Vibro-tactile stimulation of the neck reduces pain in people with cervical dystonia: a proof-of-concept study.

BACKGROUND: Pain is a common non-motor symptom in patients with cervical dystonia (CD), severely impacting their quality of life. The pathophysiology of CD is incompletely understood but it involves altered processing of proprioceptive and pain signals. OBJECTIVES: The purpose of this proof-of-concept study was to determine if vibro-tactile stimulation (VTS)-a non-invasive form of neuromodulation targeting the somatosensory system-can modulate neck pain in people with CD. METHODS: In a multi-center study, 44 CD patients received VTS to sternocleidomastoid and/or trapezius muscles for up to 45 min under 9 different stimulation conditions that either targeted a single or a pair of muscles. The primary outcome measure was a perceived pain score (PPS) rated by participants on a 100-point analogue scale. RESULTS: During VTS, 29/44 (66%) of participants experienced a reduction in PPS of at least 10% with 17/44 (39%) reporting a reduction in pain of 50% or higher. After VTS cessation, 57% of participants still reported a 10% or higher reduction in PPS. Effects were significant at the group level and persisted for up to 20 min post-treatment. No distinct optimal stimulation profiles were identified for specific CD phenotypes. Clinical markers of disease severity or duration did not predict the degree of VTS-induced pain reduction. CONCLUSION: This proof-of-concept study demonstrates the potential of VTS as a new non-invasive therapeutic option for treating neck pain associated with CD. Further research needs to delineate optimal dosage and long-term effects.

Effect of Maxillary Posterior Space Discrepancy on the Molars and Overbite in Class II Malocclusions with Different Vertical Patterns.

AIM: The purpose of this cross-sectional study was to investigate the influence of maxillary posterior space discrepancy (MPDD) on angulation and vertical position of molars in patients with skeletal class II malocclusions, presenting long, short, and normal vertical growth patterns. MATERIALS AND METHODS: In total, 120 lateral cephalograms of patients (mean age: 23 years) with skeletal class II malocclusion were evaluated. Patients were divided into six groups based on their vertical growth pattern (normal, long, and short faces) and the presence or absence of maxillary posterior discrepancy. Maxillary molars' sagittal angulation and vertical position were measured on cephalograms via Dolphin™ three-dimensional (3D) software (version 11.5). The comparison between groups with the same vertical dimension and different status of MPDD was done with independent t test. The analysis of analysis (ANOVA) was used to make pairwise comparison between all six groups. Finally, a multiple regression analysis was performed to evaluate the influence of molar position and MPDD on the anterior overbite. RESULTS: The results showed that the angulation of the maxillary first molar was not statistically different between groups with the same vertical dimension but varied in terms of MPDD. The maxillary second molar was more distally inclined in patients with MPDD than those without MPDD with short and normal facial types (p value = 0.016 and p value = 0.001, respectively). The second molar had significantly more distal angulation in long face patients than short and normal face participants, without considering the status of MPDD. The upper first and second molars were erupted more in patients with long than short or normal faces, without any influence of MPDD. CONCLUSION: The presence of MPDD caused more distal inclination of the maxillary second molar, in skeletal class II patients with short and normal vertical growth patterns. CLINICAL SIGNIFICANCE: The status of MPDD and its effect on the maxillary second molar teeth should be considered in skeletal class II patients with short and normal vertical growth patterns.

Comparison of Aberrant Behavior Checklist profiles across Prader-Willi syndrome, Down syndrome, and autism spectrum disorder.

Prader-Willi syndrome (PWS, OMIM # 176270) and Down syndrome (DS, OMIM #190685) are neurodevelopmental genetic disorders with higher rates of autism spectrum disorder (ASD). The Aberrant Behavior Checklist (ABC) is a caregiver rating scale that assesses maladaptive behaviors. Overlapping symptoms exist between PWS, DS, and ASD, including maladaptive behaviors. We aimed to evaluate ABC profiles between PWS, DS, and ASD alone (without known genetic syndrome). In addition, we hypothesized PWS and DS with a comorbid ASD positive screen or diagnosis would have similar ABC profiles to ASD alone. ABC data from the following cohorts were analyzed: PWS (Seattle Children's Hospital, n = 28, mean age = 12.8 ± 4.9 years; University of Florida, n = 35, mean age = 9.3 ± 7.1 years), DS (Johns Hopkins, n = 406, mean age = 8.1 ± 2.4 years), and ASD (University of Florida, n = 102, mean age = 10.8 ± 3.5 years). ASD alone had significantly higher ABC scores. Subgroups of PWS and DS with a comorbid ASD positive screen or diagnosis had similarities in scores with the ASD only group, with subscale patterns unique to each syndrome. The ABC indicated worse maladaptive behaviors in children with ASD, including those with genetic syndromes. Although more studies are needed to evaluate the utility and the accuracy of the ABC as a tool to screen for ASD in special populations, it may be a useful adjunct in screening those children with PWS or DS who need more in depth ASD evaluation.

