Cârța Monastery.

Description The Cârța Monastery, a former Cistercian monastery, is pictured here from one of its sides, conjuring the romanticism that is beloved in medieval ruins. The photo was taken on a sunny fall afternoon in the Țara Fagarașului region of Romania in southern Transylvania. Cârța Monastery was started around 1202 by a group of Cistercian monks from Egres Abbey in the then-kingdom of Hungary. Cistercian architecture is considered some of the most beautiful of the Middle Ages, and walking the grounds of the Monastery indeed evoked a profound sense of gratitude, awe, and peace in the shadow of its beauty that I can call up to this day. Such experiences contribute to our resilience as individuals, and as communities, and reminds us as global members of society that seeking to consistently better ourselves and our planet is a constant evolution.

Dr. Johnstone et al. Reply to Dr. Elmrayed.

We thank Dr. Elmrayed and colleagues1 for highlighting clinical cautions in using broad-spectrum micronutrients to treat attention-deficit/hyperactivity disorder (ADHD) in children, in particular manganese (Mn) levels. We appreciate the opportunity to provide additional information and rationale for the vitamin and mineral doses contained in the studied formula.

Dr. Johnstone et al. Reply to Dr. Hamilton.

We thank Dr. Hamilton1 for his interest in our research and for provoking a more nuanced and detailed approach to analyzing the relationship among treatment assignment, treatment response, and correct treatment guessing in randomized controlled trials; in this case, the Micronutrients for ADHD in Youth (MADDY) study.2.

Fruit and vegetable intake is inversely associated with severity of inattention in a pediatric population with ADHD symptoms: the MADDY Study.

OBJECTIVES: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with a U.S. pediatric prevalence of 8-10%. It presents with inattention and hyperactivity/impulsivity; frequently associated with emotional dysregulation (ED) symptoms common in Oppositional Defiant Disorder and Disruptive Mood Dysregulation Disorder. The etiology of ADHD is multi-factorial; symptom severity is associated with diet. This study examines the association of diet quality with ADHD and ED symptoms within a pediatric research cohort. METHODS: Baseline data were analyzed for 134 children aged 6-12 years with symptoms of ADHD and ED enrolled in an RCT of multinutrient supplementation. Diet quality was based on Healthy Eating Index-2015 (HEI-2015). ADHD and ED symptoms were assessed using Child and Adolescent Symptom Inventory-5 and Strengths and Difficulties Questionnaire. Linear regression models, adjusting for covariates when necessary, determined association. RESULTS: The mean HEI Total Score of 63.4 (SD = 8.8) was not significantly associated with any outcome symptoms. However, after adjusting for covariates, HEI component scores for total fruit intake (ß = -0.158, p = .037) and total vegetable intake (ß = -0.118, p = .004) were negatively associated with inattention. CONCLUSIONS: The lack of association with total diet quality could be explained by the relatively good baseline diet quality and mild symptom severity in this sample, along with measurement error from dietary intake estimates and relatively small sample size. These findings suggest that dietary intake may impact inattention in children with ADHD and ED: those eating less fruits and vegetables were likely to have more severe symptoms of inattention. Causality is not established by this cross-sectional analysis.

Unprovoked Submassive Saddle Pulmonary Embolism in an Adult Male After Pfizer COVID-19 Vaccination.

Pulmonary emboli (PEs) occur when the pulmonary artery is blocked by foreign material. In one such instance, this foreign material can be a blood clot that may occur from patient risk factors inducing a prothrombotic state. The relationship between COVID-19 vaccines and a prothrombotic state is novel and changing as our understanding of the relationship between the two evolves. The patient in this case study presented with unrelenting and progressive dyspnea, tachycardia, and unilateral lower extremity swelling two days after receiving the second dose of the Pfizer COVID-19 vaccine. After diagnostic testing, the patient was found to have a submassive saddle pulmonary embolism with subsequent right heart strain. This patient was treated with appropriate anticoagulation therapies, including heparin and apixaban, as well as thrombectomy, and made a complete recovery. The possible relationship between COVID-19 vaccines and thrombotic events supports the need for increased awareness of a potential new risk factor behind the development of PE. It is our hope that this case report will help raise awareness of an association despite the lack of incident data at this time.

Paediatric adverse event rating scale: a measure of safety or efficacy? Novel analysis from the MADDY study.

