and MSAS (0.39-0.77). Trends were observed between worse PRO scores and advanced cirrhosis and greater number of comorbidities, lending support for known-groups validity. CONCLUSIONS: The psychometric properties of the HIT-6 and PROMIS measures performed satisfactorily in this large cohort of patients with HCV starting direct acting antiviral therapy. Opportunities exist for further refinement of these PROs. Evaluation of performance over time and in under-represented subgroups is needed.

Allocating effort and anticipating pleasure in schizophrenia: Relationship with real world functioning.

BACKGROUND: Poor motivation to engage in goal-oriented behavior has been recognized as a hallmark feature of schizophrenia spectrum disorders (SZ). Low drive in SZ may be related to anticipating rewards as well as to poor working memory. However, few studies to date have examined beliefs about self-efficacy and satisfaction for future rewards (anticipatory pleasure). Additionally, few studies to date have examined how these deficits may impact SZ patients' real world functioning. METHOD: The present study examined SZ patients' (n=57) anticipatory pleasure, working memory, self-efficacy and real world functioning in relation to their negative symptom severity. RESULTS: Results revealed that SZ patients' negative symptom severity was related to decisions in effort allocation and reward probability, working memory deficits, self-efficacy and anticipatory pleasure for future reward. Effort allocation deficits also predicted patients' daily functioning skills. CONCLUSIONS: SZ patients with high levels of negative symptoms are not merely effort averse, but have more difficulty effectively allocating effort and anticipating pleasure engaging in effortful activities. It may be the case that continuously failing to achieve reinforcement from engagement and participation may lead SZ patients to form certain negative beliefs about their abilities which contributes to amotivation and cognitive deficits. Lastly, our findings provide further support for a link between SZ patients functional daily living skills their effort allocation.

Clinical effects of recent cocaine use on patients with acute schizophrenia.

OBJECTIVE: Dopamine function has been hypothesized to be involved in both producing schizophrenic symptoms and mediating cocaine's reinforcing properties. As a result, cocaine abuse in schizophrenic patients may be seen as a natural experiment that may alter the phenomenology and neurobiology of schizophrenia. This report concerns the clinical effects of cocaine abuse and cessation in schizophrenic patients at two times: when patients presented to the psychiatric emergency service and again after 4 weeks of hospitalization. METHOD: The subjects were 15 cocaine-abusing and 22 cocaine-abstaining schizophrenic patients. Diagnostic assessments were performed with the Structured Clinical Interview for DSM-III-R--Patient Version, which uses DSM-III-R criteria. All of the patients were assessed at both times with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. RESULTS: Cocaine-abusing schizophrenic patients showed fewer negative signs and more anxiety/depression at the hospital-admission assessment than their nonabusing counterparts. At retest, no group differences were detected in patients' negative signs or mood symptoms. Severity of positive symptoms was equal at both testing sessions. CONCLUSIONS: The significant difference in negative signs and mood symptoms at admission assessment was attributed to the neurobiological impact of cocaine. The role of psychostimulants in schizophrenic patients is discussed.

Visual controlled information processing resources and formal thought disorder in schizophrenia and mania.

Visual selective attentional performance under low and high processing load conditions was examined in patients with schizophrenia (n = 20), or bipolar affective disorder-manic type (n = 21) and a group of normal control subjects (n = 18). Although schizophrenic patients demonstrated significantly more impaired cognitive performance than normal controls, bipolar patients were found to be as deviant as the schizophrenic patients on almost all of the performance variables. Positive thought disorder under high processing load demands was moderately correlated with schizophrenic patients' response processing ability. In contrast, negative thought disorder ratings were found to be moderately associated with reaction time performance during high processing demands for both patient groups. These findings are discussed with regard to the relationship between selective attention, visual-motor controlled information processing deficits, and thought disorder in psychosis.

Attentional predictors of clinical change during neuroleptic treatment in schizophrenia.

Improvement in auditory selective attention performance was examined in acute schizophrenic inpatients (n = 13) both off and on medication using the digit span distraction task. Subjects were tested at drug-free baseline and weekly for three weeks during treatment with haloperidol. Improvements in distractability preceded and predicted clinical improvements. A control group of stable schizophrenic outpatients (n = 12) medicated at all testing intervals were examined during the same time period. No significant clinical or attentional changes were found in the control group over the four testing intervals. These results suggest that specific types of attentional functions are intrinsically related to the biological processes affected by neuroleptic treatment and lend preliminary support to the contention that schizophrenic symptoms are mediated by attentional impairment.

Practice-related improvement in information processing with novel antipsychotic treatment.

