Red Blood Cell Distribution Width as a Predictor of 28-Day Mortality in Critically Ill Patients With Alcohol Use Disorder

Background

Patients with alcohol use disorder (AUD) are common attendees of the intensive care unit (ICU). Early assessment of the prognosis for critically ill patients with AUD is conducive for formulating comprehensive treatment measures and improving survival rates. The purpose of this study was to explore the predictive value of red blood cell distribution width (RDW) for 28-day mortality in critically ill patients with AUD.

Methods

2,884 patients with AUD were recruited retrospectively. Data from the MIMIC-III database were collected and analyzed. A receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value of RDW. The Kaplan–Meier method and Cox regression models were used to evaluate prognostic factors.

Results

Of the 2,884 patients, there were 344 nonsurvivors (11.9%). The nonsurvivors had a higher RDW than the survivors (p < 0.001). According to ROC curve analysis, the area under the curve predicted by RDW for 28-day mortality was 0.728 (95% CI, 0.700 to 0.755) and the optimal cutoff value was 15.45% (sensitivity: 67.2%; specificity: 67.3%). Length of stay in ICU, length of stay in hospital, in-hospital mortality, and 28-day mortality in patients with an RDW > 15.45% were significantly higher than in those with an RDW ≤ 15.45% (p < 0.001). Cox regression analysis showed that an RDW > 15.45% was an independent prognostic indicator for 28-day mortality in critically ill patients with AUD (HR = 1.964, 95% CI: 1.429 to 2.698).

Conclusions

High RDW was associated with increased short-term mortality risks in critically ill patients with AUD.

     

Impact of Long-Term Alcohol Consumption and Relapse on Genome-Wide DNA Methylation Changes in Alcohol-Dependent Subjects: A Longitudinal Study

Background

Genetic factors play an important role in the development and maintenance of alcohol use disorder (AUD). Significant and widespread differences in methylation levels of multiple regions within the genome have been reported between AUD patients and healthy controls in large epigenome-wide association studies (EWASs). Also, within patient populations, methylation changes over time (both during and after withdrawal) have been identified as sensitive indicators for disease activity. The detection of changes in methylation levels is a powerful tool to further explore and understand the biological correlates and underpinnings of AUD. Although there is strong and convincing evidence for differences in methylation of various sites between AUD patients and controls, only few studies assessed changes within patients over longer periods of time while taking into account alcohol consumption, relapse, and abstinence. So far, the longest period assessed as a within-subject design using EWASs was 4 weeks.

Methods

Here, we investigated changes in whole-genome methylation levels within a sample of 69 detoxified AUD patients over a period as long as 12 months for the first time, comparing patients that relapsed within the follow-up period to those that remained abstinent.

Results

Whole-genome methylation patterns of individual CpG sites over time did not differ between abstinent and relapsing patients. However, there was a negative association between global mean methylation at the 12-month follow-up and alcohol consumption within our sample.

Conclusion

Although the present study represents the largest study of methylation levels in a sample of AUD patients with a follow-up period of 1 year and accounting for alcohol consumption and relapse to date, the sample size might still not be large enough to detect genome-wide significant effects. Therefore, large-scale, long-term studies with AUD subjects are needed to determine the utility of DNA methylation for the assessment and monitoring of persons with alcohol use disorders.

     

Stigmatization of people with alcohol use disorders: An updated systematic review of population studies

Background

We summarize research on the public stigmatization of persons with alcohol use disorder (AUD) in comparison with other mental health conditions and embed the results into a conceptual framework of the stigma process.

Methods

We conducted a systematic search using Embase, MEDLINE, PubMed and PsycINFO (via Ovid), and Web of Science for population-based studies on the public stigma in AUD and at least 1 other mental health condition, published between October 1, 2010 and December 20, 2020, thus including all studies published since the last systematic review on this topic. The study is registered with PROSPERO (registration number: CRD42020173054).

