Growth hormone deficiency, aortic dilation, and neurocognitive issues in Feingold syndrome 2.

We report three patients with Feingold 2 syndrome with the novel features of growth hormone deficiency associated with adenohypophyseal compression, aortic dilation, phalangeal joint contractures, memory, and sleep problems in addition to the typical features of microcephaly, brachymesophalangy, toe syndactyly, short stature, and cardiac anomalies. Microdeletions of chromosome 13q that include the MIR17HG gene were found in all three. One of the patients was treated successfully with growth hormone. In addition to expanding the phenotype of Feingold 2 syndrome, we suggest management of patients with Feingold 2 syndrome include echocardiography at the time of diagnosis in all patients and consideration of evaluation for growth hormone deficiency in patients with short stature.

Genotype-phenotype correlation of congenital anomalies in multiple congenital anomalies hypotonia seizures syndrome (MCAHS1)/PIGN-related epilepsy.

Mutations in PIGN, resulting in multiple congenital anomalies-hypotonia-seizures syndrome, a glycosylphosphatidylinositol anchor deficiency, have been published in four families to date. We report four patients from three unrelated families with epilepsy and hypotonia in whom whole exome sequencing yielded compound heterozygous variants in PIGN. As with previous reports Patients 1 and 2 (full siblings) have severe global developmental delay, gastroesophageal reflux disease, and minor dysmorphic features, including high palate, bitemporal narrowing, depressed nasal bridge, and micrognathia; Patient 3 had early global developmental delay with later progressive spastic quadriparesis, intellectual disability, and intractable generalized epilepsy; Patient 4 had bilateral narrowing as well but differed by the presence of hypertelorism, markedly narrow palpebral fissures, and long philtrum, had small distal phalanges of fingers 2, 3, and 4, absent distal phalanx of finger 5 and similar toe anomalies, underdeveloped nails, unusual brain anomalies, and a more severe early clinical course. These patients expand the known clinical spectrum of the disease. The severity of the presentations in conjunction with the patients' mutations suggest a genotype-phenotype correlation in which congenital anomalies are only seen in patients with biallelic loss-of-function. In addition, PIGN mutations appear to be panethnic and may be an underappreciated cause of epilepsy.

The effects of aftercare/resettlement services on crime and violence in children and youth: A systematic review.

Background: High rates of youth re-offending indicate that young custody-leavers face challenges when reintegrating into their communities. Aftercare and resettlement programs can occur pre-, during, and post-release and generally provide multiple forms of support services to address youths' transitional needs. Objectives: The present review examines (1) the impact of youth aftercare/resettlement programs on crime-related outcomes, (2) how treatment effect is moderated by participant, program, and study characteristics, (3) whether some types of interventions are more effective than others, (4) barriers/facilitators to effective program implementation, (5) the theory of change underlying resettlement interventions, and (6) available research on intervention cost. Search Methods: A comprehensive set of keywords and synonyms was combined in a Boolean search across 26 electronic databases. Multiple gray literature sources were also searched, including 23 journals, 4 meeting archives, 11 organization websites, 3 open access journal websites, and the CVs of 8 well-known researchers in the field. The search was completed in January 2023. Selection Criteria: For objectives 1-3, studies were included if they utilized a randomized controlled design or quasi-experimental comparison group design in which participants were matched on at least some baseline variables and included at least one quantitative individual-measure of crime. For objective 4, included studies presented process evaluations of aftercare/reentry programs, clearly stated their research goals, and used qualitative methods in an appropriate way to answer the stated research question. For objectives 5 and 6, no specific methods were required; any study meeting the criteria for objectives 1-4 which presented findings on theory of change or cost data were included. For all outcomes, only studies conducted in a westernized country, and published after 1991 in English, French, or German were considered. Data Collection and Analysis: Two coders conducted primary data extraction for the included studies. Data were entered into a Microsoft Excel database. After data extraction, the two coders validated the coding by cross-checking the database with each research report. Discrepancies between coders were discussed until consensus was reached. Where consensus could not be reached, a third coder was consulted. Study risk of bias was addressed using the ROBINS-I (Sterne et al., 2016), ROB-2 (Higgins et al., 2019), and the critical appraisal skills programme (CASP, 2018). Objectives 1-3 were addressed by synthesizing quantitative outcomes from rigorous impact evaluations of aftercare interventions using random effects models and meta-regression. Thematic and narrative analysis was conducted to address objectives 4-6. Results: The search resulted in 15 impact studies, representing 4,718 participants across 21 program sites, and 35 effect sizes. The 21 impact evaluations were rated as having either low/moderate bias (k = 11) or serious bias (k = 10). The synthesis of 15 impact studies found no significant effects for arrest (k = 14; OR = 1.044, 95% prediction interval [0.527, 2.075], t = 0.335) or incarceration (k = 8, OR = 0.806, 95% prediction interval [2.203, 1.433], t = -1.674). A significant pooled effect was found for conviction (k = 13, OR = 1.209, 95% prediction interval [1.000, 1.462], t = 2.256), but results were highly sensitive to the inclusion of specific studies. No meaningful pattern of results emerged in moderator analyses with respect to study, sample, program component, or program delivery characteristics. The 19 process studies were rated as either high quality (k = 12) or moderate quality (k = 7). Thematic synthesis of the process evaluations revealed 15 themes related to the strengths/challenges of program implementation. The assessment of program cost (k = 7) determined a lack of data within the literature, preventing any summative analysis. Authors' Conclusions: Current evidence is promising with respect to conviction outcomes but overall does not find that aftercare/resettlement interventions have a reliably positive impact on crime-related outcomes for young people who have offended. High variability across outcomes and reported data resulted in small sample sizes per outcome and limited moderator analyses. Multiple challenges for program implementation exist; additional rigorous research is sorely needed to further investigate the nuances of the program effects.

