Iodixanol nasal solution reduces allergic rhinoconjunctivitis signs and symptoms in Allergen BioCube®: a randomized clinical trial.

PURPOSE: Allergic rhinitis (AR) affects ~20% of the population worldwide. The objectives of this study were to evaluate the safety and efficacy of iodixanol nasal solution (Nasapaque) for AR treatment, using the Allergen BioCube® (ABC®), an environmental exposure unit. Iodixanol is a commonly used contrast media agent that shows efficacy on the signs and symptoms of AR. PATIENTS AND METHODS: Seventy-three adult subjects with AR were randomized to iodixanol or placebo treatment in a double-masked efficacy and safety study conducted outside of ragweed pollen season. In-office treatment was administered after BioCube® ragweed pollen exposure, and again 8 days later prior to ragweed exposure. Nasal and ocular efficacy and safety assessments were conducted before and after treatment. RESULTS: Iodixanol treatment resulted in statistically significantly lower total nasal symptom scores as compared to placebo at several time points post-treatment and ABC exposure. Individual nasal and ocular symptoms, notably nasal itching and ocular itching, showed evidence of lower scores in the iodixanol group. Peak nasal inspiratory flow (PNIF) improved (9%-16%) with iodixanol from baseline as compared to PNIF in the placebo group which ranged from 3% worsening to improvement of 2%. Few (9) adverse events occurred. CONCLUSION: Iodixanol nasal solution demonstrated efficacy for relief of several nasal and ocular allergic rhinoconjunctivitis signs and symptoms, and was safe and well tolerated in this early Phase II exploratory trial. Further studies with iodixanol are warranted. Allergy challenge models such as the ABC provide valuable assessments of allergen exposures and drug efficacies. STUDY IDENTIFICATION NUMBER: NCT02377895.

Preliminary study of hearing protection and non-impact, blast-induced concussion in US military personnel.

PRIMARY OBJECTIVE: To examine the relationship between hearing protection and non-impact, blast-induced concussion in US military personnel. RESEARCH DESIGN: Retrospective cohort study. METHODS AND PROCEDURES: A total of 501 US service members from the Expeditionary Medical Encounter Database with hearing protection status reported either 'worn' or 'not worn' were eligible for analysis. Clinical records were reviewed for concussion diagnoses. Univariate and multiple logistic regressions were performed. MAIN OUTCOMES AND RESULTS: Overall, 270 (53.9%) service members sustained non-impact, blast-induced concussion and 231 (46.1%) sustained other blast injuries. Only 39.6% (107 of 270) of service members with concussion wore hearing protection at the point of injury compared with 61.0% (141 of 231) of those with other injuries (p < 0.001). After adjusting for covariates, service members wearing hearing protection had significantly lower odds of concussion compared with those not wearing hearing protection (odds ratio = 0.42, 95% confidence interval = 0.29-0.62). CONCLUSIONS: To our knowledge, this preliminary study is the first to demonstrate that hearing protection is associated with lower odds of non-impact, blast-induced concussion. The benefits of using hearing protection in terms of force readiness could be significant since many service members wounded in recent conflicts were diagnosed with concussion.

Correction for Gonzalez et al., "Migraines Are Correlated with Higher Levels of Nitrate-, Nitrite-, and Nitric Oxide-Reducing Oral Microbes in the American Gut Project Cohort".

[This corrects the article DOI: 10.1128/mSystems.00105-16.].

Migraines Are Correlated with Higher Levels of Nitrate-, Nitrite-, and Nitric Oxide-Reducing Oral Microbes in the American Gut Project Cohort.

Nitrates, such as cardiac therapeutics and food additives, are common headache triggers, with nitric oxide playing an important role. Facultative anaerobic bacteria in the oral cavity may contribute migraine-triggering levels of nitric oxide through the salivary nitrate-nitrite-nitric oxide pathway. Using high-throughput sequencing technologies, we detected observable and significantly higher abundances of nitrate, nitrite, and nitric oxide reductase genes in migraineurs versus nonmigraineurs in samples collected from the oral cavity and a slight but significant difference in fecal samples. IMPORTANCE Recent work has demonstrated a potentially symbiotic relationship between oral commensal bacteria and humans through the salivary nitrate-nitrite-nitric oxide pathway (C. Duncan et al., Nat Med 1:546-551, 1995, http://dx.doi.org/10.1038/nm0695-546). Oral nitrate-reducing bacteria contribute physiologically relevant levels of nitrite and nitric oxide to the human host that may have positive downstream effects on cardiovascular health (V. Kapil et al., Free Radic Biol Med 55:93-100, 2013, http://dx.doi.org/10.1016/j.freeradbiomed.2012.11.013). In the work presented here, we used 16S rRNA Illumina sequencing to determine whether a connection exists between oral nitrate-reducing bacteria, nitrates for cardiovascular disease, and migraines, which are a common side effect of nitrate medications (U. Thadani and T. Rodgers, Expert Opin Drug Saf 5:667-674, 2006, http://dx.doi.org/10.1517/14740338.5.5.667).