Results

We identified 20,561 records, of which 24 met the inclusion criteria, reporting results from 16 unique studies conducted in 9 different countries. Compared to substance-unrelated mental disorders, persons with AUD were generally less likely to be considered mentally ill, while they were perceived as being more dangerous and responsible for their condition. Further, the public desire for social distance was consistently higher for people with AUD. We found no consistent differences in the public stigma toward persons with AUD in comparison with other substance use disorders.

Conclusion

The stigmatization of persons with AUD remains comparatively high and is distinct from that of other substance-unrelated disorders.

     

Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta-regression analysis to develop an enrichment strategy

Background

There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no “spontaneous improvement” prior to treatment initiation (high-severity population) than in a mild-severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD.

Methods

We conducted a systematic literature review on placebo-controlled RCTs for AD.We assigned retained RCTs to high- or mild-severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta-regression analysis.

Results

Among the 19 retained RCTs (comprising 1996 placebo-treated patients), 11 trials were high-severity and 8 were mild-severity RCTs. The between-study variability in AR was lower in the high-severity than in the mild-severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high-severity studies (16.8% at 3 months) than the mild-severity studies (36.7% at 3 months).

Conclusions

Pharmacological RCTs for AD should select high-severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.

     

Longitudinal assessment of drinking changes during the pandemic: The 2021 COVID-19 follow-up study to the 2019 to 2020 National Alcohol Survey

Background

Surveys of changes in drinking during the COVID-19 pandemic have primarily relied on retrospective self-report. Further, most such surveys have not included detailed measures of alcohol use patterns, such as beverage-specific consumption, nor measures of alcohol use disorder (AUD) symptoms that would allow a comprehensive understanding of changes in alcohol use.

Methods

Data from 1819 completed interviews from the N14C follow-up survey to the 2019 to 2020 National Alcohol Survey (N14) were conducted between January 30 and March 28, 2021. Questions on alcohol use from the Graduated Frequency series, beverage-specific quantity and frequency, and DSM-5 AUD items were asked in both surveys and used to estimate changes from pre-pandemic drinking to drinking during the pandemic. Analyses focus on changes in these measures over time and comparisons between key subgroups defined by gender, race/ethnicity, and age.

Results

Key findings include particularly large increases in drinking and AUD for African Americans and women, reduced drinking and heavy drinking prevalence among men and White respondents, and a concentration of increased drinking and AUD among respondents aged 35 to 49. Increases in alcohol use were found to be driven particularly by increases in drinking frequency and the consumption of spirits.

Conclusions

Results confirm prior findings of overall increases and subgroup-specific changes, and importantly, provide detailed information on the patterns of change across major socio-demographic subgroups. Substantial increases in the prevalence of DSM-5 moderate to severe AUDs are a novel finding that is of particular concern.

     

Association of Prenatal Alcohol Exposure and Offspring Depression: A Negative Control Analysis of Maternal and Partner Consumption

Background

Previous research has suggested that intrauterine alcohol exposure is associated with a variety of adverse outcomes in offspring. However, few studies have investigated its association with offspring internalizing disorders in late adolescence.

Methods

Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the associations of maternal drinking in pregnancy with offspring depression at age 18 and 24 (n = 13,480). We also examined partner drinking as a negative control for intrauterine exposure for comparison.

Results

Offspring of mothers that consumed any alcohol at 18 weeks gestation were at increased risk of having a diagnosis of depression (fully adjusted model: OR 1.17, 95% CI 1.02 to 1.34), but there was no clear evidence of association between partners’ alcohol consumption at 18 weeks gestation during pregnancy and increased risk of offspring depression (fully adjusted model: OR 0.87, 95% CI 0.74 to 1.01). Postestimation tests found a positive difference between the association of maternal and partner alcohol use on offspring depression, showing a stronger association for maternal compared with partner alcohol use (OR 1.41, CI 1.07 to 1.84).

