Beyond the black box: drug- and device-associated hypersensitivity events

Charles L Bennett1,2, Olatokunbo S Adegboro2, Elizabeth A Calhoun2, Dennis Raisch3,41Jesse Brown VA Medical Center, Chicago, IL, USA; 2University of Illinois School of Public Health, Chicago, IL, USA; 3University of New Mexico College of Pharmacy, Albuquerque, NM, USA; 4Veteran Affairs Cooperative Studies Program, Clinical Research Pharmacy, Albuquerque, NM, USABackground: Drug- and device-associated hypersensitivity reactions are serious toxicities that can result in respiratory failure or acute cardiac ischemic events, or even severe hypersensitivity syndromes such as Stevens–Johnson syndrome. These toxicities are usually poorly described in the “black box” warnings section of the product labels.Methods: Adverse event reports contained in databases maintained by the Project on Medical Research on Adverse Drug Events and Reports (Med-RADAR), product labels, safety advisories disseminated by pharmaceutical manufacturers, the Food and Drug Administration (FDA), and the Centers for Disease Control and Prevention (CDC) were reviewed.Results: Adverse event reports identified three health care workers who developed nevirapineassociated Stevens–Johnson syndrome following occupational exposure to HIV-infected blood or blood products; four persons with localized hypersensitivity and fatal cardiac events associated with rapamycin- or paclitaxel-coated coronary artery stent placements; and six persons with breast cancer who developed severe or fatal anaphylaxis after receiving adjuvant chemotherapy with Cremophor-EL containing paclitaxel. Safety advisories from the FDA, CDC, and the relevant pharmaceutical manufacturers were ambiguous in their description in “black box” warning sections of package inserts describing these serious and potentially fatal toxicities. Conclusion: Improvements are needed in pharmacovigilance and subsequent dissemination of safety advisories for drug/device-associated hypersensitivity reactions.Keywords: adverse events, hypersensivity, toxicity, dru

Older Adults' Perceptions of Clinical Fall Prevention Programs: A Qualitative Study

Objective. To investigate motivational factors and barriers to participating in fall risk assessment and management programs among diverse, low-income, community-dwelling older adults who had experienced a fall. Methods. Face-to-face interviews with 20 elderly who had accepted and 19 who had not accepted an invitation to an assessment by one of two fall prevention programs. Interviews covered healthy aging, core values, attributions/consequences of the fall, and barriers/benefits of fall prevention strategies and programs. Results. Joiners and nonjoiners of fall prevention programs were similar in their experience of loss associated with aging, core values they expressed, and emotional response to falling. One difference was that those who participated endorsed that they “needed” the program, while those who did not participate expressed a lack of need. Conclusions. Interventions targeted at a high-risk group need to address individual beliefs as well as structural and social factors (transportation issues, social networks) to enhance participation

The Impact of Patient Navigation on the Delivery of Diagnostic Breast Cancer Care in the National Patient Navigation Research Program: A Prospective Meta-Analysis.

Patient navigation is emerging as a standard in breast cancer care delivery, yet multi-site data on the impact of navigation at reducing delays along the continuum of care are lacking. The purpose of this study was to determine the effect of navigation on reaching diagnostic resolution at specific time points after an abnormal breast cancer screening test among a national sample. A prospective meta-analysis estimated the adjusted odds of achieving timely diagnostic resolution at 60, 180, and 365 days. Exploratory analyses were conducted on the pooled sample to identify which groups had the most benefit from navigation. Clinics from six medical centers serving vulnerable populations participated in the Patient Navigation Research Program. Women with an abnormal breast cancer screening test between 2007 and 2009 were included and received the patient navigation intervention or usual care. Patient navigators worked with patients and their care providers to address patient-specific barriers to care to prevent delays in diagnosis. A total of 4675 participants included predominantly racial/ethnic minorities (74 %) with public insurance (40 %) or no insurance (31 %). At 60 days and 180 days, there was no statistically significant effect of navigation on achieving timely diagnostic care, but a benefit of navigation was seen at 365 days (aOR 2.12, CI 1.36-3.29). We found an equal benefit of navigation across all groups, regardless of race/ethnicity, language, insurance status, and type of screening abnormality. Patient navigation resulted in more timely diagnostic resolution at 365 days among a diverse group of minority, low-income women with breast cancer screening abnormalities. Trial registrations clinicaltrials.gov Identifiers: NCT00613275, NCT00496678, NCT00375024, NCT01569672

