Temporal Patterns in Youth Suicide Deaths Reported in the National Violent Death Reporting System.

PURPOSE: Suicide is a leading cause of death in children and adolescents. Prevention efforts may benefit from examining temporal patterns and precipitating circumstances of youth suicide deaths. The purpose of this study was to investigate if there are distinct temporal patterns of suicide death for youth. METHODS: We examined the distributions of suicide deaths across months of the year and days of the week in youth ages 10-18 using data from the National Violent Death Reporting System. RESULTS: We found that youth suicides peaked during March, April, and October on Monday, Tuesday, and Wednesday. When disaggregated by separate years of age, we discovered unique patterns in 18-year-olds and 10-year-olds. Suicides peaked during July for 18-year-olds and on Saturday for 10-year-olds. DISCUSSION: These findings suggest a need to examine temporal patterns by separate years of age, as grouping ages together may mask unique trends.

Pathogenic NR2F1 variants cause a developmental ocular phenotype recapitulated in a mutant mouse model.

Pathogenic NR2F1 variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch-Boonstra-Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic NR2F1 variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously. The visual impairment became apparent in early childhood with small and/or tilted hypoplastic optic nerves observed in 10 cases. High-resolution optical coherence tomography imaging confirmed significant loss of retinal ganglion cells with thinning of the ganglion cell layer, consistent with electrophysiological evidence of retinal ganglion cells dysfunction. Interestingly, for those individuals with available longitudinal ophthalmological data, there was no significant deterioration in visual function during the period of follow-up. Diffusion tensor imaging tractography studies showed defective connections and disorganization of the extracortical visual pathways. To further investigate how pathogenic NR2F1 variants impact on retinal and optic nerve development, we took advantage of an Nr2f1 mutant mouse disease model. Abnormal retinogenesis in early stages of development was observed in Nr2f1 mutant mice with decreased retinal ganglion cell density and disruption of retinal ganglion cell axonal guidance from the neural retina into the optic stalk, accounting for the development of optic nerve hypoplasia. The mutant mice showed significantly reduced visual acuity based on electrophysiological parameters with marked conduction delay and decreased amplitude of the recordings in the superficial layers of the visual cortex. The clinical observations in our study cohort, supported by the mouse data, suggest an early neurodevelopmental origin for the retinal and optic nerve head defects caused by NR2F1 pathogenic variants, resulting in congenital vision loss that seems to be non-progressive. We propose NR2F1 as a major gene that orchestrates early retinal and optic nerve head development, playing a key role in the maturation of the visual system.

How the history of American Psychological Association Division 16 can shape the future of school psychology: Demonstrating organizational transformation.

Over the past 75 years, the history of Division 16 (School Psychology) has been integral to the science and practice of school psychology. As a constituent body of the American Psychological Association (APA), the division has advocated for role definitions and professional boundaries within APA and has represented the specialty of school psychology within the larger community of psychology. Since the convening of school psychology's Thayer Conference in 1955, the division has remained steadfastly committed to promoting the well-being of children. Toward this end, Division 16 has negotiated entry level debates between APA and the broad specialty of school psychology, sustained partnerships within and among APA and other organizations representing school mental health, elevated the place of technology in the profession of school psychology, and promoted the central importance of cultural competence and diversity within the discipline. The past contributions of Division 16 shape the future of the profession and the division in ways that are consistent with and add to Conoley, Power, and Gutkin's (2020) recommendations for strengthening school psychology's contributions to psychological health promotion and risk reduction in schools. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Spatial QRS-T Angle and Cognitive Decline in Older Subjects.

