Novel pathogenic variants and quantitative phenotypic analyses of Robinow syndrome: WNT signaling perturbation and phenotypic variability.

Robinow syndrome (RS) is a genetically heterogeneous disorder with six genes that converge on the WNT/planar cell polarity (PCP) signaling pathway implicated (DVL1, DVL3, FZD2, NXN, ROR2, and WNT5A). RS is characterized by skeletal dysplasia and distinctive facial and physical characteristics. To further explore the genetic heterogeneity, paralog contribution, and phenotypic variability of RS, we investigated a cohort of 22 individuals clinically diagnosed with RS from 18 unrelated families. Pathogenic or likely pathogenic variants in genes associated with RS or RS phenocopies were identified in all 22 individuals, including the first variant to be reported in DVL2. We retrospectively collected medical records of 16 individuals from this cohort and extracted clinical descriptions from 52 previously published cases. We performed Human Phenotype Ontology (HPO) based quantitative phenotypic analyses to dissect allele-specific phenotypic differences. Individuals with FZD2 variants clustered into two groups with demonstrable phenotypic differences between those with missense and truncating alleles. Probands with biallelic NXN variants clustered together with the majority of probands carrying DVL1, DVL2, and DVL3 variants, demonstrating no phenotypic distinction between the NXN-autosomal recessive and dominant forms of RS. While phenotypically similar diseases on the RS differential matched through HPO analysis, clustering using phenotype similarity score placed RS-associated phenotypes in a unique cluster containing WNT5A, FZD2, and ROR2 apart from non-RS-associated paralogs. Through human phenotype analyses of this RS cohort and OMIM clinical synopses of Mendelian disease, this study begins to tease apart specific biologic roles for non-canonical WNT-pathway proteins.

Variable clinical severity in TANGO2 deficiency: Case series and literature review.

Biallelic pathogenic variants in the TANGO2 (transport and Golgi organization 2 homolog) gene have been identified as causing a rare metabolic disorder characterized by susceptibility to recurrent rhabdomyolysis, lactic acidosis, encephalopathy, and life-threatening tachyarrhythmias. Recently published reports suggest variable clinical severity and phenotypes. This study details five new patients from two families with biallelic pathogenic variants in the TANGO2 gene identified by whole exome sequencing and includes the largest number of affected individuals from a single family reported to date. We document significant intrafamilial variability and highlight that milder phenotypes may be underrecognized. We present biochemical and clinical data to help highlight the features that aid in consideration of this condition in the differential with disorders of fatty acid oxidation. We also present a comprehensive literature review summarizing the molecular, clinical, and biochemical findings for 92 individuals across 13 publications. Of the 27 pathogenic variants reported to date, the recurrent exons 3-9 deletion represents the most common variant seen in 42% of individuals with TANGO2 deficiency. Common clinical features seen in >70% of all individuals include acute metabolic crisis, rhabdomyolysis, neurologic abnormalities, developmental delay, and intellectual disability. Findings such as elevated creatine kinase, hypothyroidism, ketotic hypoglycemia, QT prolongation, or abnormalities of long-chain acylcarnitines and urine dicarboxylic acids should raise clinical suspicion for this life-threatening condition.

Words Matter: An Antibias Workshop for Health Care Professionals to Reduce Stigmatizing Language.

Introduction: Biased language influences health care providers' perceptions of patients, impacts their clinical care, and prevents vulnerable populations from seeking treatment. Training clinicians to systematically replace biased verbal and written language is an essential step to providing equitable care. Methods: We designed and implemented an interactive workshop to teach health care professionals a framework to identify and replace stigmatizing language in clinical practice. The workshop included a reflective exercise, role-play, brief didactic session, and case-based discussion. We developed the program for a broad target audience of providers and initially delivered it at three academic conferences. We used descriptive statistics to analyze Likert-style items on course evaluations and identified themes in open-text responses. Results: A total of 66 participants completed course evaluations; most believed the workshop met its objectives (4.8 out of 5.0) and strongly agreed that they would apply skills learned (4.8). Participants planned to incorporate reflection into their verbal and written language. Potential barriers to applying course content included perceived difficulty in changing entrenched practice habits, burnout, and fatigue. Suggestions for improvement included more time for group discussions and strategies to teach skills to colleagues. Discussion: Participants found the course material highly engaging and relevant to their clinical practice. Learners left the workshop feeling motivated to engage in more mindful word choice and to share key concepts with their colleagues.

Capacity-building needs of minority health nonprofits.

This article reports on the results of a statewide assessment of the capacity-building needs of organizations that provide health services to ethnic minority groups in Ohio. The research addressed gaps in knowledge about the specific needs of these organizations for improved effectiveness and long-term sustainability. A telephone survey of 659 organizations, supplemented by focus groups with 37 participants in the state's largest cities, indicated substantial need and interest in capacity-building technical assistance in areas such as revenue-generating activities, marketing and public relations, information technology training, program evaluation, and board leadership development. The limited ability of these organizations to pay for the needed assistance creates challenges for planning approaches to meet these vital needs.

