Limited Evidence of Associations Between Executive Functioning and Alcohol Involvement In UK Adolescents.

AIMS: Deficits in motor inhibitory control and working memory have been hypothesized to be both a cause and consequence of heavy alcohol use. Adolescence is a critical developmental stage for inhibitory control and working memory, and it is also a stage when individuals are most likely to initiate alcohol use. This study aimed to examine whether inhibitory control and working memory would predict alcohol use and involvement in a group of UK adolescents. METHODS: We recruited 220 (N = 178, female) adolescents, aged between 16 and 18, from eight higher education settings in the Merseyside region of the UK. Alcohol use was examined using the Timeline Follow-Back and involvement (and related problems) using the Adolescent Alcohol Involvement Scale. A reward-based inhibitory control task (Go/No-Go) was used to examine the inhibition and reward sensitivity, and a self-ordered pointing task was used to measure working memory. RESULTS: Multiple regression demonstrated that neither inhibitory control (b = 0.02 (95% confidence interval (CI): -0.21, 0.24)) nor working memory (b = -0.12 (95% CI: -0.30, 0.07)) were significant predictors of alcohol use (units consumed). Inhibitory control (b = 0.61 (95% CI: 0.12, 1.09), specifically, in the no reward condition and school deprivation (b = 0.67 (95% CI: 0.06, 1.28) significantly predicted alcohol-related problems. CONCLUSIONS: Our findings demonstrated limited evidence that deficits in specific mechanisms of executive functioning (i.e. motor inhibition and working memory) were associated with alcohol-related problems in UK adolescents. This study adds to an increasing body of literature suggesting weak or non-existent links between inhibitory control, working memory and alcohol use.

Isolating Proactive Slowing from Reactive Inhibitory Control in Heavy Drinkers.

Background: Impaired inhibitory control is thought to contribute to alcohol (mis)use. However, current definitions of inhibitory control are over-simplified by a failure to distinguish reactive inhibitory control from proactive slowing. Objectives: To distinguish "reactive" inhibitory control and proactive slowing in heavy drinkers, and characterize associations between both constructs and individual differences in alcohol consumption. Methods: Sixty heavy drinkers completed self-reported measures of alcohol consumption, followed by two modified Stop-Signal tasks and an AX-continuous performance task in a laboratory setting. Results: Heavy drinkers demonstrated proactive slowing when inhibition was more likely but individual differences in proactive slowing and reactive stopping were unrelated to individual differences in alcohol consumption. Conclusions/Importance: Within a sample of heavy drinkers, individual differences in reactive inhibitory control and proactive slowing are unrelated to individual differences in alcohol consumption.

Novel compound heterozygous mutations in AMN cause Imerslund-Gräsbeck syndrome in two half-sisters: a case report.

BACKGROUND: Imerslund-Gräsbeck Syndrome (IGS) is a rare autosomal recessive disease characterized by intestinal vitamin B12 malabsorption. Clinical features include megaloblastic anemia, recurrent infections, failure to thrive, and proteinuria. Recessive mutations in cubilin (CUBN) and in amnionless (AMN) have been shown to cause IGS. To date, there are only about 300 cases described worldwide with only 37 different mutations found in CUBN and 30 different in the AMN gene. CASE PRESENTATION: We collected pedigree structure, clinical data, and DNA samples from 2 Caucasian English half-sisters with IGS. Molecular diagnostics was performed by direct Sanger sequencing of all 62 exons of the CUBN gene and 12 exons of the AMN gene. Because of lack of parental DNA, cloning, and sequencing of multiple plasmid clones was performed to assess the allele of identified mutations. Genetic characterization revealed 2 novel compound heterozygous AMN mutations in both half-sisters with IGS. Trans-configuration of the mutations was confirmed. CONCLUSION: We have identified novel compound heterozygous mutations in AMN in a family from the United Kingdom with clinical features of Imerslund-Gräsbeck Syndrome.

Anti-neutrophil cytoplasmic antibody (ANCA) associated small-vessel vasculitis in a patient with diabetic nephropathy and autoimmune polyendocrinopathy syndrome (APS) Type 2: a case report.

