The Role of the Insula in Classical and Dissociative PTSD: A Double Case Study.

Two service members were diagnosed with PTSD due to military trauma exposure. One presented with the classical manifestation; the other presented with the dissociative subtype. A statistical map revealed anterior localization of insula connectivity in the classical PTSD patient and posterior localization in the dissociative PTSD patient. These differences suggest that dissociative PTSD may be identified, understood, and treated as a disorder related to increased posterior insula connectivity. This double case study provides preliminary evidence for a concrete neuroanatomical discrepancy between insula function in classical and dissociative PTSD that may help explain the emergence of different coping strategies.

[Molecular diagnosis of human papillomavirus infection. The Chilean experience]. / Implementación del diagnóstico molecular del VPH: experiencia chilena en curso.

Cervical Cancer (CaCu) has a heterogeneous epidemiological behavior throughout the planet, depending on regional socioeconomic development level. Some developed countries predict a potential eradication of this cancer in the next 100 years, while in Chile it still constitutes a pending challenge. Incidence rates show a slow but sustained downward prob, however, mortality has continued to fluctuate between 500-600 cases per year. A few years ago, vaccination against Human Papillomavirus (HPV), the main causal agent for this tumor, was consolidated as a public policy, both in girls and in boys. However, the technological leap in the screening prob was pending, from cytology to molecular diagnosis of the agent (HPV). In this report, we update our most recent data (2018) regarding CaCu mortality, then review global guidelines and experiences in HPV screening. Finally, we offer an account of the strategies that our health system is promoting to address the screening of the disease and whose molecular approach generates the widest worldwide scientific consensus. We also recognize the main barriers and future challenges, which, if overcome, would allow us to be in line with the mandate of WHO to control this women's health problema.

Radiotherapy for cervical cancer: Chilean consensus of the Society of Radiation Oncology.

BACKGROUND: Cervical cancer is a public health problem in Latin America. Radiotherapy plays a fundamental role both as definitive or adjuvant treatment. There are important intra and inter-country differences regarding access and availability of radiotherapy facilities in this region. The aim of a study was to standardize the basic clinical and technical criteria for the radiation treatment of patients with CC in Chile and provide a guide for Latin American Radiation Oncologists. MATERIALS AND METHODS: Forty-one expert radiation oncologists from the Chilean Radiation Oncology Society made a consensus using the Delphi methodology. RESULTS: There was a high degree of agreement for each of the recommendations. Those with the lowest percentage were related to the definition of the conformal 3D technique as the standard for definitive external radiotherapy (81%) and the criteria for extended nodal irradiation (85%). CONCLUSIONS: These recommendations present an updated guide for radiotherapy treatment of patients with cervical cancer for Latin America. Those should be implemented according to local resources of each institution.

Efficacy and safety of Dentoxol® in the prevention of radiation-induced oral mucositis in head and neck cancer patients (ESDOM): a randomized, multicenter, double-blind, placebo-controlled, phase II trial.

PURPOSE: The aim of this study was to assess the efficacy and safety of Dentoxol mouthrinse in reducing the severity of oral mucositis (OM) secondary to radiation therapy (RT) for head and neck cancer. METHODS: A randomized, double-blind, placebo-controlled, multicenter phase II clinical trial was conducted. Subjects were asked to use Dentoxol (n = 55) or control (n = 53) mouthrinse 5 times/day during RT. Twice a week, OM was assessed clinically using the WHO scale and the Oral Mucositis Daily Questionnaire (OMDQ) was completed. RESULTS: The incidence of severe OM was 40.7% in the Dentoxol group and 51% in the control group (p = 0.265). Comparing all recorded clinical assessments, severe OM was seen in 13.3% of all assessments in the Dentoxol group vs. 21.8% in the control group (p = 0.000). There was a statistically significant lower proportion of assessments showing severe OM in the Dentoxol group at weeks 4, 5, and 6 of RT. The mean duration of severe OM was 11.95 days in the Dentoxol group vs. 14.59 days in the control group (p = 0.502). There was no difference between groups in mouth pain and its impact on function. The use of Dentoxol was safe and was not linked to any serious adverse events. CONCLUSION: The use of Dentoxol 5 times/day is safe and resulted in significantly fewer time-points with severe OM and a delay in the onset of severe OM, compared with a control rinse. A phase III clinical trial is warranted to confirm efficacy and address the limitations of this study.

