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Recruitment of seminarians is studied, using a "funnel model" to explore those predisposing conditions which contribute to the formation of a young man as a potential priest. Changing societal conditions are discussed in the context of the decline in choice of the Catholic priesthood as a career by contemporary youth. Implications for the "vocational critic are suggested in light of the data from a sample of Canadian high school students. [ABSTRACT FROM AUTHOR]

Background and Aims: Poor sleep is prevalent in inflammatory bowel disease [IBD] and is associated with increased symptom severity and decreased quality of life. To date, research is mostly cross-sectional, limiting the ability to examine the causal direction between sleep and IBD symptoms. This short report aims to assess the temporal associations among sleep quality, pain, fatigue, and physical activity in adults with IBD., Methods: Adult IBD patients [N = 18] completed a structured electronic diary two times per day [morning and evening] over 14 consecutive days. Morning diary items assessed sleep [sleep quality, wake after sleep onset, number of awakenings] and evening diary items assessed daytime IBD symptoms [abdominal pain, fatigue]. An actigraph measured daily step count [physical activity]. Generalised estimating equation models evaluated the lagged temporal associations between sleep ratings and next day pain, fatigue, and physical activity as well as reverse lagged temporal associations between daytime symptoms and physical activity and subsequent sleep ratings., Results: Poor self-reported sleep quality predicted increased next day abdominal pain and fatigue scores. Increased time awake during the night predicted decreased next day physical activity. In the reverse analyses, only the relationship between daytime abdominal pain and wake after sleep onset was significant., Conclusions: Poor sleep appears to drive IBD-related outcomes, such as pain and fatigue. These findings are a first step in demonstrating the key role of sleep in the IBD patient experience, potentially resulting in a treatment target for intervention. Future research is needed to confirm results in a larger sample., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Opioid-induced constipation (OIC) is a common condition in older adults who may not be responsive to traditional laxative therapy. OIC is defined as new or worsening constipation symptoms that occur with initiation of or altering the dose of opioid analgesia. For adult patients with OIC and noncancer pain, we recommend considering nonpharmacologic interventions (eg, dietary measures, increased physical activity, and biofeedback training) and over-the-counter laxatives, followed by prescription opioid receptor antagonists (methylnaltrexone, naloxegol, and naldemedine) if traditional over-the-counter laxatives fail. Other options may include lubiprostone, linaclotide, plecanatide, and prucalopride; however, these are not indicated for OIC specifically or studied in older adults. Because of the complex nature of absorption, distribution, metabolism, and excretion in the aging population, all agents used to treat OIC must be evaluated individually and reevaluated as patients continue to age. This review will serve as a guide to managing OIC in older adults., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Patients with inflammatory bowel disease (IBD) are at higher risk of venous thromboembolism (VTE), though physicians may be unaware of this risk or hesitant to start pharmacologic VTE prophylaxis in the presence of active gastrointestinal bleeding. We report a case of a 38-year-old patient hospitalized with acute severe ulcerative colitis (UC) who was not placed on pharmacologic VTE prophylaxis and developed bilateral pulmonary embolism (PE). The patient's UC did not respond to medical therapy. Due to his PE, the patient's total proctocolectomy was delayed six months. He also developed a large pelvic hematoma after colectomy requiring further surgical intervention. Hospitalized inflammatory bowel disease (IBD) patients require pharmacologic VTE prophylaxis unless they have life-threatening bleeding., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Medgyesy et al.)