We present a 42-year-old woman with pre-existing autoimmune polyendocrinopathy syndrome (APS) Type 2 and chronic kidney disease due to Type 1 diabetic nephropathy, who developed a rapid deterioration in renal function due to perinuclear anti-neutrophil cytoplasmic antibody (pANCA)-associated vasculitis. Although possibly a chance occurrence, ANCA have been detected more frequently in patients with a history of certain autoimmune diseases. Such an association may simply reflect an underlying tendency to immune system dysfunction in these patients and the finding of positive ANCA serology does not reliably herald the development of ANCA-associated vasculitis. However, our case illustrates that positive ANCA serology in such circumstances is not always a benign phenomenon and should still be interpreted within the clinical context. Moreover, clinicians managing patients with pre-existing autoimmune disease should maintain a low threshold for appropriate assessment should such patients develop evidence suggestive of vasculitis.

Cardiac testing for coronary artery disease in potential kidney transplant recipients: a systematic review of test accuracy studies.

BACKGROUND: Cardiovascular disease is the leading cause of death after kidney transplant. Screening for coronary artery disease is integral to pretransplant evaluation, although the relative performance of different tests is uncertain. STUDY DESIGN: Systematic review of diagnostic test accuracy studies using hierarchical summary receiver operating characteristic analysis. SETTING & POPULATION: Kidney transplant candidates undergoing pretransplant assessment. SELECTION CRITERIA OF STUDIES: Studies evaluating the accuracy of screening tests for detecting coronary artery disease. INDEX TESTS: Any non- or minimally invasive test used to diagnose coronary artery disease. REFERENCE TEST: Coronary angiography. RESULTS: 11 studies (690 participants) evaluated dobutamine stress echocardiography; 7 (317 participants), myocardial perfusion scintigraphy; 2 (129 participants), exercise stress electrocardiography; and 2 (121 participants), other tests. Dobutamine stress echocardiography had pooled sensitivity of 0.80 (95% CI, 0.64-0.90) and specificity of 0.89 (95% CI, 0.79-0.94). Myocardial perfusion scintigraphy had pooled sensitivity of 0.69 (95% CI, 0.48-0.85) and specificity of 0.77 (95% CI, 0.59-0.89). Head-to-head comparison of dobutamine stress echocardiography and myocardial perfusion scintigraphy (2 studies; 116 participants) showed that dobutamine stress echocardiography had higher specificity and at least equivalent or higher sensitivity. Indirect comparison suggested dobutamine stress echocardiography may have improved accuracy over myocardial perfusion scintigraphy (P = 0.07). LIMITATIONS: Power to detect differences in accuracy between tests is limited due to sparse data. Absence of significant coronary artery disease may not necessarily correlate with cardiac event-free survival after transplant. CONCLUSIONS: Dobutamine stress echocardiography may perform better than myocardial perfusion scintigraphy; however, additional studies directly comparing dobutamine stress echocardiography and myocardial perfusion scintigraphy are needed. Further research should focus on assessing the ability of functional tests to predict postoperative outcome.

Cardiac testing for coronary artery disease in potential kidney transplant recipients.

BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk of coronary artery disease (CAD) and adverse cardiac events. Screening for CAD is therefore an important part of preoperative evaluation for kidney transplant candidates. There is significant interest in the role of non-invasive cardiac investigations and their ability to identify patients at high risk of CAD.  OBJECTIVES: We investigated the accuracy of non-invasive cardiac screening tests compared with coronary angiography to detect CAD in patients who are potential kidney transplant recipients. SEARCH METHODS: MEDLINE and EMBASE searches (inception to November 2010) were performed to identify studies that assessed the diagnostic accuracy of non-invasive screening tests, using coronary angiography as the reference standard. We also conducted citation tracking via Web of Science and handsearched reference lists of identified primary studies and review articles.   SELECTION CRITERIA: We included in this review all diagnostic cross sectional, cohort and randomised studies of test accuracy that compared the results of any cardiac test with coronary angiography (the reference standard) relating to patients considered as potential candidates for kidney transplantation or kidney-pancreas transplantation at the time diagnostic tests were performed.  DATA COLLECTION AND ANALYSIS: We used a hierarchical modelling strategy to produce summary receiver operating characteristic (SROC) curves, and pooled estimates of sensitivity and specificity. Sensitivity analyses to determine test accuracy were performed if only studies that had full verification or applied a threshold of ≥ 70% stenosis on coronary angiography for the diagnosis of significant CAD were included. MAIN RESULTS: The following screening investigations included in the meta-analysis were: dobutamine stress echocardiography (DSE) (13 studies), myocardial perfusion scintigraphy (MPS) (nine studies), echocardiography (three studies), exercise stress electrocardiography (two studies), resting electrocardiography (three studies), and one study each of electron beam computed tomography (EBCT), exercise ventriculography, carotid intimal media thickness (CIMT) and digital subtraction fluorography (DSF). Sufficient studies were present to allow hierarchical summary receiver operating characteristic (HSROC) analysis for DSE and MPS. When including all available studies, both DSE and MPS had moderate sensitivity and specificity in detecting coronary artery stenosis in patients who are kidney transplant candidates [DSE (13 studies) - pooled sensitivity 0.79 (95% CI 0.67 to 0.88), pooled specificity 0.89 (95% CI 0.81 to 0.94); MPS (nine studies) - pooled sensitivity 0.74 (95% CI 0.54 to 0.87), pooled specificity 0.70 (95% CI 0.51 to 0.84)]. When limiting to studies which defined coronary artery stenosis using a reference threshold of ≥ 70% stenosis on coronary angiography, there was little change in these pooled estimates of accuracy [DSE (9 studies) - pooled sensitivity 0.76 (95% CI 0.60 to 0.87), specificity 0.88 (95% CI 0.78 to 0.94); MPS (7 studies) - pooled sensitivity 0.67 (95% CI 0.48 to 0.82), pooled specificity 0.77 (95% CI 0.61 to 0.88)]. There was evidence that DSE had improved accuracy over MPS (P = 0.02) when all studies were included in the analysis, but this was not significant when we excluded studies which did not avoid partial verification or use a reference standard threshold of ≥70% stenosis (P = 0.09).   AUTHORS' CONCLUSIONS: DSE may perform better than MPS but additional studies directly comparing these cardiac screening tests are needed. Absence of significant CAD may not necessarily correlate with cardiac-event free survival following transplantation. Further research should focus on assessing the ability of functional tests to predict postoperative outcome.

The Associations Between Proactive Slowing, Working Memory, Alcohol Sensitivity, and Alcohol Use.

OBJECTIVE: "Reactive" inhibitory control is associated with heavy drinking and alcohol dependence. However, the majority of research ignores the downstream influence of proactive control--the preparation to withhold responses when examining alcohol use behaviors. The potential mechanisms behind these relationships are also poorly understood. Two studies were conducted to investigate the role of proactive and reactive control in heavy drinkers, in the presence of alcohol-related cues, and to examine the potential mediating effects of working memory capacity and alcohol sensitivity. METHOD: Heavy drinkers (Study 1: n = 108; Study 2: n = 116) completed online self-reported measures of alcohol use followed by a modified stop-signal task in the presence of alcohol-related cues (Study 1: images; Study 2: words) and a self-ordered pointing task using neutral-related images (Study 1) and alcohol-related images (Study 2). RESULTS: In Study 1, craving and working memory capacity predicted alcohol use. In Study 2, working memory capacity was a negative predictor of alcohol use alongside stop-signal reaction times; however, the overall regression model was not significant. When conducting pooled analyses across both studies to increase power, only a robust association between craving and alcohol use was observed. CONCLUSIONS: These studies provide no support for the associations between alcohol use indices and working memory capacity, reactive control, and proactive slowing.

Does alcohol cue inhibitory control training survive a context shift?

Inhibitory control training (ICT) is a novel psychological intervention that aims to improve inhibitory control in response to alcohol-related cues through associative learning. Laboratory studies have demonstrated reductions in alcohol consumption following ICT compared with control/sham training, but it is unclear if these effects are robust to a change of context. In a preregistered study, we examined whether the effects of ICT would survive a context shift from a neutral context to a seminaturalistic bar setting. In a mixed design, 60 heavy drinkers (40 female) were randomly allocated to receive either ICT or control/sham training in a neutral laboratory over 2 sessions. We developed a novel variation of ICT that used multiple stop signals to establish direct stimulus-stop associations. The effects of ICT/control were measured once in the same context and once following a shift to a novel (alcohol-related) context. Our dependent variables were ad libitum alcohol consumption following training, change in inhibitory control processes, and change in alcohol value. ICT did not reduce alcohol consumption in either context compared with the control group. Furthermore, we demonstrated no effects of ICT on inhibitory control processes or alcohol value. Bayesian analyses demonstrated overall support for the null hypotheses. This study failed to find any effects of ICT on alcohol consumption or candidate psychological mechanisms. These findings illustrate the difficulty in training alcohol-inhibition associations and add to a growing body of literature suggesting that ICT holds little evidential value as a psychological intervention for alcohol use disorders. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The effect of alcohol cue exposure and acute intoxication on inhibitory control processes and ad libitum alcohol consumption.

