Vitamin B12 Supplementation in Psychiatric Practice.

PURPOSE OF REVIEW: Vitamin B12 (B12, cobalamin) deficiency has been associated with neuropsychiatric symptoms, suggesting a role for B12 supplementation both as a treatment for psychiatric symptoms due to B12 deficiency and as an augmentation strategy for pharmacological treatments of psychiatric disorders. This critical review discusses the major causes of B12 deficiency, the range of psychiatric and non-psychiatric manifestations of B12 deficiency, the indications for testing B12 levels, and the evidence for B12 supplementation for major psychiatric disorders. RECENT FINDINGS: We find that high-quality evidence shows no benefit to routine B12 supplementation for mild depressive symptoms or to prevent depression. There is very limited evidence on the role of B12 supplementation to augment antidepressants. No high-quality evidence to date suggests a role for routine B12 supplementation in any other major psychiatric disorder. No formal guidelines indicate when clinicians should test B12 levels for common psychiatric symptoms, in the absence of major risk factors for deficiency or cardinal symptoms of deficiency. No robust evidence currently supports routine B12 supplementation for major psychiatric disorders. However, psychiatrists should be aware of the important risk factors for B12 deficiency and should be able to identify symptoms of B12 deficiency, which requires prompt testing, medical workup, and treatment. Testing for B12 deficiency should be considered for atypical or severe psychiatric presentations.

Noninvasive Surrogate for Physiologic Dead Space Using the Carbon Dioxide Ventilatory Equivalent: Testing in a Single-Center Cohort, 2017-2023.

OBJECTIVES: We sought to evaluate the association between the carbon dioxide (co2) ventilatory equivalent (VEqco2 = minute ventilation/volume of co2 produced per min), a marker of dead space that does not require a blood gas measurement, and mortality risk. We compared the strength of this association to that of physiologic dead space fraction (VD/Vt = [Paco2-mixed-expired Pco2]/Paco2) as well as to other commonly used markers of dead space (i.e., the end-tidal alveolar dead space fraction [AVDSf = (Paco2-end-tidal Pco2)/Paco2], and ventilatory ratio [VR = (minute ventilation × Paco2)/(age-adjusted predicted minute ventilation × 37.5)]). DESIGN: Retrospective cohort data, 2017-2023. SETTING: Quaternary PICU. PATIENTS: One hundred thirty-one children with acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All dead space markers were calculated at the same 1-minute timepoint for each patient within the first 72 hours of using invasive mechanical ventilation. The 131 children had a median (interquartile range, IQR) age of 5.8 (IQR 1.4, 12.6) years, oxygenation index (OI) of 7.5 (IQR 4.6, 14.3), VD/Vt of 0.47 (IQR 0.38, 0.61), and mortality was 17.6% (23/131). Higher VEqco2 (p = 0.003), VD/Vt (p = 0.002), and VR (p = 0.013) were all associated with greater odds of mortality in multivariable models adjusting for OI, immunosuppressive comorbidity, and overall severity of illness. We failed to identify an association between AVDSf and mortality in the multivariable modeling. Similarly, we also failed to identify an association between OI and mortality after controlling for any dead space marker in the modeling. For the 28-day ventilator-free days outcome, we failed to identify an association between VD/Vt and the dead space markers in multivariable modeling, although OI was significant. CONCLUSIONS: VEqco2 performs similarly to VD/Vt and other surrogate dead space markers, is independently associated with mortality risk, and may be a reasonable noninvasive surrogate for VD/Vt.

Longitudinal, prospective study of head impacts in male high school football players.