Objective: The International Society of CNS Clinical Trials Methodology (ISCTM) Working Group on Rare Disease/Orphan Drug Development is dedicated to improving and streamlining trials to best develop new treatments for rare diseases. The rarity of these disorders requires a drug development strategy that differs from those of nonrare conditions. Rare disease drug development programs are challenged with small sample sizes, heterogeneous clinical presentations, and few, if any, off-the-shelf endpoints. When disease-specific clinical endpoints exist, they might not be validated and are typically not well known or broadly used in clinical practice. This paper aims to provide an overview of the special issues surrounding endpoints in rare disease drug development, with guidance, practical applications, and discussion., Discussion: The paper covers regulatory considerations in endpoint selection; identification of relevant measurement domains; methods of quantifying clinical meaningfulness; incorporation of patient- and clinician-reported outcomes; considerations for global clinician- and patient-rated clinical assessments; cognition assessment challenges in rare diseases; translation considerations; training, standardization, and calibration of assessors; and endpoint quality assurance. Additionally, it provides guidance and resources for those involved in drug development for rare diseases., Conclusion: In keeping with the mission of ISCTM and the rare disease/orphan drug development working group, this article is designed to encourage thoughtful consideration and provide insight and guidance to promote and further efforts in in central nervous system (CNS) rare disease drug development efforts., Competing Interests: DISCLOSURES: Dr. Busner is a full-time employee of Signant Health and may hold stock and/or stock options. Dr. Pandina is a full-time employee of Janssen Research & Development, LLC and a stockholder of Johnson & Johnson. Dr. Fisseha is an employee of AbbVie and may hold stock and/or stock options. Dr. Horrigan is an employee of AMO Pharma Ltd. Dr. Jacobson is an employee of Harmony Biosciences., (Copyright © 2021. Matrix Medical Communications. All rights reserved.)

Background: GSK3β is an intracellular regulatory kinase that is dysregulated in multiple tissues in type 1 myotonic dystrophy, a rare neuromuscular disorder that manifests at any age. AMO-02 (tideglusib) inhibits GSK3β activity in preclinical models of type 1 myotonic dystrophy and promotes cellular maturation as well as normalizes aberrant molecular and behavioral phenotypes. This phase 2 study assessed the pharmacokinetics, safety and tolerability, and preliminary efficacy of AMO-02 in adolescents and adults with congenital and childhood-onset type 1 myotonic dystrophy., Methods: Sixteen subjects (aged 13 to 34 years) with congenital and childhood-onset type 1 myotonic dystrophy received 12 weeks of single-blind fixed-dose oral treatment with either 400 mg (n = 8) or 1000 mg (n = 8) AMO-02 (NCT02858908). Blood samples were obtained for pharmacokinetic assessment. Safety assessments, such as laboratory tests and electrocardiograms, as well as efficacy assessments of syndromal, cognitive, and muscular functioning, were obtained., Results: AMO-02 plasma concentrations conformed to a two-compartment model with first-order absorption and elimination, and dose-dependent increases in exposure (area under the curve) were observed. AMO-02 was generally safe and well-tolerated. No early discontinuations due to adverse events or dose adjustments of AMO-02 occurred. The majority of subjects manifested clinical improvement in their central nervous system and neuromuscular symptoms after 12 weeks of treatment compared with the placebo baseline, with a larger response noted at the 1000 mg/day dose level. AMO-02 exposure (cumulative area under the curve) was significantly correlated (P < 0.01) with change from baseline on several key efficacy assessments., Conclusion: AMO-02 has favorable pharmacokinetic and clinical risk/benefit profiles meriting further study as a potential treatment for congenital and childhood-onset type 1 myotonic dystrophy., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: E-learning is a common method of continuing education for nurses that supports professional competencies and learning needs. However, variations in setting, information technology, and quality of the e-learning may impact these experiences., Objective: To explore registered nurses' perceptions of e-learning in a hospital setting., Design: A qualitative study using an Interpretive Description methodology., Setting: A small urban Northeastern Ontario hospital., Participants: Ten registered nursing staff from acute medical and surgical inpatient departments., Method: Face-to-face semi-structured interviews were conducted to explore nurses' e-learning perceptions. Interview transcripts were analyzed for themes., Results: Three key themes were found that described the participants' perceptions of e-learning and how it related to their continuing education: Unsatisfactory, Meaningful, and Enhancing learning experiences., Conclusion: E-learning can be a useful method of continuing education for registered nurses; however, there are challenges in the delivery of e-learning and an ongoing need for quality development., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To evaluate whether umbilical cord blood (CB) infusion is safe and associated with improved social and communication abilities in children with autism spectrum disorder (ASD)., Study Design: This prospective, randomized, placebo-controlled, double-blind study included 180 children with ASD, aged 2-7 