Search

BackgroundRecent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community.ObjectiveThe National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan.MethodsNDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS.ResultsThis review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade.ConclusionsThis review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.

IntroductionOur objective was to evaluate physicians' perspectives on the clinical utility of pharmacogenetic (PGx) testing in kidney, liver, heart, and lung transplantation (KLHL-Tx).MethodsA 36-question web-based survey was developed and administered to medical and surgical directors of US KLHL-Tx centers.ResultsThere were 82 respondents (10% response rate). The majority were men (78%), non-Hispanic whites (70%), medical directors (72%), and kidney transplant physicians (35%). Although 78% of respondents reported having some PGx education, most reported lack of confidence in their PGx knowledge and ability to apply a PGx test. Participants reported mixed views about the clinical utility of PGx testing-most agreed with the efficacy of PGx testing, but not the benefits relative to the risks or standard of care. While 55% reported that testing was available at their institution, only 38% ordered a PGx test in the past year, most commonly thiopurine-S-methyltransferase. Physician-reported barriers to PGx implementation included uncertainty about the clinical value of PGx testing and patient financial burden.ConclusionTogether, our findings suggest prospective PGx research and pilot implementation programs are needed to elucidate the clinical utility and value of PGx in KLHL-Tx. These initiatives should include educational efforts to inform the use of PGx testing.

BackgroundBiopsy remains the gold standard for determining fibrosis stage in patients with primary biliary cholangitis (PBC), but it is unavailable for most patients. We used data from the 11 US health systems in the FibrOtic Liver Disease Consortium to explore a combination of biochemical markers and electronic health record (EHR)-based diagnosis/procedure codes (DPCs) to identify the presence of cirrhosis in PBC patients.MethodsHistological fibrosis staging data were obtained from liver biopsies. Variables considered for the model included demographics (age, gender, race, ethnicity), total bilirubin, alkaline phosphatase, albumin, aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis 4 (FIB4) index, AST to alanine aminotransferase (ALT) ratio, and >100 DPCs associated with cirrhosis/decompensated cirrhosis, categorized into ten clusters. Using least absolute shrinkage and selection operator regression (LASSO), we derived and validated cutoffs for identifying cirrhosis.ResultsAmong 4328 PBC patients, 1350 (32%) had biopsy data; 121 (9%) were staged F4 (cirrhosis). DPC clusters (including codes related to cirrhosis and hepatocellular carcinoma diagnoses/procedures), Hispanic ethnicity, ALP, AST/ALT ratio, and total bilirubin were retained in the final model (AUROC=0.86 and 0.83 on learning and testing data, respectively); this model with two cutoffs divided patients into three categories (no cirrhosis, indeterminate, and cirrhosis) with specificities of 81.8% (for no cirrhosis) and 80.3% (for cirrhosis). A model excluding DPCs retained ALP, AST/ALT ratio, total bilirubin, Hispanic ethnicity, and gender (AUROC=0.81 and 0.78 on learning and testing data, respectively).ConclusionAn algorithm using laboratory results and DPCs can categorize a majority of PBC patients as cirrhotic or noncirrhotic with high accuracy (with a small remaining group of patients' cirrhosis status indeterminate). In the absence of biopsy data, this EHR-based model can be used to identify cirrhosis in cohorts of PBC patients for research and/or clinical follow-up.

Individuals with Down syndrome are known to have a greater prevalence of ocular conditions such as strabismus, nystagmus, elevated refractive error, poor accommodative function, elevated higher‐order optical aberrations and corneal abnormalities. Related to these conditions, individuals with Down syndrome commonly have reduced best‐corrected visual acuity at both far and near viewing distances across their lifespan. This review summarises the various optical sources of visual acuity reduction in this population and describes clinical trials that have evaluated alternative spectacle prescribing strategies to minimise these optical deficits. Although refractive corrections may still have limitations in their ability to normalise visual acuity for individuals with Down syndrome, the current literature provides evidence for eye care practitioners to consider in their prescribing practices for this population to maximise visual acuity. These considerations include accounting for the presence of elevated higher‐order aberrations when determining refractive corrections and considering bifocal lens prescriptions, even for young children with Down syndrome. [ABSTRACT FROM AUTHOR]

