Transitions, Suicidality, and Underappreciated Autism Spectrum Disorder in a High School Student.

CASE: Alex is a 14-year-old Portuguese-American boy with a psychiatric history starting at age 5 who presents to your primary care practice after an insurance change.He was delivered prematurely at 32 weeks and diagnosed with congenital hypothyroidism at the age of 6 weeks and growth hormone deficiency at the age of 2 years; he is in active treatment for both. He otherwise met developmental milestones on time yet continues to have significant fatigue despite adequate sleep and vitamin D supplementation.His family history is remarkable for maternal anxiety, depression, suicidal thoughts, and previous attempted suicide, as well as anxiety, alcoholism, depression, and attention-deficit/hyperactivity disorder (ADHD) in the extended family.Alex has had multiple psychiatric diagnoses by sequential providers. He was diagnosed with generalized anxiety disorder and ADHD by 5 years of age, major depressive disorder by 11 years of age, persistent depressive disorder by 12 years of age, and ultimately disruptive mood dysregulation disorder because of severe and persistent temper outbursts associated with negative mood and behavioral dysregulation, leading to recurrent crisis evaluations. He has been psychiatrically hospitalized twice, in the fifth and seventh grade, for suicidal ideation (SI) and elopement from home, respectively. He recently completed a 2-week acute residential placement, during which no medication changes were made. Current medications include escitalopram 20 mg daily, guanfacine 1 mg 3 times daily, sustained release bupropion 100 mg twice daily, levothyroxine, vitamin D, and a weekly somatropin injection. He has not been able to tolerate psychostimulants or nonstimulant agents because of treatment-emergent SI.Now in the ninth grade, he continues to be easily distracted by peers, with impulsive behaviors and reduced self-regulation. Despite receiving special education services since the fifth grade, his academic performance has been poor, and he has limited motivation. Previous testing indicated average in an intelligence quotient test, with relative deficits in working memory compared with above average strength in fluid reasoning. He dislikes school and has few friends. He has always been noted to be "immature." He displays temper tantrums at home and school around transitions and behavioral expectations and has complained of feeling "different" and misunderstood by peers in addition to having difficulty reading social cues. His interests include acting and playing Fortnite and other video/computer games. His screen time is limited to 1 to 2 hr/d by the family.As the new clinician, you raise the possibility of undiagnosed autism spectrum disorder as a unifying/underlying diagnosis with his mother, who disagrees and does not consent to additional workup despite your recommendations. How would you proceed with next steps to best support your patient and his family in obtaining further clarifying evaluation?

Review of Salient Investigational Drugs for the Treatment of Fragile X Syndrome.

OBJECTIVES: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability, in addition to being the commonest diagnosable cause of autism. The identification of the biochemical mechanism underlying this disorder has provided amenable targets for therapy. This review aims to provide an overview of investigational drug therapies for FXS. METHODS: The authors carried out a search of clinical and preclinical trials for FXS in PubMed and on the U.S. National Institutes of Health index of clinical trials ( www.clinicaltrials.gov ). We limited our review to Phase II trials or more preliminary and reviewed the associated publications for these studies, complemented by a review of the literature on PubMed. RESULTS: The review of the preclinical, Phase I, and Phase II trials of agents with therapeutic potential in FXS revolves around an understanding of the putative pathways in the pathogenesis of FXS. While there is significant overlap between some of these pathways, the agents can be categorized as modulators of the metabotropic glutamate receptor system, GABAergic agents, and miscellaneous modulators affecting other pathways. CONCLUSION: As trials involving agents targeting different aspects of the molecular biology proceed, common themes have emerged. With the great hope came great disappointment as the initial trials failed to demonstrate sufficient significance. In particular, the differences in outcome between the animal models and humans have highlighted the unique challenges of carrying out trials in these cognitively and behaviorally challenged individuals, as well as a dearth of clinically relevant outcome measures for use in medication trials. However, in reviewing and reframing the studies of the last decade, many important lessons have been learned, which will ultimately have a greater impact on therapeutic research in the field of developmental delay as a whole.

The Use of Antiepileptic Drugs (AEDs) for the Treatment of Pediatric Aggression and Mood Disorders.

Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs) have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the available data on ten AEDs - valproate, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, topiramate, levetiracetam, zonisamide, gabapentin and tiagabine - in an attempt to assess evidence for the efficacy of AEDs in the treatment of aggression in pediatric populations. Our review revealed modest evidence that some of the AEDs produced improvement in pediatric aggression, but controlled trials in pediatric bipolar disorder have not been promising. Valproate is the best supported AED for aggression and should be considered as a first line of treatment. When monotherapy is insufficient, combining an AED with either lithium or an atypical anti-psychotic can result in better efficacy. Additionally, our review indicates that medications with predominately GABA-ergic mechanisms of action are not effective in treating aggression, and medications which decrease glutaminergic transmission tended to have more cognitive adverse effects. Agents with multiple mechanisms of action may be more effective.

Machine safety evaluation in small metal working facilities: an evaluation of inter-rater reliability in the quantification of machine-related hazards.

