Effective skin decontamination with RSDL® (reactive skin decontamination lotion kit) following dermal exposure to a Novichok class nerve agent.

In recent years, various poisoning incidents have been reported, involving the alleged use of the so-called Novichok agents, resulting in their addition to the Schedule I list of the Organisation for the Prohibition of Chemical Warfare (OPCW). As the physicochemical properties of these agents are different from the 'classical' nerve agents, such as VX, research is needed to evaluate whether and to what extent existing countermeasures are effective. Here, we evaluated the therapeutic potential of RSDL® (Reactive Skin Decontamination Lotion Kit) for the neutralization of percutaneous toxicity caused by Novichok agents, both in vitro and in vivo. Experiments showed the three selected Novichok agents (A230, A232, A234) could be degraded by RSDL lotion, but at a different rate. The half-life of A234, in the presence of an excess of RSDL lotion, was 36 min, as compared to A230 (<5 min) and A232 (18 min). Following dermal exposure of guinea pigs to A234, application of the RSDL kit was highly effective in preventing intoxication, even when applied up until 30 min following exposure. Delayed use of the RSDL kit until the appearance of clinical signs of intoxication (3-4 h) was not able to prevent intoxication progression and deaths. This study determines RSDL decontamination as an effective treatment strategy for dermal exposure to the Novichok agent A234 and underscores the importance of early, forward use of skin decontamination, as rapidly as possible.

Integrating early palliative care for patients with HIV: provider and patient perceptions of symptoms and need for services.

Increasingly clinicians are using palliative care to address the symptomatic and psychosocial effects of disease often missed by routine clinical care, termed "early" palliative care. Within an inner-city medical center, we began a program to integrate early palliative care into HIV inpatient care. Patient symptom burden and desired services were assessed and compared to provider perceptions of patient's needs. From 2010-2012, 10 patients, with a median CD4+ T-cell count of 32.5 cells/µL, and 34 providers completed the survey. Providers ranked their patients' fatigue, sadness, anxiety, sexual dysfunction, and body image significantly higher than patients it for themselves. Patients ranked medical care, pharmacy, social work, physical therapy, and housing as significantly more important to them than providers estimated them to be. These differences may reflect the fact that physicians often overlook patients' unmet basic needs. Early palliative care may narrow this gap between providers' and patients' perceptions of needs through good communication and targeting barriers, such as housing instability, which are vital to overcome for consistent long-term follow up.

Carotid artery distensibility: a reliability study.

OBJECTIVE: Carotid distensibility (CD) is a measure of carotid artery elasticity that has been introduced as a risk factor for cardiovascular disease. Information regarding reproducibility of sonographic CD measures is limited. The objective of this study was to evaluate the inter-reader reliability of sonographic measurements of common carotid artery (CCA) diameters and derived metrics of CD. METHODS: Two independent readers (R1 and R2) measured the systolic diameter (SD) and diastolic diameter (DD) for the right CCA from the B/M-mode sonographic registrations among 118 subjects. The derived CD metrics (strain, elastic modulus [E], stiffness [beta], and CD) were calculated. The inter-reader type 3 intraclass correlation coefficients (ICC3,1) for carotid diameters were calculated. RESULTS: The mean SDs +/- standard deviation were 7.15 +/- 1.43 mm for R1 and 7.24 +/- 1.43 mm for R2. The mean DDs were 6.71 +/- 1.36 mm for R1 and 6.68 +/- 1.41 mm for R2. The mean differences of SD and DD between R1 and R2 were 0.08 +/- 0.40 mm (paired t test, P = .04) and 0.03 +/- 0.43 mm (paired t test, P = .46), respectively. Inter-reader type 3 intraclass correlation coefficients were 0.96 for SD and 0.95 for DD. We observed a significant association of demographics with carotid diameters but not with derived CD metrics or risk factors. CONCLUSIONS: Our results suggest good reproducibility of CCA diameters measured with B/M-mode sonography. However, very small changes in linear measurements of carotid diameters can have big effects on estimates of arterial mechanical properties such as strain and Young's modulus. The standard boundary identification methods may not be precise and reproducible enough for use in a clinical setting.

Gavestinel does not improve outcome after acute intracerebral hemorrhage: an analysis from the GAIN International and GAIN Americas studies.

BACKGROUND AND PURPOSE: Glycine Antagonist in Neuroprotection (GAIN) International and GAIN Americas trials were prospectively designed, randomized, placebo-controlled trials of gavestinel, a glycine-site antagonist and putative neuroprotectant drug administered within 6 hours of suspected ischemic or hemorrhagic stroke. Both trials reported that gavestinel was ineffective in ischemic stroke. This analysis reports the results in those with primary intracerebral hemorrhage. METHODS: The primary hypothesis was that gavestinel treatment did not alter outcome, measured at 3 months by the Barthel Index (BI), from acute intracerebral hemorrhage, based on pooled results from both trials. The BI scores were divided into 3 groups: 95 to 100 (independent), 60 to 90 (assisted independence), and 0 to 55 (dependent) or dead. RESULTS: In total, 3450 patients were randomized in GAIN International (N=1804) and GAIN Americas (N=1646). Of these, 571 were ultimately identified to have spontaneous intracerebral hematoma on baseline head computerized tomography scan. The difference in distribution of trichotomized BI scores at 3 months between gavestinel and placebo was not statistically significant (P=0.09). Serious adverse events were reported at similar rates in the 2 treatment groups. CONCLUSIONS: These observations from the combined GAIN International and GAIN Americas trials suggest that gavestinel is not of substantial benefit or harm to patients with primary intracerebral hemorrhage. These findings are similar to results previously reported in patients with ischemic stroke.