Conclusions

Maternal drinking in pregnancy was associated with increased risk of offspring depression at age 18. Residual confounding may explain this association, but the negative control comparison of paternal drinking provides some evidence that it may be causal, and this warrants further investigation.

     

Genes regulating levels of ω-3 long-chain polyunsaturated fatty acids are associated with alcohol use disorder and consumption,and broader externalizing behavior in humans

Background

Individual variation in the physiological response to alcohol is predictive of an individual's likelihood to develop alcohol use disorder (AUD). Evidence from diverse model organisms indicates that the levels of long-chain polyunsaturated omega-3 fatty acids (ω-3 LC-PUFAs) can modulate the behavioral response to ethanol and therefore may impact the propensity to develop AUD. While most ω-3 LC-PUFAs come from diet, humans can produce these fatty acids from shorter chain precursors through a series of enzymatic steps. Natural variation in the genes encoding these enzymes has been shown to affect ω-3 LC-PUFA levels. We hypothesized that variation in these genes could contribute to the susceptibility to develop AUD.

Methods

We identified nine genes (FADS1, FADS2, FADS3, ELOVL2, GCKR, ELOVL1, ACOX1, APOE, and PPARA) that are required to generate ω-3 LC-PUFAs and/or have been shown or predicted to affect ω-3 LC-PUFA levels. Using both set-based and gene-based analyses we examined their association with AUD and two AUD-related phenotypes, alcohol consumption, and an externalizing phenotype.

Results

We found that the set of nine genes is associated with all three phenotypes. When examined individually, GCKR, FADS2, and ACOX1 showed significant association signals with alcohol consumption. GCKR was significantly associated with AUD. ELOVL1 and APOE were associated with externalizing.

Conclusions

Taken together with observations that dietary ω-3 LC-PUFAs can affect ethanol-related phenotypes, this work suggests that these fatty acids provide a link between the environmental and genetic influences on the risk of developing AUD.

     

COVID-19 impacts on drinking and mental health in emerging adults: Longitudinal changes and moderation by economic disruption and sex

Background

There are significant concerns that the COVID-19 pandemic may have negative effects on substance use and mental health, but most studies to date are cross-sectional. In a sample of emerging adults, over a two-week period during the pandemic, the current study examined: (1) changes in drinking-related outcomes, depression, anxiety, and posttraumatic stress disorder and (2) differences in changes by sex and income loss. The intra-pandemic measures were compared to pre-pandemic measures.

Methods

Participants were 473 emerging adults (M_age = 23.84; 41.7% male) in an existing longitudinal study on alcohol misuse who were assessed from June 17 to July 1, 2020, during acute public health restrictions in Ontario, Canada. These intra-pandemic data were matched to participant pre-pandemic reports, collected an average of 5 months earlier. Assessments included validated measures of drinking, alcohol-related consequences, and mental health indicators.

Results

Longitudinal analyses revealed significant decreases in heavy drinking and adverse alcohol consequences, with no moderation by sex or income loss, but with substantial heterogeneity in changes. Significant increases in continuous measures of depression and anxiety were present, both of which were moderated by sex. Females reported significantly larger increases in depression and anxiety. Income loss >50% was significantly associated with increases in depression.

Conclusions

During the initial phase of the pandemic, reductions in heavy drinking and alcohol consequences were present in this sample of emerging adults, perhaps due to restrictions on socializing. In contrast, there was an increase in internalizing symptoms , especially in females, highlighting disparities in the mental health impacts of the pandemic.

     

A pilot study of short-term hemodynamic effects of negative pressure ventilation in chronic obstructive pulmonary disease assessed using electrical cardiometry

Background

Pulmonary rehabilitation combined with negative pressure ventilation (NPV) demonstrated benefits in patients with chronic obstructive pulmonary disease (COPD). The effect of NPV remains unknown. This study aims to clarify the short-term response of the hemodynamic outcome of NPV in patients with COPD undergoing pulmonary rehabilitation program by electrical cardiometry.

