Aims There are no treatments for the extreme hyperphagia and obesity in Prader-Willi syndrome (PWS). The bestPWS trial assessed the efficacy, safety, and tolerability of the methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib. Materials and Methods Participants with PWS (12–65 years) 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. Coprimary 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 107 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=0.0003) and 2.4 mg beloranib groups (−7.0, 95% CI −10.5 to −3.6; p=0.0001) vs placebo. Compared to placebo, weight change was greater with 1.8 mg (mean difference −8.2%, 95% CI −10.8 to −5.6; p<0.0001) and 2.4 mg beloranib (−9.5%, 95% CI −12.1 to −6.8; p<0.0001). 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 (two fatal events of pulmonary embolism and two events of deep vein thrombosis) compared to placebo. Conclusions MetAP2 inhibition with beloranib produced statistically significant and clinically meaningful improvements in hyperphagia-related behaviors 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.

BackgroundThe aim of this prospective clinical study was to compare the mean durability and the failure rates of two types of orthodontic retainers.MethodsOrthodontic patients (142) aged between 14 and 28 years were recruited in this study. The polyethylene woven ribbon (Ribbond, Seattle, WA, USA) retainer was compared with a 0.0175-in flexible spiral wire (Respond, Ormco, Glendora, CA, USA) retainer. When treatment was completed, the retainers were bonded from canine to canine in the maxillary and the mandibular arches of the participants. In the follow-up visits, the patients were re-evaluated every 3 months over a period of 18 months. The time taken for the retainers to remain without any fracture was appraised. Kaplan-Meier analysis and the logrank test were employed to identify significant differences in the survival functions between the groups. The rates of the retainers' failure between the groups were analyzed using Chi-square test.ResultsIt was revealed that the mean survival of the flexible spiral wire retainer was 15.34 ± 0.47 and 15.60 ± 0.42 months in the maxillary and mandibular arches, respectively. The mean survival of the ribbon retainer was 13.95 ± 0.55 and 14.26 ± 0.57 months in the maxillary and mandibular arches, respectively. Ribbon retainers showed a failure rate of 50% in the maxillary and 42.6% in the mandibular arches. Flexible spiral retainers showed a failure rate of 36.5% in the maxillary and 37.8% in the mandibular arches. The differences were not statistically significant. Regarding the evaluation period, the differences had limited clinical significance.ConclusionThe mean survival time and the failure rates of the polyethylene woven ribbon retainer were comparable to the flexible spiral wire retainer during the 18 months after orthodontic treatment.

Objective: The present study aimed to evaluate the effect of MOP over a 3-month period and to determine the influence of the number of perforations on the rate of canine retraction. In addition, the amount of pain and discomfort caused by the MOP method was evaluated. Trial design: A single-center, split-mouth, triple-blind, randomized, controlled trial was conducted. Methods: The clinical trial was conducted from December 2018 to July 2019 in the Orthodontic Clinic, Shiraz Dental School. Twenty-eight patients (range from16.3 to 35.2 years) who need fixed orthodontic treatment were recruited and randomly assigned to MOP1 and MOP2 groups. In each patient one side of the mouth worked as a control side which received no MOPs. Four months after first premolars extraction, patients in MOP1 group received 3 MOPs on the buccal surface of alveolar bone in the experimental side to accelerate canine retraction whereas patients in MOP2 group received 3 buccal MOPs and 3 palatal MOPs in the experimental side. The amount of canine retraction was measured every 28 days at three intervals on both sides of the mouth. Pain perception was also measured on the day of MOP procedure and subsequently at 24 h. Randomization was performed using online software RANDOM.ORG; the recruited patients were divided into two parallel groups with a 1:1 allocation ratio then the side of MOPs intervention in each subject was randomly determined with coin tossing. Triple blinding design was employed. Results: The result of the intra-examiner reliability using ICC was 0.97 (P < 0.001), indicating excellent repeatability and reliability of the measurements. The baseline characteristics between the groups were similar (P > 0.05). There was a significant difference in the rate of canine retraction between the MOP groups and the contralateral control sides, as well as between the MOP1 and MOP2 groups (P < 0.05). Conclusion: The MOP procedure was effective in accelerating orthodontic tooth movement, although the amount of acceleration was not clinically significant in the case of canine retraction. An increase in the number of MOPs resulted in a significant acceleration of the canine retraction. Trial registration: The trial was registered 30 November 2018 at the Iranian Registry of Clinical Trials (IRCT20181121 041713N1).

Background Prader–Willi syndrome (PWS) is a complex neuroendocrine disorder affecting approximately 1/15,000–1/30,000 people. Unmet medical needs of individuals with PWS make it a rare disease that models the importance of multidisciplinary approaches to care with collaboration between academic centers, medical homes, industry, and parent organizations. Multidisciplinary clinics support comprehensive, patient‐centered care for individuals with complex genetic disorders and their families. Value comes from improved communication and focuses on quality family‐centered care. Methods Interviews with medical professionals, scientists, managed care experts, parents, and individuals with PWS were conducted from July 1 to December 1, 2016. Review of the literature was used to provide support. Results Data are presented based on consensus from these interviews by specialty focusing on unique aspects of care, research, and management. We have also defined the Center of Excellence beyond the multidisciplinary clinic. Conclusion Establishment of clinics motivates collaboration to provide evidence‐based new standards of care, increases the knowledge base including through randomized controlled trials, and offers an additional resource for the community. They have a role in global telemedicine, including to rural areas with few resources, and create opportunities for clinical work to inform basic and translational research. As a care team, we are currently charged with understanding the molecular basis of PWS beyond the known genetic cause; developing appropriate clinical outcome measures and biomarkers; bringing new therapies to change the natural history of disease; improving daily patient struggles, access to care, and caregiver burden; and decreasing healthcare load. Based on experience to date with a PWS multidisciplinary clinic, we propose a design for this approach and emphasize the development of “Centers of Excellence.” We highlight the dearth of evidence for management approaches creating huge gaps in care practices as a means to illustrate the importance of the collaborative environment and translational approaches.