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Chromosomal microarray (CMA) is now widely used as first-tier testing for the detection of copy number variants (CNVs) and absence of heterozygosity (AOH) in patients with multiple congenital anomalies (MCA), autism spectrum disorder (ASD), developmental delay (DD), and/or intellectual disability (ID). Chromosome analysis is commonly used to complement CMA in the detection of balanced genomic aberrations. However, the cost-effectiveness and the impact on clinical management of chromosome analysis concomitant with CMA were not well studied, and there is no consensus on how to best utilize these two tests. To assess the clinical utility and cost-effectiveness of chromosome analysis concomitant with CMA in patients with MCA, ASD, DD, and/or ID, we retrospectively analyzed 3,360 postnatal cases for which CMA and concomitant chromosome analysis were performed in the Colorado Genetic Laboratory (CGL) at the University Of Colorado School Of Medicine. Chromosome analysis alone yielded a genetic diagnosis in two patients (0.06%) and contributed additional information to CMA results in 199 (5.92%) cases. The impact of abnormal chromosome results on patient management was primarily related to counseling for reproductive and recurrence risks assessment (101 cases, 3.01%) while a few (5 cases, 0.15%) led to changes in laboratory testing and specialist referral (25 cases, 0.74%). The incremental cost-effectiveness ratio (ICER) of combined testing demonstrated the cost of each informative chromosome finding was significantly higher for patients with clinically insignificant (CI) CMA findings versus clinically significant (CS) CMA results. Our results suggest that a stepwise approach with CMA testing with reflex to chromosome analysis on cases with CS CMA findings is a more cost-effective testing algorithm for patients with MCA, ASD, and/or DD/ID.

Introduction The burden of cardiovascular disease (CVD) is increasing in sub-Saharan Africa with untreated hypertension being a major contributing factor. Understanding the magnitude of the problem and risk factors associated with HIV and long-term antiretroviral therapy (ART) is critically important for designing effective programs for diagnosing and treating hypertension in Kenya. Methods In this cross-sectional study, we enrolled 300 persons with HIV (PWH) on long term ART (≥6 months) and 298 HIV-negative adults seeking care at the Kisumu County Hospital between September 2017 and May 2018. Hypertension was defined as blood pressure of ≥140/90mmHg or a previous hypertension diagnosis. Multivariate regression was used to assess the association between hypertension and HIV adjusting for age, sex, and known CVD risk factors. Results Overall prevalence of hypertension was 22%. PWH had a lower prevalence of hypertension than HIV-negative persons (16% vs 27% respectively; p40 years, body mass index (BMI) >25 kg/m2 and low-density lipoproteins ≥130mg/dL. Among PWH, being older than 40 years and higher BMI >30 kg/m2 were associated with hypertension. Conclusion Prevalence of hypertension was high, affecting nearly one in every 4 adults, and associated with older age, higher BMI and high low-density lipoproteins. PWH on long-term ART had significantly lower prevalence of hypertension compared to HIV-negative individuals, potentially due to increased access to healthcare services and interaction with prevention messaging. Interventions to increase screening for and prevention of hypertension in the community for all adults are warranted.

Copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) significantly contribute to the etiology of neurodevelopmental disorders, such as developmental delay (DD), intellectual disability (ID), and autism spectrum disorder (ASD). This study summarizes the results of 3.5 years of CMA testing by a CLIA-certified clinical testing laboratory 5487 patients with neurodevelopmental conditions were clinically evaluated for rare copy number variants using a 2.8-million probe custom CMA optimized for the detection of CNVs associated with neurodevelopmental disorders. We report an overall detection rate of 29.4% in our neurodevelopmental cohort, which rises to nearly 33% when cases with DD/ID and/or MCA only are considered. The detection rate for the ASD cohort is also significant, at 25%. Additionally, we find that detection rate and pathogenic yield of CMA vary significantly depending on the primary indications for testing, the age of the individuals tested, and the specialty of the ordering doctor. We also report a significant difference between the detection rate on the ultrahigh resolution optimized array in comparison to the array from which it originated. This increase in detection can significantly contribute to the efficient and effective medical management of neurodevelopmental conditions in the clinic.

Interstitial deletions of chromosome band 10q22 are rare. We report on the characterization of three overlapping de novo 10q22 deletions by high-resolution array comparative genomic hybridization in three unrelated patients. Patient 1 had a 7.9 Mb deletion in 10q21.3-q22.2 and suffered from severe feeding problems, facial dysmorphisms and profound mental retardation. Patients 2 and 3 had nearly identical deletions of 3.2 and 3.6 Mb, the proximal breakpoints of which were located at an identical low-copy repeat. Both patients were mentally retarded; patient 3 also suffered from growth retardation and hypotonia. We also report on the results of breakpoint analysis by array painting in a mentally retarded patient with a balanced chromosome translocation 46,XY,t(10;13)(q22;p13)dn. The breakpoint in 10q22 was found to disrupt C10orf11, a brain-expressed gene in the common deleted interval of patients 1-3. This finding suggests that haploinsufficiency of C10orf11 contributes to the cognitive defects in 10q22 deletion patients.

Supported employment (SE) is considered an “evidence-based” practice for people with serious mental illness. We examined inpatient hospitalizations and emergency service visits among clients in a SE program based on the Individual Placement and Support (IPS) model in comparison to a propensity score matched group of clients who did not participate in IPS. A significant interaction showed that only IPS/SE clients who were also high in regular mental health services had fewer hospitalizations and emergency service visits than matched controls. The interaction effect was moderate, even when we controlled for client functioning. These findings provide support for the integration of mental health and vocational rehabilitation services, a key feature of evidence-based SE services.

While randomized clinical trials (RCTs) have helped to establish Individual Placement and Support (IPS) programs as an evidence-based practice, it is important to evaluate whether "real world" IPS programs can be implemented with fidelity and achieve outcomes comparable to programs evaluated in RCTs. The current evaluation examined retrospectively employment outcomes for go participants from an IPS-model Services for Employment and Education (SEE) program in Massachusetts over a 4.5-year period. Evaluators accessed demographic, functioning, and employment data from three sources--SEE program records/database, clinical records, and the Massachusetts Department of Mental Health Client Tracking system. Results indicate that the SEE program maintained high IPS fidelity and achieved employment outcomes comparable or superior to other SE and IPS model programs described in the literature.