Methods

This is an observational retrospective study of COPD patients who had been treated in a pulmonary rehabilitation unit with NPV between January 2018 and December 2019 that were enrolled to analyze the hemodynamic outcomes.

Results

Thirty patients with COPD that were undergoing a pulmonary rehabilitation program and were regularly receiving NPV were enrolled. Cardiac output (p < .001) and heart rate (p < .001) showed a significant decrease after NPV. Stroke volume did not demonstrate significant change (p = .15). There was a significant decrease in thoracic fluid content (p = .016) and a significant increase in stroke volume variation (p = .038) systemic vascular resistance (p < .001) and left ventricular ejection time (p < .001). Other hemodynamic parameters were all comparable before and after NPV.

Conclusions

Negative pressure ventilation demonstrated an impact on hemodynamics in patients with chronic obstructive pulmonary disease undergoing pulmonary rehabilitation. Electrical cardiometry is a feasible method of determining the hemodynamic effects of negative pressure ventilation. Thoracic fluid content significantly decreased immediately after the NPV.

     

Resting state functional connectivity as a predictor of brief intervention response in adults with alcohol use disorder: A preliminary study

Background

Brief interventions for alcohol use disorder (AUD) are generally efficacious, albeit with variability in response. Resting state functional connectivity (rsFC) may characterize neurobiological indicators that predict the response to brief interventions and is the focus of the current investigation.

Materials and Methods

Forty-six individuals with AUD (65.2% female) completed a resting state functional magnetic resonance imaging (fMRI) scan immediately followed by a brief intervention aimed at reducing alcohol consumption. Positive clinical response was defined as a reduction in alcohol consumption by at least one World Health Organization (WHO) risk drinking level at 3-month follow-up. rsFC was analyzed using seed-to-voxel analysis with seed regions from four networks: salience network, reward network, frontoparietal network, and default mode network.

Results

At baseline, responders had greater rsFC between the following seed regions in relation to voxel-based clusters than non-responders: (i) anterior cingulate cortex (ACC) in relation to left postcentral gyrus and right supramarginal gyrus (salience network); (ii) right posterior parietal cortex in relation to right ventral ACC (salience network); (iii) right interior frontal gyrus (IFG) pars opercularis in relation to right cerebellum and right occipital fusiform gyrus (frontoparietal); and (iv) right primary motor cortex in relation to left thalamus (default mode). Lower rsFC in responders vs. nonresponders was seen between the (i) right rostral prefrontal cortex in relation to left IFG pars triangularis (frontoparietal); (ii) right IFG pars triangularis in relation to right cerebellum (frontoparietal); (iii) right IFG pars triangularis in relation to right frontal eye fields and right angular gyrus (frontoparietal); and (iv) right nucleus accumbens in relation to right orbital frontal cortex and right insula (reward).

Conclusions

Resting state functional connectivity in the frontoparietal, salience, and reward networks predicts the response to a brief intervention in individuals with AUD and could reflect greater receptivity or motivation for behavior change.

     

2-Arachidonoylglycerol-mediated endocannabinoid signaling modulates mechanical hypersensitivity associated with alcohol withdrawal in mice

Background

Alcohol use disorder (AUD) commonly occurs in patients with chronic pain, and a major barrier to achieving abstinence and preventing relapse is the emergence of hyperalgesia during alcohol withdrawal. Elucidating novel therapeutic approaches to target hyperalgesia associated with alcohol withdrawal could have important implications for treating AUD. Here, we examined the role of 2-arachidonoylglycerol (2-AG)-mediated endocannabinoid (eCB) signaling in the regulation of hyperalgesia associated with alcohol withdrawal in mice. We tested the hypothesis that pharmacological augmentation of 2-AG signaling could reduce hyperalgesia during withdrawal.

