Thirty-Day Readmissions Are Largely Not Preventable in Patients With Cirrhosis.

INTRODUCTION: Hospital readmissions are common in patients with cirrhosis, but there are few studies describing readmission preventability. We aimed to describe the incidence, causes, and risk factors for preventable readmission in this population. METHODS: We performed a prospective cohort study of patients with cirrhosis hospitalized at a single center between June 2014 and March 2020 and followed up for 30 days postdischarge. Demographic, clinical, and socioeconomic data, functional status, and quality of life were collected. Readmission preventability was independently and systematically adjudicated by 3 reviewers. Multinomial logistic regression was used to compare those with (i) preventable readmission, (ii) nonpreventable readmission/death, and (iii) no readmission. RESULTS: Of 654 patients, 246 (38%) were readmitted, and 29 (12%) were preventable readmissions. Reviewers agreed on preventability for 70% of readmissions. Twenty-two (including 2 with preventable readmission) died. The most common reasons for readmission were hepatic encephalopathy (22%), gastrointestinal bleeding (13%), acute kidney injury (13%), and ascites (6%), and these reasons were similar between preventable and nonpreventable readmissions. Preventable readmission was often related to paracentesis timeliness, diuretic adjustment monitoring, and hepatic encephalopathy treatment. Compared with nonreadmitted patients, preventable readmission was independently associated with racial and ethnic minoritized individuals (odds ratio [OR] 5.80; 95% CI, 1.96-17.13), nonmarried marital status (OR 2.88; 95% CI, 1.18-7.05), and admission in the prior 30 days (OR 3.45; 95% CI, 1.48-8.04). DISCUSSION: For patients with cirrhosis, readmission is common, but most are not preventable. Preventable readmissions are often related to ascites and hepatic encephalopathy and are associated with racial and ethnic minorities, nonmarried status, and prior admissions.

Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome.

Metabolic syndrome (MetS), characterized by hyperglycemia, obesity, and hyperlipidemia, can increase the risk of developing late-onset dementia. Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy+/- . Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. Body weight, blood glucose, total cholesterol, and triglyceride were measured to confirm the MetS phenotype. Cognition, sensorimotor function, and emotional reactivity were assessed for each genotype followed by plasma and brain tissue collection for biochemical and molecular analyses. Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy+/- mice versus C57BL/6 controls and non-agouti KKAy-/- . Behaviorally, agouti KKAy+/- revealed impairments in sensorimotor and cognitive function versus age-matched C57BL/6 and non-agouti KKAy-/- mice. Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy+/- mice. Overall, our study suggests that interaction of tau pathology with O-GlcNAc signaling may contribute to MetS-induced cognitive dysfunction in aging.

Quality of epilepsy care in a rural and deprived Scottish population.

INTRODUCTION: Epilepsy is among the commonest neurological disorders globally. Appropriate prescription and good adherence to anticonvulsants can achieve seizure freedom rates of 70%. Scotland is an affluent nation with free at point-of-access health care but there remain significant healthcare inequalities, particularly associated with deprivation. Anecdotally, epileptics in rural Ayrshire rarely engage with healthcare services. We describe the prevalence and management of epilepsy in a deprived and rural Scottish population. METHODS: Electronic records were used to obtain the following for patients with coded diagnoses of 'Epilepsy' or 'Seizures' within a general practice list of 3500 patients: demographics; diagnosis; seizure types; date and level (primary, secondary) of last review; last seizure date; anticonvulsant prescription; adherence; and any clinic discharge due to non-attendance. RESULTS: 92 patients were coded as above. 56 had a current diagnosis of epilepsy (prev 16.1/100,000). 69% had good adherence. 56% had good seizure control, with adherence associated with control. Of the 68% managed by primary care, 33% were uncontrolled and 13% had had an epilepsy review in the previous year. 45% of patients referred to secondary care were discharged for non-attendance. DISCUSSION: We demonstrate a high prevalence of epilepsy, low anticonvulsant adherence and sub-optimal rates of seizure freedom. These may be linked to poor attendance at specialist clinics. Management in primary care is challenging as evidenced by low review rates and high rates of ongoing seizures. We propose that the synergistic factors of uncontrolled epilepsy, deprivation and rurality make it difficult to attend clinics, with resultant health inequalities.