Rectal Picking Masquerading as Inflammatory Bowel Disease in Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a genetic syndrome in which individuals have multisystem medical challenges. Gastroenterological difficulties in the syndrome include decreased vomiting, constipation, delayed gastric emptying, delayed colonic transit, dysphagia, increased choking, and increased risk of gastric dilation and rupture. In addition, self-injurious behavior such as rectal picking may be present and severe enough to lead to rectal ulceration and bleeding. Many patients have extensive gastroenterological workup and treatment before their ultimate diagnosis of severe rectal picking. We describe 4 new cases of rectal picking in individuals with PWS leading to rectal bleeding and ulceration as well as a review of the literature of prior cases of severe rectal picking in PWS and potential treatment options. It is important to recognize these cases early in order to prevent unnecessary treatments and implement appropriate behavioral interventions.

Review of Current Care Models for Transgender Youth and Application to the Development of a Multidisciplinary Clinic - The Seattle Children's Hospital Experience.

Care of transgender and gender diverse youth is complex and requires a multidisciplinary approach. Many transgender patients and providers feel the limited availability of affirming, knowledgeable professionals is a barrier to obtaining care. Such care can be provided through a clinic with providers from different disciplines who are trained in the unique care of transgender youth. In this paper, we discuss the care guidelines for transgender youth and the unresolved challenges that need to be addressed during the development of a transgender clinic. We describe our experience at Seattle Children's Hospital in the development of a multidisciplinary Gender Clinic which incorporates the expertise of social work, mental health professionals, pediatric endocrinology, adolescent medicine, and bioethics. Other institutions may build from our experience, with the ultimate goal of further decreasing health disparities for young transgender patients.

Effects of MetAP2 inhibition on hyperphagia and body weight in Prader-Willi syndrome: A randomized, double-blind, placebo-controlled trial.

AIMS: There are no treatments for the extreme hyperphagia and obesity in Prader-Willi syndrome (PWS). The bestPWS clinical trial assessed the efficacy, safety and tolerability of the methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib. MATERIALS AND METHODS: Participants with PWS (12-65 years old) were randomly assigned (1:1:1) to biweekly placebo, 1.8 mg beloranib or 2.4 mg beloranib injection for 26 weeks at 15 US sites. Co-primary endpoints were the changes in hyperphagia [measured by Hyperphagia Questionnaire for Clinical Trials (HQ-CT); possible score 0-36] and weight by intention-to-treat. ClinicalTrials.gov registration: NCT02179151. RESULTS: One-hundred and seven participants were included in the intention-to-treat analysis: placebo (n = 34); 1.8 mg beloranib (n = 36); or 2.4 mg beloranib (n = 37). Improvement (reduction) in HQ-CT total score was greater in the 1.8 mg (mean difference -6.3, 95% CI -9.6 to -3.0; P = .0003) and 2.4 mg beloranib groups (-7.0, 95% CI -10.5 to -3.6; P = .0001) vs placebo. Compared with placebo, weight change was greater with 1.8 mg (mean difference - 8.2%, 95% CI -10.8 to -5.6; P < .0001) and 2.4 mg beloranib (-9.5%, 95% CI -12.1 to -6.8; P < .0001). Injection site bruising was the most frequent adverse event with beloranib. Dosing was stopped early due to an imbalance in venous thrombotic events in beloranib-treated participants (2 fatal events of pulmonary embolism and 2 events of deep vein thrombosis) compared with placebo. CONCLUSIONS: MetAP2 inhibition with beloranib produced statistically significant and clinically meaningful improvements in hyperphagia-related behaviours and weight loss in participants with PWS. Although investigation of beloranib has ceased, inhibition of MetAP2 is a novel mechanism for treating hyperphagia and obesity.

Dynamic response of C-type natriuretic peptide and its aminoterminal propeptide (NTproCNP) to growth hormone treatment in children with short stature.

