Sample records for hours post dosing
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An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.
Chen, Justin R; Buchmiller, Brett L; Khan, David A
2015-01-01
Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Kassel, Lynn E; Van Matre, Edward T; Foster, Charles J; Fish, Douglas N; Mueller, Scott W; Sherman, Deb S; Wempe, Michael F; MacLaren, Robert; Neumann, Robert T; Kiser, Tyree H
2018-06-15
Neurocritically-ill patients have clinically significant alterations in pharmacokinetic parameters of renally-eliminated medications, which may result in subtherapeutic plasma and cerebrospinal fluid antibiotic concentrations. Prospective, randomized, open-label study of adult neurocritically-ill patients treated with vancomycin and cefepime. Vancomycin 15 mg/kg and cefepime 2 g were dosed at every 8 or 12-hour intervals. The primary outcomes were the achievement of pharmacodynamic targets related to time of unbound drug above minimum inhibitory concentrations (MIC) for 60% or more of the dosing interval (fT>MIC ≥60%) for β-lactams and ratio of 24-hour area under the curve (AUC):MIC of 400 or greater for vancomycin. Twenty patients were included in the study. Patients were divided equally between the every 12-hour (n=10) and every 8-hour (n=10) dosing groups. Patients (mean age of 51.8 ± 11 years) were primarily male (60%) and Caucasian (95%), and the majority had an admission diagnosis of intracranial hemorrhage (80%). Compared to the every 12-hour group, the every 8-hour vancomycin group achieved target trough concentrations (>15 μg/ml) significantly more frequently at initial measurement (0% vs 80%, p<0.01) and at 7 to 10 days (0% vs 90%, p=0.045) and achieved pharmacodynamic targets more frequently at increasing MICs. Similarly, compared to every 12-hour dosing, the every 8-hour cefepime dosing strategy significantly increased pharmacodynamic target attainment (fT>MIC ≥60%) at an MIC of 8 μg/ml (20% vs 70%, p=0.02). This study demonstrated that more frequent dosing of vancomycin and cefepime is required to achieve optimal pharmacodynamic targets in adult neurocritically-ill patients. The need for increased total daily doses is potentially secondary to the development of augmented renal clearance. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Arsanious, David; Gage, Emmanuel; Koning, Jonathon; Sarhan, Mazin; Chaiban, Gassan; Almualim, Mohammed; Atallah, Joseph
2016-01-01
One of the potential side effects with radiofrequency ablation (RFA) includes painful cutaneous dysesthesias and increased pain due to neuritis or neurogenic inflammation. This pain may require the prescription of opioids or non-opioid analgesics to control post-procedural pain and discomfort. The goal of this study is to compare post-procedural pain scores and post-procedural oral analgesic use in patients receiving continuous thermal radiofrequency ablation versus patients receiving pulsed dose radiofrequency immediately followed by continuous thermal radiofrequency ablation for zygopophaseal joint disease. This is a prospective, double-blinded, randomized, controlled trial. Patients who met all the inclusion criteria and were not subject to any of the exclusion criteria were required to have two positive diagnostic medial branch blocks prior to undergoing randomization, intervention, and analysis. University hospital. Eligible patients were randomized in a 1:1 ratio to either receive thermal radiofrequency ablation alone (standard group) or pulsed dose radiofrequency (PDRF) immediately followed by thermal radiofrequency ablation (investigational group), all of which were performed by a single Board Certified Pain Medicine physician. Post-procedural pain levels between the two groups were assessed using the numerical pain Scale (NPS), and patients were contacted by phone on post-procedural days 1 and 2 in the morning and afternoon regarding the amount of oral analgesic medications used in the first 48 hours following the procedure. Patients who received pulsed dose radiofrequency followed by continuous radiofrequency neurotomy reported statistically significantly lower post-procedural pain scores in the first 24 hours compared to patients who received thermal radiofrequency neurotomy alone. These patients also used less oral analgesic medication in the post-procedural period. These interventions were carried out by one board accredited pain physician at one
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Radiation Dose to Post-Chernobyl Cleanup Workers
Radiation dose calculation for post-Chernobyl Cleanup Workers in Ukraine - both external radiation exposure due to fallout and internal doses due to inhalation (I131 intake) or ingestion of contaminated foodstuffs.
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Luggya, Tonny Stone; Roche, Tony; Ssemogerere, Lameck; Kintu, Andrew; Kasumba, John Mark; Kwizera, Arthur; Tindimwebwa, Jose Vb
2017-06-01
Surgery and Anesthesia cause an excessive pro-inflammatory response. Mulago Hospital is faced with staff shortage making post-operative pain management difficult.Interleukin-6 (IL-6) drives inflammatory pain, endothelial cell dysfunction and fibrogenesis. Ketamine is cheap and, readily available. We hypothesized that its attenuation of serum IL-6 was a surrogate for clinical benefit. Institutional Review Board's approval was sought and RCT was registered at clinical trials.gov (identifier number: NCT01339065). Consenting patients were randomized to receive pre-incision intravenous ketamine - 0.5mg/kg or 0.9% saline placebo in weighted dosing. Blood samples were collected and laboratory analyzed at baseline, post-operatively in PACU, 24 and 48 hours respectively. We recruited 39 patients of whom 18 were randomized to the ketamine arm and 21 in the placebo arm with follow up at 24 and 48 hours. Serum IL-6 and IL-1β levels were analyzed using ELIZA assay of pre-coated micro wells. Ketamine suppressed serum IL-6 at PACU with reduced increase at 24 hours. There was no reaction in 98% of IL-1β assayed. Low-dose ketamine attenuated early serum IL-6 levels due to surgical response with reduced 24 hour increase, but the difference was not statistically significant and we recommend more studies.
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Comparison of lornoxicam and low-dose tramadol for management of post-thyroidectomy pain.
Yücel, Ali; Yazıcı, Alper; Müderris, Togay; Gül, Fatih
2016-10-01
The present study sought to compare the analgesic efficacy and adverse effects of intravenous (IV) lornoxicam and tramadol to investigate if lornoxicam is a reasonable alternative to a weak opioid for post-thyroidectomy pain. Fifty patients of American Society of Anesthesiologists class I or II, 18 to 65 years of age, and who underwent thyroidectomy were assigned to 2 groups in a randomized manner. Group L received 8 mg of lornoxicam IV and Group T received 1 mg/kg of tramadol IV at conclusion of the operation. Pain intensity of patients was recorded at 15 and 30 minutes, and at 1, 2, 3, 4, 6, 12, and 24 hours after the initial dose with Numerical Rating Scale (NRS) and Ramsey Sedation Scale. Electrocardiogram, heart rate, systolic/diastolic and average artery pressure and peripheral oxygen saturations were monitored continuously during this period. Patients completed satisfaction questionnaires at 24th hour. Both drugs produced acceptable analgesia; however, significantly fewer patients reported 1 or more adverse events with lornoxicam than with tramadol. Most commonly seen in Group T was nausea/vomiting. NRS scores at 15 minutes, 30 minutes, and 1 hour were lower in Group L than in Group T (p<0.05), but there was no significant difference between groups after postoperative first hour. First analgesic requirement time was significantly longer in Group L compared to Group T (p<0.001). No serious complications were seen in either group. Lornoxicam is a safe and effective analgesic that may be used with fewer complications than low-dose tramadol for treatment of moderate to severe postoperative pain.
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Leffel, Joseph K.; Kosobud, Ann E; Timberlake, William
2009-01-01
Administration of several drugs of abuse on a 24-hour schedule has been shown to entrain both pre-drug (anticipatory) and post-drug (evoked) circadian activity episodes that persist for several days when the drug is withheld. The present tested the entrainment effects of fentanyl, an opioid agonist with a noted abuse liability, and haloperidol, an antipsychotic dopamine antagonist without apparent abuse liability. Adult female Sprague-Dawley rats housed under constant light in cages with attached running wheels received repeated low, medium, or high doses of either fentanyl or haloperidol on a 24-hour administration schedule followed by a 31-hour schedule (Experiment 1) or solely on a 31-hour schedule (Experiment 2). The results showed that all three doses of fentanyl entrained both pre-drug and post-drug episodes of wheel running when administered every 24░hours, and the combined pre- and post-fentanyl activity episodes persist for at least 3 days when the drug is withheld during test days. On the 31-hour schedule, fentanyl produced an ``ensuing" activity episode approximately 24░hours post-administration, but failed to produce an anticipatory episode 29–31░hours post-administration. In contrast, haloperidol injections failed to produce both pre-drug episodes on the 24-hour schedule and circadian ensuing episodes on the 31-hour schedule, and post-haloperidol suppression of activity appeared to mask the freerunning activity rhythm. Taken together, these results provide additional evidence that drugs of abuse share a common ability to entrain circadian activity episodes. PMID:19595707
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Conway, Sadie H.; Pompeii, Lisa A.; Roberts, Robert E.; Follis, Jack L.; Gimeno, David
2015-01-01
Objectives To examine the presence of a dose-response relationship between work hours and incident cardiovascular disease (CVD) in a representative sample of U.S. workers. Methods Retrospective cohort study of 1,926 individuals from the Panel Study of Income Dynamics (1986–2011) employed for at least 10 years. Restricted cubic spline regression was used to estimate the dose-response relationship of work hours with CVD. Results A dose-response relationship was observed in which an average workweek of 46 hours or more for at least 10 years was associated with increased risk of CVD. Compared to working 45 hours per week, working an additional 10 hours per week or more for at least 10 years increased CVD risk by at least 16%. Conclusions Working more than 45 work hours per week for at least 10 years may be an independent risk factor for CVD. PMID:26949870
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Conway, Sadie H; Pompeii, Lisa A; Roberts, Robert E; Follis, Jack L; Gimeno, David
2016-03-01
The aim of this study was to examine the presence of a dose-response relationship between work hours and incident cardiovascular disease (CVD) in a representative sample of U.S. workers. A retrospective cohort study of 1926 individuals from the Panel Study of Income Dynamics (1986 to 2011) employed for at least 10 years. Restricted cubic spline regression was used to estimate the dose-response relationship of work hours with CVD. A dose-response relationship was observed in which an average workweek of 46 hours or more for at least 10 years was associated with an increased risk of CVD. Compared with working 45 hours per week, working an additional 10 hours per week or more for at least 10 years increased CVD risk by at least 16%. Working more than 45 work hours per week for at least 10 years may be an independent risk factor for CVD.
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Projected 24-hour post-dose ocular itching scores post-treatment with olopatadine 0.7% versus 0.2.
Fidler, Matthew L; Ogundele, Abayomi; Covert, David; Sarangapani, Ramesh
2018-04-21
Olopatadine is an antihistamine and mast cell stabilizer used for treating allergic conjunctivitis. Olopatadine 0.7% has been recently approved for daily dosing in the US, which supersedes the previously approved 0.2% strength. The objective of this analysis was to characterize patients who have better itching relief at 24 h when taking olopatadine 0.7% treatment instead of olopatadine 0.2% (in terms of proportions of responses) and relate this to the severity of baseline itching as an indirect metric of a patient's sensitivity to antihistamines. A differential odds model was developed using data from two conjunctival allergen challenge (CAC) studies to characterize individual-level and population-level response to ocular itching following olopatadine treatment and the data was analyzed retrospectively. This modeling analysis was designed to predict 24 h ocular itching scores and to quantify the differences in 24 h itching relief following treatment with olopatadine 0.2% versus 0.7% in patients with moderate-to-high baseline itching. A one-compartment kinetic-pharmacodynamic E max model was used to determine the effect of olopatadine. Impact of baseline itching severity, vehicle effect and the drug effect on the overall itching scores post-treatment were explicitly incorporated in the model. The model quantified trends observed in the clinical data with regards to both mean scores and the proportions of patients responding to olopatadine treatment. The model predicts a higher proportion of patients in the olopatadine 0.7% versus 0.2% group will experience relief within 24 h. This prediction was confirmed with retrospective clinical data analysis. The number of allergy patients relieved with olopatadine 0.7% increased with higher baseline itching severity scores, when compared to olopatadine 0.2%.
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Validation of 1-hour post-thyroidectomy parathyroid hormone level in predicting hypocalcemia
2014-01-01
Background Prior work by our group suggested that a single one hour post-thyroidectomy parathyroid hormone (1 hr PTH) level could accurately stratify patients into high and low risk groups for the development of hypocalcemia. This study looks to validate the safety and efficacy of a protocol based on a 1 hr PTH threshold of 12 pg/ml. Study design Retrospective analysis of consecutive cohort treated with standardized protocol. Methods One hundred and twenty five consecutive patients underwent total or completion thyroidectomy and their PTH level was drawn 1-hour post operatively. Based on our previous work, patients were stratified into either a low risk group (PTH < 12 pg/ml) or a high risk group (PTH ≥ 12 pg/ml). Patients in the high risk group were immediately started on prophylactic calcium carbonate (5–10 g/d) and calcitriol (0.5-1.0 mcg/d). The outcomes were then reviewed focusing mainly on how many low risk patients developed hypocalcemia (false negative rate), and how many high risk patients failed prophylactic therapy. Results Thirty one patients (25%) were stratified as high risk, and 94 (75%) as low risk. Five (16%) of the high risk patients became hypocalcemic despite prophylactic therapy. Two of the low risk group became hypocalcemic, (negative predictive value = 98%). None of the hypocalcemic patients had anything more than mild symptoms. Conclusions A single 1-hour post-thyroidectomy PTH level is a very useful way to stratify thyroidectomy patients into high and low risk groups for development of hypocalcemia. Early implementation of oral prophylactic calcium and vitamin D in the high risk patients is a very effective way to prevent serious hypocalcemia. Complex protocols requiring multiple calcium and PTH measurements are not required to guide post-thyroidectomy management. PMID:24476535
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The effect of perioperative dexamethasone dosing on post-tonsillectomy hemorrhage risk.
Yiu, Yin; Mahida, Justin B; Cooper, Jennifer N; Elsey, Nicole M; Deans, Katherine J; Minneci, Peter C; Merrill, Tyler B; Tobias, Joseph D; Elmaraghy, Charles A
2017-07-01
Dexamethasone is currently recommended for routine prophylaxis against postoperative nausea and vomiting after tonsillectomy procedures. However, some studies have raised concern that dexamethasone use may lead to higher rates of post-tonsillectomy hemorrhage. Our objective was to determine whether higher doses of dexamethasone administered perioperatively during tonsillectomy procedures are associated with an increased risk of secondary post-tonsillectomy hemorrhage. We conducted a retrospective review of 9843 patients who underwent tonsillectomy and received dexamethasone at our institution from January 2010 to October 2014. We compared the dose of dexamethasone administered to patients who did and did not develop secondary post-tonsillectomy hemorrhage using Mann Whitney U tests. Multivariable logistic regression models were used to evaluate the association between dexamethasone dose and post-tonsillectomy hemorrhage after adjustment for demographic and clinical characteristics. A total of 280 (2.8%) patients developed secondary post-tonsillectomy hemorrhage. Patients who developed hemorrhage tended to be older (median (interquartile range) 7 (4-11) vs. 5 (3-8) years), p < 0.001) and had undergone tonsillectomy more often for chronic tonsillitis but less often for tonsillar or adenotonsillar hypertrophy or sleep disturbances. Dexamethasone dose was significantly lower on average in patients who experienced secondary post-tonsillectomy hemorrhage (median (interquartile range) 0.19 (0.14, 0.23) mg/kg vs. 0.21 (0.17, 0.30), p < 0.001). Multivariable modeling demonstrated that the dose of dexamethasone was not significantly associated with post-tonsillectomy hemorrhage after adjustment for age. There does not appear to be a dose-related increase in the risk of post-tonsillectomy hemorrhage for patients receiving dexamethasone during tonsillectomy procedures. Copyright © 2017 Elsevier B.V. All rights reserved.
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Prolonged and symptomatic bradycardia following a single dose of fingolimod.
Faber, Hans; Fischer, Hans-Jörg; Weber, Frank
2013-01-01
Fingolimod-related bradycardia is usually asymptomatic, reaches its nadir within 6 hours post-dose and recovers spontaneously. Here we report the case of a 30-year-old MS patient with vagotonia who developed symptomatic bradycardia with 33 beats per minute at nadir 39 hours after a single dose of fingolimod. Bradycardia was responsive to atropine, but returned within 2 hours. Overall, it took a week until the patient recovered. Extended monitoring is advised in patients with symptomatic bradycardia.
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Roth, Thomas; Zammit, Gary K.; Scharf, Martin B.; Farber, Robert
2007-01-01
Objective: To evaluate the efficacy and tolerability of immediate release indiplon capsules in patients with chronic insomnia using an “as-needed” dosing strategy in response to difficulty falling back to sleep following a middle of the night, nocturnal awakening. Methods: Adult outpatients (N=264; 71% female; age, 46 years) who met DSM-IV criteria for primary insomnia, with average total sleep time (TST) <6.5 hours and >8 nights in the past month with nocturnal awakenings, were randomized to 4 weeks of double-blind treatment with 10mg or 20mg indiplon capsules, or placebo. The primary endpoint was latency to sleep onset post-dosing after a middle of the night awakening (LSOpd). Secondary endpoints included patients' subjective assessment of total sleep time (sTSTpd). Next day residual effects were evaluated by a 100mm Visual Analog Scale (VAS) rating of sleepiness. Results: Both doses of indiplon significantly reduced LSOpd at all time-points. Compared to placebo (45.2 min), the 4-week least squares (LS) mean LSOpd was 36.5 min in the indiplon 10mg group (P=0.0023) and 34.4 min in the indiplon 20mg group (P<0.0001). The 4-week LS mean sTSTpd was higher in the indiplon 10mg group (253 min) and 20mg group (278 min) compared to placebo (229 min; P<0.01 for both comparisons). There was no increase observed in VAS ratings of next-day sleepiness for either dose of indiplon when compared to placebo. Indiplon was well-tolerated at both doses. Conclusions: Patients with chronic insomnia with nocturnal awakenings achieved significant and sustained improvement in sleep parameters while utilizing an as-needed post bedtime dosing strategy with indiplon capsules. Indiplon was well-tolerated, with no self-rated, next-day residual effects. Citation: Roth T; Zammit GK; Scharf MB; Farber R. Efficacy and safety of as-needed, post bedtime dosing with indiplon in insomnia patients with chronic difficulty maintaining sleep. SLEEP 2007;30(12):1731-1738. PMID:18246982
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Prince, Toni-Moi; Wimmer, Mathieu; Choi, Jennifer; Havekes, Robbert; Aton, Sara; Abel, Ted
2014-01-01
Sleep deprivation disrupts hippocampal function and plasticity. In particular, long-term memory consolidation is impaired by sleep deprivation, suggesting that a specific critical period exists following learning during which sleep is necessary. To elucidate the impact of sleep deprivation on long-term memory consolidation and synaptic plasticity, long-term memory was assessed when mice were sleep deprived following training in the hippocampus-dependent object place recognition task. We found that 3 hours of sleep deprivation significantly impaired memory when deprivation began 1 hour after training. In contrast, 3 hours of deprivation beginning immediately post-training did not impair spatial memory. Furthermore, a 3-hour sleep deprivation beginning 1 hour after training impaired hippocampal long-term potentiation (LTP), whereas sleep deprivation immediately after training did not affect LTP. Together, our findings define a specific 3-hour critical period, extending from 1 to 4 hours after training, during which sleep deprivation impairs hippocampal function. PMID:24380868
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Low dose radiation interactions with the transformation growth factor (TFG)-beta pathway
NASA Astrophysics Data System (ADS)
Maslowski, Amy Jesse
A major limiting factor for long-term, deep-space missions is the radiation dose to astronauts. Because the dose to the astronauts is a mixed field of low- and high-LET radiation, there is a need to understand the effects of both radiation types on whole tissue; however, there are limited published data on the effects of high-LET (linear-energy-transfer) radiation on tissue. Thus, we designed a perfusion chamber system for rat trachea in order to mimic in vivo respiratory tissue. We successfully maintained the perfused tracheal tissue ex vivo in a healthy and viable condition for up to three days. In addition, this project studied the effects of high-LET Fe particles on the overall transformation growth factor (TGF)-beta response after TGF-beta inactivation and compared the results to the TGF-beta response post x-ray irradiation. It was found that a TGF-beta response could be measured in the perfused tracheal tissue, for x-ray and Fe particle irradiations, despite the high autofluorescent background intrinsic to tissue. However, after comparing the TGF-beta response of x-ray irradiation to High-Z-High-energy (HZE) irradiation, there was not a significant difference in radiation types. The TGF-beta response in x-ray and HZE irradiated perfusion chambers was also measured over time post irradiation. It was found that for 6 hour and 8 hour post irradiation, the TGF-beta response was higher for lower doses of radiation than for higher doses. This is in contrast to the 0 hour fixation which found the TGF-beta response to increase with increased dose. The inverse relationship found for 6 hour and 8 hour fixation times may indicate a threshold response for TGF-beta response; i.e., for low doses, a threshold of dose must be reached for an immediate TGF-beta response, otherwise the tissue responds more slowly to the irradiation damage. This result was unexpected and will require further investigation to determine if the threshold can be determined for the 250 kVp x-rays and
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Rajan, Priya; Soundara Raghavan, S; Sharma, Deepak
2017-09-11
Traditional practice after vaginal hysterectomy was to keep the vaginal pack and urinary catheter for 24 hours post operatively. But there were studies that prolonged cathterisation was associated with urinary infection. So this study was conducted to compare the post operative outcome when the urinary catheter and vaginal pack were removed after 3 hours and after 24 hours after surgery. The study was done in the Department of Obstetrics and Gynecology, in a tertiary teaching institute of South India from September 2008 to March 2010. It was a randomised controlled trial involving 200 women undergoing vaginal surgery, who were randomly assigned to 2 groups - catheter and vaginal pack were removed either in 3 h in study group or were removed in 24 h in control group. The outcome of the study were vaginal bleeding, urinary retention, febrile morbidity, and urinary infection. There was no significant difference between the study and control groups with respect to vaginal bleeding (0 and 1%, p = 1), urinary retention (9 and 4%, p = 0.15), febrile morbidity (7 and 4%, p = 0.35), and urinary infection (26% in each group, p = 1.0). Keeping the urinary catheter and vaginal pack for 24 h following vaginal surgery does not offer any additional benefit against removing them after 3 h.
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Nachón-García, Francisco; Hurtado-Alvarado, Gabriela; Acosta-Hernández, Mario E; Peña-Escudero, Carolina; Priego-Fernández, Sergio; Alvarez-Herrera, Samantha; Becerril-Villanueva, Enrique; Pérez-Sánchez, Gilberto; Pavón, Lenin; García-García, Fabio
2018-07-15
The long-term effect of immune system activation by a low dose of lipopolysaccharide on neuro-immune-endocrine regulation is unclear. Sleep, neurotransmitter concentrations, TNF-α, and corticosterone levels were evaluated in male Wistar rats implanted with conventional sleep recordings. In this work, we found that REM sleep was reduced in the first 4 h post-injection, without affecting the total sleep time, while adrenaline concentration was reduced in the hippocampus at 24 h post-injection of LPS. Our results demonstrated that, although the acute immune response was not evident 24 h after the injection of LPS, it was able to promote the reduction of AD in the hippocampus, which may explain in part the depressive behavior reported in rodents following LPS administration. Copyright © 2018 Elsevier B.V. All rights reserved.
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Gamma-H2AX-based dose estimation for whole and partial body radiation exposure.
Horn, Simon; Barnard, Stephen; Rothkamm, Kai
2011-01-01
Most human exposures to ionising radiation are partial body exposures. However, to date only limited tools are available for rapid and accurate estimation of the dose distribution and the extent of the body spared from the exposure. These parameters are of great importance for emergency triage and clinical management of exposed individuals. Here, measurements of γ-H2AX immunofluorescence by microscopy and flow cytometry were compared as rapid biodosimetric tools for whole and partial body exposures. Ex vivo uniformly X-irradiated blood lymphocytes from one donor were used to generate a universal biexponential calibration function for γ-H2AX foci/intensity yields per unit dose for time points up to 96 hours post exposure. Foci--but not intensity--levels remained significantly above background for 96 hours for doses of 0.5 Gy or more. Foci-based dose estimates for ex vivo X-irradiated blood samples from 13 volunteers were in excellent agreement with the actual dose delivered to the targeted samples. Flow cytometric dose estimates for X-irradiated blood samples from 8 volunteers were in excellent agreement with the actual dose delivered at 1 hour post exposure but less so at 24 hours post exposure. In partial body exposures, simulated by mixing ex vivo irradiated and unirradiated lymphocytes, foci/intensity distributions were significantly over-dispersed compared to uniformly irradiated lymphocytes. For both methods and in all cases the estimated fraction of irradiated lymphocytes and dose to that fraction, calculated using the zero contaminated Poisson test and γ-H2AX calibration function, were in good agreement with the actual mixing ratios and doses delivered to the samples. In conclusion, γ-H2AX analysis of irradiated lymphocytes enables rapid and accurate assessment of whole body doses while dispersion analysis of foci or intensity distributions helps determine partial body doses and the irradiated fraction size in cases of partial body exposures.
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Yarema, Mark C; Green, Jason P; Sivilotti, Marco L A; Johnson, David W; Nettel-Aguirre, Alberto; Victorino, Charlemaigne; Spyker, Daniel A; Rumack, Barry H
2017-02-01
The interpretation of acetaminophen concentrations obtained prior to 4 hours after an acute, single overdose remains unclear. Patient care decisions in the Emergency Department could be accelerated if such concentrations could reliably exclude the need for treatment. To determine the agreement between a serum acetaminophen concentration obtained less than 4 hours after an acute ingestion and the subsequent 4 + hour concentration, and the predictive accuracy of early concentrations for identifying patients with potentially toxic exposures. A secondary analysis of patients admitted for acetaminophen poisoning at one of the 34 hospitals in eight Canadian cities from 1980 to 2005. We examined serum acetaminophen concentrations obtained less than 4 hours post-ingestion, and again 4 or more hours post-ingestion. For the diagnostic accuracy analysis, we specified a cutpoint of 100 μg/mL (662 μmol/L) obtained between 2 and 4 hours and a subsequent 4 to 20 hour acetaminophen concentration above the nomogram treatment line of 150 μg/mL (993 μmol/L). Of 2454 patients identified, 879 (36%) had a subsequent acetaminophen concentration above the nomogram treatment line. The 2-4 hour concentration demonstrated a sensitivity of 0.96 [95% CI; 0.94, 0.97] and a negative likelihood ratio of 0.070 [0.048, 0.10]. Coingested opioids reduced this sensitivity to 0.91 [0.83, 0.95], and antimuscarinics to 0.86 [0.72, 0.94]. Only very low to undetectable acetaminophen concentrations prior to 4 hours reliably excluded a subsequent concentration over the treatment line. Applying an acetaminophen concentration cutpoint of 100 μg/mL (662 μmol/L) at 2-4 hours after an acute ingestion as a threshold for repeat testing and/or treatment would occasionally miss potentially toxic exposures. Absorption of acetaminophen is only slightly delayed by coingested opioids or antimuscarinics. Our analysis validates the practice of not retesting when the first post-ingestion acetaminophen
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Murray, Nicholas G; D'Amico, Nathan R; Powell, Douglas; Mormile, Megan E; Grimes, Katelyn E; Munkasy, Barry A; Gore, Russell K; Reed-Jones, Rebecca J
2017-05-01
Approximately 90% of athletes with concussion experience a certain degree of visual system dysfunction immediately post-concussion. Of these abnormalities, gaze stability deficits are denoted as among the most common. Little research quantitatively explores these variables post-concussion. As such, the purpose of this study was to investigate and compare gaze stability between a control group of healthy non-injured athletes and a group of athletes with concussions 24-48hours post-injury. Ten collegiate NCAA Division I athletes with concussions and ten healthy control collegiate athletes completed two trials of a sport-like antisaccade postural control task, the Wii Fit Soccer Heading Game. During play all participants were instructed to minimize gaze deviations away from a central fixed area. Athletes with concussions were assessed within 24-48 post-concussion while healthy control data were collected during pre-season athletic screening. Raw ocular point of gaze coordinates were tracked with a monocular eye tracking device (240Hz) and motion capture during the postural task to determine the instantaneous gaze coordinates. This data was exported and analyzed using a custom algorithm. Independent t-tests analyzed gaze resultant distance, prosaccade errors, mean vertical velocity, and mean horizontal velocity. Athletes with concussions had significantly greater gaze resultant distance (p=0.006), prosaccade errors (p<0.001), and horizontal velocity (p=0.029) when compared to healthy controls. These data suggest that athletes with concussions had less control of gaze during play of the Wii Fit Soccer Heading Game. This could indicate a gaze stability deficit via potentially reduced cortical inhibition that is present within 24-48hours post-concussion. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Primary closure versus delayed closure for non bite traumatic wounds within 24 hours post injury.
Eliya-Masamba, Martha C; Banda, Grace W
2013-10-22
Acute traumatic wounds are one of the common reasons why people present to the emergency department. Primary closure has traditionally been reserved for traumatic wounds presenting within six hours of injury and considered 'clean' by the attending surgeon, with the rest undergoing delayed primary closure as a means of controlling wound infection. Primary closure has the potential benefit of rapid wound healing but poses the potential threat of increased wound infection. There is currently no evidence to guide clinical decision-making on the best timing for closure of traumatic wounds. To determine the effect on time to healing of primary closure versus delayed closure for non bite traumatic wounds presenting within 24 hours post injury. To explore the adverse effects of primary closure compared with delayed closure for non bite traumatic wounds presenting within 24 hours post injury. In May 2013, for this first update we searched the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions with respect to language, date of publication or study setting. Randomised controlled trials comparing primary closure with delayed closure of non bite traumatic wounds. Two review authors independently evaluated the results of the searches against the inclusion criteria. No studies met the inclusion criteria for this review. Since no studies met the inclusion criteria, neither a meta-analysis nor a narrative description of studies was possible. There is currently no systematic evidence to guide clinical decision-making regarding the timing for closure of traumatic wounds. There is a need for robust research to investigate the effect of primary closure compared with delayed closure for non bite traumatic wounds presenting within 24 hours of injury.
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Soek, Hongdeok; Won, Jong-Uk; Lee, Tae Il; Kim, Yeong-Kwang; Lee, Wanhyung; Lee, June-Hee; Roh, Jaehoon; Yoon, Jin-Ha
2016-03-01
Lack of access to hospital facilities, indicating unmet healthcare need, plays an important role in health inequity in the workplace. We aimed to investigate the association between long working hours and unmet healthcare need. We used data from the Korea National Health and Nutrition Examination Surveys collected during 2007-2012, which included 8369 participants (4765 males, 3604 females) aged 20-54 years, who were paid workers. We used a logistic regression model with gender stratification to investigate the association between working hours and unmet healthcare need. Of the 8369 participants, 855 males (17.94%) and 981 females (27.22%) experienced unmet healthcare need. After adjusting for covariates, and compared to 30-39 working hours per week, the odds ratios (OR) of unmet healthcare need were 1.07 [(95% confidence interval (95% CI) 0.76-1.51], 1.46 (95% CI 1.03-2.07), and 1.57 (95% CI 1.11-2.23) in males, and 1.13 (95% CI 0.92-1.40), 1.30 (95% CI 0.99-1.69), and 1.60 (95% CI 1.21-2.10) in females, for 40-49, 50-59, and ≥ 60 work hours per week, respectively. There was a dose-response relationship between working hours per week and unmet healthcare need in both genders. Those who work long hours are more likely to have unmet healthcare needs, the cause of which seems to be lack of time.
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Fetus dose estimation in thyroid cancer post-surgical radioiodine therapy.
Mianji, Fereidoun A; Diba, Jila Karimi; Babakhani, Asad
2015-01-01
Unrecognised pregnancy during radioisotope therapy of thyroid cancer results in hardly definable embryo/fetus exposures, particularly when the thyroid gland is already removed. Sources of such difficulty include uncertainty in data like pregnancy commencing time, amount and distribution of metastasized thyroid cells in body, effect of the thyroidectomy on the fetus dose coefficient etc. Despite all these uncertainties, estimation of the order of the fetus dose in most cases is enough for medical and legal decision-making purposes. A model for adapting the dose coefficients recommended by the well-known methods to the problem of fetus dose assessment in athyrotic patients is proposed. The model defines a correction factor for the problem and ensures that the fetus dose in athyrotic pregnant patients is less than the normal patients. A case of pregnant patient undergone post-surgical therapy by I-131 is then studied for quantitative comparison of the methods. The results draw a range for the fetus dose in athyrotic patients using the derived factor. This reduces the concerns on under- or over-estimation of the embryo/fetus dose and is helpful for personal and/or legal decision-making on abortion. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Santini, Ferruccio; Giannetti, Monica; Ricco, Ilaria; Querci, Giorgia; Saponati, Giorgio; Bokor, Daniela; Rivolta, Giovanni; Bussi, Simona; Braverman, Lewis E; Vitti, Paolo; Pinchera, Aldo
2014-07-01
Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine (T3) sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of T3. Twenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to 131I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration. At all T3S doses, serum T3S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T3S maximum concentration (Cmax) and area under the 0- to 48-hour concentration-time curve (AUC0-48h) were directly and significantly related to the administered dose. An increase in serum TT3 concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (T4) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T3S. No adverse events were reported. (1) T3S is
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High Antigen Dose Is Detrimental to Post-Exposure Vaccine Protection against Tuberculosis.
Billeskov, Rolf; Lindenstrøm, Thomas; Woodworth, Joshua; Vilaplana, Cristina; Cardona, Pere-Joan; Cassidy, Joseph P; Mortensen, Rasmus; Agger, Else Marie; Andersen, Peter
2017-01-01
Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world's population with latent Mtb infection (LTBI), and 5-10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660) TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection.
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Shikh Alsook, Mohamad Khir; Gabriel, Annick; Piret, Joëlle; Waroux, Olivier; Tonus, Céline; Connan, Delphine; Baise, Etienne; Antoine, Nadine
2015-12-18
Mesenchymal stem cells (MSCs) harvested from cadaveric tissues represent a promising approach for regenerative medicine. To date, no study has investigated whether viable MSCs could survive in cadaveric tissues from tendon or ligament up to 72 hours of post-mortem. The purpose of the present work was to find out if viable MSCs could survive in cadaveric tissues from adult equine ligaments up to 72 hours of post-mortem, and to assess their ability (i) to remain in an undifferentiated state and (ii) to divide and proliferate in the absence of any specific stimulus. MSCs were isolated from equine cadaver (EC) suspensory ligaments within 48-72 hours of post-mortem. They were evaluated for viability, proliferation, capacity for tri-lineage differentiation, expression of cell surface markers (CD90, CD105, CD73, CD45), pluripotent transcription factor (OCT-4), stage-specific embryonic antigen-1 (SSEA-1), neuron-specific class III beta-tubulin (TUJ-1), and glial fibrillary acidic protein (GFAP). As well, they were characterized by transmission electron microscope (TEM). EC-MSCs were successfully isolated and maintained for 20 passages with high cell viability and proliferation. Phase contrast microscopy revealed that cells with fibroblast-like appearance were predominant in the culture. Differentiation assays proved that EC-MSCs are able to differentiate towards mesodermal lineages (osteogenic, adipogenic, chondrogenic). Flow cytometry analysis demonstrated that EC-MSCs expressed CD90, CD105, and CD73, while being negative for the leukocyte common antigen CD45. Immunofluorescence analysis showed a high percentage of positive cells for OCT-4 and SSEA-1. Surprisingly, in absence of any stimuli, some adherent cells closely resembling neuronal and glial morphology were also observed. Interestingly, our results revealed that approximately 15 % of the cell populations were TUJ-1 positive, whereas GFAP expression was detected in only a few cells. Furthermore, TEM analysis
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High-dose prazosin for the treatment of post-traumatic stress disorder
Koola, Maju Mathew; Fawcett, Jan A.
2014-01-01
Patients with post-traumatic stress disorder (PTSD) are frequently symptomatic despite being on medications currently approved by the US Food and Drug Administration for PTSD. There is evidence to support the notion that prazosin is effective for PTSD nightmares. However, PTSD-related nightmares often do not resolve completely on a low dose of prazosin. The capacity of prazosin to treat daytime symptoms of PTSD which are distressing to patients has not been well studied. Clinicians are reluctant to increase the dose of prazosin due to side effect concerns. To date, the highest reported dose of prazosin used for PTSD is 16 mg daily. We illustrate two case reports using high-dose (up to 30 and 45 mg) prazosin for PTSD with comorbid treatment-resistant mood disorders. We report that high-dose prazosin was safe, tolerable and effective for PTSD in adults. To our knowledge, this is the first case series to highlight the importance of using high-dose prazosin for the treatment of PTSD. In patients with partial response to currently available medications for PTSD, greater utilization of high-dose prazosin for the management of PTSD may lead to better outcomes. PMID:24490030
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Sonuga-Barke, Edmund J S; Swanson, James M; Coghill, David; DeCory, Heleen H; Hatch, Simon J
2004-09-30
Methylphenidate (MPH) is commonly prescribed in the treatment of Attention-Deficit/Hyperactivity Disorder or ADHD. Concerta and Metadate CD are once-daily formulations of MPH using different delivery mechanisms resulting in different pharmacokinetic profiles. A recent study (COMACS) showed that for near-milligram (mg) equivalent daily doses, Metadate CD provides greater symptom control in the morning (1.5 through 4.5 hours post-dose), while Concerta provides greater control in the early evening (12 hours post-dose). Non-inferential comparison of effects for different dose levels of the two formulations suggested that equivalent levels of morning symptom control could be obtained with lower daily doses of Metadate CD than Concerta; the situation being reversed in the evening. The current paper presents a secondary analysis that provides a statistical test of these observations. The COMACS study was a multi-center, double-blind crossover study of Metadate CD, Concerta and placebo with each treatment administered for 1 week. Children were assigned on the basis of their pre-trial dosage to either high (Metadate CD 60 mg; Concerta 54 mg), medium (Metadate CD 40 mg; Concerta 36 mg) or low doses (Metadate CD 20 mg; Concerta 18 mg) of MPH, and attended a laboratory school on the 7th day for assessment at 7 sessions across the day. For the post-hoc comparisons across dose levels presented here, total SKAMP scores with the active treatments (adjusted for placebo response) were analyzed using an analysis of covariance, with a combined measure modeling placebo response across all time period as the covariate. Symptom control from 1.5 through 6.0 hours post-dose was as good with lower doses of Metadate CD (20 and 40 mg) as with higher doses of Concerta (36 and 54 mg, respectively). Lower daily doses of Concerta (18 and 36 mg) and higher doses of Metadate CD (40 and 60 mg, respectively) gave equivalent control at 7.5 and 12 hours with Metadate CD giving better control from1
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High Antigen Dose Is Detrimental to Post-Exposure Vaccine Protection against Tuberculosis
Billeskov, Rolf; Lindenstrøm, Thomas; Woodworth, Joshua; Vilaplana, Cristina; Cardona, Pere-Joan; Cassidy, Joseph P.; Mortensen, Rasmus; Agger, Else Marie; Andersen, Peter
2018-01-01
Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world’s population with latent Mtb infection (LTBI), and 5–10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660) TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection. PMID:29379507
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Kim, Jun Won; Kim, Tae Hyung; Kim, Jie-Hyun; Lee, Ik Jae
2018-02-21
To evaluate toxicity and treatment outcome of high-dose radiotherapy (RT) for cervical esophageal cancer (CEC). We reviewed a total of 62 consecutive patients who received definitive RT for stage I to III cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local (occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed. Grade 1, 2, and 3 esophagitis occurred in 19 (30.6%), 39 (62.9%), and 4 patients (6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients (25.8%) developed post-RT stenosis, of which 7 cases (43.8%) were malignant. Four patients (6.5%) developed tracheoesophageal fistula (TEF), of which 3 (75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4 ( P = 0.001), complete circumference involvement ( P < 0.0001), stenosis at diagnosis ( P = 0.024), and endoscopic complete response ( P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis ( P = 0.003). A higher dose (≥ 60 Gy) was not associated with occurrence of post-RT stenosis or TEF. With a median follow-up of 24.3 (range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival (OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement ( P = 0.023), stenosis at diagnosis ( P < 0.0001), and occurrence of post-RT stenosis or TEF ( P < 0.001) in univariate analysis, while stenosis at diagnosis ( P = 0.004) and occurrence of post-RT stenosis or TEF ( P = 0.023) were
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Michaels, R.A.; Kleinman, M.T.
1999-07-01
Twenty-four-hour airborne particle mass levels permissible under the NAAQS have been associated with mortality and morbidity in communities, motivating reconsideration of the standard. Reports of shorter-term mechanisms of toxic action exerted by airborne PM and PM constituents are emerging. The mechanisms are diverse, but have in common a short time frame of toxic action, from minutes to hours. In view of documented PM excursions also lasting minutes to hours, this study inquires whether such short-term mechanisms might contribute to explaining daily morbidity and mortality. Toxicology experiments have demonstrated the harmfulness of brief exposure to PM levels in the range ofmore » observed excursions. This suggests that toxicological processes initiated by short-term inhalation of PM may exert clinically important effects, and that weak associations of 24-hour-average particle mass with mortality and morbidity may represent artifacts of stronger, shorter-term associations whose full magnitude remains to be quantified. In one study, the area of lung surface developing lesions was elevated in rats breathing the same four-hour dose of aerosols, when the four-hour average rate of aerosol delivery included a short-term (five-minute) burst fifty percent above the average dose rate. Elevations were observed with each of two aerosols tested. The magnitude of the effect was higher with one of the two aerosols, whose dose rate included four excursions rather than just one excursion. Particulate matter inhaled or instilled intratracheally has produced morbidity in animals, including apnea and electrophysiological effects in dogs. Other studies reveal that PM can kill rats via electrophysiological and possibly other mechanisms. PM has also adversely affected asthmatic people in controlled clinical settings during exercise or, in one study, at rest.« less
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Early prediction of oral calcium and vitamin D requirements in post-thyroidectomy hypocalcaemia.
Al-Dhahri, Saleh F; Mubasher, Mohamed; Al-Muhawas, Fida; Alessa, Mohammed; Terkawi, Rayan S; Terkawi, Abdullah S
2014-09-01
To optimize and individualize post-thyroidectomy hypocalcemia management. A multicenter prospective cohort study. Two tertiary care hospitals. parathyroid hormone (PTH) was measured preoperatively, then at 1 and 6 hours after surgery. The required doses of calcium and vitamin D were defined as those maintaining the patients asymptomatic and their cCa ≥ 2 mmol/L. They were used as an endpoint in a generalized linear mixed effect model (GLIMMEX) aiming to identify the best predictors of these optimal required doses. Models were evaluated by goodness of fit and Receiver Operating Characteristic (ROC) curves. One hundred and sixty-eight patients were analyzed; 85.1% were female, 49.3% had BMI > 30, and 64% had vitamin D deficiency. Post-thyroidectomy hypocalcemia was found in 25.6%, of whom 18 (41.9%) were symptomatic and received intravenous calcium. First hour percentage of drop in PTH correlated positively with the severity of hypocalcemia (P < .0001). The GLIMMIX prediction model for oral calcium requirement was based on first-hour percentage change from preoperative PTH level, preoperative actual PTH, BMI, and thyroid function. The same predictors were identified for vitamin D, except that thyroid function was replaced with vitamin D status. These factors were used to build predictive equations for calcium and vitamin D doses. Our findings help to optimize management of post-thyroidectomy hypocalcemia by assisting in the early identification of those who are not at risk of hypocalcaemia and by guiding early effective management of those at risk. This may reduce complications and medical cost. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.
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ERIC Educational Resources Information Center
Behrens, Susan
2013-01-01
A colleague can't make a coffee date at a time the author proposes because it would conflict with his office hour. No student has actually made an appointment with him during the hour, but he is committed to being in his office as promised in case someone drops by. The author's reaction to her colleague's faithfulness to his posted office hour…
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SU-F-T-323: A Post-Mastectomy Radiation Therapy Dose Distribution Study Using Nanodots and Films
DOE Office of Scientific and Technical Information (OSTI.GOV)
Qian, X; Vaidya, K; Puckett, L
Purpose: In post-mastectomy radiation therapy (RT), skin dose must be accurately estimated to assess skin reactions such as erythema, desquamation and necrosis. Planning systems cannot always provide accurate dosimetry for target volumes distal to skin. Therefore, in-vivo dosimetry is necessary. A female anthropomorphic phantom was used with optically stimulated luminescence dosimeters (nanoDots) to measure dose to chest wall skin. In addition, EBT2 films was employed to measure dose to left lung and heart in post-mastectomy RT. Methods: Films and nanoDots were calibrated under full buildup conditions at 100cm SAD for 6MV photons. Five pieces of films were placed between slabsmore » of Rando phantom to assess dose to left lung and heart. Two layers of 0.5cm thick bolus were used to cover the whole left chest. Six pairs of nanoDots were placed at medical and lateral aspects on the bolus surface, between the 0.5cm bolus layers, and under the bolus. Three control nanoDots were placed on chest wall to quantify imaging dose. The phantom was CT scanned with all dosimeters in place, and treatment planning was performed with tangential fields (200cGy). All dosimeters were contoured on CT and dose was extracted. NanoDots were read using nanoDot reader and films were scanned using film scanner. The measured and calculated doses were tabulated. Results: Dose to 12 nanoDots were evaluated. Dose variance for surface nanoDots were +3.8%, +2.7%, −5% and −9.8%. Those at lateral positions, with greater beam obliquity had larger variance than the medial positions. A similar trend was observed for other nanoDots (Table1). Point doses from films for heart and the left lung were 112.7cGy and 108.7cGy, with +10.2% and +9.04% deviation from calculated values, respectively. Conclusion: Dosimetry provided by the advanced planning system was verified using NanoDots and films. Both nanoDots and films provided good estimation of dose distribution in post-mastectomy RT.« less
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NASA Astrophysics Data System (ADS)
Sanzari, Jenine K.; Cengel, Keith A.; Steven Wan, X.; Rusek, Adam; Kennedy, Ann R.
2014-07-01
NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during an SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hours post-radiation exposure.
