Mode of action studies confirm on-target engagement of lysyl-tRNA synthetase inhibitor and lead to new selection marker for Cryptosporidium.

Introduction: Cryptosporidiosis is a leading cause of diarrheal-associated morbidity and mortality, predominantly affecting children under 5 years old in low-and-middle-income countries. There is no effective treatment and no vaccine. New therapeutics are emerging from drug discovery efforts. It is critical that mode of action studies are performed alongside drug discovery to ensure the best clinical outcomes. Unfortunately, technology to identify and validate drug targets for Cryptosporidium is severely lacking. Methods: We used C. parvum lysyl-tRNA synthetase (CpKRS) and DDD01510706 as a target-compound pair to develop both chemical and genetic tools for mode of action studies for Cryptosporidium. We adapted thermal proteome profiling (TPP) for Cryptosporidium, an unbiased approach for target identification. Results: Using TPP we identified the molecular target of DDD01510706 and confirm that it is CpKRS. Genetic tools confirm that CpKRS is expressed throughout the life cycle and that this target is essential for parasite survival. Parasites genetically modified to over-express CpKRS or parasites with a mutation at the compound-binding site are resistant to treatment with DDD01510706. We leveraged these mutations to generate a second drug selection marker for genetic modification of Cryptosporidium, KRSR. This second selection marker is interchangeable with the original selection marker, NeoR, and expands the range of reverse genetic approaches available to study parasite biology. Due to the sexual nature of the Cryptosporidium life cycle, parental strains containing different drug selection markers can be crossed in vivo. Discussion: Selection with both drug markers produces highly efficient genetic crosses (>99% hybrid progeny), paving the way for forward genetics approaches in Cryptosporidium.

Defragmenting the path to diagnosis for underserved youth with Autism Spectrum Disorder in a community-based health system.

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder that affects about 1 out of every 54 youth and is characterized by impairments in social communication and functioning. ASD is a treatable condition though, and early initiation of interventions in the home and community can lead to improved long-term outcomes. Despite the clear benefits of early diagnosis and intervention, many youth, particularly from impoverished and minoritized populations, face tremendous barriers to accessing a timely formal diagnosis and critical early supports. Many of these barriers are inherent features of a fragmented health care system that even the most resourced of families struggle to navigate. Informed by the principles of coproduction of health care, value-based care design, and health equity, we present a quality improvement initiative to defragment the experience of care for underserved families seeking a timely formal diagnosis of ASD in a safety-net community-based health system. Over the course of 2.5 years, we were able to partner with families to create clinical workflows that cut in half the duration of time from first developmental concern to ASD diagnosis, and lowered the median age of ASD diagnosis in our health system by more than 3 years. We share our process and lessons learned in the hopes of helping other health systems pursuing similar goals for patient- and family-centered care design.

An Unusual and Rare Metachronous Ipsilateral Ureteric Stump Metastasis Post Radical Nephrectomy.

We report a case of recurrence of chromophobe renal cell cancer in the ipsilateral ureteric stump eight years later after the primary tumor was excised successfully. Before this detection of the recurrence, the patient had presented with recurrent episodes of hematuria four years after the radical nephrectomy was performed and the investigations were inconclusive. Eventually, the lesion was detected on flexible cystoscopy in the area of the right ureteric orifice protruding in the bladder. Transurethral resection of the tumor surprisingly revealed a chromophobe renal cancer with similar features seen in the primary tumor specimen. The patient underwent robotic-assisted laparoscopic excision of the ureteric stump with a cuff of the bladder and has been recurrence-free for five years on regular surveillance scans.

Promoting Population Behavioral Health in a Safety-Net Health System During the COVID-19 Pandemic.

The COVID-19 pandemic has been expected to lead to substantial increases in need for behavioral health care. A population health framework can facilitate the development of interventions and policies to promote the equitable distribution of care across the population. This column describes the application of population behavioral health principles in a safety-net health system during the pandemic. The approach includes stepped models of care, interventions to target individuals at high behavioral health risk, and measurement-based care. Early data suggest that these strategies have resulted in expanded behavioral health care capacity.

Sexual Health in Child and Adolescent Psychiatry: Multi-Site Implementation Through Synchronized Videoconferencing of an Educational Resource Using Standardized Patients.