Treating dissociative post-traumatic stress disorder presenting as a functional movement disorder with transcranial magnetic stimulation targeting the cingulate gyrus.

A 29-year-old woman presented with head and neck dystonia, as well as functional seizures. The patient was an active military service member with a history of combat-related trauma. Resting blood oxygen level dependent (BOLD) functional MRI (fMRI) scans of the brain demonstrated an increased anterior cingulate component of the salience network and hyper-connectivity between the insula and cingulate. Following neurological and psychiatric evaluation, she was diagnosed with dissociative post-traumatic stress disorder, partially presenting as a functional movement disorder. Inhibitory repetitive transcranial magnetic stimulation (rTMS) was prescribed with the anterior cingulate as the primary target, and supplementary motor and premotor cortices as secondary targets. The treatment was intended to suppress tremors both directly and indirectly. Thirty-six sessions later, her symptoms were in remission, and she returned to active duty. This case demonstrates the potential efficacy of fMRI-guided rTMS in the treatment of dissociative PTSD.

[The cardiovascular impact of cancer control therapy]. / Impacto cardiovascular secundario a la terapia para el control del cáncer.

Cardiovascular diseases and cancer account for 27 and 25% of mortality in Chile, respectively. In the last decades, survival of people with cancer has improved due to preventive programs, early detection strategies, advances in technology and development of new antineoplastic therapies. Consequently, a progressive number of cancer-surviving patients have been generated, who may develop cardiovascular diseases, secondary to the same cancer therapy. Cardio-Oncology has emerged as the necessary link between both specialties to promote the prevention and early detection of cardiac complications, in patients undergoing oncological therapies. The aim is to curb cardiovascular complications. Also, to acquire knowledge about the mechanisms and effects of drugs that lead to heart damage aiming to develop efficient cardioprotective therapies. In this article we review and propose a didactic organization and classification of the main cardiovascular effects of cancer control therapy. We recognize that there is still a knowledge gap in basic sciences about the mechanisms that underlie these alterations.

[The present situation of colorectal cancer in Chile]. / Situación actual del cáncer de colon en Chile: una mirada traslacional.

Colorectal (CRC) is one of the most common types of cancer worldwide. Most tumors develop from an adenoma in a period of 10 to 15 years, but some may appear without previous adenomatous lesions. Seventy-five percent of colorectal cancers are sporadic, 20% have a family component (first or second-degree relatives with CRC) and 5% have a hereditary predisposition with a Mendelian pattern. The epidemiological evolution in the recent years in Chile has a worrisome evolution and the treatment costs of advanced stages are a burden for the healthcare system. We herein highlight the main Chilean medical and scientific contributions on the pathogenesis, early diagnosis, and treatment of CRC, which lead to its better understanding, and therefore better management, based on local evidence.

[The implementation of a Biobank network for Chile]. / Una red de biobancos para Chile: investigar hoy, para curar mañana.

The concept "Biobank" is relatively new in the scientific literature, and is not yet consensually defined, even for the World Health Organization (WHO). However, the use of human samples in biomedical research is a very old activity. The organized development of Biobanks in different places has grown in the last decade. The experience in different countries and continents has been diverse. In this special article we intend to summarize, organize and communicate to the national medical and scientific community, (i) the concept of Biobank, (ii) the international experience and a map of the Research Biobanks working in Chile, (iii) the basic biomedical and essential operational aspects to manage a Biobank for Research and (iv) the impact of a National Network of Biobanks implementation in the Chilean Health System. Ethical and regulatory aspects will not be included, given their intrinsic complexity, which should be discussed elsewhere.

A phase 2, open-label study of anti-inflammatory NE3107 in patients with dementias.