BACKGROUND: Attentional deficits are prominent in schizophrenia, and skill learning is impaired. Novel antipsychotic treatment has been reported to improve certain cognitive skills in schizophrenic patients, but no information is yet available about the effect of newer medications on skill learning. METHODS: Clinically stable patients with schizophrenia (n=16) and chronically hospitalized inpatients (n=8) were recruited while receiving conventional antipsychotic treatment. Subjects were tested at baseline on a visual continuous performance test (CPT), performed alone and simultaneously with an auditory CPT. Normal controls (n=8) were also tested at baseline. The inpatients and half of the outpatients were switched to treatment with risperidone. All patients then performed the visual CPT on a daily basis and performed the dual tasks once per week, for 4weeks. RESULTS: Patients who remained on conventional medications did not improve in their performance despite the extensive practice on the test. Both chronic and stable patients receiving risperidone treatment manifested a statistically significant (P<0.05) improvement from baseline on both single and dual-task visual CPT. Stable outpatients performed significantly better at the end of the protocol than the normal controls performance at baseline (P<0.05). IMPLICATIONS: These results suggest that practice-related improvements in the performance of information processing tests are enhanced by novel antipsychotic medications. Although the specific biological mechanism of this effect is not yet known, the results may suggest that use of newer medications will enhance skill development and perhaps facilitate rehabilitation of patients with schizophrenia.

The need to integrate neuropsychological and experimental schizophrenia research.

Although the experimental and the neuropsychological approaches to the study of schizophrenic cognition have coexisted for many years, they remain detached, with virtually independent methods and literatures. The result has been a needless duplication of work and effort. In this article we review the emergence and representative research of each approach, examine model integrative studies, and suggest ways in which the two approaches can be better integrated to generate comprehensive cognitive schizophrenia theories and research.

Cognitive deficits and thought disorder: II. An 8-month followup study.

Schizophrenic (n = 21) and manic (n = 19) patients were followed up an average of 8 months after an index assessment during an acute admission. These patients were tested at both assessments with laboratory tasks measuring distractibility and reality monitoring and were examined with clinical ratings of positive and negative thought disorder. For manic patients, none of the measures predicted the patients' clinical state of followup, while negative thought disorder, although rare, was temporally stable. For the schizophrenic patients, both negative thought disorder and distractibility were temporally stable, and more severe negative thought disorder was found at index assessment in patients who were psychotic at followup. The differential utility of laboratory and clinical indices for the prediction of overall clinical state is related to these data.

Symptomatic overlap of cocaine intoxication and acute schizophrenia at emergency presentation.

Cocaine intoxication and acute abstinence alter brain dopaminergic functioning, resulting in behavioral changes closely mimicking the positive and negative symptoms of schizophrenia. In emergency room settings, recent cocaine abuse can be mistaken for schizophrenia and may cause inappropriate diagnosis and in some instances medical mismanagement. Schizophrenia patients presenting with recent cocaine abuse may also present with significant diagnostic and treatment dilemmas. This study attempts to distinguish between cocaine and schizophrenic psychosis by examining patients who present with both recent cocaine abuse and acute schizophrenia (CA+SZ), cocaine intoxication without schizophrenic illness (CA), and acute schizophrenia with no comorbid substance abuse (SZ) within the first 24 hours after arrival at the Bellevue psychiatric emergency service. Clinical assessment included the Brief Psychiatric Rating Scale, the Schedule for the Assessment of Positive Symptoms, and the Schedule for the Assessment of Negative Symptoms. Both cocaine abusing groups were required to have positive urine toxicology screens for inclusion in the study. Multivariate analysis of variance showed the CA+SZ patients present with a clinical profile that overlaps with CA patients on mood and negative symptom dimensions and overlaps with SZ patients on most positive symptoms. CA+SZ patients differed from both groups, however, by presenting with significantly more hallucinatory experiences than cocaine abusing or schizophrenia patient counterparts. Despite considerable overlap, each group of patients presented with a discernible cross-sectional symptom pattern.

Medication may be required for the development of automatic information processing in schizophrenia.

Medicated and unmedicated schizophrenic patients and normal subjects (n's = 4) were examined on the extent to which their information-processing performance became automated over time, as reflected by increased competence in dual task performance. The central task was a computerized version of the Continuous Performance Test, and the secondary task was a word-list shadowing task. Normal subjects and medicated schizophrenic patients became much more efficient at performing both tasks simultaneously with practice, with unmedicated patients showing no improvement over time.

Continuous performance tests in schizophrenic patients: stimulus and medication effects on performance.

Medicated (n = 17) and unmedicated (n = 17) schizophrenic patients were compared to a normal control group (n = 19) on their performance on auditory and visual versions of the Continuous Performance Test (CPT). Within each stimulus modality, performance was examined on lexical and nonlexical target stimuli. Neuromotor competence was assessed on the basis of motor speed and proficiency. Normal subjects made fewer errors of all types than schizophrenic patients. Unmedicated patients made significantly more errors on nonlexical stimuli than medicated patients, with medication status found not to be associated with stimulus modality effects. Motor proficiency was associated with CPT performance in the medicated patients, but not the unmedicated ones, although this difference in correlations did not account for the group differences between these patients. The authors discuss the implications of these data for the type of cognitive and attentional functions that are affected by medication in schizophrenia.

Learning and memory impairment in cocaine-dependent and comorbid schizophrenic patients.