OBJECTIVE: The Pediatric Adverse Event Rating Scale (PAERS) measured adverse events of children aged 6-12 years with ADHD and emotional dysregulation in the Micronutrients for ADHD in Youth (MADDY) study, an eight week multi-site randomized clinical trial of a broad-spectrum multinutrient treatment. Treatment sensitivity of the PAERS was assessed by calculating the treatment difference in change of the item scores from baseline to end of the RCT. METHODS: Principal component analysis retained 14 "adverse events" (out of 43 in the PAERS) that reflected ADHD symptoms and emotional dysregulation and was used to group the variables of interest. A combined score ranging from 0 to 5 was created based on symptom presence, functional impairment, and severity. Mean score change was calculated from baseline to week 8 by treatment (multinutrient vs placebo) with intention-to-treat and per-protocol samples. The study has been registered on clinicaltrials.gov as Micronutrients for ADHD in Youth (MADDY) Study, trial registration # NCT03252522 (https://clinicaltrials.gov/ct2/show/NCT03252522). RESULTS: The 126 children in the ITT sample had a mean age of 9.8 (SD = 1.7), with majority (73%) male, and 72% diagnosed with ADHD prior to the study screening. Baseline presence of PAERS symptoms was similar between treatment groups: the highest proportion was ADHD symptoms, followed by Irritable symptoms. The micronutrient group showed a greater decrease (improvement) in the mean anxiety combined score than the placebo group with a between-group difference in change of -0.36 (95% CI: -0.67, -0.04; p = .03) with ITT data and -0.48 (95% CI: -0.81, -0.15; p = .005) with per-protocol (n = 93) data. CONCLUSION: The multinutrient supplement did not result in more adverse events than placebo, suggesting it is a safe intervention. In addition to assessing actual adverse events, the PAERS may be a useful adjunct outcome measure for ADHD behaviors.

Household Food Insecurity Is Associated with Symptoms of Emotional Dysregulation in Children with Attention Deficit Hyperactivity Disorder: The MADDY Study.

The association of household food insecurity with symptoms of attention deficit hyperactivity disorder (ADHD) and emotional dysregulation in children was examined in this study. We utilized baseline data from 134 children aged 6-12 years who were enrolled in a clinical trial investigating multinutrient supplementation as a treatment for ADHD and emotional dysregulation. Household food security status was assessed using the 18-item US Household Food Security Survey Module. The symptoms of ADHD and emotional dysregulation disorders (oppositional defiant disorder (ODD) and disruptive mood dysregulation disorder (DMDD)) were assessed using the Child and Adolescent Symptom Inventory-5 and other comorbid emotional dysregulation symptoms were assessed using the Strengths and Difficulties Questionnaire (SDQ). Multiple linear regression determined associations between household food security status and symptoms of ADHD, ODD and DMDD, emotional symptoms and conduct problems. Household food insecurity was associated with more severe emotional symptoms (ß = 2.30; 95% CI = 0.87-3.73; p = 0.002), conduct problems (ß = 1.15; 95% CI = 0.01-2.30; p = 0.049) and total difficulties scores (ß = 4.59; 95% CI = 1.82-7.37; p = 0.001) after adjusting for covariates (child's sex, parent marital status, household income, parental anxiety and other parental psychopathology). In unadjusted analyses, household food insecurity was also associated with increased ODD (ß = 0.58; 95% CI = 0.21-0.95; p = 0.003) and DMDD symptoms (ß = 0.69; 95% CI = 0.20-1.19; p = 0.006), but these associations attenuated to non-significance after adjusting for all covariates. Household food insecurity was associated with more severe emotional dysregulation symptoms. Discussing and addressing food insecurity may be appropriate initial steps for youths with ADHD and emotional dysregulation.

Health Equity in Medicine.

Description Healthcare disparities exist when, due to racial, ethnic, or gender identity differences linked to social, economic or environmental factors, certain populations lack equitable access to quality healthcare and insurance coverage. Such disparities across history carry profound future implications that we have only begun to contemplate as a profession. This special issue of the HCA Healthcare Journal of Medicine examines the critical issue of health equity in medicine and how the medical community can advance health equity through inclusive behavior and interactions in clinical and educational settings, and our communities.

Pilot Mental Health Offender Program Improves Participant Outcomes and Lowers Costs in a Large Urban County.

