Clinical, Biomarker, and Research Tests Among US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: Since 2015, US government and related personnel have reported dizziness, pain, visual problems, and cognitive dysfunction after experiencing intrusive sounds and head pressure. The US government has labeled these anomalous health incidents (AHIs). Objective: To assess whether participants with AHIs differ significantly from US government control participants with respect to clinical, research, and biomarker assessments. Design, Setting, and Participants: Exploratory study conducted between June 2018 and July 2022 at the National Institutes of Health Clinical Center, involving 86 US government staff and family members with AHIs from Cuba, Austria, China, and other locations as well as 30 US government control participants. Exposures: AHIs. Main Outcomes and Measures: Participants were assessed with extensive clinical, auditory, vestibular, balance, visual, neuropsychological, and blood biomarkers (glial fibrillary acidic protein and neurofilament light) testing. The patients were analyzed based on the risk characteristics of the AHI identifying concerning cases as well as geographic location. Results: Eighty-six participants with AHIs (42 women and 44 men; mean [SD] age, 42.1 [9.1] years) and 30 vocationally matched government control participants (11 women and 19 men; mean [SD] age, 43.8 [10.1] years) were included in the analyses. Participants with AHIs were evaluated a median of 76 days (IQR, 30-537) from the most recent incident. In general, there were no significant differences between participants with AHIs and control participants in most tests of auditory, vestibular, cognitive, or visual function as well as levels of the blood biomarkers. Participants with AHIs had significantly increased fatigue, depression, posttraumatic stress, imbalance, and neurobehavioral symptoms compared with the control participants. There were no differences in these findings based on the risk characteristics of the incident or geographic location of the AHIs. Twenty-four patients (28%) with AHI presented with functional neurological disorders. Conclusions and Relevance: In this exploratory study, there were no significant differences between individuals reporting AHIs and matched control participants with respect to most clinical, research, and biomarker measures, except for objective and self-reported measures of imbalance and symptoms of fatigue, posttraumatic stress, and depression. This study did not replicate the findings of previous studies, although differences in the populations included and the timing of assessments limit direct comparisons.

Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents.

Importance: US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms. Objective: To assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group. Design, Setting, and Participants: This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022. Eighty-one participants with AHIs and 48 age- and sex-matched control participants, 29 of whom had similar employment as the AHI group, were assessed with clinical, volumetric, and functional MRI. A high-quality diffusion MRI scan and a second volumetric scan were also acquired during a different session. The structural MRI acquisition protocol was optimized to achieve high reproducibility. Forty-nine participants with AHIs had at least 1 additional imaging session approximately 6 to 12 months from the first visit. Exposure: AHIs. Main Outcomes and Measures: Group-level quantitative metrics obtained from multiple modalities: (1) volumetric measurement, voxel-wise and region of interest (ROI)-wise; (2) diffusion MRI-derived metrics, voxel-wise and ROI-wise; and (3) ROI-wise within-network resting-state functional connectivity using functional MRI. Exploratory data analyses used both standard, nonparametric tests and bayesian multilevel modeling. Results: Among the 81 participants with AHIs, the mean (SD) age was 42 (9) years and 49% were female; among the 48 control participants, the mean (SD) age was 43 (11) years and 42% were female. Imaging scans were performed as early as 14 days after experiencing AHIs with a median delay period of 80 (IQR, 36-544) days. After adjustment for multiple comparisons, no significant differences between participants with AHIs and control participants were found for any MRI modality. At an unadjusted threshold (P < .05), compared with control participants, participants with AHIs had lower intranetwork connectivity in the salience networks, a larger corpus callosum, and diffusion MRI differences in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior cerebellar peduncle, and amygdala. The structural MRI measurements were highly reproducible (median coefficient of variation <1% across all global volumetric ROIs and <1.5% for all white matter ROIs for diffusion metrics). Even individuals with large differences from control participants exhibited stable longitudinal results (typically, <±1% across visits), suggesting the absence of evolving lesions. The relationships between the imaging and clinical variables were weak (median Spearman ρ = 0.10). The study did not replicate the results of a previously published investigation of AHIs. Conclusions and Relevance: In this exploratory neuroimaging study, there were no significant differences in imaging measures of brain structure or function between individuals reporting AHIs and matched control participants after adjustment for multiple comparisons.