Head stabilization measurements as a potential evaluation tool for comparison of persons with TBI and vestibular dysfunction with healthy controls.

A large percentage of persons with traumatic brain injury incur some type of vestibular dysfunction requiring vestibular physical therapy. These injuries may affect the natural ability to stabilize the head while walking. A simple method of utilizing motion capture equipment to measure head movement while walking was used to assess improvements in head stabilization of persons undergoing computerized vestibular physical therapy and virtual reality training for treatment of their vestibular problems. Movement data from the head and sacrum during gait were obtained over several visits and then analyzed to determine improved oscillatory head movement relative to the sacrum. The data suggest that, over time with treatment, head stabilization improves and moves toward a pattern similar to that of a healthy control population. This simple analysis of measuring head stability could be transferred to smaller, portable systems that are easily utilized to measure head stability during gait for use in gait assessment and physical therapy training.

Dynamic assessment of binocular eye movement coordination: norms and functional implications.

Alignment of the two eyes is controlled by a finely tuned, fast acting system with components within the brain. Assessment of binocular alignment has classically been done statically. Eye positions are assessed in primary position and at eccentric angles to interpret the functional status of the oculomotor nerves and muscles. However, assessment of dynamic eye alignment, the coordination of the eyes during eye movements, has been less commonly carried out and has not been formalized with population norms. Clinicians are aware of slow eye movement dynamic alignment changes, such as that clinically observed in Intranuclear Ophthalmoplegia. But assessment of eye alignment during rapid eye movements, such as saccade or pursuit has not been part of neuro-ophthalmologic assessment. With the advent of inexpensive, high resolution recording systems, both eyes can be simultaneously recorded and their coordination during movement compared. Thus, we now have an opportunity to provide a laboratory based objective measurement of a gamut of binocular coordination systems. Recent research in humans has demonstrated increased variability of binocular coordination during divided attention. Variability is an interesting statistic that can be sensitively assessed in the velocity domain without extensive gaze position recalibration procedures during recording over long intervals. Variability can thus be used as a robust, long-term eye movement parameter with minimal intrusiveness to the subject. It is proposed that population studies of binocular coordination during eye movements be carried out to determine neurologic norms so that conditions such as brain injury and others can be assessed with a functional tool with objective parameters.

Blast-related ear injuries among U.S. military personnel.

Blast-related ear injuries are a concern during deployment because they can compromise a servicemember's situational awareness and adversely affect operational readiness. The objectives of this study were to describe blast-related ear injuries during Operation Iraqi Freedom, identify the effect of hearing protection worn at the point of injury, and explore hearing loss and tinnitus outcomes within one year after injury. The Expeditionary Medical Encounter Database was used to identify military personnel who survived blast-related injury, and it was linked with outpatient medical databases to obtain diagnoses of hearing loss and tinnitus. The prevalence of ear injuries was 30.7% (1,223 of 3,981). The most common ear injury diagnoses were "inner or middle ear injury involving tinnitus" and tympanic membrane (TM) rupture. Hearing protection reduced the odds of ear injury involving tinnitus. Personnel with TM rupture had higher odds of hearing loss (odds ratio [OR] = 6.65, 95% confidence interval [CI] = 5.04-8.78) and tinnitus outcomes (OR = 4.34, 95% CI = 3.12-6.04) than those without TM rupture. Ear injuries and hearing impairment are frequent consequences of blast exposure during combat deployment. Hearing protection is warranted for all servicemembers at risk of blast exposure.

Perceived stigma and barriers to mental health care in Marines attending the Combat Operational Stress Control program.

