Michael Regier

Leading Causes of Unintentional and Intentional Injury Mortality: United States, 2000–2009

OBJECTIVES We have described national trends for the 5 leading external causes of injury mortality. METHODS We used negative binomial regression and annual underlying cause-of-death data for US residents for 2000 through 2009. RESULTS Mortality rates for unintentional poisoning, unintentional falls, and suicide increased by 128%, 71%, and 15%, respectively. The unintentional motor vehicle traffic crash mortality rate declined 25%. Suicide ranked first as a cause of injury mortality, followed by motor vehicle traffic crashes, poisoning, falls, and homicide. Females had a lower injury mortality rate than did males. The adjusted fall mortality rate displayed a positive age gradient. Blacks and Hispanics had lower adjusted motor vehicle traffic crash and suicide mortality rates and higher adjusted homicide rates than did Whites, and a lower unadjusted total injury mortality rate. CONCLUSIONS Mortality rates for suicide, poisoning, and falls rose substantially over the past decade. Suicide has surpassed motor vehicle traffic crashes as the leading cause of injury mortality. Comprehensive traffic safety measures have successfully reduced the national motor vehicle traffic crash mortality rate. Similar efforts will be required to diminish the burden of other injury.

Lithium in the public water supply and suicide mortality in Texas

There is increasing evidence from ecological studies that lithium levels in drinking water are inversely associated with suicide mortality. Previous studies of this association were criticized for using inadequate statistical methods and neglecting socioeconomic confounders. This study evaluated the association between lithium levels in the public water supply and county-based suicide rates in Texas. A state-wide sample of 3123 lithium measurements in the public water supply was examined relative to suicide rates in 226 Texas counties. Linear and Poisson regression models were adjusted for socioeconomic factors in estimating the association. Lithium levels in the public water supply were negatively associated with suicide rates in most statistical analyses. The findings provide confirmatory evidence that higher lithium levels in the public drinking water are associated with lower suicide rates. This association needs clarification through examination of possible neurobiological effects of low natural lithium doses.

Nerve growth factor modulates human rhinovirus infection in airway epithelial cells by controlling ICAM-1 expression

Human rhinoviruses (HRV) are the most common agent of upper respiratory infections and an important cause of lower respiratory tract symptoms. Our previous research with other viral pathogens has shown that virus-induced airway inflammation and hyperreactivity involve neurotrophic pathways that also affect tropism and severity of the infection. The goals of this study were to analyze systematically the expression of key neurotrophic factors and receptors during HRV-16 infection of human airway epithelial cells and to test the hypothesis that neurotrophins modulate HRV infection by controlling the expression of a major cellular receptor for this virus, the intercellular adhesion molecule 1 (ICAM-1). Neurotrophins and ICAM-1 expression were analyzed at the mRNA level by real-time PCR and at the protein level by flow cytometry and immunocytochemistry. A small inhibitory RNA (siRNA) or a specific blocking antibody was utilized to suppress nerve growth factor (NGF) expression and measure its effects on viral replication and virus-induced cell death. Nasal and bronchial epithelial cells were most susceptible to HRV-16 infection at 33°C and 37°C, respectively, and a significant positive relationship was noted between expression of NGF and tropomyosin-related kinase A (TrkA) and virus copy number. ICAM-1 expression was dose dependently upregulated by exogenous NGF and significantly downregulated by NGF inhibition with corresponding decrease in HRV-16 replication. NGF inhibition also increased apoptotic death of infected cells. Our results suggest that HRV upregulates the NGF-TrkA pathway in airway epithelial cells, which in turn amplifies viral replication by increasing HRV entry via ICAM-1 receptors and by limiting apoptosis.

Incidence and Pattern of Graft-Versus-Host Disease in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation After Non-Myeloablative Conditioning with Total Lymphoid Irradiation and Antithymocyte Globulin

Nonmyeloablative (NMA) conditioning with total lymphoid irradiation and antithymocyte globulin (TLI/ATG) has been shown to protect against acute graft-versus-host disease (GVHD). We report here our institutional experience with allogeneic transplantation following NMA conditioning with TLI/ATG (n = 21). GVHD prophylaxis consisted of a combination of a calcineurin inhibitor and mycophenolate mofetil. Median patient age was 59 years. The median followup of surviving patients is 545 days. One patient experienced primary graft rejection. The median time to neutrophil engraftment was 18 days and platelet engraftment was 9.5 days. The cumulative incidence (CI) of grade II–IV acute GVHD at day +100 was 28.6% and 38.1% at day +180. The CI for grade III-IV acute GVHD was 28.6% at day +180. CI of chronic GVHD was 45.2% at 1 year. The CI of disease relapse was 9.5% at 1 year. The rate of nonrelapse mortality (NRM) was 0% at day +100 and only 9.5% at 1 year. The overall and progression free survival at 1 year was 81% and 80.4%, respectively. Our limited, retrospective data show encouraging relapse and NRM rates with TLI/ATG-based NMA conditioning, but with higher than previously reported rates of acute and chronic GVHD, underscoring the need for novel strategies designed to effectively prevent GVHD.

