A Chart Review to Assess the Response of Veterans Suffering from Tinnitus to Alpha Burst Transcranial Magnetic Stimulation.

OBJECTIVE: The purpose of this chart review was to assess the response of veterans suffering from tinnitus to Magnetic EEG/EKGguided resonance therapy and Alpha Burst Stimulation (ABS), while also investigating the safety profile of this therapy combination. EEG/EKG-guided Repetitive Transcranial Magnetic Stimulation (rTMS) delivers high-energy electromagnetic pulses to induce current flow in the neocortex. ABS provides rTMS pulses in short, high-frequency bursts. MATERIALS AND METHODS: All equipment used to evaluate and treat participants are either FDA-cleared or are exempt from clearance and listed with the United States FDA. Stimulation was delivered with a MagPro R30 and an MCF-B65 butterfly coil. Charts were reviewed from patients who had received a combination of EEG/EKG-guided rTMS and ABS therapy to relieve symptoms of tinnitus. Paired samples t-tests were performed on the Tinnitus Functional Index (TFI) and Neurobehavioral Symptom Inventory (NSI) scales. Treatment logs and therapy notes were reviewed for safety data. Adverse events or side effects were extracted from therapy notes. Linear regression was used to analyze the relationship between number of therapy sessions, and reported patient symptoms. RESULTS: Eighteen of the 23 patients reported significant improvements in tinnitus symptoms. For patients reporting improvements, there was an average 44% reduction in tinnitus symptoms and a 60% reduction in NSI scores following intervention. No patients experienced adverse side effects. The most common side effects were headache and fatigue. CONCLUSION: Based on the results from this study, noninvasive neuromodulation holds promise as a potential treatment for tinnitus. Additional investigation in controlled studies may be warranted.

Efficacy and Safety of Low-field Synchronized Transcranial Magnetic Stimulation (sTMS) for Treatment of Major Depression.

BACKGROUND: Transcranial Magnetic Stimulation (TMS) customarily uses high-field electromagnets to achieve therapeutic efficacy in Major Depressive Disorder (MDD). Low-field magnetic stimulation also may be useful for treatment of MDD, with fewer treatment-emergent adverse events. OBJECTIVE/HYPOTHESIS: To examine efficacy, safety, and tolerability of low-field magnetic stimulation synchronized to an individual's alpha frequency (IAF) (synchronized TMS, or sTMS) for treatment of MDD. METHODS: Six-week double-blind sham-controlled treatment trial of a novel device that used three rotating neodymium magnets to deliver sTMS treatment. IAF was determined from a single-channel EEG prior to first treatment. Subjects had baseline 17-item Hamilton Depression Rating Scale (HamD17) ≥ 17. RESULTS: 202 subjects comprised the intent-to-treat (ITT) sample, and 120 subjects completed treatment per-protocol (PP). There was no difference in efficacy between active and sham in the ITT sample. Subjects in the PP sample (N = 59), however, had significantly greater mean decrease in HamD17 than sham (N = 60) (-9.00 vs. -6.56, P = 0.033). PP subjects with a history of poor response or intolerance to medication showed greater improvement with sTMS than did treatment-naïve subjects (-8.58 vs. -4.25, P = 0.017). Efficacy in the PP sample reflects exclusion of subjects who received fewer than 80% of scheduled treatments or were inadvertently treated at the incorrect IAF; these subgroups failed to separate from sham. There was no difference in adverse events between sTMS and sham, and no serious adverse events attributable to sTMS. CONCLUSIONS: Results suggest that sTMS may be effective, safe, and well tolerated for treating MDD when administered as intended.

A pilot study of the use of EEG-based synchronized Transcranial Magnetic Stimulation (sTMS) for treatment of Major Depression.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD), and is based upon delivery of focal high-energy pulses of electromagnetic stimulation. We postulated that delivery of rTMS at the subject's individual alpha frequency (synchronized TMS, or sTMS) would achieve efficacy with lower energy of stimulation. We developed a device that rotates neodymium cylindrical magnets at three locations along the midline above the subject's scalp to impart low-energy, sinusoidal-waveform magnetic brain stimulation over a broad area, and performed this efficacy study. METHOD: Fifty-two subjects with MDD were enrolled in a randomized, sham controlled, double-blind treatment study (Trial Registration: NCT01683019). Forty-six subjects were included in the final analysis. Most subjects received concurrent antidepressant medications that remained unchanged during the study. Subjects were randomized to three treatment groups: 1) active sTMS with a fixed frequency at the subject's alpha frequency; 2) active sTMS with a random stimulus frequency that varied between 8 Hz and 13 Hz; and, 3) sham sTMS. 20 half-hour sTMS sessions were administered 5 days per week for 4 weeks. RESULTS: Subjects with either fixed or random frequency active sTMS had statistically significantly greater percentage reduction in depression severity compared to sham (48.5% vs. 19.3%, respectively; p = 0.001). No significant difference was found between fixed and random groups (p = 0.30). No significant side effects were reported. CONCLUSIONS: These results suggest that sTMS may be an effective treatment for MDD.

Effect of adaptive paced cardiolocomotor synchronization during running: a preliminary study.

