Greg Stoddard

In vivo human time-exposure study of orally dosed commercial silver nanoparticles.

UNLABELLED Human biodistribution, bioprocessing and possible toxicity of nanoscale silver receive increasing health assessment. We prospectively studied commercial 10- and 32-ppm nanoscale silver particle solutions in a single-blind, controlled, cross-over, intent-to-treat, design. Healthy subjects (n=60) underwent metabolic, blood counts, urinalysis, sputum induction, and chest and abdomen magnetic resonance imaging. Silver serum and urine content were determined. No clinically important changes in metabolic, hematologic, or urinalysis measures were identified. No morphological changes were detected in the lungs, heart or abdominal organs. No significant changes were noted in pulmonary reactive oxygen species or pro-inflammatory cytokine generation. In vivo oral exposure to these commercial nanoscale silver particle solutions does not prompt clinically important changes in human metabolic, hematologic, urine, physical findings or imaging morphology. Further study of increasing time exposure and dosing of silver nanoparticulate silver, and observation of additional organ systems are warranted to assert human toxicity thresholds. FROM THE CLINICAL EDITOR In this study, the effects of commercially available nanoparticles were studied in healthy volunteers, concluding no detectable toxicity with the utilized comprehensive assays and tests. As the authors rightfully state, further studies are definitely warranted. Studies like this are much needed for the more widespread application of nanomedicine.

Association of Intrapartum Antibiotic Exposure and Late-Onset Serious Bacterial Infections in Infants

Objective. Recommendations to prevent vertical transmission of group B Streptococcus (GBS) infections have resulted in many womens receiving antibiotics during labor with an associated reduction in early-onset GBS infections in their newborn infants. However, a potential relationship of intrapartum antibiotics (IPA) to the occurrence of late-onset (7–90 days) serious bacterial infections (SBIs) in term infants has not been reported. The objectives of this study were to determine whether infants with late-onset SBI were more likely than healthy control infants to have been exposed to IPA and whether there was a greater likelihood of antibiotic resistance in bacteria that were isolated from infants who had an SBI and had been exposed to IPA compared with those who had not. Methods. We used a case-control design to study the first objective. Cases were previously healthy full-term infants who were hospitalized for late-onset SBI between the ages of 7 and 90 days. Control subjects were healthy full-term infants who were known not to have an SBI in their first 90 days. Cases and control subjects were matched for hospital of delivery. In the second part of the study, rates of antibiotic resistance of bacteria that were isolated from infected infants were compared for those who had and had not been exposed to IPA. Results. Ninety case infants and 92 control subjects were studied. Considering all types of IPA, more case (41%) than control infants (27%) had been exposed to IPA (adjusted odds ratio [OR]: 1.96; 95% confidence interval [CI]: 1.05–3.66), after controlling for hospital of delivery. The association was stronger when IPA was with broad-spectrum antibiotics (adjusted OR: 4.95; 95% CI: 2.04–11.98), after controlling for hospital of delivery, penicillin IPA, maternal chorioamnionitis, and breastfeeding. Bacteria that were isolated from infected infants who had been exposed to IPA were more likely to exhibit ampicillin resistance (adjusted OR: 5.7; 95% CI: 2.3–14.3), after controlling for hospital of delivery, but not to other antibiotics that are commonly used to treat SBI in infants. Conclusions. After adjusting for potential confounders, infants with late-onset SBI were more likely to have been exposed to IPA than noninfected control infants. Pathogens that cause late-onset SBI were more likely to be resistant to ampicillin when the infant had been exposed to intrapartum antibiotics.

The impact of bridge-to-transplant ventricular assist device support on survival after cardiac transplantation

OBJECTIVE To determine the impact of bridge-to-transplant ventricular assist device support on survival after cardiac transplantation. METHODS From January 1, 1993, to April 30, 2009, a total of 525 cardiac transplants were performed. Ventricular assist devices were placed as a bridge to transplant in 110 patients. We focused our analysis on the 2 most common causes of end-stage heart failure requiring transplantation: idiopathic dilated cardiomyopathy (n = 201) and coronary artery disease (n = 213). Data including gender, age, date of transplant, cause of heart failure, prior heart transplant, placement of a ventricular assist device, type of ventricular assist device, and panel-reactive antibody sensitization were analyzed to derive Kaplan-Meier survival probabilities and multivariable Cox regression models. RESULTS In patients with idiopathic dilated cardiomyopathy who received a ventricular assist device as a bridge to transplant, survival was decreased at 1 year (P = .008) and 5 years (P = .019), but not at 10 years, posttransplant. In patients with coronary artery disease, the use of a ventricular assist device as a bridge to transplant did not influence survival at 1, 5, and 10 tears posttransplant. In patients with idiopathic dilated cardiomyopathy who received a Heartmate I (Thoratec Corp, Pleasanton, Calif) ventricular assist device as a bridge to a cardiac transplant, elevation in the pretransplant panel-reactive antibody correlated with a decrease in long-term survival. CONCLUSION In patients with idiopathic dilated cardiomyopathy, placement of a Heartmate I ventricular assist device as a bridge to a cardiac transplant is associated with an elevation in the pretransplant panel-reactive antibody and a decrease in 1- and 5-year survivals after cardiac transplantation.