BACKGROUND: Alzheimer's disease (AD) is a progressive, multifactorial, neurodegenerative disorder affecting >6 million Americans. Chronic, low-grade neuroinflammation, and insulin resistance may drive AD pathogenesis. We explored the neurophysiological and neuropsychological effects of NE3107, an oral, anti-inflammatory, insulin-sensitizing molecule, in AD. METHODS: In this phase 2, open-label study, 23 patients with mild cognitive impairment or mild dementia received 20-mg oral NE3107 twice daily for 3 months. Primary endpoints assessed changes from baseline in neurophysiological health and oxidative stress (glutathione level) using advanced neuroimaging analyses. Secondary endpoints evaluated changes from baseline in neuropsychological health using cognitive assessments, including the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment, Clinical Dementia Rating, Quick Dementia Rating Scale, Alzheimer's Disease Composite Score, and Global Rating of Change (GRC). Exploratory endpoints assessed changes from baseline in neuroinflammation biomarkers (tumor necrosis factor alpha, TNF-α) and AD (amyloid beta and phosphorylated tau [P-tau]). RESULTS: NE3107 was associated with clinician-rated improvements in cerebral blood flow and functional connectivity within the brain. In patients with MMSE ≥ 20 (mild cognitive impairment to mild AD; n = 17), NE3107 was associated with directional, but statistically nonsignificant, changes in brain glutathione levels, along with statistically significant improvements in ADAS-Cog11 (P = .017), Clinical Dementia Rating (P = .042), Quick Dementia Rating Scale (P = .002), Alzheimer's Disease Composite Score (P = .0094), and clinician-rated GRC (P < .001), as well as in cerebrospinal fluid P-tau levels (P = .034) and P-tau:amyloid beta 42 ratio (P = .04). Biomarker analyses also demonstrated directional, but statistically non-significant, changes in plasma TNF-α, consistent with the expected mechanism of NE3107. Importantly, we observed a statistically significant correlation (r = 0.59) between improvements in TNF-α levels and ADAS-Cog11 scores (P = .026) in patients with baseline MMSE ≥ 20. CONCLUSION: Our results indicate that in this study NE3107 was associated with what appear to be positive neurophysiological and neuropsychological findings, as well as evidence of improvement in biomarkers associated with neuroinflammation and AD in patients diagnosed with dementia. Our findings are consistent with previous preclinical and clinical observations and highlight a central role of neuroinflammation in AD pathogenesis.

Choosing Wisely in oncology in Latin America: what SLACOM does not recommend in the care of cancer patients in Latin America: Ten essential recommendations to avoid harmful onclogy procedures in Latin America.

Choosing Wisely is an initiative by the American Board of Internal Medicine (ABIM) and ABIM Foundation to deter unnecessary medical treatments and procedures. Faced with the burden of modern technologies and treatments, it is crucial to identify practices lacking value in daily care. The Latin American and Caribbean Society (SLACOM), comprising cancer control experts, deems it vital to tailor this initiative for enhancing cancer care in the region. Through a modified DELPHI methodology involving two rounds of electronic questionnaires and a hybrid meeting to discuss key points of contention, ten essential recommendations were identified and prioritised to avoid harmful oncology procedures in our region. These consensus-based recommendations, contextualised for Latin America, have been compiled and shared to benefit patients. The Scientific Committee, consisting of prominent oncologists and health experts, collaborates remotely to drive this project forward.

Functional MRI Lateralization [M1] of dlPFC and Implications for Transcranial Magnetic Stimulation (TMS) Targeting.