OBJECTIVE: C-type natriuretic peptide (CNP) and its aminoterminal propeptide (NTproCNP) are potential biomarkers of recombinant human growth hormone (rhGH) efficacy. The objective of this study was to describe the pharmacodynamics of plasma CNP and NTproCNP levels in response to rhGH treatment and to identify the optimal time of sampling after starting rhGH. DESIGN: This was a prospective, observational study. Subjects were treated with rhGH for 1 year, with blood sampled at regular intervals. PATIENTS: Eighteen prepubertal children, eight with low levels of GH on biochemical testing and ten with idiopathic short stature, completed the study. MEASUREMENTS: Blood levels of CNP, NTproCNP, GH, insulin-like growth factor-I, leptin and bone-specific alkaline phosphatase were measured. Anthropometrics were obtained. RESULTS: Plasma levels of both CNP and NTproCNP reached peak levels 7-28 days after starting rhGH treatment and then declined to intermediate levels through the first year. Plasma NTproCNP levels after 14 days trended towards a correlation with height velocity after 6 and 12 months of treatment. Unexpectedly, serum GH levels measured 2 and 28 days after starting rhGH correlated strongly with height velocity after 6 and 12 months of treatment. CONCLUSIONS: This study identified 14 days after starting rhGH treatment as the optimal time for assessing CNP and NTproCNP levels as biomarkers of rhGH efficacy. Additionally, we identified GH levels as a potential biomarker. Larger, prospective studies are now needed to test the clinical utility of these biomarkers.

Obesity management in Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is one of the most common genetic causes of obesity. The phenotype of obesity in PWS is unique and characterized by hyperphagia, earlier meal initiation, delayed meal termination, reduced energy expenditure, abnormal gut hormone profiles, as well as irregular responses to food in areas of the brain associated with satiety and reward. Management of obesity is necessary to avoid major morbidity. The relentless food-seeking behavior associated with PWS such as stealing, hoarding food, eating inedibles, and lying about eating, can cause turmoil both inside and outside of the home. Management is challenging for both patients and caretakers, but at this time there are limited medical therapies available besides dietary restriction and behavior management. However, current research shows promise for discovery of additional treatment options for hyperphagia and obesity management in PWS.

Effect of low-level laser irradiation on the rate and short-term stability of rotational tooth movement in dogs.

INTRODUCTION: Low-level laser therapy (LLLT) has many biostimulative effects such as acceleration of mesiodistal orthodontic tooth movement. However, its effects on the extent and short-term stability of rotational tooth movement have not been researched. The purpose of this study was to investigate the effect of low-level laser irradiation during rotational tooth movement on the rate of movement and the amount of relapse in dogs. METHODS: In this interventional study, fixed orthodontic appliances were used to rotate both mandibular lateral incisors in 8 dogs. Sixteen teeth were divided into 2 groups: the experimental group with LLLT during orthodontic force application, and a control group with orthodontic couple force application only. In the first group, the gallium-aluminum-arsenide diode laser (810 nm, 200 mw, 10 seconds, 2 J/session, 32 J/cm(2)/point) was emitted on 2 points at the buccal side of the roots on days 0, 1, 2, 3, 4, 7, 14, 21, and 28 during 4 weeks of movement, and the amount of relapse was then observed for 3 months. The extent of rotational movement was measured on dental casts, and the statistical analysis was carried out with t tests. RESULTS: There was no significant difference between the LLLT group and the control group on the amount of rotational tooth movement (P = 0.66). The mean percentages of relapse after 1 week, 1 month, and 3 months were 33.02%, 53.44%, and 60.64% in the LLLT group and 54.22%, 68.74%, and 73.92% in the control group, respectively. This demonstrates significant differences between these groups at all studied times (P ≤0.05). This difference was greatest in the first week and then decreased until the end of the third month. The greatest percentage of relapse in both groups was registered in the first week after tooth movement. CONCLUSIONS: The total energy dose of the laser used in this study could not accelerate rotational tooth movement, but it did effectively reduce the relapse tendency in teeth rotated by orthodontic movements.

Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study.

OBJECTIVE: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS). METHODS: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety. RESULTS: DCCR administration resulted in significant improvements in HQ-CT (mean [SE] -9.9 [0.77], p < 0.0001) and greater improvements in those with more severe baseline hyperphagia (HQ-CT > 22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment-emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%). CONCLUSIONS: DCCR administration to people with PWS was well tolerated and associated with broad-ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families.

