Disruption of the Atrophy-based Functional Network in Multiple Sclerosis Is Associated with Clinical Disability: Validation of a Meta-Analytic Model in Resting-State Functional MRI.

Background In multiple sclerosis (MS), gray matter (GM) atrophy exhibits a specific pattern, which correlates strongly with clinical disability. However, the mechanism of regional specificity in GM atrophy remains largely unknown. Recently, the network degeneration hypothesis (NDH) was quantitatively defined (using coordinate-based meta-analysis) as the atrophy-based functional network (AFN) model, which posits that localized GM atrophy in MS is mediated by functional networks. Purpose To test the NDH in MS in a data-driven manner using the AFN model to direct analyses in an independent test sample. Materials and Methods Model fit testing was conducted with structural equation modeling, which is based on the computation of semipartial correlations. Model verification was performed in coordinate-based data of healthy control participants from the BrainMap database (https://www.brainmap.org). Model validation was conducted in prospectively acquired resting-state functional MRI in participants with relapsing-remitting MS who were recruited between September 2018 and January 2019. Correlation analyses of model fit indices and volumetric measures with Expanded Disability Status Scale (EDSS) scores and disease duration were performed. Results Model verification of healthy control participants included 80 194 coordinates from 9035 experiments. Model verification in healthy control data resulted in excellent model fit (root mean square error of approximation, 0.037; 90% CI: 0.036, 0.039). Twenty participants (mean age, 36 years ± 9 [standard deviation]; 12 women) with relapsing-remitting MS were evaluated. Model validation in resting-state functional MRI in participants with MS resulted in deviation from optimal model fit (root mean square error of approximation, 0.071; 90% CI: 0.070, 0.072), which correlated with EDSS scores (r = 0.68; P = .002). Conclusion The atrophy-based functional network model predicts functional network disruption in multiple sclerosis (MS), thereby supporting the network degeneration hypothesis. On resting-state functional MRI scans, reduced functional network integrity in participants with MS had a strong positive correlation with clinical disability. © RSNA, 2021 Online supplemental material is available for this article.

Using the Schmahmann Syndrome Scale to Assess Cognitive Impairment in Young Adults with Metabolic Syndrome: a Hypothesis-Generating Report.

The posterior cerebellum is the most significantly compromised brain structure in individuals with metabolic syndrome (MetS) (Hum Brain Mapp 40(12):3575-3588, 2019). In light of this, we hypothesized that cognitive decline reported in patients with MetS is likely related to posterior cerebellar atrophy. In this study, we performed a post hoc analyses using T1-weighted magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) in the form of voxel-wise tract-based spatial statistics (TBSS), biometric, and psychometric data from young participants with (n = 52, aged 18-35 years) and without MetS (n = 52, aged 18-35 years). To test the predictive value of components of the Schmahmann syndrome scale (SSS), also known as the cerebellar cognitive affective syndrome scale, we used structural equation modeling to adapt available psychometric scores in our participant sample to the SSS and compare them to the composite score of all psychometric data available. Our key findings point to a statistically significant correlation between TBSS fractional anisotropy (FA) values from DTI and adapted SSS psychometric scores in individuals with MetS (r2 = .139, 95% CI = 0.009, .345). This suggests that the SSS could be applied to assess cognitive and likely neuroanatomical effects associated with MetS. We strongly suggest that future work aimed at investigating the neurocognitive effects of MetS and related comorbidities (i.e., dyslipidemia, diabetes, obesity) would benefit from implementing and further exploring the validity of the SSS in this patient population.

Why Temporal Persistence of Biometric Features, as Assessed by the Intraclass Correlation Coefficient, Is So Valuable for Classification Performance.

It is generally accepted that relatively more permanent (i.e., more temporally persistent) traits are more valuable for biometric performance than less permanent traits. Although this finding is intuitive, there is no current work identifying exactly where in the biometric analysis temporal persistence makes a difference. In this paper, we answer this question. In a recent report, we introduced the intraclass correlation coefficient (ICC) as an index of temporal persistence for such features. Here, we present a novel approach using synthetic features to study which aspects of a biometric identification study are influenced by the temporal persistence of features. What we show is that using more temporally persistent features produces effects on the similarity score distributions that explain why this quality is so key to biometric performance. The results identified with the synthetic data are largely reinforced by an analysis of two datasets, one based on eye-movements and one based on gait. There was one difference between the synthetic and real data, related to the intercorrelation of features in real data. Removing these intercorrelations for real datasets with a decorrelation step produced results which were very similar to that obtained with synthetic features.