Neighborhood poverty is associated with failure to be waitlisted and death during liver transplantation evaluation.

Liver transplantation (LT) is the final step in a complex care cascade. Little is known about how race, gender, rural versus urban residence, or neighborhood socioeconomic indicators impact a patient's likelihood of LT waitlisting or risk of death during LT evaluation. We performed a retrospective cohort study of adults referred for LT to the Indiana University Academic Medical Center from 2011 to 2018. Neighborhood socioeconomic status indicators were obtained by linking patients' addresses to their census tract defined in the 2017 American Community Survey. Descriptive statistics were used to describe completion of steps in the LT evaluation cascade. Multivariable analyses were performed to assess the factors associated with waitlisting and death during LT evaluation. There were 3454 patients referred for LT during the study period; 25.3% of those referred were waitlisted for LT. There was no difference seen in the proportion of patients from vulnerable populations who progressed to the steps of financial approval or evaluation start. There were differences in waitlisting by insurance type (22.6% of Medicaid vs. 34.3% of those who were privately insured; p < 0.01) and neighborhood poverty (quartile 1 29.6% vs. quartile 4 20.4%; p < 0.01). On multivariable analysis, neighborhood poverty was independently associated with waitlisting (odds ratio 0.56, 95% confidence interval [CI] 0.38-0.82) and death during LT evaluation (hazard ratio 1.49, 95% CI 1.09-2.09). Patients from high-poverty neighborhoods are at risk of failing to be waitlisted and death during LT evaluation.

Dextromethorphan reduces sign-tracking but not goal-tracking in male Sprague-Dawley rats.

Sign-tracking is a well-known phenomenon in appetitive Pavlovian conditioning in which subjects approach the site of a conditioned stimulus (CS) associated with an appetitive unconditioned stimulus (US) even when the two are located separately. Control of sign-tracking may be important in rehabilitation from drug dependence to help ward off relapse. Recent studies have found success in using ketamine to reduce sign-tracking. In this study, we employed a similar but unscheduled drug, dextromethorphan (DXM), which affects many of the same molecular targets as ketamine, in an attempt to reduce sign-tracking in a standard paradigm. DXM was found to reduce sign-tracking at the doses examined in this study, while goal-tracking (approaching the site of the US rather than CS) was relatively unaffected. DXM offers advantages over ketamine in terms of use with patients and may have some utility in rehabilitation.

Oncologic indications of liver transplantation and deceased donor liver allocation in the United States.

PURPOSE OF REVIEW: Liver transplantation is a standard therapy for certain liver cancers. The majority of liver transplantation in the United States is through deceased donor liver transplantation (DDLT). A significant disparity between the demand of livers and patients awaiting liver transplantation still remains, relying on United Network for Organ Sharing (UNOS) to make policies to determine priority amongst recipients, including for patients with liver cancer. We review the scope of liver transplantation in patients with liver cancer with a focus on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and unresectable colorectal liver metastases (CRLM) with respect to current liver allocation policy. RECENT FINDINGS: Recently, liver allocation changed in the United States. Under the current allocation policy, select patients with HCC and hilar CCA (hCCA) receive priority with an exception score of median MELD score at transplant (MMAT)-3. There is scope for other liver cancers, such as iCCA and CRLM to be considered, as reasonable outcomes have been achieved in these patients outside of the United States through DDLT and living donor liver transplantation (LDLT). SUMMARY: With the growing experience of liver transplantation for nonconventional oncologic indications, the current policy for prioritization of liver cancer within deceased donor liver allocation may need to be re-evaluated.

Hepatitis A immunisation in persons not previously exposed to hepatitis A.

This review is withdrawn because it is outdated. A new review is to be published by the end of 2019.