INTRODUCTION: Repetitive, subconcussive events may adversely affect the brain and cognition during sensitive periods of development. Prevention of neurocognitive consequences of concussion in high school football is therefore an important public health priority. We aimed to identify the player positions and demographic, behavioral, cognitive, and impact characteristics that predict the frequency and acceleration of head impacts in high school football players. METHODS: In this prospective study, three cohorts of adolescent male athletes (N = 53, 28.3% Hispanic) were recruited over three successive seasons in a high school American football program. Demographic and cognitive functioning were assessed at baseline prior to participating in football. Helmet sensors recorded impact frequency and acceleration. Each head impact was captured on film from five different angles. Research staff verified and characterized on-field impacts. Player-level Poisson regressions and year-level and impact-level linear mixed-effect models were used to determine demographic, behavioral, cognitive, and impact characteristics as predictors of impact frequency and acceleration. RESULTS: 4,678 valid impacts were recorded. Impact frequency positively associated with baseline symptoms of hyperactivity-impulsivity [ß(SE) = 1.05 impacts per year per unit of symptom severity (1.00), p = 0.01] and inattentiveness [ß(SE) = 1.003 impacts per year per T-score unit (1.001), p = 0.01]. Compared to quarterbacks, the highest acceleration impacts were sustained by kickers/punters [ß(SE) = 21.5 g's higher (7.1), p = 0.002], kick/punt returners [ß(SE) = 9.3 g's higher (4.4), p = 0.03], and defensive backs [ß(SE) = 4.9 g's higher (2.5), p = 0.05]. Impacts were more frequent in the second [ß(SE) = 33.4 impacts (14.2), p = 0.02)] and third [ß(SE) = 50.9 impacts (20.1), p = 0.01] year of play. Acceleration was highest in top-of-the-head impacts [ß(SE) = 4.4 g's higher (0.8), p<0.001]. CONCLUSION: Including screening questions for Attention-Deficit/Hyperactivity Disorder in pre-participation evaluations can help identify a subset of prospective football players who may be at risk for increased head impacts. Position-specific strategies to modify kickoffs and correct tackling and blocking may also reduce impact burden.

Psychedelics, With a Focus on Psilocybin: Issues for the Clinician.

There has been a burgeoning interest in psychedelics among the public, state legislatures, psychiatrists and other clinical providers, and within the research community. Increasing numbers of studies evaluating psychedelics for depression, anxiety, posttraumatic stress disorder, and substance use disorders have been conducted or are underway. While discussing psychedelics in general, the focus of this paper is on psilocybin and its mechanism, how it exerts a psychedelic effect, dosing, and a review of the treatment studies of psilocybin, which were primarily for treatment-resistant depression and cancer-related anxiety. Future directions and potential limitations of studying and regulating psilocybin and other psychedelics are also discussed.

High intensity interval training exercise increases dopamine D2 levels and modulates brain dopamine signaling.

Background: Previous research has outlined the health benefits of exercise including its therapeutic potential for substance use disorders (SUD). These data have already been utilized and it is now common to find exercise as part of SUD treatment and relapse prevention programs. However, we need to better understand different exercise regimens and determine which would be the most beneficial for SUDs. Recently, high intensity interval training (HIIT) has gained attention in comparison with aerobic and resistance exercise. Little is known regarding the neurobiological mechanisms of HIIT, including its effects on dopamine signaling and receptor levels in the brain. The present study examined the effects of chronic HIIT exercise on dopamine signaling as measured by dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and tyrosine hydroxylase (TH) quantification in the brains of male and female rats as measured by [3H] SCH 23390 and [3H] spiperone autoradiography, and TH-immunoreactive optical density values. Methods: Rats were separated in two groups: sedentary and HIIT exercise. Exercise was on a treadmill for 30 min daily (10 3 min cycles) for six weeks with progressive speed increased up to 0.8 mph (21.5 m/min). Results: Results showed for D2R-like binding, a significant effect across the ventral caudate putamen (V CPU) between sexes, such that mean D2R-like binding was 14% greater for males than females. In the nucleus accumbens shell (Nac Shell), the HIIT Exercise rats showed 16% greater D2R-like binding as compared to the sedentary rats. No significant effects of HIIT exercise were found across groups for brain D1R-like binding levels or TH expression. Conclusion: These results suggest that HIIT exercise can modulate dopamine signaling by way of increased D2R. These findings support the premise that HIIT exercise plays an important role in dopamine signaling and, may provide a potential mechanism for how HIIT exercise can impact the brain and behavior.