BACKGROUND: An abnormally wide spatial QRS-T angle on an ECG is a marker of heterogeneity in electrical activity of cardiac ventricles and is linked with cardiovascular events. Growing evidence suggests that cardiac dysfunction might signal future cognitive decline. OBJECTIVE: In this study, we investigated whether spatial QRS-T angle associates with future cognitive decline in older subjects at high cardiovascular risk. METHODS: We included 4,172 men and women (mean age 75.2±3.3 years) free of cardiac arrhythmias from the PROSPER cohort. Spatial QRS-T angle was calculated from baseline 12-lead ECGs using a matrix transformation method. Cognitive function was assessed using 4 neuropsychological tests including Stroop test, letter-digit coding test, immediate and delayed picture word learning tests. Cognitive function was assessed at baseline and repeatedly during a mean follow-up time of 3.2 years. Using linear mixed models, we calculated the annual changes of cognitive scores in sex-specific thirds of spatial QRS-T angle. RESULTS: Participants with wider spatial QRS-T angle had a steeper decline in letter-digit coding test (ß= -0.0106, p = 0.004), immediate picture-word learning test (ß= -0.0049, p = 0.001), and delayed picture-word learning test (ß= -0.0055, p = 0.013). All associations were independent of arrhythmias, cardiovascular risk factors, comorbidities, medication use, cardiovascular events, and other ECG abnormalities including QRS duration, QTc interval, T wave abnormalities, and left ventricular hypertrophy. CONCLUSION: Abnormal cardiac electrical activity characterized by wide spatial QRS-T angle associates with accelerated cognitive decline independent of conventional cardiovascular factors. These findings suggest a link between a non-traditional ECG measure of pre-clinical cardiac pathology and future cognitive decline.

Comparison of automated interval measurements by widely used algorithms in digital electrocardiographs.

BACKGROUND: Automated measurements of electrocardiographic (ECG) intervals by current-generation digital electrocardiographs are critical to computer-based ECG diagnostic statements, to serial comparison of ECGs, and to epidemiological studies of ECG findings in populations. A previous study demonstrated generally small but often significant systematic differences among 4 algorithms widely used for automated ECG in the United States and that measurement differences could be related to the degree of abnormality of the underlying tracing. Since that publication, some algorithms have been adjusted, whereas other large manufacturers of automated ECGs have asked to participate in an extension of this comparison. METHODS: Seven widely used automated algorithms for computer-based interpretation participated in this blinded study of 800 digitized ECGs provided by the Cardiac Safety Research Consortium. All tracings were different from the study of 4 algorithms reported in 2014, and the selected population was heavily weighted toward groups with known effects on the QT interval: included were 200 normal subjects, 200 normal subjects receiving moxifloxacin as part of an active control arm of thorough QT studies, 200 subjects with genetically proved long QT syndrome type 1 (LQT1), and 200 subjects with genetically proved long QT syndrome Type 2 (LQT2). RESULTS: For the entire population of 800 subjects, pairwise differences between algorithms for each mean interval value were clinically small, even where statistically significant, ranging from 0.2 to 3.6milliseconds for the PR interval, 0.1 to 8.1milliseconds for QRS duration, and 0.1 to 9.3milliseconds for QT interval. The mean value of all paired differences among algorithms was higher in the long QT groups than in normals for both QRS duration and QT intervals. Differences in mean QRS duration ranged from 0.2 to 13.3milliseconds in the LQT1 subjects and from 0.2 to 11.0milliseconds in the LQT2 subjects. Differences in measured QT duration (not corrected for heart rate) ranged from 0.2 to 10.5milliseconds in the LQT1 subjects and from 0.9 to 12.8milliseconds in the LQT2 subjects. CONCLUSIONS: Among current-generation computer-based electrocardiographs, clinically small but statistically significant differences exist between ECG interval measurements by individual algorithms. Measurement differences between algorithms for QRS duration and for QT interval are larger in long QT interval subjects than in normal subjects. Comparisons of population study norms should be aware of small systematic differences in interval measurements due to different algorithm methodologies, within-individual interval measurement comparisons should use comparable methods, and further attempts to harmonize interval measurement methodologies are warranted.

Relationship of executive functioning deficits to N-acetyl aspartate (NAA) and gamma-aminobutyric acid (GABA) in youth with bipolar disorder.