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Kim, Jun Won; Kim, Tae Hyung; Kim, Jie-Hyun; Lee, Ik Jae
2018-01-01
AIM To evaluate toxicity and treatment outcome of high-dose radiotherapy (RT) for cervical esophageal cancer (CEC). METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage I to III cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local (occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed. RESULTS Grade 1, 2, and 3 esophagitis occurred in 19 (30.6%), 39 (62.9%), and 4 patients (6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients (25.8%) developed post-RT stenosis, of which 7 cases (43.8%) were malignant. Four patients (6.5%) developed tracheoesophageal fistula (TEF), of which 3 (75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4 (P = 0.001), complete circumference involvement (P < 0.0001), stenosis at diagnosis (P = 0.024), and endoscopic complete response (P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis (P = 0.003). A higher dose (≥ 60 Gy) was not associated with occurrence of post-RT stenosis or TEF. With a median follow-up of 24.3 (range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival (OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement (P = 0.023), stenosis at diagnosis (P < 0.0001), and occurrence of post-RT stenosis or TEF (P < 0.001) in univariate analysis, while stenosis at diagnosis (P = 0.004) and occurrence of post-RT stenosis or TEF (P = 0
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Svedulf, C I; Bergbom Engberg, I L; Berthold, H; Höglund, I E
1998-03-01
To compare breast feeding at two and four months after delivery in mothers discharged early (ED = before 72 hours post delivery) and late (LD = after 72 hours post delivery), and to explore the factors of greatest importance to the successful practice of breast feeding. Ex-post facto design. In the country of Härryda, Sweden. All Swedish speaking women in the country of Härryda whose babies were born between 01.01.94 and 31.05.94 and who were registered at the Child Health Station (CHS) by the age of three months. One hundred and ninety women were invited to participate and 157 (83%) accepted. No significant difference was found in the breast feeding rates between the ED and LD group. However, ED mothers breast fed exclusively to a higher extent at two and at four months (exclusive breast feeding: at two months 89% and 86% respectively, and at four months 84% and 74% respectively, partial breast feeding: at two months 6% and 10% respectively, and at four months 5% and 12% respectively). If the woman considered that she had received encouragement and support while breast feeding for the first time, the probability of her breast feeding at two and at four months were about six times as great (Exp(B) 5.7594, df = 1, p = 0.0270; (Exp(B) 5.9781 df = 1, p = 0.0005 respectively). The length of the hospital stay had no significant effect on the incidence of breast feeding at two and four months post delivery. The most predominant factors influencing breast feeding were seen to be the mother's first experience of breast feeding and the degree of support, help and encouragement she received. Less than half of the women received a visit from the CHS nurse after their return home from hospital. The findings suggest that it is important that the midwife or nurse should prepare, support and encourage the mother when breast feeding for the first time. The midwife's or nurse's interventions are important for the incidence of breast feeding, at least during the first four months
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Investigation of vacuum pumping on the dose response of the MAGAS normoxic polymer gel dosimeter.
Venning, A J; Mather, M L; Baldock, C
2005-06-01
The effect of vacuum pumping on the dose response of the MAGAS polymer gel dosimeter has been investigated. A delay of several days post-manufacture before irradiation was previously necessary due to the slow oxygen scavenging of ascorbic acid. The MAGAS polymer gel dosimeter was vacuum pumped before gelation to remove dissolved oxygen. The MAGAS polymer gel dosimeter was poured into glass screw-top vials, which were irradiated at various times, post-manufacture to a range of doses. Magnetic resonance imaging techniques were used to determine the R2-dose response and R2-dose sensitivity of the MAGAS polymer gel. The results were compared with a control batch of MAGAS polymer gel that was not vacuum pumped. It was shown that vacuum pumping on the MAGAS polymer gel solution immediately prior to sealing in glass screw-top vials initially increases the R2-dose response and R2-dose sensitivity of the dosimeter. An increase in the R2-dose response and R2-dose sensitivity was observed with increasing time between manufacture and irradiation. Over the range of post-manufacture irradiation times investigated, the greatest R2-dose response and R2-dose sensitivity occurred at 96 hours.
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Shiue, Harn J; Taylor, Maria; Sands, Kara A
2017-10-01
Levetiracetam (LEV) is primarily renally eliminated. In end-stage renal disease (ESRD) patients on hemodialysis (HD), pharmacokinetic studies recommend daily dosing with 50% supplemental doses after 4-hour HD sessions. However, poor medication adherence after HD could result in fluctuating plasma drug levels. To compare two LEV dosing regimens, daily versus twice-daily (BID), in ESRD patients undergoing HD. Consecutive ESRD patients (April 2013 to May 2014) receiving maintenance inpatient HD and prescribed LEV prior to admission to our academic tertiary hospital were prospectively analyzed. Demographics, initial lab values, adverse reactions, seizures, and LEV regimens were recorded. LEV levels were obtained pre-HD and post-HD along with levels after receiving post-HD doses. Recovery of plasma levels after HD was assessed by comparison of levels predialysis versus postdialysis and post-HD doses. We identified 22 patients who met inclusion criteria; 14 BID and 8 daily dosing. Mean predialysis, postdialysis, and post-HD dose plasma levels were higher in patients receiving LEV BID compared with daily (43.1 ± 6.3, 19.4 ± 5.2, 34.9 ± 4.3 vs 21.1 ± 3.9, 6.9 ± 1.5, 11.9 ± 1.7 µg/mL; P < 0.05). BID post-HD levels were 41.9 ± 4.6% of predialysis levels versus 36.9 ± 7.3% with daily dosing ( P = 0.275). Post-HD dose levels were 81.4±4.3% of predialysis on LEV BID versus 65.7 ± 8.8% on LEV daily ( P = 0.045). No seizures were reported during hospital admission in either group. Compared to LEV daily, BID dosing achieved significantly higher levels and a better recovery to predialysis levels. Although limited by small numbers, a similar relationship between postdialysis levels was not detected.
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Groups of Long Evans rats 30, 50, or 70 days old were injected subcutaneously (s.c.) with a single dose of between 0 and 52 micromoles Cd/Kg as cadmium (CD) chloride. Sixty days post dosing and two hours prior to sacrifice the rats were injected s.c. with 100 IU of hCG to stimula...
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Dose and timing in neurorehabilitation: Prescribing motor therapy after stroke
Lang, Catherine E.; Lohse, Keith R.; Birkenmeier, Rebecca L.
2015-01-01
Purpose of the review Prescribing the most appropriate dose of motor therapy for individual patients is a challenge because minimal data are available and a large number of factors are unknown. This review explores the concept of dose and reviews the most recent findings in the field of neurorehabilitation, with a focus on relearning motor skills post stroke. Recent findings Appropriate dosing involves the prescription of a specific amount of an active ingredient, at a specific frequency and duration. Dosing parameters, particularly amount, are not well-defined or quantified in most studies. Compiling data across studies indicates a positive, moderate dose-response relationship, indicating that more movement practice results in better outcomes. This relationship is confounded by time post stroke however, where longer durations of scheduled therapy may not be beneficial in the first few hours, days, and/or weeks. Summary These findings suggest that substantially more movement practice may be necessary to achieve better outcomes for people living with the disabling consequences of stroke. Preclinical investigations are needed to elucidate many of the unknowns and allow for a more biologically-driven rehabilitation prescription process. Likewise, clinical investigations are needed to determine the dose-response relationships and examine the potential dose-timing interaction in humans. PMID:26402404
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Effect of single dose of omeprazole on the gastrointestinal peptide response to food.
Allen, J M; Adrian, T E; Webster, J; Howe, A; Bloom, S R
1984-02-01
The gastrointestinal peptide response to food was assessed in 6 healthy subjects following oral administration of 40 mg omeprazole. There was a small but statistically significant increase in basal plasma gastrin six hours after the dose of omeprazole, but the post-prandial plasma gastrin was not significantly increased. There was no significant effect on basal or post-prandial levels of somatostatin, insulin, pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, neurotensin, cholecystokinin, secretin, vasoactive intestinal peptide and gastrin-releasing peptide or blood glucose concentration.
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Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum.
Hansson, Anna; Rasmussen, Thomas; Kraiczi, Holger
2017-04-01
Under-dosing is a recognized problem with current nicotine replacement therapy (NRT). Therefore, a new 6mg nicotine gum has been developed. To compare the nicotine uptake from the 6mg gum versus currently available NRT products, two pharmacokinetic studies were performed. In one randomized crossover study, 44 healthy adult smokers received single doses of 6, 4, and 2mg nicotine gum, and 4mg nicotine lozenge on separate occasions. In a separate randomized crossover multiple-dose study over 11 hours, 50 healthy adult smokers received one 6mg gum every hour and 90 minutes, respectively, one 4mg gum every hour, and one 4mg lozenge every hour. In both studies, blood samples were collected over 12 hours to determine single-dose and multiple-dose pharmacokinetic variables. In the single-dose study, the amount of nicotine released from the 2, 4, and 6mg gums (1.44, 3.36, and 4.94mg) as well as the resulting maximum concentration and area under the curve (5.9, 10.1, and 13.8ng/mL, and 17.1, 30.7, 46.2ng/mL × h, respectively) increased with dose. The maximum concentration and area under the curve of the 6mg gum were 44% and 30% greater, respectively, than those for 4mg lozenge. Upon hourly administration, the steady-state average plasma nicotine concentration with 6mg gum (37.4ng/mL) was significantly higher than those for 4mg lozenge (28.3ng/mL) and 4mg gum (27.1ng/mL). Nicotine delivery via the 6mg gum results in higher plasma nicotine concentrations after a single dose and at steady state than with currently available oral NRT. Under-dosing is a recognized problem with current NRT. Therefore, a new 6mg nicotine gum has been developed. Our studies show that upon single-dose and multiple-dose administration, the 6mg gum releases and delivers more nicotine to the systemic circulation than 2mg gum, 4mg gum, and 4mg lozenge. Thus, each 6mg nicotine gum provides a higher degree of nicotine substitution and/or lasts for a longer period of time than currently available nicotine
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Haiberger, Roberta; Favia, Isabella; Romagnoli, Stefano; Cogo, Paola; Ricci, Zaccaria
2016-06-01
A post hoc analysis of a randomized controlled trial comparing the clinical effects of furosemide and ethacrynic acid was conducted. Infants undergoing cardiac surgery with cardiopulmonary bypass were included in order to explore which clinical factors are associated with diuretic dose in infants with congenital heart disease. Overall, 67 patients with median (interquartile range) age of 48 (13-139) days were enrolled. Median diuretic dose was 0.34 (0.25-0.4) mg/kg/h at the end of postoperative day (POD) 0 and it significantly decreased (p = 0.04) over the following PODs; during this period, the ratio between urine output and diuretic dose increased significantly (p = 0.04). Age (r -0.26, p = 0.02), weight (r -0.28, p = 0.01), cross-clamp time (r 0.27, p = 0.03), administration of ethacrynic acid (OR 0.01, p = 0.03), and, at the end of POD0, creatinine levels (r 0.3, p = 0.009), renal near-infrared spectroscopy saturation (-0.44, p = 0.008), whole-blood neutrophil gelatinase-associated lipocalin levels (r 0.30, p = 0.01), pH (r -0.26, p = 0.02), urinary volume (r -0.2755, p = 0.03), and fluid balance (r 0.2577, p = 0.0266) showed a significant association with diuretic dose. At multivariable logistic regression cross-clamp time (OR 1.007, p = 0.04), use of ethacrynic acid (OR 0.2, p = 0.01) and blood pH at the end of POD0 (OR 0.0001, p = 0.03) was independently associated with diuretic dose. Early resistance to loop diuretics continuous infusion is evident in post-cardiac surgery infants: Higher doses are administered to patients with lower urinary output. Independently associated variables with diuretic dose in our population appeared to be cross-clamping time, the administration of ethacrynic acid, and blood pH.
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Dee, Abigail A.; Kelly, Brian; Hampp, Christian
2010-01-01
OBJECTIVE Antibiotic timing is used as a quality standard for hospital accreditation and is an important quality measure. The study aim was to identify barriers in the process of first dose antibiotic administration on the pediatric floors at a tertiary healthcare center and carry out and test an intervention to improve turnaround time to less than one hour. METHODS We conducted a quasi-experimental pre-post study of hospitalized pediatric patients up to 18 years of age initiated on intravenous antibiotics. Every order for a first dose intravenous antibiotic was assessed on all pediatric floors (10/2008). Orders that did not meet the overall turnaround time goal of ≤ 1 hour were identified. A root cause analysis (RCA) was performed to identify reasons for delayed antibiotic administration. Barriers identified in the RCA were used to develop interventions (03/2009) to improve compliance, and the proportion of orders that met the goal was compared pre- (10/2008–02/2009) and post-intervention (04/2009–05/2009). RESULTS During the pre-intervention assessment period, 32 out of 46 total physician orders for a first dose intravenous antibiotic did not meet the one-hour overall turnaround goal. A main reason for delay was failure to label antibiotic orders as first dose. We designed an intervention that included antibiotic audits and individualized feedback to prescribers. The mean ± SD time from the written physician order to drug administration was 228 ± 58 minutes; timing improved to 55 ± 4 minutes after the intervention. The proportion of antibiotics administered within one hour improved from 42.2% to 63% (p=0.0015). CONCLUSIONS We identified system barriers associated with delayed antibiotic administration. Antibiotic timing was improved after continued surveillance and individualized feedback to providers. PMID:22477810
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Ultra-low dose (+)-naloxone restores the thermal threshold of morphine tolerant rats.
Chou, Kuang-Yi; Tsai, Ru-Yin; Tsai, Wei-Yuan; Wu, Ching-Tang; Yeh, Chun-Chang; Cherng, Chen-Hwan; Wong, Chih-Shung
2013-12-01
As known, long-term morphine infusion leads to tolerance. We previously demonstrated that both co-infusion and post-administration of ultra-low dose (±)-naloxone restores the antinociceptive effect of morphine in morphine-tolerant rats. However, whether the mechanism of the action of ultra-low dose (±)-naloxone is through opioid receptors or not. Therefore, in the present study, we further investigated the effect of ultra-low dose (+)-naloxone, it does not bind to opioid receptors, on the antinociceptive effect of morphine. Male Wistar rats were implanted with one or two intrathecal (i.t.) catheters; one catheter was connected to a mini-osmotic pump, used for morphine (15 μg/h), ultra-low dose (+)-naloxone (15 pg/h), morphine plus ultra-low dose (+)-naloxone (15 pg/h) or saline (1 μl/h) infusion for 5 days. On day 5, either ultra-low dose (+)-naloxone (15 pg) or saline (5 μl) was injected via the other catheter immediately after discontinued morphine or saline infusion. Three hours later, morphine (15 μg in 5 μl saline) or saline were given intrathecally. All rats received nociceptive tail-flick test every 30 minutes for 120 minutes after morphine challenge at different temperature (45-52°C, respective). Our results showed that, both co-infusion and post-treatment of ultra-low dose (+)-naloxone with morphine preserves the antinociceptive effect of morphine. Moreover, in the post administration rats, ultra-low dose (+)-naloxone further enhances the antinociceptive effect of morphine. This study provides an evidence for ultra-low dose (+)-naloxone as a therapeutic adjuvant for patients who need long-term opioid administration for pain management. Copyright © 2013. Published by Elsevier B.V.
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Carrera, Marinete Pinheiro; Carey, Robert J; Cruz Dias, Flávia Regina; dos Santos Sampaio, Maria de Fátima; de Matos, Liana Wermelinger
2013-01-01
Re-exposure to conditioned drug stimuli triggers re-consolidation processes. In the present study post-trial apomorphine treatments were administered in order to interact with the re-consolidation of an apomorphine conditioned/sensitized locomotor response. A low (0.05 mg/kg) and a high (2.0mg/kg) dose were used to inhibit or to enhance dopamine activity, respectively. Initially, groups received 5 daily apomorphine (2.0mg/kg)/vehicle treatments either paired or unpaired to open-field placement. The paired treatments generated a progressive locomotor response. Subsequently, all groups received a 5 min non-drug test for conditioning and a conditioned locomotor response was observed in the paired group. The groups received another apomorphine (2.0mg/kg)/vehicle treatment as a re-induction treatment. At this stage the post-trial protocol was initiated. One set of paired, unpaired and vehicle groups were given a low dose of apomorphine (0.05 mg/kg) post-trial; another set received a high dose of apomorphine (2.0mg/kg) post-trial. The remaining group set received vehicle post-trial. The low dose post-trial treatment eliminated the conditioned and sensitized locomotor response and the high dose post-trial treatment enhanced the conditioned and sensitized locomotor response. The efficacy of the post-trial apomorphine treatments to modify the conditioned and the sensitized response after a brief non-drug exposure to test cues supports the proposition that exteroceptive cues control conditioning and sensitization and that the interoceptive drug cues make little or no associational contribution to apomorphine conditioning and sensitization. In addition, the findings point to the importance of dopamine activation in both the acquisition and re-consolidation of conditioning processes. Copyright © 2012 Elsevier B.V. All rights reserved.
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Comparison of carprofen and meloxicam for 72 hours following ovariohysterectomy in dogs.
Leece, Elizabeth A; Brearley, Jacqueline C; Harding, Edward F
2005-07-01
To compare the peri- and post-operative (72 hours) analgesic effects of injectable and orally administered carprofen and meloxicam for ovariohysterectomy in dogs. Prospective, randomized clinical study. Forty-three dogs undergoing elective ovariohysterectomy. Dogs were randomly assigned to receive pre-operative carprofen, meloxicam or sterile saline by subcutaneous injection. Pre-anaesthetic medication was intramuscular acepromazine (0.02 mg kg(-1)) and methadone (0.2 mg kg(-1)). Anaesthesia was induced with either thiopentone or propofol injected to effect, and maintained with isoflurane in oxygen. Visual analogue scores (VAS) for pain and sedation were recorded at 1, 2, 3, 4 and 6 hours following tracheal extubation. Oral medication with the same treatment was continued post-operatively for 3 days, with VAS scores for pain being recorded before, and 2 hours after treatment on each day. Differences between group age, body mass, duration of general anaesthesia, time from treatment injection to tracheal extubation and time from treatment injection to first oral treatment were analysed using one-way analysis of variance and Kruskal-Wallis test. Visual analogue scores for pain and sedation were analysed using a re-randomization method. The significance level was set at p < 0.05. Meloxicam-treated subjects had lower mean VAS than the control group at 2 and 6 hours following tracheal extubation. Control group VAS were more varied than meloxicam scores (at 6 hours) and carprofen scores (at 3 and 6 hours). On the first post-operative day, pre- to post-treatment VAS scores decreased significantly after meloxicam. On day 3, scores in the meloxicam-treated group were significantly lower than control values after treatment. Changes in pre- to post-treatment VAS were greater in animals receiving either meloxicam or carprofen compared with those given saline. Both carprofen and meloxicam provided satisfactory analgesia for 72 hours following ovariohysterectomy in dogs.
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NASA Astrophysics Data System (ADS)
Wang, Chao; Zhang, Haixia; Xue, Zhixiao; Yin, Huijuan; Niu, Qing; Chen, Hongli
2015-12-01
The dielectric barrier discharge (DBD) plasma was applied to induce apoptosis of LT-12 leukemia cells. Plasma effects on cell death was evaluated by MTT assay and FCM apoptosis assay with Annexin V/PI double staining, suggesting that plasma killing cells rate and inducing cell apoptosis rate both positively were related to the plasma doses or the post-plasma time points. The cell death rates increased from 15.2% to 33.1% and the apoptosis rate raise from 23.8% to 28% when the dose raise from 60s to 120 s at 8 h post-plasma, while they increased from 15.4% to 34.9% and from 48% to 55.3% respectively at the same doses at 12 h post-plasma. Furthermore, the production of reactive oxygen species (ROS), gene and protein expression for Caspases and Bcl-2 family members were measured for exploring the related apoptotic mechanisms phenomenon. We found ROS immediately increased to 1.24 times of the original amount, then increasing to 5.39-fold at 20 h after treatment. The gene and protein expression for Caspases and Bcl-2 family members are very active at 8-12 h post-plasma. Our results demonstrate that DBD plasma can effectively induce tumor cell death through primarily related apoptotic mechanisms.
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Maryam, Y.; Sutton, Robert M.; Friess, Stuart H.; Bratinov, George; Bhalala, Utpal; Kilbaugh, Todd J.; Lampe, Joshua; Nadkarni, Vinay M.; Becker, Lance B.; Berg, Robert A.
2016-01-01
Objective Treatment algorithms for cardiac arrest are rescuer-centric and vary little from patient to patient. The objective of this study was to determine if cardiopulmonary resuscitation (CPR) targeted to arterial blood pressure and coronary perfusion pressure (CPP) rather than optimal Guideline Care would improve 24-hour survival in a porcine model of ventricular fibrillation (VF) cardiac arrest. Design Randomized interventional study Setting Preclinical animal laboratory Subjects Female 3-month old swine Interventions/Measurements After induction of anesthesia and 7 minutes of untreated VF, 16 female 3-month old swine were randomized to: 1) Blood Pressure (BP) care: titration of chest compression (CC) depth to a systolic blood pressure (SBP) of 100 mmHg and vasopressor dosing to maintain CPP >20mmHg or 2) Guideline care: CC depth targeted to 51 mm and standard Guideline vasopressor dosing. Animals received manual CPR for 10 minutes before the first defibrillation attempt and standardized post-resuscitation care for 24 hours. Main Results 24-hour survival was more likely with BP care versus Guideline care (0/8 versus 5/8, p<0.03), and all survivors had normal neurological examinations. Mean CPP prior to defibrillation was significantly higher with BP care (28±3 mmHg versus 10±6 mmHg, p<0.01). CC depth was lower with BP care (48±0.4 mmHg versus 44±0.5 mmHg, p<0.05) and number of vasopressor doses was higher with BP care (median 3 [range 1-7] versus 2 [range 2-2], p<0.01). Conclusions Individualized goal-directed hemodynamic resuscitation targeting SBP of 100 mmHg and CPP >20 mmHg improved 24-hour survival compared to Guideline care in this model of VF cardiac arrest. PMID:27414479
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Bilir, A
2013-01-01
Pain management has a particular importance after Cesarean section. This study was undertaken in order to document the efficacy and side-effects of epidural morphine instead of patient-controlled analgesia technique used for the control of post-cesarean pain during postoperative 24-48 hours. This study was performed as a retrospective review of patient charts who had received combined spinal-epidural anaesthesia. Post-cesarean analgesia was performed with epidural technique either by using (Group 1) patient-controlled epidural analgesia for 48 hours, or (Group 2) patient-controlled epidural analgesia for the first 24 hours and then single dose of 3 mg epidural morphine for the second 24 hours. Incidences of side-effects were similar in both groups. None of the patients experienced respiratory depression. Additional analgesia was used on an as-required basis in nine of 39 (23%) patients in Group 1 and six of 39 (13%) in Group 2. Small doses of epidural morphine provides up to 24 hours of pain relief from a single injection and could obviate the need for an indwelling epidural catheter on the second day of postcesarean section, thus reducing the potential for catheter-related complications.
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Wark, J D; Bensen, W; Recknor, C; Ryabitseva, O; Chiodo, J; Mesenbrink, P; de Villiers, T J
2012-02-01
Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms. Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen. In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia (n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol (n = 135), ibuprofen (n = 137) or placebo (n = 137), or placebo + placebo (n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion. The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p < 0.0001) compared with background rates of 11.1% and 16.7%, respectively, in the absence of any active treatment. Overall incidence of adverse events was comparable for patients receiving acetaminophen/paracetamol or ibuprofen. Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.
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Otsuka, Taiga; Kawazoe, Seiji; Nakashita, Shunya; Kamachi, Saori; Oeda, Satoshi; Sumida, Chinatsu; Akiyama, Takumi; Ario, Keisuke; Fujimoto, Masaru; Tabuchi, Masanobu; Noda, Takahiro
2012-08-01
Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Rectal nonsteroidal anti-inflammatory drugs (specifically, 100 mg of diclofenac or indomethacin) have shown promising prophylactic activity in post-ERCP pancreatitis (PEP). However, the 100-mg dose is higher than that ordinarily used in Japan. We performed a prospective randomized controlled study to evaluate the efficacy of low-dose rectal diclofenac for the prevention of PEP. Patients who were scheduled to undergo ERCP were randomized to receive a saline infusion either with 50 mg of rectal diclofenac (diclofenac group) or without (control group) 30 min before ERCP. The dose of diclofenac was reduced to 25 mg in patients weighing <50 kg. The primary outcome measure was the occurrence of PEP. Enrollment was terminated early because the planned interim analysis found a statistically significant intergroup difference in the occurrence of PEP. A total of 104 patients were eligible for this study; 51 patients received rectal diclofenac. Twelve patients (11.5%) developed PEP: 3.9% (2/51) in the diclofenac group and 18.9% (10/53) in the control group (p = 0.017). After ERCP, the incidence of hyperamylasemia was not significantly different between the two groups. Post-ERCP pain was significantly more frequent in the control group than in the diclofenac group (37.7 vs. 7.8%, respectively; p < 0.001). There were no adverse events related to diclofenac. Low-dose rectal diclofenac can prevent PEP.
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NASA Astrophysics Data System (ADS)
Yoon, Jihyung; Heins, David; Zhao, Xiaodong; Sanders, Mary; Zhang, Rui
2017-12-01
More and more advanced radiotherapy techniques have been adopted for post-mastectomy radiotherapies (PMRT). Patient dose reconstruction is challenging for these advanced techniques because they increase the low out-of-field dose area while the accuracy of out-of-field dose calculations by current commercial treatment planning systems (TPSs) is poor. We aim to measure and model the out-of-field radiation doses from various advanced PMRT techniques. PMRT treatment plans for an anthropomorphic phantom were generated, including volumetric modulated arc therapy with standard and flattening-filter-free photon beams, mixed beam therapy, 4-field intensity modulated radiation therapy (IMRT), and tomotherapy. We measured doses in the phantom where the TPS calculated doses were lower than 5% of the prescription dose using thermoluminescent dosimeters (TLD). The TLD measurements were corrected by two additional energy correction factors, namely out-of-beam out-of-field (OBOF) correction factor K OBOF and in-beam out-of-field (IBOF) correction factor K IBOF, which were determined by separate measurements using an ion chamber and TLD. A simple analytical model was developed to predict out-of-field dose as a function of distance from the field edge for each PMRT technique. The root mean square discrepancies between measured and calculated out-of-field doses were within 0.66 cGy Gy-1 for all techniques. The IBOF doses were highly scattered and should be evaluated case by case. One can easily combine the measured out-of-field dose here with the in-field dose calculated by the local TPS to reconstruct organ doses for a specific PMRT patient if the same treatment apparatus and technique were used.
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Bagal, Bhausaheb; Chandrasekharan, Arun; Chougle, Aliya; Khattry, Navin
2018-03-01
Hepatic veno-occlusive disease (VOD) is well recognized potentially serious regimen-related toxicity seen after stem cell transplantation. Severe VOD is associated with poor long-term outcomes with very high mortality. Besides supportive care, only defibrotide has been found to be effective in the management of VOD. The recommended dose of defibrotide is 25mg/kg/d but there has been no classical dose finding study done for this drug. A higher dose of defibrotide is associated with increased risk of bleeding and this drug is prohibitively expensive. We report our experience of using fixed low dose of defibrotide in patients with VOD. We retrospectively evaluated 511 patients who underwent stem cell transplant at our center from November 2007 and December 2015. All patients received ursodeoxycholic acid as VOD prophylaxis. Modified Seattle criterion was used for diagnosis and severity grading of VOD. Patients developing VOD were initially treated with furosemide and adequate analgesia. Defibrotide was started within 12 to 24 hours of diagnosis of VOD. All adult patients received defibrotide at a fixed dose of 200mg twice daily while two children were given dose of 100mg and 50mg twice daily. Nine (1.7%) of our patients developed VOD. Daily dose of defibrotide ranged from 5mg/kg/d to 20mg/kg/d till resolution of VOD. All patients had complete resolution of VOD. None of our patients required ventilator support or dialysis. No episodes of bleeding were observed. No dose response relationship was observed between defibrotide dose and time to resolution of VOD. Low fixed dose defibrotide initiated early seems to be effective and safe in treatment of VOD. This is relevant in a resource limited setting and warrants prospective evaluation. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.
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Is the Professor In? Faculty Presence during Office Hours
ERIC Educational Resources Information Center
Pfund, Rory A.; Rogan, Jessica D.; Burnham, Bryan R.; Norcross, John C.
2013-01-01
Two studies were conducted on the availability of full-time faculty during their posted office hours. In the first, we surveyed students and faculty at a single university on their estimates of the percentage of faculty present during office hours. Students ("N" = 380) and faculty ("N" = 176) estimated that 77% and 83% of…
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McInnes, Colin W; Vorstenbosch, Joshua; Chard, Ryan; Logsetty, Sarvesh; Buchel, Edward W; Islur, Avinash
2018-02-01
The impact of resident work hour restrictions on training and patient care remains a highly controversial topic, and to date, there lacks a formal assessment as it pertains to Canadian plastic surgery residents. To characterize the work hour profile of Canadian plastic surgery residents and assess the perspectives of residents and program directors regarding work hour restrictions related to surgical competency, resident wellness, and patient safety. An anonymous online survey developed by the authors was sent to all Canadian plastic surgery residents and program directors. Basic summary statistics were calculated. Eighty (53%) residents and 10 (77%) program directors responded. Residents reported working an average of 73 hours in hospital per week with 8 call shifts per month and sleep 4.7 hours/night while on call. Most residents (88%) reported averaging 0 post-call days off per month and 61% will work post-call without any sleep. The majority want the option of working post-call (63%) and oppose an 80-hour weekly maximum (77%). Surgical and medical errors attributed to post-call fatigue were self-reported by 26% and 49% of residents, respectively. Residents and program directors expressed concern about the ability to master surgical skills without working post-call. The majority of respondents oppose duty hour restrictions. The reason is likely multifactorial, including the desire of residents to meet perceived expectations and to master their surgical skills while supervised. If duty hour restrictions are aggressively implemented, many respondents feel that an increased duration of training may be necessary.
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Teaching hospital financial status and patient outcomes following ACGME duty hour reform.
Navathe, Amol S; Silber, Jeffrey H; Small, Dylan S; Rosen, Amy K; Romano, Patrick S; Even-Shoshan, Orit; Wang, Yanli; Zhu, Jingsan; Halenar, Michael J; Volpp, Kevin G
2013-04-01
To examine whether hospital financial health was associated with differential changes in outcomes after implementation of 2003 ACGME duty hour regulations. Observational study of 3,614,174 Medicare patients admitted to 869 teaching hospitals from July 1, 2000 to June 30, 2005. Interrupted time series analysis using logistic regression to adjust for patient comorbidities, secular trends, and hospital site. Outcomes included 30-day mortality, AHRQ Patient Safety Indicators (PSIs), failure-to-rescue (FTR) rates, and prolonged length of stay (PLOS). All eight analyses measuring the impact of duty hour reform on mortality by hospital financial health quartile, in postreform year 1 ("Post 1") or year 2 ("Post 2") versus the prereform period, were insignificant: Post 1 OR range 1.00-1.02 and Post 2 OR range 0.99-1.02. For PSIs, all six tests showed clinically insignificant effect sizes. The FTR rate analysis demonstrated nonsignificance in both postreform years (OR 1.00 for both). The PLOS outcomes varied significantly only for the combined surgical sample in Post 2, but this effect was very small, OR 1.03 (95% CI 1.02, 1.04). The impact of 2003 ACGME duty hour reform on patient outcomes did not differ by hospital financial health. This finding is somewhat reassuring, given additional financial pressure on teaching hospitals from 2011 duty hour regulations. © Health Research and Educational Trust.
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An individual (male, 36 years, 87 kg) ingested two separate doses of di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) at a rate of ~60 µg/kg. Key monoester and oxidized metabolites were identified and quantified in urine continuously collected until 48 hours post dos...
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Ewing, M M; Karper, J C; Sampietro, M L; de Vries, M R; Pettersson, K; Jukema, J W; Quax, P H A
2012-04-01
Activated cells in atherosclerotic lesions expose phosphatidylserine (PS) on their surface. Annexin A5 (AnxA5) binds to PS and is used for imaging atherosclerotic lesions. Recently, AnxA5 was shown to inhibit vascular inflammatory processes after vein grafting. Here, we report a therapeutic role for AnxA5 in post-interventional vascular remodeling in a mouse model mimicking percutaneous coronary intervention (PCI). Associations between the rs4833229 (OR = 1.29 (CI 95%), p(allelic) = 0.011) and rs6830321 (OR = 1.35 (CI 95%), p(allelic) = 0.003) SNPs in the AnxA5 gene and increased restenosis-risk in patients undergoing PCI were found in the GENDER study. To evaluate AnxA5 effects on post-interventional vascular remodeling and accelerated atherosclerosis development in vivo, hypercholesterolemic ApoE(-/-) mice underwent femoral arterial cuff placement to induce intimal thickening. Dose-dependent effects were investigated after 3 days (effects on inflammation and leukocyte recruitment) or 14 days (effects on remodeling) after cuff placement. Systemically administered AnxA5 in doses of 0.1, 0.3 and 1.0mg/kg compared to vehicle reduced early leukocyte and macrophage adherence up to 48.3% (p = 0.001) and diminished atherosclerosis development by 71.2% (p = 0.012) with a reduction in macrophage/foam cell presence. Moreover, it reduced the expression of the endoplasmic reticulum stress marker GRP78/BiP, indicating lower inflammatory activity of the cells present. AnxA5 SNPs could serve as markers for restenosis after PCI and AnxA5 therapeutically prevents vascular remodeling in a dose-dependent fashion, together indicating clinical potential for AnxA5 against post-interventional remodeling. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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Mohareb, Mina W; Abd Elghany, Mohamed; Sabry, Nirmeen A; Farid, Samar F
2016-08-01
High platelet reactivity (HPR) and suboptimal response to dual antiplatelet therapy (DAPT) may explain high recurrent rates of ischemic events in type 1 and 2 diabetes mellitus (DM) patients undergoing percutaneous coronary intervention (PCI). The aim of this study was to determine the effect of diabetes mellitus on clopidogrel activity in cardiac patients undergoing PCI. This is an observational study. Patients were categorized according to DM status into diabetic group (N.=30) and non-diabetic group (N.=33). All patients received clopidogrel in a loading dose of 600 mg before PCI. Platelet function was assessed using light transmittance aggregometry (LTA) technique at baseline (before clopidogrel administration), 24 hour after clopidogrel loading dose administration and 7-10 days after PCI. All patients were followed up for at least one year after PCI for recurrence of acute cardiac events. There was no statistically significant difference between the two groups with respect to 10 µm adenosine diphosphate (ADP)-induced platelet aggregation measured at baseline (P=0.64), 24 hours after PCI (P=0.874), and 7-10 days after PCI (0.643). Diabetics were not significantly different from non-diabetics in terms of post-PCI acute stent thrombosis (P=0.945), sub-acute stent thrombosis (P=0.945), unstable angina (P=0.29) and cardiac death (P=0.64). There was a statistically significant difference between patients with and without post-PCI acute events regarding ADP aggregation measured 24 hours and 7-10 days after PCI. The use of a high loading dose of clopidogrel (600 mg) in patients undergoing elective PCI can overcome the significant increase in post-PCI platelet aggregation and rate of acute cardiac events induced by diabetes mellitus as co-morbidity in those patients.
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Teaching Hospital Financial Status and Patient Outcomes Following ACGME Duty Hour Reform
Navathe, Amol S; Silber, Jeffrey H; Small, Dylan S; Rosen, Amy K; Romano, Patrick S; Even-Shoshan, Orit; Wang, Yanli; Zhu, Jingsan; Halenar, Michael J; Volpp, Kevin G
2013-01-01
Objective To examine whether hospital financial health was associated with differential changes in outcomes after implementation of 2003 ACGME duty hour regulations. Data Sources/Study Setting Observational study of 3,614,174 Medicare patients admitted to 869 teaching hospitals from July 1, 2000 to June 30, 2005. Study Design Interrupted time series analysis using logistic regression to adjust for patient comorbidities, secular trends, and hospital site. Outcomes included 30-day mortality, AHRQ Patient Safety Indicators (PSIs), failure-to-rescue (FTR) rates, and prolonged length of stay (PLOS). Principal Findings All eight analyses measuring the impact of duty hour reform on mortality by hospital financial health quartile, in postreform year 1 (“Post 1”) or year 2 (“Post 2”) versus the prereform period, were insignificant: Post 1 OR range 1.00–1.02 and Post 2 OR range 0.99–1.02. For PSIs, all six tests showed clinically insignificant effect sizes. The FTR rate analysis demonstrated nonsignificance in both postreform years (OR 1.00 for both). The PLOS outcomes varied significantly only for the combined surgical sample in Post 2, but this effect was very small, OR 1.03 (95% CI 1.02, 1.04). Conclusions The impact of 2003 ACGME duty hour reform on patient outcomes did not differ by hospital financial health. This finding is somewhat reassuring, given additional financial pressure on teaching hospitals from 2011 duty hour regulations. PMID:22862427
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Best Practices for Intrathecal Baclofen Therapy: Dosing and Long-Term Management.
Boster, Aaron L; Adair, Roy L; Gooch, Judith L; Nelson, Mary Elizabeth S; Toomer, Andrea; Urquidez, Joe; Saulino, Michael
2016-08-01
Intrathecal baclofen (ITB) therapy aims to reduce spasticity and provide functional control. An expert panel consulted on best practices. Pump fill and drug delivery can be started intraoperatively, with monitoring for at least eight hours. Initiate with the 500 mcg/mL concentration. The starting daily dose should be twice the effective bolus screening dose, or the screening dose if the patient had a prolonged response (greater than eight hours) or negative reactions. Oral antispasmodics can be weaned, one drug at a time beginning with oral baclofen after ITB begins. Assessment should occur within 24 hours of a dose change. For adults, daily dose increases may be 5% to 15% once every 24 hours for cerebral-origin spasticity and 10% to 30% once every 24 hours for spinal-origin spasticity. Daily dose increases can be 5% to 15% once every 24 hours for children. Inpatients should be assessed at least every 24 hours and receive rehabilitation. Step dosing can be used for outpatients who cannot return daily. Dosing options include simple continuous dosing, variable 24-hour flex dosing, or regularly scheduled boluses. Patients/caregivers should understand the care plan, responsibilities, and possible side-effects. Low-reservoir alarm dates and refill schedules should be written down, along with emergency contact information. A higher concentration at refill can extend refill intervals, and a bridge bolus must be programmed. Time changes may affect flex dosing. Pump replacement should be scheduled at least three months in advance. ITB dosing is multistep and individualized. © 2016 International Neuromodulation Society.
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LeWitt, Peter A; Poewe, Werner; Elmer, Lawrence W; Asgharnejad, Mahnaz; Boroojerdi, Babak; Grieger, Frank; Bauer, Lars
2016-01-01
Transdermal delivery of rotigotine maintains stable plasma concentrations for 24 hours. Three phase 3 studies of rotigotine as add-on to levodopa in advanced Parkinson's disease showed a significant reduction in "off" time from baseline to end of maintenance (EoM). However, detailed analyses over the range of a day have not yet been performed. The objective was to examine the time course of the efficacy profile of rotigotine throughout the day. Post hoc analysis of diary data from 3 double-blind, placebo-controlled studies of rotigotine in patients with advanced Parkinson's disease inadequately controlled with levodopa, with average "off" time of ≥2.5 h/d (CLEOPATRA-PD [NCT00244387], 16-week maintenance; PREFER, 24-week maintenance; SP921 [NCT00522379], 12-week maintenance). Patients marked 30-minute intervals as "off," "on without troublesome dyskinesia," "on with troublesome dyskinesia," or "sleep." Diaries completed on the 3 days before EoM were analyzed. A 2-sample t test was performed for comparison of rotigotine + levodopa versus placebo + levodopa for mean percentage of time per status during four 6-hour periods: 12:00AM (midnight) to 6:00AM, 6:00AM to 12:00PM (noon), noon to 6:00PM, and 6:00PM to midnight. Data were available for 967 patients (placebo + levodopa, 260; rotigotine + levodopa, 707). During the 24-hour period at EoM, an advantage in mean percentage time spent "off" and "on without troublesome dyskinesia" was observed with rotigotine + levodopa versus placebo + levodopa during the three 6-hour periods from 6:00AM to midnight (P < 0.05; exploratory analysis). These exploratory analyses of patients with motor fluctuations suggest that the efficacy of rotigotine transdermal patch, as captured by diary data, in reducing "off" time and increasing "on time without troublesome dyskinesia" may cover the full waking day.
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Transient diabetes insipidus in a preterm neonate and the challenge of desmopressin dosing.
Van der Kaay, Danielle C M; Van Heel, Willemijn J M; Dudink, Jeroen; van den Akker, Erica L T
2014-07-01
As neonatal central diabetes insipidus is rare in preterm neonates with intraventricular hemorrhage (IVH), very little is known about dosing and the route of administration of desmopressin treatment. We present a preterm neonate born at 29 weeks' gestation. Within 24 h, she developed bilateral IVH with subsequent post-hemorrhagic hydrocephalus. On the 3rd postnatal day, she developed diabetes insipidus for which she was intranasally administered 0.2 mg desmopressin. This resulted in oliguria with several hours of anuria and a 25-point drop in sodium levels within 15 h. The determination of the desmopressin dose in a preterm neonate is a challenge and there is no consistent literature about the dosing or the route of administration. We suggest starting with a low dose of intranasal desmopressin (0.05-0.1 μg) and titrate in accordance with clinical and laboratory parameters.
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75 FR 71545 - Changes to NARA Facilities' Hours of Operation
Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-24
... 2313 Red River St., Austin, TX 78705-5702. The phone number is 512-721-0200 and the fax number is 512... Archives Building is located at 700 Pennsylvania Avenue, NW., Washington, DC 20408. Hours for the Research Center and the Central Research Room are posted at http://www.archives.gov . The exhibit areas' hours of...
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Mashouf, S; Merino, T; Ravi, A
Purpose: There is strong evidence relating post-implant dosimetry for low-dose-rate (LDR) prostate seed brachytherapy to local control rates. The delineation of the prostate on CT images, however, represents a challenge due to the lack of soft tissue contrast in order to identify the prostate borders. This study aims at quantifying the sensitivity of clinically relevant dosimetric parameters to uncertainty in the contouring of prostate. Methods: CT images, post-op plans and contours of a cohort of patients (n=43) (low risk=55.8%, intermediate risk=39.5%, high risk=4.7%), who had received prostate seed brachytherapy, were imported into MIM Symphony treatment planning system. The prostate contoursmore » in post-implant CT images were expanded/contracted uniformly for margins of ±1.00 mm, ±2.00 mm, ±3.00 mm, ±4.00 mm and ±5.00 mm. The values for V100 and D90 were extracted from Dose Volume Histograms for each contour and compared. Results: Significant changes were observed in the values of D90 and V100 as well as the number of suboptimal plans for expansion or contraction margins of only few millimeters. Evaluation of coverage based on D90 was found to be less sensitive to expansion errors compared to V100. D90 led to a lower number of implants incorrectly identified with insufficient coverage for expanded contours which increases the accuracy of post-implant QA using CT images compared to V100. Conclusion: In order to establish a successful post implant QA for LDR prostate seed brachytherapy, it is necessary to identify the low and high thresholds of important dose metrics of the target volume such as D90 and V100. Since these parameters are sensitive to target volume definition, accurate identification of prostate borders would help to improve accuracy and predictive value of the post-implant QA process. In this respect, use of imaging modalities such as MRI where prostate is well delineated should prove useful.« less
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Gandhi, Ranju; Sunder, Rani
2012-01-01
Background: Analgesic efficacy of rectal acetaminophen is variable in different surgical procedures. Little data is available on its efficacy in ophthalmic surgeries. We conducted this prospective, randomized, double blind study to evaluate and compare the efficacy of single high dose and low dose rectal acetaminophen in pediatric ophthalmic surgery over a 24 hour period. Materials and Methods: 135 children scheduled for elective ophthalmic surgery were randomly allocated to one of the three groups, high, low, or control (H, L, or N) and received rectal acetaminophen 40 mg/kg, 20 mg/kg or no rectal drug respectively after induction of general anesthesia. Postoperative observations included recovery score, hourly observational pain score (OPS) up to 8 hours, time to first analgesic demand, and requirement of rescue analgesics and antiemetics over a 24 hour period. Results: Nineteen of 30 (63%) of children in group N required postoperative rescue analgesic versus 5/48 (10%) of group H (P <0.0001) and 10/47 (23%) of group L (P =0.0005) during 24 hour period. Mean time to requirement of first analgesic was 206±185 min in group H, 189±203min in group L, and 196 ±170 min in group N (P=0.985). OPS was significantly lower in group H and L compared to group N during first 8 hours. Requirement of rescue antiemetic was 18.7% in group H as compared to 23% each in group L and group N (P >0.5). Conclusions: Single dose rectal acetaminophen can provide effective postoperative analgesia for pediatric ophthalmic surgery at both high dose (40 mg/kg) and low dose (20 mg/kg) both in early postoperative and over a 24 hour period. PMID:23225924
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Educational audit on drug dose calculation learning in a Tanzanian school of nursing.
Savage, Angela Ruth
2015-06-01
Patient safety is a key concern for nurses; ability to calculate drug doses correctly is an essential skill to prevent and reduce medication errors. Literature suggests that nurses' drug calculation skills should be monitored. The aim of the study was to conduct an educational audit on drug dose calculation learning in a Tanzanian school of nursing. Specific objectives were to assess learning from targeted teaching, to identify problem areas in performance and to identify ways in which these problem areas might be addressed. A total of 268 registered nurses and nursing students in two year groups of a nursing degree programme were the subjects for the audit; they were given a pretest, then four hours of teaching, a post-test after two weeks and a second post-test after eight weeks. There was a statistically significant improvement in correct answers in the first post-test, but none between the first and second post-tests. Particular problems with drug calculations were identified by the nurses / students, and the teacher; these identified problems were not congruent. Further studies in different settings using different methods of teaching, planned continuing education for all qualified nurses, and appropriate pass marks for students in critical skills are recommended.
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The Associations Between Long Working Hours, Physical Inactivity, and Burnout.
Hu, Nien-Chih; Chen, Jong-Dar; Cheng, Tsun-Jen
2016-05-01
To examine the correlations between long working hours, physical activity, and burnout. A cross-sectional survey was administered to 1560 full-time employees, who underwent periodic health examinations in the year 2013. The subjects were divided into upper, middle, and lower tertiles according to the Copenhagen Burnout Inventory (CBI) score. The comparison of the high- and low-burnout groups revealed that long working hours were significantly correlated with burnout in a dose-dependent manner. Long working hours were more significantly associated with burnout among individuals younger than 50 years, females, and physically inactive employees. Long working hours are correlated with burnout when working over 40 hours per week and is even stronger when working over 60 hours per week. Limiting working hours to 40 weekly may be beneficial for the prevention of burnout. Physical activity helps reduce the risk of burnout.
