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1.
Am J Disaster Med ; 19(1): 45-51, 2024.
Article in English | MEDLINE | ID: mdl-38597646

ABSTRACT

OBJECTIVE: Active duty military surgeons often have limited trauma surgery experience prior to deployment. Consequently, military-civilian training programs have been developed at high-volume trauma centers to evaluate and maintain proficiencies. Advanced Surgical Skills for Exposure in Trauma (ASSET) was incorporated into the predeployment curriculum at the Army Trauma Training Detachment in 2011. This is the first study to assess whether military surgeons demonstrated improved knowledge and increased confidence after taking ASSET. DESIGN: Retrospective cohort study. SETTING: Quaternary care hospital. PATIENTS AND PARTICIPANTS: Attending military surgeons who completed ASSET between July 2011 and October 2020. MAIN OUTCOME MEASURE(S): Pre- and post-course self-reported comfort level with procedures was converted from a five-point Likert scale to a percentage and compared using paired t-tests. RESULTS: In 188 military surgeons, the median time in practice was 3 (1-8) years, with specialties in general surgery (52 percent), orthopedic surgery (29 percent), trauma (7 percent), and other disciplines (12 percent). The completed self-evaluation response rate was 80 percent (n = 151). The self-reported comfort level for all body regions improved following course completion (p < 0.001): chest (27 percent), neck (23 percent), upper extremity (22 percent), lower extremity (21 percent), and abdomen/pelvis (19 percent). The overall score on the competency test improved after completion of ASSET, with averages increasing from 62 ± 18 percent pretest to 71 ± 13 percent post-test (p < 0.001). CONCLUSIONS: After taking the ASSET course, military surgeons demonstrated improved knowledge and increased confidence in the operative skills taught in the course. The ASSET course may provide sustainment of knowledge and confidence if used at regular intervals to maintain trauma skills and deployment readiness.


Subject(s)
Military Medicine , Military Personnel , Surgeons , Traumatology , Humans , Traumatology/education , Retrospective Studies , Clinical Competence
2.
JAMA Dermatol ; 160(2): 172-178, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38170500

ABSTRACT

Importance: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer. Of the patients who develop MCC annually, only 4% are younger than 50 years. Objective: To identify genetic risk factors for early-onset MCC via genomic sequencing. Design, Setting, and Participants: The study represents a multicenter collaboration between the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Allergy and Infectious Diseases (NIAID), and the University of Washington. Participants with early-onset and later-onset MCC were prospectively enrolled in an institutional review board-approved study at the University of Washington between January 2003 and May 2019. Unrelated controls were enrolled in the NIAID Centralized Sequencing Program (CSP) between September 2017 and September 2021. Analysis was performed from September 2021 and March 2023. Early-onset MCC was defined as disease occurrence in individuals younger than 50 years. Later-onset MCC was defined as disease occurrence at age 50 years or older. Unrelated controls were evaluated by the NIAID CSP for reasons other than familial cancer syndromes, including immunological, neurological, and psychiatric disorders. Results: This case-control analysis included 1012 participants: 37 with early-onset MCC, 45 with later-onset MCC, and 930 unrelated controls. Among 37 patients with early-onset MCC, 7 (19%) had well-described variants in genes associated with cancer predisposition. Six patients had variants associated with hereditary cancer syndromes (ATM = 2, BRCA1 = 2, BRCA2 = 1, and TP53 = 1) and 1 patient had a variant associated with immunodeficiency and lymphoma (MAGT1). Compared with 930 unrelated controls, the early-onset MCC cohort was significantly enriched for cancer-predisposing pathogenic or likely pathogenic variants in these 5 genes (odds ratio, 30.35; 95% CI, 8.89-106.30; P < .001). No germline disease variants in these genes were identified in 45 patients with later-onset MCC. Additional variants in DNA repair genes were also identified among patients with MCC. Conclusions and Relevance: Because variants in certain DNA repair and cancer predisposition genes are associated with early-onset MCC, genetic counseling and testing should be considered for patients presenting at younger than 50 years.


