High resolution computed tomography pattern of usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease: Relationship to survival.

PURPOSE: Interstitial lung disease is a common extra-articular manifestation of rheumatoid arthritis (RA-ILD) and is associated with significant morbidity and mortality. However, limited data exist regarding predictors of mortality. We sought to examine the prognostic value of the high-resolution computed tomography (HRCT) patterns in patients with RA-ILD. MATERIALS AND METHODS: RA-ILD patients with HRCT patterns of usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) were identified among a longitudinal cohort of individuals evaluated at National Jewish Health. A total of 158 subjects were included in the study. For each subject, the earliest available HRCT was reviewed independently by two expert thoracic radiologists blinded to clinical data. HRCT patterns were classified as demonstrating definite UIP, possible UIP, or NSIP. Kaplan-Meier curves were generated and survival was compared among the three patterns using a log rank test for trend. RESULTS: One hundred subjects (63%) had HRCT findings classified as definite UIP, 23 (15%) as possible UIP and 35 (22%) as NSIP. No difference in survival was seen between subjects with definite UIP versus those with possible UIP. The combined group of subjects with either definite- or possible UIP had significantly worse survival than those with NSIP (log-rank p = 0.03). CONCLUSIONS: In patients with RA-ILD, patients with either definite UIP or possible UIP have equally poor survival when compared to those with an NSIP pattern.

Applying Choosing Wisely: Antinuclear Antibody (ANA) and Sub-Serology Testing in a Safety Net Hospital System.

OBJECTIVE: In 2013, the American College of Rheumatology (ACR) participated in the Choosing Wisely campaign and devised a recommendation to avoid testing antinuclear antibody (ANA) subserologies without a positive ANA and clinical suspicion of disease. The goals of our study were to describe ANA and subserology ordering practices and predictors of ordering concurrent ANA and subserologies in a safety-net hospital. METHODS: We identified ANA and subserologies (dsDNA, Sm, RNP, SSA, SSB, Scl-70 and centromere) completed at Denver Health between 1/1/2005 and 12/31/2011. Variables included demographics, primary insurance, service, and setting from which the test was ordered. We performed multivariable logistic regression to determine predictors of concurrent ordering of ANA and subserologies. RESULTS: During seven years, 3221 ANA were performed in 2771 individuals and 211 (6.6%) were performed concurrently with at least one subserology. The most common concurrent subserologies were dsDNA (21.8%), SSA (20.8%), and SSB (19.7%). In the multivariable logistic analysis, significant predictors of concurrent ANA and subserologies were the labs being ordered from subspecialty care (OR 8.12, 95% CI 5.27-12.50, p-value <0.0001) or from urgent/inpatient care (OR 3.86, 95% CI 1.78-8.38, p-value 0.001). A significant predictor of decreased odds was male gender (OR 0.32, 95% CI 0.21-0.49, p-value <0.0001). Five individuals (2.2% of the negative ANA with subserologies ordered) had a negative ANA but positive subserologies. CONCLUSION: Of 3221 ANA, 6.6% were performed concurrently with subserologies, and subspecialists were more likely to order concurrent tests. A negative ANA predicted negative subserologies with rare exceptions, which validates the ACR's recommendations.

Comparison of the 1987 American College of Rheumatology and the 2010 American College of Rheumatology/European League against Rheumatism criteria for classification of rheumatoid arthritis in the Nurses' Health Study cohorts.