Effects of exercise on mortality rates of individuals with severe mental illness.

Persons with severe mental illness have a 10-to-20-year shorter life span than the general public. Excess morbidity and mortality in this patient population has been described as a major public health challenge worldwide. Despite robust extant literature on the role of exercise in reducing morbidity and mortality, especially from cardiovascular disease and diabetes (highly prevalent in this patient population), Very few clinical programs or clinical research projects currently exist to implement and study the effects of exercise on decreasing morbidity and mortality in this highly vulnerable patient population. Given the global lack of trained mental health providers, the need to integrate healthcare providers from different disciplines, such as nurses, physical therapists, occupational therapists, physician assistants, cannot be overstated. This mini-review will provide an historic perspective and current data supporting the need to establish exercise, and other Lifestyle Psychiatry interventions, as a key component of treatment for all patients with serious mental illness.

Racial/ethnic disparities in the use of medications for opioid use disorder (MOUD) and their effects on residential drug treatment outcomes in the US.

BACKGROUND: This study examines racial/ethnic disparities in the use of medications for opioid use disorder (MOUD) in residential treatment and the influence of race/ethnicity on the association between MOUD use and treatment retention and completion. METHODS: Data were extracted from SAMHSA's 2015-2017 Treatment Episode Dataset-Discharge (TEDS-D) datasets for adult opioid admissions/discharges to short-term (ST) (30 days or less) (N = 83,032) or long-term (LT) (> 30 days) residential treatment settings (N=61,626). Logistic regression estimated the likelihood of MOUD use among racial/ethnic groups and the moderation of race/ethnicity on the probability of treatment completion and retention, controlling for background factors. RESULTS: After adjusting for covariates, compared to Whites, MOUD use was less likely for Blacks in ST (OR = 0.728) and LT settings (OR = 0.725) and slightly less likely for Hispanics in ST settings (OR = 0.859) but slightly more likely for Hispanics in LT settings (OR = 1.107). In ST settings, compared to Whites, the positive effect of MOUD on retention was enhanced for Blacks (OR = 1.191) and Hispanics (OR = 1.234), and the positive effect on treatment completion was enhanced for Hispanics (OR = 1.144). In LT settings, the negative association between MOUD and treatment completion was enhanced for Hispanics (OR = 0.776). CONCLUSIONS: Access to medications for opioid use disorder in short term residential treatment is particularly beneficial for Blacks and Hispanics, though adjusted models indicate they are less likely to receive it compared to Whites. Results are mixed for long-term residential treatment. Residential addiction treatment may represent an important setting for mitigating low rates of medication initiation and early discontinuation for minority patients.

Remdesivir for the Treatment of COVID-19: A Systematic Review of the Literature.

In March 2020, the World Health Organization declared the spread of SARS-CoV-2 a global pandemic. To date, coronavirus disease-2019 (COVID-19) has spread to over 200 countries, leading to over 1.6 million cases and over 99,000 deaths. Given that there is neither a vaccine nor proven treatment for COVID-19, there is currently an urgent need for effective pharmacotherapy. To address the need for an effective treatment of SARS-CoV-2 during the worldwide pandemic, this systematic review of intravenous (IV) remdesivir was performed. Remdesivir, an anti-viral prodrug originally developed to treat Ebola virus disease, has shown broad spectrum activity against the Coronavirus family. A recent case report reported improvement of clinical symptoms with remdesivir in a patient with COVID-19. After conducting a systematic search of 18 clinical trial registries and three large scientific databases, we identified 86 potentially eligible items. Following removal of duplicates (n = 21), eligible studies were reviewed independently by two authors. After the first round of screening, inter-rater agreement was 98.5% (κ = 0.925). After the second round of full-text screening, inter-rater agreement was 100%. A total of seven ongoing and recruiting clinical trials of remdesivir (100-200 milligrams, intravenous [IV]) were included. We identified the following primary outcomes: patients discharged (n = 2); time to clinical status improvement (n = 2); improved O2 saturation (n = 2); body temperature normalization (n = 2); and clinical status (n = 1). Secondary outcomes in all identified studies included documentation of adverse events. Phase 3 trials are expected to be completed between April 2020-2023. Therefore, despite supportive data from in vitro and in vivo studies, the clinical effectiveness of IV remdesivir for treatment of COVID-19 and potential side effects remain incompletely defined in the human population.

