Linda M. Gerber

Implications of a New Definition of Vitamin D Deficiency in a Multiracial US Adolescent Population: The National Health and Nutrition Examination Survey III

OBJECTIVE. In children, vitamin D deficiency can interfere with bone mineralization, leading to rickets. In adults, it is linked to cardiovascular disease, insulin resistance, and hypertension. Accurate estimates of the prevalence of vitamin D deficiency are complicated by the lack of consensus as to optimal vitamin D status. Currently, individuals with serum 25-hydroxyvitamin D levels of <11 ng/mL are classified as vitamin D deficient. Experts collectively have proposed that minimum levels be at least 20 ng/mL. Our objectives were to (1) determine the national prevalence of vitamin D deficiency in adolescents by using both the current and recommended cutoffs and (2) examine the implications of the new recommendation after adjustment for various factors. METHODS. Data were obtained from National Health and Nutrition Examination Survey III, a cross-sectional survey administered to a nationally representative sample of noninstitutionalized civilians aged 2 months and older. Analyses were restricted to 2955 participants aged 12 to 19 with serum 25-hydroxyvitamin D levels. Relationships between serum 25-hydroxyvitamin D levels and sociodemographic variables were evaluated by using logistic regression. RESULTS. Changing the definition of vitamin D deficiency from <11 to <20 ng/mL increased the prevalence from 2% to 14%. After adjustment for all covariates, non-Hispanic black adolescents had 20 times the risk of serum 25-hydroxyvitamin D <20 ng/mL compared with non-Hispanic white adolescents. The risk of deficiency was more than double for females compared with males. An inverse relationship between weight and serum 25-hydroxyvitamin D levels was found. Overweight adolescents had increased risk of deficiency compared with normal-weight adolescents. CONCLUSIONS. There was a disproportionate burden of vitamin D deficiency in the non-Hispanic black adolescent population. Routine supplementation and monitoring of serum levels should be considered. Females and overweight adolescents are at increased risk. The consequences of chronic vitamin D deficiency in adolescents should be prospectively investigated.

Increased mortality in patients with severe traumatic brain injury treated without intracranial pressure monitoring

OBJECT Evidence-based guidelines recommend intracranial pressure (ICP) monitoring for patients with severe traumatic brain injury (TBI), but there is limited evidence that monitoring and treating intracranial hypertension reduces mortality. This study uses a large, prospectively collected database to examine the effect on 2-week mortality of ICP reduction therapies administered to patients with severe TBI treated either with or without an ICP monitor. METHODS From a population of 2134 patients with severe TBI (Glasgow Coma Scale [GCS] Score <9), 1446 patients were treated with ICP-lowering therapies. Of those, 1202 had an ICP monitor inserted and 244 were treated without monitoring. Patients were admitted to one of 20 Level I and two Level II trauma centers, part of a New York State quality improvement program administered by the Brain Trauma Foundation between 2000 and 2009. This database also contains information on known independent early prognostic indicators of mortality, including age, admission GCS score, pupillary status, CT scanning findings, and hypotension. RESULTS Age, initial GCS score, hypotension, and CT scan findings were associated with 2-week mortality. In addition, patients of all ages treated with an ICP monitor in place had lower mortality at 2 weeks (p = 0.02) than those treated without an ICP monitor, after adjusting for parameters that independently affect mortality. CONCLUSIONS In patients with severe TBI treated for intracranial hypertension, the use of an ICP monitor is associated with significantly lower mortality when compared with patients treated without an ICP monitor. Based on these findings, the authors conclude that ICP-directed therapy in patients with severe TBI should be guided by ICP monitoring.

Effect of early nutrition on deaths due to severe traumatic brain injury

OBJECT Traumatic brain injury (TBI) remains a serious public health crisis requiring continuous improvement in pre-hospital and inhospital care. This condition results in a hypermetabolic state that increases systemic and cerebral energy requirements, but achieving adequate nutrition to meet this demand has not been a priority in reducing death due to TBI. The effect of timing and quantity of nutrition on death within the first 2 weeks of injury was analyzed in a large prospective database of adult patients with severe TBI in New York State. METHODS The study is based on 797 patients with severe TBI (Glasgow Coma Scale [GCS] score < 9) treated at 22 trauma centers enrolled in a New York State quality improvement program between 2000 and 2006. The inhospital section of the prospectively collected database includes information on age, initial GCS score, weight and height, results of CT scanning, and daily parameters such as pupillary status, arterial hypotension, GCS score, and number of calories fed per day. RESULTS Patients who were not fed within 5 and 7 days after TBI had a 2- and 4-fold increased likelihood of death, respectively. The amount of nutrition in the first 5 days was related to death; every 10-kcal/kg decrease in caloric intake was associated with a 30-40% increase in mortality rates. This held up even after controlling for factors known to affect mortality, including arterial hypotension, age, pupillary status, initial GCS score, and CT scan findings. CONCLUSIONS Nutrition is a significant predictor of death due to TBI. Together with prevention of arterial hypotension, hypoxia, and intracranial hypertension it is one of the few therapeutic interventions that can directly affect TBI outcome.