Performance of rheumatoid arthritis (RA) classification by the 2010 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria, compared to the 1987 ACR criteria, has not been assessed in population-based cohorts in which disease identification is by mailed questionnaire. Women followed in the Nurses' Health Study and Nurses' Health Study II cohorts self-reported new doctor-diagnosed RA on biennial questionnaires. Two RA experts reviewed medical records of 128 new RA self-reports to obtain individual 1987 and 2010 criteria and arrived at a consensus opinion. We compared agreement in classification by the two criteria sets (kappa), and calculated sensitivity and specificity, with reviewers' opinion as gold standard. Ninety-eight (77%) participants were classified as RA by reviewers' consensus opinion; 98 (77%) fulfilled 1987 criteria, while 79 (63%) fulfilled 2010 criteria. Seventy-two (56%) were classified as RA by both sets, 21 (16%) by neither, 26 (20%) by only 1987 criteria, and 9 (7%) by only 2010 criteria. Kappa for concordance was 0.36 (95% CI 0.20-0.53). Compared to reviewer's opinion, sensitivity and specificity were 0.93 and 0.77 for 1987 criteria, and 0.79 and 0.87 for 2010 criteria. Participants fulfilling 1987 criteria only were more likely to be seronegative. In these prospective population-based cohorts, significant discordance between 1987 ACR and 2010 ACR/EULAR criteria for classifying RA exists. Using the 2010 ACR/EULAR criteria alone had decreased sensitivity, and seronegative RA cases would be excluded in particular. Combined use of both will be necessary to maximize inclusion and allow sensitivity analyses.

Electrophysiology quantitative electroencephalography/low resolution brain electromagnetic tomography functional brain imaging (QEEG LORETA): Case report: Subjective idiopathic tinnitus - predominantly central type severe disabling tinnitus.

The clinical significance of QEEG LORETA data analysis performed sequentially within 6 months is presented in a case report of a predominantly central type severe disabling subjective idiopathic tinnitus (SIT) before and following treatment. The QEEG LORETA data is reported as Z-scores of z = ± 2.54, p < 0.013. The focus is on demonstration of patterns of brain wave oscillations reflecting multiple brain functions in multiple ROIs in the presence of the tinnitus signal (SIT). The patterns of brain activity both high, middle and low frequencies are hypothesized to reflect connectivities within and between multiple neuronal networks in brain. The Loreta source localization non auditory ROI Images at the maximal abnormality in the very narrow band frequency spectra (24.21 Hz), showed the mathematically most probable underlying sources of the scalp recorded data to be greatest in the mid-cingulate, bilateral precuneus, cingulate and the bilateral caudate nucleus. Clinical correlation of the data with the history and course of the SIT is considered an objective demonstration of the affect, behavioral, and emotional component of the SIT. The correlation of the caudate activity, SIT as the traumatic event with the clinical course of PTSD, and the clinical diagnosis of PTSD is discussed. The clinical translation for patient care is highlighted in a SIT patient with multiple comorbidities by translation of QEEG/LORETA electrophysiologic data, as an adjunct to: provide an objectivity of patterns of brain wave activity in multiple regions of interest (ROIs) reflecting multiple brain functions, in response to and in the presence of the tinnitus signal, recorded from the scalp and analyzed with the metrics of absolute power, relative power, asymmetry, and coherence, for the subjective tinnitus complaint (SIT); 2) provide an increase in the accuracy of the tinnitus diagnosis; 3) assess/monitor treatment efficacy; 4) provide a rationale for selection of a combined tinnitus targeted therapy of behavioral, pharmacologic, sound therapy modalities of treatment attempting tinnitus relief; 5) provide insight into the medical significance of the SIT; 6) attempt discriminant function analysis for identification of a particular diagnostic clinical category of CNS neuropsychiatric disease; and 7) attempt to translate what is known of the neuroscience of sensation, brain function, QEEG/LORETA source localization, for the etiology and prognosis of the individual SIT patient.

Anti-citrullinated peptide autoantibodies, human leukocyte antigen shared epitope and risk of future rheumatoid arthritis: a nested case-control study.