Introduction: Mass incarceration, particularly of the mentally ill, continues to pervade our criminal justice system. Jails in many areas have become the largest mental health facilities, especially in large urban communities, despite increasing societal recognition that those with mental illness are not best served behind bars. Misdemeanors are an often-overlooked contributor to mass incarceration, and may be preventable for those with chronic severe mental illness. Methods: This Northeast Florida pilot program, the Mental Health Offenders Program (MHOP), is based on the successful Miami Eleventh Circuit Court Criminal Mental Health Project. MHOP provided pretrial release from custody, through diversion with a customized plan of care to stabilize defendants, using court supervision to ensure compliance. Results: With community partners, the MHOP pilot enrolled 20 individuals with chronic severe mental illness and recurrent misdemeanor charges; 15 were able to continue in the program with stabilization of their mental health and reduction of county costs both documented. Conclusion: The MHOP pilot demonstrates that community resources can be successfully shifted to benefit mentally ill, non-violent offenders and the larger community by helping severely mentally ill clients achieve stability by providing healthcare, housing, and income, while decreasing costs for the community in a humane way.

Sexual Obsessions in a Patient With Schizophrenia.

Description Obsessive-compulsive symptoms in schizophrenia are often initially unrecognized or missed entirely in the diagnostic process. Sexual obsession is common in patients with schizophrenia. Therefore, identifying sexual obsession early in treatment has significant implications for appropriate multidisciplinary management and prognosis. We report the case of a Hispanic male in his 20s who presented with self-injurious behavior and worsening psychotic symptoms in the context of a recent diagnosis of schizophrenia and without a past diagnosis or historical symptoms of obsessive-compulsive disorder (OCD). This report elucidates the importance of identifying the underlying cause of self-injurious behavior, which in this young man was due to new onset OCD presenting as sexual obsession comorbid with schizophrenia. Olanzapine, paroxetine, and cognitive behavioral therapy (CBT) were administered with good therapeutic response.

Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youths: A Placebo-Controlled Randomized Clinical Trial.

OBJECTIVE: To evaluate whether micronutrients (vitamins/minerals) benefit attention-deficit/hyperactivity disorder (ADHD) and irritability in a North American pediatric sample. METHOD: A 3-site, 8-week, placebo-controlled, randomized clinical trial of micronutrients was conducted in nonmedicated children aged 6 to 12 years with ADHD and at least 1 impairing irritability symptom by parent report on the Child and Adolescent Symptom Inventory-5 (CASI-5). A priori-defined primary outcomes were Clinical Global Impression-Improvement (CGI-I) (CGI-I of 1 or 2 = treatment responder) and parent-rated CASI-5 composite score of ADHD, oppositional defiant, disruptive mood dysregulation, and peer conflict symptoms, including impairment scores. RESULTS: Of 135 randomized (mean age 9.8 years), 126 youths (93%) comprised the modified intention-to-treat population. Blinding was maintained. For the CGI-I, 54% of the micronutrient and 18% of the placebo group were responders (risk ratio = 2.97, 97.5% CI = 1.50, 5.90, p < .001). CASI-5 composite scores improved significantly for both groups (p < .01), with a mean change of -0.31 (95% CI = -0.39, -0.23) in the micronutrient group and a mean change of -0.28 (95% CI = -0.38, -0.19) in the placebo group. However, the between-group difference was not significant (mean change = -0.02; 97.5% CI = -0.16, 0.12, effect size = 0.07, p = .70). The micronutrient group grew 6 mm more than the placebo group (p = .002). No serious adverse events or clinically significant changes from baseline in blood and urine tests occurred. CONCLUSION: Micronutrients showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Micronutrients showed greater height growth. Micronutrients were well tolerated, and the majority of participants adhered to the number of capsules prescribed. This randomized controlled trial replicates safety and efficacy reported for ADHD in 2 smaller trials of a similar formula containing all vitamins and known essential minerals in amounts between the Recommended Dietary Allowance and Upper Tolerable Intake Level. CLINICAL TRIAL REGISTRATION INFORMATION: Micronutrients for ADHD in Youth (MADDY) Study; https://clinicaltrials.gov; NCT03252522.

Excited Catatonia in Autism Spectrum Disorder: A Case Series.