BACKGROUND: Although cognitive deficits in bipolar disorder (BD) have been repeatedly observed, our understanding of these impairments at a mechanistic level remains limited. Few studies that investigated cognitive impairments in bipolar illness have examined the association with brain biochemistry. This pilot study utilized proton magnetic resonance spectroscopy (1H-MRS) to evaluate the relationship between neurocognitive performance and brain metabolites in youth with BD. METHODS: Thirty participants, twenty depressed BD participants and ten healthy comparison participants, ages 13-21, completed mood and executive function measures. 1H-MRS data were also acquired from the anterior cingulate cortex (ACC) using two-dimensional (2D) J-resolved 1H-MRS sequence. Proton metabolites including N-acetyl aspartate (NAA) and gamma-aminobutyric acid (GABA) were quantified for both groups. RESULTS: Participants with BD performed significantly lower on executive functioning measures than comparison participants. There were significant positive correlations between Wisconsin Card Sorting Test (WCST) performance and NAA (p < .001) and GABA (p < .01) in the ACC in bipolar youth, such that as WCST performance increased, both NAA and GABA levels increased. LIMITATIONS: Small sample size and lack of control for medications. CONCLUSIONS: These findings build on previous observations of biochemical alterations associated with BD and indicate that executive functioning deficits in bipolar youth are correlated with NAA and GABA. These results suggest that cognitive deficits occur early in the course of illness and may reflect risk factors associated with altered neurochemistry. Further investigation of the relationship between brain metabolites and cognition in BD may lead to important information for developing novel, targeted interventions.

Correction: Antidepressant and Neurocognitive Effects of Isoflurane Anesthesia versus Electroconvulsive Therapy in Refractory Depression.

[This corrects the article DOI: 10.1371/journal.pone.0069809.].

Left Ventricular Hypertrophy and Cognitive Decline in Old Age.

BACKGROUND: Patients with advanced heart failure run a greater risk of dementia. Whether early cardiac structural changes also associate with cognitive decline is yet to be determined. OBJECTIVE: We tested whether left ventricular hypertrophy (LVH) derived from electrocardiogram associates with cognitive decline in older subjects at risk of cardiovascular disease. METHODS: We included 4,233 participants (mean age 75.2 years, 47.8% male) from PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). LVH was assessed from baseline electrocardiograms by measuring the Sokolow-Lyon index. Higher levels of Sokolow-Lyon index indicate higher degrees of LVH. Cognitive domains involving selective attention, processing speed, and immediate and delayed memory were measured at baseline and repeated during a mean follow-up of 3.2 years. RESULTS: At baseline, LVH was not associated with worse cognitive function. During follow-up, participants with higher levels of LVH had a steeper decline in cognitive function including in selective attention (p = 0.009), processing speed (p = 0.010), immediate memory (p < 0.001), and delayed memory (p = 0.002). These associations were independent of cardiovascular risk factors, co-morbidities, and medications. CONCLUSION: LVH assessed by electrocardiogram associates with steeper decline in cognitive function of older subjects independent of cardiovascular risk factors and co-morbidities. This study provides further evidence on the link between subclinical cardiac structural changes and cognitive decline in older subjects.

Comparison of the spatial QRS-T angle derived from digital ECGs recorded using conventional electrode placement with that derived from Mason-Likar electrode position.

BACKGROUND: The spatial QRS-T angle is ideally derived from orthogonal leads. We compared the spatial QRS-T angle derived from orthogonal leads reconstructed from digital 12-lead ECGs and from digital Holter ECGs recorded with the Mason-Likar (M-L) electrode positions. METHODS AND RESULTS: Orthogonal leads were constructed by the inverse Dower method and used to calculate spatial QRS-T angle by (1) a vector method and (2) a net amplitude method, in 100 volunteers. Spatial QRS-T angles from standard and M-L ECGs differed significantly (57°±18° vs 48°±20° respectively using net amplitude method and 53°±28° vs 48°±23° respectively by vector method; p<0.001). Difference in amplitudes in leads V4-V6 was also observed between Holter and standard ECGs, probably due to a difference in electrical potential at the central terminal. CONCLUSION: Mean spatial QRS-T angles derived from standard and M-L lead systems differed by 5°-9°. Though statistically significant, these differences may not be clinically significant.

