Socioeconomic and Demographic Factors Effect in Association with Driver's Medical Services after Crashes.

Motor vehicle crashes are the third leading cause of preventable-injury deaths in the United States. Previous research has found links between the socioeconomic characteristics of driver residence zip codes and crash frequencies. The objective of the study is to extend earlier work by investigating whether the socioeconomic characteristics of a driver's residence zip code influence their likelihood of resulting in post-crash medical services. Data were drawn from General Use Model (GUM) data for police crash reports linked to hospital records in Kentucky, Utah, and Ohio. Zip-code-level socioeconomic data from the American Community Survey were also incorporated into analyses. Logistic regression models were developed for each state and showed that the socioeconomic variables such as educational attainment, median housing value, gender, and age have p-values < 0.001 when tested against the odds of seeking post-crash medical services. Models for Kentucky and Utah also include the employment-to-population ratio. The results show that in addition to age and gender, educational attainment, median housing value and rurality percentage at the zip code level are associated with the likelihood of a driver seeking follow-up medical services after a crash. It is concluded that drivers from areas with lower household income and lower educational attainment are more likely to seek post-crash medical services, primarily in emergency departments. Female drivers are also more likely to seek post-crash medical services.

Long-term trajectory of kidney function in autosomal-dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst and kidney growth, which is hypothesized to cause loss of functioning renal mass and eventually end-stage kidney disease. However, the time course of decline in glomerular filtration rate (GFR) is poorly defined. The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease study is a 14-year observational cohort study of 241 adults with ADPKD. As an estimate of the rate of kidney growth, participants were stratified into 5 subclasses based on baseline age and magnetic resonance imaging measurements of total kidney volume (TKV) according to the method of Irazabal. GFR trajectories spanning over four decades of life were reconstructed and fitted using mixed polynomial models, which were validated using data from the HALT-PKD study. GFR trajectories were nonlinear, with a period of relative stability in most participants, followed by accelerating decline. The shape and slope of these trajectories were strongly associated with baseline Irazabal class. Patients with PKD1 mutations had a steeper GFR decline than patients with PKD2 mutations or with no detected mutation, largely mediated by the effect of genotype on Irazabal class. Thus, GFR decline in ADPKD is nonlinear, and its trajectory throughout adulthood can be predicted from a single measurement of kidney volume. These models can be used for clinical prognostication, clinical trial design, and patient selection for clinical interventions. Our findings support a causal link between growth in kidney volume and GFR decline, adding support for the use of TKV as a surrogate endpoint in clinical trials.

Characteristics of Single Vehicle Crashes with a Teen Driver in South Carolina, 2005-2008.