The present study investigates a potential method of optimizing effective strategies for the functional lateralization of the dorsolateral prefrontal cortex (dlPFC) while in a scanner. Effective hemisphere lateralization of the dlPFC is crucial for lowering the functional risks connected to specific interventions (such as neurosurgery and transcranial magnetic stimulation (TMS), as well as increasing the effectiveness of a given intervention by figuring out the optimal location. This task combines elements of creative problem solving, executive decision making based on an internal rule set, and working memory. A retrospective analysis was performed on a total of 58 unique participants (34 males, 24 females, Mage = 42.93 years, SDage = 16.38). Of these participants, 47 were classified as right-handed, 7 were classified as left-handed, and 4 were classified as ambidextrous, according to the Edinburgh Handedness Inventory. The imaging data were qualitatively judged by two trained, blinded investigators (neurologist and neuropsychologist) for dominant handedness (primary motor cortex) and dominant dorsolateral prefrontal cortex (dlPFC). The results demonstrated that 21.4% of right-handed individuals showed a dominant dlPFC localized to the right hemisphere rather than the assumed left, and 16.7% of left-handers were dominant in their left hemisphere. The task completed in the scanner might be an efficient method for localizing a potential dlPFC target for the purpose of brain stimulation (e.g., TMS), though further study replications are needed to extend and validate these findings.

Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans.

Background: Low intensity, transcranial focused ultrasound (tFUS) is a re-emerging brain stimulation technique with the unique capability of reaching deep brain structures non-invasively. Objective/Hypothesis: We sought to demonstrate that tFUS can selectively and accurately target and modulate deep brain structures in humans important for emotional functioning as well as learning and memory. We hypothesized that tFUS would result in significant longitudinal changes in perfusion in the targeted brain region as well as selective modulation of BOLD activity and BOLD-based functional connectivity of the target region. Methods: In this study, we collected MRI before, simultaneously during, and after tFUS of two deep brain structures on different days in sixteen healthy adults each serving as their own control. Using longitudinal arterial spin labeling (ASL) MRI and simultaneous blood oxygen level dependent (BOLD) functional MRI, we found changes in cerebral perfusion, regional brain activity and functional connectivity specific to the targeted regions of the amygdala and entorhinal cortex (ErC). Results: tFUS selectively increased perfusion in the targeted brain region and not in the contralateral homolog or either bilateral control region. Additionally, tFUS directly affected BOLD activity in a target specific fashion without engaging auditory cortex in any analysis. Finally, tFUS resulted in selective modulation of the targeted functional network connectivity. Conclusion: We demonstrate that tFUS can selectively modulate perfusion, neural activity and connectivity in deep brain structures and connected networks. Lack of auditory cortex findings suggests that the mechanism of tFUS action is not due to auditory or acoustic startle response but rather a direct neuromodulatory process. Our findings suggest that tFUS has the potential for future application as a novel therapy in a wide range of neurological and psychiatric disorders associated with subcortical pathology.

Clinical relevance of the use of Dentoxol® for oral mucositis induced by radiotherapy: A phase II clinical trial.

BACKGROUND: Severe oral mucositis associated with cancer therapy is a frequent complication that may affect a patient's systemic condition, resulting in interruption and/or prolongation of cancer therapy. Dentoxol® is a medical solution in the form of a mouthwash that has been shown to result in statistically significant improvement in the prevention of severe oral mucositis. However, knowing the measures of the clinical significance of this therapy is important for accurate decision-making. AIM: To describe the clinical impact of Dentoxol® use in severe oral mucositis. METHODS: Clinical significance was measured using the results obtained in a randomized controlled clinical trial previously conducted by the same group of researchers. The measures of clinical significance evaluated were the absolute risk or incidence, relative risk, absolute risk reduction, relative risk reduction, number needed to treat, and odds ratio. RESULTS: The data obtained show that the impact of Dentoxol® on reducing the severity of oral mucositis has important clinical relevance. CONCLUSION: The results of this study justify the incorporation of Dentoxol® mouth rinse into clinical protocols as a complement to cancer therapy to prevent and/or treat oral mucositis secondary to radiotherapy.

Transcranial Infrared Laser Stimulation for the Treatment of Traumatic Brain Injury: A Case Series.