10-Second heart rate variability and cognitive function in old age.

OBJECTIVE: To investigate the cross-sectional and longitudinal associations of 10-second heart rate variability (HRV) with various domains of cognitive function in older participants at risk of cardiovascular disease. METHODS: We studied 3,583 participants, mean age of 75.0 years, who were enrolled in the Prospective Study of Pravastatin in the Elderly at Risk. From baseline 10-second ECGs, standard deviation of normal-to-normal intervals was calculated as the index of HRV. Four cognitive domains were assessed at baseline and repeated during a mean follow-up period of 3.2 years. RESULTS: Lower HRV at baseline was associated with worse performance in reaction time (mean difference between low third vs high third of HRV = 1.96 seconds, 95% confidence interval [CI] 0.20 to 3.71) and processing speed (-0.57 digits coded, 95% CI -1.09 to -0.05). During follow-up, participants with lower HRV had a steeper decline in processing speed (mean annual change between low third vs high third of HRV = -0.16 digits coded, 95% CI -0.28 to -0.04). There was no difference in annual changes of reaction time or immediate and delayed memory among HRV thirds during follow-up. All these associations remained unchanged after adjustment for medications, cardiovascular risk factors, and comorbidities. CONCLUSIONS: Participants with lower 10-second HRV have worse performance in reaction time and processing speed and experience steeper decline in their processing speed, independent of medications, cardiovascular risk factors, and comorbidities.

Novel electrocardiographic criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

AIMS: In order to improve the electrocardiographic (ECG) diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC), we evaluated novel quantitative parameters of the QRS complex and the value of bipolar chest leads (CF leads) computed from the standard 12 leads. METHODS AND RESULTS: We analysed digital 12-lead ECGs in 44 patients with ARVC, 276 healthy subjects including 44 age and sex-matched with the patients and 36 genotyped members of ARVC families. The length and area of the terminal S wave in V1 to V3 were measured automatically using a common for all 12 leads QRS end. T wave negativity was assessed in V1 to V6 and in the bipolar CF leads computed from the standard 12 leads. The length and area of the terminal S wave were significantly shorter, whereas the S wave duration was significantly longer in ARVC patients compared with matched controls. Among members of ARVC families, those with mutations (n = 15) had shorter QRS length in V2 and V3 and smaller QRS area in lead V2 compared with those without mutations (n = 20). In ARVC patients, the CF leads were diagnostically superior to the standard unipolar precordial leads. Terminal S wave duration in V1 >48 ms or major T wave negativity in CF leads separated ARVC patients from matched controls with 90% sensitivity and 86% specificity. CONCLUSION: The terminal S wave length and area in the right precordial leads are diagnostically useful and suitable for automatic analysis in ARVC. The CF leads are diagnostically superior to the unipolar precordial leads.

Resting heart rate, heart rate variability and functional decline in old age.

BACKGROUND: Heart rate and heart rate variability, markers of cardiac autonomic function, have been linked with cardiovascular disease. We investigated whether heart rate and heart rate variability are associated with functional status in older adults, independent of cardiovascular disease. METHODS: We obtained data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). A total of 5042 participants were included in the present study, and mean follow-up was 3.2 years. Heart rate and heart rate variability were derived from baseline 10-second electrocardiograms. Heart rate variability was defined as the standard deviation of normal-to-normal RR intervals (SDNN). Functional status in basic (ADL) and instrumental (IADL) activities of daily living was measured using Barthel and Lawton scales, at baseline and during follow-up. RESULTS: The mean age of the study population was 75.3 years. At baseline, higher heart rate was associated with worse ADL and IADL, and lower SDNN was related to worse IADL (all p values < 0.05). Participants in the highest tertile of heart rate (range 71-117 beats/min) had a 1.79-fold (95% confidence interval [CI] 1.45-2.22) and 1.35-fold (95% CI 1.12-1.63) higher risk of decline in ADL and IADL, respectively (p for trend < 0.001 and 0.001, respectively). Participants in the lowest tertile of SDNN (range 1.70-13.30 ms) had 1.21-fold (95% CI 1.00-1.46) and 1.25-fold (95% CI 1.05-1.48) higher risk of decline in ADL and IADL, respectively (both p for trends < 0.05). All associations were independent of sex, medications, cardiovascular risk factors and comorbidities. INTERPRETATION: Higher resting heart rate and lower heart rate variability were associated with worse functional status and with higher risk of future functional decline in older adults, independent of cardiovascular disease. This study provides insight into the role of cardiac autonomic function in the development of functional decline.