Modeling Response Time with Power Law Distributions.

This article overviews several contemporary models that assume power law scaling is a plausible description of the skewed right tails that are typical of response time distributions. The properties and markers of these distribution functions have implications for cognitive and neurophysiological dynamics. The power law hypothesis suggests studies should collect larger samples, and that analyses may combine individual subjects' data into a single set for a distribution-function contrasts. Techniques for contrasting response time measurements are illustrated on data from a previously published study comparing the performance of children diagnosed with dyslexia and a group of age-matched controls in flanker, color naming, word naming, and arithmetic performance.

Clinical Trial of 1000 Subjects Randomized to 5 Low-Volume Bowel Preparations for Colonoscopy and Their Acceptance of Split-Dose Bowel Preparations.

BACKGROUND: We assessed the efficacy and tolerability of 5 low-volume bowel preparations for colonoscopy. STUDY: We performed an investigator-blinded, randomized trial of 5 bowel preparations: 64 ounces of Gatorade and 306 or 357 g of PEG, both given the day prior; Gatorade and 306 g PEG, 2 L PEG-electrolyte solution with ascorbic acid, and sulfate solution, all 3 given as a split dose. One thousand outpatients consumed their preparation before a morning colonoscopy. The primary endpoint was colon cleanliness assessed by the Chicago Bowel Preparation Scale (BPS). Tolerability was assessed using a subject questionnaire. Another primary endpoint was patient acceptance of a split-dose bowel preparation assessed using a subject questionnaire. RESULTS: No statistically significant differences in the modified Chicago BPS were found among Gatorade and 357 g of PEG given as a day-prior dose and the 3 split-dose arms with 98.5% of colons cleansed adequately. The Gatorade and 357 g of PEG had significantly lower Chicago BPS fluid scores and Chicago BPS total scores (indicating dryer colons that required more irrigation) than the 3 split-dose arms. The Gatorade and PEG preparations were better tolerated. Many subjects are unwilling to consume a split-dose preparation and the majority of subjects would prefer a day-prior preparation with this preference highly dependent on the type of preparation they just consumed. CONCLUSIONS: The cleanliness of the colons was not significantly different among the 3 split-dose preparations. Day-prior dosing of Gatorade and 357 g of PEG allowed the mucosa to be visualized as well as did the split-dose preparations.

Fractal coordination in adults' attention to hierarchical visual patterns.

A display that contains hierarchically nested levels of order requires the perceiver to selectively attend to one of the levels. We investigate the degree to which such selective attention is sustained by a soft-assembled emergent coordinative process, one that does not require designated executive control. In the case of emergent soft-assembly, performance from one trial to the next should show characteristic interdependence, visible in the fractal structure of reaction time. To test this hypothesis, we asked participants across three experiments to decide whether two displays matched in a certain way (e.g., in a local element). In order to gauge this coordinative process, task constraints were experimentally manipulated (e.g., familiarity, predictability, and task instruction). Obtained reaction-time data were subjected to a spectral analysis to measure the degree of interdependence among trials. As predicted, results show correlated structure across trials, significantly different from what would be predicted by an independent-process view of selective attention. Results also show that the obtained spectral scaling exponents track the degree of coupling in the task as a function of the degree of task constraints. Findings are discussed in terms of the relative organism-environment coupling to sustain an adaptive behavior.

Weight Loss with an AI-Powered Digital Platform for Lifestyle Intervention.

