Stroke Avoidance for Children in REpública Dominicana (SACRED): Protocol for a Prospective Study of Stroke Risk and Hydroxyurea Treatment in Sickle Cell Anemia.

BACKGROUND: In the Dominican Republic, where the burden of sickle cell anemia (SCA) is high, many children lack access to routine screening and preventative care. Children with SCA are at risk for stroke, an event that leads to significant morbidity and mortality. In the United States, screening via transcranial Doppler (TCD) identifies children with SCA at highest stroke risk, allowing early intervention with blood transfusions. The need for indefinite transfusions for primary stroke prevention limits their practicality in limited-resource countries. Hydroxyurea has been shown to lower TCD velocities and to prevent conversion from conditional (170 to 199 cm/sec) to abnormal (greater than or equal to 200 cm/sec) velocities. In resource-limited settings, implementation of a TCD screening program, coupled with hydroxyurea therapy, could reduce the burden of SCA and stroke. OBJECTIVE: The aims of the Stroke Avoidance for Children in REpública Dominicana (SACRED) trial are (1) to screen children with SCA for stroke risk using TCD and to determine the prevalence of elevated velocities in a cross-sectional sample; (2) to identify clinical and laboratory correlates of elevated velocities; and (3) to obtain longitudinal data on the natural history of TCD velocities and to measure therapeutic effects of hydroxyurea. METHODS: This prospective trial, designed and conducted by Cincinnati Children's Hospital Medical Center (CCHMC) and Hospital Infantil Robert Reid Cabral (HIRRC) with Centro de Obstetricia y Ginecología, includes a baseline cross-sectional epidemiological survey of the distribution of TCD velocities across a large cohort of children with SCA in the Dominican Republic. Children with conditional velocities are eligible to begin protocol-directed hydroxyurea if laboratory criteria are met. The treatment schedule begins with a fixed-dose of approximately 20 mg/kg/day for 6 months, after which it escalates to maximum tolerated dose (MTD). All participants undergo longitudinal annual TCD evaluation, while those on hydroxyurea have semi-annual evaluations during the 3-year study period. Data are collected using an Internet-based Research Electronic Data Capture (REDCap) system with forms translated into Spanish; both remote and on-site monitoring are used. RESULTS: To date, 122 children with SCA have enrolled in SACRED including 85 (69.7%, 85/122) with normal, 29 (23.8%, 29/122) with conditional, 5 (4.1%, 5/122) with abnormal, and 3 (2.5%, 3/122) with inadequate TCD velocities. Of the 29 children with conditional TCD velocities, 17 (59%, 17/29) have initiated hydroxyurea per protocol, with plans for escalation to MTD. CONCLUSIONS: The SACRED trial will provide novel epidemiologic data about the prevalence of children with SCA and increased stroke risk in the Dominican Republic. The study also includes an investigation of the impact of hydroxyurea at MTD on elevated TCD velocities, as well as clinical and laboratory parameters. The design and implementation of SACRED reflect a successful international institutional partnership, one that features local capacity building and training in research methods and clinical care. The trial's results have important implications for screening and prevention of primary stroke in children with SCA living in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02769845; https://www.clinicaltrials.gov/ct2/show/NCT02769845 (Archived by WebCite at http://www.webcitation.org/6qf6n0Egh).

Clinical correlates of anxious depression among elderly patients with depression.

OBJECTIVE: The purpose of this study was to determine the clinical correlates of comorbid anxiety and depression in a sample of older patients with major depression. METHODS: 352 patients aged 59 and older with major depression were enrolled in the Study of Depression in Later Life at Duke University, of whom 148 met criteria for lifetime generalized anxiety disorder. Participants completed self-report assessments of performance in basic and instrumental activities of daily living, social support, suicidal ideation, life satisfaction, and stressful life events. Cognitive assessment was done with the Mini-Mental State Examination. RESULTS: The prevalence of lifetime anxiety in our depressed sample was 42%. Patients with anxious depression were significantly younger, and had greater suicidal ideation, more impairment of subjective social support, and more severe depressive symptoms. CONCLUSION: In elderly patients with anxious depression, psychosocial support and suicidal ideation should be assessed. Whether improvement of subjective social support leads to reduction in anxious depression should be investigated.

Predictors of everyday functioning among older Mexican Americans vs. Anglo-Americans with schizophrenia.

OBJECTIVE: We assessed clinical, demographic, and cognitive predictors of everyday functioning in Mexican American and Anglo-American outpatients with schizophrenia. METHOD: Three groups of participants aged 40 years and over with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder were compared: 79 Anglo-Americans, 24 Mexican American patients who chose to be tested in English, and 33 Mexican American patients who preferred Spanish. The study was conducted from October 2001 to July 2004. RESULTS: On demographic, clinical, cognitive, and functional measures, Anglo-American participants were generally similar to Mexican American participants who opted for being tested in English. Mexican American participants who preferred Spanish were significantly different from the other 2 groups on several measures, including everyday functioning performance. To determine the predictors of everyday functioning, separate regression analyses were conducted for each of the 3 groups. Cognitive ability consistently accounted for the greatest proportion of variance in performance regardless of ethnicity, language preference, or education. Among the Mexican American participants, level of acculturation was the second strongest predictor of everyday functioning when the group was examined as a whole; however, acculturation was not a significant predictor when controlling for language preference. CONCLUSION: Cognitive performance and language preference (a proxy for acculturation) may play a particularly important role in predicting ability to perform everyday tasks. Further studies to better understand the potential impact of ethnicity, culture, education, and language on everyday functioning may help develop more specific and culture-sensitive intervention strategies for different ethnic groups.

Tennessee Williams.

Tennessee Williams was one of the greatest American playwrights of all time. Born into a family with a strong history of serious mental illness, Williams seemed to have had several major depressive episodes during his early adulthood, along with severe and worsening alcohol and drug dependence and abuse involving sedatives and stimulants throughout his adult life. He received treatment of variable quality and duration in middle and old age. Despite his mental illness, Williams continued to be a productive writer even after age 60, although his later works were less successful. The authors consider both the strengths and limitations of Williams' coping mechanisms.