OBJECTIVE: Teens' crash risk is highest in the first years of independent driving. Circumstances surrounding fatal crashes have been widely documented, but less is known about factors related to nonfatal teen driver crashes. This study describes single vehicle nonfatal crashes involving the youngest teen drivers (15-17 years), compares these crashes to single vehicle nonfatal crashes among adult drivers (35-44 years) and examines factors related to nonfatal injury producing crashes for teen drivers. METHODS: Police crash data linked to hospital inpatient and emergency department data for 2005-2008 from the South Carolina Crash Outcomes Data Evaluation System (CODES) were analyzed. Nonfatal, single vehicle crashes involving passenger vehicles occurring on public roadways for teen (15-17 years) drivers were compared with those for adult (35-44 years) drivers on temporal patterns and crash risk factors per licensed driver and per vehicle miles traveled. Vehicle miles traveled by age group was estimated using data from the 2009 National Household Travel Survey. Multivariable log-linear regression analysis was conducted for teen driver crashes to determine which characteristics were related to crashes resulting in a minor/moderate injury or serious injury to at least one vehicle occupant. RESULTS: Compared with adult drivers, teen drivers in South Carolina had 2.5 times the single vehicle nonfatal crash rate per licensed driver and 11 times the rate per vehicle mile traveled. Teen drivers were nearly twice as likely to be speeding at the time of the crash compared with adult drivers. Teen driver crashes per licensed driver were highest during the afternoon hours of 3:00-5:59 pm and crashes per mile driven were highest during the nighttime hours of 9:00-11:59 pm. In 66% of the teen driver crashes, the driver was the only occupant. Crashes were twice as likely to result in serious injury when teen passengers were present than when the teen driver was alone. When teen drivers crashed while transporting teen passengers, the passengers were >5 times more likely to all be restrained if the teen driver was restrained. Crashes in which the teen driver was unrestrained were 80% more likely to result in minor/moderate injury and 6 times more likely to result in serious injury compared with crashes in which the teen driver was restrained. CONCLUSIONS: Despite the reductions in teen driver crashes associated with Graduated Driver Licensing (GDL), South Carolina's teen driver crash rates remain substantially higher than those for adult drivers. Established risk factors for fatal teen driver crashes, including restraint nonuse, transporting teen passengers, and speeding also increase the risk of nonfatal injury in single vehicle crashes. As South Carolina examines strategies to further reduce teen driver crashes and associated injuries, the state could consider updating its GDL passenger restriction to either none or one passenger <21years and dropping the passenger restriction exemption for trips to and from school. Surveillance systems such as CODES that link crash data with health outcome data provide needed information to more fully understand the circumstances and consequences of teen driver nonfatal crashes and evaluate the effectiveness of strategies to improve teen driver safety.

Determining the longitudinal validity and meaningful differences in HRQL of the PedsQL™ Sickle Cell Disease Module.

BACKGROUND: Detecting change in health status over time and ascertaining meaningful changes are critical elements when using health-related quality of life (HRQL) instruments to measure patient-centered outcomes. The PedsQL™ Sickle Cell Disease module, a disease specific HRQL instrument, has previously been shown to be valid and reliable. Our objectives were to determine the longitudinal validity of the PedsQL™ Sickle Cell Disease module and the change in HRQL that is meaningful to patients. METHODS: An ancillary study was conducted utilizing a multi-center prospective trial design. Children ages 4-21 years with sickle cell disease admitted to the hospital for an acute painful vaso-oclusive crisis were eligible. Children completed HRQL assessments at three time points (in the Emergency Department, one week post-discharge, and at return to baseline (One to three months post-discharge). The primary outcome was change in HRQL score. Both distribution (effect size, standard error of measurement (SEM)) and anchor (global change assessment) based methods were used to determine the longitudinal validity and meaningful change in HRQL. Changes in HRQL meaningful to patients were identified by anchoring the change scores to the patient's perception of global improvement in pain. RESULTS: Moderate effect sizes (0.20-0.80) were determined for all domains except the Communication I and Cognitive Fatigue domains. The value of 1 SEM varied from 3.8-14.6 across all domains. Over 50% of patients improved by at least 1 SEM in Total HRQL score. A HRQL change score of 7-10 in the pain domains represented minimal perceived improvement in HRQL and a HRQL change score of 18 or greater represented moderate to large improvement. CONCLUSIONS: The PedsQL™ Sickle Cell Disease Module is responsive to changes in HRQL in patients experiencing acute painful vaso-occlusive crises. The study data establish longitudinal validity and meaningful change parameters for the PedsQL™ Sickle Cell Disease Module. TRIAL REGISTRATION: ClinicalTrials.gov (study identifier: NCT01197417 ). Date of registration: 08/30/2010.

Comparison of Clinician Suspicion Versus a Clinical Prediction Rule in Identifying Children at Risk for Intra-abdominal Injuries After Blunt Torso Trauma.