RATIONALE: Alcohol intoxication and alcohol cue exposure impair 'reactive' inhibitory control and increase motivation to drink. However, inhibitory control is a multi-component process that also comprises signal detection and proactive control. It is unknown whether intoxication and cue exposure selectively influence these subprocesses in heavy drinkers. OBJECTIVES: In two pre-registered studies, we investigated whether exposure to alcohol-related cues (study 1) and alcohol priming (study 2) impair each of these subprocesses of inhibitory control and increase motivation to drink. METHODS: In study 1, 64 heavy drinkers completed a modified stop-signal task in an alcohol context (with embedded alcohol cues) and a neutral context (with embedded neutral cues) followed by a subjective measure of craving and a bogus taste test to measure ad libitum alcohol consumption. In study 2, 36 heavy drinkers consumed an alcoholic beverage (0.6 g/kg body weight), an alcohol-placebo beverage, and water on a within-subjects basis, followed by the modified stop-signal task and a bogus taste test. RESULTS: In study 1, alcohol cue exposure did not impair inhibitory control subprocesses. Reactive control was unexpectedly better following alcohol cue exposure (compared to neutral cue exposure). However, craving and ad libitum consumption increased as expected. In study 2, reactive control was significantly impaired following the alcohol and control primes, relative to the placebo, but there was no effect on proactive slowing or signal detection. As expected, intoxication increased motivation to drink and ad libitum consumption (compared to placebo and control). CONCLUSIONS: Alcohol intoxication and cue exposure increase motivation to drink in the absence of impairments in subcomponents of inhibitory control.

Anemia after kidney transplantation is not completely explained by reduced kidney function.

BACKGROUND: Anemia is prevalent among kidney transplant recipients and likely contributes to mortality and morbidity. Prevalence of anemia is associated strongly with degree of kidney graft dysfunction; however, it remains unclear whether additional transplant-associated factors also contribute. METHODS: The aim of this study is to compare the prevalence of anemia between 2 cohorts, 1 of kidney transplant recipients (n = 851) and another from the general population (n = 732), sourced from subjects of the AusDiab study and selected by means of propensity score to provide a cohort matched for kidney function (Cockcroft-Gault creatinine clearance). RESULTS: Average hemoglobin level in kidney transplant recipients was (13.1 g/dL [131 g/L]; range, 9.0 to 18.0 g/dL), significantly less than in the general population (14.3 g/dL [143 g/L]; range, 9.7 to 20.0 g/dL). The prevalence of anemia (hemoglobin < 12.0 g/dL [<120 g/L] for females; <12.5 g/dL [<125 g/L] for males) was almost 10-fold greater in kidney transplant recipients (30.8%) versus the general population (3.4%). Average hemoglobin level was lower in the kidney-transplant-recipient cohort at all levels of creatinine clearance. Considering both cohorts pooled, multivariate analysis showed that transplant status had the strongest association with anemia, followed by sex, creatinine clearance, and age. CONCLUSION: Posttransplantation anemia cannot be attributed solely to impaired kidney function.

Hopelessness and alcohol use: The mediating role of drinking motives and outcome expectancies.

INTRODUCTION: Heavy drinking is a considerable public health concern. There is a broad evidence-base examining the separate contributions of personality characteristics, motives and alcohol-expectancies on subsequent alcohol use to identify those at risk. However, little is known about the complex relationships by which these variables may interact to predict drinking behavior. Feelings of hopelessness and anxiety sensitivity are hypothesized to be distal predictors of alcohol use, with outcome expectancies and drinking motives more proximal. Therefore, the aim of the current study was to examine whether hopelessness and anxiety sensitivity influenced alcohol use via drinking to cope and alcohol - outcome expectancies. METHODS: We recruited 230 participants to complete an online questionnaire consisting of the brief drinking motives questionnaire, the Substance Use Risk Profile scale and Brief Comprehensive Effects of Alcohol scale. We conducted path analyses using structural equation modelling. RESULTS: We demonstrated a significant direct effect of anxiety sensitivity on alcohol use, and a significant serial indirect effect of hopelessness through coping motives and alcohol outcome expectancies. CONCLUSIONS: These findings suggest feelings of hopelessness may predict alcohol consumption through a complex pathway and future research should use these findings to identify individuals at risk of increased alcohol use.