A neural signature of metabolic syndrome.

That metabolic syndrome (MetS) is associated with age-related cognitive decline is well established. The neurobiological changes underlying these cognitive deficits, however, are not well understood. The goal of this study was to determine whether MetS is associated with regional differences in gray-matter volume (GMV) using a cross-sectional, between-group contrast design in a large, ethnically homogenous sample. T1-weighted MRIs were sampled from the genetics of brain structure (GOBS) data archive for 208 Mexican-American participants: 104 participants met or exceeded standard criteria for MetS and 104 participants were age- and sex-matched metabolically healthy controls. Participants ranged in age from 18 to 74 years (37.3 ± 13.2 years, 56.7% female). Images were analyzed in a whole-brain, voxel-wise manner using voxel-based morphometry (VBM). Three contrast analyses were performed, a whole sample analysis of all 208 participants, and two post hoc half-sample analyses split by age along the median (35.5 years). Significant associations between MetS and decreased GMV were observed in multiple, spatially discrete brain regions including the posterior cerebellum, brainstem, orbitofrontal cortex, bilateral caudate nuclei, right parahippocampus, right amygdala, right insula, lingual gyrus, and right superior temporal gyrus. Age, as shown in the post hoc analyses, was demonstrated to be a significant covariate. A further functional interpretation of the structures exhibiting lower GMV in MetS reflected a significant involvement in reward perception, emotional valence, and reasoning. Additional studies are needed to characterize the influence of MetS's individual clinical components on brain structure and to explore the bidirectional association between GMV and MetS.

A novel method for expediting the development of patient-reported outcome measures and an evaluation across several populations.

Item response theory (IRT) models provide an appropriate alternative to the classical ordinal confirmatory factor analysis (CFA) during the development of patient-reported outcome measures (PROMs). Current literature has identified the assessment of IRT model fit as both challenging and underdeveloped (Sinharay & Johnson, 2003; Sinharay, Johnson, & Stern, 2006). This study evaluates the performance of Ordinal Bayesian Instrument Development (OBID), a Bayesian IRT model with a probit link function approach, through applications in two breast cancer-related instrument development studies. The primary focus is to investigate an appropriate method for comparing Bayesian IRT models in PROMs development. An exact Bayesian leave-one-out cross-validation (LOO-CV) approach (Vehtari & Lampinen, 2002) is implemented to assess prior selection for the item discrimination parameter in the IRT model and subject content experts' bias (in a statistical sense and not to be confused with psychometric bias as in differential item functioning) toward the estimation of item-to-domain correlations. Results support the utilization of content subject experts' information in establishing evidence for construct validity when sample size is small. However, the incorporation of subject experts' content information in the OBID approach can be sensitive to the level of expertise of the recruited experts. More stringent efforts need to be invested in the appropriate selection of subject experts to efficiently use the OBID approach and reduce potential bias during PROMs development.

A novel method for expediting the development of patient-reported outcome measures and an evaluation of its performance via simulation.

BACKGROUND: Developing valid and reliable patient-reported outcome measures (PROMs) is a critical step in promoting patient-centered health care, a national priority in the U.S. Small populations or rare diseases often pose difficulties in developing PROMs using traditional methods due to small samples. METHODS: To overcome the small sample size challenge while maintaining psychometric soundness, we propose an innovative Ordinal Bayesian Instrument Development (OBID) method that seamlessly integrates expert and participant data in a Bayesian item response theory (IRT) with a probit link model framework. Prior distributions obtained from expert data are imposed on the IRT model parameters and are updated with participants' data. The efficiency of OBID is evaluated by comparing its performance to classical instrument development performance using actual and simulation data. RESULTS AND DISCUSSION : The overall performance of OBID (i.e., more reliable parameter estimates, smaller mean squared errors (MSEs) and higher predictive validity) is superior to that of classical approaches when the sample size is small (e.g. less than 100 subjects). Although OBID may exhibit larger bias, it reduces the MSEs by decreasing variances. Results also closely align with recommendations in the current literature that six subject experts will be sufficient for establishing content validity evidence. However, in the presence of highly biased experts, three experts will be adequate. CONCLUSIONS: This study successfully demonstrated that the OBID approach is more efficient than the classical approach when the sample size is small. OBID promises an efficient and reliable method for researchers and clinicians in future PROMs development for small populations or rare diseases.