years, who received a single intravenous autologous (n = 56) or allogeneic (n = 63) CB infusion vs placebo (n = 61) and were evaluated at 6 months postinfusion., Results: CB infusion was safe and well tolerated. Analysis of the entire sample showed no evidence that CB was associated with improvements in the primary outcome, social communication (Vineland Adaptive Behavior Scales-3 [VABS-3] Socialization Domain), or the secondary outcomes, autism symptoms (Pervasive Developmental Disorder Behavior Inventory) and vocabulary (Expressive One-Word Picture Vocabulary Test). There was also no overall evidence of differential effects by type of CB infused. In a subanalysis of children without intellectual disability (ID), allogeneic, but not autologous, CB was associated with improvement in a larger percentage of children on the clinician-rated Clinical Global Impression-Improvement scale, but the OR for improvement was not significant. Children without ID treated with CB showed significant improvements in communication skills (VABS-3 Communication Domain), and exploratory measures including attention to toys and sustained attention (eye-tracking) and increased alpha and beta electroencephalographic power., Conclusions: Overall, a single infusion of CB was not associated with improved socialization skills or reduced autism symptoms. More research is warranted to determine whether CB infusion is an effective treatment for some children with ASD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

NNZ-2566 is a novel, small molecule being developed as a treatment for cognitive impairment in different CNS conditions, including Rett and Fragile-X syndrome, both of which are associated with moderate to severe neurodevelopmental disorder. In the current study we characterise the population pharmacokinetics of NNZ-2566 after administration of single and repeated ascending doses to healthy subjects. A meta-analytical approach was used to analyse pharmacokinetic data from 3 different studies, in which a total of 61 healthy subjects (median age: 23years, range: 19 to 38) were treated with NNZ-2566. Doses of NNZ-2566 ranged from 6.0 to 100mg/kg after oral administration and from 0.1 to 30mg/kg after intravenous administration. A two-compartment model with first order absorption and elimination was found to best describe the pharmacokinetics of NNZ-2566. Inter-individual variability was identified in clearance, absorption rate, central volume of distribution, peripheral volume of distribution and inter-compartmental clearance. Population predicted clearance and central volume of distribution were 10.35L/h and 20.23L, respectively. Dose proportionality was observed across the dose range evaluated in healthy subjects. No accumulation, metabolic inhibition or induction was observed during the course of treatment. In addition, oral bioavailability appeared to vary with food intake. The relatively short half-life of 1.4h suggests the need for a twice or three times daily regimen to maintain relevant blood levels of NNZ-2566., (Copyright © 2017. Published by Elsevier B.V.)

Background: This study aimed to determine the safety and tolerability of trofinetide and to evaluate efficacy measures in adolescent and adult females with Rett syndrome, a serious and debilitating neurodevelopmental condition for which no therapies are available for its core features., Methods: This was an exploratory, phase 2, multicenter, double-blind, placebo-controlled, dose-escalation study of the safety and tolerability of trofinetide in 56 adolescent and adult females with Rett syndrome. Subjects were randomly assigned in a 2:1 ratio to 35 mg/kg twice daily of trofinetide or placebo for 14 days; 35 mg/kg twice daily or placebo for 28 days; or 70 mg/kg twice daily or placebo for 28 days. Safety assessments included adverse events, clinical laboratory tests, vital signs, electrocardiograms, physical examinations, and concomitant medications. Efficacy measurements were categorized into four efficacy domains, which related to clinically relevant, phenotypic dimensions of impairment associated with Rett syndrome., Results: Both 35 mg/kg and 70 mg/kg dose levels of trofinetide were well tolerated and generally safe. Trofinetide at 70 mg/kg demonstrated efficacy compared with placebo based on prespecified criteria., Conclusion: Trofinetide was well tolerated in adolescent and adult females with Rett syndrome. Although this study had a relatively short duration in a small number of subjects with an advanced stage of disease, consistent efficacy trends at the higher dose were observed in several outcome measures that assess important dimensions of Rett syndrome. These results represented clinically meaningful improvement from the perspective of the clinicians as well as the caregivers., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rett syndrome (RTT) requires total caregiver attention and leads to potential difficulties throughout life. The Caregiver Burden Inventory, designed for Alzheimer disease, was modified to a RTT Caregiver Inventory Assessment (RTT CIA). Reliability and face, construct, and concurrent validity were assessed in caregivers of individuals with RTT. Chi square or Fisher's exact test for categorical variables and t tests or Wilcoxon two-sample tests for continuous variables were utilized. Survey completed by 198 caregivers; 70 caregivers completed follow-up assessment. Exploratory factor analysis revealed good agreement for physical burden, emotional burden, and social burden. Internal reliability was high (Cronbach's alpha 0.898). RTT CIA represents a reliable and valid measure, providing a needed metric of caregiver burden in this disorder.