Objective: Matters of sexuality and sexual health are common in the practice of child and adolescent psychiatry (CAP), yet clinicians can feel ill-equipped to address them with confidence. To address this gap in training and practice, we developed, implemented, and evaluated an educational module enhanced by videotaped depictions of expert clinicians interacting with professional actors performing as standardized patients (SPs). Methods: We developed an educational resource highlighting common issues of sexual health relevant to CAP practice, including sexual development, psychotropic-related side effects, and sexuality in children with autism. We wrote original scripts, based on which two clinicians interacted with three SPs. Digital recordings were edited to yield 5 clips with a cumulative running time of 20 min. The clips were interspersed during a 90-min session comprising didactic and interactive components. Due to the COVID-19 pandemic, we used synchronous videoconferencing, which allowed content dissemination to several training programs across the country. Results: We recruited 125 learners from 16 CAP training programs through the American Academy of CAP's Alliance for Learning and Innovation (AALI). Routine inquiry into adolescent patients' sexual function was uncommon, reported by only 28% of participants, with "awkward" and "uncomfortable" the most common terms mentioned in reference to the clinical task. The didactic intervention led to measurable improvements after 2 weeks in skills and knowledge (p = 0.004) and in attitudes (p < 0.001). The three items with the greatest improvement were: (a) availability of developmentally tailored resources; (b) comfort in addressing sexual development with underage patients; and (c) with parents or guardians of neuroatypical or developmentally disabled patients (p < 0.001 for each). Conclusions: A sexual health curriculum enriched by video-based examples can lead to measurable improvement in outcomes pertinent to the clinical practice of CAP. These educational materials are available for distribution, use and adaptation by local instructors. Our study also provides proof-of-principle for the use of multisite educational initiatives in CAP through synchronized videoconferencing.

Transitions in Care: A Workshop to Help Residents and Fellows Provide Safe, Effective Handoffs for Acute Psychiatric Patients.

Introduction: Focused training in care transitions is an ACGME-required component of resident education. However, there are limited published curricular resources specific to trainees in psychiatry to help develop this crucial skill. Methods: We developed a 90-minute interactive workshop on care transitions in psychiatry for general adult psychiatry residents (PGY 2-PGY 4), child and adolescent fellows, and consult-liaison fellows. Trainees collaborated in interdisciplinary teams to explore a vignette in which a patient moved through four different venues of care (outpatient, emergency department, inpatient medical, and inpatient psychiatric). Guiding questions prompted discussions of critical issues related to logistics and clinical communication for each transition between care environments. Results: In a postworkshop anonymous survey, 100% of trainee participants (n = 30) felt the workshop was successful in creating the opportunity to develop relationships with, and learn from, colleagues at other levels of psychiatry training. Ninety percent responded affirmatively that they were able to identify key elements of an effective handoff for an acute psychiatric patient. Eighty-three percent identified being able to describe logistical steps for transferring the care of patients between mental health services at their institution. Discussion: Trainee participants found the workshop beneficial for understanding the steps needed to transfer patients between levels of care safely, discussing and debating gray areas with peers and faculty, and developing interdisciplinary relationships within psychiatry. Faculty participants described an interest in using the workshop as a faculty development exercise. This workshop fills a critical gap in available curricula on transitions in care in psychiatry.

A Comparison of Health Care Expenditures for Medicaid-Insured Children with Autism Spectrum Disorder and Asthma in an Expanding Accountable Care Organization.

As value-based care continues to expand, more children with autism spectrum disorder (ASD) will be treated by accountable care organizations (ACOs), provider organizations seeking to improve population health while reducing costs. To inform ACO strategies for children with ASD, this study compared health care expenditures of children insured by a Medicaid managed care organization, empaneled to a safety net ACO, with ASD, asthma, and neither diagnosis. Compared to other study groups, children with ASD were more costly, had lower rates of acute care, and had higher rates of "leaked" care provided by home- and community-based mental health agencies outside of the ACO. These findings highlight the need for unique value-based strategies for children with ASD in a public sector ACO.

Moonlighting by Psychiatry Residents: a Survey of Residents and Training Directors.

OBJECTIVE: This study sought to assess the prevalence of moonlighting among psychiatry residents; the perceived effects of moonlighting on resident recruitment, education, and liability; and policies and practices governing oversight. METHODS: In 2013, surveys were emailed to all general psychiatry residency programs that were accredited by the Accreditation Council for Graduate Medical Education and had available contact information (n = 183). Resident surveys were emailed to program coordinators with a request to forward the survey link to their residents. RESULTS: Responses were received from 63 program directors (34% response rate) and 238 residents (about 5% of total general psychiatry residents). Most psychiatry program directors (95%) indicated that their programs permit moonlighting. Moonlighting participation increased with each year of training, culminating with 67% of fourth year residents. Most residents and faculty (87%) agreed that moonlighting enhanced resident education. Thirty-seven percent of program directors reported having no oversight procedures in place to monitor moonlighting activities. Thirty-nine percent of resident survey responders reported having no supervision for at least one of their moonlighting activities and only 9% reported always having access to on-site supervision. CONCLUSION: Though limited by a low response rate, this study found that moonlighting seems to remain prevalent among psychiatry residents and widely accepted by psychiatry residency training programs. There appears to be relatively limited program oversight for moonlighting activities, many of which seem to lack close supervision.

A Qualitative Study of Factors Affecting Morale in Psychiatry Residency Training.