BACKGROUND: Each year there are an estimated 4.2-6.7 amputations per 10,000 workers in the metal fabrication trades in the United States. The Minnesota Machine Guarding Study evaluates the effectiveness of a peer-based technical and educational intervention designed to reduce exposure to amputation hazards among workers in small machining/metal working shops. The study reported here involved the development and evaluation of methods for measuring machine safety, which will be used in the intervention study. METHODS: Using OSHA regulations, ANSI standards, and industry best practices, we developed 23 machine-safety scorecards. The safety scores were dependent on the presence or absence of guards, other safety devices and implements, and the presence or absence of acceptable administrative programs. Inter-rater reliability was assessed for the evaluation of eight types of commonly used metal fabrication machines. RESULTS: Of the 23 most common types of machines, there were a sufficient number of machines to evaluate inter-rater reliability for eight types. Three raters in four shops assessed fifty-nine machines. Overall, the kappa statistic ranged from 0.57 to 0.84, indicating good to very good concordance between raters. In general, machines did not fare well with regard to compliance with current standards. DISCUSSION: The ability to assess machine-related hazards is important in industries where it is difficult to identify and count injuries in a timely fashion. Machinists and safety professionals may use this scoring system as a means of reproducible assessment of machine safety.

Neuropsychiatric sequelae of neuroleptic malignant syndrome.

The authors review the literature on persistent sequelae of neuroleptic malignant syndrome (NMS). They highlight the clinical presentations, assessment, and management of persistent sequelae and stress the need to take preventive steps to minimize their occurrence. The authors conducted a Medline and PubMed search for papers on residual sequelae of NMS. They cross-referenced the available papers and "operationalized" the diagnostic criteria for persistent neuropsychiatric sequelae. A total of 31 cases of neuropsychiatric sequelae of NMS were identified. With reduction in mortality from NMS, persistent sequelae of NMS have assumed clinical importance. Long-term sequelae persist for weeks to months after amelioration of an acute episode. Individuals with a preexisting CNS insult are more predisposed to develop persistent sequelae. A high index of awareness for persistent sequelae is warranted because antipsychotics are widely used for psychiatric disorders besides schizophrenia. Awareness of such outcomes and the use of evidence-based strategies to minimize risk factors will help clinicians in reducing the persistent sequelae of NMS.

The syndrome of irreversible lithium-effectuated neurotoxicity.

OBJECTIVES: Persistent sequelae of lithium intoxication gained clinical attention in the 1980s and were named Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT). The authors review the published cases of SILENT reported in the literature and discuss various clinical manifestations. METHODS: The authors' inclusion criteria included persistence of sequelae for at least 2 months after the cessation of lithium administration. They conducted a MEDLINE and Pub Med search for journal articles from the year 1965 to 2004. They also cross-referenced available papers. RESULTS: The authors identified 90 cases of SILENT in peer-reviewed publications. Persistent cerebellar dysfunction was the most commonly reported sequela. Other atypical presentations have also been reported. CONCLUSION: Although the biologic mechanism remains unclear, the authors hypothesize that the putative cause of SILENT is demyelination caused by lithium at multiple sites in the nervous system, including the cerebellum. Recent advances in the understanding of the molecular basis of lithium-induced neurotoxicity may be able to provide a means of defining a pathway associated with the long-term prophylactic properties of lithium, distinct from its toxicity profile. This identification of differential gene expression patterns that distinguish between therapeutic and toxic actions of lithium may help in the discovery of new drugs for mood stabilization. Clinically and heuristically, it is important to raise the awareness of this syndrome so that clinicians are able to avoid it. A precise definition, operational diagnostic criteria, and a descriptive name will aid in the early identification and prevention of SILENT.

Adolescent work patterns and work-related injury incidence in rural Minnesota.

BACKGROUND: Although there have been many studies on working youth in the United States, we have noted none which have provided a broad picture of adolescent work practices in a rural community. METHODS: Six high schools in rural Minnesota were evaluated for adolescent work practices. Schools ranged in size from 173 to 525 students in grades 9 through 12. A 20 page self-administered survey examining work practices was administered to students. RESULTS: A total of 2,250 students completed the survey, representing 92% of the student body. Twenty-eight percent of students lived on a farm. Approximately 45% of the male students and slightly more than 21% of the females were involved in farm work. Only 2.6% of students were injured during this 8-month time period in farm-related activities, and 5.1% were injured doing non-farm work. Many students reported working long hours. CONCLUSIONS: Work represents a serious problem for rural youth. These data are significant in the context of national policy discussion concerning the failure of the Fair Labor Standards Act to regulate the agricultural environment.

Causes, nature, and outcomes of work-related injuries to adolescents working at farm and non-farm jobs in rural Minnesota.

BACKGROUND: Although there are many studies on working adolescents, information on youth who simultaneously hold jobs on both a farm and in other sectors of the economy is lacking. METHODS: Six high schools in rural Minnesota were evaluated for adolescent work practices and injury incidence. A 20-page self-administered survey was administered to students. RESULTS: A total of 2,250 students completed the survey, representing 92% of the student body. Students that simultaneously hold both farm and non-farm jobs have a significantly higher proportion of injuries. However, annual injury rates are highest for those working in non-farm only (26.7/100 full-time equivalents, FTEs) or farm only (25.9/100 FTEs) employment when compared with those working simultaneously in farm and non-farm jobs (21.9/100 FTEs). CONCLUSIONS: Many rural students employed simultaneously on farm and non-farm jobs work long hours and are at significant risk of work-related injury. The annual injury rates we estimated are higher than those reported in previous studies.