Methods

Male and female C57BL/6J mice were tested during withdrawal from a continuous access two-bottle choice (2BC) paradigm to investigate how eCB signaling modulates mechanical and thermal sensitivity during withdrawal. Mice were pretreated with the monoacylglycerol lipase (MAGL) inhibitor JZL184 to elevate levels of 2-AG. Rimonabant or AM630 were given to block CB₁ and CB₂ receptor activity, respectively. DO34 was given to reduce 2-AG by inhibiting the 2-AG synthetic enzyme diacylglycerol lipase (DAGL).

Results

After 72 h of withdrawal, male and female mice exhibited increased mechanical, but not thermal, hypersensitivity, which normalized by 7 days. This effect was reversed by pretreatment with JZL184. The effects of JZL184 were prevented by coadministration of either the CB₁ or the CB₂ antagonist. DO34, Rimonabant, and AM630 exacerbated mechanical hypersensitivity during alcohol withdrawal, causing an earlier onset and persistent hypersensitivity even 1 week into withdrawal.

Conclusions

Our findings demonstrate the critical role of 2-AG signaling in the bidirectional regulation of mechanical sensitivity during alcohol withdrawal, with enhancement of 2-AG levels reducing sensitivity, and inhibition of 2-AG signaling exacerbating sensitivity. These data suggest that 2-AG augmentation represents a novel approach to the treatment of alcohol withdrawal-associated hyperalgesia and AUD in patients with comorbid pain disorders.

     

Changes in Alcohol Use and Drinking Context due to the COVID-19 Pandemic: A Multimethod Study of College Student Drinkers

Background

In spring 2020, U.S. universities closed campuses to limit the transmission of COVID-19, resulting in an abrupt change in residence, reductions in social interaction, and in many cases, movement away from a heavy drinking culture. The present mixed-methods study explores COVID-19-related changes in college student drinking. We characterize concomitant changes in social and location drinking contexts and describe reasons attributed to changes in drinking.

Methods

We conducted two studies of the impact of the COVID-19 pandemic on drinking behavior, drinking context, and reasons for both increases and decreases in consumption among college students. Study 1 (qualitative) included 18 heavy-drinking college students (M_age = 20.2; 56% female) who completed semi-structured interviews. Study 2 (quantitative) included 312 current and former college students who reported use of alcohol and cannabis (M_age = 21.3; 62% female) and who completed an online survey.

Results

In both studies, COVID-19-related increases in drinking frequency were accompanied by decreases in quantity, heavy drinking, and drunkenness. Yet, in Study 2, although heavier drinkers reduced their drinking, among non-heavy drinkers several indices of consumption increased or remained stable . Both studies also provided evidence of reductions in social drinking with friends and roommates and at parties and increased drinking with family. Participants confirmed that their drinking decreased due to reduced social opportunities and/or settings, limited access to alcohol, and reasons related to health and self-discipline. Increases were attributed to greater opportunity (more time) and boredom and to a lesser extent, lower perceived risk of harm and to cope with distress.

Conclusion

This study documents COVID-19-related changes in drinking among college student drinkers that were attributable to changes in context, particularly a shift away from heavy drinking with peers to lighter drinking with family. Given the continued threat of COVID-19, it is imperative for researchers, administrators, and parents to understand these trends as they may have lasting effects on college student drinking behaviors.

     

Prognostic value of initial QRS analysis in anterior STEMI: Correlation with left ventricular systolic dysfunction,serum biomarkers,and cardiac outcomes

Background

The presence of pathologic Q waves on admission electrocardiogram (ECG) in patients with anterior ST-elevated myocardial infarction (STEMI) has been related to adverse cardiac outcomes. Our study evaluates the prognostic value of QRS complex and Q waves in patients with STEMI undergoing percutaneous coronary intervention.

