Adverse effects of superactivated charcoal administered to healthy volunteers.

OBJECTIVES: Activated charcoal is frequently administered to drug overdose patients, who may experience nausea and vomiting secondary to the drug overdose. Drinking a charcoal slurry orally may be difficult for them necessitating a gastric tube. The purpose of this study is to report the frequency of adverse effects from oral superactivated charcoal (SAC) given to healthy volunteers. METHODS: Healthy adult study subject volunteers were given a single 2000 mg (first 13 subjects) or 3000 mg (remaining 35 subjects) dose of acetaminophen. Subjects were randomized to receive no charcoal (ctrl) or 75 grams of SAC administered orally in a slurry 3 hours following the acetaminophen dose. The adverse effects of both groups were recorded and compared. RESULTS: There were 48 study subject runs. The mean age was 27.4 years (SD6.5). SAC was administered to 24 subjects. Adverse effect rates were as follows (*one-tail p 71kg) completed SAC consumption significantly faster than the 12 lighter subjects (18.7 vs 7.8 minutes, p = 0.04, single sided). This comparison included the two subjects (both lighter) who did not finish SAC consumption, so this difference was no longer significant when these two subjects were removed. CONCLUSIONS: Superactivated charcoal consumption is associated with significant adverse effects in some healthy volunteers, which may impede a drug overdose patient's ability to willingly drink charcoal slurry in a reasonable period of time.P20 RR11091/RR/NCRR NIH HHS/United State

Malpract ice Risk Assessm ent Among Different Approac hes For Informed Consent

Abstract Introduction: The standards for obtahing Thformed consent, set forth by the Hawaii Revised Statutes, establish that it is the physician's duty to disclose what a reasonable person objectively needs to hear in order to make an informed decision. It is the purpose of this study to report the opinions of medical malpractice attorneys to survey their opinion whether full or limited disclosure of alternative treat ments in informed consent is viewed as having a lower malpractice risk. Methods: Hawaii medical malpractice attorneys viewed a com pilation of arguments forand against both full and limited disclosure, and completed an opinion survey after reading samples of disclo sure statements h two different case scenarios: 1) a pediatric emergency department case involving a febrile child at risk for occult bacteremia, and 2) an obstetrics case Thvolving a woman with a postdate pregnancy. Results: A vast majority of respondents believe that, in general and in the obstetrics case, full disclosure results in less liability. In the pediatrics ED case, 46% chose full disclosure as having less liability, 38% believe that the same liability exists with both full and limited disclosure, and 15% believe that limited disclosure is asso ciated with less liability in this case. Conclusions: Hawaii attorneys with medical malpractice experi ence overwhelmingly agree that, in general, full disclosure is asso ciated will less medical legal liability. Full disclosure was also the option selected as associated with less liability by a majority of attorneys ha sample obstetrical case. Opinions were more diverse in the pediatrics ED case. Many attorneys stressed thatjudging the risk of liability in general is difficult, and should be done on a case by case basis

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Malpractice risk assessment among different approaches for informed consent.

INTRODUCTION: The standards for obtaining informed consent, set forth by the Hawaii Revised Statutes, establish that it is the physician's duty to disclose what a reasonable person objectively needs to hear in order to make an informed decision. It is the purpose of this study to report the opinions of medical malpractice attorneys to survey their opinion whether full or limited disclosure of alternative treatments in informed consent is viewed as having a lower malpractice risk. METHODS: Hawaii medical malpractice attorneys viewed a compilation of arguments for and against both full and limited disclosure, and completed an opinion survey after reading samples of disclosure statements in two different case scenarios: 1) a pediatric emergency department case involving a febrile child at risk for occult bacteremia, and 2) an obstetrics case involving a woman with a postdate pregnancy. RESULTS: A vast majority of respondents believe that, in general and in the obstetrics case, full disclosure results in less liability. In the pediatrics ED case, 46% chose full disclosure as having less liability, 38% believe that the same liability exists with both full and limited disclosure, and 15% believe that limited disclosure is associated with less liability in this case. CONCLUSIONS: Hawaii attorneys with medical malpractice experience overwhelmingly agree that, in general, full disclosure is associated will less medical legal liability. Full disclosure was also the option selected as associated with less liability by a majority of attorneys in a sample obstetrical case. Opinions were more diverse in the pediatrics ED case. Many attorneys stressed that judging the risk of liability in general is difficult, and should be done on a case by case basis

Acetaminophen levels 4 and 7 hours after 2000 and 3000 mg single doses in healthy adults.

PURPOSE: Therapeutic acetaminophen levels are not achieved at currently recommended doses. The purpose of this study is to determine acetaminophen levels in healthy adults after taking a single dose well in excess of the recommended dose. METHODS: 24 healthy adults received single 2 or 3 gram acetaminophen doses. Serum acetaminophen levels were drawn at 4 and 7 hours after the dose. RESULTS: The 2 gram doses (6 subjects) ranged from 23 to 40 mg/kg of body weight. The 3 gram single doses (18 subjects) ranged from 38 to 69 mg/kg of body weight. Mean 4-hour acetaminophen levels for 2 and 3 gram doses were 8.8 (SD 3.6, range 3-13) and 21.8 (SD 6.5, range 6-32) mcg/ml, respectively. Mean 7-hour acetaminophen levels for 2 and 3 gram doses were 1.5 (SD 1.4, range 0-3) and 7.7 (SD 4.6, range 0-17) mcg/ml, respectively. CONCLUSIONS: Dosing by weight (i.e., mg/kg) appears to provide a more predictable dose-response relationship. Optimal adult dosing appears to be somewhere in the 20 to 30 mg/kg range based on the premise that the 4 hour level is a trough level that should be in the low therapeutic range.P20 RR11091/RR/NCRR NIH HHS/United State

Ritual + Sustainability Science? A Portal into the Science of Aloha

In this paper, we propose that spiritual approaches rooted in the practice of Hawai‘i ritual provide a powerful portal to revealing, supporting, and enhancing our collective aloha (love, fondness, reciprocity, as with a family member) for and dedication to the places and processes that we steward. We provide a case study from Hawai‘i, where we, a group of conservation professionals known as Hālau ‘Ōhi’a, have begun to foster a collective resurgence of sacred commitment to the places and processes we steward through remembering and manifesting genealogical relationships to our landscapes through Indigenous Hawaiian ritual expression. We discuss how a ritual approach to our lands and seas makes us better stewards of our places, better members of our families and communities, and more fulfilled individuals. We assert that foundations of the spiritual and the sacred are required for effectively advancing the science of sustainability, the management of natural resources, and the conservation of nature