Subject(s)
Carcinoma, Merkel Cell , Skin Neoplasms , Humans , Middle Aged , Genetic Predisposition to Disease , Carcinoma, Merkel Cell/epidemiology , Carcinoma, Merkel Cell/genetics , Germ-Line Mutation , Skin Neoplasms/epidemiology , Skin Neoplasms/genetics , Risk Factors
3.
JAMA Dermatol ; 159(5): 536-540, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36920369

ABSTRACT

Importance: Racial and ethnic differences in skin cancer outcomes are understudied. Delineating these differences in Merkel cell carcinoma (MCC) is needed to better understand this rare disease. Objective: To determine how MCC presentation and outcomes differ across racial and ethnic groups. Design, Setting, and Participants: This retrospective cohort study included patients diagnosed with MCC and followed up from 2000 through 2018 in the 18 population-based cancer registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Patients without follow-up data were excluded. Data analysis occurred from March 12 to November 30, 2022. Main Outcomes and Measures: A Cox proportional hazards regression was conducted to determine associations between demographic variables (race and ethnicity, age, sex, and income) and clinical variables (stage at diagnosis, primary site, and diagnosis year) with MCC-specific survival. Results: Of the 9557 patients with MCC identified (6758 [70.7%] aged ≥70 years; 6008 [62.9%] male), 222 (2.3%) were Asian American or Pacific Islander, 146 (1.5%) Black, 541 (5.7%) Hispanic, and 8590 (89.9%) White. Hispanic patients had improved MCC-specific survival compared with White patients (hazard ratio, 0.82; 95% CI, 0.67-0.99; P = .04). Black patients had the lowest MCC-specific survival, but it was not statistically different from White patients (hazard ratio, 1.19; 95% CI, 0.86-1.60; P = .28). Hispanic and Black patients were less likely to present with a primary site of the head and neck than White patients (183 of 541 [33.8%] Hispanic patients and 45 of 146 [30.8%] Black patients vs 3736 of 8590 [43.5%] White patients; P < .001 and P = .002, respectively). Black patients presented more often than White patients with advanced disease at diagnosis (59 of 146 [40.4%] vs 2510 of 8590 [29.2%]; P = .004). Conclusions and Relevance: In this cohort study, there were differences between racial and ethnic groups in observed MCC outcomes and disease characteristics. Further investigations are warranted into the findings that, compared with White patients, Hispanic patients with MCC had improved outcomes and Black patients did not have worse outcomes despite presenting with more advanced disease.


Subject(s)
Carcinoma, Merkel Cell , Skin Neoplasms , Humans , Male , Female , Ethnicity , Cohort Studies , Retrospective Studies , Carcinoma, Merkel Cell/therapy
4.
Pharmacol Ther ; 243: 108355, 2023 03.
Article in English | MEDLINE | ID: mdl-36739914

ABSTRACT

Itch is an unpleasant sensation arising from a variety of dermatologic, neuropathic, systemic, and psychogenic etiologies. Various itch pathways are implicated according to the underlying etiology. A variety of pruritogens, or itch mediators, as well as receptors have been identified and provide potential therapeutic targets. Recent research has primarily focused on targeting inflammatory cytokines and Janus kinase signaling, protease-activated receptors, substance P and neurokinin, transient receptor potential-vanilloid ion channels, Mas-related G-protein-coupled receptors (MRGPRX2 and MRGPRX4), the endogenous opioid and cannabinoid balance, and phosphodiesterase 4. Periostin, a newly identified pruritogen, should be further explored with clinical trials. Drugs targeting neural sensitization including the gabergic system and P2X3 are other potential drugs for chronic itch. There is a need for more targeted therapies to improve clinical outcomes and reduce side effects.