BACKGROUND: Lifestyle intervention remains the cornerstone of weight loss programs in addition to pharmacological or surgical therapies. Artificial intelligence (AI) and other digital technologies can offer individualized approaches to lifestyle intervention to enable people with obesity to reach successful weight loss. METHODS: SureMediks, a digital lifestyle intervention platform using AI, was tested by 391 participants (58% women) with a broad range of BMI (20-78 kg/m2), with the aim of losing weight over 24 weeks in a multinational field trial. SureMediks consists of a mobile app, an Internet-connected scale, and a discipline of artificial intelligence called Expert system to provide individualized guidance and weight-loss management. RESULTS: All participants lost body weight (average 14%, range 4-22%). Almost all (98.7%) participants lost at least 5% of body weight, 75% lost at least 10%, 43% at least 15%, and 9% at least 20%, suggesting that this AI-powered lifestyle intervention was also effective in reducing the burden of obesity co-morbidities. Weight loss was partially positively correlated with female sex, accountability circle size, and participation in challenges, while it was negatively correlated with sub-goal reassignment. The latter three variables are specific features of the SureMediks weight loss program. CONCLUSION: An AI-assisted lifestyle intervention allowed people with different body sizes to lose 14% body weight on average, with 99% of them losing more than 5%, over 24 weeks. These results show that digital technologies and AI might provide a successful means to lose weight, before, during, and after pharmacological or surgical therapies.

Acute MK-801 increases measures of both sign-tracking and goal-tracking in male Sprague-Dawley rats.

Sign-tracking is a Pavlovian conditioned approach behavior thought to be important in understanding cue-driven relapse to drug use, and strategies for reducing sign-tracking may have some benefit in preventing relapse. A previous study successfully employed the NMDA receptor antagonist MK-801 in preventing the development of sign-tracking (but not goal-tracking) in a conditioned approach task. In this study, we focused on whether MK-801 would have similar effects on previously established sign-tracking behavior. MK-801 was administered after training in a standard sign-/goal-tracking task using a retractable lever as a conditioned stimulus and a sucrose pellet as unconditioned stimulus. It was found that MK-801 increased measures of both sign- and goal-tracking in subjects who had previously learned the task. The NMDA receptor appears to play a complex role in governing behavior related to sign-tracking.

Vaccines for preventing pneumococcal infection in adults.

BACKGROUND: Diseases caused by Streptococcus pneumoniae (S. pneumoniae) continue to cause substantial morbidity and mortality globally. Whilst pneumococcal polysaccharide vaccines (PPVs) have the potential to prevent disease and death, the degree of protection afforded against various clinical endpoints and within different populations is uncertain. OBJECTIVES: To assess the efficacy and effectiveness of PPVs in preventing pneumococcal disease or death in adults. We did not assess adverse events. SEARCH METHODS: We searched CENTRAL 2012, Issue 6, MEDLINE (January 1966 to June Week 2, 2012) and EMBASE (1974 to June 2012). SELECTION CRITERIA: We considered randomised controlled trials (RCTs) in adults, provided the study outcome met the definition of the outcome considered in the review. We also considered non-RCTs in adults, where the study assessed PPV effectiveness against culture-confirmed invasive pneumococcal disease (IPD), provided the study controlled for important confounding factors. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial quality of RCTs and three review authors extracted the data. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. Two review authors assessed study quality and extracted data for non-RCTs. We calculated ORs and 95% CIs using a random-effects model following the conversion of each study outcome to a log OR and standard error (SE). MAIN RESULTS: Twenty-five studies met our inclusion criteria (18 RCTs involving 64,852 participants and seven non-RCTs involving 62,294 participants). Meta-analysis of the RCTs found strong evidence of PPV efficacy against IPD with no statistical heterogeneity (OR 0.26, 95% CI 0.14 to 0.45; random-effects model, I(2) statistic = 0%). There was efficacy against all-cause pneumonia in low-income (OR 0.54, 95% CI 0.43 to 0.67, I(2) statistic = 19%) but not high-income countries in either the general population (OR 0.71, 95% CI 0.45 to 1.12, I(2) statistic = 93%) or in adults with chronic illness (OR 0.93, 95% CI 0.73 to 1.19, I(2) statistic = 10%). PPV was not associated with substantial reductions in all-cause mortality (OR 0.90, 95% CI 0.74 to 1.09; random-effects model, I(2) statistic = 69%). Vaccine efficacy against primary outcomes appeared poorer in adults with chronic illness. Non-RCTs provided evidence for protection against IPD in populations for whom the vaccine is currently utilised (OR 0.48, 95% CI 0.37 to 0.61; random-effects model, I(2) statistic = 31%). This review did not consider adverse events as it was outside the scope of the review. AUTHORS' CONCLUSIONS: This meta-analysis provides evidence supporting the recommendation for PPV to prevent IPD in adults. The evidence from RCTs is less clear with respect to adults with chronic illness. This might be because of lack of effect or lack of power in the studies. The meta-analysis does not provide evidence to support the routine use of PPV to prevent all-cause pneumonia or mortality.