Introduction: This study intended to evaluate the safety and possible therapeutic effect of transcranial infrared laser stimulation (TILS) based on photobiomodulation (PBM) among patients with traumatic brain injury (TBI). Methods: Eleven participants who were diagnosed with TBI after full neurological examination and MRI evaluation by a board-certified neurologist completed five to eight 20-minute TILS sessions using the Cytonsys CytonPro-5000 apparatus (pilot laser control, focused wavelength of 1064 nm, maximum output power of 10W, maximum optical power density of 500 mW/cm2, effective area 4.5 cm2 in diameter). Per TILS session, participants underwent a laser dose of 250 mW/cm2 continuous laser wave to each hemisphere using predetermined patient-specific coordinates. Structural imaging was used to neuronavigate individual treatment targets in the frontal cortex (Brodmann area 10). The primary safety measure for this study was the occurrence of adverse events (AEs) or serious adverse events (SAEs). The primary efficacy outcome measure was the participant-rated global rating of change (GRC) post-intervention. Secondary outcome measures included a battery of neuropsychological testing and mood questionnaires done both pre- and post-intervention. Results: All patients enrolled in this study protocol were able to tolerate the study procedures without any AEs or SAEs. Nine out of eleven participants had clinically significant improvements in GRC score (≥ +2). Neuropsychological testing and mood questionnaire outcomes also suggested a positive therapeutic effect. Conclusion: This study provides preliminary evidence supporting the safety and potential efficacy of TILS as a non-invasive clinical intervention for individuals with TBI.

Brain circuitry underlying the ABC model of anxiety.

Anxiety Disorders are prevalent and often chronic, recurrent conditions that reduce quality of life. The first-line treatments, such as serotonin reuptake inhibitors and cognitive behavioral therapy, leave a significant proportion of patients symptomatic. As psychiatry moves toward targeted circuit-based treatments, there is a need for a theory that unites the phenomenology of anxiety with its underlying neural circuits. The Alarm, Belief, Coping (ABC) theory of anxiety describes how the neural circuits associated with anxiety interact with each other and domains of the anxiety symptoms, both temporally and spatially. The latest advancements in neuroimaging techniques offer the ability to assess these circuits in vivo. Using Neurosynth, a large open-access meta-analytic imaging database, the association between terms related to specific neural circuits was explored within the ABC theory framework. Alarm-related terms were associated with the amygdala, anterior cingulum, insula, and bed nucleus of stria terminalis. Belief-related terms were associated with medial prefrontal cortex, precuneus, bilateral temporal poles, and hippocampus. Coping-related terms were associated with the ventrolateral and dorsolateral prefrontal cortices, basal ganglia, and anterior cingulate. Neural connections underlying the functional neuroanatomy of the ABC model were observed. Additionally, there was considerable interaction and overlap between circuits associated with the symptom domains. Further neuroimaging research is needed to explore the dynamic interaction between the functional domains of the ABC theory. This will pave the way for probing the neuroanatomical underpinnings of anxiety disorders and provide an evidence-based foundation for the development of targeted treatments, such as neuromodulation.

Translating state-of-the-art brain magnetic resonance imaging (MRI) techniques into clinical practice: multimodal MRI differentiates dementia subtypes in a traditional clinical setting.