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Thurman, Robin H; Yoon, Eugene; Murphy, Kellie E; Windrim, Rory; Farrugia, M Michéle
2017-12-01
Obstetricians have stressful and demanding jobs that may impact their health. A physiological measurement of cardiac function which varies with stress is heart rate variability (HRV). By measuring the cyclic variations in R-R intervals, or beat-to-beat differences, HRV reflects the continuous interplay of the controlling forces in the autonomic nervous system. Studies have shown HRV to be reduced during periods of work-induced stress, including 24-hour shifts. Our study aimed to determine if there was a correlation between length of shift worked and HRV. We hypothesised that working for a full 24-hour period is more stressful than a shorter, nighttime-only period, and HRV analyses were used to measure this objectively. Obstetricians wore an HRV monitor for 24 hours during both a regular day followed by a 14-hour night shift and a continuous 24-hour shift in labour and delivery. The 24-hour samples were analysed using standard HRV measurements. HRV measurements obtained from each physician were then compared according to shift type, with each physician acting as his or her own comparator. There were no statistically significant differences in the most important measures of HRV between 24-hour periods which included either a 14-hour overnight shift or a continuous 24-hour shift on labour and delivery. We found no significant differences in key HRV measures in obstetricians working 14 hours versus 24 hours in labour and delivery. An anecdotal increase in physician awareness of his/her own health related to working conditions was noted during the study. Future studies should attempt to control for the hours prior to a night shift, assess associated endocrine variations, and focus upon HRV in the post-shift period. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.
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LeWitt, Peter A.; Poewe, Werner; Elmer, Lawrence W.; Asgharnejad, Mahnaz; Boroojerdi, Babak; Grieger, Frank; Bauer, Lars
2016-01-01
Objectives Transdermal delivery of rotigotine maintains stable plasma concentrations for 24 hours. Three phase 3 studies of rotigotine as add-on to levodopa in advanced Parkinson's disease showed a significant reduction in “off” time from baseline to end of maintenance (EoM). However, detailed analyses over the range of a day have not yet been performed. The objective was to examine the time course of the efficacy profile of rotigotine throughout the day. Methods Post hoc analysis of diary data from 3 double-blind, placebo-controlled studies of rotigotine in patients with advanced Parkinson's disease inadequately controlled with levodopa, with average “off” time of ≥2.5 h/d (CLEOPATRA-PD [NCT00244387], 16-week maintenance; PREFER, 24-week maintenance; SP921 [NCT00522379], 12-week maintenance). Patients marked 30-minute intervals as “off,” “on without troublesome dyskinesia,” “on with troublesome dyskinesia,” or “sleep.” Diaries completed on the 3 days before EoM were analyzed. A 2-sample t test was performed for comparison of rotigotine + levodopa versus placebo + levodopa for mean percentage of time per status during four 6-hour periods: 12:00am (midnight) to 6:00am, 6:00am to 12:00pm (noon), noon to 6:00pm, and 6:00pm to midnight. Results Data were available for 967 patients (placebo + levodopa, 260; rotigotine + levodopa, 707). During the 24-hour period at EoM, an advantage in mean percentage time spent “off” and “on without troublesome dyskinesia” was observed with rotigotine + levodopa versus placebo + levodopa during the three 6-hour periods from 6:00am to midnight (P < 0.05; exploratory analysis). Conclusions These exploratory analyses of patients with motor fluctuations suggest that the efficacy of rotigotine transdermal patch, as captured by diary data, in reducing “off” time and increasing “on time without troublesome dyskinesia” may cover the full waking day. PMID:26882318
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Patient Perceptions of Whom is Most Involved in Their Care with Successive Duty Hour Limits.
Arora, Vineet M; Prochaska, Micah T; Farnan, Jeanne M; Meltzer, David O
2015-09-01
Although direct patient care is necessary for experiential learning during residency, inpatient perceptions of the roles of resident and attending physicians in their care may have changed with residency duty hours. We aimed to assess if patients' perceptions of who is most involved in their care changed with residency duty hours. This was a prospective observational study over 12 years at a single institution. Participants were 22,408 inpatients admitted to the general medicine teaching service from 2001 to 2013, who completed a 1-month follow-up phone interview. Percentage of inpatients who reported an attending, resident, or intern as most involved in their care by duty hour period (pre-2003, post-2003-pre-2011, post-2011). With successive duty hour limits, the percentage of patients who reported the attending as most involved in their care increased (pre-2003 20 %, post-2003-pre-2011 29 %, post-2011 37 %, p < 0.001). Simultaneously, fewer patients reported a housestaff physician (resident or intern) as most involved in their care (pre-2003 20 %, post-2003-pre-2011 17 %, post-2011 12 %, p < 0.001). In multinomial regression models controlling for patient age, race, gender and hospitalist as teaching attending, the relative risk ratio of naming the resident versus the attending was higher in the pre-2003 period (1.44, 95 % CI 1.28-1.62, p < 0.001) than the post-2003-pre-2011 (reference group). In contrast, the relative risk ratio for naming the resident versus the attending was lower in the post-2011 period (0.79, 95 % CI 0.68-0.93, p = 0.004) compared to the reference group. After successive residency duty hours limits, hospitalized patients were more likely to report the attending physician and less likely to report the resident or intern as most involved in their hospital care. Given the importance of experiential learning to the formation of clinical judgment for independent practice, further study on the implications of these trends for resident education
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A single-bout of one-hour spinning exercise increases troponin T in healthy subjects.
Duttaroy, Smita; Thorell, Daniel; Karlsson, Lena; Börjesson, Mats
2012-02-01
While long-term endurance exercise is known to increase cardiac biomarkers, only a few studies on short-term exercise and these markers have been reported. The aim of this study was to investigate the acute effects of a one-hour bicycle spinning on cardiac biomarkers in healthy individuals. Serum levels of high-sensitive troponin T (TnT), creatinine kinase MB fraction (CK-MB), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatinine kinase (CK) and myoglobin were measured at baseline, 1 and 24 hour after one hour of spinning exercise in ten healthy and fit (age 31.0 ± 6.6 years) individuals. TnT doubled one hour post-exercise (All values ≤ 5 - 9.7 ± 6.0 ng/L, p < 0.001). Two individuals had TnT levels above upper reference limit, URL (20.7 and 20.2 ng/L, URL = 12 ng/L). Myoglobin levels increased 72% one hour post-exercise (38 ± 20 - 66 ± 41 mg/L, p < 0.02). TnT and myoglobin levels returned to baseline 24 hour post-exercise. Serum levels of CK-MB, NT-proBNP and CK were not significantly changed. A single-bout of one-hour bicycle spinning transiently increases TnT and myoglobin in healthy subjects. Some subjects even have TnT release above URL. Thus, recently performed exercise also of short duration should be taken into consideration in the evaluation of acute chest pain with release of cardiac TnT.
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Burova, Natalia; Bychkova, Valeria; Shephard, Adrian
2018-01-01
Objective To assess the speed of relief provided by flurbiprofen 8.75 mg spray and lozenge and their effect on many of the different qualities and characteristics of throat pain and discomfort, and the many articulations of the broad term “sore throat” (ST). Patients and methods Four hundred and forty adults with recent-onset, moderate-to-severe ST due to upper respiratory tract infection (URTI) were randomized to a single dose of either flurbiprofen 8.75 mg spray (n=218) or flurbiprofen 8.75 mg lozenge (n=222). Throat swabs for bacterial culture were taken at baseline. ST relief was assessed at 1 minute, 1 and 2 hours post-dose using the Sore Throat Relief Rating Scale. The change from baseline at 1 and 2 hours post-dose in difficulty swallowing and swollen throat was assessed using the difficulty swallowing scale and the swollen throat scale, respectively. Patients’ experience of URTI symptoms was assessed using a URTI questionnaire at baseline and 2 hours post-dose. The change in Qualities of Sore Throat Index, a 10-item index of qualities of ST, from baseline at 2 hours post-dose was also measured. Results ST relief was evident in the spray and the lozenge treatment groups at 1 minute, 1 and 2 hours post-dose (P>0.05). In both groups, scores for difficulty swallowing and swollen throat significantly improved at 1 and 2 hours post-dose compared with baseline. At 2 hours post-dose, the number of patients experiencing URTI symptoms that can be attributed to or associated with ST decreased relative to baseline. The mean change from baseline to 2 hours post-dose for each individual score on the Qualities of Sore Throat Index showed significant improvements for flurbiprofen spray and lozenge (all P<0.0001). Conclusion Non-inferiority was established, and flurbiprofen spray and lozenge provided effective relief from ST pain and many of the other commonly reported qualities of ST.
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Burova, Natalia; Bychkova, Valeria; Shephard, Adrian
2018-01-01
To assess the speed of relief provided by flurbiprofen 8.75 mg spray and lozenge and their effect on many of the different qualities and characteristics of throat pain and discomfort, and the many articulations of the broad term "sore throat" (ST). Four hundred and forty adults with recent-onset, moderate-to-severe ST due to upper respiratory tract infection (URTI) were randomized to a single dose of either flurbiprofen 8.75 mg spray (n=218) or flurbiprofen 8.75 mg lozenge (n=222). Throat swabs for bacterial culture were taken at baseline. ST relief was assessed at 1 minute, 1 and 2 hours post-dose using the Sore Throat Relief Rating Scale. The change from baseline at 1 and 2 hours post-dose in difficulty swallowing and swollen throat was assessed using the difficulty swallowing scale and the swollen throat scale, respectively. Patients' experience of URTI symptoms was assessed using a URTI questionnaire at baseline and 2 hours post-dose. The change in Qualities of Sore Throat Index, a 10-item index of qualities of ST, from baseline at 2 hours post-dose was also measured. ST relief was evident in the spray and the lozenge treatment groups at 1 minute, 1 and 2 hours post-dose ( P >0.05). In both groups, scores for difficulty swallowing and swollen throat significantly improved at 1 and 2 hours post-dose compared with baseline. At 2 hours post-dose, the number of patients experiencing URTI symptoms that can be attributed to or associated with ST decreased relative to baseline. The mean change from baseline to 2 hours post-dose for each individual score on the Qualities of Sore Throat Index showed significant improvements for flurbiprofen spray and lozenge (all P <0.0001). Non-inferiority was established, and flurbiprofen spray and lozenge provided effective relief from ST pain and many of the other commonly reported qualities of ST.
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Jena, Anupam B; Schoemaker, Lena; Bhattacharya, Jay
2014-10-01
In 2003, work hours for physicians-in-training (residents) were capped by regulation at eighty hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work-hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000-09 that were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and patients' length-of-stay varied according to the number of years a physician was exposed to the 2003 duty-hour regulations during his or her residency. We examined this database of practicing Florida physicians, using a difference-in-differences analysis that compared trends in outcomes of junior physicians (those with one-year post-residency experience) pre- and post-2003 to a control group of senior physicians (those with ten or more years of post-residency experience) who were not exposed to these reforms during their residency. We found that the duty-hour reforms did not adversely affect hospital mortality and length-of-stay of patients cared for by new attending physicians who were partly or fully exposed to reduced duty hours during their own residency. However, assessment of the impact of the duty-hour reforms on other clinical outcomes is needed. Project HOPE—The People-to-People Health Foundation, Inc.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Yu, J; Thomas Jefferson UniversityHospital, Philadelphia, PA; Hardcastle, N
Purpose: To explore the feasibility of pretreatment test for iso-NTCP DGART and to compare the pretreatment test results with post-treatment evaluations. Methods: NTCP here refers to late rectal wall toxicity only and is calculated with the ring rectal wall DVH. Simulation for one time iso- NTCP DGART starts after half of the total dose was done for 10 patients to investigate if TCP gains could be achieved. Six patients were treated using a 12-fraction 4.3Gy technique and four using 16-fraction 3.63Gy technique. For each of the 12-fraction cases a VMAT plan was generated in Pinnacle3™ using the daily CT obtainedmore » prior to the 6th fraction. A pretreatment simulation was performed using only the first 6 daily CTs. The idea is to add the 6 original plan delivered doses with 6 DGART plan delivered doses by deformable dose accumulation (DDA) on each of the first 6 CTs, resulting in 6 rectal wall doses (RWDs) and NTCPs. The 95% confidence interval (95%CI) for the 6 NTCPs were computed.The posttreatment evaluation was done by: a) copy the DGART plan to 6 CTs for fraction 7–12 and calculate the 6 actual DGART delivered fractional doses; b) sum the 6 actual DGART doses with the 6 original plan delivered doses by DDA on each of the 12 CTs resulting in 12 post-treatment RWDs and NTCPs; c) boxplot the 12 post-treatment NTCPs. Results: Target dose gain is 0.76–1.93 Gy. The 95%CI widths of the pretreatment tests NTCPs were 1.1–2.7%. For 5 patients, the planned NTCP fell within the 95%CI. For 4 patients, the planned NTCP was lower than the 95%CI lines. Post-treatment results show that for 7 patients, the upper quartile was within the 95%CI; for 2 patients, the upper quartile were higher than the 95%CI. Conclusion: The pretreatment test yields conservative prediction of the actual delivered NTCP.« less
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Mavroidis, Panayiotis; Pearlstein, Kevin A; Dooley, John; Sun, Jasmine; Saripalli, Srinivas; Das, Shiva K; Wang, Andrew Z; Chen, Ronald C
2018-02-02
To estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms. Ninety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods. For the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D 50 = 64.2Gy, m = 0.50, n = 1.0; 2) D 50 = 95.0Gy, m = 0.45, n = 0.50; 3) D 50 = 83.1Gy, m = 0.56, n = 1.00; and 4) D 50 = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3. Different dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the
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Effectiveness of low-dose naltrexone in the post-detoxification treatment of opioid dependence.
Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathleen; Murray, Heather W; Wu, Li-Tzy; Hubbard, Robert
2007-10-01
The clinical use of naltrexone (NTX) in the treatment of opioid dependence has been limited because of poor compliance and inconsistent outcomes. In particular, the therapeutic benefit of extended treatment with NTX after opioid detoxification is unclear. The present study evaluated whether the augmentation with low-dose NTX during the post-detoxification treatment of opioid dependence would improve outcomes. In an open-label naturalistic design, 435 opioid-dependent patients who had completed inpatient detoxification were offered the choice of entering 1 of the 2 outpatient treatment arms: clonidine extended treatment (CET) (clonidine + psychosocial treatment), or enhanced extended treatment (EET) (oral NTX [1-10 mg/d] + CET) for 21 days. The primary outcome measure was retention in treatment. Secondary outcomes included abstinence from opioids, dropouts, and adherence to postdischarge care. One hundred sixty-two patients (37.2%) accepted EET. Subjects receiving EET stayed longer in the program (F = 64.4; P = 0.000), were less likely to drop out, used less opioids, and followed through with referral to long-term outpatient treatment in a higher number, compared with patients in the CET arm (P = 0.000 in each case). The NTX + clonidine combination was safe and well tolerated. This preliminary study indicates the potential benefit of augmentation with low-dose NTX to improve outcomes after opioid detoxification for a preferred group of patients. Randomized controlled trials are necessary to further evaluate the role of low-dose NTX in the outpatient treatment of opioid dependence.
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Addae; Awotwi; Oppong-Anane; Oddoye
2000-03-22
West African dwarf nanny goats and their single-born kids were tested to find out their behavioural response to separation and their mutual recognition during the first 48 h post-partum. The tests were conducted at 18, 24, 36 or 48 h post partum. Chi-square analyses were used to determine whether age, sex and birth weight of kids as well as h partum and parity of dams had an effect on post-partum bahaviours.In a preliminary study where the kids were not prevented from sucking prior to the tests, the majority of kids (93%) and does (86%) exhibited apparant minimal concern to separation (i.e., had scores of less than 3) and also failed to seek each other. When the kids were prevented from sucking 2 h prior to the tests, the couple showed some response to separation and made attempts to seek each other. This suggests that in goats the state of the neonate's nourishment and the fullness of the dam's udder may be important factors that determine the willingness of the kid and the dam to seek each other when separated. The behavioural response of 48-h-old kids to separation from their dams when they had not sucked for 2 h was significantly higher (P<0.05) than that of 18-h-old kids. The sex and birth-weight of 48-h-old kids did not affect their response to separation from their dams. Hours post-partum and parity of does did not affect their response to separation from their kids even though the proportion of does exhibiting the highest response was much higher in primiparous then multiparous animals (44% vs. 13%). Recognition of dams by kids was poor at 18 and 24 h with more than half (71%) the kids failing to recognize their dams. Dam recognition ability improved with age and at 48 h the majority of kids (88%) were able to recognize their dams. Does tested at 48 h post partum had better (P0.05) kid recognition than those tested at 18 and 24 h. The sex and birth weight of kids and the parity of dams had no effect on the mutual recognition of kids and their dams at 48 h
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2013-01-01
Background The receptor kinase inhibitor toceranib phosphate (Palladia) was approved for use in dogs in 2009 using a dose of 3.25 mg/kg administered every other day. Preliminary data suggests that lower doses of toeceranib may be associated with a reduced adverse event profile while maintaining sufficient drug exposure to provide biologic activity. The purpose of this study was to determine the Cmax of toceranib in dogs with solid tumors receiving 2.5-2.75 mg/kg every other day and to document the adverse events associated with this dose rate. Secondary objectives included determination of plasma VEGF concentrations in treated dogs and response to therapy. Results Dogs with solid tumors were administered toceranib at an intended target dose ranging from 2.5-2.75 mg/kg every other day and plasma samples were obtained for analysis of toceranib and VEGF plasma concentrations on days 0, 7, 14 and 30 of the study at 6 and 8 hours post drug administration. Additionally, plasma samples were obtained at 0, 1, 2, 6, 8, and 12 hours from dogs on day 30 for confirmation of Cmax. Response to therapy was assessed using standard RECIST criteria and adverse events were characterized using the VCOG-CTCAE. Toceranib administered at doses between 2.4-2.9 mg/kg every other day resulted in an average 6–8 hr plasma concentration ranging from 100–120 ng/ml, well above the 40 ng/ml concentration associated with target inhibition. Plasma VEGF concentrations increased significantly over the 30 day treatment period indicating that VEGFR2 inhibition was likely achieved in the majority of dogs. The lower doses of toceranib used in this study were associated with a substantially reduced adverse event profile compared to the established label dose of 3.25 mg/kg EOD. Conclusions Doses of toceranib ranging from 2.4-2.9 mg/kg every other day provide drug exposure considered sufficient for target inhibition while resulting in an adverse event profile substantially reduced from that
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-07
... defines a remotely managed Post Office (RMPO) as a Post Office that offers part-time window service hours... Administrative Post Office. The final rule also defines a part-time Post Office (PTPO) as a Post Office that offers part-time window service hours, is staffed by a Postal Service employee, and reports to a district...
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Radiological dose in Muria peninsula from SB-LOCA event
NASA Astrophysics Data System (ADS)
Sunarko; Suud, Zaki
2017-01-01
Dose assessment for accident condition is performed for Muria Peninsula region using source-term from Three-Mile Island unit 2 SB-LOCA accident. Xe-133, Kr-88, 1-131 and Cs-137 isotopes are considered in the calculation. The effluent is assumed to be released from a 50 m stack. Lagrangian particle dispersion method (LPDM) employing non-Gaussian dispersion coefficient in 3-dimensional mass-consistent wind-field is employed to obtain periodic surface-level concentration which is then time-integrated to obtain spatial distribution of ground-level dose. In 1-hour simulation, segmented plumes with 60 seconds duration with a total of 18.000 particles involved. Simulations using 6-hour worst-case meteorological data from Muria peninsula results in a peak external dose of around 1.668 mSv for low scenario and 6.892 mSv for high scenario in dry condition. In wet condition with 5 mm/hour and 10 mm/hour rain for the whole duration of the simulation provides only minor effect to dose. The peak external dose is below the regulatory limit of 50 mSv for effective skin dose from external gamma exposure.
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Torresi, Elena; Escolà Casas, Mònica; Polesel, Fabio; Plósz, Benedek G; Christensson, Magnus; Bester, Kai
2017-01-01
Addition of external carbon sources to post-denitrification systems is frequently used in wastewater treatment plants to enhance nitrate removal. However, little is known about the fate of micropollutants in post-denitrification systems and the influence of external carbon dosing on their removal. In this study, we assessed the effects of two different types and availability of commonly used carbon sources -methanol and ethanol- on the removal of micropollutants in biofilm systems. Two laboratory-scale moving bed biofilm reactors (MBBRs), containing AnoxKaldnes K1 carriers with acclimated biofilm from full-scale systems, were operated in continuous-flow using wastewater dosed with methanol and ethanol, respectively. Batch experiments with 22 spiked pharmaceuticals were performed to assess removal kinetics. Acetyl-sulfadiazine, atenolol, citalopram, propranolol and trimethoprim were easily biotransformed in both MBBRs (biotransformations rate constants k bio between 1.2 and 12.9 L g biomass -1 d -1 ), 13 compounds were moderately biotransformed (rate constants between 0.2 and 2 L g biomass -1 d -1 ) and 4 compounds were recalcitrant. The methanol-dosed MBBR showed higher k bio (e.g., 1.5-2.5-fold) than in the ethanol-dosed MBBR for 9 out of the 22 studied compounds, equal k bio for 10 compounds, while 3 compounds (i.e., targeted sulfonamides) were biotransformed faster in the ethanol-dosed MBBR. While biotransformation of most of the targeted compounds followed first-order kinetics, removal of venlafaxine, carbamazepine, sulfamethoxazole and sulfamethizole could be described with a cometabolic model. Analyses of the microbial composition in the biofilms using 16S rRNA amplicon sequencing revealed that the methanol-dosed MBBR contained higher microbial richness than the one dosed with ethanol, suggesting that improved biotransformation of targeted compounds could be associated with higher microbial richness. During continuous-flow operation, at conditions
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Efficient post-exposure prophylaxis against rabies by applying a four-dose DNA vaccine intranasally.
Tesoro Cruz, Emiliano; Feria Romero, Iris Angélica; López Mendoza, Juan Gabriel; Orozco Suárez, Sandra; Hernández González, Rafael; Favela, Francisco Blanco; Pérez Torres, Armando; José Alvaro Aguilar Setién
2008-12-09
We tested two post-exposure prophylaxes (PEPs) for rabies in laboratory animals; one was a traditional antirabies vaccine for humans via intramuscular route (IM), and the other was a DNA vaccine administered by intranasal route (IN). In contrast to The World Health Organization's recommended five-dose PEP, we gave only four doses without hyper-immune antirabies sera, making the PEP more rigorous. All animals were challenged with challenge virus strain (CVS); 16h later, PEP was applied. All animals that received the PEP with DNA/IN survived, and 87% of the rabbits and 80% of the mice that received the PEP with traditional antirabies vaccine/IM survived. Negative controls succumbed to infection. The expression of G protein was detected in the NALT, cerebellum, cerebral cortex (neocortex), cerebellum and hippocampus, mainly in the glial cells (microglia) and microvessels. On the other hand, plasmid construct was detected in brain and its mRNA expression in medium and posterior encephalon. The efficiency of this DNA/IN PEP is probably due to the early expression of the antigen in the brain stimulating the immune system locally.
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Berger, J S; Gonzalez, A; Hopkins, A; Alshaeri, T; Jeon, D; Wang, S; Amdur, R L; Smiley, R
2016-12-01
The appropriate dose of intrathecal morphine for post-cesarean analgesia is unclear. With the inclusion of routine non-steroidal anti-inflammatory drugs, the required dose of morphine may be significantly less than the 200-300μg common a decade ago. We performed a two-center, prospective, randomized, blinded trial comparing three doses of intrathecal morphine, combined with routine intravenous ketorolac, in 144 healthy women undergoing elective cesarean delivery. Patients received an intrathecal injection of hyperbaric bupivacaine 12mg, fentanyl 15μg and a randomized dose of 50, 100, or 150μg morphine in a volume of 2.2mL. Patients received intravenous ketorolac 30mg before leaving the operating room and 15mg intravenously every 6h for the duration of the study (24h). All received postoperative patient-controlled intravenous morphine. The primary endpoint was total intravenous morphine administered postoperatively over 24h, analyzed using mixed model regression. There were no differences between dose groups (or institutions) in intravenous morphine use over 24h. Visual analog scale scores for pain and nausea did not differ. Pruritus was greater in the 100 and 150μg groups than the 50μg group at 6h and 12h, but there was no difference between groups in nausea or pruritus treatments. Respiratory depression or significant sedation did not occur. The dose-response relationship of intrathecal morphine for multimodal post-cesarean analgesia suggests that 50μg produces analgesia similar to that produced by either 100μg or 150μg. Copyright © 2016 Elsevier Ltd. All rights reserved.
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29 CFR 778.421 - Offset hour for hour.
Code of Federal Regulations, 2010 CFR
2010-07-01
... hours standard, or in excess of the employees' normal working hours or regular working hours (as under... 29 Labor 3 2010-07-01 2010-07-01 false Offset hour for hour. 778.421 Section 778.421 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS OF GENERAL...
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Safety of intravenous alteplase within 4.5 hours for patients awakening with stroke symptoms.
Urrutia, Victor C; Faigle, Roland; Zeiler, Steven R; Marsh, Elisabeth B; Bahouth, Mona; Cerdan Trevino, Mario; Dearborn, Jennifer; Leigh, Richard; Rice, Susan; Lane, Karen; Saheed, Mustapha; Hill, Peter; Llinas, Rafael H
2018-01-01
Up to 25% of acute stroke patients first note symptoms upon awakening. We hypothesized that patients awaking with stroke symptoms may be safely treated with intravenous alteplase (IV tPA) using non-contrast head CT (NCHCT), if they meet all other standard criteria. The SAfety of Intravenous thromboLytics in stroke ON awakening (SAIL ON) was a prospective, open-label, single treatment arm, pilot safety trial of standard dose IV tPA in patients who presented with stroke symptoms within 0-4.5 hours of awakening. From January 30, 2013, to September 1, 2015, twenty consecutive wakeup stroke patients selected by NCHCT were enrolled. The primary outcome was symptomatic intracerebral hemorrhage (sICH) in the first 36 hours. Secondary outcomes included NIH stroke scale (NIHSS) at 24 hours; and modified Rankin Score (mRS), NIHSS, and Barthel index at 90 days. The average age was 65 years (range 47-83); 40% were women; 50% were African American. The average NIHSS was 6 (range 4-11). The average time from wake-up to IV tPA was 205 minutes (range 114-270). The average time from last known well to IV tPA was 580 minutes (range 353-876). The median mRS at 90 days was 1 (range 0-5). No patients had sICH; two of 20 (10%) had asymptomatic ICH on routine post IV tPA brain imaging. Administration of IV tPA was feasible and may be safe in wakeup stroke patients presenting within 4.5 hours from awakening, screened with NCHCT. An adequately powered randomized clinical trial is needed. ClinicalTrials.gov NCT01643902.
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2011-01-01
Introduction We report the impact of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, on inflammation and health-related quality of life (HRQoL) in patients with difficult-to-treat Gouty Arthritis. Methods In this eight-week, single-blind, double-dummy, dose-ranging study, patients with acute Gouty Arthritis flares who were unresponsive or intolerant to - or had contraindications for - non-steroidal anti-inflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg) (N = 143) or an intramuscular dose of triamcinolone acetonide 40 mg (N = 57). Patients assessed pain using a Likert scale, physicians assessed clinical signs of joint inflammation, and HRQoL was measured using the 36-item Short-Form Health Survey (SF-36) (acute version). Results At baseline, 98% of patients were suffering from moderate-to-extreme pain. The percentage of patients with no or mild pain was numerically greater in most canakinumab groups compared with triamcinolone acetonide from 24 to 72 hours post-dose; the difference was statistically significant for canakinumab 150 mg at these time points (P < 0.05). Treatment with canakinumab 150 mg was associated with statistically significant lower Likert scores for tenderness (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.27 to 7.89; P = 0.014) and swelling (OR, 2.7; 95% CI, 1.09 to 6.50, P = 0.032) at 72 hours compared with triamcinolone acetonide. Median C-reactive protein and serum amyloid A levels were normalized by seven days post-dose in most canakinumab groups, but remained elevated in the triamcinolone acetonide group. Improvements in physical health were observed at seven days post-dose in all treatment groups; increases in scores were highest for canakinumab 150 mg. In this group, the mean SF-36 physical component summary score increased by 12.0 points from baseline to 48.3 at seven days post-dose. SF-36 scores for physical functioning and
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Alessio, Nicola; Del Gaudio, Stefania; Capasso, Stefania; Di Bernardo, Giovanni; Cappabianca, Salvatore; Cipollaro, Marilena; Peluso, Gianfranco; Galderisi, Umberto
2015-01-01
Low doses of radiation may have profound effects on cellular function. Individuals may be exposed to low doses of radiation either intentionally for medical purposes or accidentally, such as those exposed to radiological terrorism or those who live near illegal radioactive waste dumpsites. We studied the effects of low dose radiation on human bone marrow mesenchymal stromal cells (MSC), which contain a subpopulation of stem cells able to differentiate in bone, cartilage, and fat; support hematopoiesis; and contribute to body's homeostasis. The main outcome of low radiation exposure, besides reduction of cell cycling, is the triggering of senescence, while the contribution to apoptosis is minimal. We also showed that low radiation affected the autophagic flux. We hypothesize that the autophagy prevented radiation deteriorative processes, and its decline contributed to senescence. An increase in ATM staining one and six hours post-irradiation and return to basal level at 48 hours, along with persistent gamma-H2AX staining, indicated that MSC properly activated the DNA repair signaling, though some damages remained unrepaired, mainly in non-cycling cells. This suggested that the impaired DNA repair capacity of irradiated MSC seemed mainly related to the reduced activity of a non-homologous end-joining (NHEJ) system rather than HR (homologous recombination). PMID:25544750
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Association between long working hours and sleep problems in white-collar workers.
Nakashima, Motoko; Morikawa, Yuko; Sakurai, Masaru; Nakamura, Koshi; Miura, Katsuyuki; Ishizaki, Masao; Kido, Teruhiko; Naruse, Yuchi; Suwazono, Yasushi; Nakagawa, Hideaki
2011-03-01
The purpose of this study is to examine the association between long work hours and sleep disturbance among white-collar workers. We evaluated 1510 male white-collar full-time employees, between the ages of 18 and 59 years, using a comprehensive sleep quality questionnaire, the Pittsburgh Sleep Quality Index (PSQI). All subjects worked in a light metal products factory in Japan. The mean number of monthly overtime work hours was determined using data from the previous 6 months from timecard records. Subjects were divided into five groups based on quintiles of the mean number of monthly overtime work hours: <26 h month(-1); ≥26 but <40; ≥40 but <50; ≥50 but <63; and >63. Leisure time physical activity, drinking habits just before sleep, presence of family/partner and health status were used as confounding factors in the multiple regression model. The prevalence of short sleep hours, impairment of sleep efficiency and daytime dysfunction among seven components of PSQI increased, in a dose-response relationship, with overtime work hours. The prevalence of high global score (>5.5 points) was highest in workers with overtime hours ≥50 h week(-1). The odds ratios after adjustment for confounding factors for high global score using less than 26 h as a reference group were 1.67 for workers with ≥50 h and <63 h, and 1.87 for workers with 63 h and more. To conclude, the present results suggest that long work hours correlate with reduced sleep quality in a dose-response manner. © 2010 European Sleep Research Society.
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Post-marketing monitoring of intussusception after rotavirus vaccination in Japan.
Bauchau, Vincent; Van Holle, Lionel; Mahaux, Olivia; Holl, Katsiaryna; Sugiyama, Keiji; Buyse, Hubert
2015-07-01
Rotarix(TM) was launched in November 2011 in Japan to prevent rotavirus gastroenteritis. Some studies suggest that Rotarix(TM) may have a temporal association with a risk of intussusception (IS). We assessed a possible association between IS and Rotarix(TM) vaccination in Japan. All IS cases spontaneously reported post-vaccination (Brighton collaboration levels 1, 2, and 3) were extracted from the GlaxoSmithKline spontaneous report database on the 11th of January 2013. Expected numbers of IS cases were estimated using the number of vaccine doses distributed and the Japanese incidence rate of IS stratified by month of age. The observed versus expected analysis considered the IS cases for each risk period (7 and 30 days post-vaccination) and for each vaccine dose (two doses). Before January 2013, approximately 601 000 Rotarix(TM) doses were distributed in Japan. For a risk period of 7 days post-dose 1 and post-dose 2, 10 and five IS cases were observed, whereas 3.4 and 7.6 were expected, providing an observed-to-expected ratio of 2.96 (95% confidence interval [CI]: 1.42; 5.45) and 0.66 (95% CI: 0.21; 1.53), respectively. For a risk period of 30 days post-dose 1 and post-dose 2, 14 and eight cases were observed, whereas 14.5 and 32.7 were expected, providing an observed-to-expected ratio of 0.97 (95% CI: 0.53; 1.62) and 0.24 (95% CI: 0.11; 0.48), respectively. A statistically significant excess of IS cases was observed within 7 days post-dose 1, but not post-dose 2. These results are consistent with previous observations in large post-marketing safety studies in other world regions. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
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Policicchio, Benjamin B.; Xu, Cuiling; Brocca-Cofano, Egidio; Raehtz, Kevin D.; He, Tianyu; Ma, Dongzhu; Li, Hui; Haret-Richter, George S.; Dunsmore, Tammy; Trichel, Anita; Mellors, John W.; Hahn, Beatrice H.; Shaw, George M.; Ribeiro, Ruy M.; Pandrea, Ivona; Apetrei, Cristian
2016-01-01
Viruses that persist despite seemingly effective antiretroviral treatment (ART) and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the “shock and kill” strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis)] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD) to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35–50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml) peaking at 5–12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml) that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control
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Out-of-hours work: what is the training value for paediatric senior house officers?
Onyon, Clare; Wall, David; Goodyear, Helen
2007-02-01
Out-of-hours work is needed for recognition of training posts. This article looks at the opinions of paediatric senior house officers on the training value of this work. Although senior house officers felt out-of-hours work was important for training, suggested improvements are discussed.
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Predicting success of methotrexate treatment by pretreatment HCG level and 24-hour HCG increment.
Levin, Gabriel; Saleh, Narjes A; Haj-Yahya, Rani; Matan, Liat S; Avi, Benshushan
2018-04-01
To evaluate β-human chorionic gonadotropin (β-HCG) level and its 24-hour increment as predictors of successful methotrexate treatment for ectopic pregnancy. Data were retrospectively reviewed from women with ectopic pregnancy who were treated by single-dose methotrexate (50 mg/m 2 ) at a university hospital in Jerusalem, Israel, between January 1, 2000, and June 30, 2015. Serum β-HCG before treatment and its percentage increment in the 24 hours before treatment were compared between treatment success and failure groups. Sixty-nine women were included in the study. Single-dose methotrexate treatment was successful for 44 (63.8%) women. Both mean β-HCG level and its 24-hour increment were lower for women with successful treatment than for those with failed treatment (respectively, 1224 IU\\L vs 2362 IU\\L, P=0.018; and 13.5% vs 29.6%, P=0.009). Receiver operator characteristic curve analysis yielded cutoff values of 1600 IU\\L and 14% increment with a positive predictive value of 75% and 82%, respectively, for treatment success. β-HCG level and its 24-hour increment were independent predictors of treatment outcome by logistic regression (both P<0.01). A β-HCG increment of less than 14% in the 24 hours before single-dose methotrexate and serum β-HCG of less than 1600 IU\\L were found to be good predictors of treatment success. © 2017 International Federation of Gynecology and Obstetrics.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, B; Zhang, J; Cho-Lim, J
Purpose: To compare dose distributions of conventional AP vs. VMAT treatment plans with or without bolus around post-laryngectomy stoma. Methods: Radiation dose coverage for post-laryngectomy stoma was analyzed using a set of real-case CT-simulation images. After meticulous contouring of the catheter cuff, stoma lumen, peri-stoma skin and subclinical tumor bed at the larynx, the resulting dosimetry plans were analyzed with or without a 5 mm bolus placement. Wet gauze was used to minimize the effect of any air gap. Four plans were generated: AP superclavicular (SCV) plan with or without bolus, and VMAT plan with or without bolus. A dosemore » of 60Gy in 30 fractions was prescribed at 3 cm depth for AP SCV plan, and to 95% of the PTV volume for VMAT plan. Results: For the conventional AP SCV plan, the peri-stoma skin dose is sensitive to bolus placement as well as air gap compensation by wetted gauze (V95% of 20.7%, 33.0% and 94.8% for no bolus, bolus without and with air gap compensation, respectively). For stoma lumen, the dose drops off rapidly in depth. The catheter cuff may have certain dose-buildup effect, but air gap around it and under the bolus placed can pose a more serious problem. The dose distributions of the two VMAT plans are moderately different for peri-stoma skin (V95% of 95.0% with bolus and air gap compensation, and 82.3% without bolus), but nearly identical for stoma lumen (V95% of 91.5% and 92.0%, respectively). VMAT allows beamlets with different angles of incidence that helped achieve such dose distribution around the stoma even without bolus placement. Conclusion: Overall, the dose coverage around the stoma in the VMAT plan is better than the conventional AP SCV plan. To achieve optimal dose distribution, it is still recommended to place physical bolus and reduce the air gaps.« less
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Lo, Amy; Zhu, Juanqi Nikki; Richman, Mark; Joo, Julianne; Chan, Patrick
2014-10-01
Significant improvements in order-to-administration times for critical first doses of i.v. antibiotic therapy through the use of automated dispensing cabinets (ADCs) are reported. In a retrospective pre-post analysis conducted at a large academic medical center, pharmacy and medical records were reviewed to evaluate average times to administration of first doses of i.v. piperacillin-tazobactam therapy during designated periods before and after the addition of selected i.v. antibiotics to ADCs on patient care units. Inpatients who received a specified i.v. piperacillin-tazobactam formulation were included in the analysis. The primary endpoint was the total time from prescribing to administration; the impact of ADC use on other time intervals (e.g., from scanning of orders to administration, from pharmacist verification and release of orders to administration) was also evaluated. A total of 121 subjects were included in the preimplementation (n = 65) and postimplementation (n = 56) samples. There was a significant 1.7-hour reduction in the mean ± S.D. order-to-administration time (from 4.5 ± 4.1 to 2.9 ± 2.5 hours, p = 0.009) for piperacillin-tazobactam first doses with the use of ADCs. Subgroup analyses showed significant reductions in the mean ± S.D. scan-to-administration time (from 3.3 ± 3.4 to 1.7 ± 1.5 hours, p = 0.001) and release-to-administration time (from 2.4 ± 2.4 to 1.4 ± 1.5 hours, p = 0.034). The addition of a piperacillin-tazobactam product and other commonly used i.v. antibiotics to ADCs was associated with a significantly reduced order-to-administration time for piperacillin-tazobactam first doses. This change was accounted for by a significant reduction in the time between order entry and drug administration. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.
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Okuno, Mitsuru; Shiroko, Junko; Taguchi, Daisuke; Yamaguchi, Kimihiro; Takada, Jun; Imai, Susumu; Sato, Hiroyuki; Thanabashi, Shinobu
2018-03-30
Objective A 50-100-mg rectal dose of nonsteroidal anti-inflammatory drugs (NSAIDs; diclofenac or indomethacin) has been shown to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, this is higher than the recommended 25-mg dose that is commonly administered to Japanese patients. The objective of this study was to evaluate the safety and efficacy of 25-mg rectal dose of diclofenac in preventing PEP. Methods Between January 2016 and March 2017, a total of 147 patients underwent ERCP with or without the rectal administration of diclofenac (25 mg) 20 min before the procedure. A retrospective analysis was conducted to evaluate the efficacy and safety of this dose in preventing PEP. Results Thirteen patients (8.8%) developed PEP: 3 patients (4.1%) in the diclofenac group and 10 (13.7%) in the control group (p=0.0460). After ERCP, there were no cases of gastrointestinal hemorrhage, ulceration, acute renal failure, or death. A multivariate logistic regression analysis revealed that the non-administration of rectal diclofenac was a risk factor for PEP (odds ratio=3.530; 95% confidence interval=1.017-16.35; p=0.0468). Conclusions A 25-mg rectal dose of diclofenac might prevent PEP.
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Filippi, M; Campi, A; Martinelli, V; Colombo, B; Yousry, T; Canal, N; Scotti, G; Comi, G
1995-01-01
This study was performed to evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) increases the sensitivity of brain MRI for detecting enhancing lesions in patients with primary progressive multiple sclerosis (PPMS). T1 weighted brain MRI was obtained for 10 patients with PPMS in two sessions. In the first session, one scan was obtained five to seven minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, one scan before and two scans five to seven minutes and one hour after the injection of 0.3 mmol/kg Gd-DTPA (triple dose) were obtained. Four enhancing lesions were detected in two patients when the standard dose of Gd-DTPA was used. The numbers of enhancing lesions increased to 13 and the numbers of patients with such lesions to five when the triple dose of Gd-DTPA was used and to 14 and six in the one hour delayed scans. The mean contrast ratio for enhancing lesions detected with the triple dose of Gd-DTPA was higher than those for lesions present in both the standard dose (P < 0.0009) and the one hour delayed scans (P = 0.04). These data indicate that with a triple dose of Gd-DTPA many more enhancing lesions can be detected in patients with PPMS. This is important both for planning clinical trials and for detecting the presence of inflammation in vivo in the lesions of such patients. Images PMID:8530944
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AlQahtani, Awad; Parsyan, Armen; Payne, Richard; Tabah, Roger
2014-08-01
Parathyroid dysfunction leading to symptomatic hypocalcemia is not uncommon following a total or completion thyroidectomy and is often associated with significant patient morbidity and a prolonged hospital stay. A simple, reliable indicator to identify patients at risk would permit earlier pharmacologic prophylaxis to avoid these adverse outcomes. We examined the role of intact parathormone (PTH) levels 1 hour after surgery as a predictor of post-thyroidectomy hypocalcemia. We prospectively reviewed the cases of consecutive patients undergoing total or completion thyroidectomy. Ionized calcium (Ca(2+)) and intact PTH levels were measured preoperatively and at 1-, 6- and 24-hour intervals postoperatively. The specificity, sensitivity, negative and positive predictive values of the 1-hour PTH serum levels (PTH-1) in predicting 24-hour post-thyroidectomy hypocalcemia and eucalcemia were determined. We reviewed the cases of 149 patients. Biochemical hypocalcaemia (Ca(2+) < 1.1 mmol/L) developed in 38 of 149 (25.7%) patients 24 hours after thyroidectomy. The sensitivity, specificity, positive and negative predictive values of a low PTH-1 were 89%, 100%, 97% and 100%, respectively. We found that PTH-1 levels were predictive of symptomatic hypocalcemia 24 hours after thyroidectomy. Routine use of this assay should be considered, as it could prompt the early administration of calcitriol in patients at risk of hypocalcemia and allow for the safe and timely discharge of patients expected to remain eucalcemic.
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Lai, Byron; Jeng, Brenda; Vrongistinos, Konstantinos; Jung, Taeyou
2015-06-01
The purpose of this study is to investigate the effects of a single-bout of aquatic treadmill walking (ATW) and overground treadmill walking (OTW) on the magnitude and duration of post-exercise ambulatory blood pressure (BP) in people post-stroke. Seven people post-stroke participated in a cross-sectional comparative study. BP was monitored for up to 9 hours after a 15-minute bout of ATW and OTW at approximately 70% of maximal oxygen consumption (VO2max), performed on separate days. Mean systolic and diastolic BP values were compared between both exercise conditions and a day without exercise (control). Three hours after OTW, mean SBP increased by 9% from pre-exercise baseline compared to a 3% decrease during the control day (P < 0.05). A similar trend was observed after the third hour of ATW (P = 0.06). However, ATW demonstrated a 3% overall decline in DBP after exercise compared to a 1% DBP increase of the control day (P < 0.05). Additionally, ATW showed a 6% reduction in mean systolic BP at the ninth hour post-exercise (P < 0.05) compared to baseline. Our results indicate people post-stroke can sustain sufficient walking intensities necessary to reduce BP following cardiovascular exercise. Also, these data suggest that ATW can elicit clinically meaningful reductions in DBP and night-time SBP. Thus, it is recommended for clinicians to consider ATW as a non-pharmaceutical means to regulate DBP and promote nighttime dipping of SBP in people post-stroke. However, caution is advised during the immediate hours after exercise, a period of possible BP inflation.
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Martin, Angela H; Eckert, George; Lemmon, Gary W; Sawchuk, Alan; Dalsing, Michael C
2014-04-01
This study reviews the clinical and workforce impact of a suggested protocol designed for the management of suspected acute deep venous thrombosis (DVT) in patients seen after standard vascular laboratory business hours. The protocol included the use of Wells score, D-dimer and a single dose of therapeutic anticoagulant to defer venous duplex ultrasound (VDU) testing until routine business hours unless contraindicated. Information was collected on medical history, physical exam and the timing of any diagnostic studies and treatment provided. Over 15% of studies done after-hours were deemed unnecessary by our protocol and in every individual the results were negative for an acute DVT. There were no adverse events from a one-time dose of anticoagulant. Limiting emergency VDU coverage to evaluate for acute DVT based on a management protocol can eliminate unnecessary after-hours VDU testing without having a negative impact on patient care.
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Single point estimation of phenytoin dosing: a reappraisal.
Koup, J R; Gibaldi, M; Godolphin, W
1981-11-01
A previously proposed method for estimation of phenytoin dosing requirement using a single serum sample obtained 24 hours after intravenous loading dose (18 mg/Kg) has been re-evaluated. Using more realistic values for the volume of distribution of phenytoin (0.4 to 1.2 L/Kg), simulations indicate that the proposed method will fail to consistently predict dosage requirements. Additional simulations indicate that two samples obtained during the 24 hour interval following the iv loading dose could be used to more reliably predict phenytoin dose requirement. Because of the nonlinear relationship which exists between phenytoin dose administration rate (RO) and the mean steady state serum concentration (CSS), small errors in prediction of the required RO result in much larger errors in CSS.
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Shen, Jie; Goodkin, Margot L; Tong, Warren; Attar, Mayssa
2017-01-01
Purpose Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed. Methods New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve. Results Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation. Conclusion Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties
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Estimating adolescent sleep need using dose-response modeling.
