Steven J. Verhulst

Outcome studies of low birth weight infants published in the last decade: A metaanalysis

We conducted a metaanalysis and methods review of 80 studies, published in the last decade, that explored the outcome of low birth weight infants; 27% involved infants whose birth weights were less than or equal to 2500 gm (low birth weight), 44% less than or equal to 1500 gm (very low birth weight), and 29% less than or equal to 1000 gm (extremely low birth weight). Problems found in these studies were grouped into three categories: subject and methods issues, environmental factors, and outcome measurement. The combined average intelligence quotient/developmental quotient (IQ/DQ) of all low birth weight groups was 97.77 (SD 6.19); for control subjects the mean IQ/DQ was 103.78 (SD 8.16). This difference was statistically significant but perhaps not clinically significant. No differences in mean IQ/DQ scores were found among the low birth weight, very low birth weight, and extremely low birth weight subgroups. Statistically significant differences among all groups and control subjects were found when categoric data were analyzed, as were differences among the three subgroups; however, the variety of outcome criteria makes interpretation of the categoric analyses difficult.

Prevention of noise- and drug-induced hearing loss with d-methionine ☆

A number of otoprotective agents are currently being investigated. Various types of agents have been found in animal studies to protect against hearing loss induced by cisplatin, carboplatin, aminoglycosides, or noise exposure. For over a decade we have been investigating D-methionine (D-met) as an otoprotective agent. Studies in our laboratory and others around the world have documented D-mets otoprotective action, in a variety of species, against a variety of ototoxic insults including cisplatin-, carboplatin-, aminoglycoside- and noise-induced auditory threshold elevations and cochlear hair cell loss. For cisplatin-induced ototoxicity, protection of the stria vascularis has also been documented. Further D-met has an excellent safety profile. D-met may act as both a direct and indirect antioxidant. In this report, we provide the results of three experiments, expanding findings in D-met protection in three of our translational research areas: protection from platinum based chemotherapy-, aminoglycoside- and noise-induced hearing loss. These experiments demonstrate oral D-met protection against cisplatin-induced ototoxicity, D-met protection against amikacin-induced ototoxicity, and D-met rescue from permanent noise-induced hearing loss when D-met is initiated 1h after noise exposure. These studies demonstrate some of the animal experiments needed as steps to translate a protective agent from bench to bedside.

CSF B-Cell Expansion in Opsoclonus-Myoclonus Syndrome: A Biomarker of Disease Activity

Lack of a biomarker of disease activity has hindered the therapy of childhood opsoclonus‐myoclonus syndrome (OMS), which is purported to be mediated humorally. To determine if the cerebrospinal fluid (CSF) B lymphocyte, which may traffic into the central nervous system (CNS) to produce antibody locally, is one such biomarker, B lymphocytes were immunophenotyped in the CSF and blood of 56 children with OMS and 26 pediatric controls by dual‐laser flow cytometry. Neurological severity was rated blindly from videotapes using a validated 12‐item motor evaluation scale. Children with OMS manifested a 4‐ to 7‐fold higher percentage of total B‐cells in CSF (P < 0.0001), including CD5+ (P = 0.001) and CD5− (P = 0.0004) B‐cell subsets, compared with controls, in whom the percentages were negligible and unchanging with age. CSF expansion of both B‐cell subsets increased with disease severity and decreased with disease duration (P ≤ 0.0001, ANOVA). Previous treatment with conventional immunotherapies, chemotherapy, or tumor resection had not normalized B‐cell percentages in those with lingering symptoms. These studies reveal that CSF B‐cell expansion in OMS is characteristic and often persistent. Presence of the autoreactive CD5+ B‐cell subset and correlations with neurological severity and disease duration suggest CSF B‐cell expansion is a biomarker of disease activity and possible target for B‐cell–specific therapy. Immunophenotyping of CSF lymphocytes by flow cytometry yields valuable clinical information missed by routine studies and allows crucial treatment decisions to be made rapidly.