OBJECTIVES: Emergency department (ED) identification and radiographic evaluation of children with intra-abdominal injuries who need acute intervention can be challenging. To date, it is unclear if a clinical prediction rule is superior to unstructured clinician judgment in identifying these children. The objective of this study was to compare the test characteristics of clinician suspicion with a derived clinical prediction rule to identify children at risk of intra-abdominal injuries undergoing acute intervention following blunt torso trauma. METHODS: This was a planned subanalysis of a prospective, multicenter observational study of children (<18 years old) with blunt torso trauma conducted in 20 EDs in the Pediatric Emergency Care Applied Research Network (PECARN). Clinicians documented their suspicion for the presence of intra-abdominal injuries needing acute intervention as <1, 1 to 5, 6 to 10, 11 to 50, or >50% prior to knowledge of abdominal computed tomography (CT) scanning (if performed). Intra-abdominal injuries undergoing acute intervention were defined by a therapeutic laparotomy, angiographic embolization, blood transfusion for abdominal hemorrhage, or intravenous fluid administration for 2 or more days in those with pancreatic or gastrointestinal injuries. Patients were considered to be positive for clinician suspicion if suspicion was documented as ≥1%. Suspicion ≥ 1% was compared to the presence of any variable in the prediction rule for identifying children with intra-abdominal injuries undergoing acute intervention. RESULTS: Clinicians recorded their suspicion in 11,919 (99%) of 12,044 patients enrolled in the parent study. Intra-abdominal injuries undergoing acute intervention were diagnosed in 203 (2%) patients. Abdominal CT scans were obtained in the ED in 2,302 of the 2,667 (86%, 95% confidence interval [CI] = 85% to 88%) enrolled patients with clinician suspicion ≥1% and in 3,016 of the 9,252 (33%, 95% CI = 32% to 34%) patients with clinician suspicion < 1%. Sensitivity of the prediction rule for intra-abdominal injuries undergoing acute intervention (197 of 203; 97.0%, 95% CI = 93.7% to 98.9%) was higher than that of clinician suspicion ≥1% (168 of 203; 82.8%, 95% CI = 76.9% to 87.7%; difference = 14.2%, 95% CI = 8.6% to 20.0%). Specificity of the prediction rule (4,979 of the 11,716; 42.5%, 95% CI = 41.6% to 43.4%), however, was lower than that of clinician suspicion (9,217 of the 11,716, 78.7%, 95% CI = 77.9% to 79.4%; difference = -36.2%, 95% CI = -37.3% to -35.0%). Thirty-five (0.4%, 95% CI = 0.3% to 0.5%) patients with clinician suspicion < 1% had intra-abdominal injuries that underwent acute intervention. CONCLUSIONS: The derived clinical prediction rule had a significantly higher sensitivity, but lower specificity, than clinician suspicion for identifying children with intra-abdominal injuries undergoing acute intervention. The higher specificity of clinician suspicion, however, did not translate into clinical practice, as clinicians frequently obtained abdominal CT scans in patients they considered very low risk. If validated, this prediction rule can assist in clinical decision-making around abdominal CT use in children with blunt torso trauma.

Detected renal cysts are tips of the iceberg in adults with ADPKD.

BACKGROUND AND OBJECTIVES: In autosomal dominant polycystic kidney disease, progressive renal enlargement secondary to expanding cysts is a hallmark. The total cyst load and range of cyst diameters are unknown. The purpose of this study was to quantify the total number and range of diameters of individual cysts in adults with preserved GFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective, morphometric analysis of renal cyst number and diameter using magnetic resonance images from eight adult autosomal dominant polycystic kidney disease patients was performed at baseline and after 6.9 years. Cyst number and diameter were measured in microscopic sections of nephrectomy specimens from five different adults. RESULTS: The diameters of 1010 cysts ranged from 0.9 to 77.1 mm in baseline T2 magnetic resonance images, and the mean total number of cysts increased from 682 to 1002 in 6.9 years. However, magnetic resonance imaging detects only cysts above the lower limit of detection. In 405 cysts measured in nephrectomy specimens, 70% had diameters <0.9 mm. Cyst counts by magnetic resonance in eight subjects compared with histology revealed approximately 62 times more cysts below the limit of magnetic resonance imaging detection than above it. CONCLUSIONS: This study presents quantitative data indicating that renal cysts develop in a minority of renal tubules. Increased numbers detected by magnetic resonance imaging are caused primarily by cysts below detection at baseline enlarging to a detectable diameter over time. The broad range of diameters, with a heavy concentration of microscopic cysts, may be most appropriately explained by a formation process that operates continuously throughout life.