The Department of Defense is aggressively addressing combat stress reactions (CSRs) through comprehensive Combat/Operational Stress Control (COSC) briefings/programs and referral resources for the prevention, identification, and treatment of stress reactions. The purpose of this study was to develop and administer a survey to assess perceptions of CSRs and barriers to care which affect help-seeking behavior in Marines attending the COSC program. A sample of 553 U.S. Marine Corps Officers and Enlisted personnel from Air (44%), Logistics (38%), and Infantry (18%) communities were recruited for the survey. The results suggested that misconceptions and stigma about CSRs still persist in Marines. The findings reinforced the need to facilitate treatment utilization by focusing on mental health-related stigma as well as organizational barriers.

High altitude headache and acute mountain sickness at moderate elevations in a military population during battalion-level training exercises.

Few studies have evaluated high altitude headache (HAH) and acute mountain sickness (AMS) in military populations training at moderate (1,500-2,500 m) to high altitudes (>2,500 m). In the current study, researchers interviewed active duty personnel training at Marine Corps Mountain Warfare Training Center. Participants were asked about HAH and AMS symptoms, potential risk factors, and medications used. In a sample of 192 U.S. Navy and Marine Corps personnel, 14.6% reported AMS (Lake Louise Criteria > or = 3) and 28.6% reported HAH. Dehydration and recent arrival at altitude (defined as data collected on days 2-3) were significantly associated with AMS; decreased sleep allowance was significantly associated with HAH. Although ibuprofen/Motrin users were more likely to screen positive for AMS, among AMS-positive participants, ibuprofen/Motrin users had decreased likelihood of reporting robust AMS relative to non-ibuprofen/Motrin users (p < 0.01). These results suggest that maintenance of hydration and adequate sleep allowance may be critical performance requirements at altitude. Further, ibuprofen/Motrin may be a reasonable treatment for the symptoms of AMS and HAH, although further study is warranted.

Epidemiologic study to explore links between Ménière syndrome and migraine headache.

Many authors have noted an association between Ménière syndrome and migraine headache. In an attempt to explore a possible link between these two disorders, we performed an epidemiologic study. The National Health Interview Survey (NHIS) includes interviews with tens of thousands of patients annually to estimate the incidence of various diseases. In this study the data collected from the NHIS for the years 1986 to 1988 and 1994 were analyzed to determine the incidence of Ménière syndrome and migraine headache. A total of 423,400 individuals were interviewed over the combined 4 years included in this evaluation. The incidence of migraine headache was calculated at 3.8%, and the incidence of Ménière syndrome was estimated at 0.14%. The incidence of migraine headache in patients with Ménière syndrome was estimated at 4.5%. The incidence of migraine headache was not substantially elevated in patients with Ménière syndrome when compared to the general population.

The clinical differentiation of cerebellar infarction from common vertigo syndromes.

This article summarizes the emergency department approach to diagnosing cerebellar infarction in the patient presenting with vertigo. Vertigo is defined and identification of a vertigo syndrome is discussed. The differentiation of common vertigo syndromes such as benign paroxysmal positional vertigo, Meniere's disease, migrainous vertigo, and vestibular neuritis is summarized. Confirmation of a peripheral vertigo syndrome substantially lowers the likelihood of cerebellar infarction, as do indicators of a peripheral disorder such as an abnormal head impulse test. Approximately 10% of patients with cerebellar infarction present with vertigo and no localizing neurologic deficits. The majority of these may have other signs of central vertigo, specifically direction-changing nystagmus and severe ataxia.

Quantitative electroencephalography for tinnitus--a means for data collection, analysis, and translation.

Quantitative electroencephalography (QEEG) is the technique whereby brain electrical activity in individuals is recorded as they sit quietly with their eyes closed. The electrical activity is quantified with a variety of statistical measures to characterize the huge variation in combinations of emissions from the brain. Neuroscience research has demonstrated that such resting brain activity measures may be consistently altered in conditions such as depression or dementia. A wide variety of ongoing efforts are attempting to find characterizations that reliably denote other neurological conditions. In research on tinnitus, a variety of groups have been working to characterize QEEG changes related to the presence of the abnormal sensation of sound and to the emotional distress associated with it. QEEG changes related to the tinnitus percept are in the gamma electroencephalography (EEG) band recorded from temporal lobes. Clinical depression has a reliable marker in the depression of posterior cerebral alpha EEG frequency band activity, and this same activity is found in patients with tinnitus of the severe disabling type. In the past, QEEG has suffered from inconsistent recording methods, closed data sets, and noncompatible analytical techniques. Now in the modern era, when reliable data sets are shared and hardware and software are less expensive, regular use of QEEG will be clinically important. Those prepared to make the minor investment in equipment and training will reap the benefit of objective measures of brain activity. Knowing patterns of QEEG activity related to tinnitus and its associated depression will help clinicians better manage these patients.