Short, Michelle A; Weber, Nathan; Reynolds, Chelsea; Coussens, Scott; Carskadon, Mary A
2018-04-01
This study will (1) estimate the nightly sleep need of human adolescents, (2) determine the time course and severity of sleep-related deficits when sleep is reduced below this optimal quantity, and (3) determine whether sleep restriction perturbs the circadian system as well as the sleep homeostat. Thirty-four adolescents aged 15 to 17 years spent 10 days and nine nights in the sleep laboratory. Between two baseline nights and two recovery nights with 10 hours' time in bed (TIB) per night, participants experienced either severe sleep restriction (5-hour TIB), moderate sleep restriction (7.5-hour TIB), or no sleep restriction (10-hour TIB) for five nights. A 10-minute psychomotor vigilance task (PVT; lapse = response after 500 ms) and the Karolinska Sleepiness Scale were administered every 3 hours during wake. Salivary dim-light melatonin onset was calculated at baseline and after four nights of each sleep dose to estimate circadian phase. Dose-dependent deficits to sleep duration, circadian phase timing, lapses of attention, and subjective sleepiness occurred. Less TIB resulted in less sleep, more lapses of attention, greater subjective sleepiness, and larger circadian phase delays. Sleep need estimated from 10-hour TIB sleep opportunities was approximately 9 hours, while modeling PVT lapse data suggested that 9.35 hours of sleep is needed to maintain optimal sustained attention performance. Sleep restriction perturbs homeostatic and circadian systems, leading to dose-dependent deficits to sustained attention and sleepiness. Adolescents require more sleep for optimal functioning than typically obtained.
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Boretti, F S; Sieber-Ruckstuhl, N S; Wenger-Riggenbach, B; Gerber, B; Lutz, H; Hofmann-Lehmann, R; Reusch, C E
2009-01-01
Various protocols using different doses of recombinant human thyrotropin (rhTSH) in TSH stimulation testing have been described. However, the influence of TSH dosage on thyroxine (T4) concentration has not yet been evaluated in suspected hypothyroid dogs. To evaluate the effectiveness of 2 doses of rhTSH. Fifteen dogs with clinical signs consistent with hypothyroidism and abnormal stimulation results with 75 microg rhTSH and 18 clinically healthy dogs. All dogs were stimulated with 75 and 150 microg rhTSH IV in a 1st and 2nd stimulation test, respectively. Blood samples were taken before and 6 hours after rhTSH administration for determination of total T4 concentration. Using the higher dose led to a normal test interpretation in 9 of the 15 dogs, in which stimulation had been abnormal using the lower dose. Based on follow-up information, hypothyroidism was excluded in 7 of these 9 dogs. In all 6 dogs with a blunted response to the higher dose, hypothyroidism could be confirmed. Healthy dogs showed significantly higher post-TSH T4 concentrations with the higher compared with the lower dose. Post-TSH T4 concentrations after TSH stimulation were not related to dogs' body weight in either healthy or diseased dogs. TSH dose significantly influenced test interpretation in suspected hypothyroid dogs. Differentiation between primary hypothyroidism and nonthyroidal disease was improved with 150 microg rhTSH. Because this effect was independent of the dogs' body weight, the higher dose is recommended in dogs that have concurrent disease or are receiving medication.
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Millar, W T; Davidson, S E
2013-01-01
Objective: To consider the implications of the use of biphasic rather than monophasic repair in calculations of biologically-equivalent doses for pulsed-dose-rate brachytherapy of cervix carcinoma. Methods: Calculations are presented of pulsed-dose-rate (PDR) doses equivalent to former low-dose-rate (LDR) doses, using biphasic vs monophasic repair kinetics, both for cervical carcinoma and for the organ at risk (OAR), namely the rectum. The linear-quadratic modelling calculations included effects due to varying the dose per PDR cycle, the dose reduction factor for the OAR compared with Point A, the repair kinetics and the source strength. Results: When using the recommended 1 Gy per hourly PDR cycle, different LDR-equivalent PDR rectal doses were calculated depending on the choice of monophasic or biphasic repair kinetics pertaining to the rodent central nervous and skin systems. These differences virtually disappeared when the dose per hourly cycle was increased to 1.7 Gy. This made the LDR-equivalent PDR doses more robust and independent of the choice of repair kinetics and α/β ratios as a consequence of the described concept of extended equivalence. Conclusion: The use of biphasic and monophasic repair kinetics for optimised modelling of the effects on the OAR in PDR brachytherapy suggests that an optimised PDR protocol with the dose per hourly cycle nearest to 1.7 Gy could be used. Hence, the durations of the new PDR treatments would be similar to those of the former LDR treatments and not longer as currently prescribed. Advances in knowledge: Modelling calculations indicate that equivalent PDR protocols can be developed which are less dependent on the different α/β ratios and monophasic/biphasic kinetics usually attributed to normal and tumour tissues for treatment of cervical carcinoma. PMID:23934965
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Aspirin (single dose) for perineal pain in the early postpartum period.
Molakatalla, Sujana; Shepherd, Emily; Grivell, Rosalie M
2017-02-09
reporting.We included four comparisons: aspirin versus placebo (data from 15 RCTs); 300 mg versus 600 mg aspirin (1 RCT); 600 mg versus 1200 mg aspirin (2 RCTs); and 300 mg versus 1200 mg aspirin (1 RCT). Primary outcomes Aspirin versus placeboMore women who received aspirin experienced adequate pain relief compared with women who received placebo over four to eight hours after administration (risk ratio (RR) 2.03, 95% confidence intervals (CI) 1.69 to 2.42; 13 RCTs, 1001 women; low-quality evidence). Women who received aspirin were less likely to need additional pain relief over four to eight hours after administration (RR 0.25, 95% CI 0.17 to 0.37; 10 RCTs, 744 women; very low-quality evidence). There was no difference in maternal adverse effects over four to eight hours post-administration (RR 1.08, 95% CI 0.57 to 2.06; 14 RCTs, 1067 women; very low-quality evidence). Subgroup analyses based on dose did not reveal any clear subgroup differences.There was no clear difference over four hours after administration between 300 mg and 600 mg aspirin for adequate pain relief (RR 0.82, 95% CI 0.36 to 1.86; 1 RCT, 81 women) or need for additional pain relief (RR 0.68, 95% CI 0.12 to 3.88; 1 RCT, 81 women). There were no maternal adverse effects in either aspirin group.There was no clear difference over four to eight hours after administration between 600 mg and 1200 mg aspirin for adequate pain relief (RR 0.85, 95% CI 0.52 to 1.39; 2 RCTs, 121 women), need for additional pain relief (RR 1.32, 95% CI 0.30 to 5.68; 2 RCTs, 121 women), or maternal adverse effects (RR 3.00, 95% CI 0.13 to 69.52; 2 RCTs, 121 women).There was no clear difference over four hours after administration between 300 mg and 1200 mg aspirin for adequate pain relief (RR 0.62, 95% CI 0.29 to 1.32; 1 RCT, 80 women) or need for additional pain relief (RR 2.00, 95% CI 0.19 to 21.18; 1 RCT, 80 women). There were no maternal adverse effects in either aspirin group.None of the included RCTs reported on neonatal
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Oral High-Dose Multivitamins and Minerals or Post Myocardial Infarction Patients in TACT
Lamas, Gervasio A.; Boineau, Robin; Goertz, Christine; Mark, Daniel B.; Rosenberg, Yves; Stylianou, Mario; Rozema, Theodore; Nahin, Richard L.; Lindblad, Lauren; Lewis, Eldrin F.; Drisko, Jeanne; Lee, Kerry L.
2014-01-01
Background Oral multivitamins and minerals are often used in conjunction with ethylenediamine tetra acetic acid infusions to treat atherosclerotic disease. Whether high-dose multivitamins are effective as secondary prevention of atherosclerotic disease, however, has not been established. Objective The vitamin component of the Trial to Assess Chelation Therapy assessed whether oral multivitamins reduced cardiovascular events, and were safe. Design The Trial to Assess Chelation Therapy was designed as a double-blind placebo-controlled 2×2 factorial multicenter randomized trial. Setting 134 US and Canadian academic and clinical sites participated. Patients 1708 patients, age ≥50 years, ≥6 weeks post myocardial infarction, with creatinine level ≤ 176.8 µmol/L (2.0 mg/dL). (ClinicalTrials.gov: NCT00044213). Intervention Patients were randomly assigned to an oral 28-component high-dose multivitamin and multimineral mixture or placebo. Measurements Study results were analyzed per randomized group. The primary endpoint was time to total mortality, recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina. Limited secondary endpoints and subgroup analyses were also pre-specified. Results The median age was 65 years, 18% female. The qualifying myocardial infarction had occurred 4.6 (1.6, 9.2) years prior to enrollment. The median duration of follow-up was 55 months (IQR 26, 60) overall. The median number of months during which patients took their vitamins was 31 (13, 59) in the active treatment group, and 35 (13, 60) in the placebo group (p=0.65). There were 645 (76%) vitamin patients and 646 (76%) placebo patients who completed at least 1 year of oral therapy (p=0.98); and 400 (46.9%) vitamin patients and 426 (49.8%) placebo patients who completed at least 3 years of oral therapy (p=0.23). There were 783 (46%) of patients who discontinued their vitamin regimen (390 (46%) in placebo, 394 (46%) in active; p=0.67), and 17% of
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Nixon, L James; Benson, Bradley J; Rogers, Tyson B; Sick, Brian T; Miller, Wesley J
2007-07-01
Residents have a major role in teaching students, yet little has been written about the effects of resident work hour restrictions on medical student education. Our objective was to determine the effects of resident work hour restrictions on medical student education. We compared student responses pre work hour restrictions with those completed post work hour restrictions. Students on required Internal Medicine, Surgery, and Pediatric clerkships at the University of Minnesota. Two thousand eight hundred twenty-five student responses on end-of-clerkship surveys. Students reported 1.6 more hours per week of teaching by residents (95%CI 0.8-2.6) in the post work hours era. Students' ratings of the overall quality of their teaching on the ward did not change appreciably, 0.05 points' decline on a 5-point scale (P = .05). Like the residents, students worked fewer hours per week (avg. 1.5 hours less, 95%CI 0.4-2.6). There was no change in quality or quantity of attending teaching, students' relationships with their patients, or the overall value of the clerkships. Whereas resident duty hour restrictions at our institution have had minimal effect on students' ratings of the overall teaching quality, they do report being taught more by their residents. This may be a factor of decreased resident fatigue or an increased sense of well-being; but more study is needed to clarify the causes of our observations.
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Benson, Bradley J.; Rogers, Tyson B.; Sick, Brian T.; Miller, Wesley J.
2007-01-01
Background Residents have a major role in teaching students, yet little has been written about the effects of resident work hour restrictions on medical student education. Objective Our objective was to determine the effects of resident work hour restrictions on medical student education. Design We compared student responses pre work hour restrictions with those completed post work hour restrictions. Participants Students on required Internal Medicine, Surgery, and Pediatric clerkships at the University of Minnesota. Measurements Two thousand eight hundred twenty-five student responses on end-of-clerkship surveys. Results Students reported 1.6 more hours per week of teaching by residents (95%CI 0.8–2.6) in the post work hours era. Students’ ratings of the overall quality of their teaching on the ward did not change appreciably, 0.05 points’ decline on a 5-point scale (P = .05). Like the residents, students worked fewer hours per week (avg. 1.5 hours less, 95%CI 0.4–2.6). There was no change in quality or quantity of attending teaching, students’ relationships with their patients, or the overall value of the clerkships. Conclusions Whereas resident duty hour restrictions at our institution have had minimal effect on students’ ratings of the overall teaching quality, they do report being taught more by their residents. This may be a factor of decreased resident fatigue or an increased sense of well-being; but more study is needed to clarify the causes of our observations. PMID:17450390
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Hemostatic profile and safety of pooled cryoprecipitate up to 120 hours after thawing.
Lokhandwala, Parvez M; O'Neal, Adrian; Patel, Eshan U; Brunker, Patricia A R; Gehrie, Eric A; Zheng, Gang; Kickler, Thomas S; Ness, Paul M; Tobian, Aaron A R
2018-05-01
AABB standards state that cryoprecipitate should be transfused within 4 to 6 hours after thawing. We evaluated coagulation factor levels and sterility of thawed pooled cryoprecipitate to assess whether shelf life can be safely extended. Donor cryoprecipitate pools (n = 20, 10 group A, 10 group O) were held at ambient temperature and sampled at 0, 4, 8, 24, 48, 72, 96, and 120 hours post-thawing for fibrinogen, Factor (F)VIII, and von Willebrand factor (vWF) levels. Samples were tested at 0 and 120 hours for sterility (BacT/Alert system). Sixty additional cryoprecipitate pools were evaluated after 72 hours. Longitudinal differences in component levels were determined by linear fixed-effects regression. Group O cryoprecipitate had significantly lower FVIII (p = 0.002) and vWF activity (p = 0.006) compared to group A at 0 hours, but were not statistically different in fibrinogen levels (p = 0.33). Fibrinogen levels were stable over 5 days: 501 ± 81 mg/unit (mean ± standard deviation) at 0 hours to 506 ± 102 mg/unit at 120 hours (p = 0.73). Similarly, there was no decline in vWF activity: 200 ± 53 IU/unit at 0 hours to 209 ± 57 IU/unit at 120 hours (p = 0.084). The FVIII activity significantly declined on average by 9.6 IU (95% confidence interval, 5.5-13.8) between 0 hours (111 ± 33 IU/unit) and 120 hours post-thaw (101 ± 33) (p < 0.001). No organisms were detected when cryoprecipitate pools were cultured at 0 hours, but at 120 hours Staphylococcus epidermidis was identified from one pool, potentially a contaminant introduced during repeated sampling. No cultures were positive among the 60 additional cryoprecipitate pools assessed at 72 hours. Extended cryoprecipitate storage at ambient temperature did not affect fibrinogen levels over 120 hours. Sterility of products held at ambient temperature for an extended period of time could be assessed by secondary culture. © 2018 AABB.
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AlQahtani, Awad; Parsyan, Armen; Payne, Richard; Tabah, Roger
2014-01-01
Background Parathyroid dysfunction leading to symptomatic hypocalcemia is not uncommon following a total or completion thyroidectomy and is often associated with significant patient morbidity and a prolonged hospital stay. A simple, reliable indicator to identify patients at risk would permit earlier pharmacologic prophylaxis to avoid these adverse outcomes. We examined the role of intact parathormone (PTH) levels 1 hour after surgery as a predictor of post-thyroidectomy hypocalcemia. Methods We prospectively reviewed the cases of consecutive patients undergoing total or completion thyroidectomy. Ionized calcium (Ca2+) and intact PTH levels were measured preoperatively and at 1-, 6- and 24-hour intervals postoperatively. The specificity, sensitivity, negative and positive predictive values of the 1-hour PTH serum levels (PTH-1) in predicting 24-hour post-thyroidectomy hypocalcemia and eucalcemia were determined. Results We reviewed the cases of 149 patients. Biochemical hypocalcaemia (Ca2+ < 1.1 mmol/L) developed in 38 of 149 (25.7%) patients 24 hours after thyroidectomy. The sensitivity, specificity, positive and negative predictive values of a low PTH-1 were 89%, 100%, 97% and 100%, respectively. Conclusion We found that PTH-1 levels were predictive of symptomatic hypocalcemia 24 hours after thyroidectomy. Routine use of this assay should be considered, as it could prompt the early administration of calcitriol in patients at risk of hypocalcemia and allow for the safe and timely discharge of patients expected to remain eucalcemic. PMID:25078927
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Safety of an ED High-Dose Opioid Protocol for Sickle Cell Disease Pain.
Tanabe, Paula; Martinovich, Zoran; Buckley, Barbara; Schmelzer, Annie; Paice, Judith A
2015-05-01
A nurse-initiated high dose, opioid protocol for vaso-occlusive crisis (VOC) was implemented. Total intravenous morphine sulfate equivalents (IVMSE) in mgs] and safety was evaluated. A medical record review was conducted for all ED visits in adult patients with VOC post protocol implementation. Opioids doses and routes administered during the ED stay, and six hours into the hospital admission were abstracted and total IVMSE administered calculated. Oxygen saturation (SPO2), respiratory rate (RR), administration of naloxone or vasoactive medications, evidence of respiratory arrest, or any other types of resuscitation effort were abstracted. A RR of <10 or SPO2 <92% were coded as abnormal. Descriptive statistics report the total dose. Logistic regression was used to predict abnormal events. Predictors were age, gender, ED dose (10 mg increments) administered, and time from 1st dose to discharge from ED. 72 patients, 603 visits, 276 admitted. The total (ED & hospital dose) mean (95% CI) mg IVMSE administered for all visits was 93 mg (CI 86, 100), ED visit 63 mg (CI 59, 67) and hospital 66 mg (CI 59, 72). The mean (SD) time from administration of 1st analgesic dose to discharge from the ED was 203 (143) minutes, (range = 30-1396 minutes). During two visits, patients experienced a RR <10; while 61 visits were associated with a SPO2 <92%. No medications were administered, or resuscitative measures required. Controlling for demographics and evaluated at the average total ED dose, the longer patients were in the ED, patients were 1.359 times more likely to experience an abnormal vital sign. Controlling for demographics and evaluated at the average total time in the ED, for every 10 mg increase in IVMSE, patients were 1.057 times more likely to experience an abnormal vital sign. The effect of ED dose on the odds of experiencing an abnormal vital sign decreased by a multiplicative factor of 0.0970 for every 1 hour increase in time until discharge. The larger the dose
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Shimazu, T; Yukioka, T; Hubbard, G B; Langlinais, P C; Mason, A D; Pruitt, B A
1987-01-01
The dose responsiveness of selected physiologic indices was studied in a sheep model of smoke inhalation injury. In this model, graded severity of injury was achieved by changing the contact time with smoke (defined by "unit"), whereas other variables were kept constant. Blood gas and cardiopulmonary indices were measured in 70 sheep, including 12 controls, either 24 or 72 hours after exposure to 3, 6, 9, 12, 15, or 18 units of smoke. A 12-unit dose of smoke was fatal within 72 hours and an 18-unit dose was fatal within 24 hours. The best correlation between smoke dose and response was observed in arterial oxygen tension 24 hours after exposure. At 24 hours, most of the cardiopulmonary indices showed significant change only after a 12-unit exposure. Although the exact shape of the dose-response curve could not be defined, sigmoid or curved linear shape was suggested, reflecting the progressive deterioration. Images Fig. 3. Fig. 4A. Fig. 4B. PMID:3606236
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Topical nasal decongestant oxymetazoline (0.05%) provides relief of nasal symptoms for 12 hours.
Druce, H M; Ramsey, D L; Karnati, S; Carr, A N
2018-05-22
Nasal congestion, often referred to as stuffy nose or blocked nose is one of the most prevalent and bothersome symptoms of an upper respiratory tract infection. Oxymetazoline, a widely used intranasal decongestant, offers fast symptom relief, but little is known about the duration of effect. The results of 2 randomized, double-blind, vehicle-controlled, single-dose, parallel, clinical studies (Study 1, n=67; Study 2, n=61) in which the efficacy of an oxymetazoline (0.05% Oxy) nasal spray in patients with acute coryzal rhinitis was assessed over a 12-hour time-period. Data were collected on both subjective relief of nasal congestion (6-point nasal congestion scale) and objective measures of nasal patency (anterior rhinomanometry) in both studies. A pooled study analysis showed statistically significant changes from baseline in subjective nasal congestion for 0.05% oxymetazoline and vehicle at each hourly time-point from Hour 1 through Hour 12 (marginally significant at Hour 11). An objective measure of nasal flow was statistically significant at each time-point up to 12 hours. Adverse events on either treatment were infrequent. The number of subjects who achieved an improvement in subjective nasal congestion scores of at least 1.0 was significantly higher in the Oxy group vs. vehicle at all hourly time-points on a 6-point nasal congestion scale. This study shows for the first time, that oxymetazoline provides both statistically significant and clinically meaningful relief of nasal congestion and improves nasal airflow for up to 12 hours following a single dose.
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A single low-dose of hydrocortisone enhances cognitive functioning in HIV-infected women.
Rubin, Leah H; Phan, K Luan; Keating, Sheila M; Maki, Pauline M
2018-06-14
Low-dose hydrocortisone (LDH) enhances aspects of learning and memory in select populations including patients with PTSD and HIV-infected men. HIV-infected women show impairments in learning and memory, but the cognitive effects of LDH in HIV-infected women are unknown. Double-blind, placebo-controlled, cross-over study examining the time-dependent effects of a single low-dose administration of hydrocortisone (10 mg oral) on cognition in 36 HIV-infected women. Participants were first randomized to LDH or placebo and then received the opposite treatment one month later. Cognitive performance was assessed 30 minutes and 4 hours after pill administration to assess, respectively nongenomic and genomic effects. Self-reported stress/anxiety and salivary cortisol were assessed throughout sessions. LDH significantly increased salivary cortisol levels versus placebo; levels returned to baseline 4-hours post-administration. At the 30-minute assessment, LDH enhanced verbal learning and delayed memory, working memory, behavioral inhibition, and visuospatial abilities. At the 4-hour assessment, LDH enhanced verbal learning and delayed memory compared to placebo. LDH-induced cognitive benefits related to reductions in cytokines and to a lesser extent to increases in cortisol. The extended benefits from 30 minutes to 4 hours of a single administration of LDH on learning and delayed memory suggest that targeting the HPA axis may have potential clinical utility in HIV-infected women. These findings contrast with our findings in HIV-infected men who showed improved learning only at the 30-minute assessment. Larger, longer-term studies are underway to verify possible cognitive enhancing effects of LDH and the clinical significance of these effects in HIV.
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Wallace, Michael P; Stewart, Catherine E; Moseley, Merrick J; Stephens, David A; Fielder, Alistair R
2016-12-01
To generate a statistical model for personalizing a patient's occlusion therapy regimen. Statistical modelling was undertaken on a combined data set of the Monitored Occlusion Treatment of Amblyopia Study (MOTAS) and the Randomized Occlusion Treatment of Amblyopia Study (ROTAS). This exercise permits the calculation of future patients' total effective dose (TED)-that predicted to achieve their best attainable visual acuity. Daily patching regimens (hours/day) can be calculated from the TED. Occlusion data for 149 study participants with amblyopia (anisometropic in 50, strabismic in 43, and mixed in 56) were analyzed. Median time to best observed visual acuity was 63 days (25% and 75% quartiles; 28 and 91 days). Median visual acuity in the amblyopic eye at start of occlusion was 0.40 logMAR (quartiles 0.22 and 0.68 logMAR) and at end of occlusion was 0.12 (quartiles 0.025 and 0.32 logMAR). Median lower and upper estimates of TED were 120 hours (quartiles 34 and 242 hours), and 176 hours (quartiles 84 and 316 hours). The data suggest a piecewise linear relationship (P = 0.008) between patching dose-rate (hours/day) and TED with a single breakpoint estimated at 2.16 (standard error 0.51) hours/day, suggesting doses below 2.16 hours/day are less effective. We introduce the concept of TED of occlusion. Predictors for TED are visual acuity deficit, amblyopia type, and age at start of occlusion therapy. Dose-rates prescribed within the model range from 2.5 to 12 hours/day and can be revised dynamically throughout treatment in response to recorded patient compliance: a personalized dosing strategy.
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76 FR 61098 - Guidance for 1-Hour SO2
Federal Register 2010, 2011, 2012, 2013, 2014
2011-10-03
...Notice is hereby given that the EPA has posted its draft non- binding guidance titled, ``Guidance for 1-Hour SO2 NAAQS SIP Submissions'' on its Web site. The EPA invites public comments on this guidance document during the comment period specified below, and plans to issue an updated version of the guidance after reviewing timely submitted comments.
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Maze, Ian S.; Wright, Geraldine A.; Mustard, Julie A.
2006-01-01
Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses lead to hemolymph ethanol levels of approximately 40 to 100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 hr post-ingestion for low doses and at 24 to 48 hours for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior. PMID:17070538
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NASA Astrophysics Data System (ADS)
Ramadan, Samy S.; Sridharan, Vijayalakshmi; Koturbash, Igor; Miousse, Isabelle R.; Hauer-Jensen, Martin; Nelson, Gregory A.; Boerma, Marjan
2016-02-01
Purpose: Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a ;priming; dose of protons on the cardiac cellular and molecular response to a ;challenge; dose of 56Fe in a mouse model. Methods: Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of 56Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of 56Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. Results: Exposure to 56Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before 56Fe prevented all of the responses to 56Fe. Conclusions: This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions.
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Ramadan, Samy S; Sridharan, Vijayalakshmi; Koturbash, Igor; Miousse, Isabelle R; Hauer-Jensen, Martin; Nelson, Gregory A; Boerma, Marjan
2016-02-01
Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a "priming" dose of protons on the cardiac cellular and molecular response to a "challenge" dose of (56)Fe in a mouse model. Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of (56)Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of (56)Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. Exposure to (56)Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before (56)Fe prevented all of the responses to (56)Fe. This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions. Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.
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Ramadan, Samy S.; Sridharan, Vijayalakshmi; Koturbash, Igor; Miousse, Isabelle R.; Hauer-Jensen, Martin; Nelson, Gregory A.; Boerma, Marjan
2015-01-01
Purpose Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a “priming” dose of protons on the cardiac cellular and molecular response to a “challenge” dose of 56Fe in a mouse model. Methods Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of 56Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of 56Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. Results Exposure to 56Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before 56Fe prevented all of the responses to 56Fe. Conclusions This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions. PMID:26948008
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Schwartz, Jill L.; Rountree, Wes; Kashuba, Angela D. M.; Brache, Vivian; Creinin, Mitchell D.; Poindexter, Alfred; Kearney, Brian P.
2011-01-01
Background Tenofovir (TFV) gel is being evaluated as a microbicide with pericoital and daily regimens. To inhibit viral replication locally, an adequate concentration in the genital tract is critical. Methods and Findings Forty-nine participants entered a two-phase study: single-dose (SD) and multi-dose (MD), were randomized to collection of genital tract samples (endocervical cells [ECC], cervicovaginal aspirate and vaginal biopsies) at one of seven time points [0.5, 1, 2, 4, 6, 8, or 24 hr(s)] post-dose following SD exposure of 4 mL 1% TFV gel and received a single dose. Forty-seven were randomized to once (QD) or twice daily (BID) dosing for 2 weeks and to collection of genital tract samples at 4, 8 or 24 hrs after the final dose, but two discontinued prior to gel application. Blood was collected during both phases at the seven times post-dose. TFV exposure was low in blood plasma for SD and MD; median Cmax was 4.0 and 3.4 ng/mL, respectively (C≤29 ng/mL). TFV concentrations were high in aspirates and tissue after SD and MD, ranging from 1.2×104 to 9.9×106 ng/mL and 2.1×102 to 1.4×106 ng/mL, respectively, and did not noticeably differ between proximal and distal tissue. TFV diphosphate (TFV-DP), the intracellular active metabolite, was high in ECC, ranging from 7.1×103 to 8.8×106 ng/mL. TFV-DP was detectable in approximately 40% of the tissue samples, ranging from 1.8×102 to 3.5×104 ng/mL. AUC for tissue TFV-DP was two logs higher after MD compared to SD, with no noticeable differences when comparing QD and BID. Conclusions Single-dose and multiple-dose TFV gel exposure resulted in high genital tract concentrations for at least 24 hours post-dose with minimal systemic absorption. These results support further study of TFV gel for HIV prevention. Trial registration ClinicalTrials.gov NCT00561496 PMID:22039430
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Has the 80-hour work week increased faculty hours?
Winslow, Emily R; Berger, Lisa; Klingensmith, Mary E
2004-01-01
The 80-hour work week has affected not only surgical residents but also faculty. The aim of this study was to determine the effect of resident hour restrictions on faculty hours and attitudes. Anonymous survey. A single, large academic medical center. All faculty in the Departments of Surgery, Neurosurgery, Orthopedics, and Otolaryngology. Faculty were surveyed 6 months before and 6 months after the institution of the resident 80-hour work week. Surgeons detailed hours worked over 1 week and answered yes/no questions about changes in patient care and resident education. P values were determined by Chi-square tests or Student t-tests as appropriate. Of the 118 surveys distributed, 88 were returned (75%). Respondents were evenly divided between general surgeons (GS) and subspecialists (SS). Initially, 70% of faculty predicted that resident work-hour restrictions would increase faculty hours; however, only 47% of faculty felt that this had occurred. When current faculty work hours were compared with previously collected data, no differences were found. Faculty reported working an average of 69.9 +/- 12.2 hours per week this year, compared with 70.4 +/- 12.5 hours last year. When asked about the global impact of the 80-hour work week on faculty, 46% viewed the changes as harmful to the faculty. More concerning, 50% of all faculty felt the care their patients received was worse than previously, with only 2% feeling patient care had improved. This perception was significantly more common among GS faculty (70% GS vs 37% SS; p < 0.01), 94% of whom felt that the current lack of continuity compromises patient care. When the data were stratified by faculty work hours, interesting differences are seen. Of those faculty with work weeks less than 60 hours, only 6% thought the changes were harmful to patients and 64% thought resident training had suffered. In contrast, of those faculty who worked greater than 80 hours per week, 56% thought patients were harmed (p = 0.03) and 100
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Resident Work Hour Restrictions and Change Management: A Cautionary Tale.
Fang, Z Amy; Hudson, Darren
2015-01-01
Residents are a significant part of coverage in many hospitals. Resident associations are negotiating work hour limits to prevent fatigue-induced medical errors. Our intensive care unit experienced an unexpected resident shortage and used the opportunity to trial a shift schedule for one month. Post-surveys were sent to nurses, attending physicians and residents to evaluate the effects on staff interactions, patient safety and education quality. The trial was clearly a failure on all fronts. Work hour restrictions are a reality in medical education, and administrators need to start considering alternative staffing models and discussing alternative schedules with their medicine faculty.
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Isotretinoin kinetics after 80 to 320 mg oral doses.
Colburn, W A; Gibson, D M
1985-04-01
Twelve healthy male subjects received 80, 160, 240, and 320 mg doses of oral isotretinoin as multiples of 40 mg capsules separated by 2-week washout periods in a randomized, crossover design. Blood samples were drawn at specific times over a 72-hour period after dosing. Blood concentrations of isotretinoin as well as its major metabolite, 4-oxo-isotretinoin, were determined by a specific HPLC method. In addition to the normal laboratory battery of tests, serum triglyceride levels were determined before the first dose and again 72 hours after each of the four doses. Mean (+/- SD) maximum concentrations after 80 to 320 mg doses were 366 +/- 159, 820 +/- 474, 1056 +/- 547, and 981 +/- 381 ng/ml, whereas the respective AUC0-infinity values were 3690 +/- 1280, 7030 +/- 4140, 9780 +/- 6080, and 9040 +/- 2900 ng X hr/ml. The observed apparent elimination t1/2 remained approximately the same (14.7 hours) for each dose. The maximum concentration and AUC values for isotretinoin appear to be dose proportional from 80 to 240 mg but plateau at the 320 mg dose level. Therefore, because isotretinoin blood concentrations may not increase with higher doses in the fasting state, single, oral doses in excess of 240 mg should be used with caution. The data also suggest that elevated triglyceride levels are not a simple function of isotretinoin blood concentrations across the entire study population and dose range studied, but that in subjects with triglyceride levels in excess of the normal range triglyceride levels were positively related to isotretinoin blood concentrations.
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Günther, Kamilla Nyborg; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose; Wicktor, Petra; Banner, Jytte; Linnet, Kristian
2018-04-01
Drug analysis in hair is useful when seeking to establish drug intake over a period of months to years. Segmental hair analysis can also document whether psychiatric patients are receiving a stable intake of antipsychotics. This study describes segmental analysis of the antipsychotic drug quetiapine in post-mortem hair samples from long-term quetiapine users by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The aim was to obtain more knowledge on quetiapine concentrations in hair and to relate the concentration in hair to the administered dose and the post-mortem concentration in femoral blood. We analyzed hair samples from 22 deceased quetiapine-treated individuals, who were divided into two groups: natural hair colour and dyed/bleached hair. Two to six 1cm long segments were analyzed per individual, depending on the length of the hair, with 6cm corresponding to the last six months before death. The average daily quetiapine dose and average concentration in hair for the last six months prior to death were examined for potential correlation. Estimated doses ranged from 45 to 1040mg quetiapine daily over the period, and the average concentration in hair ranged from 0.18 to 13ng/mg. A significant positive correlation was observed between estimated daily dosage of quetiapine and average concentration in hair for individuals with natural hair colour (p=0.00005), but statistical significance was not reached for individuals with dyed/bleached hair (p=0.31). The individual coefficient of variation (CV) of the quetiapine concentrations between segments ranged from 3 to 34% for individuals with natural hair colour and 22-62% for individuals with dyed/bleached hair. Dose-adjusted concentrations in hair were significantly lower in females with dyed/bleached hair than in individuals with natural hair colour. The quetiapine concentrations in post-mortem femoral blood and in the proximal hair segment, segment 1 (S1), representing
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Feng; Waters, Katrina M.; Miller, John H.
2010-11-30
Background: High doses of ionizing radiation result in biological damage, however the precise relationships between long term health effects, including cancer, and low dose exposures remain poorly understood and are currently extrapolated using high dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose dependent responses to radiation. Principle Findings: We have identified 6845 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts one hour post-exposure. Dual statistical analyses based on spectral counts and peakmore » intensities identified 287 phosphopeptides (from 231 proteins) and 244 phosphopeptides (from 182 proteins) that varied significantly following exposure to 2 and 50 cGy respectively. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatics analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role of MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Conlcusions: Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provides a basis for the systems level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at
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Spierings, Egilius L H; Volkerts, Edmund R; Heitland, Ivo; Thomson, Heather
2014-02-01
The maximum plasma concentration (Cmax ) of oxymorphone extended release (ER) 20 mg and 40 mg is approximately 50% higher in fed than in fasted subjects, with most of the difference in area-under-the-curve (AUC) occurring in the first 4 hours post-dose. Hence, the US FDA recommends in the approved labeling that oxymorphone ER is taken at least 1 hour before or 2 hours after eating. In order to determine the potential impact on cognitive performance of the increased absorption of oxymorphone ER, fed versus fasting, we conducted a randomized, rater-blinded, crossover study in 30 opioid-tolerant subjects, using tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). The subjects randomly received 40 mg oxymorphone ER after a high-fat meal of approximately 1,010 kCal or after fasting for 8-12 hours, and were tested 1 hour and 3 hours post-dose. The CANTAB tests, Spatial Recognition Memory (SRM) and Spatial Working Memory (SWM), showed no statistically significant differences between the fed and fasting conditions. However, sustained attention, as measured by the Rapid Visual Information Processing (RVP) CANTAB test, showed a statistically significant interaction of fed versus fasting and post-dose time of testing (F[1,28] = 6.88, P = 0.01), suggesting that 40 mg oxymorphone ER after a high-fat meal versus fasting mitigates the learning effect in this particular cognition domain from 1 hour to 3 hours post-dose. Oxymorphone 40 mg ER affected cognitive performance similarly within 3 hours post-dose, whether given on an empty stomach or after a high-fat meal, suggesting that the effect of food on plasma concentration may not be relevant in the medication's impact on cognition. Wiley Periodicals, Inc.
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Jones, Arden M; Jones, Kevin B
2007-01-01
The restriction of the resident physician work week to 80 hours has had dramatic affects on resident education and life-style. While effects on mood, psychological distress, and burn-out have been studied, the resultant changes in tangible quality of life have received little attention. birth rate was considered a measurable, relevant outcome. The resident marital and parental status by duty month was collected from a single orthopaedic surgical residency program for the four academic years preceding and following the implementation of the 80-hour work week. the number of births to residents during these periods were also tallied. The relative prevalence of positive marital status changed very little between residents in the two time durations from 66 to 71 percent, but parental status increased from 27 to 43 percent. The number of births per married resident duty year also increased from 0.23 pre-restrictions to 0.32 post-restrictions. While the individual decisions involved in generating these observed changes are complex and difficult to entirely decipher, it is thought that an increased perception of life-control within the work-hour restrictions may have prompted the dramatic changes in birth rate among resident families. PMID:17907445
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Jones, Arden M; Jones, Kevin B
2007-01-01
The restriction of the resident physician work week to 80 hours has had dramatic affects on resident education and life-style. While effects on mood, psychological distress, and burn-out have been studied, the resultant changes in tangible quality of life have received little attention. Birth rate was considered a measurable, relevant outcome. The resident marital and parental status by duty month was collected from a single orthopaedic surgical residency program for the four academic years preceding and following the implementation of the 80-hour work week. The number of births to residents during these periods were also tallied. The relative prevalence of positive marital status changed very little between residents in the two time durations from 66 to 71 percent, but parental status increased from 27 to 43 percent. The number of births per married resident duty year also increased from 0.23 pre-restrictions to 0.32 post-restrictions. While the individual decisions involved in generating these observed changes are complex and difficult to entirely decipher, it is thought that an increased perception of life-control within the work-hour restrictions may have prompted the dramatic changes in birth rate among resident families.
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[Post-partum eclampsia: epidemiology and prognosis].
Sabiri, B; Moussalit, A; Salmi, S; El Youssoufi, S; Miguil, M
2007-05-01
The post-partum eclampsia occurs usually in the first 48 hours, its incidence is between 13 and 37% of all eclampsia. The goal of this prospective study was to analyse the epidemiologic data and the prognosis of this complication in the post-partum stage. We enrolled between January 1st 2000 to December 31st 2003 all eclampsia admitted to the intensive care unit of the maternity of the university hospital centre Ibn Rochd of Casablanca, Morocco. We noted for each patient epidemiologic, clinical, biological and radiologic data. We releaved outcomoe also. Two groups are individualized: 1) group 1 (N=247): when eclampsia diagnosed in the prepartum stage; 2) group 2 (N=58): when crisis diagnosed in the post-partum stage. We compared the groups (student test), p<0.05 was significative. The incidence of eclampsia in the post-partum in this study was 19% (58 over 305). Eighty-two percent had the crisis in the first 24 hours; we noted a crisis in the sixth, seventh and lately in the sixtieth day. The major proportion of patients are nulliparous (64%), young (mean age: 24 years), without prenatal care, and has high blood pressure (48%), low GCS (mean: 12) and massive proteinuria>3 g/24 hours (37%). The post-partum eclampsia has best out come than these occurring in prepartum, with significantly (p<0.05) less high blood pressure, hellp syndrome and less placental abruption. Eclampsia is still frequent in our service; it seems less bad when occurring in the post-partum stage. We must give more attention for severe preeclamptic patient in this period.
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New Approach To Hour-By-Hour Weather Forecast
NASA Astrophysics Data System (ADS)
Liao, Q. Q.; Wang, B.
2017-12-01
Fine hourly forecast in single station weather forecast is required in many human production and life application situations. Most previous MOS (Model Output Statistics) which used a linear regression model are hard to solve nonlinear natures of the weather prediction and forecast accuracy has not been sufficient at high temporal resolution. This study is to predict the future meteorological elements including temperature, precipitation, relative humidity and wind speed in a local region over a relatively short period of time at hourly level. By means of hour-to-hour NWP (Numeral Weather Prediction)meteorological field from Forcastio (https://darksky.net/dev/docs/forecast) and real-time instrumental observation including 29 stations in Yunnan and 3 stations in Tianjin of China from June to October 2016, predictions are made of the 24-hour hour-by-hour ahead. This study presents an ensemble approach to combine the information of instrumental observation itself and NWP. Use autoregressive-moving-average (ARMA) model to predict future values of the observation time series. Put newest NWP products into the equations derived from the multiple linear regression MOS technique. Handle residual series of MOS outputs with autoregressive (AR) model for the linear property presented in time series. Due to the complexity of non-linear property of atmospheric flow, support vector machine (SVM) is also introduced . Therefore basic data quality control and cross validation makes it able to optimize the model function parameters , and do 24 hours ahead residual reduction with AR/SVM model. Results show that AR model technique is better than corresponding multi-variant MOS regression method especially at the early 4 hours when the predictor is temperature. MOS-AR combined model which is comparable to MOS-SVM model outperform than MOS. Both of their root mean square error and correlation coefficients for 2 m temperature are reduced to 1.6 degree Celsius and 0.91 respectively. The
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Bernstein, David I.; Jackson, Lisa; Patel, Shital M.; El Sahly, Hana M.; Spearman, Paul; Rouphael, Nadine; Rudge, Thomas L.; Hill, Heather; Goll, Johannes B.
2014-01-01
Background Strategies to implement post exposure prophylaxis (PEP) in case of an anthrax bioterror event are needed. To increase the number of doses of vaccine available we evaluated reducing the amount of vaccine administered at each of the vaccinations, and reducing the number of doses administered. Methods Healthy male and non-pregnant female subjects between the ages of 18 and 65 were enrolled and randomized 1:1:1:1 to one of four study arms to receive 0.5 mL (standard dose) of vaccine subcutaneously (SQ) at: A) days 0, 14; B) days 0 and 28; C) days 0, 14, and 28; or D) 0.25 ml at days 0, 14, and 28. A booster was provided on day 180. Safety was assessed after each dose. Blood was obtained on days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84, 100, 180, and 201 and both Toxin Neutralizing antibody and anti-PA IgG antibody measured. Results Almost all subjects developed some local reactions with 46% to 64% reported to be of moderate severity and 3.3% severe during the primary series. Vaccine groups that included a day 14 dose induced a ≥4 fold antibody rise in more subjects on days 21, 28 and 35 than the arm without a day 14 dose. However, schedules with a full day 28 dose induced higher peak levels of antibody that persisted longer. The half dose regimen did not induce antibody as well as the full dose study arms. Conclusion Depending on the extent of the outbreak, effectiveness of antibiotics and availability of vaccine, the full dose 0, 28 or 0, 14, 28 schedules may have advantages. PMID:25239484
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Bernstein, David I; Jackson, Lisa; Patel, Shital M; El Sahly, Hana M; Spearman, Paul; Rouphael, Nadine; Rudge, Thomas L; Hill, Heather; Goll, Johannes B
2014-10-29
Strategies to implement post exposure prophylaxis (PEP) in case of an anthrax bioterror event are needed. To increase the number of doses of vaccine available we evaluated reducing the amount of vaccine administered at each of the vaccinations, and reducing the number of doses administered. Healthy male and non-pregnant female subjects between the ages of 18 and 65 were enrolled and randomized 1:1:1:1 to one of four study arms to receive 0.5 mL (standard dose) of vaccine subcutaneously (SQ) at: (A) days 0, 14; (B) days 0 and 28; (C) days 0, 14, and 28; or (D) 0.25 mL at days 0, 14, and 28. A booster was provided on day 180. Safety was assessed after each dose. Blood was obtained on days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84, 100, 180, and 201 and both Toxin Neutralizing antibody and anti-PA IgG antibody measured. Almost all subjects developed some local reactions with 46-64% reported to be of moderate severity and 3.3% severe during the primary series. Vaccine groups that included a day 14 dose induced a ≥ 4 fold antibody rise in more subjects on days 21, 28, and 35 than the arm without a day 14 dose. However, schedules with a full day 28 dose induced higher peak levels of antibody that persisted longer. The half dose regimen did not induce antibody as well as the full dose study arms. Depending on the extent of the outbreak, effectiveness of antibiotics and availability of vaccine, the full dose 0, 28 or 0, 14, 28 schedules may have advantages. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Sethi, Sanjay; Fogarty, Charles; Hanania, Nicola A; Martinez, Fernando J; Rennard, Stephen; Fries, Michael; Orevillo, Chad; Darken, Patrick; St Rose, Earl; Strom, Shannon; Fischer, Tracy; Golden, Michael; Dwivedi, Sarvajna; Reisner, Colin
2016-11-17
Background: Co-Suspension™ Delivery Technology offers a novel pharmaceutical platform for inhaled drug therapy. This randomized, double-blind, placebo-controlled, single-dose study (NCT01349868) evaluated the efficacy of a range of doses for formoterol fumarate (FF) delivered using Co-Suspension delivery technology via a pressurized metered dose inhaler (MDI) versus placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Secondary objectives included determination of non-inferior efficacy and systemic exposure compared with open-label Foradil ® 12 μg (Foradil ® Aerolizer ® ; formoterol fumarate dry powder inhaler). Methods: Patients received each of the 6 study treatments (FF MDI [7.2, 9.6 and 19.2μg], placebo MDI and open-label Foradil ® [12 and 24µg]), separated by 3-10 days. Spirometry was performed 60 and 30 minutes prior to and at regular intervals up to 12 hours post-administration of study drug. The primary outcome measure was the change in forced expiratory volume in 1 second (FEV 1 ) area under the curve between 0 and 12 hours (AUC 0-12 ) relative to test day baseline. Results: A total of 50 patients were randomized to study treatment sequences. All doses of FF MDI demonstrated superiority to placebo ( p <0.0001) and non-inferiority to Foradil ® 12μg, on bronchodilator outcome measures. No serious adverse events were reported during the study. Conclusions: This study demonstrates non-inferiority of bronchodilator response and bioequivalent exposure of FF MDI 9.6μg to Foradil ® 12μg, with both agents exhibiting a similar safety profile in patients with moderate-to-severe COPD. This study supports the selection of FF MDI 9.6µg for further evaluation in Phase III trials.
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Pre- versus post-exercise protein intake has similar effects on muscular adaptations.
Schoenfeld, Brad Jon; Aragon, Alan; Wilborn, Colin; Urbina, Stacie L; Hayward, Sara E; Krieger, James
2017-01-01
The purpose of this study was to test the anabolic window theory by investigating muscle strength, hypertrophy, and body composition changes in response to an equal dose of protein consumed either immediately pre- versus post-resistance training (RT) in trained men. Subjects were 21 resistance-trained men (>1 year RT experience) recruited from a university population. After baseline testing, participants were randomly assigned to 1 of 2 experimental groups: a group that consumed a supplement containing 25 g protein and 1 g carbohydrate immediately prior to exercise (PRE-SUPP) ( n = 9) or a group that consumed the same supplement immediately post-exercise (POST-SUPP) ( n = 12). The RT protocol consisted of three weekly sessions performed on non-consecutive days for 10 weeks. A total-body routine was employed with three sets of 8-12 repetitions for each exercise. Results showed that pre- and post-workout protein consumption had similar effects on all measures studied ( p > 0.05). These findings refute the contention of a narrow post-exercise anabolic window to maximize the muscular response and instead lends support to the theory that the interval for protein intake may be as wide as several hours or perhaps more after a training bout depending on when the pre-workout meal was consumed.