Response to Sijtsma and van der Ark (2015): "Conceptions of reliability revisited and practical recommendations".

Sijtsma and van der Ark present a broad set of models and methods for reliability estimation, and their discussion of similarities and differences provides clear information for nurse researchers to move forward in their instrument development projects. In particular, we applaud the authors' clear exposition of the factor analytic model and its utility for providing a framework for unifying reliability and validity. However, we do not want to be constrained only to the point estimates. We also need to ascertain the uncertainty in the point estimate-usually in the form of a 95% confidence interval-or, as the Bayesians refer to, a credible interval. Another issue not discussed by Sijtsma and van der Ark is conditional standard errors of measurement along the score scale measuring latent traits or true scores. In our response, practical tools for estimating intervals and a brief discussion of conditional standard errors of measurement are presented.

Is the Polar F6 heart rate monitor less accurate during aerobic bench stepping because of arm movements?

Because of the well-documented linear relationship between heart rate and oxygen consumption (VO2), heart rate is commonly used to estimate energy expenditure during exercise. However, previous research suggests that heart rate increases without a concomitant rise in VO2 when arm movements are added to exercise. If so, this could impact the accuracy of heart rate monitors in estimating energy expenditure during combined arm and leg exercise. This study compared the cardiorespiratory responses to a bench step aerobics routine performed with and without arm movements and evaluated whether the accuracy of the Polar F6 heart rate monitor in predicting energy expenditure was impacted by the inclusion of arm movements. Thirty-two women performed the same routine with and without arm movements while stepping up and down off of a 15.24-cm bench at a cadence of 128 b·min-1. Heart rate and VO2 increased, whereas oxygen pulse (VO2·heart rate-1) decreased when arm movements were added (p < 0.001). However, the differences between the energy expenditure estimated by the Polar F6 heart rate monitor and the energy expenditure measured by indirect calorimetry were similar during the same aerobic bench stepping routine performed with and without arms (Δ∼2 kCal·min-1, p ≥ 0.05). Results confirm that arm movements during aerobic bench stepping elicit a disproportionate rise in heart rate relative to V[Combining Dot Above]O2. However, results do not support that these movements increase the prediction error in energy expenditure, as the Polar F6 heart rate monitor over predicted energy expenditure when arm movements were involved and when they were not involved.

Structural equation modeling of treatment-related changes in neural connectivity for youth with PTSD.

BACKGROUND: Previous studies suggest that improvement in symptoms of posttraumatic stress disorder (PTSD) is accompanied by changes in neural connectivity, however, few studies have investigated directional (effective) connectivity. The current study assesses treatment-related changes in effective connectivity in youth with PTSD undergoing Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). METHODS: Functional MRI scans before and after 16 weeks of TF-CBT for 20 youth with PTSD, or the same time interval for 20 healthy controls (HC) were included in the analysis. Structural equation modeling was used to model group differences in directional connectivity at baseline, and changes in connectivity from pre- to post-treatment. RESULTS: At baseline, the PTSD group, relative to the HC group, had significantly greater connectivity in the path from dorsal cingulate to anterior cingulate and from dorsal cingulate to posterior cingulate corticies. From pre- to post-treatment, connectivity in these paths decreased significantly in the PTSD group, as did connectivity from right hippocampus to left superior temporal gyrus. Connectivity from the left amygdala to the lateral orbital frontal cortex was significantly lower in PTSD vs HC at baseline, but did not change from pre- to post-treatment. CONCLUSION: Although based on a small sample, these results converge with previous studies in suggesting a central role for the dorsal cingulate cortex in PTSD symptoms. The direction of this connectivity suggests that the dorsal cingulate is the source of modulation of anterior and posterior cingulate cortex during trauma-focused cognitive behavioral therapy.

Safety and effectiveness of transvenous lead extraction in octogenarians.