BACKGROUND: This study sought to validate the clinical utility of multimodal magnetic resonance imaging (MRI) techniques in the assessment of neurodegenerative disorders. We intended to demonstrate that advanced neuroimaging techniques commonly used in research can effectively be employed in clinical practice to accurately differentiate heathy aging and dementia subtypes. METHODS: Twenty patients with dementia of the Alzheimer's type (DAT) and 18 patients with Parkinson's disease dementia (PDD) were identified using gold-standard techniques. Twenty-three healthy, age and sex matched control participants were also recruited. All participants underwent multimodal MRI including T1 structural, diffusion tensor imaging (DTI), arterial spin labeling (ASL), and magnetic resonance spectroscopy (MRS). MRI modalities were evaluated by trained neuroimaging readers and were separately assessed using cross-validated, iterative discriminant function analyses with subsequent feature reduction techniques. In this way, each modality was evaluated for its ability to differentiate patients with dementia from healthy controls as well as to differentiate dementia subtypes. RESULTS: Following individual and group feature reduction, each of the multimodal MRI metrics except MRS successfully differentiated healthy aging from dementia and also demonstrated distinct dementia subtypes. Using the following ten metrics, excellent separation (95.5% accuracy, 92.3% sensitivity; 100.0% specificity) was achieved between healthy aging and neurodegenerative conditions: volume of the left frontal pole, left occipital pole, right posterior superior temporal gyrus, left posterior cingulate gyrus, right planum temporale; perfusion of the left hippocampus and left occipital lobe; fractional anisotropy (FA) of the forceps major and bilateral anterior thalamic radiation. Using volume of the left frontal pole, right posterior superior temporal gyrus, left posterior cingulate gyrus, perfusion of the left hippocampus and left occipital lobe; FA of the forceps major and bilateral anterior thalamic radiation, neurodegenerative subtypes were accurately differentiated as well (87.8% accuracy, 95.2% sensitivity; 85.0% specificity). CONCLUSIONS: Regional volumetrics, DTI metrics, and ASL successfully differentiated dementia patients from controls with sufficient sensitivity to differentiate dementia subtypes. Similarly, feature reduction results suggest that advanced analyses can meaningfully identify brain regions with the most positive predictive value and discriminant validity. Together, these advanced neuroimaging techniques can contribute significantly to diagnosis and treatment planning for individual patients.

Treatment of Dementia With Bosutinib: An Open-Label Study of a Tyrosine Kinase Inhibitor.

OBJECTIVE: The pursuit of an effective therapeutic intervention for dementia has inspired interest in the class of medications known as tyrosine kinase inhibitors such as bosutinib. METHODS: Thirty-one patients with probable Alzheimer dementia or Parkinson spectrum disorder with dementia completed 12 months of bosutinib therapy and an additional 12 months of follow-up. The Clinical Dementia Rating scale (as estimated by the Quick Dementia Rating System [QDRS]) was the primary cognitive status outcome measure. Secondary outcome measures included the Repeatable Battery Assessment of Neuropsychological Status (RBANS) and the Montreal Cognitive Assessment. Cox regression methods were used to compare results with population-based estimates of cognitive decline. RESULTS: The present article reports on cognitive outcomes obtained at 12 months for 31 participants and up to 24 months for a 16-participant subset. Safety and tolerability of bosutinib were confirmed among the study population (Mage = 73.7 years, SDage = 14 years). Bosutinib was associated with less worsening in Clinical Dementia Rating (CDR) scores (hazard ratio = -0.62, p < 0.001, 95% confidence interval [CI]: -1.02 to -0.30) and less decline in RBANS performance (hazard ratio = -3.42, p < 0.001, 95% CI: -3.59 to -3.72) during the year of treatment than population-based estimates of decline. In the 24-month follow-up, wherein 16 patients were observed after 1 year postintervention, 31.2% of participants exhibited worsened CDR levels compared with their 12-month performances. CONCLUSIONS: Results support an overall positive outcome after 1 year of bosutinib. Future studies should explore the relationship between tyrosine kinases and neurodegenerative pathology as well as related avenues of treatment.

Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy.

OBJECTIVE: Transcranial Focused Ultrasound (tFUS) is a promising new potential neuromodulation tool. However, the safety of tFUS neuromodulation has not yet been assessed adequately. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of tFUS neuromodulation. Histological changes in tissue after tFUS can be examined after surgical resection, while further potential safety concerns can be assessed using neuropsychological testing. METHODS: Neuropsychological functions were assessed in eight patients before and after focused ultrasound sonication of the temporal lobe at intensities up to 5760 mW/cm2. Using the BrainSonix Pulsar 1002, tFUS was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed using various batteries. Histological changes were assessed using hematoxylin and eosin staining, among others. RESULTS: With respect to safety, the histological analysis did not reveal any detectable damage to the tissue, except for one subject for whom the histology findings were inconclusive. In addition, neuropsychological testing did not show any statistically significant changes in any test, except for a slight decrease in performance on one of the tests after tFUS. SIGNIFICANCE: This study supports the hypothesis that low-intensity Transcranial Focused Ultrasound (tFUS) used for neuromodulation of brain circuits at intensities up to 5760 mW/cm2 may be safe for use in human research. However, due to methodological limitations in this study and inconclusive findings, more work is warranted to establish the safety. Future directions include greater number of sonications as well as longer exposure at higher intensity levels to further assess the safety of tFUS for modulation of neuronal circuits.