Evaluation of torsional strength and torque presentation of coated rectangular stainless steel archwires, an in vitro study.

OBJECTIVES: An in vitro experimental study was performed to evaluate the torsional strength and torque released by esthetic coated archwires. MATERIALS AND METHODS: A total of 52 coated (study group) and 52 stainless steel (control group) rectangular archwires from two manufacturers (brand I: Gestenco International AB, Gothenburg, Sweden and brand II: Ortho Technology, Lutz, FL, USA) in two sizes (0.019â€¯× 0.025 and 0.017â€¯× 0.0250-inch) were evaluated. The straight parts on both ends of each preformed archwire were cut in 30 mm segments. A specially designed experimental device was attached to the universal testing machine (Model Z020, Zwick Roell, Ulm, Germany) to measure torsional strength and to calculate the clinically significant torque interval. The groups were compared based on their brand, presence of coating and size using three-way analysis of variance (ANOVA) test at a significance level of 5%. RESULTS: The results revealed that coating of the wires of brand 1 resulted in a significant reduction of torsional strength in both wire sizes (P-value = 0.0001). For the wires of brand 2, coating of the 0.017â€¯× 0.025-in wire resulted in a significant reduction in torsional strength. However, for the 0.019â€¯× 0.025 in wire size, the presence of coating significantly increased the torsional strength (P-value = 0.0001). Coating did not affect the measured clinical torque interval of the analyzed wires when a torque between 5 and 20 Nmm was applied (P-value = 0.062). CONCLUSIONS: Mechanical behavior of coated archwires depends mainly on the thickness of their inner core alloy. Reduction in the diameter of the inner alloy resulted in reduced torsional strength. Despite lower mean torsional strength, in the settings of this study, coated and conventional wires demonstrated comparable torque angles if loaded in the typical range of activation.

Leuprolide Acetate for Puberty Suppression in Transgender and Gender Diverse Youth: A Comparison of Subcutaneous Eligard Versus Intramuscular Lupron.

PURPOSE: To compare the efficacy of intramuscular Lupron and subcutaneous Eligard, two formulations of leuprolide, for puberty suppression in transgender and gender diverse (TGD) youth. METHODS: A retrospective chart review of TGD youth receiving Lupron or Eligard 22.5 mg every 3 months was conducted to determine hormone levels obtained 1 hour after an injection (1hrPost) and patient-reported clinical puberty suppression. RESULTS: Forty eight patients were analyzed: 33% assigned female at birth of which 25% were premenarchal, mean age at first injection 13.7 years, and 50% received concurrent gender affirming hormones. Of these, 13% received Lupron, 52% Eligard, and 35% initially received Lupron then transitioned to Eligard due to drug shortages. There were 55 incidents of 1hrPost levels, 42 after Eligard and 13 after Lupron. Clinical puberty suppression occurred in all patients; however, biochemical suppression occurred in 90% of Eligard and 69% of Lupron (p = .06). DISCUSSION: Eligard and Lupron were both effective in suppressing clinical puberty progression in our population of TGD youth, of which 50% were receiving concurrent gender affirming hormones.

Low Pretreatment Bone Mineral Density in Gender Diverse Youth.

Gender diverse adolescents have low pretreatment bone mineral density (BMD), with variable changes in BMD after initiation of gender-affirming treatment. We aimed to assess factors associated with low BMD in gender diverse youth. Sixty-four patients were included in our analysis (73% assigned male at birth). Subtotal whole-body BMD Z-scores were low in 30% of patients, and total lumbar spine BMD Z-scores low in 14%. There was a positive association with body mass index, and no association with vitamin D level. Male sex assigned at birth was associated with lower pretreatment BMD, with lower average BMD Z-scores compared to previous studies.

Diazoxide Choline Extended-Release Tablet in People With Prader-Willi Syndrome: A Double-Blind, Placebo-Controlled Trial.