INTRODUCTION: The aim of this study was to characterize anti-citrullinated peptide antibody (ACPA) serostatus in pre-clinical rheumatoid arthritis (RA) with and without Human Leukocyte Antigen-Shared Epitope (HLA-SE) alleles. METHODS: We identified 192 women in the Nurses' Health Study cohorts with blood samples obtained 4 months to 17 years prior to medical record-confirmed RA diagnosis. Three controls were selected matched on age, cohort, menopausal status and post-menopausal hormone use. Reactivities to 18 ACPAs were measured using a custom BioPlex platform. We used conditional logistic regression to calculate the relative risk (RR) of RA for any ACPA-positive and peptide-specific ACPA-positive and examined RRs by time between blood draw and RA onset. Measures of multiplicative and additive interaction between any ACPA-positive and HLA-SE were calculated. RESULTS: All ACPAs by peptide groups were significantly associated with RA risk, RRs ranged from 4.7 to 11.7. The association between ACPA and RA varied over time with the strongest association in those with blood draw less than 5 years before onset (RR 17.0 [95% CI 5.8 to 53.7]) and no association 10 or more years prior to onset (RR 1.4 [95% CI 0.5 to 4.3]). Individuals with both HLA-SE and any ACPA-positive had the highest risk of RA. HLA-SE-positive RA cases showed reactivity to more ACPA types than HLA-SE negative (χ2 test for trend, P = 0.01). CONCLUSIONS: There is increasing ACPA reactivity up to 10 years before RA onset with the strongest association within 5 years of RA onset. The magnitude of the response to ACPAs, in combination with the presence of HLA-SE, is most important for identifying those individuals with the highest risk of RA.

Epstein-Barr virus serologic abnormalities and risk of rheumatoid arthritis among women.

BACKGROUND: Epstein-Barr virus (EBV) infection and the immune response may be involved in the pathogenesis of rheumatoid arthritis (RA). Past studies have suggested an association between EBV and RA. METHODS: We studied the association between EBV serologies and RA risk in a nested case-control study in the Nurses' Health Study (NHS) cohorts. We confirmed incident RA cases from 1990 to 2002 by questionnaire and medical record review. Each incident case with blood collected prior to RA symptoms was matched with a healthy participant by time of day and date of blood collection, birth year, menopausal status and postmenopausal hormone use. Immunofluorescence assays measured serologic EBV responses: viral capsid antigen, early-antigen-diffuse and early antigen-complex (restricted and diffuse), Epstein Barr nuclear antigen (EBNA)-1, EBNA-2 and cytomegalovirus (CMV), as control. All were reported as titers, except CMV, which was reported as positive or negative. Antinuclear antibody positive samples were excluded. Elevated EBV antibody titers were defined as the upper 20% (or nearest titer) among controls. Conditional logistic regression analyses modeled RA risk associated with elevated EBV titers or the presence/absence of CMV, further adjusted for pack-years smoking and alcohol intake. RESULTS: Eighty-seven incident RA cases were identified. Mean time to RA after blood draw was 6.2 (± 3.5) years in NHS and 1.9 (± 0.6) years in NHS II. Antibody titers against EBV were not significantly different between pre-RA cases and controls. CONCLUSIONS: In this prospective study of women, we observed no association between EBV serologies and RA risk.

The tympanic membrane displacement test and tinnitus: preliminary report on clinical observations, applications, and implications.