Marked reduction in mortality in patients with severe traumatic brain injury.

OBJECT In spite of evidence that use of the Brain Trauma Foundation Guidelines for the Management of Severe Traumatic Brain Injury (Guidelines) would dramatically reduce morbidity and mortality, adherence to these Guidelines remains variable across trauma centers. The authors analyzed 2-week mortality due to severe traumatic brain injury (TBI) from 2001 through 2009 in New York State and examined the trends in adherence to the Guidelines. METHODS The authors calculated trends in adherence to the Guidelines and age-adjusted 2-week mortality rates between January 1, 2001, and December 31, 2009. Univariate and multivariate logistic regression analyses were performed to evaluate the effect of time period on case-fatality. Intracranial pressure (ICP) monitor insertion was modeled in a 2-level hierarchical model using generalized linear mixed effects to allow for clustering by different centers. RESULTS From 2001 to 2009, the case-fatality rate decreased from 22% to 13% (p < 0.0001), a change that remained significant after adjusting for factors that independently predict mortality (adjusted OR 0.52, 95% CI 0.39-0.70; p < 0.0001). Guidelines adherence increased, with the percentage of patients with ICP monitoring increasing from 56% to 75% (p < 0.0001). Adherence to cerebral perfusion pressure treatment thresholds increased from 15% to 48% (p < 0.0001). The proportion of patients having an ICP elevation greater than 25 mm Hg dropped from 42% to 29% (p = 0.0001). CONCLUSIONS There was a significant reduction in TBI mortality between 2001 and 2009 in New York State. Increase in Guidelines adherence occurred at the same time as the pronounced decrease in 2-week mortality and decreased rate of intracranial hypertension, suggesting a causal relationship between Guidelines adherence and improved outcomes. Our findings warrant future investigation to identify methods for increasing and sustaining adherence to evidence-based Guidelines recommendations.

Estimation of 24-hour sodium excretion from spot urine samples.

J Clin Hypertens (Greenwich). 2010;12:174–180. ©2010 Wiley Periodicals, Inc.

Association of C-Reactive Protein and Microalbuminuria (from the National Health and Nutrition Examination Surveys, 1999 to 2004)

Chronic kidney disease and cardiovascular disease share many risk factors. Injury to the vascular endothelium, measured by elevated levels of serum C-reactive protein (CRP), may play a role in kidney and cardiovascular disease. We therefore examined the association of CRP with microalbuminuria, a marker of early kidney injury. We conducted a cross-sectional analysis of a nationally representative, population-based survey. Weighted multiple logistic regression was used to study the association between CRP and microalbuminuria, adjusting for well-known risk factors. CRP was analyzed by a continuous variable and two categorized variables using quartiles and clinically recommended cutpoints. CRP concentration was positively associated with microalbuminuria. In the multivariate model, a one unit (in milligrams per liter) increase in CRP concentration was associated with a 2% increased odds of microalbuminuria (odds ratio 1.02, 95% confidence interval [CI] 1.01 to 1.02, p=0.0003). When CRP concentrations were stratified by clinically recommended cutpoints, compared with persons with CRP concentrations<1 mg/dl, persons with CRP concentrations between 1 and 3 mg/L and >3 mg/L were 1.15 times (95% CI 0.94 to 1.42) and 1.33 times (95% CI 1.08 to 1.65) more likely to have microalbuminuria, respectively. In subgroup analyses, the strength of association was comparable or stronger. In conclusion, elevated CRP levels were associated with microalbuminuria in a large, nationally representative data set. Vascular inflammation, as measured by CRP, may be a common contributor to early heart and kidney disease.

Hot flashes are associated with increased ambulatory systolic blood pressure.

Objective: To determine the association between ambulatory blood pressure (BP) and hot flash experience. Design: The participants in the study were 154 women (mean age = 46 years, range = 18-65 years), who were evaluated as part of a cross-sectional study on ethnicity, socioeconomic status, and diurnal BP patterns. Participants could be either normotensive or mildly hypertensive. Participants wore an ambulatory BP monitor for 24 hours and recorded their awake and sleep times. Hot flashes were assessed using an everyday complaint questionnaire that embeds symptoms associated with menopause into a list of everyday complaints. Results: Thirty-three percent of participants reported having had hot flashes during the 2 weeks before they completed the questionnaire. Compared with women who did not report hot flashes, mean awake and sleep systolic BP values were significantly higher (P < 0.004 and P = 0.007, respectively) in women who reported having had hot flashes. Hot flashes continued to independently predict average awake and sleep systolic BP (both P = 0.03) after controlling for age, race/ethnicity, body mass index, and menopausal status. Hot flashes were not associated with diastolic BP or nocturnal dipping of BP. Conclusions: Hot flashes are associated with increased awake and sleep systolic BP independent of menopausal status. Further investigation is warranted to elucidate the mechanisms by which hot flashes are associated with BP.