A youth development program: lasting impact.

The purpose of the study was to examine whether participation in a youth development program positively impacted participants' adult outcomes. Length of time adolescents spent in a comprehensive youth development program was correlated to their adult outcomes and functioning was assessed. All 141 adult past participants of a youth development program were identified. A survey was administered to 97% of the past participants located. School completion, higher education, alcohol and drug use, pregnancy and childbearing, employment, and involvement with the juvenile and adult justice systems were assessed. Degree of involvement in the program (low, medium, and high) was calculated and correlated with outcomes. Of the six areas surveyed, statistically significant findings (p<0.05) were obtained in three: education, employment, and criminal justice. Nonsignificant, but positive, trends were observed in the areas of pregnancy/parenthood and illicit drug use. Best outcomes were achieved with those who participated for at least 201 days.

Treatment outcomes: first time versus treatment-experienced clients.

A sample of treatment seeking clients was assessed at intake and 6, 12, 24 and 30 months later. Treatment-naive and treatment-experienced clients were compared in terms of baseline characteristics, 6-month outcomes, and predictors of these outcomes. Long-term outcomes of clients achieving an initially successful outcome were compared for the two groups. Results revealed significant short-term improvement for both groups, although treatment-experienced clients reported more serious drug use. The most consistent significant predictors of substance use outcomes were baseline severity of substance use and self-help participation. Outcome predictors unique to each group were also identified. Long-term outcomes for clients with an initial successful outcome tended to be better for treatment-experienced than treatment-naive clients. Both groups tended to have poorer outcomes as the follow-up duration increased. The results suggest that common and unique predictors of outcomes be considered in treating these two groups of clients. Additionally, treatment-naive clients may be at increased risk for poor outcomes even when initial success is achieved.

Economic benefits of substance abuse treatment: findings from Cuyahoga County, Ohio.

We estimated long-term economic benefits and treatment costs for a sample of substance abuse clients who received treatment in Cuyahoga County, Ohio, using health, criminal activity, and earnings data from the Persistent Effects of Treatment Studies. Clients were interviewed at baseline and 6, 12, 24, and 30 months following baseline. We find positive benefits from substance abuse treatment, almost of all of which were derived from reduced criminal activity and increased real earnings, with overall benefit-to-cost ratios ranging from 2.8 to 4.1. The reductions in costs to society were found to be persistent over the long-term, 30-month follow-up period. On average, treatment was found to be cost beneficial regardless of the number of times a client entered treatment in the baseline or follow-up periods. Clients who entered residential treatment and then step down to less intensive care showed greater treatment benefits than clients who only received residential treatment.

Predictors of alcohol and crack cocaine use outcomes over a 3-year follow-up in treatment seekers.

This study identified predictors of long-term alcohol and crack cocaine use outcomes in individuals participating in the Persistent Effects of Treatment Study. The domains that were assessed included motivation, self-efficacy, social support, psychiatric severity, employment, housing status, and self-help group attendance at baseline and 6, 12, 24, and 30 month follow-ups. In alcohol users, higher perceived seriousness of substance use problems, self-efficacy, and self-help group attendance, as well as lower social support for substance use, consistently predicted better alcohol use outcomes in the subsequent assessment period. In crack cocaine users, only self-efficacy consistently predicted cocaine use outcomes. Higher self-efficacy during follow-up was predicted by lower perceived seriousness of substance use and lower alcohol use frequency in the prior assessment period, whereas greater self-help group attendance was predicted by greater perceived seriousness of substance use, and lower substance use frequency.

Understanding residents' work: moving beyond counting hours to assessing educational value.

PURPOSE: To begin to understand how residents' work affects their own educations and the hospitals in which most of their training takes place, the authors undertook a systematic review of the literature analyzing residents' activities. This review sought to analyze resident physicians' activities to assess the educational value of residents' work. METHOD: The published literature was searched in 2001 using the Medline and Science Citation Index databases, and the unpublished literature was searched using bibliographies and key informants. One hundred six studies were rated for methodological rigor using the Cochrane Collaboration protocol, as modified by Bland et al. for nonclinical trials. Only those studies undertaken following the Bell Commission's report in 1987 and whose methodological rigor score fell at or above the median for all studies rated were included in the data synthesis. Results data from 16 studies that included over 1,000 residents in six different specialties, were combined under the definitions of types of residents' activities: marginal, patient care, teaching and learning, and other. RESULTS: This preliminary analysis found that residents devoted approximately 36% of their effort to direct patient care necessary to achieve specialty-specific learning objectives, 15% to the residency program's organized teaching activities, and potentially as much as 35% to delivering patient care of marginal or no educational value. An additional 16% of residents' waking time on duty was spent in other, unspecified activities. CONCLUSION: It is possible and potentially valuable to consider not only the number of hours worked by residents, but the educational content of their work when considering residency work and hour reforms