Decreased Mortality Associated With Prompt Gram Staining of Blood Cultures

Gram stains of positive blood cultures are the most important factor influencing appropriate therapy. The sooner appropriate therapy is initiated, the better. Therefore, it is reasonable to expect that the sooner Gram stains are performed, the better. To determine the value of timely Gram stains and whether improvement in Gram stain turnaround time (TAT) is feasible, we compared data for matched pairs of patients with cultures processed promptly (<1 hour TAT) with data for patients with cultures not processed promptly (> or =1 hour TAT) and then monitored TAT by control charting.In 99 matched pairs, average difference in time to detection of positive blood cultures within a pair of patients was less than 0.1 hour. For the less than 1 hour TAT group, the average TAT and crude mortality were 0.1 hour and 10.1%, respectively; for the 1 hour or longer TAT group, they were 3.3 hours and 19.2%, respectively (P < .0001 and P = .0389, respectively). After multifaceted efforts, we achieved significant improvement in the TAT for Gram stains.

Direct, standardized assessment of clinical competence

Summary. Doctor ratings of clerkship performance are often discounted as not accurately reflecting clinical competence. Such ratings are influenced by the following uncontrolled variables: case difficulty; differing rater focus and standards; lack of agreement on what constitutes acceptable performance; and collective patient care responsibility masks individual contributions. Standardized direct measures of clinical competence were developed to control these factors and allow direct comparisons of student performance. Students saw 18 patients representing frequently occurring and important patient problems. Student actions and decisions were recorded and subsequent responses to questions revealed knowledge of pathophysiology, basis for actions, use and interpretation of laboratory investigations, and management. Actions and responses were graded using a pre‐set key. The examination covered 73% of designated clinical competencies. Examination scores corresponded with independent measures of clinical competence. Reliability studies indicated that new cases can be substituted in subsequent years with confidence that scores will maintain similar meaning. Costs are £6.95 per student per case, which is modest considering the quality and quantity of information acquired. Methods described are practical for evaluation of clerks and residents and for licensing and specialty certification examinations.

A Longitudinal Study of Students' Perceptions of Using Deep Breathing Meditation to Reduce Testing Stresses

Background: Stress can impact student performance. Yet few medical schools provide students with a consistent opportunity to develop and regularly practice stress-reduction techniques to aid them academically. Description: A curriculum component designed to assist 64 postbaccalaureate minority students in developing and practicing a stress-management technique was implemented on a regular basis from June 2004 to April 2006. Students participated in Deep Breathing Meditation exercises in two classes and completed pre-, post-, and follow-up surveys each academic year. Evaluation: Students reported having perceptions of decreased test anxiety, nervousness, self-doubt, and concentration loss, using the technique outside of the two classes, and believing it helped them academically and would help them as a physician. Conclusions: The Deep Breathing Meditation technique was successfully implemented each academic year, and it provided students with a promising solution for meeting challenging academic and professional situations.

Effects of a Physical Activity Behavior Change Intervention on Inflammation and Related Health Outcomes in Breast Cancer Survivors Pilot Randomized Trial

Background. The goal of this pilot study was to determine the magnitude and direction of intervention effect sizes for inflammatory-related serum markers and relevant health outcomes among breast cancer survivors (BCSs) receiving a physical activity behavior change intervention compared with usual care. Methods. This randomized controlled trial enrolled 28 stage I, II, or IIIA BCSs who were post–primary treatment and not regular exercisers. Participants were assigned to either a 3-month physical activity behavior change intervention group (ING) or usual care group (UCG). Intervention included supervised aerobic (150 weekly minutes, moderate-intensity) and resistance (2 sessions per week) exercise that gradually shifted to home-based exercise. Outcomes were assessed at baseline and 3 months. Results. Cardiorespiratory fitness significantly improved in the ING versus the UCG (between-group difference = 3.8 mL/kg/min; d = 1.1; P = .015). Self-reported sleep latency was significantly reduced in the ING versus the UCG (between group difference = −0.5; d = −1.2; P = .02) as was serum leptin (between-group difference = −9.0 ng/mL; d = −1.0; P = .031). Small to medium nonsignificant negative effect sizes were noted for interleukin (IL)-10 and tumor necrosis factor (TNF)-α and ratios of IL-6 to IL-10, IL-8 to IL-10, and TNF-α to IL-10, whereas nonsignificant positive effect sizes were noted for IL-6 and high-molecular-weight adiponectin. Conclusions. Physical activity behavior change interventions in BCSs can achieve large effect size changes for several health outcomes. Although effect sizes for inflammatory markers were often small and not significant, changes were in the hypothesized direction for all except IL-6 and IL-10.