OBJECTIVE: Resident morale is an important yet poorly understood aspect of the residency training experience. Despite implications for program quality, resident satisfaction, patient care, and recruitment, little is known about the variables influencing this complex phenomenon. This study sought to identify important factors affecting morale in psychiatry residency training. METHODS: The authors conducted four semi-structured focus groups at a moderately sized, urban, psychiatry residency program during the 2013-2014 academic year. They used qualitative data analysis techniques, including grounded theory and content analysis, to identify key themes affecting resident morale across training levels. RESULTS: Twenty-seven residents participated in the focus groups with equal distribution across post-graduate years (PGY) 1-4. Five major conceptual categories affecting resident morale emerged: Sense of Community, Individual Motivators, Clinical Work, Feeling Cared For, and Trust in the Administration. CONCLUSIONS: Morale is an important topic in residency education. The qualitative results suggest that factors related to a Sense of Community and Individual Motivators generally enhanced resident morale whereas factors related to a lack of Feeling Cared For and Trust in the Administration tended to contribute to lower morale. The authors describe the possible interventions to promote stronger program morale suggested by these findings.

Electroconvulsive therapy for the treatment of refractory mania.

We present the case of a patient with treatment-refractory mania. The patient had been tried on numerous medications, to which she either did not respond well or on which she developed severe side effects, However, the patient improved rapidly when treated with unilateral electropercussive therapy (ECT) following a court order. We outline the legal barriers that have been raised against the use of ECT in patients with mania, who often refuse treatment, and the irony that ECT can be safer than medications for some patients. ECT is underutilized in mania but deserves more frequent consideration. (Journal of Psychiatric Practice. 2011;17:61-66).

Discharge antithrombotic strategies among patients with acute coronary syndrome previously on warfarin anticoagulation: physician practice in the CRUSADE registry.

BACKGROUND: Patients experiencing acute coronary syndromes (ACS) with high-risk features frequently undergo percutaneous coronary intervention (PCI) with stent placement, prompting the requisite administration of aspirin and clopidogrel. The current management of ACS patients with a concomitant indication for warfarin anticoagulant therapy is a question of growing interest and clinical relevance. METHODS: We analyzed discharge antithrombotic medication use among all patients with non-ST-segment elevation (NSTE) ACS enrolled in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines (CRUSADE) initiative who were receiving warfarin at the time of hospital admission. Multivariable logistic regression was used to determine factors associated with a decision to discontinue warfarin at discharge. RESULTS: Among 5673 patients with ACS previously on home warfarin, 1357 (24%) were not discharged on warfarin. In the subset of 1247 patients who underwent coronary stenting, 60% were prescribed triple anticoagulation therapy (aspirin, clopidogrel, and warfarin), 31% were given aspirin and clopidogrel without warfarin, and 3% received warfarin and aspirin without clopidogrel. Factors associated with a decision not to continue warfarin at the time of hospital discharge included in-hospital red blood cell transfusion, non-white race, prior stroke, and discharge clopidogrel use. The decision to continue warfarin at discharge correlated with perceived bleeding risk and was unaffected by patients' stroke risk. CONCLUSION: Physician practices vary with regard to the perceived optimal antithrombotic strategy at time of hospital discharge among patients with ACS with a concomitant indication for warfarin. Decisions are influenced primarily by other medication use and anticipated bleeding risk. Further research is needed to guide patient care based on the safety and efficacy of antiplatelet-anticoagulant combined pharmacotherapy.

Case report--ancient schwannoma of the scrotum.

BACKGROUND: Scrotal schwannoma is a rare neoplasm and poses a diagnostic challenge to urologists. This article describes a rare case of ancient scrotal schwannoma and reviews the current modality of investigation and treatment of this tumour. CASE REPORT: A 28 year old man presented with a 3-month history of an asymptomatic scrotal swelling. Ultrasonography and computer topography revealed an intra-scrotal and extra-testicular mass without local invasion. Surgical excision was undertaken and histology was an ancient schwannoma of the scrotum. CONCLUSION: Schwannoma is a benign encapsulating neoplasm with an overall low incidence, occurring mostly in the head and neck region and seldom in the scrotum. Histology shows two distinctive patterns, Antoni type A and B areas. Variations of schwannoma such as cellular, ancient, glandular and epithelioid are observed based on the appearances. Ancient schwannoma exhibits pleomorphism without mitosis as the result of cellular degeneration, which can lead to an erroneous diagnosis of malignancy. Imaging modalities are non-specific for schwannomas, but can define tumour size, site and extension. The mainstay treatment is complete excision, although local recurrence may occur in large and incompletely excised lesions. Malignant change is exceedingly rare.

Description of a program for social language intervention: "if you can have a conversation, you can have a relationship".

Adolescents with impaired language comprehension and formulation skills often experience difficulty keeping up with the linguistic and social demands of peer interaction. This clinical exchange describes an individualized treatment program designed to increase the conversational skill of an adolescent male with language impairment. Treatment focused on increasing awareness of the listener's needs and on balancing the exchange of conversational turns. Clinical performance, parent report, and client report were used to assess outcomes.

Description of a Program for Social Language Intervention: If You Can Have a Conversation, You Can Have a Relationship.

Adolescents with impaired language comprehension and formulation skills often experience difficulty keeping up with the linguistic and social demands of peer interaction. This clinical exchange describes an individualized treatment program designed to increase the conversational skill of an adolescent male with language impairment. Treatment focused on increasing awareness of the listener's needs and on balancing the exchange of conversational turns. Clinical performance, parent report, and client report were used to assess outcomes.