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Temple, Anthony R; Zimmerman, Brenda; Gelotte, Cathy; Kuffner, Edwin K
2017-01-01
Compare efficacy and safety of 10 to 15 mg/kg with 20 to 30 mg/kg acetaminophen in febrile children 6 months to ≤ 11 years from 3 double-blind, randomized, single or multiple dose studies. Doses were compared on sum of the temperature differences (SUMDIFF), maximum temperature difference (MAXDIFF), temperature differences at each time point, and dose by time interactions. Alanine aminotransferase (ALT) was evaluated in the 72-hour duration study. A single dose of acetaminophen 20 to 30 mg/kg produced a greater effect on temperature decrement and duration of antipyretic effect over 8 hours than a single dose of 10 to 15 mg/kg. When equivalent total doses (i.e., 2 doses of 10 to 15 mg/kg given at 4-hour intervals and 1 dose of 20 to 30 mg/kg) were given over the initial 8-hour period, there were no significant temperature differences. Over a 72-hour period, 10 to 15 mg/kg acetaminophen administered every 4 hours maintained a more consistent temperature decrement than 20 to 30 mg/kg acetaminophen administered every 8 hours. Following doses of 60 to 90 mg/kg/day for up to 72 hours, no child had a clinically important increase in ALT from baseline. The number of children with reported adverse events was similar between doses. Data demonstrate the antipyretic effect of acetaminophen is dependent on total dose over a given time interval. These 3 studies provide clinical evidence that the recommended standard acetaminophen dose of 10 to 15 mg/kg is a safe and effective dose for treating fever in pediatric patients when administered as a single dose or as multiple doses for up to 72 hours.
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Persistent tachycardia in clozapine treated patients: A 24-hour ambulatory electrocardiogram study.
Nilsson, Björn M; Lindström, Leif; Mohsen, Issam; Holmlöv, Karolina; Bodén, Robert
2018-03-27
Tachycardia is associated with cardiovascular mortality. Tachycardia is also a known clozapine adverse effect. However, whether clozapine-associated tachycardia is persistent is not known. Thirty clozapine-treated patients with clinical tachycardia were investigated with 24-hour ambulatory electrocardiography (ECG). Baseline peripheral heart rate (HR) was 106.7±7.8. The ambulatory ECG 24-hour-HR was 98.7±9.7. Baseline HR and 24-hour-HR correlated strongly (r=0.74, p=0.000003). Daytime HR was 106.4±9.9 and nighttime HR 89.2±12.0. Low dose bisoprolol reduced HR significantly. The high 24-hour-HR indicates a persistent tachycardia. Tachycardia should not discourage from clozapine use but the findings indicate a need of guidelines for detection and treatment of clozapine-associated tachycardia. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
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Babu, Ranjith; Thomas, Steven; Hazzard, Matthew A; Friedman, Allan H; Sampson, John H; Adamson, Cory; Zomorodi, Ali R; Haglund, Michael M; Patil, Chirag G; Boakye, Maxwell; Lad, Shivanand P
2014-08-01
On July 1, 2003, the Accreditation Council for Graduate Medical Education (ACGME) implemented duty-hour restrictions for resident physicians due to concerns for patient and resident safety. Though duty-hour restrictions have increased resident quality of life, studies have shown mixed results with respect to patient outcomes. In this study, the authors have evaluated the effect of duty-hour restrictions on morbidity, mortality, length of stay, and charges in patients who underwent brain tumor and cerebrovascular procedures. The Nationwide Inpatient Sample was used to evaluate the effect of duty-hour restrictions on complications, mortality, length of stay, and charges by comparing the pre-reform (2000-2002) and post-reform (2005-2008) periods. Outcomes were compared between nonteaching and teaching hospitals using a difference-in-differences (DID) method. A total of 90,648 patients were included in the analysis. The overall complication rate was 11.7%, with the rates not significantly differing between the pre- and post-duty hour eras (p = 0.26). Examination of hospital teaching status revealed that complication rates decreased in nonteaching hospitals (12.1% vs 10.4%, p = 0.0004) and remained stable in teaching institutions (11.8% vs 11.9%, p = 0.73) in the post-reform era. Multivariate analysis demonstrated a significantly higher complication risk in teaching institutions (OR 1.33 [95% CI 1.11-1.59], p = 0.0022), with no significant change in nonteaching hospitals (OR 1.11 [95% CI 0.91-1.37], p = 0.31). A DID analysis to compare the magnitude in change between teaching and nonteaching institutions revealed that teaching hospitals had a significantly greater increase in complications during the post-reform era than nonteaching hospitals (p = 0.040). The overall mortality rate was 3.0%, with a significant decrease occurring in the post-reform era in both nonteaching (5.0% vs 3.2%, p < 0.0001) and teaching (3.2% vs 2.3%, p < 0.0001) hospitals. DID analysis to
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Erwin, Paul Campbell; Sheeler, Lorinda; Lott, John M
2009-01-01
An outbreak of foodborne hepatitis A infection compelled two regional health departments in eastern Tennessee to implement an emergency mass clinic for providing hepatitis immune serum globulin (ISG) to several thousand potentially exposed people. For the mass clinic framework, we utilized the smallpox post-event clinic plans of the Centers for Disease Control and Prevention (CDC), although the plans had only been exercised for smallpox. Following CDC's guidelines for staffing and organizing the mass clinic, we provided 5,038 doses of ISG during a total of 24 hours of clinic operation, using 3,467 person-hours, or 1.45 ISG doses per person-hour-very close to the 1.58 doses per person-hour targeted in CDC's smallpox post-event clinic plans. The mass clinic showed that CDC's smallpox post-event clinic guidelines were feasible, practical, and adaptable to other mass clinic situations.
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Cognitive Performance Effects of Bilastine 20 mg During 6 Hours at 8000 ft Cabin Altitude.
Valk, Pierre J L; Simons, Ries; Jetten, Andrea M; Valiente, Román; Labeaga, Luis
2016-07-01
Bilastine is a new oral, second generation antihistamine used in the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. It is considered a nonsedating antihistamine and might be recommended for use in pilots, pending research on the effects on flying-related performance under hypobaric conditions that prevail in an airliner. We assessed the effects of a single dose of bilastine 20 mg on alertness and complex task performance of healthy volunteers in a hypobaric chamber at 75.2 kPa (8000 ft/2438 m cabin altitude). In a randomized, double-blind, crossover study, 24 volunteers received a single dose of bilastine 20 mg, hydroxyzine 50 mg (active control), and placebo. Using the Vigilance and Tracking Task, Multi-Attribute Task Battery, and Stanford Sleepiness Scale, assessments were made before and up to 6 h after intake of the study medication. Bilastine 20 mg had no impairing effects on sleepiness levels, vigilance, or complex task performance for up to 6 h post-dose. Hydroxyzine 50 mg (active control) was associated with significant sleepiness and impaired performance across this time period, confirming the sensitivity of the tests. Bilastine 20 mg did not cause sleepiness or impaired performance on tasks related to flying. It is anticipated that a single dose of bilastine 20 mg will not affect flying performance. Bilastine may provide a safe therapeutic alternative for pilots suffering from allergic rhinitis or urticaria. Our findings might also have implications for the treatment of allergic disorders of personnel involved in other safety-sensitive jobs. Valk PJL, Simons R, Jetten AM, Valiente R, Labeaga L. Cognitive performance effects of bilastine 20 mg during 6 hours at 8000 ft cabin altitude. Aerosp Med Hum Perform. 2016; 87(7):622-627.
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Single dose oral diclofenac for acute postoperative pain in adults
Derry, Philip; Derry, Sheena; Moore, R Andrew; McQuay, Henry J
2014-01-01
Background Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), available as a potassium salt (immediate-release) or sodium salt (delayed-release). This review updates an earlier review published in The Cochrane Database of Systematic Reviews (Issue 2, 2004) on ‘Single dose oral diclofenac for postoperative pain’. Objectives To assess single dose oral diclofenac for the treatment of acute postoperative pain. Search methods Cochrane CENTRAL, MEDLINE, EMBASE, Biological Abstracts, the Oxford Pain Relief Database, and reference lists of articles were searched; last search December 2008. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed studies for inclusion and quality, and extracted data. The area under the pain relief versus time curve was used to derive the proportion of participants with at least 50% pain relief over 4 to 6 hours, using validated equations. Relative benefit (risk) and number needed to treat to benefit (NNT) were calculated. Information on adverse events, time to remedication, and participants needing additional analgesia was also collected. Main results Fifteen studies (eight additional studies) with 1512 participants more than doubled the information available at each dose. Overall 50% to 60% of participants experienced at least 50% pain relief over 4 to 6 hours at any dose with diclofenac, compared to 10 to 20% with placebo, giving NNTs of about 2.5 for doses of 25 mg to 100 mg (similar to earlier review); no dose response was demonstrated. At 50 mg and 100 mg, NNTs for diclofenac potassium (2.1 (1.8 to 2.4) and 1.9 (1.7 to 2.2)) were significantly lower (better) than for diclofenac sodium (6.7 (4.2 to 17) and 4.5 (3.2 to 7.7)). The median time to use of rescue medication was 2 hours for placebo, 4.3 hours for diclofenac 50 mg and 4.9 hours
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Modi, Nishit B; Dresser, Mark J; Simon, Mary; Lin, Denise; Desai, Dhaval; Gupta, Suneel
2006-03-01
Dapoxetine is a serotonin transporter inhibitor currently in development for the treatment of premature ejaculation. This randomized, 2-sequence, 2-treatment crossover study assessed the single- and multiple-dose pharmacokinetics of dapoxetine following once-daily administration of dapoxetine 30 mg and 60 mg to healthy male volunteers. Dapoxetine was rapidly absorbed following oral administration, with peak plasma concentrations reached approximately 1 hour after dosing; plasma concentrations after single doses of dapoxetine decreased rapidly to approximately 5% of peak concentrations by 24 hours. Elimination was biphasic, with an initial half-life of approximately 1.4 hours and a terminal half-life of approximately 20 hours. Dapoxetine showed time-invariant pharmacokinetics and dose proportionality between doses, and its pharmacokinetics was unaffected by multiple dosing. The pharmacokinetics of dapoxetine metabolites, desmethyldapoxetine and dapoxetine-N-oxide, was similarly unaffected by multiple dosing. There were no serious adverse events; the most commonly reported adverse events were diarrhea, dizziness, and nausea.
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Kompithra, Rajeev Zachariah; Paul, Anu; Manoharan, Divya; Babji, Sudhir; Sarkar, Rajiv; Mathew, Leni G; Kang, Gagandeep
2014-08-11
This study was undertaken to compare the immunogenicity of a three dose and five dose schedule of an oral live-attenuated human rotavirus vaccine, Rotarix in south Indian infants. Healthy infants (N=90), six to seven weeks of age were enrolled to receive three doses (n=45) or five doses of Rotarix vaccine (n=45) along with other scheduled vaccines, each dose separated by a four week interval. Blood samples were taken before vaccination and one month post-dose three in the Rotarix three dose group and one month post-dose five in the Rotarix five dose group; all were tested for anti-rotavirus IgA by an antibody sandwich enzyme immunoassay. At baseline, >50% of infants had >20 units of anti-rotavirus IgA. The seroconversion rates after three and five doses were low and not significantly different in the two groups. However, among vaccine responders, children seropositive at baseline showed a much greater absolute increase in IgA antibody levels than children seronegative at baseline. Rotarix vaccine showed low immunogenicity in south Indian children and increasing the number of doses did not increase the proportion of infants seroconverting after vaccination. Copyright © 2014. Published by Elsevier Ltd.
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A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis.
Elmunzer, B Joseph; Scheiman, James M; Lehman, Glen A; Chak, Amitabh; Mosler, Patrick; Higgins, Peter D R; Hayward, Rodney A; Romagnuolo, Joseph; Elta, Grace H; Sherman, Stuart; Waljee, Akbar K; Repaka, Aparna; Atkinson, Matthew R; Cote, Gregory A; Kwon, Richard S; McHenry, Lee; Piraka, Cyrus R; Wamsteker, Erik J; Watkins, James L; Korsnes, Sheryl J; Schmidt, Suzette E; Turner, Sarah M; Nicholson, Sylvia; Fogel, Evan L
2012-04-12
Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). In this multicenter, randomized, placebo-controlled, double-blind clinical trial, we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP. Patients were determined to be at high risk on the basis of validated patient- and procedure-related risk factors. The primary outcome was post-ERCP pancreatitis, which was defined as new upper abdominal pain, an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least 2 nights. A total of 602 patients were enrolled and completed follow-up. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in the indomethacin group and in 52 of 307 patients (16.9%) in the placebo group (P=0.005). Moderate-to-severe pancreatitis developed in 13 patients (4.4%) in the indomethacin group and in 27 patients (8.8%) in the placebo group (P=0.03). Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00820612.).
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Chang, Lynn
2014-01-01
Purpose To report outcomes on 5 patients treated with salvage partial low-dose-rate (LDR) 125-iodine (125I) permanent prostate seed brachytherapy (BT) for biopsy-proven locally persistent prostate cancer, following failure of dose-escalated external beam radiotherapy (EBRT). Material and methods A retrospective review of the Fox Chase Cancer Center prostate cancer database identified five patients treated with salvage partial LDR 125I seed implant for locally persistent disease following dose-escalated EBRT to 76-84 Gy in 2 Gy per fraction equivalent. All patients had post-EBRT biopsies confirming unilateral locally persistent prostate cancer. Pre-treatment, EBRT and BT details, as well as post-treatment characteristics were documented and assessed. Results The median follow-up post-implant was 41 months. All five patients exhibited low acute genitourinary and gastrointestinal toxicities. Increased erectile dysfunction was noted in three patients. There were no biochemical failures following salvage LDR 125I seed BT to date, with a median post-salvage PSA of 0.4 ng/mL. Conclusions In carefully selected patients with local persistence of disease, partial LDR 125I permanent prostate seed implant appears to be a feasible option for salvage local therapy with an acceptable toxicity profile. Further study is needed to determine long-term results of this approach. PMID:25337135
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Brown, Justin C; Schmitz, Kathryn H
2017-01-01
In a post hoc analysis, we quantified the risk of musculoskeletal injury (MSI) associated with different volumes of aerobic exercise in a randomized trial. Premenopausal women (n = 119) were randomized to one of three groups: low-dose aerobic exercise (150 min·per week), high-dose aerobic exercise (300 min·per week) or control (usual activity) for 5 months. Compared to the control group, the risk of reporting an acute MSI increased with higher volumes of aerobic exercise, with a similar pattern observed for recurrent MSI. The risk of reporting an MSI severe enough to impair activities of daily living did not increase with higher volumes of aerobic exercise. Approximately half of MSI were causally attributed to aerobic exercise. The risk of experiencing an acute or recurrent MSI increases with higher volumes of aerobic exercise; however, the risk of experiencing an MSI severe enough to impair activities of daily living does not increase with higher volumes of aerobic exercise.
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Lemon, Jennifer A.; Taylor, Kristina; Verdecchia, Kyle; ...
2014-01-01
Apoptotic and DNA damage endpoints are frequently used as surrogate markers of cancer risk, and have been well-studied in the Trp53+/- mouse model. We report the effect of differing Trp53 gene status on the dose response of ionizing radiation exposures (0.01-2 Gy), with the unique perspective of determining if effects of gene status remain at extended time points. Here we report no difference in the dose response for radiation-induced DNA double-strand breaks in bone marrow and genomic instability (MN-RET levels) in peripheral blood, between wild-type ( Trp53+/+) and heterozygous ( Trp53+/-) mice. The dose response for Trp53+/+ mice showed highermore » initial levels of radiation-induced lymphocyte apoptosis relative to Trp53+/- between 0 and 1 Gy. Although this trend was observed up to 12 hours post-irradiation, both genotypes ultimately reached the same level of apoptosis at 14 hours, suggesting the importance of late-onset p53-independent apoptotic responses in this mouse model. Expected radiation-induced G1 cell cycle delay was observed in Trp53+/+ but not Trp53+/-. Although p53 has an important role in cancer risk, we have shown its influence on radiation dose response can be temporally variable. This research highlights the importance of caution when using haematopoietic endpoints as surrogates to extrapolate radiation-induced cancer risk estimation.« less
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Kim, Youl-Ri; Eom, Jin-Sup; Yang, Jae-Won; Kang, Jiwon; Treasure, Janet
2015-01-01
Social difficulties and problems related to eating behaviour are common features of both anorexia nervosa (AN) and bulimia nervosa (BN). The aim of this study was to examine the impact of intranasal oxytocin on consummatory behaviour and emotional recognition in patients with AN and BN in comparison to healthy controls. A total of 102 women, including 35 patients with anorexia nervosa (AN), 34 patients with bulimia nervosa (BN), and 33 healthy university students of comparable age and intelligence, participated in a double-blind, single dose placebo-controlled cross-over study. A single dose of intranasal administration of oxytocin (40 IU) (or a placebo) was followed by an emotional recognition task and an apple juice drink. Food intake was then recorded for 24 hours post-test. Oxytocin produced no significant change in appetite in the acute or 24 hours free living settings in healthy controls, whereas there was a decrease in calorie consumption over 24 hours in patients with BN. Oxytocin produced a small increase in emotion recognition sensitivity in healthy controls and in patients with BN, In patients with AN, oxytocin had no effect on emotion recognition sensitivity or on consummatory behaviour. The impact of oxytocin on appetite and social cognition varied between people with AN and BN. A single dose of intranasal oxytocin decreased caloric intake over 24 hours in people with BN. People with BN showed enhanced emotional sensitivity under oxytocin condition similar to healthy controls. Those effects of oxytocin were not found in patients with AN. ClinicalTrials.gov KCT00000716.
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High Dose Cytosine Arabinoside in the consolidation of adult acute myeloid leukemia.
Rahman, M H; Khan, M A; Islam, M S; Afrose, S; Ara, T
2012-04-01
This interventional study was done to evaluate the duration of remission with High Dose Cytosine Arabinoside (Ara-C) as post-remission chemotherapy in the consolidation of adult acute myeloid leukemia. A total of 32 patients were included in this study. Among them, 19 were male and 13 were female and the age of the patients ranges from 15-60 years. We use High Dose Cytosine Arabinoside 1.5-2.5 g/m2 i.v, 12 hourly, over 2-3 hours on day 1, 3 and 5 in a 28 days cycle. This study was done during the period of April 2007 to March 2009 in the department of hematology, Dhaka Medical College & Hospital. History, clinical features and laboratory investigations were included. Among 32 patients, 5 patients (15.6%) received one cycle, 20 patients (62.5%) received two cycles and 7 patients (21.9%) received three cycles. The mean ± SD duration of remission (disease free survival) was 5.20 ± 3.83 months who received one cycle, 9.55 ± 3.30 months and 10.71 ± 1.70 months who received two cycles and three cycles respectively. The adverse effects of the therapy were neutropenia and neutropenic fever, purpuric rash, gum bleeding, mucositis and peripheral neuropathy. The supportive materials needed were antibiotics (both prophylactic and treatment) 86.13%, blood and blood products 51.7% and G-CSF 14.9% patients of all cycles. High Dose Ara-C (HiDAC) is a safe and cost effective consolidation treatment for AML patients in complete remission. This therapy merits multi-center control study to define its efficacy and cost-effectiveness in contrast to our socio-economic condition.
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Doses for post-Chernobyl epidemiological studies: are they reliable?
Drozdovitch, Vladimir; Chumak, Vadim; Kesminiene, Ausrele; Ostroumova, Evgenia; Bouville, André
2016-09-01
On 26 April 2016, thirty years will have elapsed since the occurrence of the Chernobyl accident, which has so far been the most severe in the history of the nuclear reactor industry. Numerous epidemiological studies were conducted to evaluate the possible health consequences of the accident. Since the credibility of the association between the radiation exposure and health outcome is highly dependent on the adequacy of the dosimetric quantities used in these studies, this paper makes an effort to overview the methods used to estimate individual doses and the associated uncertainties in the main analytical epidemiological studies (i.e. cohort or case-control) related to the Chernobyl accident. Based on the thorough analysis and comparison with other radiation studies, the authors conclude that individual doses for the Chernobyl analytical epidemiological studies have been calculated with a relatively high degree of reliability and well-characterized uncertainties, and that they compare favorably with many other non-Chernobyl studies. The major strengths of the Chernobyl studies are: (1) they are grounded on a large number of measurements, either performed on humans or made in the environment; and (2) extensive effort has been invested to evaluate the uncertainties associated with the dose estimates. Nevertheless, gaps in the methodology are identified and suggestions for the possible improvement of the current dose estimates are made.
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Cocaine self-administration under variable-dose schedules in squirrel monkeys.
Panlilio, Leigh V; Thorndike, Eric B; Schindler, Charles W
2006-06-01
Squirrel monkeys self-administered cocaine under a variable-dose schedule, with the dose varied from injection to injection. As in earlier studies with rats, post-injection pauses varied as a monotonic function of dose, allowing a cocaine dose-effect curve to be obtained during each session. These curves were shifted by pretreatment with dopamine antagonists, demonstrating that this procedure may provide an efficient means of evaluating treatments that affect drug self-administration. However, drug intake eventually became "dysregulated" after extensive training (100-300 sessions), with relatively short pauses following all doses. Dose-sensitivity was restored by adding a 60-s timeout period after each injection, suggesting that dysregulation occurred because the monkeys developed a tendency to self-administer another injection before the previous injection had been adequately distributed. Finally, when the response requirement under the variable-dose schedule was increased from 1 to 10, both the post-injection pause and the rate of responding following the pause ("run rates") were found to vary with dose. The dose-dependency of run rates suggests that post-injection pauses reflect not only motivational factors, such as satiety, but also the direct effects of cocaine on leverpressing.
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Itoh, Kouichi; Inamine, Moriyoshi; Oshima, Wataru; Kotani, Masaharu; Chiba, Yoichi; Ueno, Masaki; Ishihara, Yasuhiro
2015-05-22
The management of status epilepticus (SE) is important to prevent mortality and the development of post-SE symptomatic epilepsy. Acquired epilepsy after an initial brain insult by SE can be experimentally reproduced in the murine model of SE induced by pilocarpine. In the present study, we evaluated the possibility of treatment with a high-dose of levetiracetam in this model. Repeated treatment with high-dose levetiracetam after termination of SE by diazepam significantly prevented the incidence of spontaneous recurrent seizures and mortality for at least 28 days. To determine the brain alterations after SE, magnetic resonance imaging was performed. Both T2-weighted imaging and diffusion-weighted imaging showed changes in the limbic regions. These changes in the limbic regions demonstrated the development of cytotoxic edema three hours after SE, followed by the development of vasogenic edema two days after SE. In the pilocarpine-SE model, the incidence of spontaneous recurrent seizures after SE was strongly associated with neuronal damage within a few hours to days after SE by the development of vasogenic edema via the breakdown of the blood-brain barrier in the limbic regions. High-dose levetiracetam significantly suppressed the parameters in the limbic areas. These data indicate that repeated treatment with high-dose levetiracetam for at least two days after SE termination by diazepam is important for controlling the neuronal damage by preventing brain edema. Therefore, these findings suggest that early treatment with high-dose levetiracetam after SE termination by diazepam may protect against adverse sequelae via the inhibition of neurotoxicity induced by brain edema events. Copyright © 2015 Elsevier B.V. All rights reserved.
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Heard, K; Rumack, B H; Green, J L; Bucher-Bartelson, B; Heard, S; Bronstein, A C; Dart, R C
2014-06-01
Acetylcysteine prevents hepatic injury when administered soon after acetaminophen overdose. The most commonly used treatment protocols are a 72-hour oral and a 21-hour intravenous (IV) protocol. Between 1984 and 1994, 409 patients were enrolled in a study to describe the outcomes of patients who were treated using a 48-hour IV protocol. In 1991, an interim analysis reported the first 223 patients. The objective of this manuscript is to report the rates of hepatotoxicity and adverse events occurring during a 48-hour IV acetylcysteine protocol in the entire 409 patient cohort. This was a multicenter, single-arm, open-label clinical trial enrolling patients who presented with a toxic serum acetaminophen concentration within 24 h of acute acetaminophen ingestion. Patients were treated with 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses. Serum aminotransferase activities were measured every 8 h during the protocol, and adverse events were recorded. The primary outcome was the percentage of subjects who developed hepatotoxicity defined as a peak serum aminotransferase greater than 1000 IU/L. Four hundred and nine patients were enrolled, and 309 met inclusion for the outcome analysis. The overall percentage of patients developing hepatotoxicity was 18.1%, and 3.4% of patients treated within 10 h developed hepatotoxicity. One acetaminophen-related death occurred in a patient treated at 22 h. Adverse events occurred in 28.9% of enrolled subjects; the most common adverse events were nausea, vomiting, and flushing, and no events were rated as serious by the investigator. Acetaminophen-overdosed patients treated with IV acetylcysteine administered as 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses had a low rate of hepatotoxicity and few adverse events. This protocol delivers a higher dose of acetylcysteine which may be useful in selected cases involving very large overdoses.
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Working hours and risk of gestational hypertension and pre-eclampsia.
Chang, Pei-Jen; Chu, Li-Ching; Hsieh, Wu-Shiun; Chuang, Yi-Li; Lin, Shio-Jean; Chen, Pau-Chung
2010-01-01
The potential impact of employment on maternal health, particularly in relation to gestational hypertension and pre-eclampsia, has been subject to research. However, there is limited evidence on associations between shift work and long working hours on the incidence of these conditions. To evaluate potential associations between maternal shift work and long working hours during pregnancy and gestational hypertension or pre-eclampsia. Multistage stratified systematic sampling was used to recruit 24 200 post-partum women from the Taiwan national birth registration database in 2005. Subjects underwent home interview 6 months after their deliveries by structured questionnaire to obtain characteristics of maternal employment and potential confounders. Diagnosis of gestational hypertension and pre-eclampsia was obtained from the birth registration. There was no association between employment status and gestational hypertension or pre-eclampsia. Also, no significant association between gestational hypertension or pre-eclampsia and maternal shift work or long working hours during pregnancy was found in all or primiparous women. There was no convincing evidence that maternal shift work or long working hours had a higher risk of gestational hypertension or pre-eclampsia. However, further research is warranted to confirm these negative findings.
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Neighborhood walkability, income, and hour-by-hour physical activity patterns.
Arvidsson, Daniel; Eriksson, Ulf; Lönn, Sara Larsson; Sundquist, Kristina
2013-04-01
This study aimed to investigate both the mean daily physical activity and the hour-by-hour physical activity patterns across the day using accelerometry and how they are associated with neighborhood walkability and individual income. Moderate physical activity (MPA) was assessed by accelerometry in 2252 adults in the city of Stockholm, Sweden. Neighborhood walkability (residential density, street connectivity, and land use mix) was objectively assessed within 1000m network buffers around the participants' residence and individual income was self-reported. Living in a high walkability neighborhood was associated with more mean daily MPA compared with living in a low walkability neighborhood on weekdays and weekend days. Hour-by-hour analyses showed that this association appeared mainly in the afternoon/early evening during weekdays, whereas it appeared across the middle of the day during weekend days. Individual income was associated with mean daily MPA on weekend days. On weekdays, the hour-by-hour analyses showed that high income was associated with more MPA around noon and in late afternoon/early evening, whereas low income was associated with more MPA at the hours before noon and in the early afternoon. During the weekend, high income was more consistently associated with higher MPA. Hour-by-hour accelerometry physical activity patterns provides a more comprehensive picture of the associations between neighborhood walkability and individual income and physical activity and the variability of these associations across the day.
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Morphological changes induced by different doses of gamma irradiation in garlic sprouts
NASA Astrophysics Data System (ADS)
Pellegrini, C. N.; Croci, C. A.; Orioli, G. A.
2000-03-01
The objective of this work was to evaluate the effects of different doses of gamma rays applied in dormancy and post-dormancy on garlic bulbs in relation with some morphophysiological parameters. High (commercial) doses cause the complete inhibition of sprouting and mitosis (due to nuclear aberrations). Relatively low doses show no effects on bulbs but doses of 10 Gy applied in post-dormancy reduce sprouting and stop mitosis. This inhibition becomes noticeable from 150 days post-harvest onwards. Exogenous growth regulators can reverse these effects. Results may reinforce the good practice of radioinhibition processes in garlic.
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Chen, Horng H; Anstrom, Kevin J; Givertz, Michael M; Stevenson, Lynne W; Semigran, Marc J; Goldsmith, Steven R; Bart, Bradley A; Bull, David A; Stehlik, Josef; LeWinter, Martin M; Konstam, Marvin A; Huggins, Gordon S; Rouleau, Jean L; O'Meara, Eileen; Tang, W H Wilson; Starling, Randall C; Butler, Javed; Deswal, Anita; Felker, G Michael; O'Connor, Christopher M; Bonita, Raphael E; Margulies, Kenneth B; Cappola, Thomas P; Ofili, Elizabeth O; Mann, Douglas L; Dávila-Román, Víctor G; McNulty, Steven E; Borlaug, Barry A; Velazquez, Eric J; Lee, Kerry L; Shah, Monica R; Hernandez, Adrian F; Braunwald, Eugene; Redfield, Margaret M
2013-12-18
Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 μg/kg/min) or low-dose nesiritide (0.005 μg/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119). Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, -714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, -0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo
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Performance of KCl:Eu2+ storage phosphor dosimeters for low dose measurements
Li, H. Harold; Hansel, Rachael; Knutson, Nels; Yang, Deshan
2013-01-01
Recent research has demonstrated that europium doped potassium chloride (KCl:Eu2+) storage phosphor material has the potential to become the physical foundation of a novel and reusable dosimetry system using either film-like devices or devices similar to thermoluminescent dosimeter (TLD) chips. The purposes of this work are to quantify the performance of KCl:Eu2+ prototype dosimeters for low dose measurements and to demonstrate how it can be incorporated into clinical application for in vivo peripheral dose measurements. Pellet-style KCl:Eu2+ dosimeters, 6 mm in diameter, and 1 mm thick, were fabricated in-house for this study. The dosimeters were read using a laboratory photostimulated luminescence detection system. KCl:Eu2+ prototype storage phosphor dosimeter was capable of measuring a dose-to-water as low as 0.01 cGy from a 6 MV photon beam with a signal-to-noise ratio greater than 6. A pre-readout thermal annealing procedure enabled the dosimeter to be read within an hour post irradiation. After receiving large accumulated doses (~10 kGy), the dosimeters retained linear response in the low dose region with only a 20 percent loss of sensitivity comparing to a fresh sample (zero Gy history). The energy-dependence encountered during low dose peripheral measurements could be accounted for via a single point outside-field calibration per each beam quality. With further development the KCl:Eu2+− based dosimeter could become a versatile and durable dosimetry tool with large dynamic range (sub-cGy to 100 Gy). PMID:23735856
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Colton, Katharine; Yang, S; Hu, P F; Chen, H H; Bonds, B; Stansbury, L G; Scalea, T M; Stein, D M
2016-05-01
Past work has shown the importance of the "pressure times time dose" (PTD) of intracranial hypertension (intracranial pressure [ICP] > 19 mm Hg) in predicting outcome after severe traumatic brain injury. We used automated data collection to measure the effect of common medications on the duration and dose of intracranial hypertension. Patients >17 years old, admitted and requiring ICP monitoring between 2008 and 2010 at a single, large urban tertiary care facility, were retrospectively enrolled. Timing and dose of ICP-directed therapy were recorded from paper and electronic medical records. The ICP data were collected automatically at 6-second intervals and averaged over 5 minutes. The percentage of time of intracranial hypertension (PTI) and PTD (mm Hg h) were calculated. A total of 98 patients with 664 treatment instances were identified. Baseline PTD ranged from 27 (before administration of propofol and fentanyl) to 150 mm Hg h (before mannitol). A "small" dose of hypertonic saline (HTS; ≤250 mL 3%) reduced PTD by 38% in the first hour and 37% in the second hour and reduced the time with ICP >19 by 38% and 39% after 1 and 2 hours, respectively. A "large" dose of HTS reduced PTD by 40% in the first hour and 63% in the second (PTI reduction of 36% and 50%, respectively). An increased dose of propofol or fentanyl infusion failed to decrease PTD but reduced PTI between 14% (propofol alone) and 30% (combined increase in propofol and fentanyl, after 2 hours). Barbiturates failed to decrease PTD but decreased PTI by 30% up to 2 hours after administration. All reductions reported are significantly changed from baseline, P < .05. Baseline PTD values before drug administration reflects varied patient criticality, with much higher values seen before the use of mannitol or barbiturates. Treatment with HTS reduced PTD and PTI burden significantly more than escalation of sedation or pain management, and this effect remained significant at 2 hours after administration.
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Performance of commercial platforms for rapid genotyping of polymorphisms affecting warfarin dose.
King, Cristi R; Porche-Sorbet, Rhonda M; Gage, Brian F; Ridker, Paul M; Renaud, Yannick; Phillips, Michael S; Eby, Charles
2008-06-01
Initiation of warfarin therapy is associated with bleeding owing to its narrow therapeutic window and unpredictable therapeutic dose. Pharmacogenetic-based dosing algorithms can improve accuracy of initial warfarin dosing but require rapid genotyping for cytochrome P-450 2C9 (CYP2C9) *2 and *3 single nucleotide polymorphisms (SNPs) and a vitamin K epoxide reductase (VKORC1) SNP. We evaluated 4 commercial systems: INFINITI analyzer (AutoGenomics, Carlsbad, CA), Invader assay (Third Wave Technologies, Madison, WI), Tag-It Mutation Detection assay (Luminex Molecular Diagnostics, formerly Tm Bioscience, Toronto, Canada), and Pyrosequencing (Biotage, Uppsala, Sweden). We genotyped 112 DNA samples and resolved any discrepancies with bidirectional sequencing. The INFINITI analyzer was 100% accurate for all SNPs and required 8 hours. Invader and Tag-It were 100% accurate for CYP2C9 SNPs, 99% accurate for VKORC1 -1639/3673 SNP, and required 3 hours and 8 hours, respectively. Pyrosequencing was 99% accurate for CYP2C9 *2, 100% accurate for CYP2C9 *3, and 100% accurate for VKORC1 and required 4 hours. Current commercial platforms provide accurate and rapid genotypes for pharmacogenetic dosing during initiation of warfarin therapy.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
de Garavilla, L.; Chermak, T.; Valentine, H.L.
1990-02-26
The novel, low-molecular weight, organo-metallic complex Mn-DFO functions in vitro as an SOD-mimic effectively dismutating the superoxide radical. Oxygen-derived free radicals appear to be involved in the pathology of both endotoxic (ENDO) and hemorrhagic (HEM) shock whereby treatment with SOD is associated with improvements in survival. Therefore, the following models were utilized to evaluate the in vivo activity of Mn-DFO. Male rats (350-450g) were anesthetized with ketamine (100mg/kg, ip) and subjected to HEM hypotension by withdrawing approximately 40% of the animals' blood volume over a 10 minute period. MABP was maintained constant at 40mmHg for 60 minutes, followed by completemore » autoreinfusion. Survival was reduced to 20% in the control group at 24 hour post-reinfusion. A single post-shock dose of Mn-DFO (10mg/kg, iv) more than doubled the survival rate for up to 24 hour post-reinfusion as compared to control. Female mice (CFmal and-1, 20-25g) were challenged with 500ug of ENDO and 0.8ug of actinomycin/animal and dosed 1 hour pre and post with Mn-DFO (30mg/kg/dose, iv). Survival improved from 60% in the control group to 100% in the Mn-DFO group at 18 hours post ENDO challenge. Using a multiple dosing regimen, Mn-DFO significantly improved survival for up to 48 hours post-ENDO. Thus, unlike other SOD-mimics, Mn-DFO appears to exhibit in vivo activity.« less
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Radioiodine (1-131) Dose for the Treatment of Hyperthyroidism in Rajavithi Hospital.
Kuanrakcharoen, Pichit
2016-02-01
The main cause of hyperthyroidism is diffuse toxic goiter (Graves' disease), and the treatment of choice after medical therapy failure is radioiodine (I-131). There are two common methods of determining the optimal I-131 dose: calculated dose or fixed dose. The calculated dose method is based on the following formula: 75-200 microcuri/gram of thyroid gland divided by the percentage of radioiodine uptake at 24 hours (24-hour RAIU). As this is quite complex, some centers use fixed doses, such as 5, 10 or 15 mCi because it is simpler. At Rajavithi Hospital, the applied dose of I-131 is determined based on the thyroid gland weight assessed by palpation and other clinical factors. To study the mean I-131 dose for the initial treatment of hyperthyroidism in Rajavithi Hospital, to find the clinical factors that correlate with I-131 treatment dose, and to devise a formula to predict the optimal I-131 treatment dose. This was a retrospective study of 510 patients with a diagnosis of hyperthyroidism who received initial I-131 treatment at the Department of Nuclear Medicine in Rajavithi Hospital between January 2014 and June 2015. Baseline characteristics including age, sex, age at diagnosis, duration of antithyroid drug (ATD) therapy, gland weight (g), 3-hour RAIU and I-131 treatment dose were reviewed from medical records. The mean age ± SD was 41.93 ± 14.11 years (range 14-81 years), and the male to female ratio was 4.1:1. The mean duration of ATD therapy was 3.54 ± 4.02 years (min-max, 0.8-40.6 years). The mean gland weight was 54.35 ± 32.95 grams, and the mean 3-hour RAIU was 55.5 ± 23.69%. The mean I-131 treatment dose was 14.84 ± 5.71 mCi (min-max, 7-30 mCi). There was no significant correlation between dose and age, age at diagnosis, duration of A TD therapy or 3-hour RAIU. The study showed a significant correlation between I-131 dose and gland size, r = 0.938 (p < 0.001), and the regression relationship equation was: 1-131 dose = 0.235 gland size, r = 0.938. I
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Caplice, Noel M; DeVoe, Mary C; Choi, Janet; Dahly, Darren; Murphy, Theodore; Spitzer, Ernest; Van Geuns, Robert; Maher, Michael M; Tuite, David; Kerins, David M; Ali, Mohammed T; Kalyar, Imtiaz; Fahy, Eoin F; Khider, Wisam; Kelly, Peter; Kearney, Peter P; Curtin, Ronan J; O'Shea, Conor; Vaughan, Carl J; Eustace, Joseph A; McFadden, Eugene P
2018-06-01
Residual and significant postinfarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models, low-dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodeling effects. We studied the safety and efficacy of immediate post-PCI low-dose intracoronary IGF1 infusion in STEMI patients. Using a double-blind, placebo-controlled, multidose study design, we randomized 47 STEMI patients with significantly reduced (≤40%) LV ejection fraction (LVEF) after successful PCI to single intracoronary infusion of placebo (n = 15), 1.5 ng IGF1 (n = 16), or 15 ng IGF1 (n = 16). All received optimal medical therapy. Safety end points were freedom from hypoglycemia, hypotension, or significant arrhythmias within 1 hour of therapy. The primary efficacy end point was LVEF, and secondary end points were LV volumes, mass, stroke volume, and infarct size at 2-month follow-up, all assessed by magnetic resonance imaging. Treatment effects were estimated by analysis of covariance adjusted for baseline (24 hours) outcome. No significant differences in safety end points occurred between treatment groups out to 30 days (χ 2 test, P value = .77). There were no statistically significant differences in baseline (24 hours post STEMI) clinical characteristics or LVEF among groups. LVEF at 2 months, compared to baseline, increased in all groups, with no statistically significant differences related to treatment assignment. However, compared with placebo or 1.5 ng IGF1, treatment with 15 ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (P = .018), LV mass (P = .004), and stroke volume (P = .016). Late gadolinium enhancement (±SD) at 2 months was lower in 15 ng IGF1 (34.5 ± 29.6 g) compared to placebo (49.1 ± 19.3 g) or 1.5 ng IGF1 (47.4 ± 22.4 g) treated patients
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Udani, Jay K.; Brown, Donald J.; Tan, Maria Olivia C.; Hardy, Mary
2013-01-01
Objective 7-Hydroxymaitairesinol (7-HMR) is a naturally occurring plant lignan found in whole grains and the Norway spruce (Piciea abies). The purpose of this study was to evaluate the bioavailability of a proprietary 7-HMR product (HMRlignan, Linnea SA, Locarno, Switzerland) through measurement of lignan metabolites and metabolic precursors. Methods A single-blind, parallel, pharmacokinetic and dose-comparison study was conducted on 22 post-menopausal females not receiving hormone replacement therapy. Subjects were enrolled in either a 36 mg/d (low-dose) or 72 mg/d dose (high-dose) regimen for 8 weeks. Primary measured outcomes included plasma levels of 7-HMR and enterolactone (ENL), and single-dose pharmacokinetic analysis was performed on a subset of subjects in the low-dose group. Safety data and adverse event reports were collected as well as data on hot flash frequency and severity. Results Pharmacokinetic studies demonstrated 7-HMR Cmax = 757.08 ng/ml at 1 hour and ENL Cmax = 4.8 ng/ml at 24 hours. From baseline to week 8, plasma 7-HMR levels increased by 191% in the low-dose group (p < 0.01) and by 1238% in the high-dose group (p < 0.05). Plasma ENL levels consistently increased as much as 157% from baseline in the low-dose group and 137% in the high-dose group. Additionally, the mean number of weekly hot flashes decreased by 50%, from 28.0/week to 14.3/week (p < 0.05) in the high-dose group. No significant safety issues were identified in this study. Conclusion The results demonstrate that HMRlignan is quickly absorbed into the plasma and is metabolized to ENL in healthy postmenopausal women. Clinically, the data demonstrate a statistically significant improvement in hot flash frequency. Doses up to 72 mg/d HMRlignan for 8 weeks were safe and well tolerated in this population. PMID:24606716
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Globus, Ruth K.
one month after irradiation (IR). At four months post-IR, these animals were comparable to sham-treated controls with regards to the abovementioned structural parameters. Irradation at 1 or 10 cGy did not result in any significant changes in bone structural parameters. (3) Irradiation of 16-wk old male mice with high doses of 56Fe or proton (50 or 200cGy), but not at low doses (5 or 10cGy), showed a similar loss of cancellous BV/TV and trabecular number at five weeks post-IR. (4) Age-related bone loss overtook acute radiation-induced decrements in bone structure within four months post-IR with 100 cGy gamma and 12 months post-IR with 200 cGy iron. Transgenic mice globally overexpressing human catalase gene in mitochondria did not exhibit cancellous bone loss as assessed at four month post-IR with 10 cGy proton, 50 cGy iron, or in combination. (5) The cellular and molecular mechanisms responsible for loss of bone with radiation are mediated primarily through increased osteoclastogenesis. Our data provide evidence that there are increases in gene expression of TNF alpha and MCP1 in the bone marrow cells 24 hours post-IR and of osteoclastogenic differentiation factor RANKL by day 3. These cytokines in the marrow may stimulate mature osteoclasts or drive osteoclastogenesis from precursors. (6) Osteoblastogenesis from marrow progenitors evaluated ex vivo decreased following whole body 56Fe irradiation at a dose threshold between 20 and 50 cGy whereas osteoclastogenesis ex vivo increased with doses as low as 10cGy two days post-IR of mice. However, the latter finding was not observed in more than a single experiment. (7) Gamma irradiation of cells in vitro requires relatively high doses (200cGy) to disturb normal osteoblastogenesis and osteoclastogenesis as evidenced by decrements in mineralized nodule formation, osteoclast counts, and expression of osteoblast related genes such as runx2, col1a1. (8) We also investigated the effect of antioxidants on osteoblastogenesis
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Radiation measurements and doses at SST altitudes
NASA Technical Reports Server (NTRS)
Foelsche, T.
1972-01-01
Radiation components and dose equivalents due to galactic and solar cosmic rays in the high atmosphere, especially at SST altitudes, are presented. The dose equivalent rate for the flight personnel flying 500 hours per year in cruise altitudes of 60,000-65,000 feet (18-19.5 km) in high magnetic latitudes is about 0.75-1.0 rem per year averaged over the solar cycle, or about 15-20 percent of the maximum permissible dose rate.
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Wuytack, Francesca; Smith, Valerie; Cleary, Brian J
2016-07-14
-hospitalisation due to perineal pain; breastfeeding (fully or mixed) at discharge; breastfeeding (fully or mixed) at six weeks; perineal pain at six weeks; maternal views; postpartum depression; instrumental measures of disability due to perineal pain. NSAID versus placeboCompared to women who received a placebo, more women who received a single dose NSAID achieved adequate pain relief at four hours (risk ratio (RR) 1.91, 95% confidence interval (CI) 1.64 to 2.23, 10 studies, 1573 participants (low-quality evidence)) and adequate pain relief at six hours (RR 1.92, 95% CI 1.69 to 2.17, 17 studies, 2079 participants (very low-quality evidence)). Women who received a NSAID were also less likely to need additional analgesia compared to women who received placebo at four hours (RR 0.39, 95% CI 0.26 to 0.58, four studies, 486 participants (low-quality evidence)) and at six hours after initial administration (RR 0.32, 95% CI 0.26 to 0.40, 10 studies, 1012 participants (low-quality evidence)). Fourteen maternal adverse effects were reported in the NSAID group (drowsiness (5), abdominal discomfort (2), weakness (1), dizziness (2), headache (2), moderate epigastralgia (1), not specified (1)) and eight in the placebo group (drowsiness (2), light headed (1), nausea (1), backache (1), dizziness (1), epigastric pain (1), not specified (1)), although not all studies assessed adverse effects. There was no difference in overall maternal adverse effects between NSAIDs and placebo at six hours post-administration (RR 1.38, 95% CI 0.71 to 2.70, 13 studies, 1388 participants (very low-quality evidence)). One small study (with two treatment arms) assessed maternal adverse effects at four hours post-administration, but there were no maternal adverse effects observed (one study, 90 participants (low-quality evidence)). Neonatal adverse effects were not assessed in any of the included studies. NSAID versus paracetamolNSAIDs versus paracetamol were also more effective for adequate pain relief at four hours
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Zohar, Joseph; Yahalom, Hila; Kozlovsky, Nitsan; Cwikel-Hamzany, Shlomit; Matar, Michael A; Kaplan, Zeev; Yehuda, Rachel; Cohen, Hagit
2011-11-01
High-dose corticosteroids have been reported to reduce symptoms of acute stress and post-traumatic stress in polytrauma patients and in animal studies. The underlying mechanism of action remains largely unclear. These issues were addressed in parallel in the clinical and preclinical studies below. In this preliminary study, 25 patients with acute stress symptoms were administered a single intravenous bolus of high-dose hydrocortisone (100-140 mg) or placebo within 6 h of a traumatic event in a prospective, randomized, double-blind, placebo-controlled pilot study. Early single high-dose hydrocortisone intervention attenuated the core symptoms of both the acute stress and of subsequent PTSD in patients. High-dose hydrocortisone treatment given in the first few hours after a traumatic experience was associated with significant favorable changes in the trajectory of exposure to trauma, as expressed by the reduced risk of the development of PTSD post-trauma. In parallel, a comparative study of morphological arborization in dentate gyrus and its modulating molecules was performed in stress-exposed animals treated with high-dose hydrocortisone. Steroid-treated stressed animals displayed significantly increased dendritic growth and spine density, with increased levels of brain-derived neurotrophic factor (BDNF) and obtunded postsynaptic density-95 (PSD-95) levels. The animal study provided insights into the potential mechanism of this intervention, as it identified relevant morphological and biochemical associations to the clinical observations. Thus, evidence from clinical and animal studies suggests that there is a "window of opportunity" in the early aftermath of trauma to help those who are vulnerable to the development of chronic PTSD. Copyright © 2011 Elsevier B.V. and ECNP. All rights reserved.