The time-efficiency principle: time as the key diagnostic strategy in primary care.

The test and retest opportunity afforded by reviewing a patient over time substantially increases the total gain in certainty when making a diagnosis in low-prevalence settings (the time-efficiency principle). This approach safely and efficiently reduces the number of patients who need to be formally tested in order to make a correct diagnosis for a person. Time, in terms of observed disease trajectory, provides a vital mechanism for achieving this task. It remains the best strategy for delivering near-optimal diagnoses in low-prevalence settings and should be used to its full advantage.

Effects of bupropion on sign- and goal-tracking in male Sprague Dawley rats.

Relapse into addiction is often triggered by cues that have a Pavlovian association with drugs and drug-taking. Sign-tracking involves approach of and interaction with Pavlovian conditioned signals for appetitive events (as opposed to goal-tracking, which involves approach of the site of the appetitive events themselves) and may be important in understanding cue-driven relapse. Bupropion is an atypical antidepressant and smoking cessation aid with effects on dopamine and norepinephrine that may have some utility in reducing sign-tracking. Male Sprague-Dawley rats were trained in a task where sign- and goal-tracking were possible and then administered doses of bupropion during a test phase. Bupropion decreased measures of sign-tracking and increased goal-tracking. This suggests that bupropion might be a useful adjunct medication for many kinds of behavioral disorders in which cue-driven behavior is problematic.

Effects of three serotonin reuptake inhibitors on sign-tracking in male Sprague-Dawley rats.

Sign-tracking is a behavior with relevance to cue-triggered relapse addiction, a Pavlovian conditioned approach behavior directed at the conditioned stimulus. The study examined one strategy for reducing the magnetic pull of drug-associated conditioned stimuli, using selective serotonin reuptake inhibitors (SSRIs) citalopram (0, 10, and 20 mg/kg), escitalopram (0, 10, and 20 mg/kg) and fluoxetine (0, 5, and 10 mg/kg). Male Sprague-Dawley rats were first trained in a standard sign-tracking task and then acutely administered these drugs in a series of three experiments. In each study, it was found that measures of sign-tracking were reduced, although effects on goal-tracking were different between drugs. This study provides evidence that administration of serotonergic antidepressants is effective in reducing sign-tracking and may have some efficacy in preventing cue-triggered relapse.

Embodied nonlinear dynamics of cognitive performance.

Study participants are typically unable to generate binary button-press sequences that pass as classically random sequences, such as from successive "fair coin" flips. Instead, their sequences repeat or alternate between responses too often. These deviations from randomness are commonly explained in terms of limitations or idiosyncrasies in cognitive processing. This article tests a novel hypothesis that randomness departures in participant-generated binary sequences are driven by coordination dynamics; alternating and repeating sequences are related to bimanual coordination attractors. Participants (N = 128) were asked to generate sequences that were representative of a random sequence, by successively pressing either of two buttons across 1,600 trials. Statistical analyses identify the binary button-press dynamics with a discrete sine-circle version of the Haken, Kelso, Bunz bimanual coordination model. Permutation analyses revealed the most common one- to five-trial subsequences were identified with the most dynamically stable coordinative relationships, consistent with bimanual coordination predictions. The sequences were consistent with scaling noises. Thus, participants' sequences departed from classical randomness by virtue of membership in a more inclusive category of variability that subsumes classical randomness. Recurrence quantification analysis revealed the mixture of stochasticity and determinism in the sequences was better approximated by the sine-circle model than by phase-randomized surrogate data sets that preserved both the power spectral densities and distributions of each participant's sequence. A relationship between randomness production and two-alternative forced-choice performance is established that constrains response time distribution models. The article's organization illustrates a nonreductive approach to inference for cognitive systems, inspired by statistical physics concepts such as renormalization group theory and universality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Hepatitis A immunisation in persons not previously exposed to hepatitis A.