Methods

We prospectively analyzed the specific characteristics of QRS complex and pathologic Q waves on admission and on discharge ECG in 144 patients hospitalized for anterior STEMI. We correlated these findings with the development of left ventricular systolic dysfunction (LVSD), appearance of heart failure (HF) or death during follow-up, and levels of several biomarkers obtained 6 months after the index event.

Results

Multivariate logistic regression analysis showed that QRS width (odds ratios [OR] 1.05, p = .001) on admission ECG and the sum of Q-wave depth (OR 1.06, p = .002) on discharge ECG were independent predictors of LVSD development. Moreover, QRS width on admission ECG was related to an increased risk of HF or death (OR 1.03, p = .026). Regarding biomarkers, QRS width on admission ECG revealed a statistically significant relationship with the levels of NT-pro-BNP at 6 months (0.29, p = .004); the sum of Q-wave depth (0.27, p = .012) and width (0.25, p = .021) on admission ECG was related to the higher levels of hs-cTnI; the sum of the voltages in precordial leads both on admission ECG (−0.26, p = .011) and discharge ECG (0.24, p = .046) was related to the lower levels of parathormone.

Conclusions

Assessment of QRS complex width and pathologic Q waves on admission and discharge ECGs aids in predicting long-term prognosis in patients with STEMI.

     

Is talk cheap? Correspondence between self-attributions about changes in drinking and longitudinal changes in drinking during the 2019 coronavirus pandemic

Background

There are concerns that the coronavirus disease 2019 (COVID-19) pandemic may increase drinking, but most accounts to date are cross-sectional studies of self-attributions about alcohol-related impacts and the accuracy of those perceptions has not been investigated. The current study examined the correspondence between self-attributions of pandemic-related changes in drinking and longitudinally-measured changes in drinking and alcohol-related consequences in a sample of emerging adults.

Methods

In an existing ongoing longitudinal study on alcohol misuse (≥1 heavy episodic drinking day/month) in emerging adults, 473 individuals (M_age = 23.8; 41.7% male) received a supplemental assessment from June 17th to July 1st, 2020, during public health restrictions in Ontario, Canada. These intrapandemic data were matched to the most recent assessment prior to the pandemic (~8 months earlier). Self-attributions about changes in drinking were assessed globally (i.e., increases/decreases/no change) and with higher resolution questions clarifying the magnitude of changes.

Results

Global self-attributions about changes in drinking substantively paralleled longitudinal changes in weekly drinking days (DD). In the longitudinal data, individuals’ who self-reported increases in drinking exhibited significant increases; individuals’ who self-reported decreases exhibited significant decreases; and individuals who self-reported no change exhibited nonsignificant changes. Higher resolution items likewise revealed longitudinal patterns of weekly drinking that were substantively consistent with self-attributions. Heavy DD and alcohol-related consequences exhibited similar patterns, but only individuals who self-reported large increases in drinking exhibited increases on these outcomes. Individuals who reported large increases in drinking also exhibited significant increases in depression and posttraumatic stress disorder symptoms.

Conclusions

Self-attributions about drinking closely corresponded to longitudinal changes in drinking, supporting the validity of self-attributions in population-level surveys, particularly in young adults. Notably, a subgroup was identified that exhibited pronounced increases for all alcohol-related outcomes and concurrent increases in internalizing psychopathology.

     

Psychological factors and cardiac repolarization instability during anger in implantable cardioverter defibrillator patients

Background

Evidence indicates that emotions such as anger are associated with increased incidence of sudden cardiac death, but the biological mechanisms remain unclear. We tested the hypothesis that, in patients with sudden death vulnerability, anger would be associated with arrhythmic vulnerability, indexed by cardiac repolarization instability.

Methods

Patients with coronary artery disease (CAD) and an implantable cardioverter defibrillator (ICD; n = 41) and healthy controls (n = 26) gave an anger-inducing speech (anger recall), rated their current (state) anger, and completed measures of trait (chronic) levels of Anger and Hostility. Repolarization instability was measured using QT Variability Index (QTVI) at resting baseline and during anger recall using continuous ECG.