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Combination Treatment of Glioblastoma by Low-Dose Radiation and Genistein.
Atefeh, Zamanian; Vahid, Changizi; Hasan, Nedaie; Saeed, Amanpour; Mahnaz, Haddadi
2016-01-01
Gioblastoma multiforme as a chemoresistant and radioresistant malignant cell line needs to novel strategies to treatment. Low-dose hyper-radiosensitivity (LDHRS) seems to be an effective phenomenon to irradiation that can save normal brain fibroblasts. Genistein which is a soy isoflavone can be cytotoxic in some tumor cell lines. So we determined to study the effect of combining these two treatment modalities. After 30 hours incubation with Genistein in different concentrations on U87MG cell line, proliferation and clonogenicity were conducted by both clonogenic and MTT assays. A conventional 2Gy radiation dose was compared with 10 doses of 0.2Gy gamma irradiation with 3 minutes and 1 hour intervals. Finally, concurrent effect of these modalities was assessed. Based on acquired cell doubling time (30 hours), one doubling time treatment by Genistein could decrease clonogenicity. U87MG cell line exhibited HRS at low dose irradiations. 2Gy irradiation was more effective than ultra-fractionation methods in comparison with control group. All groups with 50uM concentration of Genistein showed decrease in the survival. This decrease compared with control group, in 10x0.2Gy with 3 minutes intervals plus 50uM Genistein was significant and for groups with the same dose of Genistein but along with continuous 2Gy was more significant. In one day treatment regimen, 10x0.2Gy ultra-fractionation with 3 minutes and 1 hour intervals seems to be less effective than conventional 2Gy irradiation, however adding 50uM Genistein can decrease survival more. Although 2Gy conventional dose plus 50uM Genistein was the most effective regimen. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Roberts, A. G.; Barker, S. N.; Phillips, R. N.
1981-09-01
Volume IV of the report on the 1000 hour programme consists of three appendices giving details of the enginmering/construction aspects of the plant and reports from Stal-Laval Turbin A.B. Appendix N has been entered individually. (LTN)
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Imbelloni, Luiz Eduardo; Sant’Anna, Raphael; Fornasari, Marcos; Fialho, José Carlos
2011-01-01
Background Laparoscopic cholecystectomy has the advantages of causing less postoperative pain and requiring a short hospital stay, and therefore is the treatment of choice for cholelithiasis. This study was designed to compare spinal anesthesia using hyperbaric bupivacaine given as a conventional dose by lumbar puncture or as a low-dose by thoracic puncture. Methods A total of 140 patients with symptomatic gallstone disease were randomized to undergo laparoscopic cholecystectomy with low-pressure CO2 pneumoperitoneum under spinal anesthesia using either conventional lumbar spinal anesthesia (hyperbaric bupivacaine 15 mg and fentanyl 20 mg) or low-dose thoracic spinal anesthesia (hyperbaric bupivacaine 7.5 mg and fentanyl 20 μg). Intraoperative parameters, postoperative pain, complications, recovery time, and patient satisfaction at follow-up were compared between the two treatment groups. Results All procedures were completed under spinal anesthesia, with no cases needing conversion to general anesthesia. Values for time for block to reach the T3 dermatomal level, duration of motor and sensory block, and hypotensive events were significantly lower with low-dose bupivacaine. Postoperative pain was higher for low-dose hyperbaric bupivacaine at 6 and 12 hours. All patients were discharged after 24 hours. Follow-up 1 week postoperatively showed all patients to be satisfied and to be keen advocates of spinal anesthesia. Conclusion Laparoscopic cholecystectomy can be performed successfully under spinal anesthesia. A small dose of hyperbaric bupivacaine 7.5 mg and 20 μg fentanyl provides adequate spinal anesthesia for laparoscopy and, in comparison with hyperbaric bupivacaine 15% and fentanyl 20 μg, causes markedly less hypotension. The low-dose strategy may have an advantage in ambulatory patients because of the earlier recovery of motor and sensory function and earlier discharge. PMID:22915892
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Multi-level effects of low dose rate ionizing radiation on southern toad, Anaxyrus [Bufo] terrestris
Stark, Karolina; Scott, David E.; Tsyusko, Olga; ...
2015-04-30
Despite their potential vulnerability to contaminants from exposure at multiple life stages, amphibians are one of the least studied groups of vertebrates in ecotoxicology, and research on radiation effects in amphibians is scarce. We used multiple endpoints to assess the radiosensitivity of the southern toad ( Anaxyrus [Bufo] terrestris) during its pre-terrestrial stages of development –embryonic, larval, and metamorphic. Toads were exposed, from several hours after oviposition through metamorphosis (up to 77 days later), to four low dose rates of ¹³⁷Cs at 0.13, 2.4, 21, and 222 mGy d⁻¹, resulting in total doses up to 15.8 Gy. Radiation treatments didmore » not affect hatching success of embryos, larval survival, or the length of the larval period. The individual family variation in hatching success of embryos was larger than the radiation response. In contrast, newly metamorphosed individuals from the higher dose-rate treatments had higher mass and mass/length body indices, a measure which may relate to higher post-metamorphic survival. The increased mass and index at higher dose rates may indicate that the chronic, low dose rate radiation exposures triggered secondary responses. Additionally, the increases in growth were linked to a decrease in DNA damage (as measured by the Comet Assay) in red blood cells at a dose rate of 21mGy d⁻¹ and a total dose of 1.1 Gy. In conclusion, the complex effects of low dose rates of ionizing radiation may trigger growth and cellular repair mechanisms in amphibian larvae.« less
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Organizational interventions in response to duty hour reforms.
Law, Madelyn P; Orlando, Elaina; Baker, G Ross
2014-01-01
Changes in resident duty hours in Europe and North America have had a major impact on the internal organizational dynamics of health care organizations. This paper examines, and assesses the impact of, organizational interventions that were a direct response to these duty hour reforms. The academic literature was searched through the SCOPUS database using the search terms "resident duty hours" and "European Working Time Directive," together with terms related to organizational factors. The search was limited to English-language literature published between January 2003 and January 2012. Studies were included if they reported an organizational intervention and measured an organizational outcome. Twenty-five articles were included from the United States (n=18), the United Kingdom (n=5), Hong Kong (n=1), and Australia (n=1). They all described single-site projects; the majority used post-intervention surveys (n=15) and audit techniques (n=4). The studies assessed organizational measures, including relationships among staff, work satisfaction, continuity of care, workflow, compliance, workload, and cost. Interventions included using new technologies to improve handovers and communications, changing staff mixes, and introducing new shift structures, all of which had varying effects on the organizational measures listed previously. Little research has assessed the organizational impact of duty hour reforms; however, the literature reviewed demonstrates that many organizations are using new technologies, new personnel, and revised and innovative shift structures to compensate for reduced resident coverage and to decrease the risk of limited continuity of care. Future research in this area should focus on both micro (e.g., use of technology, shift changes, staff mix) and macro (e.g., culture, leadership support) organizational aspects to aid in our understanding of how best to respond to these duty hour reforms.
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Single dose parenteral hyposensitization to poison ivy urushiol in guinea pigs.
Walker, L A; Watson, E S; elSohly, M A
1995-08-01
Studies were carried out in guinea pigs to evaluate the potential for single dose hyposensitization to poison ivy urushiol dermatitis. Sensitization was induced by topical application of 1 mg of poison ivy urushiol to the back of the neck. In the first series of studies, three different analogs of poison ivy urushiol were studied: 1) a mixture of pentadecyl and heptadecyl catechols (PDC/HDC), the saturated side chain analog of the natural urushiol mixture; 2) a mixture of the diacetate esters of PDC and HDC (PDC/HDC Ac), the esterified form of the saturated sidechain analogs; 3) 2-n-pentadecyl hydroquinone diacetate (HQ Ac). Each of these compounds was administered as 5 mg of the free catechol i.m. each week for three weeks. A vehicle group received only corn oil injections. Reactivity to poison ivy urushiol (PIU) challenge was evaluated in skin tests at 1 and 5 weeks post-treatment. PDC/HDC Ac induced a marked reduction in both the incidence and the severity of lesions induced by PIU at both 1 and at 5 weeks post-treatment. Other analogs were ineffective at 5 weeks post-treatment, and were less effective than PDC/HDC Ac at 1 week post-treatment. In a second series of experiments, the efficacy of PDC/HDC Ac was evaluated in both single and multiple dose regiments. One treatment group received 5 mg of PDC/HDC Ac intramuscularly each week for 4 weeks, while another treatment group received a single dose of 20 mg PDC/HDC Ac i.m. Corresponding vehicle control groups were also included. At 1 week post-treatment in the single dose group, the PDC/HDC Ac was only modestly effective, with some reduction of severity of lesions at the higher challenge doses of PIU. However, at 4 and 7 weeks post-treatment, both the incidence and the severity of the lesions at all challenge doses were reduced. In the multiple dose group, the incidence and severity of lesions are reduced at 1 week and 4 weeks post-treatment (4 weeks and 7 weeks after the initial dose) but were not significantly
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A Trial of Extending Hemodialysis Hours and Quality of Life.
Jardine, Meg J; Zuo, Li; Gray, Nicholas A; de Zoysa, Janak R; Chan, Christopher T; Gallagher, Martin P; Monaghan, Helen; Grieve, Stuart M; Puranik, Rajesh; Lin, Hongli; Eris, Josette M; Zhang, Ling; Xu, Jinsheng; Howard, Kirsten; Lo, Serigne; Cass, Alan; Perkovic, Vlado
2017-06-01
The relationship between increased hemodialysis hours and patient outcomes remains unclear. We randomized (1:1) 200 adult recipients of standard maintenance hemodialysis from in-center and home-based hemodialysis programs to extended weekly (≥24 hours) or standard (target 12-15 hours, maximum 18 hours) hemodialysis hours for 12 months. The primary outcome was change in quality of life from baseline assessed by the EuroQol 5 dimension instrument (3 level) (EQ-5D). Secondary outcomes included medication usage, clinical laboratory values, vascular access events, and change in left ventricular mass index. At 12 months, median weekly hemodialysis hours were 24.0 (interquartile range, 23.6-24.0) and 12.0 (interquartile range, 12.0-16.0) in the extended and standard groups, respectively. Change in EQ-5D score at study end did not differ between groups (mean difference, 0.04 [95% confidence interval, -0.03 to 0.11]; P =0.29). Extended hours were associated with lower phosphate and potassium levels and higher hemoglobin levels. Blood pressure (BP) did not differ between groups at study end. Extended hours were associated with fewer BP-lowering agents and phosphate-binding medications, but were not associated with erythropoietin dosing. In a substudy with 95 patients, we detected no difference between groups in left ventricular mass index (mean difference, -6.0 [95% confidence interval, -14.8 to 2.7] g/m 2 ; P =0.18). Five deaths occurred in the extended group and two in the standard group ( P =0.44); two participants in each group withdrew consent. Similar numbers of patients experienced vascular access events in the two groups. Thus, extending weekly hemodialysis hours did not alter overall EQ-5D quality of life score, but was associated with improvement in some laboratory parameters and reductions in medication burden. (Clinicaltrials.gov identifier: NCT00649298). Copyright © 2017 by the American Society of Nephrology.
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Babu, Ranjith; Thomas, Steven; Hazzard, Matthew A.; Friedman, Allan H.; Sampson, John H.; Adamson, Cory; Zomorodi, Ali R.; Haglund, Michael M.; Patil, Chirag G.; Boakye, Maxwell; Lad, Shivanand P.
2015-01-01
Object On July 1, 2003, the Accreditation Council for Graduate Medical Education (ACGME) implemented duty-hour restrictions for resident physicians due to concerns for patient and resident safety. Though duty-hour restrictions have increased resident quality of life, studies have shown mixed results with respect to patient outcomes. In this study, the authors have evaluated the effect of duty-hour restrictions on morbidity, mortality, length of stay, and charges in patients who underwent brain tumor and cerebrovascular procedures. Methods The Nationwide Inpatient Sample was used to evaluate the effect of duty-hour restrictions on complications, mortality, length of stay, and charges by comparing the pre-reform (2000–2002) and post-reform (2005–2008) periods. Outcomes were compared between nonteaching and teaching hospitals using a difference-in-differences (DID) method. Results A total of 90,648 patients were included in the analysis. The overall complication rate was 11.7%, with the rates not significantly differing between the pre –and post–duty hour eras (p = 0.26). Examination of hospital teaching status revealed that complication rates decreased in nonteaching hospitals (12.1% vs 10.4%, p = 0.0004) and remained stable in teaching institutions (11.8% vs 11.9%, p = 0.73) in the post-reform era. Multivariate analysis demonstrated a significantly higher complication risk in teaching institutions (OR 1.33 [95% CI 1.11–1.59], p = 0.0022), with no significant change in nonteaching hospitals (OR 1.11 [95% CI 0.91–1.37], p = 0.31). A DID analysis to compare the magnitude in change between teaching and nonteaching institutions revealed that teaching hospitals had a significantly greater increase in complications during the post-reform era than nonteaching hospitals (p = 0.040). The overall mortality rate was 3.0%, with a significant decrease occurring in the post-reform era in both nonteaching (5.0% vs 3.2%, p < 0.0001) and teaching (3.2% vs 2.3%, p < 0
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Nawroth, Frank; Tandler-Schneider, Andreas; Bilger, Wilma
2015-01-01
This prospective, noninterventional, post-marketing surveillance study evaluated doses of recombinant human follicle-stimulating hormone (r-hFSH) using the redesigned follitropin alfa pen in women who were anovulatory or oligomenorrheic and undergoing ovulation induction (OI) alone or OI with intrauterine insemination. The primary endpoint was the proportion of patients who achieved monofollicular or bifollicular development (defined as one or two follicles ≥15 mm). Secondary endpoints included characteristics of ovulation stimulation treatment, such as mean total and mean daily r-hFSH doses. Data were analyzed for 3,193 patients from 30 German fertility centers. The proportion of patients with monofollicular or bifollicular development was 71.1% (n=2,270 of a total of 3,193 patients; intent-to-treat population). The mean±standard deviation total and daily doses of r-hFSH were 696.9±542.5 IU and 61.7±29.4 IU, respectively. The three doses prescribed most frequently were: 37.5 IU (n=703 from N=3,189; 22.0%), 50.0 IU (n=1,056 from N=3,189; 33.1%), and 75.0 IU (n=738 from N=3,189; 23.1%) on the first day of stimulation; and 37.5 IU (n=465 from N=3,189; 14.6%), 50.0 IU (n=922 from N=3,189; 28.9%), and 75.0 IU (n=895 from N=3,189; 28.1%) on the last day of stimulation. This noninterventional, post-marketing surveillance study found that monofollicular or bifollicular development was achieved in 71% of patients studied and the small dose increment (12.5 IU) of the redesigned follitropin alfa pen allowed individualized treatment of women undergoing OI.
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Cui, Yimin; Song, Yan; Wang, Jessie; Yu, Zhigang; Schuster, Alan; Barrett, Yu Chen; Frost, Charles
2013-01-01
Background The pharmacokinetics (PK), pharmacodynamics (PD), and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study. Subjects and methods Eighteen subjects 18–45 years of age were randomly assigned (2:1 ratio) to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4–9). The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations. Results PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported. Conclusion Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race. PMID:24353445
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Basher, Ariful; Maruf, Shomik; Nath, Proggananda; Hasnain, Md Golam; Mukit, Muhammod Abdul; Anuwarul, Azim; Aktar, Fatima; Nath, Rupen; Hossain, Afm Akhtar; Milton, Abul Hasnat; Mondal, Dinesh; Mohammad Sumsuzzaman, Abul Khair; Rahman, Ridwanur; Faiz, M A
2017-10-01
Post kala-azar dermal leishmaniasis (PKDL) is a skin manifestation which usually appears after visceral leishmaniasis. It is now proved that PKDL patients serve as a reservoir for anthropometric leishmanial transmission. Hence, to achieve the kala-azar elimination target set by the World Health Organization in the Indian Subcontinent, PKDL cases should be given priority. The goal of treatment for PKDL should be early reepithelizlization and rapid cure, but unfortunately this has been difficult to achieve, especially for patients with severe lesions. Therefore, we describe here four cases of PKDL who had widespread nodular and macular lesions and were treated with two cycles of LAmB doses with 20 mg/kg body weight divided into four equal doses (each dose contains 5 mg/kg) administered every alternate day. This treatment schedule achieved 100% treatment success with the minimal safety concern.
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Can zero-hour cortical biopsy predict early graft outcomes after living donor renal transplantation?
Rathore, Ranjeet Singh; Mehta, Nisarg; Mehta, Sony Bhaskar; Babu, Manas; Bansal, Devesh; Pillai, Biju S; Sam, Mohan P; Krishnamoorthy, Hariharan
2017-11-01
The aim of this study was to identify relevance of subclinical pathological findings in the kidneys of living donors and correlate these with early graft renal function. This was a prospective study on 84 living donor kidney transplant recipients over a period of two years. In all the donors, cortical wedge biopsy was taken and sent for assessment of glomerular, mesangial, and tubule status. The graft function of patients with normal histology was compared with those of abnormal histological findings at one, three, and six months, and one year post-surgery. Most abnormal histological findings were of mild degree. Glomerulosclerosis (GS, 25%), interstitial fibrosis (IF, 13%), acute tubular necrosis (ATN 5%), and focal tubal atrophy (FTA, 5%) were the commonly observed pathological findings in zero-hour biopsies. Only those donors who had histological changes of IF and ATN showed progressive deterioration of renal function at one month, three months, six months, and one year post-transplantation. In donors with other histological changes, no significant effect on graft function was observed. Zero-hour cortical biopsy gave us an idea of the general status of the donor kidney and presence or absence of subclinical pathological lesions. A mild degree of subclinical and pathological findings on zero-hour biopsy did not affect early graft renal function in living donor kidney transplantation. Zero-hour cortical biopsy could also help in discriminating donor-derived lesions from de novo alterations in the kidney that could happen subsequently.
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Smith, P A; Wright, B M; Mackey, R W; Milsop, H W; Yates, S C
1998-01-01
The study examined the impact of change, from slowly rotating continuous 8-hour shifts to more rapidly rotating continuous 8-hour and 12-hour shifts, on the health and quality of life of shift workers. Self-report survey data were collected from 72 shift workers at 3 sewage treatment plants before and several months after roster change. After the change 1 plant first worked a rapidly rotating, 8-hour shift roster and then worked a 12-hour shift roster, and the other 2 plants worked continuous 12-hour shift rosters. After the change the shift workers at each plant reported increased satisfaction with roster design, a decrease in physical and psychological circadian malaise associated with shift work, improved day sleep quality, less tiredness, and improvements in the quality of home, social and work life. A between-plant comparison of the rapidly rotating 8-hour and 12-hour shift rosters showed greater improvements had been obtained with the 12-hour shift roster, and no significant differences in tiredness or sleep quality between the redesigned 8- and 12-hour shift rosters. However, a within-plant matched-pairs comparison at the 1st plant of the rapidly rotating 8-hour shift roster and the 12-hour shift roster showed no significant differences. The results show that the prior level of support for change may best explain the impact of roster redesign on individual well-being. They lend further support to shift worker participation in roster design.
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Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.
2014-01-01
Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (<120 mg furosemide equivalent, n=131) outpatient diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486
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A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.
Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi
2015-06-25
Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.
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A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles
Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F.; Hamaoka, Takafumi
2015-01-01
Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously. PMID:26109079
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Huang, Lin; Wickramasekara, Samanthi I; Akinyeke, Tunde; Stewart, Blair S; Jiang, Yuan; Raber, Jacob; Maier, Claudia S
2016-05-17
Recent advances in the field of biodosimetry have shown that the response of biological systems to ionizing radiation is complex and depends on the type and dose of radiation, the tissue(s) exposed, and the time lapsed after exposure. The biological effects of low dose radiation on learning and memory are not well understood. An ion mobility-enhanced data-independent acquisition (MS(E)) approach in conjunction with the ISOQuant software tool was utilized for label-free quantification of hippocampal proteins with the goal of determining protein alteration associated with low-dose whole body ionizing radiation (X-rays, 1Gy) of 5.5-month-old male C57BL/6J mice post contextual fear conditioning training. Global proteome analysis revealed deregulation of 73 proteins (out of 399 proteins). Deregulated proteins indicated adverse effects of irradiation on myelination and perturbation of energy metabolism pathways involving a shift from the TCA cycle to glutamate oxidation. Our findings also indicate that proteins associated with synaptic activity, including vesicle recycling and neurotransmission, were altered in the irradiated mice. The elevated LTP and decreased LTD suggest improved synaptic transmission and enhanced efficiency of neurotransmitter release which would be consistent with the observed comparable contextual fear memory performance of the mice following post-training whole body or sham-irradiation. This study is significant because the biological consequences of low dose radiation on learning and memory are complex and not yet well understood. We conducted a IMS-enhanced MS(E)-based label-free quantitative proteomic analysis of hippocampal tissue with the goal of determining protein alteration associated with low-dose whole body ionizing radiation (X-ray, 1Gy) of 5.5-month-old male C57BL/6J mice post contextual fear conditioning training. The IMS-enhanced MS(E) approach in conjunction with ISOQuant software was robust and accurate with low median CV values of
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Carlson, Nicole S.; Corwin, Elizabeth J.; Lowe, Nancy K.
2017-01-01
Background Synthetic oxytocin, the primary tool for labor augmentation, is less effective among obese women, leading to more unplanned cesarean deliveries for slow labor progress. It is not known if obese women require higher doses of oxytocin due to maternal, fetal, or labor factors related to maternal obesity. Objectives This study had two main objectives: 1) Examine the influence of maternal body mass index (BMI) on hourly doses of oxytocin from augmentation initiation until vaginal delivery in obese women; and 2) Examine the influence of other maternal, fetal, and labor factors on hourly doses of oxytocin in obese women. Study design Longitudinal study of a cohort (N = 136) of healthy, nulliparous, spontaneously laboring obese women (BMI ≥ 30 kg/m2) who received oxytocin augmentation and achieved vaginal delivery. We performed iterative multilevel analyses to examine the influence of maternal BMI and other factors on hourly oxytocin doses. Results Maternal BMI explained 16.56% (95% CI [13.7-20.04], p < 0.001) of the variance in hourly oxytocin doses received in a multilevel model controlling for influence of maternal, fetal, and labor characteristics. Maternal age, gestational age, status of amniotic membranes at hospital admission, and admission cervical dilation examination were not significant; however, neonatal birthweight and cervical dilation at oxytocin initiation were significant predictors of hourly oxytocin dose in these women (p < 0.001). Conclusions Even when parturition preparation has progressed adequately for spontaneous labor initiation, there still may be some obesity-related blunting of myometrial contractility and response to oxytocin used for augmentation. PMID:28347147
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Carlson, Nicole S; Corwin, Elizabeth J; Lowe, Nancy K
2017-07-01
Synthetic oxytocin, the primary tool for labor augmentation, is less effective among obese women, leading to more unplanned cesarean deliveries for slow labor progress. It is not known if obese women require higher doses of oxytocin due to maternal, fetal, or labor factors related to maternal obesity. This study had two main objectives: (1) examine the influence of maternal body mass index (BMI) on hourly doses of oxytocin from augmentation initiation until vaginal delivery in obese women; and (2) examine the influence of other maternal, fetal, and labor factors on hourly doses of oxytocin in obese women. Longitudinal study of a cohort ( N = 136) of healthy, nulliparous, spontaneously laboring obese women (BMI ≥ 30 kg/m 2 ) who received oxytocin augmentation and achieved vaginal delivery. We performed iterative multilevel analyses to examine the influence of maternal BMI and other factors on hourly oxytocin doses. Maternal BMI explained 16.56% (95% confidence interval [CI] = [13.7, 20.04], p < .001) of the variance in hourly oxytocin doses received in a multilevel model controlling for influence of maternal, fetal, and labor characteristics. Maternal age, gestational age, status of amniotic membranes at hospital admission, and admission cervical dilation examination were not significant; however, neonatal birthweight and cervical dilation at oxytocin initiation were significant predictors of hourly oxytocin dose in these women ( p < .001). Even when parturition preparation has progressed adequately for spontaneous labor initiation, there still may be some obesity-related blunting of myometrial contractility and response to oxytocin used for augmentation.
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Sankar, A; Ayyangar, Komanduri M; Nehru, R Mothilal; Kurup, P G Gopalakrishna; Murali, V; Enke, Charles A; Velmurugan, J
2006-01-01
The quantitative dose validation of intensity-modulated radiation therapy (IMRT) plans require 2-dimensional (2D) high-resolution dosimetry systems with uniform response over its sensitive region. The present work deals with clinical use of commercially available self-developing Radio Chromic Film, Gafchromic EBT film, for IMRT dose verification. Dose response curves were generated for the films using a VXR-16 film scanner. The results obtained with EBT films were compared with the results of Kodak extended dose range 2 (EDR2) films. The EBT film had a linear response between the dose range of 0 to 600 cGy. The dose-related characteristics of the EBT film, such as post irradiation color growth with time, film uniformity, and effect of scanning orientation, were studied. There was up to 8.6% increase in the color density between 2 to 40 hours after irradiation. There was a considerable variation, up to 8.5%, in the film uniformity over its sensitive region. The quantitative differences between calculated and measured dose distributions were analyzed using DTA and Gamma index with the tolerance of 3% dose difference and 3-mm distance agreement. The EDR2 films showed consistent results with the calculated dose distributions, whereas the results obtained using EBT were inconsistent. The variation in the film uniformity limits the use of EBT film for conventional large-field IMRT verification. For IMRT of smaller field sizes (4.5 x 4.5 cm), the results obtained with EBT were comparable with results of EDR2 films.
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A Case Report on Dyskinesia Following Rivastigmine Patch 13.3 mg/24 hours for Alzheimer's Disease
Diaz, Maria Cristina B.; Rosales, Raymond L.
2015-01-01
Abstract Current reports on movement disorder adverse effects of acetylcholinesterase inhibitors only include extrapyramidal symptoms and myoclonus. Here is a case of an 81-year-old female Filipino with dementia who presented with first-onset generalized choreiform movements. The etiology of the clinical finding of dyskinesia was investigated through laboratories, neuroimaging, and electroencephalogram, all of which yielded negative results. Review of her medications included the rivastigmine (Exelon) patch, which had just been increased to 13.3 mg/24-hour-dose 3 months prior. With all other possible causes excluded, a trial discontinuation of rivastigmine, showed decreased frequency of the dyskinesia 48 hours after, with complete resolution after 6 days, and no recurrence since then. This case thus presents a probable association or causality between the choreiform movement and rivastigmine at 13.3 mg/24-hour-dose patch because of clear temporal proximity, lack of alternative explanations, and a reversal of the dyskinesia upon medicament discontinuation. PMID:26313774
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Dose estimates for the solid waste performance assessment
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rittman, P.D.
1994-08-30
The Solid Waste Performance Assessment calculations by PNL in 1990 were redone to incorporate changes in methods and parameters since then. The ten scenarios found in their report were reduced to three, the Post-Drilling Resident, the Post-Excavation Resident, and an All Pathways Irrigator. In addition, estimates of population dose to people along the Columbia River are also included. The attached report describes the methods and parameters used in the calculations, and derives dose factors for each scenario. In addition, waste concentrations, ground water concentrations, and river water concentrations needed to reach the performance objectives of 100 mrem/yr and 500 person-rem/yrmore » are computed. Internal dose factors from DOE-0071 were applied when computing internal dose. External dose rate factors came from the GENII Version 1.485 software package. Dose calculations were carried out on a spreadsheet. The calculations are described in detail in the report for 63 nuclides, including 5 not presently in the GENII libraries. The spreadsheet calculations were checked by comparison with GENII, as described in Appendix D.« less
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Nawroth, Frank; Tandler-Schneider, Andreas; Bilger, Wilma
2015-01-01
This prospective, noninterventional, post-marketing surveillance study evaluated doses of recombinant human follicle-stimulating hormone (r-hFSH) using the redesigned follitropin alfa pen in women who were anovulatory or oligomenorrheic and undergoing ovulation induction (OI) alone or OI with intrauterine insemination. The primary endpoint was the proportion of patients who achieved monofollicular or bifollicular development (defined as one or two follicles ≥15 mm). Secondary endpoints included characteristics of ovulation stimulation treatment, such as mean total and mean daily r-hFSH doses. Data were analyzed for 3,193 patients from 30 German fertility centers. The proportion of patients with monofollicular or bifollicular development was 71.1% (n=2,270 of a total of 3,193 patients; intent-to-treat population). The mean±standard deviation total and daily doses of r-hFSH were 696.9±542.5 IU and 61.7±29.4 IU, respectively. The three doses prescribed most frequently were: 37.5 IU (n=703 from N=3,189; 22.0%), 50.0 IU (n=1,056 from N=3,189; 33.1%), and 75.0 IU (n=738 from N=3,189; 23.1%) on the first day of stimulation; and 37.5 IU (n=465 from N=3,189; 14.6%), 50.0 IU (n=922 from N=3,189; 28.9%), and 75.0 IU (n=895 from N=3,189; 28.1%) on the last day of stimulation. This noninterventional, post-marketing surveillance study found that monofollicular or bifollicular development was achieved in 71% of patients studied and the small dose increment (12.5 IU) of the redesigned follitropin alfa pen allowed individualized treatment of women undergoing OI. PMID:25926755
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Glue, Paul; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, Cheung-Tak; Friedhoff, Lawrence
2015-02-01
Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid-dependent subjects. The objectives of this Phase I study were to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of noribogaine. In this ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, 4 cohorts (n = 9) received oral doses of 3, 10, 30, or 60 mg or matching placebo, with intensive safety and pharmacokinetic assessments out to 216 hours, along with pharmacodynamic assessments sensitive to the effects of mu-opioid agonists. Noribogaine was rapidly absorbed, with peak concentrations occurring 2-3 hours after oral dosing, and showed dose-linear increases of area under the concentration-time curve (AUC) and Cmax between 3 and 60 mg. The drug was slowly eliminated, with mean half-life estimates of 28-49 hours across dose groups. Apparent volume of distribution was high (mean 1417-3086 L across dose groups). No safety or tolerability issues were identified in any cohort. No mu-opioid agonist pharmacodynamic effects were noted in pupillometry or cold-pressor testing. Single oral doses of noribogaine 3-60 mg were safe and well tolerated in healthy volunteers. © 2014, The American College of Clinical Pharmacology.
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Brooks, Christine; Vickers, Amy Manning; Aryal, Subhash
2013-04-01
The objective of this study was to compare the differences in lipid loss from 24 samples of banked donor human milk (DHM) among 3 feeding methods: DHM given by syringe pump over 1 hour, 2 hours, and by bolus/gravity gavage. Comparative, descriptive. There were no human subjects. Twenty-four samples of 8 oz of DHM were divided into four 60-mL aliquots. Timed feedings were given by Medfusion 2001 syringe pumps with syringes connected to narrow-lumened extension sets designed for enteral feedings and connected to standard silastic enteral feeding tubes. Gravity feedings were given using the identical syringes connected to the same silastic feeding tubes. All aliquots were analyzed with the York Dairy Analyzer. Univariate repeated-measures analyses of variance were used for the omnibus testing for overall differences between the feeding methods. Lipid content expressed as grams per deciliter at the end of each feeding method was compared with the prefed control samples using the Dunnett's test. The Tukey correction was used for other pairwise multiple comparisons. The univariate repeated-measures analysis of variance conducted to test for overall differences between feeding methods showed a significant difference between the methods (F = 58.57, df = 3, 69, P < .0001). Post hoc analysis using the Dunnett's approach revealed that there was a significant difference in fat content between the control sample and the 1-hour and 2-hours feeding methods (P < .0001), but we did not find any significant difference in fat content between the control and the gravity feeding methods (P = .3296). Pairwise comparison using the Tukey correction revealed a significant difference between both gravity and 1-hour feeding methods (P < .0001), and gravity and 2-hour feeding method (P < .0001). There was no significant difference in lipid content between the 1-hour and 2-hour feeding methods (P = .2729). Unlike gravity feedings, the timed feedings resulted in a statistically significant loss
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Comparison of post operative morbidity between laparoscopic and open appendectomy in children.
Saha, N; Saha, D K; Rahman, M A; Islam, M K; Aziz, M A
2010-07-01
This prospective comparative study was conducted in the department of Pediatric Surgery, Dhaka Shishu (children) Hospital during the period of June 2007 to September 2008 with the children of <12 years, diagnosed as acute Appendicitis. Patient selection was done by simple random technique by means of lottery. For open Appendectomy (OA) conventional method & for Laparoscopic Appendectomy (LA) 3 trocher technique was applied. Data was analyzed with the help of SPSS version 10. In this study 60 cases with acute Appendicitis including both gender were studied by two groups, group-A include 30 cases for laparoscopic and group-B include 30 cases for open appendectomy. Postoperative pain was assessed in both groups by using FLACC scale and compared at 1st 6-hours, 24 hours, 72 hours, 96 hours & at day 7. At 1st 6-hours, most of the children 24(80%) of group A had moderate pain whereas 17(56.7%) children of group B had severe pain (p<0.001). At 24 hours most of the patient 17(56.7%) of group A had mild pain compared to 27 (90%) patients of group B had moderate pain (p<0.0001). At 48 hours in group A most of the children 23(76.7%) had mild pain compared to moderate pain in 18(60%) children of group B (p<0.0001). Subsequently at 72 hours and at 96 hours most of the patients of LA group were free of pain compared to OA group. At final follow-up on day 7, 29(96.7%) children of group A had no pain compared to 26(86.7%) of group B. Regarding analgesics requirement both qualitative & quantitative requirements of analgesics were less in LA group than OA group. About post operative wound infection in group A only 1(3.3%) case had developed post operative wound infection whereas in group B 7(23.3 %) cases had. The mean (+/-SD) of post operative length of hospital stay was 52.00+/-11.62 (range 48-96) hours for group A and 76.00+/-12.74 (range 48-96) hours for group B children (p<0.001). Laparoscopic Appendectomy is more effective, preferable & superior procedure than that of open
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One-Hour PTH after Thyroidectomy Predicts Symptomatic Hypocalcemia
Nocon, Cheryl; Nagar, Sapna; Kaplan, Edwin L.; Angelos, Peter; Grogan, Raymon H.
2015-01-01
Background A major morbidity following total thyroidectomy is hypocalcemia. While many clinical factors and laboratory studies have been correlated with both biochemical and symptomatic hypocalcemia, the ideal use and timing of these tests the remains unclear. We hypothesize one-hour (PACU) PTH will identify patients at risk for symptomatic hypocalcemia. Methods This prospective study evaluated 196 patients undergoing total thyroidectomy. Serum calcium and PTH levels were measured one hour after surgery and on postoperative day 1 (POD1). Performance of a central compartment lymph node dissection, parathyroid autotransplantation, indication for procedure, pathology, and presence of parathyroid tissue in the pathology specimen were recorded. Results Of 196 patients, 9 (4.6%) developed symptomatic hypocalcemia. 34 (17.3%) had a 1-hour PACU PTH ≤ 10 pg/dL while 31 (15.8%) had a POD1 PTH of ≤ 10. Five (56%) of the nine symptomatic patients underwent central compartment lymph node dissection, 4 (44%) had parathyroid autotransplantation and 4 (44%) had a PACU PTH ≤10. PACU and POD1 PTH levels were correlated (R2=0.682). Multivariate regression identified central compartment dissection, autotransplantation, and PACU or POD1 PTH correlated with symptomatic hypocalcemia. PACU PTH, POD1 PTH, PACU Ca, malignant final pathology, and Age ≤ 45 years correlated with biochemical hypocalcemia. Conclusion 1-hour postoperative PACU PTH is equivalent to POD1 PTH in predicting the development of symptomatic hypocalcemia. Biochemical hypocalcemia was not predictive of symptoms in the immediate post-operative period. Lymph node dissection and parathyroid autotransplantation correlated with symptomatic hypocalcemia and improve the sensitivity of biochemical screening alone. PMID:27020834
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Jonker, Emile F F; Visser, Leonardus G
2017-09-01
The current standard 3-dose intramuscular rabies PrEP schedule suffers from a number of disadvantages that severely limit accessibility and availability. The cost of is often prohibitive, it requires 3 visits to the clinic, and there are regular vaccine shortages. Volunteers ( N = 30) were randomly assigned to 4 study arms: 1 standard dose intramuscular (IM) dose of PVRV (purified Vero cell rabies vaccine, Verorab), and 1/5th, 2/5th or 3/5th- fractional intradermal (ID) dose of PVRV in a single visit. All subjects received a simulated rabies post-exposure prophylaxis (D0, D3) 1 year later. Rabies virus neutralizing antibodies (RVNA) were determined by virus neutralization microtest (FAVN) on D0, D7, D28, Y1 and Y1 + D7. 28 out of 30 subjects (93%) seroconverted 1 month after primary vaccination; 1 subject in the 1-dose IM arm and 1 in the 1/5th-fractional dose ID arm did not. After 1 year, 22 out of 30 subjects (73%) no longer had RVNA above 0.5 IU/ml, with no discernible difference between study groups. After 1 year, all 30 subjects mounted a booster response within 7 days after simulated PEP, with the highest titers found in the single dose IM group ( P < 0.03). This dose finding study demonstrates that priming with a single dose of rabies vaccine was sufficient to induce an adequate anamnestic antibody response to rabies PEP in all subjects 1 year later, even in those in whom the RVNA threshold of 0.5 IU/ml was not reached after priming. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
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Iskra-Golec, I; Fafrowicz, M; Marek, T; Costa, G; Folkard, S; Foret, J; Kundi, M; Smith, L
2001-12-01
Experiments consisting of baseline, bright light and physical exercise studies were carried out to compare the effect of a 9-hour delay in sleep-wakefulness timing, and the effects of bright light and physical exercise interventions on 24-hour patterns of performance, mood and body temperature were examined. Each study comprised a 24-hour constant routine at the beginning followed by 3 night shifts and 24-hour constant routine at the end. Performance on tasks differing in cognitive load, mood and body temperature was measured during each constant routine and the interventions were applied during the night shifts. The 24-hour pattern of alertness and performance on the tasks with low cognitive load in post-treatment conditions followed the change in sleep-wakefulness timing while more cognitively loaded tasks tended to show a reverse trend when compared to pre-treatment conditions. There was a phase delay around 4 hours in circadian rhythms of body temperature in post-treatment conditions.
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The effect of different water immersion temperatures on post-exercise parasympathetic reactivation.
de Oliveira Ottone, Vinícius; de Castro Magalhães, Flávio; de Paula, Fabrício; Avelar, Núbia Carelli Pereira; Aguiar, Paula Fernandes; da Matta Sampaio, Pâmela Fiche; Duarte, Tamiris Campos; Costa, Karine Beatriz; Araújo, Tatiane Líliam; Coimbra, Cândido Celso; Nakamura, Fábio Yuzo; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel
2014-01-01
We evaluated the effect of different water immersion (WI) temperatures on post-exercise cardiac parasympathetic reactivation. Eight young, physically active men participated in four experimental conditions composed of resting (REST), exercise session (resistance and endurance exercises), post-exercise recovery strategies, including 15 min of WI at 15°C (CWI), 28°C (TWI), 38°C (HWI) or control (CTRL, seated at room temperature), followed by passive resting. The following indices were assessed before and during WI, 30 min post-WI and 4 hours post-exercise: mean R-R (mR-R), the natural logarithm (ln) of the square root of the mean of the sum of the squares of differences between adjacent normal R-R (ln rMSSD) and the ln of instantaneous beat-to-beat variability (ln SD1). The results showed that during WI mRR was reduced for CTRL, TWI and HWI versus REST, and ln rMSSD and ln SD1 were reduced for TWI and HWI versus REST. During post-WI, mRR, ln rMSSD and ln SD1 were reduced for HWI versus REST, and mRR values for CWI were higher versus CTRL. Four hours post exercise, mRR was reduced for HWI versus REST, although no difference was observed among conditions. We conclude that CWI accelerates, while HWI blunts post-exercise parasympathetic reactivation, but these recovery strategies are short-lasting and not evident 4 hours after the exercise session.
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The Effect of Different Water Immersion Temperatures on Post-Exercise Parasympathetic Reactivation
de Oliveira Ottone, Vinícius; de Castro Magalhães, Flávio; de Paula, Fabrício; Avelar, Núbia Carelli Pereira; Aguiar, Paula Fernandes; da Matta Sampaio, Pâmela Fiche; Duarte, Tamiris Campos; Costa, Karine Beatriz; Araújo, Tatiane Líliam; Coimbra, Cândido Celso; Nakamura, Fábio Yuzo; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel
2014-01-01
Purpose We evaluated the effect of different water immersion (WI) temperatures on post-exercise cardiac parasympathetic reactivation. Methods Eight young, physically active men participated in four experimental conditions composed of resting (REST), exercise session (resistance and endurance exercises), post-exercise recovery strategies, including 15 min of WI at 15°C (CWI), 28°C (TWI), 38°C (HWI) or control (CTRL, seated at room temperature), followed by passive resting. The following indices were assessed before and during WI, 30 min post-WI and 4 hours post-exercise: mean R-R (mR-R), the natural logarithm (ln) of the square root of the mean of the sum of the squares of differences between adjacent normal R–R (ln rMSSD) and the ln of instantaneous beat-to-beat variability (ln SD1). Results The results showed that during WI mRR was reduced for CTRL, TWI and HWI versus REST, and ln rMSSD and ln SD1 were reduced for TWI and HWI versus REST. During post-WI, mRR, ln rMSSD and ln SD1 were reduced for HWI versus REST, and mRR values for CWI were higher versus CTRL. Four hours post exercise, mRR was reduced for HWI versus REST, although no difference was observed among conditions. Conclusions We conclude that CWI accelerates, while HWI blunts post-exercise parasympathetic reactivation, but these recovery strategies are short-lasting and not evident 4 hours after the exercise session. PMID:25437181
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O'Rand, Michael G; Hamil, Katherine G; Adevai, Tiffany; Zelinski, Mary
2018-01-01
Men have two practical choices for contraception; the condom which has a high typical use failure rate or vasectomy. New male hormonal and non-hormonal contraceptives are under development that target either the production of sperm (spermatogenesis) or the delivery of sperm. One particular target is the sperm protein EPPIN, which is present on the surface of human spermatozoa. EP055 is a small organic compound that targets EPPIN on the surface of sperm and inhibits motility. EP055 was tested in cynomolgus (Macaca fascicularis) males to determine its plasma half-life after intravenous (i.v.) infusion of a single dose and for binding to its target tissues. Our initial study demonstrated a plasma half-life for EP055 of 10.6 minutes. In a second study examination of macaque testis, epididymis, and plasma after i.v. infusion of a single dose of compound EP055 (63.25 mg/kg) demonstrated that EP055 was detected in testis and epididymis two hours and six hours post-infusion. We initiated a trial in rhesus (Macaca mulatta) males to assess the availability of EP055 in semen and its effect on sperm motility as a measure of the drug's efficacy. Four macaques were infused with a low dose (75-80 mg/kg) followed by a recovery period and a subsequent high dose (125-130 mg/kg) of EP055. After high dose administration, sperm motility fell to approximately 20% of pretreatment levels within 6 hours post-infusion; no normal motility was observed at 30 hours post-infusion. Recovery of sperm motility was obvious by 78 hours post-infusion; with full recovery in all animals by 18 days post-infusion. EP055 has the potential to be a male contraceptive that would provide a reversible, short-lived pharmacological alternative.
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Urinary Phenylacetylglutamine as Dosing Biomarker for Patients with Urea Cycle Disorders
Mokhtarani, M; Diaz, GA; Rhead, W; Lichter-Konecki, U; Bartley, J; Feigenbaum, A; Longo, N; Berquist, W; Berry, SA; Gallagher, R; Bartholomew, D; Harding, CO; Korson, MS; McCandless, SE; Smith, W; Vockley, J; Bart, S; Kronn, D; Zori, R; Cederbaum, S; Dorrani, N; Merritt, JL; Sreenath-Nagamani, Sandesh; Summar, M; LeMons, C; Dickinson, K; Coakley, DF; Moors, TL; Lee, B; Scharschmidt, BF
2013-01-01
We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). Study Design These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6–17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. Results Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 1.5–31.8 g/day and of sodium phenylbutyrate ranging from 1.3–31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% –5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% -to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r=0.730, p<0.001) or as total 24-hour excretion (r=0.791 p<0.001), followed by plasma phenylacetylglutamine AUC24-hour, plasma phenylacetic acid AUC24-hour and phenylbutyric acid AUC24-hour. Plasma phenylacetic acid levels in adult and pediatric patients did not show a consistent relationship with either urinary phenylacetylglutamine or ammonia control. Conclusion The findings are collectively consistent with substantial yet variable pre-systemic (1st pass) conversion of phenylbutyric acid to
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Urinary phenylacetylglutamine as dosing biomarker for patients with urea cycle disorders.
Mokhtarani, M; Diaz, G A; Rhead, W; Lichter-Konecki, U; Bartley, J; Feigenbaum, A; Longo, N; Berquist, W; Berry, S A; Gallagher, R; Bartholomew, D; Harding, C O; Korson, M S; McCandless, S E; Smith, W; Vockley, J; Bart, S; Kronn, D; Zori, R; Cederbaum, S; Dorrani, N; Merritt, J L; Sreenath-Nagamani, Sandesh; Summar, M; Lemons, C; Dickinson, K; Coakley, D F; Moors, T L; Lee, B; Scharschmidt, B F
2012-11-01
We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6-17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 1.5 to 31.8 g/day and of sodium phenylbutyrate ranging from 1.3 to 31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% to 5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r = 0.730, p < 0.001) or as total 24-hour excretion (r = 0.791 p<0.001), followed by plasma phenylacetylglutamine AUC(24-hour), plasma phenylacetic acid AUC(24-hour) and phenylbutyric acid AUC(24-hour). Plasma phenylacetic acid levels in adult and pediatric patients did not show a consistent relationship with either urinary phenylacetylglutamine or ammonia control. The findings are collectively consistent with substantial yet variable pre-systemic (1st pass) conversion of phenylbutyric acid to phenylacetic acid and
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An Analysis of Anxiety-Related Postings on Sina Weibo.