Subject(s)
Pruritus , Transient Receptor Potential Channels , Humans , Pruritus/drug therapy , Pruritus/etiology , Cytokines/metabolism , Transient Receptor Potential Channels/metabolism , Signal Transduction , Receptors, G-Protein-Coupled/metabolism , Nerve Tissue Proteins/metabolism , Receptors, Neuropeptide
6.
J Eur Acad Dermatol Venereol ; 37(2): 231-242, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36251409

ABSTRACT

Skin carcinomas are the most common form of cancer, and every year thousands of people die from skin cancer-related malignancies. Chronic inflammation is linked to the development and progression of cancer in multiple organ systems - about 20% of all human cancers are a result of chronic inflammation - skin included. While acute inflammation under normal circumstances is a mechanism for host defence and tissue regeneration following insult by trauma or infection by pathogens, over the long term it can drive oncogenic transformation of epithelial cells and promote cancer development, growth and metastasis. Therefore, inflammatory conditions may put individuals at a higher risk to developing skin malignancies. Many skin conditions are characterized by chronic inflammatory processes. These conditions may be particularly susceptible to malignant transformation and predispose patients to develop skin malignancies. As more pathophysiology of chronic inflammatory skin conditions is unveiled, we find that many of these conditions are characterized by immune dysregulation and signalling that result in chronic activation and upregulation of pro-inflammatory chemokines and cytokines, leading to downstream processes that further exacerbate inflammatory processes and cause abnormal cell growth and apoptosis. Here, we review the major chronic cutaneous inflammatory diseases that may have an increased risk of skin malignancies, including atopic dermatitis, psoriasis, discoid lupus erythematosus, lichen planus, hidradenitis suppurativa, prurigo nodularis, lichen sclerosus, systemic sclerosis and morphea, chronic leg ulcers, seborrheic keratoses and basal cell carcinoma. We evaluate the evidence for increased incidence and prevalence, the risk factors associated, the populations at heightened risk and the best management practices.


Subject(s)
Hidradenitis Suppurativa , Psoriasis , Skin Neoplasms , Humans , Skin , Inflammation/complications , Chronic Disease
8.
Cancer Biol Ther ; 23(1): 1-3, 2022 12 31.
Article in English | MEDLINE | ID: mdl-36404405

ABSTRACT

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer that predominantly impacts White patients. Overall incidence and the proportion of minority patients with MCC are both rising. In the more common skin cancer, melanoma, racial disparities are well-documented in stage at presentation and patient survival. Whether racial and ethnic disparities exist in MCC remains unclear. The study of MCC disparities is hampered by limitations in data registries, including SEER and NCDB, and an evolving natural history due to the advent of immunotherapy. Published MCC immunotherapy clinical trials consistently reported the racial diversity among enrolled subjects but failed to include patients' ethnicities. Efforts to improve data capture in cancer registries and create multi-institutional clinical databases will allow for more effective study of racial and ethnic disparities in rare cancers like MCC. Such studies are needed to advance policies promoting equity in care.


Subject(s)
Carcinoma, Merkel Cell , Melanoma , Skin Neoplasms , Humans , Carcinoma, Merkel Cell/therapy , Carcinoma, Merkel Cell/pathology , Skin Neoplasms/therapy , Skin Neoplasms/pathology , Immunotherapy , Immunologic Factors
9.
Acta Derm Venereol ; 102: adv00796, 2022 Oct 19.
Article in English | MEDLINE | ID: mdl-36250769

ABSTRACT

Lichen simplex chronicus is a form of chronic localized pruritus with a secondary dermatitis, and one of the most common types of chronic itch conditions, estimated to affect more than 10% of the general population. However, despite its prevalence and burden, there has been limited research into the pathogenesis and aetiology of lichen simplex chronicus, which, historically, made it a challenging condition to treat. In recent years, our understanding of this condition, along with that of pruritus and the itch-scratch cycle, has increased greatly, enabling a substantial increase in treatment options. In addition, there are several new promising treatments currently in development and trials. This article discusses the definition, epidemiology, clinical characteristics, pathophysiology, and current therapeutic options for lichen simplex chronicus, in order to highlight recent advancements in this field.