Results

ICD patients had significantly higher QTVI at baseline and during anger recall compared with controls, indicating greater arrhythmic vulnerability overall. QTVI increased from baseline to anger recall to a similar extent in both groups. In ICD patients but not controls, during anger recall, self-rated anger was related to QTVI (r = .44, p = .007). Trait (chronic) Anger Expression (r = .26, p = .04), Anger Control (r = −.26, p = .04), and Hostility (r = .25, p = .05) were each associated with the change in QTVI from baseline to anger recall (ΔQTVI). Moderation analyses evaluated whether psychological trait associations with ΔQTVI were specific to the ICD group. Results indicated that Hostility scores predicted ΔQTVI from baseline to anger recall in ICD patients (β = 0.07, p = .01), but not in controls.

Conclusions

Anger increases repolarization lability, but in patients with CAD and arrhythmic vulnerability, chronic and acute anger interact to trigger cardiac repolarization lability associated with susceptibility to malignant arrhythmias.

     

Prevalence of fetal alcohol spectrum disorder in Greater Manchester,UK: An active case ascertainment study

Background

Despite high levels of prenatal alcohol exposure in the UK, evidence on the prevalence of fetal alcohol spectrum disorders (FASD) is lacking. This paper reports on FASD prevalence in a small sample of children in primary school.

Methods

A 2-phase active case ascertainment study was conducted in 3 mainstream primary schools in Greater Manchester, UK. Schools were located in areas that ranged from relatively deprived to relatively affluent. Initial screening of children aged 8–9 years used prespecified criteria for elevated FASD risk (small for age; special educational needs; currently/previously in care; significant social/emotional/mental health symptoms). Screen-positive children were invited for detailed ascertainment of FASD using gold standard measures that included medical history, facial dysmorphology, neurological impairment, executive function, and behavioral difficulties.

Results

Of 220 eligible children, 50 (23%) screened positive and 12% (26/220) proceeded to Phase 2 assessment. Twenty had a developmental disorder, of whom 4 had FASD and 4 were assessed as possible FASD. The crude prevalence rate of FASD in these schools was 1.8% (95% CI: 1.0%, 3.4%) and when including possible cases was 3.6% (2.1%, 6.3%). None of these children had previously been identified with a developmental diagnosis.

Conclusions

FASD was found to be common in these schools and most of these children's needs had not previously been identified. A larger, more definitive study that uses a random sampling technique stratified by deprivation level to select schools is needed to make inferences regarding the population prevalence of FASD.

     

Differential diagnosis between LQT1 and LQT2 by QT/RR relationships using 24-hour Holter monitoring: A multicenter cross-sectional study

Background

The clinical course and therapeutic strategies in the congenital long QT syndrome (LQTS) are genotype-specific. However, accurate estimation of LQTS genotype is often difficult from the standard 12-lead ECG.

Objectives

This study aims to evaluate the utility of QT/RR slope analysis by the 24-hour Holter monitoring for differential diagnosis of LQTS genotype between LQT1 and LQT2.

Methods

This cross-sectional study enrolled 54 genetically identified LQTS patients (29 LQT1 and 25 LQT2) recruited from three medical institutions. The QT-apex (QTa) interval and the QT-end (QTe) interval at each 15-second were plotted against the RR intervals, and the linear regression (QTa/RR and QTe/RR slopes, respectively) was calculated from the entire 24-hour and separately during the day or night-time periods of the Holter recordings.

Results

The QTe/RR and QTa/RR slopes at the entire 24-hour were significantly steeper in LQT2 compared to those in LQT1 patients (0.262 ± 0.063 vs. 0.204 ± 0.055, p = .0007; 0.233 ± 0.052 vs. 0.181 ± 0.040, p = .0002, respectively). The QTe interval was significantly longer, and QTe/RR and QTa/RR slopes at daytime were significantly steeper in LQT2 than in LQT1 patients. The receiver operating curve analysis revealed that the QTa/RR slope of 0.211 at the entire 24-hour Holter was the best cutoff value for differential diagnosis between LQT1 and LQT2 (sensitivity: 80.0%, specificity: 75.0%, and area under curve: 0.804 [95%CI = 0.68–0.93]).

