Low Vision Rehabilitation for Adult African Americans in Two Settings.

PURPOSE: The Vision Rehabilitation for African Americans with Central Vision Impairment (VISRAC) study is a demonstration project evaluating how modifications in vision rehabilitation can improve the use of functional vision. METHODS: Fifty-five African Americans 40 years of age and older with central vision impairment were randomly assigned to receive either clinic-based (CB) or home-based (HB) low vision rehabilitation services. Forty-eight subjects completed the study. The primary outcome was the change in functional vision in activities of daily living, as assessed with the Veteran's Administration Low-Vision Visual Function Questionnaire (VFQ-48). This included scores for overall visual ability and visual ability domains (reading, mobility, visual information processing, and visual motor skills). Each score was normalized into logit estimates by Rasch analysis. Linear regression models were used to compare the difference in the total score and each domain score between the two intervention groups. The significance level for each comparison was set at 0.05. RESULTS: Both CB and HB groups showed significant improvement in overall visual ability at the final visit compared with baseline. The CB group showed greater improvement than the HB group (mean of 1.28 vs. 0.87 logits change), though the group difference is not significant (p = 0.057). The CB group visual motor skills score showed significant improvement over the HB group score (mean of 3.30 vs. 1.34 logits change, p = 0.044). The differences in improvement of the reading and visual information processing scores were not significant (p = 0.054 and p = 0.509) between groups. Neither group had significant improvement in the mobility score, which was not part of the rehabilitation program. CONCLUSIONS: Vision rehabilitation is effective for this study population regardless of location. Possible reasons why the CB group performed better than the HB group include a number of psychosocial factors as well as the more standardized distraction-free work environment within the clinic setting.

Prematurity and respiratory outcomes program (PROP): study protocol of a prospective multicenter study of respiratory outcomes of preterm infants in the United States.

BACKGROUND: With improved survival rates, short- and long-term respiratory complications of premature birth are increasing, adding significantly to financial and health burdens in the United States. In response, in May 2010, the National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute (NHLBI) funded a 5-year $18.5 million research initiative to ultimately improve strategies for managing the respiratory complications of preterm and low birth weight infants. Using a collaborative, multi-disciplinary structure, the resulting Prematurity and Respiratory Outcomes Program (PROP) seeks to understand factors that correlate with future risk for respiratory morbidity. METHODS/DESIGN: The PROP is an observational prospective cohort study performed by a consortium of six clinical centers (incorporating tertiary neonatal intensive care units [NICU] at 13 sites) and a data-coordinating center working in collaboration with the NHLBI. Each clinical center contributes subjects to the study, enrolling infants with gestational ages 23 0/7 to 28 6/7 weeks with an anticipated target of 750 survivors at 36 weeks post-menstrual age. In addition, each center brings specific areas of scientific focus to the Program. The primary study hypothesis is that in survivors of extreme prematurity specific biologic, physiologic and clinical data predicts respiratory morbidity between discharge and 1 year corrected age. Analytic statistical methodology includes model-based and non-model-based analyses, descriptive analyses and generalized linear mixed models. DISCUSSION: PROP incorporates aspects of NICU care to develop objective biomarkers and outcome measures of respiratory morbidity in the <29 week gestation population beyond just the NICU hospitalization, thereby leading to novel understanding of the nature and natural history of neonatal lung disease and of potential mechanistic and therapeutic targets in at-risk subjects. TRIAL REGISTRATION: Clinical Trials.gov NCT01435187.

Respiratory consequences of prematurity: evolution of a diagnosis and development of a comprehensive approach.