Subject(s)
Neurodermatitis , Humans , Neurodermatitis/diagnosis , Neurodermatitis/epidemiology , Neurodermatitis/therapy , Pruritus/diagnosis , Pruritus/epidemiology , Pruritus/etiology
12.
Dermatol Ther ; 35(9): e15719, 2022 09.
Article in English | MEDLINE | ID: mdl-35841269

ABSTRACT

Acne affects approximately 9% of people worldwide and is the most common skin condition in the USA. There are abundant topical and oral treatment options available for patients with acne. First-line agents include topical retinoids, azelaic acid, benzoyl peroxide, and combinations of these agents. For recalcitrant or more severe acne, oral medications, including oral antibiotics, isotretinoin, or hormonal therapy, may be considered. This review will also discuss the many advances being made in the treatment of acne vulgaris, from the development of microencapsulated medications to targeted treatments.


Subject(s)
Acne Vulgaris , Dermatologic Agents , Acne Vulgaris/diagnosis , Acne Vulgaris/drug therapy , Anti-Bacterial Agents/therapeutic use , Benzoyl Peroxide/therapeutic use , Dermatologic Agents/therapeutic use , Humans , Isotretinoin/therapeutic use
14.
J Cosmet Dermatol ; 21(10): 4249-4253, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35500136

ABSTRACT

Social media networks serve as convenient platforms for the dissemination of information, including that which pertains to healthcare. However, social media networks may also disseminate incorrect information, and may even propagate potentially harmful skincare trends. Since its inception in 2016, TikTok, a social media platform wherein users can create and share videos, has served as a tool for the propagation of multiple, potentially dangerous cosmetic trends, most recently the usage of fibroblast pens. Fibroblast pens, also known as plasma pens, are toted to produce a variety of skincare benefits. However, many of the pens being sold commercially, and subsequently used on TikTok, are not FDA-regulated. Potential adverse effects include the development of dyspigmentation, scarring, and mechanical burns of the skin. This study assessed social media content to improve our understanding of fibroblast pen usage amongst TikTok creators. An initial search of public TikTok posts tagged with "#PlasmaPen," "#PlasmaPenTreatment," "#FibroblastPlasma," or "#FibroblastPlasmaPen" identified 200 posts, of which 78 were eliminated after accounting for overlapping posts between hashtags, posts that were later deleted by the user, and those in languages other than English. We analyzed posts according to creator type and classified them into four main themes. The 78 videos were later re-viewed to provide more detailed subdivisions within the four main themes. Analysis showed that 36% of the posts were created by lay-person TikTok users, followed by 25% of posts being created by self-proclaimed fibroblast skin tightening specialists. Major themes include advertisement of the fibroblast pen (61%), experience with the fibroblast pen (26%), education on the fibroblast pen's uses and benefits (6.5%), and warnings related to usage of the pen (6.5%). TikTok users are more likely to encounter a post regarding fibroblast pen usage from uncredentialled, non-medical professional accounts. Only 6.5% of posts were created with the intention of serving as a warning to users, with most of these posts being created by medical doctors. Dermatologists should be aware of the misinformation regarding fibroblast pens and consider posting on social media to raise awareness about this potentially dangerous skincare trend.