CONTEXT: Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region, characterized by hypotonia, neurocognitive problems, behavioral difficulties, endocrinopathies, and hyperphagia resulting in severe obesity if not controlled. OBJECTIVE: The primary end point was change from baseline in hyperphagia using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Other end points included Global Impression Scores, and changes in body composition, behaviors, and hormones. METHODS: In DESTINY PWS, a 13-week, randomized, double-blind, placebo-controlled, phase 3 trial, 127 participants with PWS aged 4 years and older with hyperphagia were randomly assigned 2:1 to diazoxide choline extended-release tablet (DCCR) or placebo. RESULTS: DCCR did not significantly improve hyperphagia (HQ-CT least-square mean (LSmean) [SE] -5.94 [0.879] vs -4.27 [1.145]; P = .198), but did so in participants with severe hyperphagia (LSmean [SE] -9.67 [1.429] vs -4.26 [1.896]; P = .012). Two of 3 secondary end points were improved (Clinical Global Impression of Improvement [CGI-I]; P = .029; fat mass; P = .023). In an analysis of results generated pre-COVID, the primary (HQ-CT; P = .037) and secondary end points were all improved (CGI-I; P = .015; Caregiver Global Impression of Change; P = .031; fat mass; P = .003). In general, DCCR was well tolerated with 83.3% in the DCCR group experiencing a treatment-emergent adverse event and 73.8% in the placebo group (not significant). CONCLUSION: DCCR did not significantly improve hyperphagia in the primary analysis but did in participants with severe baseline hyperphagia and in the pre-COVID analysis. DCCR treatment was associated with significant improvements in body composition and clinician-reported outcomes.

Persistent Müllerian duct syndrome: 8 new cases in Southern California and a review of the literature.

Persistent Müllerian Duct Syndrome (PMDS) is a 46,XY disorder of sex development (DSD) in which Müllerian structures are found in genotypic males with normally virilized external genitalia and unilateral or bilateral cryptorchidism. It is usually diagnosed incidentally during surgical repair of cryptorchidism or inguinal hernia. The majority of cases are due to a mutation of the anti-Müllerian hormone (AMH) gene or the AMH receptor, type II (AMH-RII) gene. Management of patients with PMDS requires a multidisciplinary approach. Long-term prognosis is good although fertility appears to be decreased and there may be a risk of malignancy due to cryptorchidism and retained Müllerian remnants. We describe 8 new cases of PMDS diagnosed in Southern California in the past 10 years and review the literature.

Use of nano-hydroxyapatite serum and different finishing/polishing techniques to reduce enamel staining of debonding after orthodontic treatment : A randomized clinical trial.

PURPOSE: The aim of this study was to assess the effect of nano-hydroxyapatite serum and different finishing, polishing techniques on color alterations of enamel caused by debonding procedures after comprehensive orthodontic treatment by use of a spectrophotometer. METHODS: This randomized clinical trial recruited 20 participants with previous non-extraction orthodontic treatment and acceptable hygiene to evaluate enamel staining after orthodontic debonding. The usage of a carbide bur alone, as the conventional method, and the combination use of carbide burs and Sof-Lex discs (3M™ ESPE, St. Paul, MN, USA) were compared to each other followed by 10 days application of nano-hydroxyapatite after debonding. Then the enamel staining was evaluated by a reflectance spectrophotometer in three periods: immediately, and 2 and 4 months after debonding. RESULTS: The comparison of the groups showed a significant interaction between Sof-Lex groups and the control side after the first interval of the study (p = 0.042). Application of nano-hydroxyapatite demonstrated no significant difference in color parameters between upper and lower arches of the participants at all intervals of this study (p > 0.05). The mean total color change (ΔE) in all groups and between all intervals had been clinically perceptible (ΔE > 3.3). CONCLUSIONS: The applied concentrations of nano-hydroxyapatite had no significant effect in reducing tooth color changes after debonding in orthodontic treatment. Sof-Lex discs can significantly reduce tooth color changes in a short time.

The effect of multiple enamel conditioning on enamel micro-hardness.

Background: White spot formation is one of the common side effects in orthodontic treatments and multiple enamel conditioning might happen even during on session of fixed orthodontic treatments. The aim of the present study was to evaluate the impact of multiple enamel conditioning with different methods on enamel micro-hardness (MH). Materials and Methods: In this In vitro experimental study, the buccal surfaces of 105 extracted premolars were evaluated in seven groups: One control and six experimental groups. The enamel conditioning was performed in three ways: Etching with phosphoric acid 37%, etching with phosphoric acid 37% followed by primer application and conditioning with self-etch primer. The conditioning process in each way was also performed twice consecutively. The specimens were submitted in pH cycling model with demineralization and re-mineralization solutions for 14 days. Afterward Vickers MH test was applied with 0.981N force on the teeth for 10 s indentation time. Data were analyzed using One-Way ANOVA and Tukey HSD (honestly significant difference) test for multiple comparisons. A value of P < 0.05 was considered statistically significant. Results: MH analysis showed statistically significant differences between the control group and the other conditioned groups (P < 0.05). The groups conditioned with acid-etch and primer, particularly twice, showed the lowest amount of MH in comparison to other groups. Self-etch primer had the least effect on MH of the enamel. Single time etching without using primer, made no considerable difference when compared to multiple etching. Conclusion: Etching process and covering the enamel with primer decrease enamel MH. Using self-etch primer is a more conservative method of enamel conditioning.