Bronchopulmonary dysplasia (BPD) is the most common respiratory consequence of premature birth and contributes to significant short- and long-term morbidity, mortality and resource utilization. Initially defined as a radiographic, clinical and histopathological entity, the chronic lung disease known as BPD has evolved as obstetrical and neonatal care have improved the survival of lower gestational age infants. Now, definitions based on the need for supplementary oxygen at 28 days and/or 36 weeks provide a useful reference point in the neonatal intensive-care unit (NICU), but are no longer based on histopathological findings, and are neither designed to predict longer term respiratory consequences nor to study the evolution of a multifactorial disease. The aims of this review are to critically examine the evolution of the diagnosis of BPD and the challenges inherent to current classifications. We found that the increasing use of respiratory support strategies that administer ambient air without supplementary oxygen confounds oxygen-based definitions of BPD. Furthermore, lack of reproducible, genetic, biochemical and physiological biomarkers limits the ability to identify an impending BPD for early intervention, quantify disease severity for standardized classification and approaches and reliably predict the long-term outcomes. More comprehensive, multidisciplinary approaches to overcome these challenges involve longitudinal observation of extremely preterm infants, not only those with BPD, using genetic, environmental, physiological and clinical data as well as large databases of patient samples. The Prematurity and Respiratory Outcomes Program (PROP) will provide such a framework to address these challenges through high-resolution characterization of both NICU and post-NICU discharge outcomes.

Shorter time to target temperature is associated with poor neurologic outcome in post-arrest patients treated with targeted temperature management.

INTRODUCTION: Time to achieve target temperature varies substantially for patients who undergo targeted temperature management (TTM) after cardiac arrest. The association between arrival at target temperature and neurologic outcome is poorly understood. We hypothesized that shorter time from initiation of cooling to target temperature ("induction") will be associated with worse neurologic outcome, reflecting more profound underlying brain injury and impaired thermoregulatory control. METHODS: This was a multicenter retrospective study analyzing data from the Penn Alliance for Therapeutic Hypothermia (PATH) Registry. We examined the association between time from arrest to return of spontaneous circulation (ROSC) ("downtime"), ROSC to initiation of TTM ("pre-induction") and "induction" with cerebral performance category (CPC). RESULTS: A total of 321 patients were analyzed, of whom 30.8% (99/321) had a good neurologic outcome. Downtime for survivors with good outcome was 11 (IQR 6-27) min vs. 21 (IQR 10-36) min (p=0.002) for those with poor outcome. Pre-induction did not vary between good and poor outcomes (98 (IQR 36-230) min vs. 114 (IQR 34-260) (p=ns)). Induction time in the good outcome cohort was 237 (IQR 142-361) min compared to 180 (IQR 100-276) min (p=0.004). Patients were categorized by induction time (<120min, 120-300min, >300min). Using multivariable logistic regression adjusted for age, initial rhythm, and downtime, induction time >300min was associated with good neurologic outcome when compared to those with an induction time <120min. CONCLUSION: In this multicenter cohort of post-arrest TTM patients, shorter induction time was associated with poor neurologic outcome.

Immune markers predictive of neuropsychiatric symptoms in HIV-infected youth.

The purpose of this study was to evaluate possible associations between systemic immune dysregulation (activated CD8(+) T lymphocytes and natural killer [NK] cell count/function) and symptoms of depression and anxiety in youth with horizontally (behaviorally) acquired HIV infection. This secondary analysis of a previously collected prospective cohort included 323 youth with horizontally acquired HIV infection enrolled in the Reaching for Excellence in Adolescent Care and Health (REACH) cohort of the NICHD/NIH. A multivariable linear regression model with generalized estimating equations for intraindividual repeated measures was used to examine the relationship between flow cytometry measurements of activated T lymphocytes (CD8(+) CD38(+)), NK cells (CD3(-) CD16(+) CD56(+)), and NK cell functional activity (lytic units per NK cell and per peripheral blood mononuclear cell) and their association with subsequent symptoms of depression (Center for Epidemiologic Studies depression scale) and anxiety (Revised Children's Manifest Anxiety Scale). Higher measures of NK cell functional activity were associated with fewer anxiety symptoms measured 12 months later in crude and adjusted analyses. Higher counts of activated T cells were associated with fewer depression symptoms measured 12 months later in adjusted analysis. NK cell function and activated T-lymphocyte count may be related to subsequent symptoms of depression and anxiety.

Factors associated with a willingness to accept rapid HIV testing in an urban emergency department.