Subject(s)
Physicians , Social Media , Humans , Communication , Fibroblasts
15.
Lasers Med Sci ; 37(6): 2581-2587, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35604505

ABSTRACT

Tattoos have become ingrained in our society and have served varied purposes throughout human civilization. So long as tattoos have existed, there has been demand for their removal. Lasers are currently the modality of choice in the removal of tattoos, as they are more efficacious than previously used methods. The most common lasers are the 532 nm and 1064 nm neodymium-doped yttrium aluminum garnet lasers, the quality-switched 694 nm Ruby laser, and the quality-switched 755 nm alexandrite laser. However, picosecond lasers are rapidly gaining favor in tattoo removal. An in-depth understanding of laser principles and how they can be applied in the setting of tattoo removal is key. Also, a greater understanding of the origin of and colors within a tattoo, the presence of tattoo layering, and a patient's Fitzpatrick skin type increase the odds of satisfactory results. This review provides dermatologists with a comprehensive summary on laser fundamentals, an overview on treatment principles, and recent developments in the field of laser tattoo removal.


Subject(s)
Laser Therapy , Lasers, Solid-State , Plastic Surgery Procedures , Tattooing , Humans , Laser Therapy/methods , Lasers, Solid-State/therapeutic use
16.
Dermatol Ther ; 35(6): e15501, 2022 06.
Article in English | MEDLINE | ID: mdl-35393669

ABSTRACT

Basal cell carcinoma (BCC) remains the most common malignancy worldwide. BCC pathogenesis is a result of the interplay between one's environment, genetics, and phenotypic factors. BCC has a low mortality but given its increasing incidence and potential to cause local destruction thus resulting in significant morbidity, it is vital for dermatologists to remain up to date with recent updates in this malignancy's pathogenesis and treatment. This article provides a comprehensive review of the pathogenesis of BCC as well as the current treatments available and clinical trials underway. We also touch upon the updated National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology in respect to BCC's recommended treatment modalities.


Subject(s)
Carcinoma, Basal Cell , Skin Neoplasms , Carcinoma, Basal Cell/drug therapy , Carcinoma, Basal Cell/therapy , Humans , Skin Neoplasms/diagnosis , Skin Neoplasms/etiology , Skin Neoplasms/therapy
17.
Dermatol Ther ; 35(3): e15292, 2022 03.
Article in English | MEDLINE | ID: mdl-34967084

ABSTRACT

Merkel cell carcinoma is a rare neuroendocrine carcinoma that typically appears in sun-exposed areas of the elderly. It has a poor prognosis and with its incidence projected to increase, it is vital for dermatologists to remain up to date with recent updates in this malignancy's pathogenesis and treatment. In the past few decades Merkel cell carcinoma's pathogenesis, more specifically its relation to the Merkel cell polyomavirus, has sparked further interest in the study of this carcinoma. Most cases are attributed to malignant transformation secondary to the Merkel cell polyomavirus, with a minority derived from DNA damage resulting from ultraviolet radiation. Investigators have also determined that there are immunologic influences in the development and prognosis of Merkel cell carcinoma, as individuals with HIV, solid organ transplants, and lymphoproliferative malignancies are at a greater risk of developing this carcinoma. In addition, this immunologic link carries treatment value, as immunologic therapies are currently being investigated. This article provides a comprehensive review of the epidemiology and pathogenesis of Merkel cell carcinoma as well as the current treatments available and clinical trials underway. We also touch upon the updated National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology in respect to its diagnosis and recommended treatment modalities.


Subject(s)
Carcinoma, Merkel Cell , Merkel cell polyomavirus , Skin Neoplasms , Aged , Carcinoma, Merkel Cell/diagnosis , Carcinoma, Merkel Cell/etiology , Carcinoma, Merkel Cell/therapy , Humans , Merkel cell polyomavirus/genetics , Prognosis , Skin Neoplasms/diagnosis , Skin Neoplasms/etiology , Skin Neoplasms/therapy , Ultraviolet Rays
18.
Mol Autism ; 12(1): 50, 2021 07 08.
Article in English | MEDLINE | ID: mdl-34238350

ABSTRACT

BACKGROUND: Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. METHODS: Cerebrospinal fluid and blood samples were collected from N = 76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n = 43), samples were collected thrice over a 10-month period. The following statistical tests were used: "Case 2A" intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. RESULTS: All biological measures (except AKT) showed significant test-retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n = 57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n = 75 of the subjects). CONCLUSIONS: These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys.