Effects of caffeine on postural stability.

The purpose of this study was to investigate the effects of a caffeine-containing "energy drink" on postural stability. Twenty-three young adult participants stood on a balance-measuring platform for two intervals of 30 seconds each, once with eyes open and once with eyes closed. Subjects performed the tasks before and 1 hour after consumption. Results showed no significant effect, either with eyes open or eyes closed, on movement of the body's center of pressure.

Tinnitus treatment with customized sounds.

Recent studies have indicated that the pathophysiological basis for tinnitus may be abnormal activity in the auditory areas of the brain rather than aberrant activity in the periphery. Tinnitus-related activity leads to changes in tonotopic representation in auditory cortex. However, such reorganization can be reversed through training-induced changes in the response pattern of cortical neurons. We address this problem by using customized sounds that reproduce the subjective experience to reduce overactive auditory circuits. The results of two preliminary studies indicate that customized sound therapy (CST*) aimed at this central dysfunction reduces tinnitus quickly and safely. Participants described immediate relief, showed changes on the Tinnitus Handicap Questionnaire, and reported changes in hearing threshold within 3 weeks. We also saw changes in the intensity dependence of the auditory N100 in tinnitus patients, supporting the idea that tinnitus reflects a reorganization of tonotopic maps in the auditory cortex. The main correlate of this reorganization was the enhanced contrast between responses to the perceived tinnitus pitch and tones approximately one octave lower. After 3 weeks of CST, the intensity dependence to the tinnitus pitch decreased, making these responses more similar to those from normal subjects responding to tones in the same frequency.

A randomized controlled trial of cognitive-behavior therapy for tinnitus.

This study is a randomized, waitlist-controlled trial testing the effect of a brief, "manualized" cognitive-behavioral group therapy on distress associated with tinnitus, quality of well-being, psychological distress including depression, and internal focus. Cognitive-behavioral therapy (CBT) included training in activity planning, relaxation training and, primarily, cognitive restructuring. Sixty-five participants were recruited, and 41 completed treatment. Participants were randomly assigned to receive 8 weeks of manualized group CBT either immediately or after an 8-week waiting period. Participants completed outcome measures at the time of their random assignment and at 8, 16, and 52 weeks later. Repeated-measure analysis of covariance revealed significant group-by-time interactions on measures of tinnitus distress and depression, indicating that CBT led to greater improvement in those symptoms. The current results suggest that CBT, applied in a group format using a manual, can reduce the negative emotional distress, including depression, associated with tinnitus.

Task performance and eye activity: predicting behavior relating to cognitive workload.

INTRODUCTION: The focus of this study was to examine oculomotor behavioral changes while subjects performed auditory and driving tasks. METHODS: There were 13 participants who completed 3 10-min tasks consisting of driving only, the Paced Auditory Serial Addition Task (PASAT) only, and a dual task of both driving and auditory tasks. For each participant, changes in six measures were assessed as a function of cognitive workload, specifically changes in eye activity, including blink frequency, blink duration, fixation frequency, fixation duration, pupil diameter, and horizontal vergence. In addition, deviations in lateral lane position were assessed as a measure of driving behavior. RESULTS: Compared with the subjects' behavior in the driving-only task, results showed an increase in blink frequency during the combined driving and auditory task. Also, during the dual task the mean pupil diameter and horizontal vergence increased when subjects performed well in the auditory task in contrast to when the subjects performed poorly. Evidence of visual tunneling or reduced range of scanning and decreases in rearview mirror and odometer glances appeared when subjects performed the driving and auditory dual task. There was no significant change in fixation frequency. However, decreased fixation duration appeared to predict upcoming errors in the auditory task. Pupil diameter changes were significantly higher when performing well on the auditory task than when subjects were performing poorly. CONCLUSION: Eye behavior trends reported in this study may provide insight to human behavior corresponding with cognitive workload, which may in turn be utilized to produce reliable workload indicators and applications that predict poor performance in real time.

Antidepressant therapy in tinnitus.