Anti-PD-1 synergizes with cyclophosphamide to induce potent anti-tumor vaccine effects through novel mechanisms.

Programmed death-1 receptor (PD-1) is expressed on T cells following TCR activation. Binding of this receptor to its cognate ligands, programmed death ligand (PDL)-1 and PDL-2, down-regulates signals by the TCR, promoting T-cell anergy and apoptosis, thus leading to immune suppression. Here, we find that using an anti-PD-1 antibody (CT-011) with Treg-cell depletion by low-dose cyclophosphamide (CPM), combined with a tumor vaccine, induces synergistic antigen-specific immune responses and reveals novel activities of each agent in this combination. This strategy led to complete regression of established tumors in a significant percentage of treated animals, with survival prolongation. We show for the first time that combining CT-011 and CPM significantly increases the number of vaccine-induced tumor-infiltrating CD8(+) T cells, with simultaneous decrease in infiltrating Treg cells. Interestingly, we find that CT-011 prolongs Treg-cell inhibition induced by CPM, leading to a sustainable significant synergistic decrease of splenic and tumor-infiltrated Treg cells. Surprisingly, we find that the anti-tumor effect elicited by the combination of CT-011 and CPM is dependent on both CD8(+) and CD4(+) T-cell responses, although the antigen we used is a class I MHC-restricted peptide. Thus, we describe a novel and effective therapeutic approach by combining multiple strategies to target several tumor-mediated immune inhibitory mechanisms.

My journey in dental ethics.

My ethics journal passed through these phases: personal inspiration by those I admire in the profession, struggle to incorporate their ideals in daily practice, working with like-minded colleagues, and formal education and exposure to broader and diverse interests. Now it is time to help others with their journeys.

Evidence of extraordinary growth in the progressive enlargement of renal cysts.

BACKGROUND AND OBJECTIVES: In autosomal dominant polycystic kidney disease, cysts derived from tubules are detected at birth by ultrasound (threshold for detection >7.0 mm); thus, fetal cyst growth rates must exceed 2300%/yr. In adults, the combined renal cyst component enlarges at approximately 12%/yr by growth of individual cysts. To explore this discrepancy, the growth rates of individual cysts were determined in adult polycystic kidneys. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Diameter, volume, and growth rates of individual cysts were measured by magnetic resonance in 30 individual cysts in three adult patients over a span of 3 years. Results were confirmed in 22 cysts measured in five patients by computed tomography over a span of 11 years. RESULTS: Mean cyst diameters were 20.4 +/- 9.9 mm (range 7.1 to 40.5 mm) at baseline and 25.8 +/- 15.6 mm (range 7.8 to 49.6 mm) after 3 years. Mean cyst volumes, determined by manual segmentation and summation of magnetic resonance cross sections, were 8.7 +/- 12.9 cm(3) (0.3 to 43.3 cm(3)) and 24.2 +/- 66.3 cm(3) (0.3 to 364.8 cm(3)) after 3 years. Mean cyst growth rates ranged from 6.9 to 23.9%/yr; the maximum growth rate was 71.1%/yr, far less than required to develop a 7-mm diameter cyst in utero. Results were similar in 22 cysts examined by computed tomography. CONCLUSIONS: It was concluded that renal cysts detected by ultrasound in newborns must have grown at exuberant rates in utero; thereafter, expansion appears to proceed at much slower rates.

Using probabilistic linkage of multiple databases to describe burn injuries in Utah.