A simulation-based evaluation of methods to estimate the impact of an adverse event on hospital length of stay

Introduction:We used agent-based simulation to examine the problem of time-varying confounding when estimating the effect of an adverse event on hospital length of stay. Conventional analytic methods were compared with inverse probability weighting (IPW). Methods:A cohort of hospitalized patients, at risk for experiencing an adverse event, was simulated. Synthetic individuals were assigned a severity of illness score on admission. The score varied during hospitalization according to an autoregressive equation. A linear relationship between severity of illness and the logarithm of the discharge rate was assumed. Depending on the model conditions, adverse event status was influenced by prior severity of illness and, in turn, influenced subsequent severity. Conditions were varied to represent different levels of confounding and categories of effect. The simulation output was analyzed by Cox proportional hazards regression and by a weighted regression analysis, using the method of IPW. The magnitude of bias was calculated for each method of analysis. Results:Estimates of the population causal hazard ratio based on IPW were consistently unbiased across a range of conditions. In contrast, hazard ratio estimates generated by Cox proportional hazards regression demonstrated substantial bias when severity of illness was both a time-varying confounder and intermediate variable. The direction and magnitude of bias depended on how severity of illness was incorporated into the Cox regression model. Conclusions:In this simulation study, IPW exhibited less bias than conventional regression methods when used to analyze the impact of adverse event status on hospital length of stay.

Low-Back Pain Ratings for Lifetime, 1-Month Period, and Point Prevalences in a Large Occupational Population

Objective: This manuscript systematically quantifies multiple measures of low-back pain (LBP) prevalence by pain rating in a large, multisite cohort of workers. Background: Published LBP prevalence rates vary. Studies rely on one measure of LBP and none report prevalence stratified by pain rating. Method: Cross-sectional analyses of baseline data from a multicenter prospective cohort study were performed to evaluate differences in lifetime prevalence, 1-month period prevalence, and point prevalence of LBP. Workers were from 28 different employment settings in 4 diverse U.S. states. All workers completed computerized questionnaires and structured interviews. LBP prevalence measures were stratified by pain ratings. Results: A total of 828 subjects had complete health data at baseline. Lifetime prevalence, 1-month period prevalence, and point prevalence for any LBP (≥1/10) were 63.4%, 44.0%, and 20.8% respectively. Prevalence of LBP decreased with increasing pain ratings. As an example, using a threshold of LBP ≥ 3/10 pain, prevalence measures were 61.0%, 37.6%, and 16.7% respectively. A threshold of LBP ≥ 5/10 had prevalence measures of 51.2%, 22.9%, and 9.9% respectively. Age, systolic and diastolic blood pressure, high cholesterol, high blood pressure, and tobacco use were statistically significantly related to lifetime prevalence of LBP. Conclusion: Lifetime LBP prevalence, 1-month period prevalence, and point prevalence stratified by pain ratings demonstrate a wide variation of prevalence measures of LBP and self-reported pain ratings. Higher pain rating thresholds yield lower prevalence measures and may impact assessments of risk factors. Differences in pain ratings may allow for focused surveillance within an occupational cohort.

Assessment of orally dosed commercial silver nanoparticles on human ex vivo platelet aggregation

Abstract Enhanced in vitro human and ex vivo rat platelet aggregation from direct exposure to silver nanoparticles is previously reported. Given the increasing human use of engineered silver nanoscale products, platelet aggregation prompted by silver nanoparticles may contribute to human cardiovascular events. To understand how direct washed platelet exposure to silver nanoparticles translates to ex vivo platelet aggregation, the authors conducted a placebo-controlled, single-blind, dose-monitored, cross-over study design in 18 healthy human volunteers. After 2 weeks of daily oral silver nanoparticle ingestion, platelet aggregation was evaluated by light transmission aggregometry in response to collagen and ADP agonists, both at baseline and after silver nanoparticle or placebo diluent oral dosing. Final percent aggregation (PA) and the changes in PA were determined using a paired design (i.e., active and placebo solutions). Enhanced ex vivo platelet activation was not detectable at peak serum silver concentrations <10 µg/L. Further studies of colloidal silver nanoparticles on human platelet activities are warranted.

Impact of donor left ventricular hypertrophy on survival after heart transplant.

Left ventricular hypertrophy (LVH) of the donor heart is believed to increase the risk of allograft failure after transplant. However this effect is not well quantified, with variable findings from single‐center studies. The United Network for Organ Sharing database was used to analyze the effect of donor LVH on recipient survival. Three cohorts, selected in accordance with the American Society of Echocardiography guidelines, were examined: recipients of allografts without LVH (<1.1 cm), with mild LVH (1.1–1.3 cm) and with moderate–severe LVH (≥1.4 cm). The study group included 2626 patients with follow‐up of up to 3.3 years. Mild LVH was present in 38% and moderate‐severe LVH in 5.6% of allografts. Predictors of mortality included a number of donor and recipient characteristics, but not LVH. However, a subgroup analysis showed an increased risk of death in recipients of allografts with LVH and donor age >55 years, and in recipients of allografts with LVH and ischemic time ≥4 h. In the contemporary era, close to half of all transplanted allografts demonstrate LVH, and survival of these recipients is similar to those without LVH. However, the use of allografts with LVH in association with other high‐risk characteristics may result in increased mortality.