Gait parameters associated with balance in healthy 2- to 4-year-old children

The use of validated measurements of gait and balance are crucial to establish baseline function and assess effectiveness of therapeutic interventions. Gait in children changes with motor development requiring frequent observations to effectively track progress. Standardized baseline spatiotemporal measurements and a greater understanding of the relationship between gait and balance would provide important feedback to clinicians regarding the effectiveness of rehabilitation and guide treatment modifications. 84 subjects (2.0-4.9 years) walked along the GAITRite(®), a walkway that records spatiotemporal parameters. The Pediatric Balance Scale (PBS) was administered to assess balance. Comparison of spatiotemporal parameter means between age groups showed trends associated with motor development similar to the ones described in the literature such as decreased cadence and increased step/stride length with increasing age. However, no significant differences in normalized spatiotemporal parameters were found between age groups. Age, leg length, cadence, step/stride length, step/stance time, and single/double support time showed significant correlation with balance scores. When the parameters were grouped into spatial, temporal, and age-related components using principal components analysis and included in a multiple regression model, they significantly predicted 51% of the balance score variance. Age-related components most strongly predicted balance outcomes. We suggest that balance can potentially be evaluated by assessment of spatial, temporal, and age-related characteristics of gait such as step length, cadence, and leg length. This suggests the possibility of developing new gait measurement technology that could provide functional assessment and track improvements during rehabilitation regimens. If the same model can be applied to monitor treatment efficacy in children with gait abnormalities remains to be addressed.

Smartphone assessment of knee flexion compared to radiographic standards

BACKGROUND Measuring knee range of motion (ROM) is an important assessment for the outcomes of total knee arthroplasty. Recent technological advances have led to the development and use of accelerometer-based smartphone applications to measure knee ROM. The purpose of this study was to develop, standardize, and validate methods of utilizing smartphone accelerometer technology compared to radiographic standards, visual estimation, and goniometric evaluation. METHODS Participants used visual estimation, a long-arm goniometer, and a smartphone accelerometer to determine range of motion of a cadaveric lower extremity; these results were compared to radiographs taken at the same angles. RESULTS The optimal smartphone position was determined to be on top of the leg at the distal femur and proximal tibia location. Between methods, it was found that the smartphone and goniometer were comparably reliable in measuring knee flexion (ICC=0.94; 95% CI: 0.91-0.96). Visual estimation was found to be the least reliable method of measurement. CONCLUSIONS The results suggested that the smartphone accelerometer was non-inferior when compared to the other measurement techniques, demonstrated similar deviations from radiographic standards, and did not appear to be influenced by the person performing the measurements or the girth of the extremity.

Retrospective cross-sectional pilot study of rifaximin dosing for the prevention of recurrent hepatic encephalopathy

Standard treatment for hepatic encephalopathy (HE) includes medications that reduce ammonia and bacterial translocation in the gut. Rifaximin can be used off‐label for the reduction of overt HE. The study purpose was to determine efficacy of traditional rifaximin dosing (400 mg three times daily) compared with newer dosing (550 mg twice daily) via readmission rates for the prevention of recurrent HE. This was a retrospective, observational, cross‐sectional pilot study conducted in a tertiary medical center. A total of 226 patients 18–89 years of age with documentation of HE via ICD‐9 code who started rifaximin therapy while inpatient between April 2009 and June 2014 were evaluated. Data collected included rifaximin dosing, other medications used to treat HE, duration of therapy, time to readmission, and various laboratory values. There were no differences in readmission rates at 30 days, 60 days, or 6 months between treatment groups. Additionally, there was no difference in the odds of readmission between the treatment groups (OR = 0.77, 95% CI: [0.201, 4.365], P = 0.718). Patients had a low overall probability of readmission over the observational period. Based on average wholesale price data, the cost for a 9‐day supply of rifaximin for the 400‐mg dosing regimen is

Impact of Tissue Plasminogen Activator Dosing on Patients Weighing More Than 100 kg on 3-Month Outcomes in Acute Ischemic Stroke

952.56 versus

Long-term pharmacotherapy for elevated low density lipoprotein levels in children: A retrospective analysis

605.16 for the 550‐mg dosing regimen. The rifaximin 550‐mg dosing strategy should be utilized in hospitalized patients for the prevention of recurrent HE as there was no difference in readmission rate or time to readmission between dosing groups. The 550‐mg regimen had a lower acquisition cost for a 9‐day duration of treatment in the studied institution.

An Inexpensive, Interdisciplinary, Methodology to Conduct an Impact Study of Homeless Persons on Hospital Based Services

BACKGROUND AND PURPOSE The landmark National Institute of Neurological Disorders and Stroke (NINDS) tissue plasminogen activator (tPA) trial established the effectiveness and dosing of intravenous tPA for acute ischemic stroke (AIS) at .9 mg/kg with a maximum dose of 90 mg. Since the publication of the NINDS trial in 1995, there has been a drastic increase in the amount of obesity and the average weight of adults in the United States, which has caused an increase in the number of patients receiving 90 mg of alteplase for AIS. This retrospective trial was an attempt to see if reduced-dose tPA is as effective as full .9 mg/kg dosing. METHODS We performed a single-center retrospective analysis to assess the dosing rate and 90-day outcomes comparing maximum dosage (90 mg) and standard dosage (.9 mg/kg) of tPA. RESULTS A total of 301 patients were included in the analysis with 64 (21%) receiving less than .9 mg/kg dosing. The adjusted binary logistic regression model showed a statistically significant association toward a good outcome for increases in tPA dose rate (odds ratio = 1.7, P = .027) when compared against a poor outcome. Our analysis showed that patients receiving doses of alteplase closer to .9 mg/kg had a higher likelihood of a modified Rankin Scale score of 0-1 at 90 days. CONCLUSIONS With the growth of obesity in the United States and the lack of data supporting dose capping of alteplase, it remains unclear if this dosing practice should continue to be accepted without question. Further studies are needed to assess optimum dosing practices particularly given the obesity epidemic.