Normal limits of the electrocardiogram in Indians.

AIMS: The objective of the study was to develop normal limits of the ECG in an apparently healthy population of South Asians living in India. METHODS: Three centres contributed to recording 12 lead ECGs on identical digital electrocardiographs. Apparently healthy volunteers were recruited and ECGs were first transferred to a local database and then to Glasgow where all ECGs were analysed by the same University of Glasgow ECG Interpretation Program. RESULTS: A total of 963 individuals were recruited into the study (30.4% female) with an age range of 18-83 years. QRS duration was longer in males than females, QT interval was longer in females than males, and QRS voltages in general were higher in males than females and in younger compared to older individuals. CONCLUSION: Findings in general paralleled those in other populations and suggested that criteria for a white Caucasian population could be applied to a South Asian Indian population.

Outpatient management of low-risk patients with upper gastrointestinal bleeding: can we safely extend the Glasgow Blatchford Score in clinical practice?

BACKGROUND AND AIM: The Glasgow Blatchford Score (GBS) is a validated prognostic score for patients presenting with upper gastrointestinal (GI) bleeding (UGIB). The score predicts the need for therapeutic intervention or death, and studies have suggested that outpatient management is safe for patients with a GBS of zero. Our aim was to assess whether we could safely extend the threshold for outpatient management to patients with GBS≤1. METHODS: Following assessment of our historical data, our UGIB protocol was changed to recommend outpatient management for patients with a GBS≤1, unless required for other reasons. Data on all patients presenting with UGIB over the following 12 months were prospectively recorded, including GBS and clinical Rockall scores. Adverse outcomes were defined by a 30-day combined endpoint of death, endotherapy, interventional radiology, surgery or transfusion. Negative predictive value (NPV) of GBS≤1 for adverse outcomes in UGIB was calculated. RESULTS: A total of 514 patients presented with UGIB in the 12 month study period. Of the patients, 183 (35.6%) had GBS≤1 (111, GBS=0; 72, GBS=1). Of these, 88 (48.1%) were managed as outpatients, and none had an adverse outcome. Of the 95 (51.9%) patients with GBS≤1 managed as inpatients, 80 (84.2%) had comorbidities requiring inpatient care. Within this admitted group with GBS≤1, one patient required transfusion and one died from a nongastrointestinal malignancy. GBS≤1 had an NPV of 99.45% (95% confidence interval 95.53-99.97%) in predicting adverse outcomes within 30 days. CONCLUSION: GBS≤1 has a high NPV for adverse outcomes in UGIB. This suggests outpatient management of patients with UGIB and that GBS≤1 is safe in our population.

Comparison of automated measurements of electrocardiographic intervals and durations by computer-based algorithms of digital electrocardiographs.