Safety, efficacy, and tolerability of early initiation of noninvasive positive pressure ventilation in pediatric patients admitted with status asthmaticus: A pilot study*

Objectives: Although noninvasive positive pressure ventilation is increasingly used for respiratory distress, there is not much data supporting its use in children with status asthmaticus. The objective of this study was to determine safety, tolerability, and efficacy of early initiation of noninvasive positive pressure ventilation in addition to standard of care in the management of children admitted with status asthmaticus. Study Design: A prospective, randomized, controlled, clinical trial. Patients: Twenty patients (1–18 yrs old) admitted to the pediatric intensive care unit with status asthmaticus. Methods and Main Results: Children were randomized to receive either noninvasive positive pressure ventilation plus standard of care (noninvasive positive pressure ventilation group) or standard of care alone (standard group). Improvement in clinical asthma score was significantly greater in noninvasive positive pressure ventilation group compared to standard group at 2 hrs, 4–8 hrs, 12–16 hrs, and 24 hrs after initiation of interventions (p < .01). A significant decrease in respiratory rate at ≥24 hrs oxygen requirement after 2 hrs was noted in noninvasive positive pressure ventilation group as compared to standard group (p = .01 and p = .03, respectively). Although statistically not significant, fewer children in the noninvasive positive pressure ventilation group required adjunct therapy compared to standard group (11% vs. 50%; p = .07). There were no major adverse events related to noninvasive positive pressure ventilation. Nine out of ten patients tolerated noninvasive positive pressure ventilation through the duration of the study; noninvasive positive pressure ventilation had to be discontinued in one patient because of persistent cough. Conclusions: Early initiation of noninvasive positive pressure ventilation, along with short acting &bgr;-agonists and systemic steroids, can be safe, well-tolerated, and effective in the management of children with status asthmaticus.

Reliability of performance on standardized patient cases: A comparison of consistency measures based on generalizability theory

Standardized patient cases have assumed an important role in the assessment of clinical competence in recent years. The reliability (consistency) of performance across standardized patient cases has been determined with consistency measures derived from generalizability theory—namely, the generalizability coefficient, Ep2; the dependability index, ; and the dependability index with cutoff, ϕ(C). These three consistency measures can be computed for quantitatively scored cases and for dichotomously scored cases; hence, six consistency measures could be computed for a given examination. Our purpose was to draw attention to the sizable differences among the computed values of these consistency measures for a new set of clinical competence examination data and to provide a review of the interpretations of the different measures. The findings showed considerable differences among the consistency measures, the number of cases needed to achieve the 0.80 reliability level, and the time required to administer th...

Predictive utility of the Bayley Infant Neurodevelopmental Screener (BINS) risk status classifications: clinical interpretation and application

Predictive validity and clinical implications of the increasingly popular Bayley Infant Neurodevelopmental Screener (BINS) risk status classifications have not been previously reported. In this longitudinal follow‐up study, the BINS was administered to high‐risk infants at 6, 12, and 24 months of age, and the McCarthy Scales at 3 years of age. Ninety‐two children were evaluated at 6 and 36 months, 105 at 12 and 36 months, and 118 at 24 and 36 months; 190, 125, and 140 infants were included in the comparisons at 6 to 12, 6 to 24, and 12 to 24 months. BINS risk status was classified as low, moderate, or high; or as a binary variable, LOWRISK/HIGHRISK. The three BINS items groups were moderately correlated. Consistency was most variable in the moderate‐risk group. BINS risk was predictive of 36‐month function in 18 out of 18 comparisons. Odds ratios, ranging from 2.76 to 54.70, were significant in 15 out of 18 logistic models. An early high‐risk classification was associated with increased probability of later developmental morbidity. The BINS offers an alternative to detailed assessment in high‐volume clinical applications and has good concurrent and predictive validity.