More than 1 million burn injuries occur in the United States each year and as many as half of these injuries require medical treatment. Most data used to describe burns are from national databases derived from random or purposive samples of injuries. Few studies describe burn rates within a state. Comprehensive descriptions of burns are warranted so as to develop and monitor tailored prevention programs and to educate health care providers. The purpose of this study was to identify and describe all burns requiring acute medical care in Utah to define burn prevention and care issues within the state. Probabilistic linkage of five databases was performed. Probabilistic linkage identified all burn injuries occurring in Utah during a 5-year period that were treated by EMS, admitted to an emergency department or hospital/burn center, or resulted in death. During the 5-year study period, 24,934 burns were identified. More men than women were injured (61% compared with 39%, respectively). One third of burns occurred to individuals aged younger than 18 years and 3% occurred to the elderly (>65 years). The majority of injuries were treated in the emergency department. Scald burns were the most common etiology. The mortality rate was 0.4%. The results of this study and future studies using this methodology may be used to identify populations at increased risk for burns and to target burn prevention and outreach medical education more appropriately.

A model-based time-reversal of left ventricular motion improves cardiac motion analysis using tagged MRI data.

BACKGROUND: Myocardial motion is an important observable for the assessment of heart condition. Accurate estimates of ventricular (LV) wall motion are required for quantifying myocardial deformation and assessing local tissue function and viability. Harmonic Phase (HARP) analysis was developed for measuring regional LV motion using tagged magnetic resonance imaging (tMRI) data. With current computer-aided postprocessing tools including HARP analysis, large motions experienced by myocardial tissue are, however, often intractable to measure. This paper addresses this issue and provides a solution to make such measurements possible. METHODS: To improve the estimation performance of large cardiac motions while analyzing tMRI data sets, we propose a two-step solution. The first step involves constructing a model to describe average systolic motion of the LV wall within a subject group. The second step involves time-reversal of the model applied as a spatial coordinate transformation to digitally relax the contracted LV wall in the experimental data of a single subject to the beginning of systole. Cardiac tMRI scans were performed on four healthy rats and used for developing the forward LV model. Algorithms were implemented for preprocessing the tMRI data, optimizing the model parameters and performing the HARP analysis. Slices from the midventricular level were then analyzed for all systolic phases. RESULTS: The time-reversal operation derived from the LV model accounted for the bulk portion of the myocardial motion, which was the average motion experienced within the overall subject population. In analyzing the individual tMRI data sets, removing this average with the time-reversal operation left small magnitude residual motion unique to the case. This remaining residual portion of the motion was estimated robustly using the HARP analysis. CONCLUSION: Utilizing a combination of the forward LV model and its time reversal improves the performance of motion estimation in evaluating the cardiac function.

Inhaled nitric oxide in the treatment of persistent pulmonary hypertension/ hypoxic respiratory failure in neonates: an update.

Persistent pulmonary hypertension (PPHN) and subsequent hypoxic respiratory failure is seen in association with numerous diseases and conditions in the neonate. This includes infections such as group B streptococcus, meconium aspiration syndrome, perinatal asphyxia, congenital diaphragmatic hernia, congenital heart disease, and as an idiopathic phenomenon. Conventional therapy of persistent pulmonary hypertension is discussed, as well as integrated with current treatment modalities such as surfactant replacement therapy and high frequency ventilation. The molecular action of nitric oxide including its relationship to neonatal cardiopulmonary transition at birth and the human neonatal clinical experience with term infants from 1992 to the present is explored. Also, the current use of inhaled nitric oxide in preterm infants is reviewed. Additionally, the follow-up of infants treated with inhaled nitric oxide is summarized, and novel therapies including inhaled prostacyclin and other pulmonary vasodilators such as sildenafil are introduced.

Current management of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a medical conundrum that challenges the physicians who care for these patients. Despite early prenatal diagnosis and optimal medical management, the results are disappointing. This lack of consistent success leaves the clinician frustrated. We present the current status of fetal surgery and novel approaches to ventilation as well as other unusual therapeutic approaches. Two cases are presented and a summary of our 11-year experience with CDH is reviewed. We conclude with complications and long-term outcomes.