Focused transcranial ultrasound for treatment of neurodegenerative dementia.

INTRODUCTION: Preclinical studies support investigation of focused ultrasound for breakdown of cerebral pathologies in neurodegenerative conditions including Alzheimer's disease (AD) and Parkinson's disease (PD). METHODS: A focused transcranial Doppler device with probes (2 MHz, 520 mW/cm2) affixed bilaterally was used to target the hippocampus (AD) or substantia nigra (PD) with functional magnetic resonance imaging navigation for enhanced plaque removal. A total of 22 patients (n = 11 AD, n = 11 PD) underwent 8 consecutive, weekly, 1-hour treatments wherein sleep was encouraged naturally or pharmacologically. Cognitive and motor functioning assessment was carried out using standardized evaluations at baseline and conclusion. RESULTS: Of all, 62.5% of patients had one or more improved cognitive scores without data incongruence, 87% had stable or improved fine motor scores, and 87.5% had stable or improved gross motor scores. No adverse events were reported. DISCUSSION: The safety of focused transcranial Doppler and possible enhancement in patient functioning were suggested by outcome data.

Improved recovery of repeat intoxicated drivers using fingernails and blood spots to monitor alcohol and other substance abuse.

OBJECTIVES: This study reports the results of a pilot program in Kenosha County that used a combination of direct biomarkers extracted from blood spots and nails to monitor repeat intoxicated drivers for their use of alcohol and drugs with a detection window spanning from 3 weeks to several months. The objectives were to test whether the direct biomarkers phosphatidylethanol (PEth), ethylglucuronide (EtG), and 5 drug metabolites would (1) help assessors obtain a more objective evaluation of repeat offenders during the assessment interview, (2) allow for timely identification of relapses and improve classification of drivers into risk categories, and (3) predict recidivism by identifying offenders most likely to obtain a subsequent operating while intoxicated (OWI) offense within 4 years of enrollment in the program. METHODS: All (N = 261) repeat offenders were tested using PEth obtained from blood spots and EtG obtained from fingernails; 159 participants were also tested for a 5 drugs of abuse nail panel. Drivers were tested immediately after the assessment interview (baseline) and at 3, 6, 9, and 12 months after baseline. Based on biomarker results and self-reports of abstinence, offenders were classified into different risk categories and required to follow specific testing timelines based on the program's decision tree. RESULTS: The baseline analysis shows that 60% of drivers tested positive for alcohol biomarkers (EtG, PEth, or both) at the assessment interview, with lower detection rates (0-11%) for the 5 drug metabolites. The comparison of biomarkers results to self-reports of abstinence identified 28% of all offenders as high risk and assigned them to more frequent testing and more intense monitoring. The longitudinal analysis shows that 56% (completers) of participants completed the program successfully and the remaining 44% (noncompliant) terminated prematurely. Two thirds (68%) of the completers were able to reduce or control their drinking and one third relapsed at least one time during their mandated monitoring periods. After a brief intervention by the assessors, 79% of relapsers tested negative for biomarkers in their repeat tests. The rearrest analysis showed that offenders classified in the noncompliant and relapsers groups were 7 times more likely to receive a new OWI 4 years after enrollment compared to drivers classified as abstainers or controllers. Refractory drivers were monitored the longest and reported no subsequent rearrests. CONCLUSION: These findings demonstrate the benefits of more individualized interventions with repeat OWI offenders and calls for further development of multimodal approaches in traffic medicine including those that use direct alcohol biomarkers as evidence-based practices to reduce recidivism.