Abdominal obesity and risk of ischemic stroke: the Northern Manhattan Stroke Study.

BACKGROUND AND PURPOSE: Obesity is well recognized as a risk factor for coronary heart disease and mortality. The relationship between abdominal obesity and ischemic stroke remains less clear. Our aim was to evaluate abdominal obesity as an independent risk factor for ischemic stroke in a multiethnic community. METHODS: A population-based, incident case-control study was conducted July 1993 through June 1997 in northern Manhattan, New York, NY. Cases (n=576) of first ischemic stroke (66% >or=BORDER="0">65 years of age; 56% women; 17% whites; 26% blacks; 55% Hispanics) were enrolled and matched by age, sex, and race-ethnicity to stroke-free community controls (n=1142). All subjects were interviewed and examined and had measurements of waist-to-hip ratio (WHR). Odds ratios (ORs) of ischemic stroke were calculated with gender-specific quartiles (GQs) and gender-specific medians of WHR adjusted for stroke risk factors and body mass index (BMI). RESULTS: Compared with the first quartile, the third and fourth quartiles of WHR had an increased risk of stroke (GQ3: OR, 2.4; 95% CI, 1.5 to 3.9; GQ4: OR, 3.0; 95% CI, 1.8 to 4.8) adjusted for other risk factors and BMI. Those with WHR equal to or greater than the median had an overall OR of 3.0 (95% CI, 2.1 to 4.2) for ischemic stroke even after adjustment for other risk factors and BMI. Increased WHR was associated with a greater risk of stroke in men and women and in all race-ethnic groups. The effect of WHR was stronger among younger persons (test for heterogeneity, P<0.0002) (<65 years of age: OR, 4.4; 95%CI, 2.2 to 9.0; >or=65 years of age: OR, 2.2; 95% CI, 1.4 to 3.2). WHR was associated with an increased risk among those with and without large-artery atherosclerotic stroke. CONCLUSIONS: Abdominal obesity is an independent, potent risk factor for ischemic stroke in all race-ethnic groups. It is a stronger risk factor than BMI and has a greater effect among younger persons. Prevention of obesity and weight reduction need greater emphasis in stroke prevention programs.

Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes: the Northern Manhattan Prospective Cohort Study.

BACKGROUND AND PURPOSE: Atherosclerosis is a complex disorder with hereditary and environmental causes. Carotid artery intima-media wall thickness (IMT) is a useful measure of atherosclerosis. The objective of this study was to determine the association between carotid IMT and functional promoter variants of stromelysin-1 (MMP3: -1612 5A>6A), interleukin-6 (IL6: -174G>C), and hepatic lipase (HL: -480C>T) genes. METHODS: B-mode carotid ultrasound was performed among 87 subjects (mean age, 70+/-12 years; 55% women; 60% Caribbean-Hispanic, 25% black, and 13% white) from the Northern Manhattan Prospective Cohort Study. Carotid IMT was calculated as a composite measure (mean of the maximum IMT in the bifurcation, the common carotid artery, and the internal carotid artery). RESULTS: For all polymorphisms, genotype distribution was not significantly different from Hardy-Weinberg equilibrium. The frequencies of the rare alleles were as follows: MMP3 -1612 5A>6A, 0.31 (95% CI, 0.25 to 0.39); IL6 -174 G>C, 0.20 (95% CI, 0.13 to 0.25); and HL -480 C>T, 0.45 (95% CI, 0.35 to 0.50). Carotid IMT in the sample was 0.78+/-0.18 mm. Subjects with the MMP3 genotype 6A6A had 8% greater mean carotid IMT than the other MMP3 genotypes combined (0.95+/-0.17 versus 0.87+/-0.15 mm; P=0.04). Subjects with the IL6 genotype GG had 11% greater IMT (0.85+/-0.17 versus 0.76+/-0.16 mm; P=0.03), and those with the HL genotype CC had 13% greater IMT (0.87+/-20 versus 0.76+/-0.18 mm; P=0.02) than the other genotypes combined. Adjustment for other risk factors did not change these associations. CONCLUSIONS: Carotid IMT is higher among subjects homozygous for functional variants in genes related to matrix deposition (MMP3 -16126A), inflammation (IL6 -174G), and lipid metabolism (HL -480C). These associations were independent of race-ethnicity and some environmental exposures. Further studies are needed to confirm these genotype-phenotype associations.