Procedures for the Comparative Testing of Noninvasive Neuroassessment Devices.

A sequential process for comparison testing of noninvasive neuroassessment devices is presented. Comparison testing of devices in a clinical population should be preceded by computational research and reliability testing with healthy populations, as opposed to proceeding immediately to testing with clinical participants. A five-step process is outlined as follows: 1. Complete a preliminary literature review identifying candidate measures. 2. Conduct systematic simulation studies to determine the computational properties and data requirements of candidate measures. 3. Establish the test-retest reliability of each measure in a healthy comparison population and the clinical population of interest. 4. Investigate the clinical validity of reliable measures in appropriately defined clinical populations. 5. Complete device usability assessment (weight, simplicity of use, cost effectiveness, ruggedness) only for devices and measures that are promising after steps 1 through 4 are completed. Usability may be considered throughout the device evaluation process but such considerations are subordinate to the higher priorities addressed in steps 1 through 4.

Statistical Issues in TBI Clinical Studies.

The identification and longitudinal assessment of traumatic brain injury presents several challenges. Because these injuries can have subtle effects, efforts to find quantitative physiological measures that can be used to characterize traumatic brain injury are receiving increased attention. The results of this research must be considered with care. Six reasons for cautious assessment are outlined in this paper. None of the issues raised here are new. They are standard elements in the technical literature that describes the mathematical analysis of clinical data. The purpose of this paper is to draw attention to these issues because they need to be considered when clinicians evaluate the usefulness of this research. In some instances these points are demonstrated by simulation studies of diagnostic processes. We take as an additional objective the explicit presentation of the mathematical methods used to reach these conclusions. This material is in the appendices. The following points are made: (1) A statistically significant separation of a clinical population from a control population does not ensure a successful diagnostic procedure. (2) Adding more variables to a diagnostic discrimination can, in some instances, actually reduce classification accuracy. (3) A high sensitivity and specificity in a TBI versus control population classification does not ensure diagnostic successes when the method is applied in a more general neuropsychiatric population. (4) Evaluation of treatment effectiveness must recognize that high variability is a pronounced characteristic of an injured central nervous system and that results can be confounded by either disease progression or spontaneous recovery. A large pre-treatment versus post-treatment effect size does not, of itself, establish a successful treatment. (5) A procedure for discriminating between treatment responders and non-responders requires, minimally, a two phase investigation. This procedure must include a mechanism to discriminate between treatment responders, placebo responders, and spontaneous recovery. (6) A search for prodromes of neuropsychiatric disorders following traumatic brain injury can be implemented with these procedures.

Patient Characterization Protocols for Psychophysiological Studies of Traumatic Brain Injury and Post-TBI Psychiatric Disorders.

Psychophysiological investigations of traumatic brain injury (TBI) are being conducted for several reasons, including the objective of learning more about the underlying physiological mechanisms of the pathological processes that can be initiated by a head injury. Additional goals include the development of objective physiologically based measures that can be used to monitor the response to treatment and to identify minimally symptomatic individuals who are at risk of delayed-onset neuropsychiatric disorders following injury. Research programs studying TBI search for relationships between psychophysiological measures, particularly ERP (event-related potential) component properties (e.g., timing, amplitude, scalp distribution), and a participant's clinical condition. Moreover, the complex relationships between brain injury and psychiatric disorders are receiving increased research attention, and ERP technologies are making contributions to this effort. This review has two objectives supporting such research efforts. The first is to review evidence indicating that TBI is a significant risk factor for post-injury neuropsychiatric disorders. The second objective is to introduce ERP researchers who are not familiar with neuropsychiatric assessment to the instruments that are available for characterizing TBI, post-concussion syndrome, and psychiatric disorders. Specific recommendations within this very large literature are made. We have proceeded on the assumption that, as is typically the case in an ERP laboratory, the investigators are not clinically qualified and that they will not have access to participant medical records.

Communication patterns in a psychotherapy following traumatic brain injury: a quantitative case study based on symbolic dynamics.