Tian, Xianyun; He, Fang; Batterham, Philip; Wang, Zheng; Yu, Guang
2017-07-13
This study examines anxiety-related postings on Sina Weibo to gain insight into social networking about mental health. The themes of a random sample of anxiety-related postings ( n = 1000) were assessed. The disclosure of anxiety was the most common theme. The prevalence of anxiety was higher in certain areas where the economy is stronger than others, and the people living there suffered from more stress. Users who talked about feeling anxious tended to be more active on social media during leisure hours and less active during work hours. Our findings may be developed to detect and help individuals who may suffer from anxiety disorders at a low cost.
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Botsis, Taxiarchis; Foster, Matthew; Arya, Nina; Kreimeyer, Kory; Pandey, Abhishek; Arya, Deepa
2017-04-26
To evaluate the feasibility of automated dose and adverse event information retrieval in supporting the identification of safety patterns. We extracted all rabbit Anti-Thymocyte Globulin (rATG) reports submitted to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) from the product's initial licensure in April 16, 1984 through February 8, 2016. We processed the narratives using the Medication Extraction (MedEx) and the Event-based Text-mining of Health Electronic Records (ETHER) systems and retrieved the appropriate medication, clinical, and temporal information. When necessary, the extracted information was manually curated. This process resulted in a high quality dataset that was analyzed with the Pattern-based and Advanced Network Analyzer for Clinical Evaluation and Assessment (PANACEA) to explore the association of rATG dosing with post-transplant lymphoproliferative disorder (PTLD). Although manual curation was necessary to improve the data quality, MedEx and ETHER supported the extraction of the appropriate information. We created a final dataset of 1,380 cases with complete information for rATG dosing and date of administration. Analysis in PANACEA found that PTLD was associated with cumulative doses of rATG >8 mg/kg, even in periods where most of the submissions to FAERS reported low doses of rATG. We demonstrated the feasibility of investigating a dose-related safety pattern for a particular product in FAERS using a set of automated tools.
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Deep venous thrombophlebitis: detection with 4-hour versus 24-hour platelet scintigraphy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Seabold, J.E.; Conrad, G.R.; Ponto, J.A.
Thirty-one nonheparinized patients with suspected deep venous thrombophlebitis (DVT) underwent contrast venography and indium-111 platelet scintigraphy (In-111 PS). Venography permitted identification of acute DVT in 12 of 31 cases (39%). One additional patient was considered to have acute DVT despite nonconclusive venography results. In-111 PS results were positive at 4 hours in nine of 13 cases (69%) and at 24 hours in 12 of 13 cases (92%). Two of four patients with false-negative 4-hour In-111 PS studies had received warfarin. Thus, the sensitivity of 4-hour In-111 PS in patients not receiving anticoagulants was 82%. Venography results were negative for acutemore » DVT in 18 cases, and 4-hour In-111 PS studies were negative or equivocal in each. In-111 PS is an alternative to contrast venography for detecting acute DVT. If 4-hour In-111 PS results are positive, anticoagulation can be initiated. Delayed images are necessary if the 4-hour images are negative or equivocal.« less
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Boucher, Bradley A; Hudson, Joanna Q; Hill, David M; Swanson, Joseph M; Wood, G Christopher; Laizure, S Casey; Arnold-Ross, Angela; Hu, Zhe-Yi; Hickerson, William L
2016-12-01
High-dose continuous venovenous hemofiltration (CVVH) is a continuous renal replacement therapy (CRRT) used frequently in patients with burns. However, antibiotic dosing is based on inference from studies assessing substantially different methods of CRRT. To address this knowledge gap for imipenem/cilastatin (I/C), we evaluated the systemic and extracorporeal clearances (CLs) of I/C in patients with burns undergoing high-dose CVVH. Prospective clinical pharmacokinetic study. Ten adult patients with burns receiving I/C for a documented infection and requiring high-dose CVVH were studied. Blood and effluent samples for analysis of I/C concentrations were collected for up to 6 hours after the I/C infusion for calculation of I/C total CL (CL T otal ), CL by CVVH (CL HF ), half-life during CVVH, volume of distribution at steady state (Vd ss ), and the percentage of drug eliminated by CVVH. In this patient sample, the mean age was 50 ± 17 years, total body surface area burns was 23 ± 27%, and 80% were male. Nine patients were treated with high-dose CVVH for acute kidney injury and one patient for sepsis. The mean delivered CVVH dose was 52 ± 14 ml/kg/hour (range 32-74 ml/kg/hr). The imipenem CL HF was 3.27 ± 0.48 L/hour, which accounted for 23 ± 4% of the CL T otal (14.74 ± 4.75 L/hr). Cilastatin CL HF was 1.98 ± 0.56 L/hour, which accounted for 45 ± 19% of the CL T otal (5.16 + 2.44 L/hr). The imipenem and cilastatin half-lives were 1.77 ± 0.38 hours and 4.21 ± 2.31 hours, respectively. Imipenem and cilastatin Vd ss were 35.1 ± 10.3 and 32.8 ± 13.8 L, respectively. Efficient removal of I/C by high-dose CVVH, a high overall clearance, and a high volume of distribution in burn intensive care unit patients undergoing this CRRT method warrant aggressive dosing to treat serious infections effectively depending on the infection site and/or pathogen. © 2016 Pharmacotherapy Publications, Inc.
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Helling, Thomas S; Kaswan, Sumesh; Boccardo, Justin; Bost, James E
2010-09-01
Resident duty hour restriction was instituted to improve patient safety, but actual impact on patient care is unclear. We sought to determine the effect of duty hour restriction on trauma outcomes in Level I trauma centers (TCs; surgery residency programs) versus Level II TCs (those with no surgery residency programs) within the state of Pennsylvania, using noninferiority as our hypothesis testing. Outcomes (mortality and length of stay [LOS]) were compared in Level II TCs without surgery residencies (n = 7) with Level I TCs (with surgery residencies; n = 14) PRE80 (2001-2003) and POST80 (2004-2007). The subcategories of critically injured patients, Injury Severity Score (ISS) >15, ISS >25, Trauma and Injury Severity Score (TRISS) ≤ 50, Abbreviated Injury Scale (AIS) head/chest/abdomen score >3, age >65 years, mechanism, and shock, functioned as outcome predictors. There was a decrease in mortality overall PRE80 to POST80 for Level I and II TCs. There was a decrease in mortality in Level I TCs POST80 in ISS >15 (16.5% vs. 14.8%, p = 0.0001), AIS (head) score >3 (20.8% vs. 17.8%, p < 0.0001), age >65 years (12.2% vs. 10.7%, p = 0.0013), and blunt mechanism (5.2% vs. 4.6%, p = 0.0004). LOS was reduced in ISS >15, AIS (head) score >3, age >65 years, and penetrating mechanism in Level I TCs POST80. A similar but more profound decrease was also seen in Level II TCs PRE80 and POST80 (ISS >15, 25; AIS (head) score; shock; blunt mechanism; and TRISS ≤ 50). Testing for inhomogeneity identified less-severely injured patients at Level II TCs POST80 compared with Level I TCs in certain subcategories (ISS >15, 25; AIS (head) score; shock; blunt mechanism; and TRISS ≤ 50) regarding mortality and LOS (TRISS >50%). Decreases in mortality and LOS during the study periods were likely not related to resident work hour restriction but rather to overall improvement in outcomes seen at Level II (no residents) and Level I (residents) TCs. Resident work hour restrictions had no
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Bartolomé, Iris; Llidó, Anna; Darbra, Sònia; Pallarès, Marc
2018-06-21
Neuroactive steroids (NS) such as allopregnanolone are crucial for brain development and adult behaviour. Early post-natal alterations of NS by administering finasteride induce a decrease in the sensitivity to stimulant effects of low alcohol doses, an increase in alcohol consumption, and a decrease in ventrostriatal dopamine and serotonin levels. The aim of the present study is to observe if the effects of the 5HT3 receptor antagonist ondansetron on initial alcohol consumption are modulated by post-natal NS manipulation. For this purpose, allopregnanolone, finasteride, or vehicle was injected from day 5 to 9. In adulthood, a novel object preference test was carried out in order to detect a possible novelty-seeking pattern in our animals, which has been related to vulnerability to drug abuse. The subjects then had access to two bottles (alcohol or control solutions) one hour daily for two consecutive weeks. Ondansetron (0.01 mg/kg, 0.1 mg/kg or vehicle) was administered before the hour of consumption in the initial phase (days 1, 2, 3) of the procedure, and after prolonged alcohol intake (days 11, 12, 13). Results indicated that finasteride animals showed a higher preference to explore the new object, as well as a higher alcohol consumption than the rest of the groups. Moreover, 0.1 mg/kg of ondansetron decreased alcohol consumption, but only in the post-natal finasteride group, suggesting a possible increase in 5HT3 receptor sensitivity in these animals. In conclusion, NS manipulation in crucial stages of development, such as early post-natal periods, seems to play an important role on the effects of ondansetron on alcohol intake and in the vulnerability to develop drug use or abuse. Copyright © 2018. Published by Elsevier Inc.
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Steg, Philippe Gabriel; Jolly, Sanjit S; Mehta, Shamir R; Afzal, Rizwan; Xavier, Denis; Rupprecht, Hans-Jurgen; López-Sendón, Jose L; Budaj, Andrzej; Diaz, Rafael; Avezum, Alvaro; Widimsky, Petr; Rao, Sunil V; Chrolavicius, Susan; Meeks, Brandi; Joyner, Campbell; Pogue, Janice; Yusuf, Salim
2010-09-22
The optimal unfractionated heparin regimen for percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes treated with fondaparinux is uncertain. To compare the safety of 2 unfractionated heparin regimens during PCI in high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux. Double-blind randomized parallel-group trial in 179 hospitals in 18 countries involving 2026 patients undergoing PCI within 72 hours, nested within a cohort of 3235 high-risk patients with non-ST-segment elevation acute coronary syndromes initially treated with fondaparinux enrolled from February 2009 to March 2010. Patients received intravenously either low-dose unfractionated heparin, 50 U/kg, regardless of use of glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors or standard-dose unfractionated heparin, 85 U/kg (60 U/kg with GpIIb-IIIa inhibitors), adjusted by blinded activated clotting time (ACT). Composite of major bleeding, minor bleeding, or major vascular access-site complications up to 48 hours after PCI. Key secondary outcomes include composite of major bleeding at 48 hours with death, myocardial infarction, or target vessel revascularization within day 30. The primary outcome occurred in 4.7% of those in the low-dose group vs 5.8% in the standard-dose group (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.54-1.19; P = .27). The rates of major bleeding were not different but the rates of minor bleeding were lower with 0.7% in the low-dose group vs 1.7% in the standard-dose group (OR, 0.40; 95% CI, 0.16-0.97; P = .04). For the key secondary outcome, the rates for low-dose group were 5.8% vs 3.9% in the standard-dose group (OR, 1.51; 95% CI, 1.00-2.28; P = .05) and for death, myocardial infarction, or target vessel revascularization it was 4.5% for the low-dose group vs 2.9% for the standard-dose group (OR, 1.58; 95% CI, 0.98-2.53; P = .06). Catheter thrombus rates were very low (0
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Ng, S C; Habib, A S; Sodha, S; Carvalho, B; Sultan, P
2018-02-01
The optimal local-anaesthetic (LA) dose for transversus-abdominis-plane (TAP) block is unclear. In this meta-analysis, we aimed to determine whether TAP blocks for Caesarean delivery (CD) with low-dose (LD) LA demonstrated non-inferiority in terms of analgesic efficacy, compared with high-dose (HD) LA. A literature search was performed for randomised controlled trials examining the analgesic efficacy of TAP blocks vs control after CD. The different dosing used in these studies was classified as HD or LD (bupivacaine equivalents >50 or ≤50 mg per block side, respectively). The pooled results of each dose group vs control were indirectly compared using the Q test. The primary outcome was 24 h opioid consumption. Secondary outcomes included 6 and 24 h postoperative pain scores, time to first analgesia, 6 h opioid consumption, opioid-related side-effects, and maternal satisfaction. Fourteen studies consisting of 770 women (389 TAP and 381 control) were included. Compared with controls, the 24 h opioid consumption (milligram morphine equivalents) was lower in HD [mean difference (MD) 95% confidence interval (CI) -22.41 (-38.56, -6.26); P=0.007; I 2 =93%] and LD [MD 95% CI -16.29 (-29.74, -2.84); P=0.02; I 2 =98%] TAP groups. However, no differences were demonstrated between the HD and LD groups (P=0.57). There were also no differences between the HD and LD groups for the 6 h opioid consumption, time to first analgesia, 6 and 24 h pain scores, postoperative nausea and vomiting, pruritus, and maternal satisfaction. Low-dose TAP blocks for Caesarean delivery provide analgesia and opioid-sparing effects comparable with the high-dose blocks. This suggests that lower doses can be used to reduce local anaesthetic toxicity risk without compromising the analgesic efficacy. Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
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Moeller, Andrew; Webber, Jordan; Epstein, Ian
2016-07-13
Resident duty hours have recently been under criticism, with concerns for resident and patient well-being. Historically, call shifts have been long, and some residency training programs have now restricted shift lengths. Data and opinions about the effects of such restrictions are conflicting. The Internal Medicine Residency Program at Dalhousie University recently moved from a traditional call structure to a day float/night float system. This study evaluated how this change in duty hours affected resident perceptions in several key domains. Senior residents from an internal medicine training program in Canada responded to an anonymous online survey immediately before and 6 months after the implementation of duty hour reform. The survey contained questions relating to three major domains: resident wellness, ability to deliver quality health care, and medical education experience. Mean pre- and post-intervention scores were compared using the t-test for paired samples. Twenty-three of 27 (85 %) senior residents completed both pre- and post-reform surveys. Residents perceived significant changes in many domains with duty hour reform. These included improved general wellness, less exposure to personal harm, fewer feelings of isolation, less potential for error, improvement in clinical skills expertise, increased work efficiency, more successful teaching, increased proficiency in medical skills, more successful learning, and fewer rotation disruptions. Senior residents in a Canadian internal medicine training program perceived significant benefits in medical education experience, ability to deliver healthcare, and resident wellness after implementation of duty hour reform.
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White, Stephanie S; Kasimanickam, Ramanathan K; Kasimanickam, Vanmathy R
2016-08-01
Timed artificial insemination protocols in beef cattle are designed to synchronize ovulation in a greater proportion of females while simultaneously achieving acceptable pregnancy rates and a concise calving season. Protocols achieving such goals reduce time and labor associated with estrus detection and make advanced reproductive technologies implementable for beef producers. The objective of the study was to determine the effect of three different PGF2α (PGF) dosage schemes on artificial insemination (AI) pregnancy rates in beef heifers. We hypothesized that two doses of PGF administered concurrently at the time of controlled internal drug release (CIDR) removal would attain similar pregnancy rates compared with two doses given 6-hours apart-one at CIDR removal and the next 6 hours later in the 5-day CO-Synch progesterone-based synchronization protocol. Angus heifers (n = 875) at six locations in Washington, Idaho, and Oregon states were included in this study. Heifers within locations were assigned a body condition score (BCS). All heifers received a CIDR (1.38 g of progesterone) and 100 μg IM of GnRH on Day 0. The CIDRs were removed on Day 5, heifers were randomly allocated to one of three protocol groups: 1PGF (n = 291), received 25 mg IM of dinoprost (PGF); 2CO-PGF (n = 291), received 50 mg IM of dinoprost at CIDR removal, 2PGF (n = 293), received 25 mg IM of dinoprost at CIDR removal, and an additional 25 mg IM of dinoprost 6 hours later. Each heifer was given GnRH (100 μg, IM) and artificially inseminated at 56 hours after CIDR removal. Heifers were examined for pregnancy status between 50 and 70 days after AI to determine time of conception. A mixed-model procedure (PROC GLIMMIX of SAS) was used to evaluate the effect of treatments (1PGF, 2CO-PGF, and 2PGF) on AI pregnancy rates. Models included were treatments, BCS categories (≤5 and >5), and treatment by BCS category interaction. Location (state), handling facilities, handlers
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Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs.
Larson, Jeanne C; Allstadt, Sara D; Fan, Timothy M; Khanna, Chand; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Legendre, Alfred M; Galyon, Gina D; LeBlanc, Amy K; Martin-Jimenez, Tomas
2016-01-01
To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. 5 healthy purpose-bred hounds. The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.
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Cheung, Joseph Y; Mueller, Daniel; Blum, Marissa; Ravreby, Hannah; Williams, Paul; Moyer, Darilyn; Caroline, Malka; Zack, Chad; Fisher, Susan G; Feldman, Arthur M
2015-09-01
Implementation of more stringent regulations on duty hours and supervision by the Accreditation Council for Graduate Medical Education in July 2011 makes it challenging to design inpatient Medicine teaching service that complies with the duty hour restrictions while optimizing continuity of patient care. To prospectively compare two inpatient Medicine teaching service structures with respect to residents' impression of continuity of patient care (primary outcome), time available for teaching, resident satisfaction and length-of-stay (secondary endpoints). Observational pre-post study. Surveys were conducted both before and after Conventional Medicine teaching service was changed to a novel model (MegaTeam). Academic General Medicine inpatient teaching service. Surveys before and after MegaTeam implementation were completed by 68.5% and 72.2% of internal medicine residents, respectively. Comparing conventional with MegaTeam, the % of residents who agreed or strongly agreed that the (i) ability to care for majority of patients from admission to discharge increased from 29.7% to 86.6% (p<0.01); (ii) the concern that number of handoffs was too many decreased from 91.9% to 18.2% (p<0.01); (iii) ability to provide appropriate supervision to interns increased from 38.1% to 70.7% (p<0.01); (iv) overall resident satisfaction with inpatient Medicine teaching service increased from 24.7% to 56.4% (p<0.01); and (v) length-of-stay on inpatient Medicine service decreased from 5.3±6.2 to 4.9±6.8 days (p<0.03). According to our residents, the MegaTeam structure promotes continuity of patient care, decreases number of handoffs, provides adequate supervision and teaching of interns and medical students, increases resident overall satisfaction and decreases length-of-stay. Copyright © 2015 Elsevier Inc. All rights reserved.
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The 80-hour work week: will we have less-experienced graduating surgeons?
Jarman, Benjamin T; Miller, Marcus R; Brown, R Shane; Armen, Scott B; Bozaan, Anthony G; Ho, George T; Hartranft, Thomas H
2004-01-01
Our primary concern when modifying the Mount Carmel Medical Center surgical residency to comply with the "80-hour work week" was the effect on operative experience. Our goal was to measure the impact that work-hour restrictions have on operative volumes and to evaluate the potential benefit of a night rotation to minimize the number of "lost operations." Categorical surgical residents (PGY I-IV) recorded missed surgical procedures on post-call days from September 1, 2002 to March 31, 2004. The data collection is split between the pre-night rotation (September 1, 2002 to March 31, 2003) and post-night rotation (April 1, 2003 to March 31, 2004) periods. The post-night rotation period is further divided to account for the end of the academic year. Previous graduate operative logs were reviewed for comparison. Mount Carmel Health System is a tertiary referral, community-based hospital in Columbus, Ohio. Categorical general surgery residents (Postgraduate Years I to V). In the 7-month period, extending from September 1, 2002 to March 31, 2003, the average number of missed cases for successive levels was PGY I: 21, PGY II: 31, PGY III: 26, and PGY IV: 40. From April 1, 2003 to June 30, 2003, the average number of missed cases for successive levels was PGY I: 3, PGY II: 7, PGY III: 5, and PGY IV: 6. From July 1, 2003 to March 31, 2004, the average number of missed cases for successive levels was PGY I: 34, PGY II: 8, PGY III: 14, and PGY IV: 30. Before the implementation of a night rotation, residents were projected to miss an average of 202 operations over 4 years. After implementation of a night rotation, the projected loss would drop to 107 operations over 4 years. Work-hour restrictions result in a significant decrease in operative experience. This detriment can be partially alleviated with the institution of a night rotation to better regulate in-house call.
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Landy, Stephen; DeRossett, Sarah E.; Rapoport, Alan; Rothrock, John; Ames, Michael H.; McDonald, Susan A.; Burch, Steven P.
2007-01-01
Objective To describe return to normal function, productivity, and satisfaction of patients with moderate or severe migraine attacks treated with combined sumatriptan/naproxen sodium, sumatriptan alone, naproxen sodium alone, or placebo. Patients, design, and setting Patients in 2 identical, US, phase 3, randomized, double-blind, parallel-group, placebo-controlled, single-dose, multicenter studies treated a single moderate or severe migraine attack with sumatriptan/naproxen sodium (85 mg sumatriptan formulated with RT Technology and 500 mg naproxen sodium in a single-tablet formulation), sumatriptan, naproxen sodium, or placebo. Main outcome measures Ability to function (not impaired, mildly impaired, severely impaired, or required bed rest) was collected in diary cards completed immediately prior to treatment, every 30 minutes for the first 2 hours, and hourly from 2 to 24 hours while awake. Patients completed the Productivity Assessment Questionnaire (PAQ) 24 hours after study drug administration. The Patient Perception of Migraine Questionnaire (PPMQ) was administered at screening and 24 hours post treatment to capture patient satisfaction. Results Compared with the other groups, the sumatriptan/naproxen sodium group reported significantly higher levels of normal or mildly impaired functioning as early as 2 and 4 hours after dosing. They also demonstrated greater reductions in workplace productivity loss compared with placebo in both studies, and were consistently more satisfied with their treatment compared with patients in other treatment groups and compared with their usual medications. Conclusions Treatment with sumatriptan/naproxen sodium allowed significantly more subjects to return to normal or mildly impaired functioning more quickly, and sumatriptan/naproxen sodium patients were significantly more satisfied with their treatment compared with other treatment groups. Overall productivity loss was significantly reduced following use of sumatriptan
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Potter, J; Robinson, T; Ford, G; James, M; Jenkins, D; Mistri, A; Bulpitt, C; Drummond, A; Jagger, C; Knight, J; Markus, H; Beevers, G; Dewey, M; Lees, K; Moore, A; Paul, S
2005-03-01
High and low blood pressure (BP) levels are common following acute stroke, with up to 60% of patients being hypertensive (SBP > 160 mmHg) and nearly 20% having relative hypotension (SBP < or = 140 mmHg), within the first few hours of ictus, both conditions being associated with an adverse prognosis. At present, the optimum management of blood pressure in the immediate post-stroke period is unclear. The primary aim of the Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS) Pilot Trial is to assess whether hypertension and relative hypotension, manipulated therapeutically in the first 24 h following acute stroke, affects short-term outcome measures. The CHHIPS Pilot Trial is a UK based multi-centre, randomized, double-blind, placebo-controlled, titrated dose trial. Acute stroke and medical units in teaching and district general hospitals, in the UK. The CHHIPS Pilot Study aims to recruit 2050 patients, with clinically suspected stroke, confirmed by brain imaging, who have no compelling indication or contraindication for BP manipulation. The primary outcome measure will be the effects of acute pressor therapy (initiated < or = 12 h from stroke onset) or depressor therapy (started < or = 24 h post-ictus) on death and dependency at 14 days post-stroke. Secondary outcome measures will include the influence of therapy on early neurological deterioration, the effectiveness of treatment in manipulating BP levels, the influence of time to treatment and stroke type on response and a cost-effectiveness analysis.
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Lavender essence for post-cesarean pain.
Hadi, Niaz; Hanid, Ali Akbar
2011-06-01
Post cesarean (CS) pain is a challenging problem for the obstetricians, because it may interfere with mother and baby's well-being. Many approaches have been ever proposed to diminish this pain, each one with particular benefits and limitations. Aromatherapy is a complementary therapy especially for controlling pain. This study aimed at evaluating the effect of lavender essence on post CS pain. In a single-blind clinical trial, 200 term pregnant women with planned elective CS were recruited in a 12 month period of time. They were randomized in two 100-patient groups; received either lavender essence (the case group) or a similar clinically neutral aromatic material (the control group) thorough oxygen mask for 3 min 3 h after receiving similar intravenous analgesics. The Visual Analogue Scale (VAS) was employed to determine the level of post CS pain. The VAS was documented half hour after first intervention. Eight and 16 h later, the aromatherapy was repeated and half hour after each intervention, corresponding VAS was documented. The two groups were matched for demographics and obstetrical history. The baseline VAS was comparable between the two groups. The mean VAS decreased significantly by 16 h after the first intervention in both groups (p < 0.001). However, this amelioration of pain was significantly more prominent in the cases group comparing with that in the controls in all documented stages half hour, 8 and 16 h after the first intervention (p < 0.001 for all measurements). In conclusion, aromatherapy by using lavender essence is a successful and safe complementary therapy in reducing pain after CS.
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Liposomal bupivacaine as a single-injection peripheral nerve block: a dose-response study.
Ilfeld, Brian M; Malhotra, Nisha; Furnish, Timothy J; Donohue, Michael C; Madison, Sarah J
2013-11-01
Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration of <24 hours. A liposomal bupivacaine formulation (EXPAREL, Pacira Pharmaceuticals, Inc., San Diego, CA), releasing bupivacaine over 96 hours, recently gained Food and Drug Administration approval exclusively for wound infiltration but not peripheral nerve blocks. Bilateral single-injection femoral nerve blocks were administered in healthy volunteers (n = 14). For each block, liposomal bupivacaine (0-80 mg) was mixed with normal saline to produce 30 mL of study fluid. Each subject received 2 different doses, 1 on each side, applied randomly in a double-masked fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. There were statistically significant dose responses in MVIC (0.09%/mg, SE = 0.03, 95% confidence interval [CI], 0.04-0.14, P = 0.002) and tolerance to cutaneous current (-0.03 mA/mg, SE = 0.01, 95% CI, -0.04 to -0.02, P < 0.001), however, in the opposite direction than expected (the higher the dose, the lower the observed effect). This inverse relationship is biologically implausible and most likely due to the limited sample size and the subjective nature of the measurement instruments. While peak effects occurred within 24 hours after block administration in 75% of cases (95% CI, 43%-93%), block duration usually lasted much longer: for bupivacaine doses >40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 hours in 100% of subjects (95% CI, 56%-100%). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI, 54%-100%). Motor block duration was not correlated with bupivacaine dose (0.06 hour/mg, SE = 0
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Tables View the latest hourly text summary CLICK ON UNDERLINED HOUR / SHADED BOX FOR THE LATEST CYCLE 00z Dump Tables View the latest rap text summary CLICK ON UNDERLINED HOUR / SHADED BOX FOR THE LATEST CYCLE Data Dump Tables View the latest model data text summary NAM GFS GDS CLICK ON UNDERLINED HOUR / SHADED
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Vesikari, Timo; Hardt, Roland; Rümke, Hans C; Icardi, Giancarlo; Montero, Jordi; Thomas, Stéphane; Sadorge, Christine; Fiquet, Anne
2013-04-01
Disease protection provided by herpes zoster (HZ) vaccination tends to reduce as age increases. This study was designed to ascertain whether a second dose of the HZ vaccine, Zostavax(®), would increase varicella zoster virus (VZV)-specific immune response among individuals aged ≥ 70 y. Individuals aged ≥ 70 y were randomized to receive HZ vaccine in one of three schedules: a single dose (0.65 mL), two doses at 0 and 1 mo, or two doses at 0 and 3 mo. VZV antibody titers were measured at baseline, 4 weeks after each vaccine dose, and 12 mo after the last dose. In total, 759 participants (mean age 76.1 y) were randomized to receive vaccination. Antibody responses were similar after a single dose or two doses of HZ vaccine [post-dose 2/post-dose 1 geometric mean titer (GMT) ratios for the 1-mo or 3-mo schedules were 1.11, 95% confidence interval (CI) 1.02-1.22 and 0.78, 95% CI 0.73-0.85], respectively). The 12-mo post-dose 2/12-mo post-dose 1 GMT ratio was similar for the 1-mo schedule and for the 3-mo schedule (1.06, 95% CI 0.96-1.17 and 1.08, 95% CI 0.98-1.19, respectively). Similar immune responses were observed in participants aged 70-79 y and those aged ≥ 80 y. HZ vaccine was generally well tolerated, with no evidence of increased adverse event incidence after the second dose with either schedule. Compared with a single-dose regimen, two-dose vaccination did not increase VZV antibody responses among individuals aged ≥ 70 y. Antibody persistence after 12 mo was similar with all three schedules.
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Meyer, Anna Sina P; Ostrowski, Sisse R; Kjaergaard, Jesper; Johansson, Pär I; Hassager, Christian
2016-08-02
, [soluble thrombomodulin (sTM), sE-selectin, syndecan-1, soluble vascular endothelial growth factor (sVEGF), nucleosomes] and sympathoadrenal over activation (epinephrine/norepinephrine) from baseline to 48 hours post-randomization. The secondary endpoints of this trial will include: (1) the hemostatic profile [change in functional hemostatic blood test (thrombelastography (TEG) and whole blood platelet aggregometry (multiplate)) blood cell and endothelial cell-derived microparticles]; (2) feasibility of blood pressure target intervention (target 90 %); (3) interaction of primary endpoints and blood pressure target; (4) levels of neuron-specific enolase at 48 hours post-inclusion according to blood pressure targets. The ENDO-RCA study is a pilot study trial that investigates safety and efficacy of low-dose infusion of prostacyclin administration as compared to standard therapy in post-cardiac arrest syndrome patients. Trial registration at ClinicalTrials.gov (identifier NCT02685618 ) on 18 February 2016.
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Early outcomes following low dose naltrexone enhancement of opioid detoxification.
Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathleen; Gottheil, Edward; Wu, Li-Tzy; Gorelick, David A
2009-01-01
Although withdrawal severity and treatment completion are the initial focus of opioid detoxification, post-detoxification outcome better defines effective interventions. Very low dose naltrexone (VLNTX) in addition to methadone taper was recently associated with attenuated withdrawal intensity during detoxification. We describe the results of a seven-day follow-up evaluation of 96 subjects who completed inpatient detoxification consisting of the addition of VLNTX (0.125 or 0.250 mg per day) or placebo to methadone taper in a double blind, randomized investigation. Individuals receiving VLNTX during detoxification reported reduced withdrawal and drug use during the first 24 hours after discharge. VLNTX addition was also associated with higher rates of negative drug tests for opioids and cannabis and increased engagement in outpatient treatment after one week. Further studies are needed to test the utility of this approach in easing the transition from detoxification to various follow-up treatment modalities designed to address opioid dependence.
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Gene Expression Changes in Mouse Intestinal Tissue Following Whole-Body Proton or Gamma-Irradiation
NASA Technical Reports Server (NTRS)
Purgason, Ashley; Zhang, Ye; Mangala, Lingegowda; Nie, Ying; Gridley, Daila; Hamilton, Stanley R.; Seidel, Derek V.; Wu, Honglu
2014-01-01
Crew members face potential consequences following exposure to the space radiation environment including acute radiation syndrome and cancer. The space radiation environment is ample with protons, and numerous studies have been devoted to the understanding of the health consequences of proton exposures. In this project, C57BL/6 mice underwent whole-body exposure to 250 MeV of protons at doses of 0, 0.1, 0.5, 2 and 6 Gy and the gastrointestinal (GI) tract of each animal was dissected four hours post-irradiation. Standard H&E staining methods to screen for morphologic changes in the tissue showed an increase in apoptotic lesions for even the lowest dose of 0.1 Gy, and the percentage of apoptotic cells increased with increasing dose. Results of gene expression changes showed consistent up- or down- regulation, up to 10 fold, of a number of genes across exposure doses that may play a role in proton-induced oxidative stress including Gpx2. A separate study in C57BL/6 mice using the same four hour time point but whole-body gamma-irradiation showed damage to the small intestine with lesions appearing at the smallest dose of 0.05 Gy and increasing with increasing absorbed dose. Expressions of genes associated with oxidative stress processes were analyzed at four hours and twenty-four hours after exposure to gamma rays. We saw a much greater number of genes with significant up- or down-regulation twenty-four hours post-exposure as compared to the four hour time point. At both four hours and twenty-four hours post-exposure, Duox1 and Mpo underwent up-regulation for the highest dose of 6 Gy. Both protons and gamma rays lead to significant variation in gene expressions and these changes may provide insight into the mechanism of injury seen in the GI tract following radiation exposure. We have also completed experiments using a BALB/c mouse model undergoing whole-body exposure to protons. Doses of 0, 0.1, 1 and 2 Gy were used and results will be compared to the work mentioned
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Cohen, Roger B.; Jones, Suzanne F.; Aggarwal, Charu; von Mehren, Margaret; Cheng, Jonathan; Spigel, David R.; Greco, F. Anthony; Mariani, Mariangela; Rocchetti, Maurizio; Ceruti, Roberta; Comis, Silvia; Laffranchi, Bernard; Moll, Jurgen; Burris, Howard A.
2009-01-01
Purpose This study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of the intravenous pan-aurora kinase inhibitor PHA-739358, danusertib, in patients with advanced solid tumors. Experimental Design In Part 1, patients received escalating doses of danusertib (24-h infusion every 14 days) without filgrastim (G-CSF). Febrile neutropenia was the dose-limiting toxicity without G-CSF. Further dose escalation was performed in part 2 with G-CSF. Blood samples were collected for danusertib pharmacokinetics and pharmacodynamics. Skin biopsies were collected to assess histone H3 phosphorylation (pH3). Results Fifty-six patients were treated, 40 in part 1 and 16 in part 2. Febrile neutropenia was the dose limiting toxicity in Part 1 without G-CSF. Most other adverse events were grade 1–2, occurring at doses ≥360 mg/m2 with similar incidence in parts 1 and 2. The MTD without G-CSF is 500 mg/m2. The recommended phase 2 dose (RP2D) in Part 2 with G-CSF is 750 mg/m2. Danusertib demonstrated dose-proportional pharmacokinetics in parts 1 and 2 with a median half-life of 18–26 hours. pH3 modulation in skin biopsies was observed at ≥500 mg/m2. One patient with refractory small cell lung cancer (1000 mg/m2 with G-CSF) had an objective response lasting 23 weeks. One patient with refractory ovarian cancer had 27% tumor regression and 30% CA125 decline. Conclusions Danusertib was well tolerated with target inhibition in skin at ≥500 mg/m2. Preliminary evidence of anti-tumor activity, including a PR and several occurrences of prolonged stable disease (SD), was seen across a variety of advanced refractory cancers. Phase II studies are ongoing. PMID:19825950
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Out-of-office hours' elective surgical intensive care admissions and their associated complications.
Morgan, David J R; Ho, Kwok Ming; Ong, Yang Jian; Kolybaba, Marlene L
2017-11-01
The 'weekend' effect is a controversial theory that links reduced staffing levels, staffing seniority and supportive services at hospitals during 'out-of-office hours' time periods with worsening patient outcomes. It is uncertain whether admitting elective surgery patients to intensive care units (ICU) during 'out-of-office hours' time periods mitigates this affect through higher staffing ratios and seniority. Over a 3-year period in Western Australia's largest private hospital, this retrospective nested-cohort study compared all elective surgical patients admitted to the ICU based on whether their admission occurred 'in-office hours' (Monday-Friday 08.00-18.00 hours) or 'out-of-office hours' (all other times). The main outcomes were surgical complications using the Dindo-Clavien classification and length-of-stay data. Of the total 4363 ICU admissions, 3584 ICU admissions were planned following elective surgery resulting in 2515 (70.2%) in-office hours and 1069 (29.8%) out-of-office hours elective ICU surgical admissions. Out-of-office hours ICU admissions following elective surgery were associated with an increased risk of infection (P = 0.029), blood transfusion (P = 0.020), total parental nutrition (P < 0.001) and unplanned re-operations (P = 0.027). Out-of-office hours ICU admissions were also associated with an increased hospital length-of-stay, with (1.74 days longer, P < 0.0001) and without (2.8 days longer, P < 0.001) adjusting for severity of acute and chronic illnesses and inter-hospital transfers (12.3 versus 9.8%, P = 0.024). Hospital mortality (1.2 versus 0.7%, P = 0.111) was low and similar between both groups. Out-of-office hours ICU admissions following elective surgery is common and associated with serious post-operative complications culminating in significantly longer hospital length-of-stays and greater transfers with important patient and health economic implications. © 2017 Royal Australasian College of Surgeons.
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Shou, Wilson Z; Naidong, Weng
2003-01-01
It has become increasingly popular in drug development to conduct discovery pharmacokinetic (PK) studies in order to evaluate important PK parameters of new chemical entities (NCEs) early in the discovery process. In these studies, dosing vehicles are typically employed in high concentrations to dissolve the test compounds in dose formulations. This can pose significant problems for the liquid chromatography/tandem mass spectrometric (LC/MS/MS) analysis of incurred samples due to potential signal suppression of the analytes caused by the vehicles. In this paper, model test compounds in rat plasma were analyzed using a generic fast gradient LC/MS/MS method. Commonly used dosing vehicles, including poly(ethylene glycol) 400 (PEG 400), polysorbate 80 (Tween 80), hydroxypropyl beta-cyclodextrin, and N,N-dimethylacetamide, were fortified into rat plasma at 5 mg/mL before extraction. Their effects on the sample analysis results were evaluated by the method of post-column infusion. Results thus obtained indicated that polymeric vehicles such as PEG 400 and Tween 80 caused significant suppression (> 50%, compared with results obtained from plasma samples free from vehicles) to certain analytes, when minimum sample cleanup was used and the analytes happened to co-elute with the vehicles. Effective means to minimize this 'dosing vehicle effect' included better chromatographic separations, better sample cleanup, and alternative ionization methods. Finally, a real-world example is given to illustrate the suppression problem posed by high levels of PEG 400 in sample analysis, and to discuss steps taken in overcoming the problem. A simple but effective means of identifying a 'dosing vehicle effect' is also proposed. Copyright 2003 John Wiley & Sons, Ltd.
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Pereira, Sandrine; Malard, Véronique; Ravanat, Jean-Luc; Davin, Anne-Hélène; Armengaud, Jean; Foray, Nicolas; Adam-Guillermin, Christelle
2014-01-01
The term “bystander effect” is used to describe an effect in which cells that have not been exposed to radiation are affected by irradiated cells though various intracellular signaling mechanisms. In this study we analyzed the kinetics and mechanisms of bystander effect and radioadaptation in embryonic zebrafish cells (ZF4) exposed to chronic low dose of gamma rays. ZF4 cells were irradiated for 4 hours with total doses of gamma irradiation ranging from 0.01–0.1 Gy. In two experimental conditions, the transfer of irradiated cells or culture medium from irradiated cells results in the occurrence of DNA double strand breaks in non-irradiated cells (assessed by the number of γ-H2AX foci) that are repaired at 24 hours post-irradiation whatever the dose. At low total irradiation doses the bystander effect observed does not affect DNA repair mechanisms in targeted and bystander cells. An increase in global methylation of ZF4 cells was observed in irradiated cells and bystander cells compared to control cells. We observed that pre-irradiated cells which are then irradiated for a second time with the same doses contained significantly less γ-H2AX foci than in 24 h gamma-irradiated control cells. We also showed that bystander cells that have been in contact with the pre-irradiated cells and then irradiated alone present less γ-H2AX foci compared to the control cells. This radioadaptation effect is significantly more pronounced at the highest doses. To determine the factors involved in the early events of the bystander effect, we performed an extensive comparative proteomic study of the ZF4 secretomes upon irradiation. In the experimental conditions assayed here, we showed that the early events of bystander effect are probably not due to the secretion of specific proteins neither the oxidation of these secreted proteins. These results suggest that early bystander effect may be due probably to a combination of multiple factors. PMID:24667817
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Tyl, Benoît; Kabbaj, Meriam; Azzam, Sara; Sologuren, Ander; Valiente, Román; Reinbolt, Elizabeth; Roupe, Kathryn; Blanco, Nathalie; Wheeler, William
2012-06-01
The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively), and bilastine 20 mg administered with ketoconazole 400 mg. Time-matched, triplicate electrocardiograms (ECGs) were recorded with 13 time points extracted predose and 16 extracted over 72 hours post day 4 dosing. Four QT/RR corrections were implemented: QTcB; QTcF; a linear individual correction (QTcNi), the primary correction; and a nonlinear one (QTcNnl). Moxifloxacin was associated with a significant increase in QTcNi at all time points between 1 and 12 hours, inclusively. Bilastine administration at 20 mg and 100 mg had no clinically significant impact on QTc (maximum increase in QTcNi, 5.02 ms; upper confidence limit [UCL] of the 1-sided, 95% confidence interval, 7.87 ms). Concomitant administration of ketoconazole and bilastine 20 mg induced a clinically relevant increase in QTc (maximum increase in QTcNi, 9.3 ms; UCL, 12.16 ms). This result was most likely related to the cardiac effect of ketoconazole because for all time points, bilastine plasma concentrations were lower than those observed following the supratherapeutic dose.
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Organizational interventions in response to duty hour reforms
2014-01-01
Background Changes in resident duty hours in Europe and North America have had a major impact on the internal organizational dynamics of health care organizations. This paper examines, and assesses the impact of, organizational interventions that were a direct response to these duty hour reforms. Methods The academic literature was searched through the SCOPUS database using the search terms “resident duty hours” and “European Working Time Directive,” together with terms related to organizational factors. The search was limited to English-language literature published between January 2003 and January 2012. Studies were included if they reported an organizational intervention and measured an organizational outcome. Results Twenty-five articles were included from the United States (n = 18), the United Kingdom (n = 5), Hong Kong (n = 1), and Australia (n = 1). They all described single-site projects; the majority used post-intervention surveys (n = 15) and audit techniques (n = 4). The studies assessed organizational measures, including relationships among staff, work satisfaction, continuity of care, workflow, compliance, workload, and cost. Interventions included using new technologies to improve handovers and communications, changing staff mixes, and introducing new shift structures, all of which had varying effects on the organizational measures listed previously. Conclusions Little research has assessed the organizational impact of duty hour reforms; however, the literature reviewed demonstrates that many organizations are using new technologies, new personnel, and revised and innovative shift structures to compensate for reduced resident coverage and to decrease the risk of limited continuity of care. Future research in this area should focus on both micro (e.g., use of technology, shift changes, staff mix) and macro (e.g., culture, leadership support) organizational aspects to aid in our understanding of how best to respond to these duty hour reforms
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48-hours administration of fenoterol in spontaneous preterm labor - does it affect fetal preload?
Grzesiak, Mariusz; Forys, Sebastian; Sobczak, Malgorzata; Ahmed, Rehana B; Wilczynski, Jan
2013-01-01
to investigate whether any changes in the preload index (PLI) occur within the first 48 hours of fenoterol intravenous tocolysis. Doppler evaluation of placental and fetal circulation was performed in 36 pregnant women prior to fenoterol administration and after 24/48 hours. Measurements were obtained from a longitudinal section of the inferior vena cava (IVC) and preload index was calculated. To determine changes over time, an all study variable analysis of variance (ANOVA) for repeated measurements, followed by Tukey-Kramer's multiple comparison test was used. The effects of additional clinical covariates were checked. The maternal heart rate values were significantly increased after 24 hours and 48 hours in comparison to pre-treatment values. No significant changes in fetal heart rate were observed during treatment. The fetal IVC PLI values were significantly reduced after 24 hours and 48 hours of treatment. The increase in PLI values when comparing 24 and 48 hours results were not statistically significant. These observations were consistent with ANOVA post-hoc analysis. 48 hours intravenous administration of fenoterol appears not to alter inferior vena cava blood flow by itself. The reduction in PLI values may reflect lower fetal preload conditions during the course of successful tocolytic treatment. Therefore, Doppler IVC PLI measurement should be considered as a possible additional assessment method of effectiveness of treatment. However, other Doppler venous blood flow parameters should be assessed to confirm the results and clarify whether maternal corticosteroids administration may be interfering with the results.
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Single-dose pharmacokinetic study of 13-cis-retinoic acid in man.
Besner, J G; Leclaire, R; Band, P; Meloche, S; Deschamps, M; Mailhot, S; Moisan, R; Diorio, G
1985-03-01
A pharmacokinetic study of 13-cis-retinoic acid was performed in nine patients following administration of a single oral dose of 80 mg. An average lag time of 1.2 hours was observed, followed by fast absorption, with a mean half-life of 0.5 hour. Peak plasmatic concentration of 733 ng/ml occurred at 2.3 hours. The disposition profile showed a rapid distribution half-life of 1.3 hours and a terminal elimination half-life of 24.7 hours. No 13-cis-retinoic acid was detected unchanged in urine. An important interpatient variability was noted.
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Systematic review of 23-hour (outpatient) stay laparoscopic gastric bypass surgery.
Thomas, Harun; Agrawal, Sanjay
2011-10-01
The laparoscopic Roux-en-Y gastric bypass (LRYGB) is generally considered the gold-standard bariatric procedure. It has a usual inpatient stay of 3 days. There have been few reports of gastric bypass patients being discharged within 23 hours of surgery, but its safety and feasibility has not been reviewed before. The aim of this study was to review the published literature on 23-hour stay post-LRYGB. Systematic search was performed in Medline, Embase, and Cochrane library using the medical subject heading terms "ambulatory surgical procedures" and "bariatric surgery" with further free text search and cross references. All articles on 23-hour LRYGB that described patient selection criteria, 23-hour discharge, complications, and readmissions were reviewed. Data were extracted by two independent reviewers. There were no randomized controlled trials. Four cohort studies were included in this review. The patients age ranged from 14 to 70 years, mean body mass index ranged from 41.2 to 49.25, and the mean operative time ranged from 112.8 to 169 minutes. 1852/2201(84.14%) patients could be discharged within 23 hours. Forty-eight patients (2.18%) developed complications and 40 patients (1.82%) were readmitted. The commonest 30-day complications were anastomotic strictures (16), gastrointestinal bleeding (9), and internal hernias (9). Five patients developed anastomotic leak and 2 patients developed pulmonary embolism. Two patients died but neither was discharged after their bypass surgery. There is a paucity of data regarding 23-hour discharge after LRYGB. The evidence suggests that it is feasible in selected patients. However, further studies are necessary to assess its safety and acceptability.