UNLABELLED: The tympanic membrane displacement test (TMDT) is an attempt to record intracranial pressure (ICP) reflective of an intracranial pulse pressure amplitude wave (IPPA) transmitted to the inner ear and tympanic membrane with a probe placed into the external ear canal. Twelve tinnitus patients, divided into two groups, who were resistant to attempts to achieve tinnitus control or relief were selected for the TMDT. The group 1 TMDT recordings were obtained on one session test date, and group 2 (n = 6) recordings were obtained sequentially on different session test dates. Patient selection with the medical audiologic tinnitus patient protocol (MATPP) identified all to have a nonpulsatile, predominantly central-type severe disabling subjective idiopathic tinnitus (SIT) resistant to attempts for tinnitus relief with instrumentation or medication. Associated complaints in all selected SIT patients included persistent ear blockage in the SIT ear, normal middle-ear function, controlled secondary endolymphatic hydrops in the SIT ear, sensorineural hearing loss of high frequency, hyperacusis, occasional vertigo, and central nervous system complaints of headache, head pressure, and cognitive interference in memory and/or speech expression. Clinical concern is for the presence of an increased ICP reflecting an idiopathic intracranial hypertension (IIH) which, if not identified and treated, may be a factor influencing the clinical course of this particular cohort of SIT patients, highlighted by persistent ear blockage and associated complaints as described. OBJECTIVES: We set out to accomplish a number of goals: (1) To identify abnormal intracranial pulse pressure (IPPA ICP) with the extracranial TMD in a preselected particular cohort of SIT patients clinically suspected (by use of the MATPP) to have an abnormal ICP (i.e., IIH); (2) to identify the abnormal IPPA ICP as a positive indicator for IIH and as a factor - not an etiology - influencing the clinical course of SIT in a preselected cohort of SIT patients; (3) to identify with the TMDT in SIT patients spontaneous nonevoked recordings of intra-aural pressure and test-retest reliability of the TMDT; (4) to identify with the TMDT levels of normal and abnormal IPPA ICP in real time in the clinical course of SIT (i.e., an objective diagnostic and treatment monitor function of the TMD targeting ICP and IIH before and after treatment); (5) to attempt to establish a correlation of treatment efficacy, targeting preand post-ICP as a manifestation of IIH, with SIT subjective tinnitus relief; (6) to identify the limitations and complications of the TMDT; and (7) to share with the reader the evolution of a new science of brain pulsatility and a technology having a clinical application for otology and neurotology complaints of hearing loss, tinnitus, ear blockage, and vertigo. The results reported in the literature complement and alter conventional medical teaching focusing on brain pulsation, absolute intracranial pressure, and brain disease. METHOD: The Southampton Tympanic Membrane Displacement Analyzer was used to record spontaneous intra-aural pressure waves in 12 SIT patients. Patients selected for the TMDT were divided into two groups: Group 1 (n = 6) recordings were obtained on one session test date, and group 2 (n = 6) recordings were obtained sequentially on different session test dates. Multiple recordings were attempted in all patients to identify test-retest reliability in both groups. An attempt for treatment and control of an elevated ICP with or without reduced cerebral compliance (CC) was recommended in 4 patients. RESULTS: With single and multiple recordings using the TMDT, the IPPA (i.e., ICP) was demonstrated to be abnormal and to fluctuate in the clinical course of 10 of the 12 predominantly central-type tinnitus patients (SIT): abnormal IIPA with reduced CC in 8 of 12 patients and normal IPPA with reduced compliance in 2 of 12. Tinnitus treatment results targeting ICP as a manifestation of IIH with Diamox were positive in the short term in 2 patients and incomplete in 3. The SIT relief is reflective of fluctuation in the ICP and the overall issue of multifactorial brain pulsatility. CONCLUSIONS: (1) The TMDT demonstrated repeated and consistent spontaneous nonevoked recordings of displacement of the tympanic membrane, reflective of intra-aural pressure, abnormal IPPA ICP in a preselected particular cohort of SIT patients clinically suspected to have an abnormal ICP (i.e., IIH). (2) Test-retest reliability of the TMDT was positive. (3) The results of the TMDT application for identification of an elevated ICP and reduced CC were positive in 10 of 12 particular preselected patients with nonpulsatile, predominantly central-type SIT resistant to attempts for tinnitus relief with instrumentation or medication. These positive findings support clinical and basic science investigations previously reported in the literature. (4) The clinical significance of these preliminary results of an elevated ICP in a particular cohort of SIT patients supports the clinical impression of the presence of an IIH and its influence on the clinical course and overall treatment of SIT. (5) A final conclusion as to the clinical significance of an elevated ICP and reduced CC for IIH and the diagnosis and treatment of tinnitus remains to be established.

Principles of tinnitology: tinnitus diagnosis and treatment a tinnitus-targeted therapy.