Notions of Preprocedural Patient Anxiety in the Realm of IR.

PURPOSE: To determine the views and current practice preferences of interventional radiologists and allied healthcare providers regarding management of preprocedural anxiety. MATERIALS AND METHODS: From March to April 2018, members of the Society of Interventional Radiology were surveyed regarding their opinions in the assessment and management of patient anxiety. Degree of responsibility for the management of anxiety was also queried through the use of a scale (1 = no responsibility; 2 = some responsibility; 3 = major responsibility). RESULTS: Of 1163 respondents (23.8% response rate), most described preprocedural anxiety as somewhat to very important in their practice (n = 961, 82.6%), somewhat to very important to the patients (n = 1087, 93.5%), and at least sometimes interfering with delivery of care (n = 815, 70.1%). Most respondents did not measure preprocedural anxiety directly (n = 953, 81.9%), but would address it if raised by the patient (n = 911, 82.9%). Patient education (n = 921, 79.1%), medications (n = 801, 68.8%), and therapeutic or empathetic interactions (n = 665, 56.4%) were most preferred to manage anxiety. Radiologists, nurses, patients, primary care providers, family members, and psychologists or psychiatrists were all allocated responsibility to reduce anxiety. CONCLUSIONS: Interventional radiologists and other providers are aware of the importance of preprocedural anxiety. Despite the notion that most radiologists did not address anxiety directly, most indicated a willingness to discuss the issue if raised by patients. Patient education, medications, and several other techniques are preferred to manage preprocedural anxiety. Responsibility to reduce anxiety is perceived to be shared among radiologists, nurses, patients, family members, and other health care providers.

How long does it take to complete outpatient substance use disorder treatment? Disparities among Blacks, Hispanics, and Whites in the US.

This research investigates racial and ethnic disparities in outpatient substance use disorder treatment completion and duration in treatment, for different substances, across the US, using the national 2014 Treatment Episode Dataset-Discharge (TEDS-D) data set. Moderated fixed effects logistic regression models assessed effects of race/ethnicity on length of stay in treatment and treatment completion for different substances of use. Moderated models also assessed the differential effect of length of stay on treatment completion among Blacks, Hispanics, and Whites. While Blacks and Hispanics both have significantly lower treatment completion rates than Whites, treatment duration is substantially similar across the three groups. Blacks and Hispanics generally take longer to complete treatment than Whites, though this varies by substance for Hispanics. Disparities in treatment completion persist even after controlling for treatment duration. These results indicate that observed racial and ethnic disparities in treatment completion are not due to differences in length of stay in treatment. Economic, cultural, accessibility, or, potentially, discriminatory, factors may suppress the likelihood of treatment completion for minorities and result in longer treatment durations required for completion. Recognition by treatment providers of the unique challenges to treatment completion faced by minorities may enhance treatment outcomes for minorities in the US.

Addressing the Need for Clinical Trial End Points in Autosomal Dominant Polycystic Kidney Disease: A Report From the Polycystic Kidney Disease Outcomes Consortium (PKDOC).

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Expansion of multiple cysts throughout both kidneys is thought to lead to progressive loss of kidney function and kidney failure in some patients. In recent years, much has been learned about the pathophysiology of ADPKD. However, to date, only one therapy has been approved in the United States and in other regions for the treatment of ADPKD. Feasible end points and a clear regulatory pathway may stimulate further development in this area and ultimately lead to more treatments for ADPKD successfully reaching the market. In July 2016, the PKD Outcomes Consortium under the auspices of the Critical Path Institute and the PKD Foundation convened a PKD Summit to facilitate a discussion among patients, regulators, pharmaceutical sponsors, and academic clinical trialists regarding trial end points and the regulatory path to approval of new drugs for ADPKD. Following the summit, participants continued the dialogue using regularly scheduled teleconferences. This article addresses key considerations related to the design of clinical trials in ADPKD based on these discussions.