Spectra Optia granulocyte apheresis collections result in higher collection efficiency of viable, functional neutrophils in a randomized, crossover, multicenter trial.

BACKGROUND: Granulocyte transfusion from healthy donors is used in the treatment of patients with granulocyte function defects, or transient neutropenia and severe bacterial or fungal infections resistant to maximal antimicrobial treatment. STUDY DESIGN AND METHODS: This study evaluated the performance and safety of the newly developed granulocyte collection protocol of the Spectra Optia in a prospective, multicenter, open-label, randomized, paired crossover trial compared with the COBE Spectra apheresis system in a population of 32 evaluable healthy subjects. All subjects received granulocyte-colony-stimulating factor and dexamethasone before collection. RESULTS: Granulocyte procedures from Spectra Optia apheresis procedures had an approximately 23% higher polymorphonuclear (PMN) collection efficiency (CE) than the COBE Spectra collections (mean, 53.7% vs. 43.2%; p < 0.01), while the platelet CE (10.9% vs. 10.8%, respectively) and hematocrit (7.4% vs. 7.4%) were comparable between collections on both devices. Spectra Optia collections generated a higher total PMN yield per liter of blood processed than those produced by the COBE Spectra (with means of 8.6 × 10(10) vs. 6.8 × 10(10) , respectively). Granulocyte viability was more than 99% with both devices, and chemotaxic and bacterial killing activities of circulating versus collected granulocytes were similarly preserved. Fewer operator adjustments were required with Spectra Optia and there was no significant difference in the number or intensity of adverse events between instruments. CONCLUSION: CE of the granulocyte collection procedure with the Spectra Optia was approximately 10 percentage points higher than with the COBE Spectra, required less operator involvement, and is safe for clinical implementation.

A synaptic strategy for consolidation of convergent visuotopic maps.

The mechanisms by which experience guides refinement of converging afferent pathways are poorly understood. We describe a vision-driven refinement of corticocollicular inputs that determines the consolidation of retinal and visual cortical (VC) synapses on individual neurons in the superficial superior colliculus (sSC). Highly refined corticocollicular terminals form 1-2 days after eye-opening (EO), accompanied by VC-dependent filopodia sprouting on proximal dendrites, and PSD-95 and VC-dependent quadrupling of functional synapses. Delayed EO eliminates synapses, corticocollicular terminals, and spines on VC-recipient dendrites. Awake recordings after EO show that VC and retina cooperate to activate sSC neurons, and VC light responses precede sSC responses within intervals promoting potentiation. Eyelid closure is associated with more protracted cortical visual responses, causing the majority of VC spikes to follow those of the colliculus. These data implicate spike-timing plasticity as a mechanism for cortical input survival, and support a cooperative strategy for retinal and cortical coinnervation of the sSC.

Contextual errors and failures in individualizing patient care: a multicenter study.

BACKGROUND: A contextual error occurs when a physician overlooks elements of a patient's environment or behavior that are essential to planning appropriate care. In contrast to biomedical errors, which are not patient-specific, contextual errors represent a failure to individualize care. OBJECTIVE: To explore the frequency and circumstances under which physicians probe contextual and biomedical red flags and avoid treatment error by incorporating what they learn from these probes. DESIGN: An incomplete randomized block design in which unannounced, standardized patients visited 111 internal medicine attending physicians between April 2007 and April 2009 and presented variants of 4 scenarios. In all scenarios, patients presented both a contextual and a biomedical red flag. Responses to probing about flags varied in whether they revealed an underlying complicating biomedical or contextual factor (or both) that would lead to errors in management if overlooked. SETTING: 14 practices, including 2 academic clinics, 2 community-based primary care networks with multiple sites, a core safety net provider, and 3 U.S. Department of Veterans Affairs facilities. MEASUREMENTS: Primary outcomes were the proportion of visits in which physicians probed for contextual and biomedical factors in response to hints or red flags and the proportion of visits that resulted in error-free treatment plans. RESULTS: Physicians probed fewer contextual red flags (51%) than biomedical red flags (63%). Probing for contextual or biomedical information in response to red flags was usually necessary but not sufficient for an error-free plan of care. Physicians provided error-free care in 73% of the uncomplicated encounters, 38% of the biomedically complicated encounters, 22% of the contextually complicated encounters, and 9% of the combined biomedically and contextually complicated encounters. LIMITATIONS: Only 4 case scenarios were used. The study assessed physicians' propensity to make errors when every encounter provided an opportunity to do so and did not measure actual error rates that occur in primary care settings because of inattention to context. CONCLUSION: Inattention to contextual information, such as a patient's transportation needs, economic situation, or caretaker responsibilities, can lead to contextual error, which is not currently measured in assessments of physician performance. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs Health Services Research and Development Service

Intertemporal tradeoffs: perceiving the risk in the benefits of marijuana in a prospective study of adolescents and young adults.