Impairments in verbal learning and memory functioning have been found to be cardinal features among individuals with schizophrenia as well as among non-schizophrenic cocaine abusers. Cognitive deficits in these areas, moreover, have been associated with poor treatment response and short-term outcome. Little is known, however, about the acute effects of cocaine abuse on schizophrenic patients' learning and memory functioning. Consequently, a potentially reversible and treatable source of cognitive impairment has been virtually ignored. The present study examined the extent of verbal learning and memory impairment in a group of cocaine-dependent schizophrenic patients (n=42) and a group of non-schizophrenic cocaine-dependent patients (n=21) within 72 h of the last cocaine use using the California Verbal Learning Test (CVLT). Schizophrenic patients (n=34) without any substance-use disorders were also tested in an identical time frame and served as a comparison group. Results revealed that all groups demonstrated significant learning and memory impairment relative to CVLT published age and gender corrected norms. Both cocaine-dependent and non-substance abusing schizophrenic groups presented a very similar pattern of impaired learning and recall performance across all CVLT task domains. Comorbid patients, in contrast, presented with marked deficits in their ability to learn and recall verbal information relative to either schizophrenic or cocaine-only groups. Moreover, the cocaine-abusing schizophrenic patients showed significant forgetfulness of the information that they did acquire during delayed recall conditions. The performance deficits exhibited by cocaine-abusing schizophrenic patients differed not only in relative severity of impairment, but also qualitatively in their increased rates of forgetfulness of acquired information. These results are interpreted in terms of the neurobiological substrates of learning and memory and the neurobiological impact of cocaine on schizophrenic patients' cognition during the early phase of inpatient hospitalization. These results suggest that comorbid patients should be targeted for specialized remediation efforts at the beginning phases of inpatient treatment.

Empirical assessment of the factorial structure of clinical symptoms in schizophrenic patients: formal thought disorder.

Male schizophrenic patients (n = 142) were examined with a clinical assessment of their language dysfunctions with the Scale for the Assessment of Thought, Language, and Communication (TLC). Confirmatory factor analyses were conducted to test the relative fit of several differential theoretical models of the factorial structure of thought disorders. The models examined were positive-negative thought disorder, a three-factor model based on the results of an earlier exploratory factor analysis, and a simpler verbal productivity-disconnection model that can be extracted from other exploratory analyses and empirical studies. The positive-negative thought disorder model failed to fit the data, while the three-factor model fit the data, but no better than the simpler verbal productivity-disconnection model.

Clinical research on antipsychotics in bipolar disorder.

Antipsychotics are commonly used in bipolar disorder, both for acute mania and in maintenance treatment. The authors review available clinical research concerning the use of both conventional and atypical antipsychotics in bipolar disorder and present recommendations for a number of key clinical situations based on this review. They also consider a number of important related questions, including whether there is evidence for an increased risk of tardive dyskinesia (TD) in patients with bipolar disorder, the potential role for antipsychotics in the treatment of bipolar depression, the role of antipsychotics in maintenance treatment of bipolar disorder, the potential for antipsychotics to induce depression in bipolar illness, and whether antipsychotics can be considered mood stabilizers with a place as monotherapy for bipolar mania. They conclude that standard treatment for acute mania should begin with a mood stabilizer, with benzodiazepines used as an adjunct for mild agitation or insomnia and antipsychotics used as an adjunct for highly agitated, psychotic, or severely manic patients. They also conclude that atypical antipsychotics are preferable to conventional antispychotics because of their more favorable side effect profile and reduced risk of tardive dyskinesia. They review the evidence for using atypical antipsychotics as first-line monotherapy for mania and conclude that more evidence concerning the risk of TD and their efficacy as maintenance treatment in bipolar disorder is needed before a conclusion can be made. Should the eventual risk of TD associated with atypical antipsychotics be found to be minimal and their efficacy in maintenance treatment found to be high, they could eventually be considered first line monotherapy for bipolar disorder. They conclude that treatment with an antipsychotic during bipolar depression should be limited to those patients who have psychosis and that atypical antipsychotics are preferred over conventional antipsychotics in this situation, not only because of their reduced risk of side effects but also because theoretically they may have antidepressant efficacy due to their effects on the serotonin system. The clinical research findings summarized in the article are, for the most part, supported by a recently published guideline based on a consensus of clinical experts.

Development and preliminary validation of a questionnaire assessment of expressed emotion.

A questionnaire for management of expressed emotion was constructed. It consisted of two scales, criticism and emotional overinvolvement. The questionnaire and the Camberwell Family Interview were then administered to relatives of schizophrenics and preliminary assessments of scale reliabilities and concurrent validities were done. Both questionnaire scales were reliable. With respect to validity the criticism scale correctly classified 88% of the subjects relative to the criticism scale of the interview. The emotional overinvolvement scale was less satisfactory (67%) but still assisted in classification of over-all expressed emotion. Expressed emotion, classification by the questionnaire, correctly identified 84% of the subjects with respect to the interview.