Trends and Predictors for Vagotomy When Performing Oversew of Acute Bleeding Duodenal Ulcer in the United States

BackgroundIn the era of Helicobacter pylori treatment, the role of vagotomy in bleeding duodenal ulcers is debatable. National outcomes were evaluated to determine the current surgical treatment and use of vagotomy for bleeding duodenal ulcers.MethodsData from the Nationwide Inpatient Sample (NIS) were used from years 1999 to 2003. Patients were selected using diagnostic codes for acute duodenal ulcer bleed and procedure codes for simple oversew of a bleeding ulcer and vagotomy. Data were analyzed using multiple linear and logistic regression.ResultsBetween 1999 and 2003, 100,931 patients with an acute bleeding duodenal ulcer were identified. Over time, there was a decrease in the number of acute bleeding ulcers (p = 0.027) and a decrease in the number of vagotomies (p = 0.027). A high co-morbidity index [odds ratio (OR), 0.60, p = 0.017], operation in the Midwest (OR 0.50, p < 0.001) and operation in the West (OR 0.68, p = 0.034) were predictive of no vagotomy during surgery for a bleeding duodenal ulcer.ConclusionsA vagotomy is not commonly performed during surgical treatment of an acute bleeding duodenal ulcer. This variation in practice was not fully explained by patient characteristics. We must seek new evidence to determine the safety of combined medical and surgical management of this clinical problem.

Understanding Depressive Symptoms and Psychosocial Stressors on Twitter: A Corpus-Based Study

Background With a lifetime prevalence of 16.2%, major depressive disorder is the fifth biggest contributor to the disease burden in the United States. Objective The aim of this study, building on previous work qualitatively analyzing depression-related Twitter data, was to describe the development of a comprehensive annotation scheme (ie, coding scheme) for manually annotating Twitter data with Diagnostic and Statistical Manual of Mental Disorders, Edition 5 (DSM 5) major depressive symptoms (eg, depressed mood, weight change, psychomotor agitation, or retardation) and Diagnostic and Statistical Manual of Mental Disorders, Edition IV (DSM-IV) psychosocial stressors (eg, educational problems, problems with primary support group, housing problems). Methods Using this annotation scheme, we developed an annotated corpus, Depressive Symptom and Psychosocial Stressors Acquired Depression, the SAD corpus, consisting of 9300 tweets randomly sampled from the Twitter application programming interface (API) using depression-related keywords (eg, depressed, gloomy, grief). An analysis of our annotated corpus yielded several key results. Results First, 72.09% (6829/9473) of tweets containing relevant keywords were nonindicative of depressive symptoms (eg, “we’re in for a new economic depression”). Second, the most prevalent symptoms in our dataset were depressed mood and fatigue or loss of energy. Third, less than 2% of tweets contained more than one depression related category (eg, diminished ability to think or concentrate, depressed mood). Finally, we found very high positive correlations between some depression-related symptoms in our annotated dataset (eg, fatigue or loss of energy and educational problems; educational problems and diminished ability to think). Conclusions We successfully developed an annotation scheme and an annotated corpus, the SAD corpus, consisting of 9300 tweets randomly-selected from the Twitter application programming interface using depression-related keywords. Our analyses suggest that keyword queries alone might not be suitable for public health monitoring because context can change the meaning of keyword in a statement. However, postprocessing approaches could be useful for reducing the noise and improving the signal needed to detect depression symptoms using social media.

Assessing Pictograph Recognition: A Comparison of Crowdsourcing and Traditional Survey Approaches

Background Compared to traditional methods of participant recruitment, online crowdsourcing platforms provide a fast and low-cost alternative. Amazon Mechanical Turk (MTurk) is a large and well-known crowdsourcing service. It has developed into the leading platform for crowdsourcing recruitment. Objective To explore the application of online crowdsourcing for health informatics research, specifically the testing of medical pictographs. Methods A set of pictographs created for cardiovascular hospital discharge instructions was tested for recognition. This set of illustrations (n=486) was first tested through an in-person survey in a hospital setting (n=150) and then using online MTurk participants (n=150). We analyzed these survey results to determine their comparability. Results Both the demographics and the pictograph recognition rates of online participants were different from those of the in-person participants. In the multivariable linear regression model comparing the 2 groups, the MTurk group scored significantly higher than the hospital sample after adjusting for potential demographic characteristics (adjusted mean difference 0.18, 95% CI 0.08-0.28, P<.001). The adjusted mean ratings were 2.95 (95% CI 2.89-3.02) for the in-person hospital sample and 3.14 (95% CI 3.07-3.20) for the online MTurk sample on a 4-point Likert scale (1=totally incorrect, 4=totally correct). Conclusions The findings suggest that crowdsourcing is a viable complement to traditional in-person surveys, but it cannot replace them.