PURPOSE: Intertemporal tradeoffs characterize the decision to use drugs: pleasure now traded off against the possibility of pain later. Traditional approaches have examined whether individuals use drugs because they either seek immediate benefit or fail to appreciate long-term risk. We asked whether risk taking might also result from failing to appreciate benefits. We refer to this as risk in the benefits (RIBs), an understanding that one's first drug experience can be so good, that a person may not want (or be able) to stop, putting him/her on a path that leads directly to addiction. METHODS: In total, 304 participants, 160 adolescents and 144 young adults, participated in a longitudinal study on marijuana use and other risky health behaviors. RESULTS: The failure to perceive the RIBs of marijuana use led to increased risk taking 1 year later within 3 different health behaviors: alcohol, tobacco, and sexual risk-taking. Greater appreciation of RIBs predicted significantly less future risk taking over-and-above all the traditional cognitive and behavioral predictors, and RIBs were the only significant cognitive predictor when all were included in 1 model. RIBs also partially mediated the relationship between past and future risk taking, over and above the strongest predictors of risk taking. CONCLUSIONS: Failing to appreciate the impact of short-term benefits within the context of long-term risk increased future risk taking. Interventions that enhance the salience of RIBs may represent a new approach to reducing the likelihood that individuals will take risks with their health.

Forecasting changes in preference over the life span: a qualitative study of African-American men's prostate cancer decision making.

GOALS OF WORK: The goal of this study was to explore the processes by which African-American men, at greatest risk, might forecast and manage health changes as they age if they were diagnosed with prostate cancer. PATIENTS AND METHODS: Twenty-nine African-American men, 40-70 years old, with no history of prostate cancer, participated in four focus groups and four follow-up individual interviews. Transcripts were analyzed using Grounded Theory, with thematic analysis and constant comparison of data. MAIN RESULTS: There was a curvilinear relationship between age and participants' preference for quality versus quantity of life in deciding to treat prostate cancer. Two mechanisms accounted for this: a change with age in the (1) reference point for judging value and (2) decision-making goal. CONCLUSIONS: With increasing long-term survivorship, it is vital to understand the multiple decisions cancer patients will face as they continue to age. The current study is an initial step in studying how patients might anticipate and manage such changes.

Evaluating physician performance at individualizing care: a pilot study tracking contextual errors in medical decision making.

OBJECTIVES: Clinical decision making requires 2 distinct cognitive skills: the ability to classify patients' conditions into diagnostic and management categories that permit the application of research evidence and the ability to individualize or-more specifically-to contextualize care for patients whose circumstances and needs require variation from the standard approach to care. The purpose of this study was to develop and test a methodology for measuring physicians' performance at contextualizing care and compare it to their performance at planning biomedically appropriate care. METHODS: First, the authors drafted 3 cases, each with 4 variations, 3 of which are embedded with biomedical and/or contextual information that is essential to planning care. Once the cases were validated as instruments for assessing physician performance, 54 internal medicine residents were then presented with opportunities to make these preidentified biomedical or contextual errors, and data were collected on information elicitation and error making. RESULTS: The case validation process was successful in that, in the final iteration, the physicians who received the contextual variant of cases proposed an alternate plan of care to those who received the baseline variant 100% of the time. The subsequent piloting of these validated cases unmasked previously unmeasured differences in physician performance at contextualizing care. The findings, which reflect the performance characteristics of the study population, are presented. CONCLUSIONS: This pilot study demonstrates a methodology for measuring physician performance at contextualizing care and illustrates the contribution of such information to an overall assessment of physician practice.

Being there is important, but getting there matters too: the role of path in the valuation process.