OBJECTIVE: To provide to the tinnitus professional a rationale for establishing accuracy in tinnitus diagnosis and the selection of modalities of therapy (i.e., medication, instrumentation, and surgery) for attempting tinnitus relief for patients with tinnitus diagnosed by completion of a medical-audiological tinnitus protocol (MATPP) and clinical course and found to be subjective idiopathic tinnitus of the severe disabling type (SIT). BACKGROUND: The completion of a MATPP has been recommended since 1977 for each tinnitus patient in an attempt to establish an accurate diagnosis. A tinnitus-targeted therapy (TTT), a combined treatment of medication and instrumentation focusing on pharmacotherapy, has evolved from our ongoing clinical experience since 1977 (now in excess of 10,000 SIT patients) [1-4]. Principles for SIT treatment have evolved from the TTT experience that provides a rationale for attempting tinnitus relief. In this report, the term tinnitus refers to SIT. METHOD: The strategies of TTT are based on the clinical translation for SIT diagnosis and treatment of (1) fundamentals of neuro-otological diagnosis; (2) fundamentals of sensory physiology; (3) extrapolation for treatment of known underlying neurochemistries from nuclear medicine imaging results e.g. single-photon emission computed tomography and positron emission tomography; (4) hypothesis of mechanism of tinnitus production , Tinnitus Dysynchrony Synchrony Theory (TDST) [5] , and hypothesis of the transformation-transition of the sensation of an aberrant auditory sensation-tinnitus (i.e., sensory component)-to one of affect (i.e., the emotional-behavioral component), Final Common Pathway of Tinnitus (FCP)[8]; and (5) innovative application of drug therapies designed for indications other than tinnitus [2,3]. RESULTS AND CONCLUSION: The ongoing clinical application of a rationale based on principles of diagnosis and treatment for SIT, which has evolved from our TTT clinical experience in SIT patients, continues to result in long-term tinnitus relief: in excess of 1 year in approximately 75% to 85% with medication and in 10% to 15% with instrumentation. SIT patients resistant to therapy persist at 10% to 15%.

Identification of undiagnosed inflammatory arthritis in a community health fair screen.

OBJECTIVE: To identify individuals with undiagnosed inflammatory arthritis (IA) and rheumatoid arthritis (RA) in a community health fair screen, and to establish in a health fair setting the diagnostic accuracy of combinations of the Connective Tissue Disease Screening Questionnaire (CSQ) and autoantibody testing for IA. METHODS: Screening for IA/RA was performed at health fair sites using a combination of the CSQ, joint examination, rheumatoid factor, and anti-cyclic citrullinated peptide (anti-CCP) antibody testing. IA was defined as > or =1 swollen joint suggestive of synovitis on joint examination by a trained clinician. RESULTS: Six hundred one subjects were screened; 51.0% participated because of joint symptoms (pain, stiffness, or swelling). Eighty-four subjects (14.0%) had > or =1 swollen joint, designated as IA on joint examination. Of the 601 subjects screened, 9 (1.5%) had IA and met > or =4 of 7 American College of Rheumatology criteria for RA but had no prior diagnosis of RA, and 15 (2.5%) had IA and RF and/or anti-CCP positivity, suggesting early RA. The diagnostic accuracy of combinations of the CSQ and autoantibody testing for the identification of IA yielded maximal sensitivity, specificity, and positive and negative predictive values of 95.3%, 99.2%, 71.4%, and 97.7%, respectively. CONCLUSION: Health fair screening may be an effective approach for the identification of individuals with undiagnosed IA/RA. A combination of the CSQ and autoantibody testing alone has clinically useful diagnostic accuracy for the detection of IA. Decisions regarding which methodology to use for future health fair IA/RA screening will depend on goals of screening and funding.

Final common pathway for tinnitus: theoretical and clinical implications of neuroanatomical substrates.