PurposeThe purpose of this article is to evaluate optic nerve head (ONH) characteristics in an ethnically diverse cohort of young U.S. adults.MethodsIn this study, 409 myopes and 206 nonmyopes (median age 22 years) completed measures including biometry and spectral domain optical coherence tomography from enface (ovality and torsion) and cross-sectional (tilt and crescent width) scans. Associated factors were evaluated using multivariable models.ResultsIn myopic versus nonmyopic right eyes, median tilt (6.0° vs. 2.4°; P < 0.0001) and frequency of crescents (49% vs. 10%; P < 0.0001) were higher in myopes. Right eyes with crescents had higher median tilts (8.8° [myopic], 9.0° [nonmyopic]) than those without crescent (2.5° [myopic], 2.1° [nonmyopic]), irrespective of refractive group (both P < 0.0001). Torsion was similar between groups, with a slight difference in ovality (0.89 vs. 0.91; P < 0.03). Data in the left eyes were similar, and modeling was done only for the right myopic eyes. Multivariable models showed that an increased tilt was associated with ethnicity (P < 0.001), the presence of crescent (P < 0.001), and smaller ONH diameter (P < 0.0031), with interactions between ethnicity and crescent (P = 0.002). Specifically, ONH tilt was significantly higher in Asian eyes without crescent (P < 0.0001 for all comparisons), and crescent width was associated with increased tilt in non-Asian eyes (P < 0.02). Crescent width was associated with ethnicity (greatest in Asians) and disc tilt. Interactions were observed between tilt and ethnicity, whereby tilt had a greater effect on crescent width in non-Asian eyes, and crescent width was associated with increased tilt in non-Asian eyes.ConclusionsThe data clarify the influence of ethnicity and myopia on ONH characteristics in young adults and may inform future studies of biomechanical properties or of retinal pathology of the myopic eye.

ObjectiveIdentification and refinement of psychometric properties of the Reproductive Coercion Scale (RCS) for use in survey research and clinical practice.Study designYoung women aged 16-29 years seeking services in 24 Pennsylvania and 5 California family planning clinics completed questionnaires. Data were pooled for analysis (n=4674), and underlying domains were assessed using Horn's Parallel Analysis and Exploratory Factor Analysis. Multidimensional Item Response Theory was used to refine the scale and assess reliability and validity of a short-form RCS.ResultsThe full, nine-item RCS had two underlying domains: pregnancy coercion and condom manipulation. Five items were retained in the short form: three about pregnancy coercion (e.g., "told you not to use birth control…") and two for condom manipulation (e.g., "taken off the condom while you were having sex…"; one of these items is the combination of two original items on damaging the condom that were combined because of similar statistical properties and face validity and a third item on removing the condom was retained on its own). Recent reproductive coercion was reported by 6.7% and 6.3% of the sample with the full and short-form RCS, respectively. Characteristics of women reporting reproductive coercion were similar with both forms.ConclusionFindings indicate that reproductive coercion includes pregnancy coercion and deliberate manipulation of condoms to promote pregnancy. Moreover, women experience reproductive coercion across a continuum of severity. We selected items that varied in RC severity and discrimination to generate a five-item short-form RCS for survey research and clinical practice.ImplicationsThis study assesses the psychometric properties of the RCS, identifying pregnancy coercion and condom manipulation as underlying domains of reproductive coercion. Recommendations for using the RCS in research and clinical practice are discussed.

PurposeHigh-quality optical coherence tomography (OCT) macular scans make it possible to distinguish a range of normal and diseased states by characterising foveal pit shape. Existing mathematical models lack the flexibility to capture all known pit variations and thus characterise the pit with limited accuracy. This study aimed to develop a new model that provides a more robust characterisation of individual foveal pit variations.MethodsA Sloped Piecemeal Gaussian (SPG) model, consisting of a linear combination of a tilted line and a piecemeal Gaussian function (two halves of a Gaussian connected by a separate straight line), was developed to fit retinal thickness data with the flexibility to characterise different degrees of pit asymmetry and pit bottom flatness. It fitted the raw pit data between the two rims of the fovea to improve accuracy. The model was tested on 3488 macular scans from both eyes of 581 young adults (376 myopes and 206 non-myopes, mean (S.D.) age 21.9 (1.4) years). Estimates for retinal thickness, wall height and slope, pit depth and width were derived from the best-fitting model curve. Ten variations of Gaussian and Difference of Gaussian models were fitted to the same scans and compared with the SPG model for goodness of fit (by Root mean square error, RMSE), model complexity (by the Bayesian Information Criteria) and model fidelity.ResultsThe SPG model produced excellent goodness of fit (mean RMSE = 4.25 and 3.89 μm; 95% CI: 4.20, 4.30 and 3.86, 3.93 for fitting horizontal and vertical profiles respectively). The SPG model showed pit asymmetry, with average nasal walls 17.6 (11.6) μm higher and 0.96 (0.61)° steeper than temporal walls and average superior walls 7.0 (12.2) μm higher and 0.41 (0.65)° steeper than the inferior walls. The SPG model also revealed a continuum of human foveal shapes, from round bottoms to extended flat bottoms (up to 563 μm). 49.1% of foveal profiles were best fitted with a flat bottom >30 μm wide. Compared with the other tested models, the SPG was the preferred model overall based on the Bayesian Information Criteria.ConclusionsThe SPG is a new parsimonious mathematical model that improves upon other models by accounting for wall asymmetry and flat pit bottoms, providing an excellent fit and more faithful characterisation of typical foveal pit shapes and their known variations. This new model may be helpful in distinguishing normal foveal shape variations by refractive status as well by other characteristics such as sex, ethnicity and age.