PROTOCOL: The effects of resettlement/re-entry services on crime and violence in children and youth: A systematic review.

This is the protocol for a Campbell systematic review. The goal of the study is to examine the impacts of aftercare/resettlement interventions on youth with respect to criminogenic outcomes, and to examine factors related to intervention success. Specific objectives are as follows: (1) What is the impact of aftercare/resettlement interventions on youth with respect to outcomes of crime and violence? (2) How is the treatment effect of aftercare/resettlement interventions on crime and violence outcomes moderated by factors such as participant (e.g., age, race, ethnicity, sex, offender type), treatment (e.g., intensity and quality of implementation), methodological (e.g., measurement of crime, study design, timing of follow-up measures), and study characteristics (e.g., date of publication, peer-reviewed status)? (3) Are some types of aftercare/resettlement interventions more effective than others? (4) What are the barriers and facilitators to effective implementation of aftercare/resettlement interventions? (5) What are the mechanisms (theory of change) underlying aftercare/resettlement interventions? (6) What does the available research suggest regarding the cost of aftercare/resettlement interventions?

Not just a carrier: Clinical presentation and management of patients with heterozygous disease-causing alkaline phosphatase (ALPL) variants identified through expanded carrier screening.

Hypophosphatasia (HPP) is an underrecognized, complex bone mineralization disorder with variable manifestations caused by one or two deleterious variants in the alkaline phosphatase (ALPL) gene. Expanded carrier screening (ECS), inclusive of ALPL, intends to inform reproductive risk but may incidentally reveal an HPP diagnosis with 50% familial risks. We sought to investigate at-risk individuals and develop a multidisciplinary referral and evaluation protocol for ECS-identified ALPL heterozygosity. A retrospective database query of ECS results from 8 years to 1 month for heterozygous pathogenic/likely pathogenic ALPL variants was completed. We implemented a clinical protocol for diagnostic testing and imaging, counseling, and interdisciplinary care management for identified patients, and outcomes were documented. Heterozygous ALPL variants were identified in 12/2248 unrelated patients undergoing ECS (0.53%; heterozygote frequency 1/187). Of 10 individuals successfully contacted, all demonstrated symptomatology and/or alkaline phosphatase values consistent with HPP. ECS may reveal incidental health risks, including recognition of missed HPP diagnoses in ALPL heterozygotes. In our cohort, all ECS-identified ALPL heterozygotes with clinical and/or biochemical data available demonstrated features of HPP. Referral to a genetics professional familiar with HPP is indicated for family history assessment, genetic counseling, cascade testing, and long-term bone health management.

Acute Myocardial Infarction Cohorts Defined by International Classification of Diseases, Tenth Revision Versus Diagnosis-Related Groups: Analysis of Diagnostic Agreement and Quality Measures in an Integrated Health System.

BACKGROUND: Among Medicare value-based payment programs for acute myocardial infarction (AMI), the Hospital Readmissions Reduction Program uses International Classification of Diseases, Tenth Revision (ICD-10) codes to identify the program denominator, while the Bundled Payments for Care Improvement Advanced program uses diagnosis-related groups (DRGs). The extent to which these programs target similar patients, whether they target the intended population (type 1 myocardial infarction), and whether outcomes are comparable between cohorts is not known. METHODS: In a retrospective study of 2176 patients hospitalized in an integrated health system, a cohort of patients assigned a principal ICD-10 diagnosis of AMI and a cohort of patients assigned an AMI DRG were compared according to patient-level agreement and outcomes such as mortality and readmission. RESULTS: One thousand nine hundred thirty-five patients were included in the ICD-10 cohort compared with 662 patients in the DRG cohort. Only 421 patients were included in both AMI cohorts (19.3% agreement). DRG cohort patients were older (70 versus 65 years, P<0.001), more often female (48% versus 30%, P<0.001), and had higher rates of heart failure (52% versus 33%, P<0.001) and kidney disease (42% versus 25%, P<0.001). Comparing outcomes, the DRG cohort had significantly higher unadjusted rates of 30-day mortality (6.6% versus 2.5%, P<0.001), 1-year mortality (21% versus 8%, P<0.001), and 90-day readmission (26% versus 19%, P=0.006) than the ICD-10 cohort. Two observations help explain these differences: 61% of ICD-10 cohort patients were assigned procedural DRGs for revascularization instead of an AMI DRG, and type 1 myocardial infarction patients made up a smaller proportion of the DRG cohort (34%) than the ICD-10 cohort (78%). CONCLUSIONS: The method used to identify denominators for value-based payment programs has important implications for the patient characteristics and outcomes of the populations. As national and local quality initiatives mature, an emphasis on ICD-10 codes to define AMI cohorts would better represent type 1 myocardial infarction patients.