Prognostic value of cardiac tests in potential kidney transplant recipients: a systematic review.

BACKGROUND: Whether abnormal myocardial perfusion scintigraphy (MPS), dobutamine stress echocardiography (DSE) or coronary angiography, performed during preoperative evaluation for potential kidney transplant recipients, predicts future cardiovascular morbidity is unclear. We assessed test performance for predicting all-cause mortality, cardiovascular mortality and major adverse cardiac events (MACE). METHODS: We searched MEDLINE and EMBASE (to February 2014), appraised studies, and calculated risk differences and relative risk ratios (RRR) with 95% confidence intervals (95% CI) using random effects meta-analysis. RESULTS: Fifty-two studies (7401 participants) contributed data to the meta-analysis. Among the different tests, similar numbers of patients experienced MACE after an abnormal test result compared with a normal result (risk difference: MPS 20 per 100 patients tested [95% CI, 0.11-0.29], DSE 24 [95% CI, 0.10-0.38], and coronary angiography 20 [95% CI, 0.08-0.32; P = 0.91]). Although there was some evidence that coronary angiography was better at predicting all-cause mortality than MPS (RRR, 0.69; 95% CI, 0.49-0.96; P = 0.03) and DSE (RRR, 0.72; 95% CI, 0.50-1.02; P = 0.06), noninvasive tests were as good as coronary angiography at predicting cardiovascular mortality (RRR, MPS, 0.89; 95% CI, 0.38-2.10; P = 0.78; DSE, 1.09; 95% CI, 0.12-10.05; P = 0.93), and MACE (RRR: MPS, 1.09; 95% CI, 0.64-1.86; P = 0.74; DSE, 1.56; 95% CI, 0.71-3.45; P = 0.25). CONCLUSIONS: Noninvasive tests are as good as coronary angiography at predicting future adverse cardiovascular events in advanced chronic kidney disease. However, a substantial number of people with negative test results go on to experience adverse cardiac events.

Prevention of chemotherapy-induced intraperitoneal adhesion formation in rats by icodextrin at a range of concentrations.

OBJECTIVE: Two controlled in vivo studies in rats have investigated the effect of icodextrin solution on intraperitoneal chemotherapy-induced adhesion formation. The first study evaluated the effect of three concentrations of icodextrin (4, 15, 20% w/v) in comparison to a phosphate-buffered saline (PBS) control in response to intraperitoneal doxorubicin (n = 40). The second study compared the effect of 4% icodextrin to Ringers' lactate solution (RLS) control in response to intraperitoneal bleomycin (n = 30). METHODS: Doxorubicin and bleomycin were administered via a continuous pump and as a single bolus (bleomycin only). Doxorubicin 2 ml (23.2 microg/ml) was delivered via pump in conjunction with 20 ml of 4, 15, or 20% icodextrin or PBS (n = 10 per group). In the bleomycin experiments rats received either 2 ml (0.77 U/ml) bleomycin delivered via pump in conjunction with 15 ml 4% icodextrin or RLS, or 0.77 or 0.077 U bleomycin delivered in 15 ml 4% icodextrin or RLS administered as a bolus injection (n = 5 per group). Seven days after the initiation of doxorubicin treatment and 9 days after initiation of bleomycin treatment, the rats were euthanized by CO(2) and the extent of peritoneal adhesion formation was evaluated using an 8-point scoring system. RESULTS: When icodextrin was administered in conjunction with doxorubicin there was a reduction in the formation of adhesions compared to PBS. Efficacy increased with the concentration of icodextrin used. The lowest dose of bleomycin (0.077 U) caused very few adhesions. Results with bleomycin 0.77 U/ml (pump) and 0.77 U (bolus) showed that 4% icodextrin was significantly more effective than RLS at preventing adhesion formation, irrespective of the dosing regimen. CONCLUSIONS: These studies suggest that 4% icodextrin may reduce adhesion formation caused by intraperitoneal chemotherapy.