ObjectiveWe assessed the effectiveness of a provider-delivered intervention targeting reproductive coercion, an important factor in unintended pregnancy.Study designWe randomized 25 family planning clinics (17 clusters) to deliver an education/counseling intervention or usual care. Reproductive coercion and partner violence victimization at 1 year follow-up were primary outcomes. Unintended pregnancy, recognition of sexual and reproductive coercion, self-efficacy to use and use of harm reduction behaviors to reduce victimization and contraception nonuse, and knowledge and use of partner violence resources were secondary outcomes. Analyses included all available data using an intention-to-treat approach.ResultsAmong 4009 females ages 16 to 29 years seeking care, 3687 completed a baseline survey prior to clinic visit from October 2011 to November 2012; 3017 provided data at 12-20weeks post-baseline (T2) and 2926 at 12months post-baseline (T3) (79% retention). Intervention effects were not significant for reproductive coercion [adjusted risk ratio (ARR) 1.50 (95% confidence interval 0.95-2.35)] or partner violence [ARR 1.07 (0.84-1.38)]. Intervention participants reported improved knowledge of partner violence resources [ARR 4.25 (3.29-5.50)] and self-efficacy to enact harm reduction behaviors [adjusted mean difference 0.06 (0.02-0.10)]. In time point-specific models which included moderating effects of exposure to reproductive coercion at baseline, a higher reproductive coercion score at baseline was associated with a decrease in reproductive coercion 1 year later (T3). Use and sharing of the domestic violence hotline number also increased.ConclusionThis brief clinic intervention did not reduce partner violence victimization. The intervention enhanced two outcomes that may increase safety for women, specifically awareness of partner violence resources and self-efficacy to enact harm reduction behaviors. It also appeared to reduce reproductive coercion among women experiencing multiple forms of such abuse.

BackgroundAntibiotics are commonly implicated in Stevens-Johnson syndrome (SJS), overlap syndrome (SJS-TEN), and Toxic Epidermal Necrolysis (TEN), rare disorders of skin and mucosal membranes, often the result of adverse drug reactions. The objective of this study is to examine associations between SJS, SJS-TEN, and TEN and antibiotic exposure overlapping diagnosis, and 3, 6, and 12 months before diagnosis.MethodsA case-control study was conducted using PharMetrics LifeLink® Health Plan Claims Database (2001-2013). Cases had ≥1 diagnoses of SJS/TEN identified using ICD-9 codes, and ≥1 year of continuous health plan enrollment before earliest diagnosis. Controls were randomly selected from patients with no diagnoses of SJS/TEN, and matched to cases 4:1 on age, gender, and amount of continuous health plan enrollment. Multivariate logistic regression was used to estimate odds ratios for varying antibiotic exposures.Results192 cases and 768 controls were included. Odds of an antibiotic fill overlapping diagnosis was ten times higher for cases than controls (OR=10.4; 95% CI 5.1, 21.1). Most common antibiotics overlapping diagnosis were aminopenicillins and cephalosporins, however associations between specific antibiotics and SJS/TEN were not significant (OR=1.03; 95% CI 0.6, 1.9). Unadjusted ORs for 3 (OR=1.05; 95% CI 1.03-1.07), 6 (OR=1.03; 95% CI 1.02, 1.04), and 12 months (OR=1.02; 95% CI 1.01, 1.02) before diagnosis show lower associations further in the past between antibiotics and reaction.ConclusionsA significant association was found between overlapping antibiotic exposure and SJS/TEN. Likely due to small sample sizes, associations between specific antibiotic classes and SJS/TEN were not significant; further studies should be pursued to examine specific antibiotics.