Internal Medicine Residents' Perceptions of Nephrology as a Career: A Focus Group Study.

Background: Interest in nephrology as a career has declined dramatically over the past several years. Only 62% of nephrology fellowship positions are filled for the upcoming 2020 appointment year. The purpose of this study was to identify perceptions, attitudes, motivators, and barriers to a career in nephrology among internal medicine residents. Methods: We recruited focus groups of internal medicine residents (N=25) from the University of Colorado, and asked questions aimed at exploring perceptions, attitudes, and barriers to a career in nephrology, and ways to increase interest in nephrology. All focus groups were conducted on the University of Colorado Denver Anschutz Medical Campus. Focus group sessions were recorded and transcribed. Thematic analysis was used to identify key concepts and themes. Results: Residents described many barriers to a career in nephrology, including lack of exposure, lack of advances in the field, low monetary compensation, high complexity, lack of role models/mentors, and low-prestige/noncompetitive nature of the field. Most residents had no exposure to outpatient nephrology. Lack of new therapeutics was a significant deterrent to nephrology. Nephrology teaching in medical school was described as not clinically relevant and too complicated. Several residents felt they were not smart enough for nephrology. Only three residents had a role model within nephrology. Residents used the word "stigmatized" to describe nephrology, and discussed how low prestige decreased their interest in a field. Participants expressed suggestions to increase interest in nephrology through earlier and more outpatient nephrology exposure, enhanced interactions with nephrologists, and research and advancements in the field. Conclusions: Residents identified several modifiable barriers to a career in nephrology. Changing how nephrology is taught in medical school, enhancing interactions with nephrologists through increased exposure, and highlighting research and advancements in nephrology may change the perception of nephrology and increase the number of residents entering the field.

Endoscopic surgery for patients with syndromic craniosynostosis and the requirement for additional open surgery.

OBJECTIVE Recent reports have described early endoscopic suturectomy as a treatment option for patients with syndromic craniosynostosis, but such patients often require subsequent calvarial remodeling. The authors describe their experience with this patient population and seek to identify predictors of sufficiency of endoscopic surgery alone. METHODS The medical records of patients with syndromic craniosynostosis who underwent endoscopic repair were retrospectively reviewed. Demographic data, operative details, and follow-up data were collected. RESULTS A total of 6 patients with syndromic craniosynostosis underwent endoscopic surgery followed by helmet therapy during the study period. Of these, 3 patients were male. The involved syndromes included Crouzon, Pfeiffer, Jackson-Weiss, Muenke, Saethre-Chotzen, and craniosynostosis-3 (n = 1 each). The patients underwent endoscopic surgery at a median age of 2.1 months (range 0.9-4.1 months). The median estimated blood loss was 30 ml (range 20-100 ml), with 2 patients requiring a transfusion. The median length of stay in the hospital was 1.5 days (range 1-4 days), and the median follow-up was 29.0 months (range 16.8-81.7 months), with 1 patient (16.7%) requiring an open revision. Three patients (50%) were classified as Whitaker Category I at the last follow-up. The patients for whom additional open surgery was performed or recommended (Whitaker Category IV) were the oldest patients in the cohort, ranging from 2.6 to 4.1 months at the time of surgery. CONCLUSIONS This series demonstrates that endoscopic surgery can be sufficient to treat syndromic craniosynostosis without subsequent open calvarial remodeling over a median follow-up period of at least 2 years. The findings suggest that younger age at the time of endoscopic surgery may be an important factor in determining the sufficiency of this procedure. Even among patients who require subsequent open calvarial remodeling, early endoscopic surgery may allow for growth and development of the brain and skull while delaying the need for open remodeling until the patient is older and can better tolerate the procedure.

Haploinsufficiency of ZNF462 is associated with craniofacial anomalies, corpus callosum dysgenesis, ptosis, and developmental delay.

The introduction of whole-exome sequencing into the Pediatric Genetics clinic has increased the identification of novel genes associated with neurodevelopmental disorders and congenital anomalies. This agnostic approach has shed light on multiple proteins and pathways not previously known to be associated with disease. Here we report eight subjects from six families with predicted loss of function variants in ZNF462, a zinc-finger protein of unknown function. These individuals have overlapping phenotypes that include ptosis, metopic ridging, craniosynostosis, dysgenesis of the corpus callosum, and developmental delay. We propose that ZNF462 plays an important role in embryonic development, and is associated with craniofacial and neurodevelopmental abnormalities.