Objective: This study aimed to compare the efficacy of lamotrigine versus placebo in 10- to 17-year-olds with bipolar I disorder (BP-I) who were receiving conventional bipolar disorder treatment., Method: In this randomized withdrawal trial, patients with BP-I of at least moderate severity received lamotrigine during an ≤18-week open-label phase. Patients who maintained a stable lamotrigine dose for ≥2 weeks and Clinical Global Impression-Bipolar Severity of Illness (CGI-BP[S]) score of ≤3 for ≥6 consecutive weeks were randomized to double-blind lamotrigine or placebo for ≤36 weeks., Results: Of 301 patients enrolled, 298 comprised the open-label intention-to-treat population, with 173 (58%) randomized. Of these patients, 41 (24%) completed the study. In the open-label phase, the mean (SD) baseline CGI-BP(S) rating was 4.4 (0.57), and the mean (standard error [SE]) time to stabilization was 101 (1.6) days. During the randomized phase, mean (SE) time to occurrence of a bipolar event (TOBE) for lamotrigine versus placebo (primary endpoint) was 155 (14.7) versus 50 (3.8), 163 (12.2) versus 120 (12.2), and 136 (15.4) versus 107 (13.8) days for the 3 index mood states (depressed, manic/hypomanic, mixed). The primary stratified log-rank analysis of TOBE was not statistically significant (hazard ratio [HR] = 0.63; p = .072); however, the prespecified Cox regression analysis favored lamotrigine (p = .047). In 13- to 17-year-olds, log-rank analysis of TOBE significantly favored lamotrigine (HR = 0.46; p = .015), but not in 10- to 12-year-olds (HR = 0.93; p = .877). Dermatologic events were reported in 4% (open-label phase) and 2% (randomized phase) of patients receiving lamotrigine. Suicidality-related adverse events were reported in 7% (open-label phase) and 7% (randomized phase) of patients receiving lamotrigine., Conclusion: Although the primary analysis failed to detect a benefit of add-on lamotrigine for BP-I in 10- to 17-year-olds, lamotrigine may be effective in a subset of older adolescents. Clinical trial registration information-Lamictal as Add-on Treatment for Bipolar I Disorder in Pediatric Patients; http://clinicaltrials.gov/; NCT00723450., (Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Rett syndrome is a genetically based neurodevelopmental disorder. Although the clinical consequences of Rett syndrome are profound and lifelong, currently no approved drug treatments are available specifically targeted to Rett symptoms. High quality outcome measures, specific to the core symptoms of a disorder are a critical component of well-designed clinical trials for individuals with neurodevelopmental disorders. The Clinical Global Impression Scale is a measure of global clinical change with strong face validity that has been widely used as an outcome measure in clinical trials of central nervous system disorders. Despite its favorable assay sensitivity in clinical trials, as a global measure, the Clinical Global Impression Scale is not specific to the signs and symptoms of the disorder under study. Development of key anchors for the scale, specific to the disorder being assessed, holds promise for enhancing the validity and reliability of the measure for disorders such as Rett syndrome., (© The Author(s) 2015.)