An International Study of Emotional Response to Bilateral Vision Loss Using a Novel Graphical Online Assessment Tool.

BACKGROUND: Leber׳s hereditary optic neuropathy usually causes rapid bilateral blindness in young adults, and thus represents a unique and severe psychologic stressor. OBJECTIVE: We aimed to describe adjustment to this major life event, using a new tool to enhance recall of past affective states by using life event-related context. This is the largest (n = 116 with Leber׳s hereditary optic neuropathy), and first study reporting on the emotional aspects of this nontrauma cause of blindness. METHODS: We developed a new online survey tool that allowed study subjects to report their mood over a long period of time, corresponding with dates of relevant life events. RESULTS: The new method provided data of great richness for qualitative and quantitative analysis. Three groups were identified: a group in which majority of them had severe sadness at the point of vision loss followed by a period of recovery, a group whose sadness had not recovered, and a group for whom vision loss was not a major cause of sadness compared with other life events. We identified numerous factors that were important in psychologic recovery, and premorbid psychologic symptoms were more frequent in those who had not yet recovered. CONCLUSIONS: These data may assist behavioral health providers in identifying patients with vision loss to be at risk of mental health problems and in developing support and treatment interventions. We believe this new method has great potential for studying psychologic adjustment retrospectively.

Neuropsychiatric aspects of concussion.

Over the past decade, concussion has become the most widely discussed injury in contact sports. However, concussions also occur in several other settings, such as non-contact sports, elderly individuals, young children, military personnel, and victims of domestic violence. Concussion is frequently undiagnosed as a cause of psychiatric morbidity, especially when the patient has no history of loss of consciousness or direct head trauma. Almost all of the extant literature focuses on traumatic brain injury and assumes that concussion is merely a mild form of traumatic brain injury, which has resulted in a lack of understanding about what concussion is, and how to diagnose, monitor, and treat its varied neuropsychiatric symptoms. In this Review, we address key issues so that the psychiatric clinician can better understand and treat patients with a clinical phenotype that might be the direct result of, or be exacerbated by, concussion. Future research needs to focus on prospective clinical trials in all affected patient populations (ie, those affected by concussion and those affected by various degrees of traumatic brain injury), the identification of reliable biomarkers that can be used to assist with diagnosis and treatment response, and the development of effective treatment interventions. Clearly differentiating concussion from traumatic brain injury is essential to achieve reliable and clinically relevant outcomes.

A One Health overview, facilitating advances in comparative medicine and translational research.

TABLE OF CONTENTS: A1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O'ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O'BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman.

Geospatial technology and the "exposome": new perspectives on addiction.

Addiction represents one of the greatest public health problems facing the United States. Advances in addiction research have focused on the neurobiology of this disease. We discuss potential new breakthroughs in understanding the other side of gene-environment interactions-the environmental context or "exposome" of addiction. Such research has recently been made possible by advances in geospatial technologies together with new mobile and sensor computing platforms. These advances have fostered interdisciplinary collaborations focusing on the intersection of environment and behavior in addiction research. Although issues of privacy protection for study participants remain, these advances could potentially improve our understanding of initiation of drug use and relapse and help develop innovative technology-based interventions to improve treatment and continuing care services.

Treatment of adults with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a clinically important neuropsychiatric developmental disorder that affects children, adolescents, and adults. The disorder is characterized by core symptoms of inattention, hyperactivity, distractibility, impulsivity, and impaired executive functioning. It is estimated that 2% to 5% of the adult population in the United States has ADHD. Adults with ADHD are at an increased risk for experiencing comorbid psychiatric disorders, including mood disorders, anxiety disorders, and substance use disorders. The authors provide a brief clinical overview of ADHD and the treatment of adults with this disorder.