Cardiolocomotor synchronization (CLS) has been well established for individuals engaged in rhythmic activity, such as walking, running, or cycling. When frequency of the activity is at or near the heart rate, entrainment occurs. CLS has been shown in many cases to improve the efficiency of locomotor activity, improving stroke volume, reducing blood pressure variability, and lowering the oxygen uptake (VO2). Instead of a 1:1 frequency ratio of activity to heart rate, an investigation was performed to determine if different harmonic coupling at other simple integer ratios (e.g. 1:2, 2:3, 3:2) could achieve any performance benefits. CLS was ensured by pacing the stride rate according to the measured heartbeat (i.e., adaptive paced CLS, or forced CLS). An algorithm was designed that determined the simplest ratio (lowest denominator) that, when multiplied by the heart rate will fall within an individualized, predetermined comfortable pacing range for the user. The algorithm was implemented on an iPhone 4, which generated a 'tick-tock' sound through the iPhone's headphones. A sham-controlled crossover study was performed with 15 volunteers of various fitness levels. Subjects ran a 3 mile (4.83 km) simulated training run at their normal pace on two consecutive days (randomized one adaptive pacing, one sham). Adaptive pacing resulted in faster runs run times, with subjects running an average of 26:03 ± 3:23 for adaptive pacing and 26:38 ± 3:31 for sham (F = 5.46, p < 0.05). The increase in heart rate from the start of the race as estimated by an exponential time constant was significantly longer during adaptive pacing, τ = 0.99 ± 0.30, compared to sham, τ = 1.53 ± 0.34 (t = -6.62, p < 0.01). Eighty-seven percent of runners found it easy to adjust their stride length to match the pacing signal with seventy-nine percent reporting that pacing helped their performance. These results suggest that adaptive paced CLS may have a beneficial effect on running performance and may be useful as a training aid. Key PointsSham-controlled crossover study using 15 experienced runners running 3 miles (4.83 km).Adaptive CLS pacing resulted in statistically significant 35 second average decrease in run-time (p < 0.05).Increase in heart rate during the run was significantly slower during adaptive pacing (p < 0.01).

The relationship between brain oscillatory activity and therapeutic effectiveness of transcranial magnetic stimulation in the treatment of major depressive disorder.

Major depressive disorder (MDD) is marked by disturbances in brain functional connectivity. This connectivity is modulated by rhythmic oscillations of brain electrical activity, which enable coordinated functions across brain regions. Oscillatory activity plays a central role in regulating thinking and memory, mood, cerebral blood flow, and neurotransmitter levels, and restoration of normal oscillatory patterns is associated with effective treatment of MDD. Repetitive transcranial magnetic stimulation (rTMS) is a robust treatment for MDD, but the mechanism of action (MOA) of its benefits for mood disorders remains incompletely understood. Benefits of rTMS have been tied to enhanced neuroplasticity in specific brain pathways. We summarize here the evidence that rTMS entrains and resets thalamocortical oscillators, normalizes regulation and facilitates reemergence of intrinsic cerebral rhythms, and through this mechanism restores normal brain function. This entrainment and resetting may be a critical step in engendering neuroplastic changes and the antidepressant effects of rTMS. It may be possible to modify the method of rTMS administration to enhance this MOA and achieve better antidepressant effectiveness. We propose that rTMS can be administered: (1) synchronized to a patient's individual alpha frequency (IAF), or synchronized rTMS (sTMS); (2) as a low magnetic field strength sinusoidal waveform; and, (3) broadly to multiple brain areas simultaneously. We present here the theory and evidence indicating that these modifications could enhance the therapeutic effectiveness of rTMS for the treatment of MDD.

The intended-and unintended-consequences of healthcare reform.

Healthcare reform will affect providers by: Changing employer-sponsored health plans. Cutting Medicare payment. Expanding Medicaid coverage. Penalizing excessive avoidable readmissions. Increasing Medicaid payment to primary care physicians. Increasing payment to community health centers. Changing patient-provider relationships.

Immunologic control of tumors by in vivo Fc gamma receptor-targeted antigen loading in conjunction with double-stranded RNA-mediated immune modulation.

Despite the expression of non-self or neo-epitopes, many tumors such as lymphoid malignancies or cancers induced by oncogenic viruses are able to gradually overcome the immune defense mechanisms and spread. Using a preclinical model of hematological malignancy, we show that Ig-associated idiotypic determinants are recognized by the immune system in a fashion that results in immune deviation, allowing tumor progression and establishment of metastases. Using gene-targeted mice, we show that anti-idiotypic MHC class I-restricted immunity is promoted by ITAM motif (ITAM+) FcgammaR, but kept in check by ITIM motif (ITIM+) FcgammaRIIB-mediated mechanisms. In addition to interfering with the functionality of ITIM+ FcgammaR, effective anti-idiotypic and antitumoral immunity can be achieved by FcgammaR-targeted delivery of epitope in conjunction with administration of stimulatory motifs such as dsRNA, correcting the ineffective response to idiotypic epitopes. The immune process initiated by FcgammaR-mediated targeting of epitope together with dsRNA, resulted in control of tumor growth, establishment of immune memory and protection against tumors bearing antigenic variants. In summary, targeted delivery of MHC class I-restricted epitopes via ITAM+ FcgammaR, in conjunction with use of TLR-binding immune stimulatory motifs such as dsRNA, overcomes suboptimal responses to idiotypic determinants and may constitute a novel approach for the treatment of a broad range of malignancies. Finally, the results shed light on the mechanisms regulating the idiotypic network and managing the diversity associated with immune receptors.

Consumer-driven health plans: implications for providers.

By shifting more healthcare costs to workers, employers are hoping to slow the rise in company costs. It is too early to tell whether these consumer-driven health plans will address the issue of soaring costs. However, one thing is certain: They will have ramifications for healthcare providers.

Two numbers you need to know.

By examining two numbers--managed care denial and recovery rates--hospitals can assess the effectiveness of their denial management efforts and payer performance and best focus efforts on payer contract compliance to achieve prompt payment.

Navigating payment pitfalls in managed care.

Healthcare providers need to identify and address payment problems relating to denied or underpaid claims. Before contract renegotiation, providers should identify the total dollar amount of claims that are denied or underpaid for each payer. Providers should choose managed care contract information systems that can grow with the hospital's managed care volume. Providers should identify all underpayment problems before negotiating a settlement with a payer.