Subject(s)
Autistic Disorder , Animals , Biomarkers , Humans , Macaca mulatta , Male , Phosphatidylinositol 3-Kinases , Reproducibility of Results , Social Behavior , Sociological Factors
19.
J Psychiatr Res ; 140: 436-442, 2021 08.
Article in English | MEDLINE | ID: mdl-34147931

ABSTRACT

People with schizophrenia (SCZ) and bipolar disorder (BD) have challenges in self-evaluation of their cognitive and functional performance (introspective accuracy). They also manifest response biases, with tendencies toward overestimation. This study aimed to examine objective test performance, momentary judgments of performance, momentary confidence, and subsequent global judgments of performance on a metacognitive version of the Wisconsin Card Sorting Test (WCST). This sample included 99 participants with SCZ and 67 with BD. After each of the 64 WCST trials, participants reported whether they believed their sort was correct and how confident they were in that judgment, they then received performance feedback. After completion of the entire task, participants generated a global performance judgment. On average, the SCZ group got 31 sorts correct, reporting being correct on 49 whereas the BD group got 37 trials correct but reported being correct on 53. For participants with BD, sorting performance correlated with trial x trial accuracy judgments, confidence, and predicted global judgments. For SCZ participants, performance minimally correlated with trial x trial accuracy judgments, confidence, and global judgments, while trial x trial confidence was strongly associated with trial x trial accuracy judgments (r = 0.58). Our findings suggest that confidence in participants with BD is correlated with task performance, whereas in SCZ confidence was entirely associated with self-generated performance judgments. SCZ participants manifested challenges with utilization of feedback. Global judgments of performance were predicted by task performance and confidence for BD participants, with performance and confidence judgments occurring prior to generation of the global performance judgments.


Subject(s)
Bipolar Disorder , Schizophrenia , Bias , Bipolar Disorder/diagnosis , Cognition , Humans , Wisconsin Card Sorting Test
20.
Sci Transl Med ; 11(491)2019 05 08.
Article in English | MEDLINE | ID: mdl-31043522

ABSTRACT

The social impairments of autism spectrum disorder (ASD) have a major impact on quality of life, yet there are no medications that effectively treat these core social behavior deficits. Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. Using a double-blind, randomized, placebo-controlled, parallel study design, we tested the efficacy and tolerability of a 4-week intranasal AVP daily treatment in 30 children with ASD. AVP-treated participants aged 6 to 9.5 years received the maximum daily target dose of 24 International Units (IU); participants aged 9.6 to 12.9 years received the maximum daily target dose of 32 IU. Intranasal AVP treatment compared to placebo enhanced social abilities as assessed by change from baseline in this phase 2 trial's primary outcome measure, the Social Responsiveness Scale, 2nd Edition total score (SRS-2 T score; F 1,20 = 9.853; P = 0.0052; ηp 2 = 33.0%; Cohen's d = 1.40). AVP treatment also diminished anxiety symptoms and some repetitive behaviors. Most of these findings were more pronounced when we accounted for pretreatment AVP concentrations in blood. AVP was well tolerated with minimal side effects. No AVP-treated participants dropped out of the trial, and there were no differences in the rate of adverse events reported between treatment conditions. Last, no changes from baseline were observed in vital signs, electrocardiogram tracings, height and body weight, or clinical chemistry measurements after 4 weeks of AVP treatment. These preliminary findings suggest that AVP has potential for treating social impairments in children with ASD.


Subject(s)
Autism Spectrum Disorder/drug therapy , Social Behavior , Vasopressins/administration & dosage , Vasopressins/therapeutic use , Administration, Intranasal , Child , Female , Humans , Male , Pilot Projects , Placebos , Treatment Outcome , Vasopressins/adverse effects
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