BACKGROUND: In many parts of the world, hepatitis A infection represents a significant cause of morbidity and socio-economic loss. Whilst hepatitis A vaccines have the potential to prevent disease, the degree of protection afforded against clinical outcomes and within different populations remains uncertain. There are two types of hepatitis A virus (HAV) vaccine, inactivated and live attenuated. It is important to determine the efficacy and safety for both vaccine types. OBJECTIVES: To determine the clinical protective efficacy, sero-protective efficacy, and safety and harms of hepatitis A vaccination in persons not previously exposed to hepatitis A. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and China National Knowledge Infrastructure (CNKI) up to November 2011. SELECTION CRITERIA: Randomised clinical trials comparing HAV vaccine with placebo, no intervention, or appropriate control vaccines in participants of all ages. DATA COLLECTION AND ANALYSIS: Data extraction and risk of bias assessment were undertaken by two authors and verified by a third author. Where required, authors contacted investigators to obtain missing data. The primary outcome was the occurrence of clinically apparent hepatitis A (infectious hepatitis). The secondary outcomes were lack of sero-protective anti-HAV immunoglobulin G (IgG), and number and types of adverse events. Results were presented as relative risks (RR) with 95% confidence intervals (CI). Dichotomous outcomes were reported as risk ratio (RR) with 95% confidence interval (CI), using intention-to-treat analysis. We conducted assessment of risk of bias to evaluate the risk of systematic errors (bias) and trial sequential analyses to estimate the risk of random errors (the play of chance). MAIN RESULTS: We included a total of 11 clinical studies, of which only three were considered to have low risk of bias; two were quasi-randomised studies in which we only addressed harms. Nine randomised trials with 732,380 participants addressed the primary outcome of clinically confirmed hepatitis A. Of these, four trials assessed the inactivated hepatitis A vaccine (41,690 participants) and five trials assessed the live attenuated hepatitis A vaccine (690,690 participants). In the three randomised trials with low risk of bias (all assessing inactivated vaccine), clinically apparent hepatitis A occurred in 9/20,684 (0.04%) versus 92/20,746 (0.44%) participants in the HAV vaccine and control groups respectively (RR 0.09, 95% CI 0.03 to 0.30). In all nine randomised trials, clinically apparent hepatitis A occurred in 31/375,726 (0.01%) versus 505/356,654 (0.18%) participants in the HAV vaccine and control groups respectively (RR 0.09, 95% CI 0.05 to 0.17). These results were supported by trial sequential analyses. Subgroup analyses confirmed the clinical effectiveness of both inactivated hepatitis A vaccines (RR 0.09, 95% CI 0.03 to 0.30) and live attenuated hepatitis A vaccines (RR 0.07, 95% CI 0.03 to 0.17) on clinically confirmed hepatitis A. Inactivated hepatitis A vaccines had a significant effect on reducing the lack of sero-protection (less than 20 mIU/L) (RR 0.01, 95% CI 0.00 to 0.03). No trial reported on a sero-protective threshold less than 10 mIU/L. The risk of both non-serious local and systemic adverse events was comparable to placebo for the inactivated HAV vaccines. There were insufficient data to draw conclusions on adverse events for the live attenuated HAV vaccine. AUTHORS' CONCLUSIONS: Hepatitis A vaccines are effective for pre-exposure prophylaxis of hepatitis A in susceptible individuals. This review demonstrated significant protection for at least two years with the inactivated HAV vaccine and at least five years with the live attenuated HAV vaccine. There was evidence to support the safety of the inactivated hepatitis A vaccine. More high quality evidence is required to determine the safety of live attenuated vaccines.