OBJECTIVE: Review the literature on the co-morbidity of depression and anxiety with tinnitus. Briefly consider proposed mechanisms by which antidepressants might be helpful for tinnitus, including treatment of co-morbid depression and anxiety and a more direct serotonergic mechanism of tinnitus. Survey the literature on antidepressants and tinnitus including tinnitus reported as a side effect of antidepressants (phenelzine, amitriptyline, protriptyline, doxepin, imipramine, fluoxetine, trazadone, bupropion, venlafaxine), tinnitus associated with withdrawal of antidepressants (venlafaxine and sertraline) and antidepressants as a treatment for tinnitus (case reports--fluoxetine and paroxetine, retrospective reviews--imipramine and selective serotonin reuptake inhibitors, single blind trials of amitriptyline and double blind placebo controlled trials of trimipramine, nortriptyline, paroxetine and sertraline). Provide suggestions on future directions, specifically replication of prior studies and a dose finding study of paroxetine for the treatment of tinnitus.

Cognitive neuroscience in tinnitus research: a current review.

Advances in methods of examining the human brain have led to a dramatic increase in specific knowledge about the origins of tinnitus. Neural modeling, behavioral measurements of hearing performance and psychological state, neuro-morphology, metabolic measurements of neural activity, electromagnetic recordings of synaptic potentials, and optical measurements of action potentials are all modalities that have provided insights or the promise of new information about the pathophysiology of tinnitus. This review examines these techniques and their contributions to knowledge about tinnitus.

Randomized placebo-controlled trial of a selective serotonin reuptake inhibitor in the treatment of nondepressed tinnitus subjects.

OBJECTIVE: To assess the efficacy of a selective serotonin reuptake inhibitor (paroxetine) for relief of tinnitus. DESIGN: One hundred twenty tinnitus sufferers participated in a randomized double-blind placebo-controlled trial. Paroxetine or placebo was increased to a maximally tolerated dose (up to 50 mg/day), and patients were treated for a total of 31 days at the maximal dose. METHODS: Patients with chronic tinnitus were recruited from our university-based specialty clinic by referral from otolaryngologists and audiologists in the local community and by advertisement. Patients with psychotic or substance use disorders or suicidal ideation were excluded, as were those using psychoactive medications (this resulted in only 1 subject with major depression in the study) or any other medications that interact with paroxetine and those with inability to hear at one's tinnitus sensation level. Fifty-eight percent of patients were male, 92% were Caucasian, and the average age was 57. OUTCOMES MEASURES: Tinnitus matching, the Tinnitus Handicap Questionnaire, the question: How severe (bothered, aggravating) is your tinnitus? Quality of Well-Being and other psychological questionnaires. RESULTS: Paroxetine was not statistically superior to placebo on the following tinnitus measures (tinnitus matching, 5- or 10-db drop, Tinnitus Handicap Questionnaire, quality of well-being measures, how severe, how bothered, positive change). There was a significant improvement in the single item question, How aggravating is your tinnitus? for those in the paroxetine group compared with the placebo group. CONCLUSIONS: These results suggest that the majority of individuals in this study did not benefit from paroxetine in a consistent fashion. Further work remains to be done to determine if subgroups of patients (e.g., those who tolerate higher doses, those who are depressed) may benefit.

The Dix-Hallpike test and the canalith repositioning maneuver.

The Dix-Hallpike test and the canalith repositioning maneuver (CRM) are used to diagnose and treat benign positional vertigo (BPV). Dix-Hallpike is the standard procedure for diagnosis of BPV, but if the horizontal canal is not tested for BPV and the Dix-Hallpike is only carried out once, the condition may not be diagnosed and appropriately treated. We describe our method of testing for BPV and treating it with CRM. The Dix-Hallpike test involves rapidly moving the patient from a sitting position to "head hanging," where the patient's head is at least 10 degrees below horizontal. This is performed initially for the posterior semicircular canals. If these movements fail to elicit vertigo and nystagmus, tests of the horizontal semicircular canals are performed by laying the patient on each side. Importantly, if there is no vertigo or nystagmus elicited by testing the horizontal semi-circular canals, the posterior semicircular canals are tested again. It appears that being held in the head hanging positions and then left and right lateral positions will often allow the canaliths to collect such that the Dix-Hallpike test will become positive. Failure to repeat the tests of the posterior semicircular canals may result in a falsely negative test. Testing the horizontal canals and repeating the Dix-Hallpike test will reduce the likelihood of patients undergoing extra testing or other consequences of misdiagnosis. If, during any of this testing, a movement elicits vertigo or nystagmus, the appropriate CRM is then carried out.