Jeremiah Menk

Primed low-frequency repetitive transcranial magnetic stimulation and constraint-induced movement therapy in pediatric hemiparesis: a randomized controlled trial.

The aim of this study was to determine the feasibility and efficacy of five treatments of 6 Hz primed, low‐frequency, repetitive transcranial magnetic stimulation (rTMS) combined with constraint‐induced movement therapy (CIMT) to promote recovery of the paretic hand in children with congenital hemiparesis.

The Effects of Incident and Persistent Behavioral Problems on Change in Caregiver Burden and Nursing Home Admission of Persons With Dementia

Background:The individual contributions of behavior problems to key and related outcomes in dementia, such as nursing home admission (NHA) or caregiver burden, remain unclear. Objectives:This study sought to determine the ramifications of temporal change in individual behavior problems when accounting for increases in caregiver burden and time to NHA. Although burden is sometimes conceptualized as an antecedent to NHA, it has also emerged as a relevant outcome in dementia caregiving research. Methods:A sample of 4545 dementia caregivers who participated in the Medicare Alzheimer disease Demonstration Evaluation was selected for this secondary analysis. Various patterns of change in individual behavior problems were considered as predictors of increases in caregiver burden and time to NHA over a 3-year period via mixed effects and Cox proportional hazards models, respectively. Results:Caregivers who did not indicate a care recipients dangerous behavior initially but did so subsequently (ie, an “incident” behavior problem) were more likely to experience increases in burden (P < 0.0026). Alternatively, the persistent occurrence of behavior disturbances (particularly memory problems) emerged as the strongest predictors of time to NHA. Discussion:The findings of this study suggest the benefit of examining temporal patterns of individual behavioral disturbances, and that incident and persistent problems account for different dementia outcomes over time. Considering the temporal ramifications and potency of specific behavior problems can facilitate the targeted and timely delivery of effective clinical interventions.

Does Caregiver Burden Mediate the Effects of Behavioral Disturbances on Nursing Home Admission

OBJECTIVES The primary objective of this study was to determine whether caregiving burden mediated the relationship between specific behavior disturbances and time to nursing home admission (NHA) for persons with dementia (i.e., Alzheimer disease or a related disorder). DESIGN The study used secondary longitudinal data from the Medicare Alzheimers Disease Demonstration, a Medicare-covered home care benefit and case management program for family caregivers of persons with dementia. Primary caregivers of persons with dementia were assessed via in-person and telephone interviews every 6 months over a 3-year period. SETTING Dementia caregivers were recruited from eight catchment areas throughout the United States. PARTICIPANTS The baseline sample included 5,831 dementia caregivers. Just more than 40% (43.9%; N = 2,556) of persons with dementia permanently entered a nursing home during the 3-year study period. MEASUREMENTS Individual behavior problems were measured with the Memory and Behavior Problem Checklist. Caregiving burden was assessed with a short version of the Zarit Burden Inventory. Key covariates, including sociodemographic background, functional status, and service utilization, were also considered. RESULTS Event history analyses revealed that time-varying measures of caregiver burden fully mediated the relationship between four behavioral disturbances (episodes of combativeness, property destruction, repetitive questions, and reliving the past) and NHA. CONCLUSIONS The findings highlight the multifaceted, complex pathway to NHA for persons with dementia and their family caregivers. The results emphasize the need for comprehensive treatment approaches that incorporate the burden of caregivers and the behavioral/psychiatric symptoms of persons with dementia simultaneously.

Safety and Feasibility of Transcranial Direct Current Stimulation in Pediatric Hemiparesis: Randomized Controlled Preliminary Study

Background Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation that has shown improved adult stroke outcomes. Applying tDCS in children with congenital hemiparesis has not yet been explored. Objective The primary objective of this study was to explore the safety and feasibility of single-session tDCS through an adverse events profile and symptom assessment within a double-blind, randomized placebo-controlled preliminary study in children with congenital hemiparesis. A secondary objective was to assess the stability of hand and cognitive function. Design A double-blind, randomized placebo-controlled pretest/posttest/follow-up study was conducted. Setting The study was conducted in a university pediatric research laboratory. Participants Thirteen children, ages 7 to 18 years, with congenital hemiparesis participated. Measurements Adverse events/safety assessment and hand function were measured. Intervention Participants were randomly assigned to either an intervention group or a control group, with safety and functional assessments at pretest, at posttest on the same day, and at a 1-week follow-up session. An intervention of 10 minutes of 0.7 mA tDCS was applied to bilateral primary motor cortices. The tDCS intervention was considered safe if there was no individual decline of 25% or group decline of 2 standard deviations for motor evoked potentials (MEPs) and behavioral data and no report of adverse events. Results No major adverse events were found, including no seizures. Two participants did not complete the study due to lack of MEP and discomfort. For the 11 participants who completed the study, group differences in MEPs and behavioral data did not exceed 2 standard deviations in those who received the tDCS (n=5) and those in the control group (n=6). The study was completed without the need for stopping per medical monitor and biostatisticial analysis. Limitations A limitation of the study was the small sample size, with data available for 11 participants. Conclusions Based on the results of this study, tDCS appears to be safe, feasible, and well tolerated in most children with hemiparesis. Future investigations of serial sessions of tDCS in conjunction with rehabilitation in pediatric hemiparesis are indicated to explore the benefit of a synergistic approach to improving hand function.

Repair of “Simple” Total Anomalous Pulmonary Venous Connection: A Review From the Pediatric Cardiac Care Consortium

BACKGROUND Outcomes for repair of total anomalous pulmonary venous connection (TAPVC) from individual institutions suggest a significant improvement in mortality over the past several decades. The purpose of this study is to review the outcomes after repair of TAPVC from a large multiinstitutional registry. METHODS A retrospective review of the multiinstitutional database, the Pediatric Cardiac Care Consortium (PCCC), was used to identify patients with the diagnosis of TAPVC who underwent complete correction between 1982 and 2007. Data reviewed included age, decade of primary operation, anatomic type, presentation, and in-hospital mortality. RESULTS Of the 118,084 surgical procedures submitted to the PCCC, 2,191 (1.9%) consisted of primary surgical correction of TAPVC. Sixty-one percent of the cohort was male, with 6.8% reported as premature. Overall in-hospital surgical mortality for simple TAPVC was 13%. Mortality was 20% from 1982 to 1989, 16% from 1990 to 1999, and 8% from 2000 to 2007. Obstruction to the anomalous pulmonary venous connection occurred in 29%, with a mortality of 26%. CONCLUSIONS Surgical outcomes from repair of congenital cardiac anomalies have significantly improved over the past several decades. Multiinstitutional large databases are needed to confirm results published from single-institution experiences. Although improvements in surgical repair of TAPVC have occurred over the past three decades, specific subtypes still experience significant mortality.

The association between cognition and academic performance in Ugandan children surviving malaria with neurological involvement.

Background The contribution of different cognitive abilities to academic performance in children surviving cerebral insult can guide the choice of interventions to improve cognitive and academic outcomes. This studys objective was to identify which cognitive abilities are associated with academic performance in children after malaria with neurological involvement. Methods 62 Ugandan children with a history of malaria with neurological involvement were assessed for cognitive ability (working memory, reasoning, learning, visual spatial skills, attention) and academic performance (reading, spelling, arithmetic) three months after the illness. Linear regressions were fit for each academic score with the five cognitive outcomes entered as predictors. Adjusters in the analysis were age, sex, education, nutrition, and home environment. Exploratory factor analysis (EFA) and structural equation models (SEM) were used to determine the nature of the association between cognition and academic performance. Predictive residual sum of squares was used to determine which combination of cognitive scores was needed to predict academic performance. Results In regressions of a single academic score on all five cognitive outcomes and adjusters, only Working Memory was associated with Reading (coefficient estimate = 0.36, 95% confidence interval = 0.10 to 0.63, p<0.01) and Spelling (0.46, 0.13 to 0.78, p<0.01), Visual Spatial Skills was associated with Arithmetic (0.15, 0.03 to 0.26, p<0.05), and Learning was associated with Reading (0.06, 0.00 to 0.11, p<0.05). One latent cognitive factor was identified using EFA. The SEM found a strong association between this latent cognitive ability and each academic performance measure (P<0.0001). Working memory, visual spatial ability and learning were the best predictors of academic performance. Conclusion Academic performance is strongly associated with the latent variable labelled “cognitive ability” which captures most of the variation in the individual specific cognitive outcome measures. Working memory, visual spatial skills, and learning together stood out as the best combination to predict academic performance.

Safety of Primed Repetitive Transcranial Magnetic Stimulation and Modified Constraint-Induced Movement Therapy in a Randomized Controlled Trial in Pediatric Hemiparesis

OBJECTIVE To investigate the safety of combining a 6-Hz primed low-frequency repetitive transcranial magnetic stimulation (rTMS) intervention in the contralesional hemisphere with a modified constraint-induced movement therapy (mCIMT) program in children with congenital hemiparesis. DESIGN Phase 1 randomized, double-blinded, placebo-controlled pretest/posttest trial. SETTING University academic facility and pediatric specialty hospital. PARTICIPANTS Subjects (N = 19; age range, 8-17 y) with congenital hemiparesis caused by ischemic stroke or periventricular leukomalacia. No subject withdrew because of adverse events. All subjects included completed the study. INTERVENTIONS Subjects were randomized to 1 of 2 groups: either real rTMS plus mCIMT (n = 10) or sham rTMS plus mCIMT (n = 9). MAIN OUTCOME MEASURES Adverse events, physician assessment, ipsilateral hand function, stereognosis, cognitive function, subject report of symptoms assessment, and subject questionnaire. RESULTS No major adverse events occurred. Minor adverse events were found in both groups. The most common events were headaches (real: 50%, sham: 89%; P = .14) and cast irritation (real: 30%, sham: 44%; P = .65). No differences between groups in secondary cognitive and unaffected hand motor measures were found. CONCLUSIONS Primed rTMS can be used safely with mCIMT in congenital hemiparesis. We provide new information on the use of rTMS in combination with mCIMT in children. These findings could be useful in research and future clinical applications in advancing function in congenital hemiparesis.

Synergistic effect of combined transcranial direct current stimulation/constraint- induced movement therapy in children and young adults with hemiparesis: study protocol

BackgroundPerinatal stroke occurs in more than 1 in 2,500 live births and resultant congenital hemiparesis necessitates investigation into interventions which may improve long-term function and decreased burden of care beyond current therapies (http://www.cdc.gov/ncbddd/cp/data.html). Constraint-Induced Movement Therapy (CIMT) is recognized as an effective hemiparesis rehabilitation intervention . Transcranial direct current stimulation as an adjunct treatment to CIMT may potentiate neuroplastic responses and improve motor function. The methodology of a clinical trial in children designed as a placebo-controlled, serial –session, non-invasive brain stimulation trial incorporating CIMT is described here. The primary hypotheses are 1) that no serious adverse events will occur in children receiving non-invasive brain stimulation and 2) that children in the stimulation intervention group will show significant improvements in hand motor function compared to children in the placebo stimulation control group.Methods/designA randomized, controlled, double-blinded clinical trial. Twenty children and/or young adults (ages 8–21) with congenital hemiparesis, will be enrolled. The intervention group will receive ten 2-hour sessions of transcranial direct current stimulation combined with constraint-induced movement therapy and the control group will receive sham stimulation with CIMT. The primary outcome measure is safety assessment of transcranial direct current stimulation by physician evaluation, vital sign monitoring and symptom reports. Additionally, hand function will be evaluated using the Assisting Hand Assessment, grip strength and assessment of goals using the Canadian Occupational Performance Measure. Neuroimaging will confirm diagnoses, corticospinal tract integrity and cortical activation. Motor cortical excitability will also be examined using transcranial magnetic stimulation techniques.DiscussionCombining non-invasive brain stimulation and CIMT interventions has the potential to improve motor function in children with congenital hemiparesis beyond each intervention independently. Such a combined intervention has the potential to benefit an individual throughout their lifetime.Trial registrationClinicaltrials.gov, NCT02250092Registered 18 September 2014

In‐Hospital Vital Status and Heart Transplants After Intervention for Congenital Heart Disease in the Pediatric Cardiac Care Consortium: Completeness of Ascertainment Using the National Death Index and United Network for Organ Sharing Datasets

Background The long‐term outcomes of patients undergoing interventions for congenital heart disease (CHD) remain largely unknown. We linked the Pediatric Cardiac Care Consortium (PCCC) with the National Death Index (NDI) and the United Network for Organ Sharing Dataset (UNOS) registries to study mortality and transplant occurring up to 32 years postintervention. The objective of the current analysis was to determine the sensitivity of this linkage in identifying patients who are known to have died or undergone heart transplant. Methods and Results We used direct identifiers from 59 324 subjects registered in the PCCC between 1982 and 2003 to test for completeness of case ascertainment of subjects with known vital and heart transplant status by linkage with the NDI and UNOS registries. Of the 4612 in‐hospital deaths, 3873 were identified by the NDI as “true” matches for a sensitivity of 84.0% (95% CI, 82.9–85.0). There was no difference in sensitivity across 25 congenital cardiovascular conditions after adjustment for age, sex, race, presence of first name, death year, and residence at death. Of 455 known heart transplants in the PCCC, there were 408 matches in the UNOS registry, for a sensitivity of 89.7% (95% CI, 86.9–92.3). An additional 4851 deaths and 363 transplants that occurred outside the PCCC were identified through 2014. Conclusions The linkage of the PCCC with the NDI and UNOS national registries is feasible with a satisfactory sensitivity. This linkage provides a conservative estimate of the long‐term death and heart transplant events in this cohort.

A network approach to modeling comorbid internalizing and alcohol use disorders.

Internalizing disorders co-occur with alcohol use disorder (AUD) at a rate that exceeds chance and compromise conventional AUD treatment. The “vicious cycle” model of comorbidity specifies drinking to cope (DTC) as a link between these disorders that, when not directly addressed, undermines the effectiveness of conventional treatments. Interventions based on this model have proven successful but there is no direct evidence for how and to what extent DTC contributes to the maintenance of comorbidity. In the present study, we used network analysis to depict associations between syndrome-specific groupings of internalizing symptoms, alcohol craving, and drinking behavior, as well as DTC and other extradiagnostic variables specified in the vicious cycle model (e.g., perceived stress and coping self-efficacy). Network analyses of 362 individuals with comorbid anxiety and AUD assessed at the beginning of residential AUD treatment indicated that while internalizing conditions and drinking elements had only weak direct associations, they were strongly connected with DTC and perceived stress. Consistent with this, centrality indices showed that DTC ranked as the most central/important element in the network in terms of its “connectedness” to all other network elements. A series of model simulations—in which individual elements were statistically controlled for—demonstrated that DTC accounted for all the relationships between the drinking-related elements and internalizing elements in the network; no other variable had this effect. Taken together, our findings suggest that DTC may serve as a “keystone” process in maintaining comorbidity between internalizing disorders and AUD.