Introduction: Autistic catatonia is an under-recognized debilitating syndrome with long-lasting negative effects for families, healthcare workers, and high-cost to the healthcare system. In this report, we describe two cases of excited catatonia in young men diagnosed with autism. Both endured a delay to diagnosis and difficulty to obtain appropriate treatment. Main concern: Each patient had a change in behavior from their baseline but with differences in severity and onset. The diagnosis in the first patient was made after only 3 months as the change was dramatic and sudden. Yet, despite a confirmed diagnosis, it was difficult to treat as the importance of M-ECT was not recognized by the clinicians. The second patient had been suffering for more than 5 years with a slow progression of worsening aggressive symptoms. The aggression was so uncontrollable that the patient required sedation, intubation and daily ECT. Both suffered from agitation, unprovoked aggression, urinary incontinence, stereotypic, and OCD behaviors and compulsive masturbation. Primary Diagnosis, intervention/outcomes: Both patients were diagnosed with autism, one high-functioning, attending high school and working a part-time job, the second low-functioning, nearly non-verbal, isolated to home and ABA school. The first patient's diagnosis of catatonia was only suspected after five psychiatric admissions and more than 20 medication trials. Lorazepam challenge was effective, he was treated with a short series of ECT but each time the treatments were tapered, the aggression returned. Ultimately, stabilized on weekly ECT. The second patient's behavior was escalating over a 5 month period, to the point, the aggression was uncontrollable. He presented to the ED under involuntary hold and the behavior could not be stabilized to the point that emergent ECT was initiated. Conclusion: Two cases of autistic catatonia diagnosed and treated within a year time span at a small community hospital indicates that this diagnosis is more common than previously recognized. We propose screening all patients with neurodevelopmental disorders with the Bush-Francis and Kanner scales to diagnose and treat them appropriately.

Elements of the New Conversation.

These comments include established behavioral treatment preceding and augmenting stimulant use to prevent or reduce dosing, nutritional approaches with placebo-controlled evidence, and possible effects of stimulant on micronutrient levels.

Development of a Composite Primary Outcome Score for Children with Attention-Deficit/Hyperactivity Disorder and Emotional Dysregulation.

Objective: Study goals were to (1) provide a rationale for developing a composite primary outcome score that includes symptom severity for attention-deficit/hyperactivity disorder (ADHD) and emotional dysregulation, plus symptom-induced impairment; (2) demonstrate weighting methods to calculate the composite score using a sample of children diagnosed with ADHD and aggression; and (3) identify the optimal weighting method most sensitive to change, as measured by effect sizes. Methods: We conducted secondary data analyses from the previously conducted Treatment of Severe Childhood Aggression (TOSCA) study. Children aged 6-12 years were recruited through academic medical centers or community referrals. The composite primary outcome comprised the ADHD, oppositional defiant disorder, disruptive mood dysregulation disorder, and peer conflict subscales from the Child and Adolescent Symptom Inventory (CASI), a DSM (Diagnostic and Statistical Manual)-referenced rating scale of symptom severity and symptom-induced impairment. Five weighting methods were tested based on input from senior statisticians. Results: The composite score demonstrated a larger (Cohen's d) effect size than the individual CASI subscales, irrespective of the weighting method (10%-55% larger). Across all weighting methods, effect sizes were similar and substantial: approximately a two-standard deviation symptom reduction (range: -1.97 to -2.04), highest for equal item and equal subscale weighting, was demonstrated, from baseline to week 9, among all TOSCA participants. The composite score showed a medium positive correlation with the Clinical Global Impressions-Severity scores, 0.46-0.47 for all weighting methods. Conclusions: A composite score that included severity and impairment ratings of ADHD and emotional dysregulation demonstrated a more robust pre-post change than individual subscales. This composite may be a more useful indicator of clinically relevant improvement in heterogeneous samples with ADHD than single subscales, avoiding some of the statistical limitations associated with multiple comparisons. Among the five similar weighting methods, the two best appear to be the equal item and equal subscale weighting methods.

Why I Brought My Mother Home.

Background According to the Alzheimer's Association, in the United States more than 16 million adult family members provide care for a relative with Alzheimer's disease or other dementia. The economic value contributed by unpaid caregivers is $234 billion dollars. Such caregivers are vital to the ability of the U.S. to meet caretaking needs, as the projected number of individuals suffering from dementia will nearly triple over the next 30 years. A meta-analysis found that decisions to provide family caretaking are rooted in long-standing family relationships. This essay explores one family's decision to move from long-term institutional care back to family-based care in the home setting. https://www.alz.org Greenwood N, Smith R. Motivations for being informal carers of people living with dementia: a systematic review of qualitative literature. BMC Geriatr. 2019;19(1):169. Published 2019 Jun 17. https://doi.org/10.1186/s12877-019-1185-0.