Sotos syndrome with a novel mutation in the NSD1 gene associated with congenital hypothyroidism.

Childhood overgrowth syndromes are relatively rare. A generalized overgrowth syndrome should be suspected when tall stature and macrocephaly are present, after ruling out nutritional excess and endocrinopathies. Sotos syndrome is a well-described overgrowth syndrome due to haploinsufficiency of the NSD1 gene. We present a case of an infant with permanent congenital hypothyroidism, who had tall stature and macrocephaly by 7 months of age. He was noted to have typical facial features, mild gross motor and speech delay, and scoliosis by 13 months of age. Gene sequencing revealed a heterozygous novel c6076_6087del12: p.Asn2026_Thr2029del variant in exon 20 of the NSD1 gene, pathogenic for Sotos syndrome. Congenital hypothyroidism with Sotos syndrome has been infrequently reported and may expand the spectrum of disease characteristics. Early diagnosis of overgrowth syndromes is important for developmental follow up and multidisciplinary care coordination.

Gender Diverse Youth on Fertility and Future Family: A Qualitative Analysis.

PURPOSE: Gender-affirming treatment for transgender and nonbinary adolescents has been shown to decrease anxiety, depression, and suicidality, but treatments have medical consequences. Specifically, hormone replacement and pubertal blocking may impact patients' fertility and childbearing capabilities. We interviewed gender diverse adolescents regarding their thoughts on family and fertility. METHODS: We completed semistructured interviews with 23 gender diverse adolescents recruited from the Seattle Children's Gender Clinic. Interviewees included transfeminine, transmasculine, and nonbinary youth. Interviews were recorded, transcribed, and analyzed using Braun and Clarke's theory of thematic analysis, a flexible framework for qualitative analysis. RESULTS: Gender diverse adolescents have myriad views on fertility, but four main themes were identified: (1) an interest in future family, including ideas regarding adoption and biological children; (2) barriers to fertility, including cost and procedure-related dysphoria; (3) factors unique to the developmental stage of adolescents, including the age discordance of making fertility decisions as a teenager and parental influence on decision-making; and (4) suggestions for clinicians approaching fertility counseling with adolescents considering hormone therapy. CONCLUSIONS: Many gender diverse youth asserted an interest in building families, although the process of fertility preservation remains fraught. Relative to other studies, our participants were hopeful, imaginative, and interested in having children. Participants wanted to receive specific counseling on fertility, to receive help navigating the logistics of fertility preservation, and to be listened to when their hopes for children (or no children) were stated. Further research is needed to create care paradigms that address fertility of transgender youth in an affirming, developmentally appropriate manner.

Behavioral features in Prader-Willi syndrome (PWS): consensus paper from the International PWS Clinical Trial Consortium.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder associated with a characteristic behavioral phenotype that includes severe hyperphagia and a variety of other behavioral challenges such as temper outbursts and anxiety. These behaviors have a significant and dramatic impact on the daily functioning and quality of life for the person with PWS and their families. To date, effective therapies addressing these behavioral challenges have proven elusive, but several potential treatments are on the horizon. However, a limiting factor for treatment studies in PWS is the lack of consensus in the field regarding how to best define and measure the complex and interrelated behavioral features of this syndrome. The International PWS Clinical Trials Consortium (PWS-CTC, www.pwsctc.org ) includes expert PWS scientists, clinicians, and patient advocacy organization representatives focused on facilitating clinical trials in this rare disease. To address the above gap in the field, members of the PWS-CTC "Behavior Outcomes Working Group" sought to develop a unified understanding of the key behavioral features in PWS and build a consensus regarding their definition and description. The primary focus of this paper is to present consensus definitions and descriptions of key phenotypic PWS behaviors including hyperphagia, temper outbursts, anxiety, obsessive-compulsive behaviors, rigidity, and social cognition deficits. Patient vignettes are provided to illustrate the interrelatedness and impact of these behaviors. We also review some available assessment tools as well as new instruments in development which may be useful in measuring these behavioral features in PWS.