Response to intracranial hypertension treatment as a predictor of death in patients with severe traumatic brain injury.

OBJECT The normalization of increased intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI) is assumed to limit secondary brain injury and improve outcome. Despite evidence-based recommendations for monitoring and treatment of elevated ICP, there are few studies that show an association between response to ICP-directed therapeutic regimens and adjusted mortality rate. This study utilizes a large prospective database to examine the effect of response to ICP-lowering therapy on risk of death within the first 2 weeks of injury in patients who sustained TBI and are older than 16 years. METHODS The current study is based on 1426 patients with severe TBI (Glasgow Coma Scale [GCS] score < 9) of whom 388 were treated for elevated ICP (> 25 mm Hg) between 2000 and 2008 at 22 trauma centers enrolled in a New York State quality improvement program. This prospectively collected database also contains information including age, admission GCS score, pupillary status, CT scanning parameters, and hypotension, which are all known early prognostic indicators of death. Treatment of elevated ICP consisted of administration of mannitol, hypertonic saline, barbiturates, and/or drainage of CSF or decompressive craniectomy. The factors predicting ICP response to treatment and predicting death at 2 weeks were evaluated using logistic regression analyses. RESULTS Increasing age and fewer hours of elevated ICP on Day 1 were found to be significant predictors (p = 0.001 and 0.0003, respectively) of a positive response to treatment. Response to ICP-lowering therapy (p = 0.03), younger age (p < 0.0001), fewer hours of elevated ICP (p < 0.0001), and absence of arterial hypotension on Day 1 (p = 0.001) significantly predicted reduced risk of death. CONCLUSIONS Patients who responded to ICP-lowering treatment had a 64% lower risk of death at 2 weeks than those who did not respond after adjusting for factors that independently predict risk of death.

Predicting 14-Day Mortality after Severe Traumatic Brain Injury: Application of the IMPACT Models in the Brain Trauma Foundation TBI-trac® New York State Database

Prognostic models for outcome prediction in patients with traumatic brain injury (TBI) are important instruments in both clinical practice and research. To remain current a continuous process of model validation is necessary. We aimed to investigate the performance of the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic models in predicting mortality in a contemporary New York State TBI registry developed and maintained by the Brain Trauma Foundation. The Brain Trauma Foundation (BTF) TBI-trac® database contains data on 3125 patients who sustained severe TBI (Glasgow Coma Scale [GCS] score ≤ 8) in New York State between 2000 and 2009. The outcome measure was 14-day mortality. To predict 14-day mortality with admission data, we adapted the IMPACT Core and Extended models. Performance of the models was assessed by determining calibration (agreement between observed and predicted outcomes), and discrimination (separation of those patients who die from those who survive). Calibration was explored graphically with calibration plots. Discrimination was expressed by the area under the receiver operating characteristic (ROC) curve (AUC). A total of 2513 out of 3125 patients in the BTF database met the inclusion criteria. The 14-day mortality rate was 23%. The models showed excellent calibration. Mean predicted probabilities were 20% for the Core model and 24% for the Extended model. Both models showed good discrimination with AUCs of 0.79 (Core) and 0.83 (Extended). We conclude that the IMPACT models validly predict 14-day mortality in the BTF database, confirming generalizability of these models for outcome prediction in TBI patients.

Pediatric delirium and associated risk factors: a single-center prospective observational study.

Objective: To describe a single-institution pilot study regarding prevalence and risk factors for delirium in critically ill children. Design: A prospective observational study, with secondary analysis of data collected during the validation of a pediatric delirium screening tool, the Cornell Assessment of Pediatric Delirium. Setting: This study took place in the PICU at an urban academic medical center. Patients: Ninety-nine consecutive patients, ages newborn to 21 years. Intervention: Subjects underwent a psychiatric evaluation for delirium based on the Diagnostic and Statistical Manual IV criteria. Measurements and Main Results: Prevalence of delirium in this sample was 21%. In multivariate analysis, risk factors associated with the diagnosis of delirium were presence of developmental delay, need for mechanical ventilation, and age 2–5 years. Conclusions: In our institution, pediatric delirium is a prevalent problem, with identifiable risk factors. Further large-scale prospective studies are required to explore multi-institutional prevalence, modifiable risk factors, therapeutic interventions, and effect on long-term outcomes.