A final common pathway (FCP) for tinnitus has been hypothesized since 1989 for all clinical types of tinnitus, particularly subjective idiopathic tinnitus (SIT) of the severe disabling type. This was intended to explain the transformation-transition of the sensation of an aberrant auditory sensation-tinnitus (i.e., the sensory component)-to one of affect (i.e., the emotional-behavioral component) or, conversely, that an emotional-behavioral stimulus (affect) can result in the clinical manifestation of a sensation (a sensory stimulus). Understanding the pathophysiology of this transformation is fundamental for the diagnosis of tinnitus and the treatment of the patient, and it presents a dilemma to basic science, neuroscience, and clinical medicine. Clinically, tinnitus is not a unitary symptom; it constitutes many clinical types; can have its origin in the auditory or nonauditory systems and in the peripheral or central nervous system; and may be clinically manifest or subclinical. Accumulating evidence is presented to support the original hypothesis of an FCP. The resolution of this dilemma involves sensory processing (i.e., the integration, identification, and understanding of the ongoing, underlying, simultaneous, multiple associated brain function processes not only from one sensory modality but from multiple sensory modalities accompanying and associated with an FCP). In the FCP, the predominant brain function process is that of the sensory-affect transformation of a sensation and its conscious awareness by the affected patient. The neuroanatomical substrates identified in 1989 in tinnitus patients (reported originally in 1991 and published in 1995) are presented as a common framework for the hypothesis of an FCP. They further the understanding of the clinical heterogeneity of the tinnitus symptom, clinically manifest as multiple brain functions associated with the clinical course of tinnitus patients, particularly those with SIT. The FCP provides a model for tinnitus theory, diagnosis, and treatment. The FCP is not a tinnitus theory. Specifically, it is a hypothesis that attempts to explain how an aberrant auditory sensory stimulus becomes transformed into one of affect and somatomotor response. The neuroanatomical substrates of the FCP provide a basis for the identification of the involved neurocircuitries and neurochemistries. The physiology and biochemistry underlying the neuroanatomical substrates of the FCP provide a basis for translation for tinnitus diagnosis and treatment. The neuroanatomical substrates of the FCP are presented as algorithms of (1) components of a sensation (i.e., sensory, affect, and psychomotor), a translation from basic sensory physiology for tinnitus; (2) clinically manifest biophysiological brain functions and underlying processes associated with the tinnitus; (3) a model for investigation of metabolic-electrophysiological correlates for tinnitus; (4) the basis for an integrated theory of tinnitus and brain function (i.e., tinnitus dyssynchrony-synchrony theory; (5) a model for the identification of underlying neurocircuitries and neurochemistries involved in brain for the sensory-affect transformation of an aberrant auditory stimulus (tinnitus); (6) a model for the selection-introduction of innovative therapies attempting tinnitus relief; and (7) its clinical translation for objective monitoring systems for the determination of the efficacy of modalities of therapy attempting tinnitus relief. The hypothesis of the FCP for tinnitus and the identified neuroanatomical substrates, when viewed in terms of the physiology of sensory processing, is considered to be expanded and broader in its application for all sensations, normal or aberrant.

Subjective idiopathic tinnitus and palliative care: a plan for diagnosis and treatment.

This article integrates the highlights of the authors' clinical experiences derived from existing protocols for tinnitus diagnosis and treatment with the evolving discipline of palliation medicine. Specifically, it demonstrates how the inclusion of principles of palliation medicine contributes to the efficacy of treatment.

The role of the insula cortex in the final common pathway for tinnitus: experience using ultra-high-frequency therapy.

The insula cortex (Brodmann's 13-16) has distinct auditory and multisensory areas that have been identified through imaging to be active or hypoactive in cases of severe tinnitus. As such, the insula is a candidate for inclusion in the final common pathway (FCP) for tinnitus. The insula has connection with the prefrontal and auditory cortices, amygdala, thalamus, parabrachial nucleus, orbitofrontal cortex, striate, cuneus, and cerebellum. The insula, as part of the medial temporal lobe system-which also includes the amygdala and the hippocampus-modulates its metabolic activity after high-frequency stimulation. The FCP is characterized by numerous areas in the lemniscal and extralemniscal pathways, including the auditory regions in the thalamus, the cortex, and the cerebellum. It is suggested that elements of the FCP, formulated into a general model of tinnitus, should be considered as beads on a string in designing treatment strategies. This view is the direct result of our past and recent new experiences using ultra-high-frequency sound therapy in cases of severe disabling tinnitus, presented at this time. Behaviorally, tinnitus symptoms decrease by self-report and changes in minimal masking levels with high-frequency sound therapy. The use of multisensory vibration stimulation (somatosensory and high-frequency jointly) should also be explored to maintain or reprogram the auditory cor tical map and induce activity in the FCP circuit, including the parabrachial nucleus and the in sula, which may be the physiological substrate of tinnitus behavioral tests.

Central nervous system neurodegeneration and tinnitus: a clinical experience. Part II: translational neurovascular theory of neurodegenerative CNS disease and tinnitus.