PURPOSE: Traditional decision-analytic models presume that utilities are invariant to context. The influence of 2 types of context on patients' utility assessments was examined here the path by which one reaches a health state and personal experience with a health state. METHODS: Three groups of patients were interviewed: men older than age 49 years with prostate cancer but no diabetes (CaP), diabetes but no prostate cancer (DM), and neither disease (ND). The utility of erectile dysfunction (ED) was assessed using a standard gamble (SG). Each subject completed 2 SGs: 1) a no-context version that gave no explanation for the cause of ED and 2) a contextualized version in which prostate cancer treatment, the failure to manage diabetes, or the natural course of aging was said to be the cause. RESULTS: Patients with disease assigned higher utilities to ED in a matching context than in discrepant contexts. Regression models found that the valuation process was also sensitive to the match between disease path in the utility assessment and patients' personal experiences. CONCLUSIONS: These findings lend insight into why acontextual utility assessments typically used in decision analyses have not been able to predict patient behavior as well as expected. The valuation process appears to change systematically when context is specified, suggesting that unspecified contexts rather than random error may lead to fluctuations in the values assigned to identical health states.

A chairside aid for shared decision making in dentistry: a randomized controlled trial.

The concept of shared decision making (SDM) is an important emerging trend in clinical medicine but has received little or no attention in the dental literature. Decision aids can play a useful role in SDM by helping patients and clinicians choose among reasonable alternative treatment options. The purpose of this study was to develop and test an Endodontic Decision Board (EndoDB) for chairside use to help clarify treatment alternatives, benefits, risks, prognosis, and costs when root canal therapy or extraction of a tooth was indicated. The hypothesis was that the use of the EndoDB would lead to improved patient knowledge, greater satisfaction with the decision-making process, and no difference in anxiety when compared to the standard discussion and informed consent process (usual care). The EndoDB was tested in a randomized controlled trial in a postgraduate endodontics clinic. After treatment discussion, a brief questionnaire was completed by the patient to measure knowledge, satisfaction, and anxiety. Patients in the EndoDB group (n=32) demonstrated a small, but statistically significant, increase in knowledge (t-test; difference=+0.37; p=0.03) compared to the usual care group (n=35). There was no difference between groups in the measures of satisfaction or anxiety (Mann-Whitney U-test; p>0.05). Decision aids may emerge as a useful tool to facilitate SDM and evidence-based clinical practice.

How perceived risk and personal and clinical experience affect medical students' decisions to seek treatment for major depression.

PURPOSE: To examine the role of perceived risk, and personal and clinical experience in medical students' treatment seeking behavior for major depression. METHOD: In 2003, a questionnaire was administered to 173 first-year and 164 fourth-year medical students at Northwestern University's Feinberg School of Medicine to assess students' perception of risk for major depression in the general population and personal and clinical experience with major depression. Treatment-seeking behavior was examined using a hypothetical scenario. Data analysis used analysis of variance and regression models. RESULTS: A total of 157 (91%) first-year and 108 (66%) fourth-year students completed the questionnaire. The majority overestimated the risk for major depression in the general population (p <.001), although respondents were more accurate for risk in the medical student population. The significant predictors for willingness to diagnose depression in the scenario were: risk perception (beta =.176, p <.01), clinical experience (beta =.173, p <.01) and personal treatment for major depression (beta =.188, p <.01). Significant predictors for willingness to refer to a professional were personal treatment (beta =.136, p <.05) and having a close friend treated for major depression (beta =.176, p <.01). CONCLUSIONS: Students' hesitation to seek treatment may be explained by the overestimation of risk, which has been shown to cause increased anxiety and avoidance of health seeking behavior. Interestingly, personal experience was found to be a significant predictor of treatment seeking behavior. This information can be used in preparing health risk communication messages for medical students.

Beyond invulnerability: the importance of benefits in adolescents' decision to drink alcohol.

Some investigators propose that adolescents engage in risky behaviors mainly because they perceive themselves to be invulnerable to risk. However, studies have typically not included perceived benefits. In the current study, 5th, 7th, and 9th graders were surveyed about their perceptions of and experience with alcohol and tobacco. Results indicated that perceptions of the benefits were significantly related to drinking and smoking 6 months later, over and above perceptions of the risks, age of the respondent, and experience level. Further, the importance of benefits was replicated across 3 separate analyses. Experience with alcohol alone, especially positive experience, was also related to perception and behavior. These findings are discussed in terms of how to improve messages and influence adolescents' decisions regarding risk-taking behaviors.