Update on extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) consists of the application of intermediate-term cardiopulmonary bypass for the treatment of potentially reversible heart and/or lung failure in the neonate, child, and adult. Applications in the neonate include congenital diaphragmatic hernia, pulmonary hypertension, meconium aspiration syndrome, and pre- and post-operative congenital heart surgery support. In the older child, myocarditis, infections, and respiratory failure (RSV and ARDS) are the most frequent indications, in addition to peri-operative cardiac surgical support. A review of the institutional experiences at the University of Louisville spanning a 15-year period and comparison international data will be presented, along with a pertinent review of the literature. Technical considerations, complications, and long-term outcomes will be reviewed, and the potential interface between ECMO and other, less invasive technologies, i.e., high-frequency ventilation, replacement surfactant, and nitric oxide, will be discussed.

Status report: inhaled nitric oxide in persistent pulmonary hypertension/hypoxic respiratory failure of neonate.

Persistent pulmonary hypertension is seen in association with a number of diseases and conditions in the newborn including perinatal asphyxia, meconium aspiration syndrome, Group B strep sepsis, and certain surgical conditions such as congenital diaphragmatic hernia. The conventional therapy of persistent pulmonary hypertension is discussed as well as the adjunctive role of surfactant replacement therapy and high frequency ventilation. The mechanism of action of inhaled nitric oxide as a selective pulmonary vasodilator is explained. Human neonatal clinical experience is chronicled from the original studies of Roberts in 1992 and Kinsella in 1993. A review of three large prospective randomized trials of nitric oxide is presented as well as a summary of new areas of investigation including the use of nitric oxide in pre-term infants and the use of nitric oxide in the prevention of chronic lung disease. Current dosing recommendations are presented as well as guidelines recently published from the American Academy of Pediatrics. A review of follow up literature in relationship to patients receiving inhaled nitric oxide is also summarized.

Cost of managing digital diagnostic images for a 614-bed hospital.

The cost of recording and archiving digital diagnostic imaging data is presented for a Radiology Department serving a 614 bed University-Hospital with a large outpatient population. Digital diagnostic imaging modalities include computed tomography, nuclear medicine, ultrasound, and digital radiography. The archiving media include multiformat video film recordings, magnetic tapes, and disc storage. The estimated cost per patient for the archiving of digital diagnostic imaging data is presented.

Regional Neuropeptide Pathology in Alzheimer's Disease: Corticotropin-Releasing Factor and Somatostatin.

BACKGROUND: the neuropeptides most consistently reported to be altered in Alzheimer's disease are corticotropin-releasing factor and somatostatin (somatotropin-release inhibiting factor), although this has been previously assessed in a limited number of brain regions. METHODS: in order to comprehensively characterize the involvement of these two anatomically distinct neuropeptide systems in Alzheimer's disease and to determine if they are equally involved in the associated pathology, we measured the concentration of corticotropin-releasing factor and somatostatin in post-mortem brain tissue. Radioimmunoassay of 24 cortical and 13 sub-cortical brain regions from 16 cases of neuropathologically confirmed AD and 9 non-Alzheimer's disease controls were performed and significant differences in group regional neuropeptide concentrations were sought using the Student Newman-Keuls test after ANOVA. RESULTS: comparison of group mean regional neuropeptide concentrations revealed several brain regions where both peptides were decreased in Alzheimer's disease and some regions where only one of the two peptides were decreased, while still other regions exhibited no changes in either peptide. These changes were principally found in frontal and temporal cortex, with few subcortical regions exhibiting pathologic changes in peptide concentration. Regional peptide content was correlated among peptides and with duration of dementia in several brain regions. CONCLUSIONS: these data support the hypothesis that the somatostatin- and corticotropin-releasing factor containing neurons are pathologically involved in AD and that the involved neurons are limited to specific areas of the brain.