INTRODUCTION: As the population ages, the number of elderly patients with implantable cardiac devices referred for transvenous lead extraction will dramatically increase in Western countries. The safety and effectiveness of lead extraction in elderly patients has not been well evaluated. We report the safety and effectiveness of transvenous lead extraction in octogenarians. METHODS AND RESULTS: From January 2005 to January 2011, we reviewed data from consecutive patients ≥ 80 years referred to our institutions for transvenous lead extraction because of cardiac device infection or lead malfunction. Clinical characteristics, procedural features, and periprocedural major and minor complications were compared between octogenarians and younger patients. Out of 849 patients undergoing lead extraction in the participating institutions during the study period, 150 (18%) patients were octogenarians (mean age 84 years; range 80-96; 64% males). A significantly higher percentage of octogenarians presented with chronic renal failure (55% vs 26%; P < 0.001), history of malignancy (22% vs 6%; P < 0.001), and chronic obstructive pulmonary disease (46% vs 19%; P < 0.001). Complete lead extraction rates were similar in the 2 age groups (97% in octogenarians vs 96% in patients <80 years; P = 0.39). Periprocedural death occurred in 2 (1.3%) patients ≥80 years and in 5 (0.72%) patients <80 years (P = 0.45 for comparison). No differences in terms of other periprocedural major and minor complications were found between the 2 age groups. CONCLUSION: Despite presenting with a significantly higher rate of comorbidities, transvenous lead extraction can be performed safely and successfully in octogenarians.

Psychometric properties of the Disability Identity Development Scale: Confirmatory factor and bifactor analyses.

PURPOSE/OBJECTIVE: This work provides comprehensive analyses targeting the factor structure and dimensionality of the Disability Identity Development Scale (DIDS). In Forber-Pratt et al., 2020, disability was defined broadly to include individuals with visible or hidden disabilities across many disability groups (i.e., physical, intellectual, learning, or chronic illness). RESEARCH METHOD/DESIGN: Retained items from previous exploratory factor analysis were administered to a sample of adults with disabilities (n = 1,126) ranging in age from 18-78 years. Confirmatory factor analytics (CFA) including traditional CFA, and bifactor confirmatory analyses were used to examine the dimensionality and structure of the DIDS. RESULTS: Traditional CFA provided lack of evidence in support of the oblique four-factor structure previously reported. Bifactor confirmatory analysis revealed items on the DIDS are consistent with unidimensional, and to a lesser degree multidimensional solutions (i.e., items lacked a level of content diversity to substantiate a complex, reliable multifactor structure). DISCUSSION/CONCLUSION: Analytic results on the DIDS revealed reasonable psychometric properties as a measure of disability identity. Our results support using a sum or total score of disability identity. Results of this work are an important contribution to a growing body of literature supporting, and investigating, disability identity development. Furthermore, the DIDS measure with its resulting composite score of disability identity has the potential to inform clinicians in the field of rehabilitation psychology as well as informing future targeted interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Feasibility, acceptability and costs of nurse-led Alpha-Stim cranial electrostimulation to treat anxiety and depression in university students.

BACKGROUND: Only a relatively low proportion of university students seek help for anxiety and depression disorders, partly because they dislike current drug and psychological treatment options and would prefer home-based care. The aim of this study is to determine the feasibility, acceptability and cost utility of Alpha-Stim cranial electrostimulation (CES) delivered through a nurse led primary care clinic as a daily treatment for anxiety and depression symptoms by the student at home in contrast to usual primary care. METHOD: Feasibility and acceptability of a nurse led clinic offering Alpha-Stim CES in terms of the take up and completion of the six-week course of Alpha-Stim CES. Change in score on the GAD-7 and PHQ-9 as measures of anxiety and depression symptoms at baseline and at 8 weeks following a course of Alpha-Stim CES. Similar evaluation in a non-randomised control group attending a family doctor over the same period. Cost-utility analysis of the nurse led Alpha-Stim CES and family doctor pathways with participants failing to improve following further NICE Guideline clinical care (facilitated self-help and cognitive behaviour therapy). RESULTS: Of 47 students (mean age 22.1, years, 79% female opting for Alpha-Stim CES at the nurse-led clinic 46 (97.9%) completed a 6-week daily course. Forty-seven (47) students comprised a comparison group receiving usual family doctor care. Both Alpha-Stim CES and usual family doctor care were associated with large effect size reductions in GAD-7 and PHQ-9 scores from baseline to 8 weeks. There were no adverse effects and only one participant showed a clinically important deterioration in the Alpha-Stim group. In the cost utility analysis, Alpha-Stim CES was a cheaper option than usual family doctor care under all deterministic or probabilistic assumptions. CONCLUSION: Nurse delivered Alpha-Stim CES may be a feasible, acceptable and cheaper way of providing greater choice and home-based care for some university students seeking help from primary care with new presentations of anxiety and depression.