Emergency Departments (EDs) provide primary healthcare to many underserved persons without access to preventive healthcare elsewhere. We conducted a cross-sectional study to test the hypothesis that patients are more likely to express a willingness to accept rapid HIV testing in the ED if they lack access to preventive healthcare elsewhere. Medicaid insurance, younger age, lack of a usual place of healthcare, high perceived HIV risk, and actual HIV risk were associated with increased HIV test acceptance. These results support the need for and acceptability of rapid HIV testing in the ED particularly for individuals who may lack access to this preventive healthcare screening elsewhere.

A pharmacogenetic versus a clinical algorithm for warfarin dosing.

BACKGROUND: The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results. METHODS: We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy. RESULTS: At 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy. CONCLUSIONS: Genotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657.).

Rationale and design of the Clarification of Optimal Anticoagulation through Genetics trial.

BACKGROUND: Current dosing practices for warfarin are empiric and result in the need for frequent dose changes as the international normalized ratio gets too high or too low. As a result, patients are put at increased risk for thromboembolism, bleeding, and premature discontinuation of anticoagulation therapy. Prior research has identified clinical and genetic factors that can alter warfarin dose requirements, but few randomized clinical trials have examined the utility of using clinical and genetic information to improve anticoagulation control or clinical outcomes among a large, diverse group of patients initiating warfarin. METHODS: The COAG trial is a multicenter, double-blind, randomized trial comparing 2 approaches to guiding warfarin therapy initiation: initiation of warfarin therapy based on algorithms using clinical information plus an individual's genotype using genes known to influence warfarin response ("genotype-guided dosing") versus only clinical information ("clinical-guided dosing") (www.clinicaltrials.gov Identifier: NCT00839657). RESULTS: The COAG trial design is described. The study hypothesis is that, among 1,022 enrolled patients, genotype-guided dosing relative to clinical-guided dosing during the initial dosing period will increase the percentage of time that patients spend in the therapeutic international normalized ratio range in the first 4 weeks of therapy. CONCLUSION: The COAG will determine if genetic information provides added benefit above and beyond clinical information alone.

Association between efavirenz-based compared with nevirapine-based antiretroviral regimens and virological failure in HIV-infected children.

IMPORTANCE: Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited. OBJECTIVE: To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of children (aged 3-16 years) who initiated efavirenz-based (n = 421) or nevirapine-based (n = 383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana. MAIN OUTCOMES AND MEASURES: The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis. RESULTS: With a median follow-up time of 69 months (range, 6-112 months; interquartile range, 23-87 months), 57 children (13.5%; 95% CI, 10.4%-17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%-31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%-4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%-7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4-2.7; log rank P < .001, favoring efavirenz). None of the measured covariates affected the estimated hazard ratio in the multivariable analyses. CONCLUSIONS AND RELEVANCE: Among children aged 3 to 16 years infected with HIV and treated at a clinic in Botswana, the use of efavirenz compared with nevirapine as initial antiretroviral treatment was associated with less virological failure. These findings may warrant additional research evaluating the use of efavirenz and nevirapine for pediatric patients.

The association of cerebral palsy with birth asphyxia: a definitional quagmire.

AIM: The aim of this study was to investigate whether current literature provides a useful body of evidence reflecting the proportion of cerebral palsy (CP) that is attributable to birth asphyxia. METHOD: We identified 23 studies conducted between 1986 and 2010 that provided data on intrapartum risks of CP. RESULTS: The proportion of CP with birth asphyxia as a precursor (case exposure rate) varied from less than 3% to over 50% in the 23 studies reviewed. The studies were heterogeneous in many regards, including the definitions for birth asphyxia and the outcome of CP. INTERPRETATIONS: Current data do not support the belief, widely held in the medical and legal communities, that birth asphyxia can be recognized reliably and specifically, or that much of CP is due to birth asphyxia. The very high case exposure rates linking birth asphyxia to CP can probably be attributed to several factors: the fact that the clinical picture at birth cannot specifically identify birth asphyxia; the definition of CP employed; and confusion of proximal effects - results - with causes. Further research is needed.