Symmetric data-driven fusion of diffusion tensor MRI: Age differences in white matter

In the past 20 years, white matter (WM) microstructure has been studied predominantly using diffusion tensor imaging (DTI). Decreases in fractional anisotropy (FA) and increases in mean (MD) and radial diffusivity (RD) have been consistently reported in healthy aging and neurodegenerative diseases. To date, DTI parameters have been studied individually (e.g., only FA) and separately (i.e., without using the joint information across them). This approach gives limited insights into WM pathology, increases the number of multiple comparisons, and yields inconsistent correlations with cognition. To take full advantage of the information in a DTI dataset, we present the first application of symmetric fusion to study healthy aging WM. This data-driven approach allows simultaneous examination of age differences in all four DTI parameters. We used multiset canonical correlation analysis with joint independent component analysis (mCCA + jICA) in cognitively healthy adults (age 20-33

Older Adults\u27 Perceptions of Clinical Fall Prevention Programs: A Qualitative Study

Objective: To investigate motivational factors and barriers to participating in fall risk assessment and management programs among diverse, low-income, community-dwelling older adults who had experienced a fall. Methods: Face-to-face interviews with 20 elderly who had accepted and 19 who had not accepted an invitation to an assessment by one of two fall prevention programs. Interviews covered healthy aging, core values, attributions/consequences of the fall, and barriers/benefits of fall prevention strategies and programs. Results: Joiners and nonjoiners of fall prevention programs were similar in their experience of loss associated with aging, core values they expressed, and emotional response to falling. One difference was that those who participated endorsed that they “needed” the program, while those who did not participate expressed a lack of need. Conclusions: Interventions targeted at a high-risk group need to address individual beliefs as well as structural and social factors (transportation issues, social networks) to enhance participation

Plasma metabolomics and clinical predictors of survival differences in COPD patients

Background: Plasma metabolomics profile (PMP) in COPD has been associated with clinical characteristics, but PMP''s relationship to survival has not been reported. We determined PMP differences between patients with COPD who died an average of 2 years after enrollment (Non-survivors, NS) compared to those who survived (S) and also with age matched controls (C). Methods: We studied prospectively 90 patients with severe COPD and 30 controls. NS were divided in discovery and validation cohorts (30 patients each) and the results compared to the PMP of 30 S and C. All participants completed lung function tests, dyspnea scores, quality of life, exercise capacity, BODE index, and plasma metabolomics by liquid and gas chromatography/mass spectometry (LC/MS, LC/MS2, GC/MS). Statistically, we used Random Forest Analysis (RFA) and Support Vector Machine (SVM) to determine metabolites that differentiated the 3 groups and compared the ability of metabolites vs. clinical characteristics to classify patients into survivors and non-survivors. Results: There were 79 metabolites statistically different between S and NS [p < 0.05 and false discovery rate (q value) < 0.1]. RFA and SVM classification of COPD survivors and non-survivors had a predicted accuracy of 74 and 85% respectively. Elevation of tricyclic acid cycle intermediates branched amino acids depletion and increase in lactate, fructose and xylonate showed the most relevant differences between S vs. NS suggesting alteration in mitochondrial oxidative energy generation. PMP had similar predictive power for risk of death as information provided by clinical characteristics. Conclusions: A plasma metabolomic profile characterized by an oxidative energy production difference between survivors and non-survivors was observed in COPD patients 2 years before death

Personality Assessment Inventory internalizing and externalizing structure in veterans with posttraumatic stress disorder: Associations with aggression: PTSD and Aggression