Perampanel-Induced Cataplexy in a Young Male with Generalized Epilepsy.

Description Perampanel (Fycompa) is a newer anti-epileptic drug believed to exert its effects in the central nervous system by inhibiting post-synaptic glutamate receptors. However, the precise therapeutic mechanism is unknown. The most common neuropsychiatric side effect is affective dysregulation; there are also reports of psychosis. We describe a 32 year old African American male with recurring generalized tonic-clonic (GTC) seizures, who presented to our hospital with onset of mood lability for several months, after Perampanel was added to his antiepileptic medications. Perampanel administration was temporarily withheld, and subsequently on restarting, noted to be coincident with neuropsychiatric symptomatology, including motor weakness in emotional contexts. The mechanisms underlying cataplexy are complex and, in our patient, most likely induced by an interaction between Perampanel and the wakeful inhibition of the sublaterodorsal nucleus projections.

Informing Strategy to Ensure Detection: Perceptions of Coronavirus Testing in a Southeastern U.S. Urban Homeless Population.

Introduction: Attitudes of those in the homeless population toward testing, particularly during a pandemic, are critical to understand, so that they and their communities may be safely triaged and protected. Homeless persons are more likely to be exposed during viral epidemics, and have greater vulnerability for more severe viral illness, due to greater medical comorbidities. The literature reflects a dearth of published papers describing the perceptions, interest, and motivations of homeless people to seek or receive viral testing, despite their status as a high-risk population. Methods: A quality improvement project consisting of a cross-sectional survey took place at 8 SARS-CoV-2 infection testing sites (local shelters and drop-in sites) within Duval County, Jacksonville, FL. Results: The vast majority of homeless individuals approached for testing completed demographic data and a checklist of beliefs and attitudes about testing (N=764) and underwent COVID-19 nasopharyngeal swab testing (n=679). Mean age was 48; 66% were male, and the predominant race was Black (51%) with 89% of non-Hispanic ethnicity. Of the total participants, 59.2% wanted testing and 4.6% declined testing. Attitudes toward testing varied by site and by wanting vs. not wanting to be tested. Top reasons in those wanting testing included curiosity; a belief that faith would protect them from the virus; and having shelter encouragement to be tested. Top attitudes among those not wanting to be tested were: shelter encouraged me; curiosity; and receiving a gift card. For the total group of subjects, being offered a $10 gift card did not affect their desire to be tested. Those who were not faith-influenced were less likely to want testing. Conclusion: Findings from selected literature and this quality improvement study support the use of a variety of strategies to encourage participation in testing events with large numbers of homeless individuals, including education, gift cards, shelter staff encouragement, involvement of local faith leaders and more broad support by the community. An additional qualitative study would complement these findings, as populations appear to differ in beliefs and attitudes depending on their location and other demographics. Motivational strategies to influence testing rates can be fine-tuned if beliefs, perceptions and attitudes are better understood.

Rationale and design of an international randomized placebo-controlled trial of a 36-ingredient micronutrient supplement for children with ADHD and irritable mood: The Micronutrients for ADHD in Youth (MADDY) study.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a chronic neurodevelopmental disorder affecting up to 9% of children and substantial numbers of adults. Existing pharmacologic treatments often improve symptoms, but concerns exist over side effects, stigma, potential long-term health effects, and residual irritability, often treated with adjunctive antipsychotics. To address public and clinician demand for non-pharmacologic evidence-based treatments, this study will examine efficacy of a 36-ingredient micronutrient (vitamin/mineral) supplement as treatment for children with ADHD and irritability. METHODS: An international team of experts in ADHD, mood dysregulation, nutrition, epidemiology, and clinical trials conferred to develop/refine a protocol powered to detect a medium effect. The study will employ a fully-blind randomized controlled trial (RCT) design, comparing the micronutrient supplement to matched placebo in 135 children aged 6-12 with ADHD symptoms and irritability, based on the parent-rated Child and Adolescent Symptom Inventory-5 (CASI-5). Irritability will be measured by at least one symptom of oppositional defiant disorder (ODD) or disruptive mood dysregulation disorder (DMDD). Based on research suggesting an irritable ADHD subtype, the primary outcome will be a composite score comprised of the CASI-5 subscales: ADHD, ODD, DMDD, and the Peer Conflict Scale, which assesses anger and aggression perpetrated towards peers. Participants will provide biological samples (blood, urine, saliva, hair and stool) to explore the micronutrients' mechanisms of action. DISCUSSION: This study is the first adequately powered RCT in North America to examine both behavioral responses to, and biological mechanisms of, micronutrients for ADHD and irritability in children. If found efficacious, broad-spectrum micronutrients, given at therapeutic doses, may provide an evidence-based alternative to prescription medications for ADHD and associated irritability. TRIAL REGISTRATION: NCT03252522. Registered 26 July 2017.