Metabolic syndrome predictors of brain gray matter volume in an age-stratified community sample of 776 Mexican- American adults: Results from the genetics of brain structure image archive.

Introduction: This project aimed to investigate the association between biometric components of metabolic syndrome (MetS) with gray matter volume (GMV) obtained with magnetic resonance imaging (MRI) from a large cohort of community-based adults (n = 776) subdivided by age and sex and employing brain regions of interest defined previously as the "Neural Signature of MetS" (NS-MetS). Methods: Lipid profiles, biometrics, and regional brain GMV were obtained from the Genetics of Brain Structure (GOBS) image archive. Participants underwent T1-weighted MR imaging. MetS components (waist circumference, fasting plasma glucose, triglycerides, HDL cholesterol, and blood pressure) were defined using the National Cholesterol Education Program Adult Treatment Panel III. Subjects were grouped by age: early adult (18-25 years), young adult (26-45 years), and middle-aged adult (46-65 years). Linear regression modeling was used to investigate associations between MetS components and GMV in five brain regions comprising the NS-MetS: cerebellum, brainstem, orbitofrontal cortex, right insular/limbic cluster and caudate. Results: In both men and women of each age group, waist circumference was the single component most strongly correlated with decreased GMV across all NS-MetS regions. The brain region most strongly correlated to all MetS components was the posterior cerebellum. Conclusion: The posterior cerebellum emerged as the region most significantly associated with MetS individual components, as the only region to show decreased GMV in young adults, and the region with the greatest variance between men and women. We propose that future studies investigating neurological effects of MetS and its comorbidities-namely diabetes and obesity-should consider the NS-MetS and the differential effects of age and sex.

Positioning of left ventricular pacing lead guided by intracardiac echocardiography with vector velocity imaging during cardiac resynchronization therapy procedure.

INTRODUCTION: Intraoperative modality for "real-time" left ventricular (LV) dyssynchrony quantification and optimal resynchronization is not established. This study determined the feasibility, safety, and efficacy of intracardiac echocardiography (ICE), coupled with vector velocity imaging (VVI), to evaluate LV dyssynchrony and to guide LV lead placement at the time of cardiac resynchronization therapy (CRT) implant. METHODS: One hundred and four consecutive heart failure patients undergoing ICE-guided (Group 1, N = 50) or conventional (Group 2, N = 54) CRT implant were included in the study. For Group 1 patients, LV dyssynchrony and resynchronization were evaluated by VVI including visual algorithms and the maximum differences in time-to-peak (MD-TTP) radial strain. Based on the findings, the final LV lead site was determined and optimal resynchronization was achieved. CRT responders were defined using standard criteria 6 months after implantation. RESULTS: Both groups underwent CRT implant with no complications. In Group 1, intraprocedural optimal resynchronization by VVI including visual algorithms and MD-TTP was a predictor discriminating CRT response with a sensitivity of 95% and specificity of 89%. Use of ICE/VVI increased number of and predicted CRT responders (82% in Group 1 vs 63% in Group 2; OR = 2.68, 95% CI 1.08-6.65, P = 0.03). CONCLUSION: ICE can be safely performed during CRT implantation. "Real-time" VVI appears to be helpful in determining the final LV lead position and pacing mode that allow better intraprocedural resynchronization. VVI-optimized acute resynchronization predicts CRT response and this approach is associated with higher number of CRT responders.

Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-site randomized controlled trial with a secondary 6-month open-label phase.