BACKGROUND AND PURPOSE: Automated measurements of electrocardiographic (ECG) intervals are widely used by clinicians for individual patient diagnosis and by investigators in population studies. We examined whether clinically significant systematic differences exist in ECG intervals measured by current generation digital electrocardiographs from different manufacturers and whether differences, if present, are dependent on the degree of abnormality of the selected ECGs. METHODS: Measurements of RR interval, PR interval, QRS duration, and QT interval were made blindly by 4 major manufacturers of digital electrocardiographs used in the United States from 600 XML files of ECG tracings stored in the US FDA ECG warehouse and released for the purpose of this study by the Cardiac Safety Research Consortium. Included were 3 groups based on expected QT interval and degree of repolarization abnormality, comprising 200 ECGs each from (1) placebo or baseline study period in normal subjects during thorough QT studies, (2) peak moxifloxacin effect in otherwise normal subjects during thorough QT studies, and (3) patients with genotyped variants of congenital long QT syndrome (LQTS). RESULTS: Differences of means between manufacturers were generally small in the normal and moxifloxacin subjects, but in the LQTS patients, differences of means ranged from 2.0 to 14.0 ms for QRS duration and from 0.8 to 18.1 ms for the QT interval. Mean absolute differences between algorithms were similar for QRS duration and QT intervals in the normal and in the moxifloxacin subjects (mean ≤6 ms) but were significantly larger in patients with LQTS. CONCLUSIONS: Small but statistically significant group differences in mean interval and duration measurements and means of individual absolute differences exist among automated algorithms of widely used, current generation digital electrocardiographs. Measurement differences, including QRS duration and the QT interval, are greatest for the most abnormal ECGs.

Automatic detection of end QRS notching or slurring.

The purpose of this study was to define criteria suited to automated detection of end QRS notching and slurring and to evaluate their accuracy. One hundred resting 12 lead ECGs from young adult men, split randomly into equal training and test sets, were examined independently by two reviewers for the presence of such notching or slurring. Consensus was reached by re-examination. Logic was added to the Glasgow resting ECG program to automate the detection of the phenomenon. After training, the automated detection had a sensitivity (SE) of 92.1% and a specificity (SP) of 96.6%. For the test set, SE was 90.5%, SP 96.5%. Two populations of healthy subjects--one Caucasian, one Nigerian--were analysed using the automated method. The prevalence of notching/slurring with peak/onset amplitude respectively ≥ 0.1 mV in two contiguous inferolateral leads was 23% and 29% respectively. In conclusion, the detection of end QRS notching or slurring can be automated with a high degree of accuracy.

J wave patterns--morphology, prevalence and nomenclature.

The recent resurgence of interest in early repolarization has demonstrated a variation in the definition of the term and a consequent variation in the prevalence of the pattern in different studies. This can vary from 35% in males and 21.5% in females if ST elevation is not considered part of the definition, to 3.3% and 0.5% in females with the inclusion of ST elevation. In contrast, the prevalence of the Brugada Syndrome is in the order of 0.1%-0.2% in Japan for example and has been found to be significantly lower in Denmark. Standardisation of measurement definitions, particularly for early repolarisation, is required.

Antidepressant and neurocognitive effects of isoflurane anesthesia versus electroconvulsive therapy in refractory depression.

BACKGROUND: Many patients have serious depression that is nonresponsive to medications, but refuse electroconvulsive therapy (ECT). Early research suggested that isoflurane anesthesia may be an effective alternative to ECT. Subsequent studies altered drug, dose or number of treatments, and failed to replicate this success, halting research on isoflurane's antidepressant effects for a decade. Our aim was to re-examine whether isoflurane has antidepressant effects comparable to ECT, with less adverse effects on cognition. METHOD: Patients with medication-refractory depression received an average of 10 treatments of bifrontal ECT (n = 20) or isoflurane (n = 8) over 3 weeks. Depression severity (Hamilton Rating Scale for Depression-24) and neurocognitive responses (anterograde and retrograde memory, processing speed and verbal fluency) were assessed at Pretreatment, Post all treatments and 4-week Follow-up. RESULTS: Both treatments produced significant reductions in depression scores at Post-treatment and 4-week Follow-up; however, ECT had modestly better antidepressant effect at follow-up in severity-matched patients. Immediately Post-treatment, ECT (but not isoflurane) patients showed declines in memory, fluency, and processing speed. At Follow-up, only autobiographical memory remained below Pretreatment level for ECT patients, but isoflurane patients had greater test-retest neurocognitive score improvement. CONCLUSIONS: Our data reconfirm that isoflurane has an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial.