Yanna Song

Comparing the performance of three generations of ActiGraph accelerometers

ActiGraph accelerometers are a useful tool for objective assessment of physical activity in clinical and epidemiological studies. Several generations of ActiGraph are being used; however, little work has been done to verify that measurements are consistent across generations. This study employed mechanical oscillations to characterize the dynamic response and intermonitor variability of three generations of ActiGraph monitors, from the oldest 7164 (n = 13), 71256 (n = 12), to the newest GT1M (n = 12). The response due to independent radius (22.1-60.4 mm) and frequency (25-250 rpm) changes were measured, as well as intermonitor variability within each generation. The 7164 and 71256 have similar relationships between activity counts and radius (P = 0.229) but were significantly different from the GT1M (P < 0.001). The frequency responses were nonlinear in all three generations. Although the response curve shapes were similar, the differences between generations at various frequencies were significant (P < 0.017), especially in the extremes of the measurement range. Intermonitor variability was markedly reduced in the GT1M compared with the 7164 and 71256. Other measurement differences between generations include decreased peak counts and decreased sensitivity in low-frequency detection in the GT1M. The results of this study revealed an improvement of the intermonitor variability by the GT1M monitor. However, the reduced sensitivity in low-count ranges in the GT1M may not be well suited for monitoring sedentary or light-intensity movements. Furthermore, the algorithms for energy expenditure predictions developed using older 7164 monitors may need to be modified for the GT1M.

Treating obstructive sleep apnea in adults with epilepsy : A randomized pilot trial

Objective: Small uncontrolled series suggest that treatment of obstructive sleep apnea (OSA) in patients with epilepsy may improve seizure control. Prior to conducting a definitive randomized controlled trial, we addressed critical design issues in a pilot study. Methods: We identified a cohort of adult patients with medically refractory epilepsy and coexisting OSA, documented by polysomnography (PSG). After an 8-week baseline period, subjects with OSA were randomized to therapeutic or sham continuous positive airway pressure (CPAP) for 10 weeks. Subjects maintained seizure calendars and antiepileptic drug dosages were held constant. Results: Sixty-eight subjects with suspected OSA were enrolled and 35 subjects randomized to therapeutic CPAP (22 subjects) or sham (13 subjects) CPAP. Male gender and an elevated sleep apnea questionnaire score were predictive of OSA on PSG. Nineteen subjects in the therapeutic group and all 13 subjects in the sham group completed the trial. Baseline apnea-hypopnea index (AHI) and CPAP adherence were comparable between groups. A significant reduction in AHI was observed in the therapeutic CPAP group as compared to the sham group. Subjects, study coordinators, and principal investigators were unable to predict treatment allocation. Conclusions: This pilot study provided critical information related to study design and feasibility for planning a comprehensive trial to test the hypothesis that treating obstructive sleep apnea in patients with epilepsy improves seizure control.

Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

BACKGROUND Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinsons disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. METHODS Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. RESULTS As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. CONCLUSIONS This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD.

Common atrial fibrillation risk alleles at 4q25 predict recurrence after catheter-based atrial fibrillation ablation

BACKGROUND Common single nucleotide polymorphisms at chromosome 4q25 (rs2200733, rs10033464) are associated with both lone and typical atrial fibrillation (AF). Risk alleles at 4q25 have recently been shown to predict recurrence of AF after ablation in a population of predominately lone AF, but lone AF represents only 5%-30% of AF cases. OBJECTIVE To test the hypothesis that 4q25 AF risk alleles can predict response to AF ablation in the majority of AF cases. METHODS Patients enrolled in the Vanderbilt AF Registry underwent 378 catheter-based AF ablations (median age 60 years; 71% men; 89% typical AF) between 2004 and 2011. The primary end point was time to recurrence of any nonsinus atrial tachyarrhythmia (atrial tachycardia, atrial flutter, or AF). RESULTS Two-hundred atrial tachycardia, atrial flutter, or AF recurrences (53%) were observed. In multivariable analysis, the rs2200733 risk allele predicted a 24% shorter recurrence-free time (survival time ratio 0.76; 95% confidence interval [CI] 0.6-0.95; P = .016) compared with wild type. The heterozygous haplotype demonstrated a 21% shorter recurrence-free time (survival time ratio 0.79; 95% CI 0.62-0.99) and the homozygous risk allele carriers a 39% shorter recurrence-free time (survival time ratio 0.61; 95% CI 0.37-1.0; P = .037). CONCLUSIONS Risk alleles at the 4q25 loci predict impaired clinical response to AF ablation in a population of patients with predominately typical AF. Our findings suggest that the rs2200733 polymorphism may hold promise as an objectively measured patient characteristic that can be used as a clinical tool for selecting patients for AF ablation.

Vitamin D Therapy in Individuals With Prehypertension or Hypertension The DAYLIGHT Trial

Background— A large body of epidemiological and experimental evidence suggests that vitamin D deficiency may promote hypertension. This raises the possibility that vitamin D supplementation could be a simple intervention to reduce blood pressure, but data from prospective, randomized trials are limited. Methods and Results— A double-blind, randomized, controlled trial was conducted at 4 sites in the United States. We enrolled 534 individuals 18 to 50 years of age with low vitamin D status (25-hydroxyvitamin D levels ⩽25 ng/mL) and systolic blood pressure of 120 to 159 mm Hg. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D3 for 6 months. The primary end point was change in mean 24-hour systolic blood pressure. Secondary end points included change in ambulatory diastolic blood pressure and clinic systolic and diastolic blood pressures. The median age was 38 years, and 62% of participants were men. Forty-six percent of participants were white, and 48% were black. The median 25-hydroxyvitamin D level at baseline was 15.3 ng/mL. Four-hundred fifty-five participants (85%) had at least 1 follow-up blood pressure measurement; 383 participants (72%) completed the full 6-month study. At the end of the study, there was no significant difference in the primary end point (change in mean 24-hour systolic blood pressure, −0.8 versus −1.6 mm Hg in the high-dose and low-dose arms; P=0.71) or in any of the secondary end points. Furthermore, there was no evidence of association between change in 25-hydroxyvitamin D and change in 24-hour systolic blood pressure at 6 months (Spearman correlation coefficient, −0.05, P=0.34). Results were consistent across prespecified subgroups. Conclusions— Vitamin D supplementation did not reduce blood pressure in individuals with prehypertension or stage I hypertension and vitamin D deficiency. Our findings suggest that the association between vitamin D status and elevated blood pressure noted in observational studies is not causal. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01240512.

Reliability of Quantitative Sudomotor Axon Reflex Testing and Quantitative Sensory Testing in Neuropathy of Impaired Glucose Regulation

Reproducible neurophysiologic testing paradigms are critical for multicenter studies of neuropathy associated with impaired glucose regulation (IGR), yet the best methodologies and endpoints remain to be established. This study evaluates the reproducibility of neurophysiologic tests within a multicenter research setting. Twenty‐three participants with neuropathy and IGR were recruited from two study sites. The reproducibility of quantitative sudomotor axon reflex test (QSART) and quantitative sensory test (QST) (using the CASE IV system) was determined in a subset of patients at two sessions, and it was calculated from intraclass correlation coefficients (ICCs). QST (cold detection threshold: ICC = 0.80; vibration detection threshold: ICC = 0.75) was more reproducible than QSART (ICC foot = 0.52). The performance of multiple tests in one setting did not improve reproducibility of QST. QST reproducibility in our IGR patients was similar to reports of other studies. QSART reproducibility was significantly lower than QST. In this group of patients, the reproducibility of QSART was unacceptable for use as a secondary endpoint measure in clinical research trials. Muscle Nerve, 2008

Anti‐Remodeling and Anti‐Fibrotic Effects of the Neuregulin‐1β Glial Growth Factor 2 in a Large Animal Model of Heart Failure

Background Neuregulin‐1β (NRG‐1β) is a growth factor critical for cardiac development and repair with therapeutic potential for heart failure. We previously showed that the glial growth factor 2 (GGF2) isoform of NRG‐1β improves cardiac function in rodents after myocardial infarction (MI), but its efficacy in a large animal model of cardiac injury has not been examined. We therefore sought to examine the effects of GGF2 on ventricular remodeling, cardiac function, and global transcription in post‐MI swine, as well as potential mechanisms for anti‐remodeling effects. Methods and Results MI was induced in anesthetized swine (n=23) by intracoronary balloon occlusion. At 1 week post‐MI, survivors (n=13) received GGF2 treatment (intravenous, biweekly for 4 weeks; n=8) or were untreated (n=5). At 5 weeks post‐MI, fractional shortening was higher (32.8% versus 25.3%, P=0.019), and left ventricular (LV) end‐diastolic dimension lower (4.5 versus 5.3 cm, P=0.003) in GGF2‐treated animals. Treatment altered expression of 528 genes, as measured by microarrays, including collagens, basal lamina components, and matricellular proteins. GGF2‐treated pigs exhibited improvements in LV cardiomyocyte mitochondria and intercalated disk structures and showed less fibrosis, altered matrix structure, and fewer myofibroblasts (myoFbs), based on trichrome staining, electron microscopy, and immunostaining. In vitro experiments with isolated murine and rat cardiac fibroblasts demonstrate that NRG‐1β reduces myoFbs, and suppresses TGFβ‐induced phospho‐SMAD3 as well as αSMA expression. Conclusions These results suggest that GGF2/NRG‐1β prevents adverse remodeling after injury in part via anti‐fibrotic effects in the heart.

Examining the role of positive and negative affect in recovery from spine surgery

Summary Multivariable mixed‐model linear regression analyses illustrated the unique relation between postoperative positive affect and functional status and postoperative negative affect and pain interference and disability after spine surgery. Abstract Consistent evidence supports a significant association between lower positive affect and higher negative affect and increased pain and disability in adults with chronic pain. However, examining this relation in surgical populations has received little empirical consideration. The primary purpose of this study was to determine whether preoperative and postoperative positive and negative affect predict pain, disability, and functional status after spine surgery. A secondary objective was to assess the relation of depression to postoperative outcomes compared with positive and negative affect. Participants were 141 patients treated by spine surgery for lumbar or cervical degeneration. Data collection occurred at baseline and 6 weeks and 3 months postoperatively. Affect was measured with the Positive and Negative Affect Schedule. Multivariable mixed‐model linear regression analyses found that preoperative variables were not predictive of postoperative pain, disability and functional status. However, multivariable postoperative analysis found that 6‐week positive affect predicted functional status, and 6‐week negative affect predicted pain interference and pain‐related disability at 3 months following surgery. Postoperative depression demonstrated statistically significant and stronger associations with pain intensity, pain interference, and pain‐related disability at 3‐month follow‐up, as compared with negative affect. Results suggest that positive affect and depression are important variables to target when seeking to improve postoperative outcomes in a spine surgery population. Recommendations include postoperative screening for positive affect and depression, and treating depression as well as focusing on rehabilitation strategies to bolster positive affect so as to improve functional outcomes after spine surgery.

Effects of epidural steroid injections on blood glucose levels in patients with diabetes mellitus.

Study Design. A prospective cohort study. Objective. To evaluate the effects of epidural steroid injections (ESIs) on blood glucose levels in patients with diabetes mellitus. Summary of Background Data. ESIs are commonly used in the treatment of multiple spinal disorders. Corticosteroid injections have been evaluated in the total joints and hand literature showing systemic effects to diabetics. Methods. Diabetic patients who were scheduled for an ESI were given an opportunity to enroll in our IRB-approved study. We collected the patients most recent hemoglobin A1c (hA1c) and then asked them to track their blood glucose numbers at least twice per day for 2 weeks prior to and after their ESIs. Results. We noted a statistically significant increase in blood glucose levels in diabetic patients (n = 30) after ESI. The mean blood glucose level prior to ESI was 160.18 ± 47.46, and, after ESI, it was 286.13 ± 111.11. This represents an average 125.96 ± 100.97 increase in blood glucose levels after injection. Using a nonlinear mixed effect model, the estimated half-life of this increase was 1.06 days (95% CI 0.80, 1.58), meaning that the patients were back within their normal standard deviation mean glucose levels within 2 days of injection. There was no association between observed glucose level change and preinjection hA1c levels or age (Spearman = 0.0326 and −0.1091 separately), indicating that there is no correlation between preinjection hA1c levels and systemic response to ESI. Conclusion. ESIs were noted to cause a significant increase in the blood glucose levels in diabetics. There was no correlation between preinjection diabetic control, represented by hA1c levels, and postinjection response. Diabetics who are candidates for ESI should be counseled that a blood glucose increase may be apparent post intervention, but effects should not last longer than approximately 2 days.

A sleep habits questionnaire for children with autism spectrum disorders.

Sleep difficulties in children with autism spectrum disorders are common, with poor sleep hygiene a contributing factor. We developed the Family Inventory of Sleep Habits to measure sleep hygiene in this population. Its validity and reliability in 2 groups of children aged 4 to 10 years, those with a clinical diagnosis of autism spectrum disorders, and those who are typically developing are described. In both groups, total and modified (reflecting insomnia subscales) scores on the Childrens Sleep Habits Questionnaire showed significant negative correlations with the total score. The Peabody Picture Vocabulary Test-III was significantly correlated with total score in the autism spectrum group but not in the typically developing group. Age and socioeconomic status were not correlated with total score in either group. This preliminary work suggests that the Family Inventory of Sleep Habits is a valid and reliable measure of sleep hygiene in autism spectrum disorders.