BACKGROUND: Chronic pain is a significant problem for many individuals following spinal cord injury (SCI). Unfortunately, SCI-related neuropathic pain has proven to be largely refractory to analgesic medications and other available treatments. Cranial electrotherapy stimulation (CES) has been effective in managing some types of pain. It involves the application of a small amount of current through the head via ear clip electrodes. OBJECTIVE: Explore the effectiveness of CES for neuropathic pain in persons with SCI and chronic pain. STUDY DESIGN: Multi-site, double-blind, sham-controlled study. PARTICIPANTS: Adults with SCI and chronic neuropathic pain at or below the level of injury were randomized to receive active or sham CES. INTERVENTION: Application of active CES or sham CES 1 hour daily for 21 days. Six-month open-label phase to assess 'as-needed' CES use. OUTCOME MEASURES: Change in pre- to post-session pain ratings as well as change in pain intensity, pain interference, pain quality, pain beliefs and coping strategies, general physical and mental health status, depressive symptomatology, perceived stress, and anxiety pre- to post-treatment. RESULTS: The active group reported a significantly greater average decrease in pain during daily treatments than the sham group (Kruskal-Wallis chi-square = 4.70, P < 0.05). During the 21-day trial, there was a significant group × time interaction for only one outcome variable; the active group showed larger pre- to post-treatment decreases in pain interference than the sham group did (F = 8.50, P < 0.01, d = 0.59). CONCLUSIONS: On average, CES appears to have provided a small but statistically significant improvement in pain intensity and pain interference with few troublesome side effects. Individual results varied from no pain relief to a great deal of relief.

Four decades of plant community change in the Alpine tundra of southwest Yukon, Canada.

Repeat measurements from long-term plots provide precise data for studying plant community change. In 2010, we visited a remote location in Yukon, Canada, where a detailed survey of alpine tundra communities was conducted in 1968. Plant community composition was resurveyed on the same four slopes using the same methods as the original study. Species richness and diversity increased significantly over the 42 years and non-metric multidimensional scaling indicated that community composition had also changed significantly. However, the direction and magnitude of change varied with aspect. Dominant species were not replaced or eliminated but, instead, declined in relative importance. Fine-scale changes in vegetation were evident from repeat photography and dendro-ecological analysis of erect shrubs, supporting the community-level analysis. The period of study corresponds to a mean annual temperature increase of 2 degrees C, suggesting that climate warming has influenced these changes.

Multi-decadal changes in tundra environments and ecosystems: synthesis of the International Polar Year-Back to the Future project (IPY-BTF).

Understanding the responses of tundra systems to global change has global implications. Most tundra regions lack sustained environmental monitoring and one of the only ways to document multi-decadal change is to resample historic research sites. The International Polar Year (IPY) provided a unique opportunity for such research through the Back to the Future (BTF) project (IPY project #512). This article synthesizes the results from 13 papers within this Ambio Special Issue. Abiotic changes include glacial recession in the Altai Mountains, Russia; increased snow depth and hardness, permafrost warming, and increased growing season length in sub-arctic Sweden; drying of ponds in Greenland; increased nutrient availability in Alaskan tundra ponds, and warming at most locations studied. Biotic changes ranged from relatively minor plant community change at two sites in Greenland to moderate change in the Yukon, and to dramatic increases in shrub and tree density on Herschel Island, and in subarctic Sweden. The population of geese tripled at one site in northeast Greenland where biomass in non-grazed plots doubled. A model parameterized using results from a BTF study forecasts substantial declines in all snowbeds and increases in shrub tundra on Niwot Ridge, Colorado over the next century. In general, results support and provide improved capacities for validating experimental manipulation, remote sensing, and modeling studies.

A meta-analysis of cranial electrotherapy stimulation in the treatment of depression.

BACKGROUND: Depression rates have reached historic highs, with 49% of Americans reporting unabating symptoms and signs of depression, representing a 12% increase compared to the same time in 2019. With depression as a moderating factor for suicide, the need for efficacious treatments for depression has never been more pronounced. Although the armamentarium of the psychiatrist seems impressive having multiple medications and psychotherapy options, with guidelines for combination and augmentation treatments; many patients do not improve or are not suitable candidates for the usual, customary and reasonable (UCR) depression treatments. The use of various forms of brain stimulation technology as a complementary or alternative treatment for depression is growing and is expected to be part of the armamentarium of most psychiatrists by 2030. One form of brain stimulation, available in a phone sized prescription device, is cranial electrical stimulation (CES) which has been used as a treatment for depression since the 1970s. We have conducted two meta-analyses of CES research for depression separating randomized controlled trials (N = 5) from non-randomized studies on interventions (N = 12). For the double-blind RCTs 100 µA was used for 1 hour per day as 100 µA is a subsensory level of current so identical sham treatment devices could be used. METHODS: Our literature review followed Cooper's Taxonomy of Literature Reviews that is appropriate for the behavioral and physical sciences and the PRISMA reporting guidelines. The evaluation of strengths and limitations of the research studies included in this report adheres to recommended published guidelines in the Cochrane Handbook for Systematic Reviews of Interventions, and in the Handbook of Research Synthesis and Meta-Analysis. We used the Cohen's d effect size summary metric in all analyses. Homogeneity of effect sizes within the fixed and random effects models are reported. Meta-analyses were performed using the Compressive Meta-Analysis, version 3 program. RESULTS: The 5 RCTs represent a combined N of 242 and the 12 NRSIs represent 16 data sets with a combined N of 1173 for total of 1415 subjects across 17 studies. There were male and female subjects, from adolescents to 60 years old. The average effect for the 5 RCTs was calculated as d = -0.69 (i.e., the mean depression level at posttest for the active group was -0.69 standard deviations lower than the mean depression level for the sham group), a medium effect. The additional 12 NRSI studies analyzed show a small effect of d = -0.43 in favor of the active treatment group. CONCLUSION: We conclude that CES has a small to medium significant effect in symptoms of depression across moderate to severe patients in civilian, military, veterans, advanced cancer and pediatric populations.