Bipolar disorder in youth is associated with increased levels of vitamin D-binding protein.

Genetic, dietary, and inflammatory factors contribute to the etiology of major mood disorders (MMD), thus impeding the identification of specific biomarkers to assist in diagnosis and treatment. We tested association of vitamin D and inflammatory markers in 36 adolescents with bipolar disorder (BD) and major depressive disorder (MDD) forms of MMD and without MMD (non-mood control). We also assessed the overall level of inflammation using a cell-based reporter assay for nuclear factor kappa-B (NFκB) activation and measuring antibodies to oxidized LDL. We found that these factors were similar between non-mood and MMD youth. To identify potential biomarkers, we developed a screening immunoprecipitation-sequencing approach based on inflammatory brain glia maturation factor beta (GMFß). We discovered that a homolog of GMFß in human plasma is vitamin D-binding protein (DBP) and validated this finding using immunoprecipitation with anti-DBP antibodies and mass spectrometry/sequencing analysis. We quantified DBP levels in participants by western blot. DBP levels in BD participants were significantly higher (136%) than in participants without MMD (100%). The increase in DBP levels in MDD participants (121.1%) was not statistically different from these groups. The DBP responds early to cellular damage by binding of structural proteins and activating inflammatory cells. A product of enzymatic cleavage of DBP has been described as macrophage-activating factor. Circulating DBP is comprised of heterogenous high and low molecular fractions that are only partially recognized by mono- and polyclonal ELISA and are not suitable for the quantitative comparison of DBP in non-mood and MDD participants. Our data suggest DBP as a marker candidate of BD warranting its validation in a larger cohort of adolescent and adult MMD patients.

ω-3 and ω-6 Fatty Acid Supplementation May Reduce Autism Symptoms Based on Parent Report in Preterm Toddlers.

Background: Children born preterm are at increased risk of autism spectrum disorder (ASD). n-3 (ω-3) Combined with n-6 (ω-6) fatty acids including γ-linolenic acid (GLA) may benefit children born preterm showing early signs of ASD. Previous trials have reported that docosahexaenoic acid (DHA) promotes cognitive development in preterm neonates and n-3 fatty acids combined with GLA improve attention-deficit-hyperactivity disorder. Objectives: The objectives of the pilot Preemie Tots Trial were 1) to confirm the feasibility of a full-scale trial in toddlers born very preterm and exhibiting ASD symptoms and 2) to explore the effects of supplementation on parent-reported ASD symptoms and related behaviors. Methods: This was a 90-d randomized, fully blinded, placebo-controlled trial in 31 children 18-38 mo of age who were born at ≤29 wk of gestation. One group was assigned to daily Omega-3-6-9 Junior (Nordic Naturals, Inc.) treatment (including 338 mg eicosapentaenoic acid, 225 mg DHA, and 83 mg GLA), and the other group received canola oil (124 mg palmitic acid, 39 mg stearic acid, 513 mg linoleic acid, 225 mg α-linolenic acid, and 1346 mg oleic acid). Mixed-effects regression analyses followed intent-to-treat analysis and explored effects on parent-reported ASD symptoms and related behaviors. Results: Of 31 children randomly assigned, 28 had complete outcome data. After accounting for baseline scores, those assigned to treatment exhibited a greater reduction in ASD symptoms per the Brief Infant Toddler Social Emotional Assessment ASD scale than did those assigned to placebo (difference in change = - 2.1 points; 95% CI: - 4.1, - 0.2 points; standardized effect size = - 0.71). No other outcome measure reflected a similar magnitude or a significant effect. Conclusions: This pilot trial confirmed adequate numbers of children enrolled and participated fully in the trial. No safety concerns were noted. It also found clinically-significant improvements in ASD symptoms for children randomly assigned to receive Omega-3-6-9 Junior, but effects were confined to one subscale. A future full-scale trial is warranted given the lack of effective treatments for this population. This trial was registered at www.clinicaltrials.gov as NCT01683565.