BackgroundWomen ages 16-29 utilizing family planning clinics for medical services experience higher rates of intimate partner violence (IPV) and reproductive coercion (RC) than their same-age peers, increasing risk for unintended pregnancy and related poor reproductive health outcomes. Brief interventions integrated into routine family planning care have shown promise in reducing risk for RC, but longer-term intervention effects on partner violence victimization, RC, and unintended pregnancy have not been examined.Methods/designThe 'Addressing Reproductive Coercion in Health Settings (ARCHES)' Intervention Study is a cluster randomized controlled trial evaluating the effectiveness of a brief, clinician-delivered universal education and counseling intervention to reduce IPV, RC and unintended pregnancy compared to standard-of-care in family planning clinic settings. The ARCHES intervention was refined based on formative research. Twenty five family planning clinics were randomized (in 17 clusters) to either a three hour training for all family planning clinic staff on how to deliver the ARCHES intervention or to a standard-of-care control condition. All women ages 16-29 seeking care in these family planning clinics were eligible to participate. Consenting clients use laptop computers to answer survey questions immediately prior to their clinic visit, a brief exit survey immediately after the clinic visit, a first follow up survey 12-20 weeks after the baseline visit (T2), and a final survey 12 months after the baseline (T3). Medical record chart review provides additional data about IPV and RC assessment and disclosure, sexual and reproductive health diagnoses, and health care utilization. Of 4009 women approached and determined to be eligible based on age (16-29 years old), 3687 (92 % participation) completed the baseline survey and were included in the sample.DiscussionThe ARCHES Intervention Study is a community-partnered study designed to provide arigorous assessment of the short (3-4 months) and long-term (12 months) effects of a brief, clinician-delivered universal education and counseling intervention to reduce IPC, RC and unintended pregnancy in family planning clinic settings. The trial features a cluster randomized controlled trial design, a comprehensive data collection schedule and a large sample size with excellent retention.Trial registrationClinicialTrials.gov NCT01459458. Registered 10 October 2011.

The United Nations Educational, Scientific and Cultural Organization (UNESCO) Associated Schools Network is an international organization that can help teachers and students learn more about practical ways to apply social justice themes at an academic, personal, social, and global level. Learning processes are holistic and multi-dimensional within this context. Different strands of transformative learning theory that include individual perspective transformation, planetary-global transformative education, non-western ways of knowing, and emancipatory teaching reflect key UNESCO themes. Specific examples of perspectives of social justice held by teachers, administrators, and counsellors and adult learning centres from Winnipeg, Canada are highlighted. This article emphasizes the importance of extending ways of knowing and learning that have the potential to create more dynamic and culturally-inclusive learning environments. Implications for curriculum innovation and creative educational leadership will be addressed. This article is framed from the perspectives of a principal, teacher, and researcher.

PurposeTo examine the relationship of choroidal thickness with axial length (AL) and myopia in young adult eyes in the ethnically diverse Correction of Myopia Evaluation Trial (COMET) cohort.DesignCross-sectional, multicenter study.MethodsIn addition to measures of myopia by cycloplegic autorefraction and AL by A-scan ultrasonography, participants underwent optical coherence tomography imaging of the choroid in both eyes at their last visit (14 years after baseline). Using digital calipers, 2 independent readers measured choroidal thickness in the right eye (left eye if poor quality; n = 37) at 7 locations: fovea and 750, 1500, and 2250 μm nasal (N) and temporal (T) to the fovea.ResultsChoroidal thickness measurements were available from 294 of 346 (85%) imaged participants (mean age: 24.3 ± 1.4 years; 44.9% male) with mean myopia of -5.3 ± 2.0 diopters and mean AL of 25.5 ± 1.0 mm. Overall, choroidal thickness varied by location (P < .0001) and was thickest at the fovea (273.8 ± 70.9 μm) and thinnest nasally (N2250, 191.5 ± 69.3 μm). Multivariable analyses showed significantly thinner choroids in eyes with more myopia and longer AL at all locations except T2250 (P ≤ .001) and presence of peripapillary crescent at all locations except T1500 and T2250 (P ≤ .0001). Choroidal thickness varied by ethnicity at N2250 (P < .0001), with Asians having the thinnest and African Americans the thickest choroids.ConclusionChoroids are thinner in longer, more myopic young adult eyes. The thinning was most prominent nasally and in eyes with a crescent. In the furthest nasal location, ethnicity was associated with choroidal thickness. The findings suggest that choroidal thickness should be evaluated, especially in the nasal regions where myopic degenerations are most commonly seen clinically.