Differential effects of cranial electrotherapy stimulation on changes in anxiety and depression symptoms over time in patients with generalized anxiety disorder.

BACKGROUND: Cranial electrotherapy stimulation (CES) is a safe and well-tolerated 6-12 week treatment that is clinically and cost effective on both anxiety and depression symptoms resulting in sustained remission of these symptoms at 12 and 24 weeks in generalized anxiety disorder (GAD) patients. The aim of the current report was to explore whether the effectiveness of CES was related to its effects on depression or anxiety over time METHODS: A consecutive sample of 161 eligible patients with GAD was recruited from two publicly funded services in England while they waited for individual cognitive behaviour therapy (CBT) after failing to achieve remission on the GAD-7 with computerised CBT. They received 60 minutes per day Alpha-Stim CES for 6-12 weeks. Outcomes were changes in PHQ-9, GAD-7 score from baseline to 4, 6, 8, 12 and 24 weeks. Latent variable cross-lagged panel analysis permitted an analysis of the differential effects of anxiety and depression with CES treatment over time. RESULTS: Anxiety at baseline significantly predicted depression at week 4 (standardized regression weight = .40, p<0.001). Depression at week 12 significantly predicted anxiety at week 24 (standardized regression weight = .28, p<0.05). LIMITATIONS: Not a randomized controlled trial but further analysis of a prospective observational cohort. High rates of loss to follow up by 24 weeks. CONCLUSION: Sustained effectiveness required a CES response to anxiety symptoms in first 4 weeks and improvement in depression symptoms by 12 weeks.

Revisiting Reliability: Using Sampling Utterances and Grammatical Analysis Revised (SUGAR) to Compare 25- and 50-Utterance Language Samples.

Purpose The goal of this study was to determine whether the results obtained from a 25-utterance conversational language sample were as reliable as those obtained from a 50-utterance sample. Method Robust conversational language samples from 220 children with typically developing language (106 boys, 114 girls) ranging in age from 3;2 to 7;10 (years;months) were collected. The language samples were randomly assigned to one of two conditions: a 25-utterance condition and a 50-utterance condition. Transcripts were examined for three metrics, including mean length of utteranceSUGAR, words per sentence, and clauses per sentence. Results Data were analyzed using two methods. A linear mixed-model analysis was used to assess absolute and relative reliability, and the Bland-Altman procedure was used to assess absolute reliability and clinical acceptability. Results of the mixed-model analysis indicated that mean length of utteranceSUGAR and words per sentence demonstrated relative reliability; however, none of the metrics demonstrated absolute reliability. In contrast, results of the Bland-Altman scatter plots indicated that all three metrics demonstrated absolute reliability because 94%-96% of participants' scores fell within the limits of agreement. Taken together, the results suggested that the statistically significant differences indicated by the mixed-model analysis were not clinically significant. Conclusion These results highlighted the importance of using different methods of analysis in studies of reliability. The findings indicated that reliable language sample results can be obtained from 25-utterance samples. Furthermore, by including practices already in use (e.g., collecting samples ≤ 50 utterances) and including only minimal changes to current practices, the methods used in this study are feasible for school-based clinicians, could be easily integrated into clinical practice, and could increase the use of evidence-based assessment practices in schools.