Posttraumatic stress disorder (PTSD) is associated with aggressive behavior in veterans, and difficulty controlling aggressive urges has been identified as a primary postdeployment readjustment concern. Yet only a fraction of veterans with PTSD commit violent acts. The goals of this study were to (1) examine the higher-order factor structure of Personality Assessment Inventory (PAI) scales in a sample of U.S. military veterans seeking treatment for PTSD; and (2) to evaluate the incremental validity of higher-order latent factors of the PAI over PTSD symptom severity in modeling aggression. The study sample included male U.S. Vietnam (n = 433) and Iraq/Afghanistan (n = 165) veterans who were seeking treatment for PTSD at an outpatient Veterans Affairs (VA) clinic. Measures included the Clinician Administered PTSD Scale, the PAI, and the Conflict Tactics Scale. The sample was randomly split into two equal subsamples (n’s = 299) to allow for cross-validation of statistically derived factors. Parallel analysis, variable clustering analysis, and confirmatory factor analyses were used to evaluate the factor structure, and regression was used to examine the association of factor scores with self-reports of aggression over the past year. Three factors were identified: internalizing, externalizing, and substance abuse. Externalizing explained unique variance in aggression beyond PTSD symptom severity and demographic factors, while internalizing and substance abuse did not. Service era was unrelated to reports of aggression. The constructs of internalizing versus externalizing dimensions of PTSD may have utility in identifying characteristics of combat veterans in the greatest need of treatment to help manage aggressive urges

Effects of Timber Harvest on Amphibian Populations: Understanding Mechanisms from Forest Experiments

Accompanying appendix may be accessed at: http://hdl.handle.net/10355/1365Harvesting timber is a common form of land use that has the potential to cause declines in amphibian populations. It is essential to understand the behavior and fate of individuals and the resulting consequences for vital rates (birth, death, immigration, emigration) under different forest management conditions.We report on experimental studies conducted in three regions of the United States to identify mechanisms of responses by pond-breeding amphibians to timber harvest treatments. Our studies demonstrate that life stages related to oviposition and larval performance in the aquatic stage are sometimes affected positively by clearcutting, whereas effects on juvenile and adult terrestrial stages are mostly negative

Outcomes and efficacy of thoracic surgery biopsy for tumor molecular profiling in patients with advanced lung cancer

BackgroundMolecular testing of patients with advanced non–small cell lung cancer for personalized therapy often is limited by insufficient specimen from nonsurgical biopsies. We measured the feasibility, patient safety, and clinical impact of thoracic surgical tumor biopsy in patients with stage IV non–small cell lung cancer.MethodsThis is a single institution retrospective analysis. Patients with stage IV non–small cell lung cancer undergoing elective surgical tissue biopsy for molecular analysis were evaluated from March 2011 to November 2012. Perioperative specific variables were measured.ResultsTwenty-five patients with known or suspected stage IV non–small cell lung cancer undergoing surgical biopsy were identified. All cases were discussed at a multidisciplinary thoracic oncology conference or a multidisciplinary thoracic oncology clinic. Preoperative histologies included adenocarcinoma in 20 patients (80.0%) and squamous cell carcinoma in 2 patients (8.0%). Surgical procedures consisted of video-assisted thoracic surgery wedge biopsy (16, 64%), video-assisted thoracic surgery pleural biopsy (4, 16.0%), mediastinoscopy (2, 8.0%), supraclavicular/cervical lymph node excisional biopsy (3, 12.0%), and rib/chest wall resection (2, 8.0%). There were no deaths and 5 postoperative complications (20.0%). Surgery identified potentially targetable molecular information in 19 of the total patients undergoing operation (76.0%) and changed the treatment strategy in 14 patients (56.0%); 10 of the total cohort (40.0%) were enrolled into therapeutic targeted clinical trials.ConclusionsThese data suggest that thoracic surgical biopsy can be safely performed in appropriately selected patients with stage IV non–small cell lung cancer and direct personalized therapy and enrollment into relevant clinical trials. Patients with advanced-stage non–small cell lung cancer should be discussed in a multidisciplinary setting to determine the need and strategy for thoracic surgical biopsy for molecular analysis