Tolerability of NGX-4010, a capsaicin 8% patch, in conjunction with three topical anesthetic formulations for the treatment of neuropathic pain

Lynn R Webster1, John F Peppin2, Frederick T Murphy3,4, Jeffrey K Tobias5, Geertrui F Vanhove51Lifetree Clinical Research and Pain Clinic, Lifetree Medical Inc, Salt Lake City, UT, USA; 2Clinical Research Division, The Pain Treatment Center of the Bluegrass, Lexington, KY, USA; 3Altoona Center for Clinical Research, Duncansville, PA, USA; 4University of Pennsylvania, School of Medicine, Philadelphia, PA, USA; 5NeurogesX Inc, San Mateo, CA, USABackground: The objective of this study was to assess the safety, tolerability, and preliminary efficacy of NGX-4010, a capsaicin 8% patch, following pretreatment with three different topical anesthetics in patients with peripheral neuropathic pain.Methods: This open-label, multicenter study enrolled 117 patients with post-herpetic neuralgia, HIV-associated distal sensory polyneuropathy, or painful diabetic neuropathy. Patients received pretreatment with one of three lidocaine 4%-based topical anesthetics (L.M.X.4® [Ferndale Laboratories Inc, Ferndale, MI], Topicaine® Gel [Estela Basso, Jupiter, FL], or Betacaine Enhanced Gel 4 [Tiberius Inc, Tampa, FL]) for 60 minutes followed by a single 60- or 90-minute NGX-4010 application, and were followed for 12 weeks. Tolerability and safety measures included “pain now” Numeric Pain Rating Scale (NPRS) scores, dermal assessments, medication use for treatment-related pain, adverse events (AEs), clinical laboratory parameters, physical examinations, and vital signs. The primary efficacy variable was the percentage change in mean NPRS scores for “average pain for the past 24 hours” from baseline to weeks 2 through 12.Results: Treatment with NGX-4010 following pretreatment with any of the three topical anesthetics was generally safe and well tolerated. Nearly all patients completed ≥90% of the planned NGX-4010 application duration. The most common treatment-related AEs, application-site burning and application-site pain, were transient, mostly mild or moderate, and could be adequately managed by local cooling or short-acting oral opioid analgesics. Although slightly more patients used medication for treatment-related discomfort following pretreatment with Topicaine compared with L.M.X.4 or Betacaine, there were no statistical differences between the topical anesthetics. Neuropathic pain reduction from baseline to weeks 2 through 12 was approximately 30% and was similar among the topical anesthetics; the proportion of responders ranged from 45% to 50%.Conclusion: Treatment with NGX-4010 following pretreatment with any of the three topical anesthetics was generally safe and well tolerated; no significant differences in the parameters measured were noted between the pretreatment groups.Keywords: neuropathic pain, capsaicin patch, tolerability, topical anesthetic

“Life at the River is a Living Hell:” a qualitative study of trauma, mental health, substance use and HIV risk behavior among female fish traders from the Kafue Flatlands in Zambia

Abstract Background In Western settings, the relationship between trauma history, posttraumatic stress disorder, substance use, and HIV risk behavior, is well established. Although female fish traders in Zambia are affected by HIV at rates estimated to be 4–14 times higher than the national prevalence, no studies have examined the co-occurring issues of trauma, substance use and HIV risk behavior among this vulnerable population. The current study examined: 1) trauma history, trauma symptoms and HIV risk behaviors and 2) the relationship between these co-occurring issues among female fish traders from the Kafue Flatlands in Zambia. Methods Twenty individual semi-structured qualitative interviews and a focus group discussion (n = 12 participants) were conducted with female fish traders in the Kafue Flatlands of Zambia. Template analysis was used to examine the data. Results The findings indicate that female fish traders in Zambia are at risk of multiple and ongoing traumatic events and daily stressors, severe mental health symptoms (including western conceptualizations of disorders such as anxiety, depression, post-traumatic stress disorder (PTSD) and complicated grief, as well as local idioms of distress), substance abuse, and HIV sexual risk behaviors. The results suggest a relationship between trauma and HIV sexual risk behavior in this population. Conclusions The indication of these co-occurring issues demonstrates the need for HIV prevention intervention efforts, which account for trauma, mobility, and psychosocial outcomes in order to reduce HIV sexual risk behavior among female fish traders in Zambia.http://deepblue.lib.umich.edu/bitstream/2027.42/136165/1/12905_2017_Article_369.pd

Outcomes After Virologic Failure of First-Line ART in South Africa

Article approval pendingTo determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART)

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial

Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI

Regional Similarities and NOx‐Related Increases in Biogenic Secondary Organic Aerosol in Summertime Southeastern United States