BACKGROUND: The role of psychotherapy in the treatment of traumatic brain injury is receiving increased attention. The evaluation of psychotherapy with these patients has been conducted largely in the absence of quantitative data concerning the therapy itself. Quantitative methods for characterizing the sequence-sensitive structure of patient-therapist communication are now being developed with the objective of improving the effectiveness of psychotherapy following traumatic brain injury. METHODS: The content of three therapy session transcripts (sessions were separated by four months) obtained from a patient with a history of several motor vehicle accidents who was receiving dialectical behavior therapy was scored and analyzed using methods derived from the mathematical theory of symbolic dynamics. RESULTS: The analysis of symbol frequencies was largely uninformative. When repeated triples were examined a marked pattern of change in content was observed over the three sessions. The context free grammar complexity and the Lempel-Ziv complexity were calculated for each therapy session. For both measures, the rate of complexity generation, expressed as bits per minute, increased longitudinally during the course of therapy. The between-session increases in complexity generation rates are consistent with calculations of mutual information. Taken together these results indicate that there was a quantifiable increase in the variability of patient-therapist verbal behavior during the course of therapy. Comparison of complexity values against values obtained from equiprobable random surrogates established the presence of a nonrandom structure in patient-therapist dialog (P = .002). CONCLUSIONS: While recognizing that only limited conclusions can be based on a case history, it can be noted that these quantitative observations are consistent with qualitative clinical observations of increases in the flexibility of discourse during therapy. These procedures can be of particular value in the examination of therapies following traumatic brain injury because, in some presentations, these therapies are complicated by deficits that result in subtle distortions of language that produce significant post-injury social impairment. Independently of the mathematical analysis applied to the investigation of therapy-generated symbol sequences, our experience suggests that the procedures presented here are of value in training therapists.

Concept paper: a virtual centralized IRB system.

CONTEXT: As the volume and complexity of research have increased, the amount of time spent on Institutional Review Board (IRB) review has decreased. The complexity of research has expanded, requiring increasingly specialized knowledge to review it. Dilemma: Under the current system, increasing numbers of research studies requiring expertise in ethics, new technologies or diverse study designs place a substantial burden upon local IRBs and often result in substantial variability among their reviews. This lack of uniformity in the review process creates uneven human subjects' protection thus undermining the intent of the Common Rule. OBJECTIVES: To outline a scenario for expert centralized IRB review via implementation of a national virtual IRB review system overseen by the Office for Human Research Protections (OHRP). CONCLUSIONS: The complicated ethical issues and science involved in much of current research warrant an expert review panel. Centralized review would enable expert review specific to the research at hand, ensure consistency in human subjects protection, reduce the burden on local IRBs, and may reduce time spent obtaining approval. A centralized virtual system would allow IRB members to remain at their institutions while providing unprecedented expert review through currently available technology, and make information regarding monitoring and adverse event reporting available online in real-time.

Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial.

BACKGROUND: Evidence on the efficacy of acupuncture for reducing the pain and dysfunction of osteoarthritis is equivocal. OBJECTIVE: To determine whether acupuncture provides greater pain relief and improved function compared with sham acupuncture or education in patients with osteoarthritis of the knee. DESIGN: Randomized, controlled trial. SETTING: Two outpatient clinics (an integrative medicine facility and a rheumatology facility) located in academic teaching hospitals and 1 clinical trials facility. PATIENTS: 570 patients with osteoarthritis of the knee (mean age [+/-SD], 65.5 +/- 8.4 years). INTERVENTION: 23 true acupuncture sessions over 26 weeks. Controls received 6 two-hour sessions over 12 weeks or 23 sham acupuncture sessions over 26 weeks. MEASUREMENTS: Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores at 8 and 26 weeks. Secondary outcomes were patient global assessment, 6-minute walk distance, and physical health scores of the 36-Item Short-Form Health Survey (SF-36). RESULTS: Participants in the true acupuncture group experienced greater improvement in WOMAC function scores than the sham acupuncture group at 8 weeks (mean difference, -2.9 [95% CI, -5.0 to -0.8]; P = 0.01) but not in WOMAC pain score (mean difference, -0.5 [CI, -1.2 to 0.2]; P = 0.18) or the patient global assessment (mean difference, 0.16 [CI, -0.02 to 0.34]; P > 0.2). At 26 weeks, the true acupuncture group experienced significantly greater improvement than the sham group in the WOMAC function score (mean difference, -2.5 [CI, -4.7 to -0.4]; P = 0.01), WOMAC pain score (mean difference, -0.87 [CI, -1.58 to -0.16];P = 0.003), and patient global assessment (mean difference, 0.26 [CI, 0.07 to 0.45]; P = 0.02). LIMITATIONS: At 26 weeks, 43% of the participants in the education group and 25% in each of the true and sham acupuncture groups were not available for analysis. CONCLUSIONS: Acupuncture seems to provide improvement in function and pain relief as an adjunctive therapy for osteoarthritis of the knee when compared with credible sham acupuncture and education control groups.