Conclusion

The continuous 24-hour QT/RR analysis using the Holter monitoring may be useful to predict the genotype of congenital LQTS, particularly for LQT1 and LQT2.

     

Higher FT4 level within the normal range predicts the outcome of cryoballoon ablation in paroxysmal atrial fibrillation patients without structural heart disease

Background

Accumulated evidence has indicated that a high-normal FT4 level is an independent risk factor for the clinical progression of AF. However, the association between elevated FT4 concentration within the normal range and AF recurrence after cryoballoon ablation in China is unknown.

Methods

This retrospective and observational study included 453 AF patients who underwent cryoballoon ablation from January 2016 to August 2018. Patients were classified into quartiles based on preprocedural serum FT4 concentration. The clinical characteristics of the patients and the long-term rate of AF recurrence after ablation were assessed.

Results

After a mean follow-up period of 17.4 ± 9.0 months, 91 (20.1%) patients suffered from AF recurrence. The AF recurrence rate by FT4 quartile was 17.7%, 19.0%, 21.4%, and 22.3% for participants with FT4 in quartile 1, 2, 3, and 4, respectively (p < .001). On multivariate Cox regression, FT4 concentration (HR: 1.187, 95% CI: 1.093–1.290, p < .001) and left atrial diameter (HR: 1.052, 95% CI: 1.014–1.092, p = .007) were significant predictors of AF recurrence. When stratifying for AF type, the rate of postoperative recurrence was independently increased as FT4 concentration increased in paroxysmal AF, but not in persistent AF (p < .001 in paroxysmal AF and p = .977 in persistent AF).

Conclusion

Higher FT4 level within the normal range predicted the outcome of cryoballoon ablation in Chinese paroxysmal AF patients without structural heart disease.

     

Clinical utility of 12-lead electrocardiogram in evaluating heart disease in patients with muscular dystrophy: Assessment of left ventricular hypertrophy,conduction disease,and cardiomyopathy

Introduction

Heart disease remains a leading cause of mortality in patients with muscular dystrophy (MD), and cardiac assessment by standard imaging modalities is challenging due to the prominence of physical limitations.

Methods

In this prospective cohort study of 169 MD patients and 34 negative control patients, we demonstrate the clinical utility of a 12-lead electrocardiogram (ECG) as an effective modality for the assessment of cardiac status in patients with MD. We assessed the utility of conventional criteria for electrocardiogram-indicated left ventricular hypertrophy (ECG-LVH) as well as ECG morphologies.

Results

Cornell voltage, Cornell voltage-duration, Sokolow–Lyon voltage, and Romhilt-Estes point score criteria demonstrated low sensitivity and minimal positive predictive value for ECG-LVH when compared with cardiac imaging. Patients with LBBB had a high probability of a cardiomyopathy (relative risk [RR], 2.75; 95% confidence interval [CI], 2.14–3.53; p < .001), and patients with QRS fragmentation (fQRS) had a high probability of a cardiomyopathy (RR, 1.76; 95% CI, 1.20–2.59; p = .004), requiring cardiac medication and device intervention. We found that an R/S ratio >1 in V1 and V2 is highly specific (specificity, 0.89; negative predictive value [NPV], 0.89 and specificity, 0.82; NPV, 0.89, respectively) for patients with dystrophinopathies compared with other types of MD.

Conclusion

The identification of LBBB and fQRS was linked to cardiomyopathy in patients with MD, while ECG-LVH was of limited utility. Importantly, these findings can be applied to effectively screen a broad cohort of MD patients for structural heart disease and prompt further evaluation and therapeutic intervention.