The translation of a neurovascular hypothesis for Alzheimer's disease to subjective idiopathic tinnitus (SIT) is presented as a challenge to the predominantly sensorineural view of SIT and its clinical application for tinnitus treatment. The concept of neurovascular dysfunction and neurodegeneration (ND) in SIT patients has been proposed and reported as an etiology in a particular subset of tinnitus patients with a diagnosis of medical-audiological tinnitus, through a medical-audiological tinnitus patient protocol, to be a predominantly central-type, severe, disabling SIT (n = 54 of 96). A medical-audiological ND tinnitus profile was the basis for selection of 18 SIT patients (n = 18 of 54) for nuclear medicine brain imaging (i.e., single-photon emission computed tomography or positron emission tomography, or both). Objective findings were reported in 16 of this cohort of 18 SIT patients selected for nuclear medicine imaging (88.9%). Classification of central nervous system (CNS) ND and tinnitus differentiated between (1) ND, nonspecific and of unknown etiology; (2) ND manifested by perfusion asymmetries in brain associated with ischemia (n = 11 of 18); and (3) ND CNS disease consistent with nuclear medicine criteria for senile dementia Alzheimer's-type disease (n = 5 of 18). The diagnosis was associated with cerebrovascular disease (n = 16 of 18). The identification of pathological processes of inflammation and ischemia, linked to ND, in a particular cohort of SIT patients may provide a basis for establishing the medical significance and treatment of SIT and influence the clinical course of the tinnitus.

Clear Tinnitus, middle-ear pressure, and tinnitus relief: a prospective trial.

GOAL: Our goal was to establish the efficacy, in a 12-week period, of Clear Tinnitus for tinnitus relief in patients with tinnitus of the severe, disabling type. HYPOTHESIS: We hypothesized that tinnitus relief with Clear Tinnitus reflects improvement in the sensory component of the tinnitus complaint by controlling the factor of aeration of the middle ears and improving eustachian tube function. METHOD: In a prospective clinical trial of a homeopathic preparation--Clear Tinnitus--we attempted to identify in 15 tinnitus patients (14 male, 1 female; mean age, 47.6 years) its clinical efficacy for establishing tinnitus relief for a 3-month period. We employed a descriptive data analysis method across dimensions of risk to evaluate a base of multidimensional evidence and establish support for our hypothesis. A medical-audiological tinnitus patient protocol completed by each patient identified the clinical type of tinnitus as predominantly cochlear, with a central and middle-ear component bilaterally. We identified fluctuation in middle-ear pressure (MEP) via patients' clinical history, supported by physical examination and established with tympanometry, as a factor influencing the clinical course of the tinnitus in each patient. RESULTS: Eleven of 15 patients completed the study. Seven responders reported tinnitus relief; four did not respond. Descriptive data analysis failed to detect any trends in a change in response with audiometric tests across the hearing spectrum; thus, we could derive no coefficients of hearing change. Evaluation revealed high-frequency tinnitus in 11 patients. The Feldmann masking curve comparison at the start and end of the study showed no significant change in the 11 patients. There was no significant alteration in the minimum masking levels or loudness discomfort levels before and after the study. Tympanometry and MEP measurement indicated a significant difference in MEP with an improvement on average of -58.18 in the right ear and -40.90 in the left ear for the 11 patients. Quantitative electroencephalography analysis revealed a marked difference in the number of significant abnormal recordings between the different frequency bands, with the delta band significantly higher than the theta, alpha, and beta bands for both the overall cohort of patients (n = 11) and those reporting tinnitus relief (n = 7). The tinnitus outcome questionnaires--the tinnitus intensity index, the tinnitus annoyance index, and the tinnitus reaction questionnaire--revealed a significant difference for the patients (7 of 11) obtaining tinnitus relief. Results of the tinnitus stress test, the tinnitus handicap index, and the measurement of depression scale before and after the study were not statistically significant. CONCLUSIONS: Patients who completed the study demonstrated with tympanometry a statistical and clinical significance in MEP improvement or maintenance of MEP (or both). Patients with tinnitus of the severe disabling type selected for this study and responding to Clear Tinnitus reported tinnitus relief accompanied by improvement in or maintenance of MEP of the middle ears. The statistical and clinical significance of Clear Tinnitus for establishing tinnitus relief remains to be established with a larger cohort of tinnitus patients.