During the 2013 Southern Oxidant and Aerosol Study, Fourier transform infrared spectroscopy (FTIR) and aerosol mass spectrometer (AMS) measurements of submicron mass were collected at Look Rock (LRK), Tennessee, and Centreville (CTR), Alabama. Carbon monoxide and submicron sulfate and organic mass concentrations were 15–60% higher at CTR than at LRK, but their time series had moderate correlations (r ~ 0.5). However, NOx had no correlation (r = 0.08) between the two sites with nighttime‐to‐early‐morning peaks 3–10 times higher at CTR than at LRK. Organic mass (OM) sources identified by FTIR Positive Matrix Factorization (PMF) had three very similar factors at both sites: fossil fuel combustion‐related organic aerosols, mixed organic aerosols, and biogenic organic aerosols (BOA). The BOA spectrum from FTIR is similar (cosine similarity > 0.6) to that of lab‐generated particle mass from the photochemical oxidation of both isoprene and monoterpenes under high NOx conditions from chamber experiments. The BOA mass fraction was highest during the night at CTR but in the afternoon at LRK. AMS PMF resulted in two similar pairs of factors at both sites and a third nighttime NOx‐related factor (33% of OM) at CTR but a daytime nitrate‐related factor (28% of OM) at LRK. NOx was correlated with BOA and LO‐OOA for NOx concentrations higher than 1 ppb at both sites, producing 0.5 ± 0.1 μg/m3 for CTR‐LO‐OOA and 1.0 ± 0.3 μg/m3 for CTR‐BOA additional biogenic OM for each 1 ppb increase of NOx.Key PointsAerosol concentration and composition are largely similar at two different forested sites during summertime in the southeastern United StatesFTIR of ambient biogenic SOA factors are similar to isoprene and monoterpene chamber experiment, supporting NOx‐related oxidation pathwaysNOx increases biogenic SOA by 0.5 ± 0.1 μg/m3 for CTR‐LO‐OOA and 1.0 ± 0.3 μg/m3 for CTR‐BOA for each ppb NOx above 1 ppb at Centreville but not at Look Rock (where NOx was usually below 1 ppb)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146465/1/jgrd54860-sup-0001-SI.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146465/2/jgrd54860.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146465/3/jgrd54860_am.pd

Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development.

Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life

Implications of NiMH Hysteresis on HEV Battery Testing and Performance

Nickel Metal-Hydride (NiMH) is an advanced high-power battery technology that is presently employed in Hybrid Electric Vehicles (HEVs) and is one of several technologies undergoing continuing research and development by FreedomCAR. Unlike some other HEV battery technologies, NiMH exhibits a strong hysteresis effect upon charge and discharge. This hysteresis has a profound impact on the ability to monitor state-of-charge and battery performance. Researchers at the Idaho National Engineering and Environmental Laboratory (INEEL) have been investigating the implications of NiMH hysteresis on HEV battery testing and performance. Experimental results, insights, and recommendations are presented

Development of the interRAI Pressure Ulcer Risk Scale (PURS) for use in long-term care and home care settings

<p>Abstract</p> <p>Background</p> <p>In long-term care (LTC) homes in the province of Ontario, implementation of the Minimum Data Set (MDS) assessment and The Braden Scale for predicting pressure ulcer risk were occurring simultaneously. The purpose of this study was, using available data sources, to develop a bedside MDS-based scale to identify individuals under care at various levels of risk for developing pressure ulcers in order to facilitate targeting risk factors for prevention.</p> <p>Methods</p> <p>Data for developing the interRAI Pressure Ulcer Risk Scale (interRAI PURS) were available from 2 Ontario sources: three LTC homes with 257 residents assessed during the same time frame with the MDS and Braden Scale for Predicting Pressure Sore Risk, and eighty-nine Ontario LTC homes with 12,896 residents with baseline/reassessment MDS data (median time 91 days), between 2005-2007. All assessments were done by trained clinical staff, and baseline assessments were restricted to those with no recorded pressure ulcer. MDS baseline/reassessment samples used in further testing included 13,062 patients of Ontario Complex Continuing Care Hospitals (CCC) and 73,183 Ontario long-stay home care (HC) clients.</p> <p>Results</p> <p>A data-informed Braden Scale cross-walk scale using MDS items was devised from the 3-facility dataset, and tested in the larger longitudinal LTC homes data for its association with a future new pressure ulcer, giving a c-statistic of 0.676. Informed by this, LTC homes data along with evidence from the clinical literature was used to create an alternate-form 7-item additive scale, the interRAI PURS, with good distributional characteristics and c-statistic of 0.708. Testing of the scale in CCC and HC longitudinal data showed strong association with development of a new pressure ulcer.</p> <p>Conclusions</p> <p>interRAI PURS differentiates risk of developing pressure ulcers among facility-based residents and home care recipients. As an output from an MDS assessment, it eliminates duplicated effort required for separate pressure ulcer risk scoring. Moreover, it can be done manually at the bedside during critical early days in an admission when the full MDS has yet to be completed. It can be calculated with established MDS instruments as well as with the newer interRAI suite instruments designed to follow persons across various care settings (interRAI Long-Term Care Facilities, interRAI Home Care, interRAI Palliative Care).</p