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Choi, Dongseok; Dickey, Jamie; Wessel, Kristen; Girard, Donald E
2006-10-17
To assess the impact of work hours' limitations required by the Accreditation Council for Graduate Medical Education (ACGME) on residents' career satisfaction, emotions and attitudes. A validated survey instrument was used to assess residents' levels of career satisfaction, emotions and attitudes before and after the ACGME duty hour requirements were implemented. The "pre" implementation survey was distributed in December 2002 and the "post" implementation one in December 2004. Only the latter included work-hour related questions. The response rates were 56% for the 2002 and 72% for the 2004 surveys respectively. Although career satisfaction remained unchanged, numerous changes occurred in both emotions and attitudes. Compared to those residents who did not violate work-hour requirements, those who did were significantly more negative in attitudes and emotions. With the implementation of the ACGME work hour limitations, the training experience became more negative for those residents who violated the work hour limits and had a small positive impact on those who did not violate them. Graduate medical education leaders must innovate to make the experiences for selected residents improved and still maintain compliance with the work hour requirements.
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Choi, Dongseok; Dickey, Jamie; Wessel, Kristen; Girard, Donald E
2006-01-01
Background To assess the impact of work hours' limitations required by the Accreditation Council for Graduate Medical Education (ACGME) on residents' career satisfaction, emotions and attitudes. Methods A validated survey instrument was used to assess residents' levels of career satisfaction, emotions and attitudes before and after the ACGME duty hour requirements were implemented. The "pre" implementation survey was distributed in December 2002 and the "post" implementation one in December 2004. Only the latter included work-hour related questions. Results The response rates were 56% for the 2002 and 72% for the 2004 surveys respectively. Although career satisfaction remained unchanged, numerous changes occurred in both emotions and attitudes. Compared to those residents who did not violate work-hour requirements, those who did were significantly more negative in attitudes and emotions. Conclusion With the implementation of the ACGME work hour limitations, the training experience became more negative for those residents who violated the work hour limits and had a small positive impact on those who did not violate them. Graduate medical education leaders must innovate to make the experiences for selected residents improved and still maintain compliance with the work hour requirements. PMID:17044940
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Junior doctors' extended work hours and the effects on their performance: the Irish case.
Flinn, Fiona; Armstrong, Claire
2011-04-01
To explore the relationship between junior doctors' long working hours and their performance in a variety of cognitive and clinical decision-making tests. Also, to consider the implications of performance decrements in such tests for healthcare quality. A within-subject design was used to eliminate variation related to individual differences. Each participant was tested twice, once post call and once rested. At each session, participants were tested on cognitive functioning and clinical decision-making. The study was based on six acute Irish hospitals during 2008. Thirty junior hospital doctors, ages ranged from 23 to 30 years; of them, 17 of the participants were female and 13 were male. Measures Cognitive functioning was measured by the MindStreams Global Assessment Battery (NeuroTrax Corp., NY, USA). This is a set of computerized tests, designed for use in medical settings, that assesses performance in memory, executive function, visual spatial perception, verbal function, attention, information processing speed and motor skills. Clinical decision-making was tested using Key Features Problems. Each Key Features Problem consists of a case scenario and then three to four questions about this scenario. In an effort to make it more realistic, the speed with which participants completed the three problems was also recorded. Participants' global cognitive scores, attention, information processing speed and motor skills were significantly worse post call than when rested. They also took longer to complete clinical decision-making questions in the post-call condition and obtained lower scores than when rested. There are significant negative changes in doctors' cognitive functioning and clinical decision-making performance that appear to be attributable to long working hours. This therefore raises the important question of whether working long hours decreases healthcare quality and compromises patient safety.
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Dungan, Kathleen; Hall, Christine; Schuster, Dara; Osei, Kwame
2011-01-01
Objective The objective was to determine the efficacy of an algorithim containing aspart dosed according to carbohydrate intake and one of 3 initial doses of detemir in stable cardiac surgery patients requiring intravenous (IV) insulin. Methods Patients were extubated, off pressors and otherwise stable, requiring at least 1 unit/hr of IV insulin at least 48 hours following surgery. Subjects were randomized to once daily detemir at 50, 65, or 80% of IV basal insulin requirements and received aspart according to carbohydrate intake. The dose of detemir was adjusted daily over 72 hours. Results The number of patients with an initial morning glucose 80–130 mg/dl was 36, 63, and 56% of patients at the 50, 65, and 80% doses (p=0.12) (n=82). However, the mean overall glucose at 24 and 72 hours was similar between groups, and 86, 93, and 92% achieved a mean glucose 80–180 mg/dl at 72 hours (p=0.60). Hypoglycemia (<65 mg/dl) only occurred in the 65% (21%) and 80% (12%) groups over the first 72 hours (p=0.02 in the 50% compared to the 65 and 80% groups combined) with one event <40 mg/dl in the 80% group. There was no loss of glycemic control by the end of the once daily dosing interval. Conclusions Glycemic targets can be achieved without hypoglycemia by 72 hours in most cardiac surgery patients requiring IV insulin with a regimen containing an initial detemir dose of 50% of basal IV insulin requirements and prandial and supplemental insulin. PMID:21550950
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Lima, Jessica Ferraz Carvalho; Lima, Adriano Fonseca; Humel, Maria Malerba Colombi; Paulillo, Luis Alexandre Maffei Sartini; Marchi, Giselle Maria; Ferraz, Caio Cezar Randi
2015-01-01
The aim of this in vitro study was to evaluate the influence of different irrigation protocols on the bond strength, at different root depths, of fiber posts cemented with a self-adhesive cement 24 hours after endodontic treatment. Fifty-six bovine incisor roots were endodontically prepared and separated into 7 groups (n = 8) according to irrigation protocols: group 1, sterile saline (control); group 2, chlorhexidine (CHX) gel 2% and saline; group 3, sodium hypochlorite (NaOCl) 5.25% and saline; group 4, CHX and saline (final irrigation with ethylenediaminetetraacetic acid [EDTA] 17%); group 5, NaOCl and saline (final irrigation with EDTA); group 6, CHX and saline (final irrigation with NaOCl and EDTA); and group 7, NaOCl (final irrigation with CHX and EDTA). No statistically significant difference was found among the groups. Within the limitations of this study, it can be concluded that the different irrigation protocols did not influence the bond strength of self-adhesive resin cement, which presented similar behaviors at the 3 root depths studied.
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Ng, Juki; Chwalisz, Kristof; Carter, David C; Klein, Cheri E
2017-05-01
Elagolix is a nonpeptide, oral gonadotropin-releasing hormone (GnRH) antagonist being developed for sex-hormone-dependent diseases in women. We evaluated the pharmacokinetics and pharmacodynamics of elagolix. This study was a randomized, double-blind, placebo-controlled, multiple-ascending dose study in 45 healthy premenopausal women at a research unit. Elagolix [150 mg once daily or 100, 200, 300, or 400 mg twice daily (BID)] or placebo was administered for 21 days. Main outcome measures were elagolix pharmacokinetics, suppression of gonadotropics [follicle-stimulating hormone (FSH), luteinizing hormone (LH)] and ovarian hormones [estradiol (E2), progesterone (P)], and adverse events. Elagolix was rapidly absorbed after oral dosing, reaching maximum concentrations at 1.0 to 1.5 hours, with a half-life of 4 to 6 hours. FSH, LH, and E2 were suppressed within hours of elagolix administration on day 1. Dose-dependent suppression of E2 was observed, with maximum suppression achieved with elagolix 200 mg BID. Dose-dependent suppression of FSH and LH was also observed, with maximal or near-maximal suppression achieved at 300 mg BID and 200 mg BID, respectively. At elagolix doses ≥100 mg BID, P concentrations remained at anovulatory levels throughout 21 days of dosing. The most frequently reported adverse events were headache and hot flush. Elagolix administration allows for modulation of gonadotropin and ovarian hormone concentrations, from partial suppression at lower doses to nearly full suppression at higher doses. The results of this study provide a rationale for elagolix dose selection for treatment of sex hormone-dependent diseases in women. Copyright © 2017 Endocrine Society
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Extended hours hemodialysis and survival: extended hours, extended evidence?
Wald, Ron; Perl, Jeffrey
2016-12-01
Extended-hours hemodialysis presents another approach to the intensification of therapy for maintenance hemodialysis recipients. Smaller studies have demonstrated several potential benefits with this modality, but the impact on patient-centered outcomes has been unclear. We review the largest published study to compare survival among patients who received extended-hours hemodialysis with those who received conventional hemodialysis. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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Impact of Mobile Dose-Tracking Technology on Medication Distribution at an Academic Medical Center.
Kelm, Matthew; Campbell, Udobi
2016-05-01
Medication dose-tracking technologies have the potential to improve efficiency and reduce costs associated with re-dispensing doses reported as missing. Data describing this technology and its impact on the medication use process are limited. The purpose of this study is to assess the impact of dose-tracking technology on pharmacy workload and drug expense at an academic, acute care medical center. Dose-tracking technology was implemented in June 2014. Pre-implementation data were collected from February to April 2014. Post-implementation data were collected from July to September 2014. The primary endpoint was the percent of re-dispensed oral syringe and compounded sterile product (CSP) doses within the pre- and post-implementation periods per 1,000 discharges. Secondary endpoints included pharmaceutical expense generated from re-dispensing doses, labor costs, and staff satisfaction with the medication distribution process. We observed an average 6% decrease in re-dispensing of oral syringe and CSP doses from pre- to post-implementation (15,440 vs 14,547 doses; p = .047). However, when values were adjusted per 1,000 discharges, this trend did not reach statistical significance (p = .074). Pharmaceutical expense generated from re-dispensing doses was significantly reduced from pre- to post-implementation ($834,830 vs $746,466 [savings of $88,364]; p = .047). We estimated that $2,563 worth of technician labor was avoided in re-dispensing missing doses. We also saw significant improvement in staff perception of technology assisting in reducing missing doses (p = .0003), as well as improvement in effectiveness of resolving or minimizing missing doses (p = .01). The use of mobile dose-tracking technology demonstrated meaningful reductions in both the number of doses re-dispensed and cost of pharmaceuticals dispensed.
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Single dose oral paracetamol (acetaminophen) for postoperative pain in adults
Toms, Laurence; McQuay, Henry J; Derry, Sheena; Moore, R Andrew
2014-01-01
Background This is an updated version of the original Cochrane review published in Issue 1, 2004 - this original review had been split from a previous title on ‘Single dose paracetamol (acetaminophen) with and without codeine for postoperative pain’. The last version of this review concluded that paracetamol is an effective analgesic for postoperative pain, but additional trials have since been published. This review sought to evaluate the efficacy and safety of paracetamol using current data, and to compare the findings with other analgesics evaluated in the same way. Objectives To assess the efficacy of single dose oral paracetamol for the treatment of acute postoperative pain. Search methods We searched The Cochrane Library, MEDLINE, EMBASE, the Oxford Pain Relief Database and reference lists of articles to update an existing version of the review in July 2008. Selection criteria Randomised, double-blind, placebo-controlled clinical trials of paracetamol for acute postoperative pain in adults. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Area under the “pain relief versus time” curve was used to derive the proportion of participants with paracetamol or placebo experiencing at least 50% pain relief over four to six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated, with 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use, were sought as measures of duration of analgesia. Information on adverse events and withdrawals was also collected. Main results Fifty-one studies, with 5762 participants, were included: 3277 participants were treated with a single oral dose of paracetamol and 2425 with placebo. About half of participants treated with paracetamol at standard doses achieved at least 50% pain relief over four to six hours, compared with about 20% treated with placebo. NNTs for at
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Chandasana, Hardik; Prasad, Yarra Durga; Chhonker, Yashpal S; Chaitanya, Telaprolu K; Mishra, Nripendra N; Mitra, Kalyan; Shukla, Praveen K; Bhatta, Rabi S
2014-12-30
Natamycin is the only approved medication for the treatment of mycotic keratitis. Current dosage regimen include one drop of natamycin suspension (5% w/v) instilled in the conjunctival sac at hourly or two hourly intervals for several days which has poor patient compliance. The purpose of the present study was to design a corneal targeted nanoformulation in order to reduce dose and dosing frequency of natamycin and evaluate its pharmacokinetic/pharmacodynamic indices in comparison with clinical marketed preparation. The nanoparticles prepared by nanoprecipitation method were in nanometer size range with high entrapment efficiency and positive surface charge. In-vitro release studies indicated prolonged release of natamycin up to 8h. In-vitro antifungal activity was comparable with marketed preparation. The performance of nanoformulations was evaluated in rabbit eyes. The concentration of natamycin in tear fluid was determined by using LC-MS/MS. The pharmacokinetic parameters such as area under the curve, t½ and mean residence time were significantly higher and clearance was significantly lower for nanoformulations with that of marketed preparation. The optimized dosing schedule to maintain natamycin concentration above tenfold of MIC90 was one instillation in every 5h. Moreover, 1/5th dose reduction of nanoformulation was also effective. Copyright © 2014 Elsevier B.V. All rights reserved.
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Sanchez-Migallon Guzman, David; Flammer, Keven; Papich, Mark G; Grooters, Amy M; Shaw, Shannon; Applegate, Jeff; Tully, Thomas N
2010-04-01
To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). 15 clinically normal adult Hispaniolan Amazon parrots. Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.
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Radiation Dose-rate Reduction Pattern in Well-differentiated Thyroid Cancer Treated with I-131.
Khan, Shahbaz Ahmad; Khan, Muhammad Saqib; Arif, Muhammad; Durr-e-Sabih; Rahim, Muhammad Kashif; Ahmad, Israr
2015-07-01
To determine the patterns of dose rate reduction in single and multiple radioiodine (I-131) therapies in cases of well differentiated thyroid cancer patients. Analytical series. Department of Nuclear Medicine and Radiation Physics, Multan Institute of Nuclear Medicine and Radiotherapy (MINAR), Multan, Pakistan, from December 2006 to December 2013. Ninety three patients (167 therapies) with well differentiated thyroid cancer treated with different doses of I-131 as an in-patient were inducted. Fifty four patients were given only single I-131 therapy dose ranging from 70 mCi (2590 MBq) to 150 mCi (5550 MBq). Thirty nine patients were treated with multiple I-131 radioisotope therapy doses ranging from 80 mCi (2960 MBq) to 250 mCi (9250 MBq). T-test was applied on the sample data showed statistically significant difference between the two groups with p-value (p < 0.01) less than 0.05 taken as significant. There were 68 females and 25 males with an age range of 15 to 80 years. Mean age of the patients were 36 years. Among the 93 cases of first time Radio Active Iodine (RAI) therapy, 59 cases (63%) were discharged after 48 hours. Among 39 patients who received RAI therapy second time or more, most were discharged earlier after achieving acceptable discharge dose rate i.e 25 µSv/hour; 2 out of 39 (5%) were discharged after 48 hours. In 58% patients, given single I-131 therapy dose, majority of these were discharged after 48 hours without any major complications. For well differentiated thyroid cancer patients, rapid dose rate reduction is seen in patients receiving second or subsequent radioiodine (RAI) therapy, as compared to first time receiving RAI therapy.
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Serum tocopherol levels in very preterm infants after a single dose of vitamin E at birth.
Bell, Edward F; Hansen, Nellie I; Brion, Luc P; Ehrenkranz, Richard A; Kennedy, Kathleen A; Walsh, Michele C; Shankaran, Seetha; Acarregui, Michael J; Johnson, Karen J; Hale, Ellen C; Messina, Lynn A; Crawford, Margaret M; Laptook, Abbot R; Goldberg, Ronald N; Van Meurs, Krisa P; Carlo, Waldemar A; Poindexter, Brenda B; Faix, Roger G; Carlton, David P; Watterberg, Kristi L; Ellsbury, Dan L; Das, Abhik; Higgins, Rosemary D
2013-12-01
Our aim was to examine the impact of a single enteral dose of vitamin E on serum tocopherol levels. The study was undertaken to see whether a single dose of vitamin E soon after birth can rapidly increase the low α-tocopherol levels seen in very preterm infants. If so, this intervention could be tested as a means of reducing the risk of intracranial hemorrhage. Ninety-three infants <27 weeks' gestation and <1000 g were randomly assigned to receive a single dose of vitamin E or placebo by gastric tube within 4 hours of birth. The vitamin E group received 50 IU/kg of vitamin E as dl-α-tocopheryl acetate (Aquasol E). The placebo group received sterile water. Blood samples were taken for measurement of serum tocopherol levels by high-performance liquid chromatography before dosing and 24 hours and 7 days after dosing. Eighty-eight infants received the study drug and were included in the analyses. The α-tocopherol levels were similar between the groups at baseline but higher in the vitamin E group at 24 hours (median 0.63 mg/dL vs. 0.42 mg/dL, P = .003) and 7 days (2.21 mg/dL vs 1.86 mg/dL, P = .04). There were no differences between groups in γ-tocopherol levels. At 24 hours, 30% of vitamin E infants and 62% of placebo infants had α-tocopherol levels <0.5 mg/dL. A 50-IU/kg dose of vitamin E raised serum α-tocopherol levels, but to consistently achieve α-tocopherol levels >0.5 mg/dL, a higher dose or several doses of vitamin E may be needed.
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Turner, D; Luzio, S; Gray, B J; Bain, S C; Hanley, S; Richards, A; Rhydderch, D C; Martin, R; Campbell, M D; Kilduff, L P; West, D J; Bracken, R M
2016-04-01
To develop an algorithm that delivers an individualized dose of rapid-acting insulin after morning resistance exercise to counter post-exercise hyperglycaemia in individuals with Type 1 diabetes. Eight people with Type 1 diabetes, aged 34 ± 7 years with HbA1c concentrations 72 ± 12 mmol/mol (8.7 ± 1.1%), attended our laboratory on two separate mornings after fasting, having taken their usual basal insulin the previous evening. These people performed a resistance exercise session comprising six exercises for two sets of 10 repetitions at 60% of the maximum amount of force that was generated in one maximal contraction (60% 1RM). In a randomized and counterbalanced order, the participants were administered an individualized dose of rapid-acting insulin (2 ± 1 units, range 0-4 units) immediately after resistance exercise (insulin session) by means of an algorithm or were not administered this (no-insulin session). Venous blood glucose concentrations were measured for 125 min after resistance exercise. Data (mean ± sem values) were analysed using anova (P ≤ 0.05). Participants had immediate post-resistance exercise hyperglycaemia (insulin session 13.0 ± 1.6 vs. no-insulin session 12.7 ± 1.5 mmol/l; P = 0.834). The decline in blood glucose concentration between peak and 125 min after exercise was greater in the insulin exercise session than in the no-insulin session (3.3 ± 1.0 vs. 1.3 ± 0.4 mmol/l: P = 0.015). There were no episodes of hypoglycaemia (blood glucose <3.9 mmol/l). Administration of rapid-acting insulin according to an individualized algorithm reduced the hyperglycaemia associated with morning resistance exercise without causing hypoglycaemia in the 2 h post-exercise period in people with Type 1 diabetes. © 2015 Diabetes UK.
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A real-time computer model to assess resident work-hours scenarios.
McDonald, Furman S; Ramakrishna, Gautam; Schultz, Henry J
2002-07-01
To accurately model residents' work hours and assess options to forthrightly meet Residency Review Committee-Internal Medicine (RRC-IM) requirements. The requirements limiting residents' work hours are clearly defined by the Accreditation Council for Graduate Medical Education (ACGME) and the RRC-IM: "When averaged over any four-week rotation or assignment, residents must not spend more than 80 hours per week in patient care duties."(1) The call for the profession to realistically address work-hours violations is of paramount importance.(2) Unfortunately, work hours are hard to calculate. We developed an electronic model of residents' work-hours scenarios using Microsoft Excel 97. This model allows the input of multiple parameters (i.e., call frequency, call position, days off, short-call, weeks per rotation, outpatient weeks, clinic day of the week, additional time due to clinic) and start and stop times for post-call, non-call, short-call, and weekend days. For each resident on a rotation, the model graphically demonstrates call schedules, plots clinic days, and portrays all possible and preferred days off. We tested the model for accuracy in several scenarios. For example, the model predicted average work hours of 85.1 hours per week for fourth-night-call rotations. This was compared with logs of actual work hours of 84.6 hours per week. Model accuracy for this scenario was 99.4% (95% CI 96.2%-100%). The model prospectively predicted work hours of 89.9 hours/week in the cardiac intensive care unit (CCU). Subsequent surveys found mean CCU work hours of 88, 1 hours per week. Model accuracy for this scenario was 98% (95% CI 93.2-100%). Thus validated, we then used the model to test proposed scenarios for complying with RRC-IM limits. The flexibility of the model allowed demonstration of the full range of work-hours scenarios in every rotation of our 36-month program. Demonstrations of status-quo work-hours scenarios were presented to faculty as well as real
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Vanderlei, Franciele M; de Albuquerque, Maíra C; de Almeida, Aline C; Machado, Aryane F; Netto, Jayme; Pastre, Carlos M
2017-10-01
Cold water immersion (CWI) is a commonly used recuperative strategy. However there is a lack of standardization of protocols considering the duration and temperature of application of the technique and the stress model. Therefore it is important to study the issue of dose response in a specific stress model. Thus the objective was to analyze and compare the effects of CWI during intense post-exercise recovery using different durations and temperatures of immersion. One hundred and five male individuals were divided into five groups: one control group (CG) and four recovery groups (G1: 5' at 9±1 °C; G2: 5' at 14±1 °C; G3: 15' at 9±1 °C; G4: 15' at 14±1 °C). The volunteers were submitted to an exhaustion protocol that consisted of a jump program and the Wingate Test. Immediately after the exhaustion protocol, the volunteers were directed to a tank with water and ice, where they were immersed for the recovery procedure, during which blood samples were collected for later lactate and creatine kinase (CK) analysis. Variables were collected prior to the exercise and 24, 48, 72, and 96 hours after its completion. For the CK concentration, 15 minutes at 14 °C was the best intervention option, considering the values at 72 hours after exercise, while for the moment of peak lactate an advantage was observed for immersion for 5 minutes at 14 °C. Regarding the perception of recovery, CWI for 5 minutes at 14 °C performed better long-term, from the time of the intervention to 96 hours post-exercise. For pain, no form of immersion responded better than the CG at the immediately post-intervention moment. There were no differences in behavior between the CWI intervention groups for the outcomes studied.
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Yaromina, Ala; Granzier, Marlies; Biemans, Rianne; Lieuwes, Natasja; van Elmpt, Wouter; Shakirin, Georgy; Dubois, Ludwig; Lambin, Philippe
2017-09-01
We tested a novel treatment approach combining (1) targeting radioresistant hypoxic tumour cells with the hypoxia-activated prodrug TH-302 and (2) inverse radiation dose-painting to boost selectively non-hypoxic tumour sub-volumes having no/low drug uptake. 18 F-HX4 hypoxia tracer uptake measured with a clinical PET/CT scanner was used as a surrogate of TH-302 activity in rhabdomyosarcomas growing in immunocompetent rats. Low or high drug uptake volume (LDUV/HDUV) was defined as 40% of the GTV with the lowest or highest 18 F-HX4 uptake, respectively. Two hours post TH-302/saline administration, animals received either single dose radiotherapy (RT) uniformly (15 or 18.5Gy) or a dose-painted non-uniform radiation (15Gy) with 50% higher dose to LDUV or HDUV (18.5Gy). Treatment plans were created using Eclipse treatment planning system and radiation was delivered using VMAT. Tumour response was quantified as time to reach 3 times starting tumour volume. Non-uniform RT boosting tumour sub-volume with low TH-302 uptake (LDUV) was superior to the same dose escalation to HDUV (p<0.0001) and uniform RT with the same mean dose 15Gy (p=0.0077). Noteworthy, dose escalation to LDUV required on average 3.5Gy lower dose to the GTV to achieve similar tumour response as uniform dose escalation. The results support targeted dose escalation to non-hypoxic tumour sub-volume with no/low activity of hypoxia-activated prodrugs. This strategy applies on average a lower radiation dose and is as effective as uniform dose escalation to the entire tumour. It could be applied to other type of drugs provided that their distribution can be imaged. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.
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Radiation dose to the global flying population.
Alvarez, Luis E; Eastham, Sebastian D; Barrett, Steven R H
2016-03-01
Civil airliner passengers and crew are exposed to elevated levels of radiation relative to being at sea level. Previous studies have assessed the radiation dose received in particular cases or for cohort studies. Here we present the first estimate of the total radiation dose received by the worldwide civilian flying population. We simulated flights globally from 2000 to 2013 using schedule data, applying a radiation propagation code to estimate the dose associated with each flight. Passengers flying in Europe and North America exceed the International Commission on Radiological Protection annual dose limits at an annual average of 510 or 420 flight hours per year, respectively. However, this falls to 160 or 120 h on specific routes under maximum exposure conditions.
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Pergolide: multiple-dose pharmacokinetics in patients with mild to moderate Parkinson disease.
Thalamas, Claire; Rajman, Iris; Kulisevsky, Jaime; Lledó, Alberto; Mackie, Alison E; Blin, Olivier; Gillespie, Todd A; Seger, Mary; Rascol, Olivier
2005-01-01
The primary objective of this study was to describe the pharmacokinetics of oral pergolide in patients with mild to moderate Parkinson disease using a new high-performance liquid chromatography-tandem mass spectrometry assay. A secondary objective was to investigate the relationship between plasma concentrations and efficacy. Fourteen patients with a diagnosis of Parkinson disease completed this multicenter, open-label, dose-escalating study. Pergolide was administered for 58 days, using increasing daily doses from 0.05 mg daily up to 1 mg three times daily and then tapering the dose. The steady-state pharmacokinetic profile and motor score were determined at dose levels of 0.25, 0.5, and 1 mg three times a day and during elimination after the last dose. Pergolide was absorbed with a median time to maximum concentration of 2 to 3 hours across the dose range. Systemic exposure appeared to increase proportionally with dose over the range of 0.25 to 1 mg three times daily within a patient, but there was a large variability in exposures between patients (interpatient coefficients of variation were 56.4% for the area under the curve). Pergolide was widely distributed (volume of distribution, approximately 14,000 L) and was eliminated with a mean half-life of 21 hours. Motor scores improved as both peak plasma pergolide concentrations and exposure increased. No unexpected safety concerns were identified. Pergolide is absorbed relatively quickly into the systemic circulation, has a large apparent volume of distribution, and has a relatively long half-life (mean, 21 hours). This prolonged half-life is of particular interest, given the current hypothesis that more continuous dopaminergic receptor stimulation may reduce motor complications in patients with Parkinson disease.
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Polis, Ingeborgh; Dockx, Robrecht; Vlerick, Lise; Dobbeleir, Andre; Goethals, Ingeborg; Saunders, Jimmy; Sadones, Nele; Baeken, Chris; De Vos, Filip; Peremans, Kathelijne
2017-01-01
Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended. PMID:28644875
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Taylor, Olivia; Van Laeken, Nick; Polis, Ingeborgh; Dockx, Robrecht; Vlerick, Lise; Dobbeleir, Andre; Goethals, Ingeborg; Saunders, Jimmy; Sadones, Nele; Baeken, Chris; De Vos, Filip; Peremans, Kathelijne
2017-01-01
Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended.
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Battes, Linda C; Pedersen, Susanne S; Oemrawsingh, Rohit M; van Geuns, Robert J; Al Amri, Ibtihal; Regar, Evelyn; de Jaegere, Peter P T; Serruys, Patrick; van Domburg, Ron T
2012-02-01
Beta blocker therapy may induce depressive symptoms, although current evidence is conflicting. We examined the association between beta blocker therapy and depressive symptoms in percutaneous coronary intervention (PCI) patients and the extent to which there is a dose-response relationship between beta blocker dose and depressive symptoms. Patients treated with PCI (N=685) completed the depression scale of the Hospital Anxiety and Depression Scale 1 and 12 months post PCI. Information about type and dose of beta blocker use was extracted from medical records. Of all patients, 68% (466/685) were on beta blocker therapy at baseline. In adjusted analysis, beta blocker use at 1 month post PCI (OR: 0.82; 95% CI: 0.53-1.26) was not significantly associated with depressive symptoms. At 12 months post PCI, there was a significant relationship between beta blocker use and depressive symptoms (OR: 0.51; 95% CI: 0.31-0.84), with beta blocker therapy associated with a 49% risk reduction in depressive symptoms. There was a dose-response relationship between beta blocker dose and depressive symptoms 12 months post PCI, with the risk reduction in depressive symptoms in relation to a low dose being 36% (OR: 0.64; 95% CI: 0.37-1.10) and 58% (OR: 0.42; 95% CI: 0.24-0.76) in relation to a high dose. Patients treated with beta blocker therapy were less likely to experience depressive symptoms 12 months post PCI, with there being a dose-response relationship with a higher dose providing a more pronounced protective effect. Copyright © 2011 Elsevier B.V. All rights reserved.
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Lower Dose of Prostate Cancer Drug with Food
In a small clinical trial, researchers compared the efficacy of a low dose of the cancer drug abiraterone (Zytiga) taken with a low-fat breakfast with a full dose taken on an empty stomach, as directed on the drug’s label. Learn what they found in this Cancer Currents blog post.
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Gloude, Nicholas J; Jodele, Sonata; Teusink-Cross, Ashley; Grimley, Michael; Davies, Stella M; Lane, Adam; Myers, Kasiani C
2018-01-01
Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplant (HSCT), with high mortality in severe cases and until recently very limited therapeutic options consisting largely of supportive care. Defibrotide was recently approved in the United States for the treatment of severe VOD in patients with renal or pulmonary dysfunction after HSCT. Our group previously published on the use of high-dose methylprednisolone (500 mg/m 2 per dose every 12 hours for 6 doses) in patients with VOD, showing good success. A small subset of these individuals were also treated with defibrotide, but additional studies using the combination of high-dose methylprednisolone and defibrotide for the treatment of VOD are lacking. We present a single-institution retrospective chart review of 15 HSCT patients with VOD treated with the combination of high-dose methylprednisolone and defibrotide. VOD developed at a median of 17 days post-HSCT, and combination therapy was initiated within 1 day of VOD diagnosis. Twelve of 15 patients (80%) had multiorgan failure. Our single-center experience using both high-dose methylprednisolone and defibrotide showed a day +100 survival rate of 73% and an overall VOD complete resolution rate of 66.7%, higher than the rates reported in the recent literature using defibrotide alone (40% to 50% day +100 overall survival). These data suggest that the combination of high-dose steroids and defibrotide may be superior to defibrotide alone and warrant further investigation. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
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A clinical audit cycle of post-operative hypothermia in dogs.
Rose, N; Kwong, G P S; Pang, D S J
2016-09-01
Use of clinical audits to assess and improve perioperative hypothermia management in client-owned dogs. Two clinical audits were performed. In Audit 1 data were collected to determine the incidence and duration of perioperative hypothermia (defined as rectal temperatures <37·0°C). The results from Audit 1 were used to reach consensus on changes to be implemented to improve temperature management, including re-defining hypothermia as rectal temperature <37·5°C. Audit 2 was performed after 1 month with changes in place. Audit 1 revealed a high incidence of post-operative hypothermia (88·0%) and prolonged time periods (7·5 hours) to reach normothermia. Consensus changes were to use a forced air warmer on all dogs and measure rectal temperatures hourly post-operatively until temperature ≥37·5°C. After 1 month with the implemented changes, Audit 2 identified a significant reduction in the time to achieve a rectal temperature of ≥37·5°C, with 75% of dogs achieving this goal by 3·5 hours. The incidence of hypothermia at tracheal extubation remained high in Audit 2 (97·3% with a rectal temperature <37·5°C). Post-operative hypothermia was improved through simple changes in practice, showing that clinical audit is a useful tool for monitoring post-operative hypothermia and improving patient care. Overall management of perioperative hypothermia could be further improved with earlier intervention. © 2016 British Small Animal Veterinary Association.
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Bae, Sung-Heui; Yoon, Jangho
2014-10-01
To examine the degree to which states' work hour regulations for nurses-policies regarding mandatory overtime and consecutive work hours-decrease mandatory overtime practice and hours of work among registered nurses. We analyzed a nationally representative sample of registered nurses from the National Sample Survey of Registered Nurses for years 2004 and 2008. We obtained difference-in-differences estimates of the effect of the nurse work hour policies on the likelihood of working mandatory overtime, working more than 40 hours per week, and working more than 60 hours per week for all staff nurses working in hospitals and nursing homes. The mandatory overtime and consecutive work hour regulations were significantly associated with 3.9 percentage-point decreases in the likelihood of working overtime mandatorily and 11.5 percentage-point decreases in the likelihood of working more than 40 hours per week, respectively. State mandatory overtime and consecutive work hour policies are effective in reducing nurse work hours. The consecutive work hour policy appears to be a better regulatory tool for reducing long work hours for nurses. © Health Research and Educational Trust.
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Bae, Sung-Heui; Yoon, Jangho
2014-01-01
Objectives To examine the degree to which states’ work hour regulations for nurses—policies regarding mandatory overtime and consecutive work hours—decrease mandatory overtime practice and hours of work among registered nurses. Methods We analyzed a nationally representative sample of registered nurses from the National Sample Survey of Registered Nurses for years 2004 and 2008. We obtained difference-in-differences estimates of the effect of the nurse work hour policies on the likelihood of working mandatory overtime, working more than 40 hours per week, and working more than 60 hours per week for all staff nurses working in hospitals and nursing homes. Principal Findings The mandatory overtime and consecutive work hour regulations were significantly associated with 3.9 percentage-point decreases in the likelihood of working overtime mandatorily and 11.5 percentage-point decreases in the likelihood of working more than 40 hours per week, respectively. Conclusions State mandatory overtime and consecutive work hour policies are effective in reducing nurse work hours. The consecutive work hour policy appears to be a better regulatory tool for reducing long work hours for nurses. PMID:24779701
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Zhang, Haiying; Jiao, Ling; Cui, Songye; Wang, Liang; Tan, Jian; Zhang, Guizhi; He, Yajing; Ruan, Shuzhou; Fan, Saijun; Zhang, Wenyi
2014-01-01
Radiation safety is an integral part of targeted radionuclide therapy. The aim of this work was to study the external dose rate and retained body activity as functions of time in differentiated thyroid carcinoma patients receiving 131I therapy. Seventy patients were stratified into two groups: the ablation group (A) and the follow-up group (FU). The patients’ external dose rate was measured, and simultaneously, their retained body radiation activity was monitored at various time points. The equations of the external dose rate and the retained body activity, described as a function of hours post administration, were fitted. Additionally, the release time for patients was calculated. The reduction in activity in the group receiving a second or subsequent treatment was more rapid than the group receiving only the initial treatment. Most important, an expeditious method was established to indirectly evaluate the retained body activity of patients by measuring the external dose rate with a portable radiation survey meter. By this method, the calculated external dose rate limits are 19.2, 8.85, 5.08 and 2.32 μSv·h−1 at 1, 1.5, 2 and 3 m, respectively, according to a patient’s released threshold level of retained body activity <400 MBq. This study is beneficial for radiation safety decision-making. PMID:25337944
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Work shift duration: a review comparing eight hour and 12 hour shift systems.
Smith, L; Folkard, S; Tucker, P; Macdonald, I
1998-04-01
Shiftwork is now a major feature of working life across a broad range of industries. The features of the shift systems operated can impact on the wellbeing, performance, and sleep of shiftworkers. This paper reviews the current state of knowledge on one major characteristic of shift rotas-namely, shift duration. Evidence comparing the relative effects of eight hour and 12 hour shifts on fatigue and job performance, safety, sleep, and physical and psychological health are considered. At the organisational level, factors such as the mode of system implementation, attitudes towards shift rotas, sickness absence and turnover, overtime, and moonlighting are discussed. Manual and electronic searches of the shiftwork research literature were conducted to obtain information on comparisons between eight hour and 12 hour shifts. The research findings are largely equivocal. The bulk of the evidence suggests few differences between eight and 12 hour shifts in the way they affect people. There may even be advantages to 12 hour shifts in terms of lower stress levels, better physical and psychological wellbeing, improved durations and quality of off duty sleep as well as improvements in family relations. On the negative side, the main concerns are fatigue and safety. It is noted that a 12 hour shift does not equate with being active for only 12 hours. There can be considerable extension of the person's time awake either side of the shift. However, the effects of longer term exposure to extended work days have been relatively uncharted in any systematic way. Longitudinal comparative research into the chronic impact of the compressed working week is needed.
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Le Brigand, H; Morille, P; Garnier, B; Bogaty-Yver, J; Samama, M; Spriet, A
A comparative clinical trial was undertaken in 2420 patients undergoing thoracic surgery during a 4-year period (1973-1977); 40% of the patients had bronchial cancer. Random allocation was not considered as being possible by the surgeons and was replaced by allocation according to the time of operation. There were three protocol groups: Protocol A: First morning operations (1007 patients): subcutaneous calcium heparin, 5000 units (Ul) 2 hours and 30 minutes before surgery then every 12 hours for 15 days. Protocol B: Second morning operations (932 patients): same dose and duration of treatment; the first injection took place 24 to 72 hours after the surgical procedure. The doses were increased from the fourth day after surgery in order to obtain a moderately prolonged partial thromboplastin time (difference patient-control: 7 to 14 seconds). Protocol 0: 481 patients received no anticoagulant treatment because of a contraindication or minor surgical procedure. Preliminary results showed and increase of per-operative bleeding (p less than 0.01) in treated patients; this was very well accepted by the surgeons. Among the heparin-treated patients, 11 pulmonary emboli out of 13 were observed in patients with bronchial cancer. Of these 13, 10 were fatal with 9 being verified at autopsy. The pulmonary emboli episodes occurred significantly earlier in protocol B than in protocol A. Fatal pulmonary embolism in patients with bronchial cancer was significantly more frequent in protocol B (7 cases) than in protocol A (1 case); P less than 0.01. These results have shown a low frequency of fatal pulmonary emboli in patients without bronchial cancer receiving twice-daily subcutaneous injections of heparin (2 of 1102 operated subjects). The rate was higher in patients with bronchial cancer and this results supports a recommended thrice-daily dose in such patients. In addition, the pre-operative administration of heparin is useful in preventing early post-operative pulmonary embolism.
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Huss, Michael; Ginsberg, Ylva; Arngrim, Torben; Philipsen, Alexandra; Carter, Katherine; Chen, Chien-Wei; Gandhi, Preetam; Kumar, Vinod
2014-09-01
In the management of attention-deficit hyperactivity disorder (ADHD) in adults it is important to recognize that individual patients respond to a wide range of methylphenidate doses. Studies with methylphenidate modified release long acting (MPH-LA) in children have reported the need for treatment optimization for improved outcomes. We report the results from a post hoc analysis of a 5-week dose optimization phase from a large randomized, placebo-controlled, multicenter 40-week study (9-week double-blind dose confirmation phase, 5-week open-label dose optimization phase, and 26-week double-blind maintenance of effect phase). Patients entering the open-label dose optimization phase initiated treatment with MPH-LA 20 mg/day; up/down titrated to their optimal dose (at which there was balance between control of symptoms and side effects) of 40, 60, or 80 mg/day in increments of 20 mg/week by week 12 or 13. Safety was assessed by monitoring the adverse events (AEs) and serious AEs. Efficacy was assessed by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Attention-Deficit Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores. At the end of the dose confirmation phase, similar numbers of patients were treated optimally with each of the 40, 60, and 80 mg/day doses (152, 177, and 160, respectively) for MPH-LA. Mean improvement from baseline in the dose confirmation phase in total scores of DSM-IV ADHD RS and SDS were 23.5 ± 9.90 and 9.7 ± 7.36, respectively. Dose optimization with MPH-LA (40, 60, or 80 mg/day) improved treatment outcomes and was well-tolerated in adult ADHD patients.
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Luo, Rosa; Bozigian, Haig; Jimenez, Roland; Loewen, Gordon; O'Brien, Christopher F
2017-08-01
Valbenazine (VBZ) is a vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia. The safety, tolerability and pharmacokinetics of VBZ following single and repeat once-daily (QD) dosing were evaluated in 2 randomized, single-center, double-blind studies in healthy male subjects. In the first study, 2 cohorts of 8 subjects were administered single doses (SD) of placebo (PBO; N = 2/period) or VBZ (N = 6/period; 1, 2, 5, or 12.5 mg for Cohort 1 and 12.5, 25, 50, or 75 mg for Cohort 2) using a sequential escalation scheme. The second study consisted of 2 phases. In the initial phase, subjects were administered SD PBO (N = 2/period) or VBZ (N = 6/period; 75, 100, 125 or 150 mg) with sequential escalation. In the second phase, subjects received PBO, or 50 or 100 mg VBZ (N = 4:8:8) QD for 8 days (Cohort 1) or PBO or 50 mg VBZ (N = 6:6) QD for 8 days (Cohort 2). For both studies, plasma concentrations of VBZ and its active metabolite, NBI-98782, were determined. Safety was assessed throughout the studies. PK parameters were determined using noncompartmental methods. In both studies, VBZ was rapidly absorbed with peak concentrations typically observed within 1.5 hours. Peak NBI-98782 concentrations were typically observed at 4.0 to 9.0 hours. Terminal elimination half-life for both VBZ and NBI-98782 was ~20 hours. Across the 1 to 150 mg SD range evaluated across the studies, VBZ and NBI-98782 C max and AUC increased dose-proportionally from 50 to 150 mg and more than dose-proportionally from 1 to 50 mg. QD VBZ and NBI-98782 C max and AUC parameters were also dose-proportional between the 50 and 100 mg doses. Steady-state for both analytes appeared to be achieved by Day 8. The accumulation index was ~1.5 for VBZ and ~2.5 for NBI-98782. Peak to trough fluctuation was approximately 250% for VBZ and 70% for NBI-98782. Across both studies, NBI-98782 exposure was approximately 20%-30% that of VBZ based on molar ratios. In the first study
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Luo, Rosa; Bozigian, Haig; Jimenez, Roland; Loewen, Gordon; O’Brien, Christopher F.
2017-01-01
Valbenazine (VBZ) is a vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia. The safety, tolerability and pharmacokinetics of VBZ following single and repeat once-daily (QD) dosing were evaluated in 2 randomized, single-center, double-blind studies in healthy male subjects. In the first study, 2 cohorts of 8 subjects were administered single doses (SD) of placebo (PBO; N = 2/period) or VBZ (N = 6/period; 1, 2, 5, or 12.5 mg for Cohort 1 and 12.5, 25, 50, or 75 mg for Cohort 2) using a sequential escalation scheme. The second study consisted of 2 phases. In the initial phase, subjects were administered SD PBO (N = 2/period) or VBZ (N = 6/period; 75, 100, 125 or 150 mg) with sequential escalation. In the second phase, subjects received PBO, or 50 or 100 mg VBZ (N = 4:8:8) QD for 8 days (Cohort 1) or PBO or 50 mg VBZ (N = 6:6) QD for 8 days (Cohort 2). For both studies, plasma concentrations of VBZ and its active metabolite, NBI-98782, were determined. Safety was assessed throughout the studies. PK parameters were determined using noncompartmental methods. In both studies, VBZ was rapidly absorbed with peak concentrations typically observed within 1.5 hours. Peak NBI-98782 concentrations were typically observed at 4.0 to 9.0 hours. Terminal elimination half-life for both VBZ and NBI-98782 was ~20 hours. Across the 1 to 150 mg SD range evaluated across the studies, VBZ and NBI-98782 Cmax and AUC increased dose-proportionally from 50 to 150 mg and more than dose-proportionally from 1 to 50 mg. QD VBZ and NBI-98782 Cmax and AUC parameters were also dose-proportional between the 50 and 100 mg doses. Steady-state for both analytes appeared to be achieved by Day 8. The accumulation index was ~1.5 for VBZ and ~2.5 for NBI-98782. Peak to trough fluctuation was approximately 250% for VBZ and 70% for NBI-98782. Across both studies, NBI-98782 exposure was approximately 20%–30% that of VBZ based on molar ratios. In the first study
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Onset of Labor in Post-Term Pregnancy by Chamomile.
Gholami, Fereshte; Neisani Samani, Leila; Kashanian, Maryam; Naseri, Mohsen; Hosseini, Agha Fateme; Hashemi Nejad, Seyed Abbas
2016-11-01
Post-term pregnancy is an important factor in perinatal mortality and morbidity. Generally, to reduce perinatal mortality in pregnancy, the delivery is done before adverse perinatal morbidity occurs. To prevent prolonged pregnancy, labor is induced with chemical drugs and complementary therapies. Due to the side effects and contraindications of chemical medicine, the use of herbs has been investigated in the induction of labor in post-term pregnancy. This study was done to identify the effect of chamomile on inducing labor in women with post-term pregnancy of Shahid Akbarabadi hospital in Tehran in 2013. This double-blind clinical trial study was performed in Iran on 80 post-term pregnant women with a gestational age of 40 weeks or more, a single pregnancy, 18 - 35 years old, cephalic presentation, an estimated fetal weight of 2500 - 4000 grams, an absence of uterine contraction, a cervical Bishop score of less than 4, the safety of the membrane, and low-risk pregnancy; they were randomly assigned to one of two groups of 40 women. Each of the participants was given a bottle containing 42 capsules (500 mg each) and took 2 capsules every 8 hours. The data were collected through the questionnaire of demographic observational, and examinal characteristics. Descriptive statistics, independent samples t-test, and Fisher's exact test using SPSS (16/win) were used to determine and compare the effects of drugs on inducing labor in the groups. After a week of using the first dose, the results showed that in 92.5% of the chamomile group and 62.5% in the placebo group, delivery symptoms started after taking the oral capsules, and there were significant statistical differences between the two groups for the onset of labor (P = 0.003) There was a noticeable statistical difference between the two groups regarding the mean interval time to the onset of labor pain after taking the capsules (P = 0.000). In this study¸ chamomile stimulated labor in post-term pregnancy. With further
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Onset of Labor in Post-Term Pregnancy by Chamomile
Gholami, Fereshte; Neisani Samani, Leila; Kashanian, Maryam; Naseri, Mohsen; Hosseini, Agha Fateme; Hashemi Nejad, Seyed Abbas
2016-01-01
Background Post-term pregnancy is an important factor in perinatal mortality and morbidity. Generally, to reduce perinatal mortality in pregnancy, the delivery is done before adverse perinatal morbidity occurs. To prevent prolonged pregnancy, labor is induced with chemical drugs and complementary therapies. Due to the side effects and contraindications of chemical medicine, the use of herbs has been investigated in the induction of labor in post-term pregnancy. Objectives This study was done to identify the effect of chamomile on inducing labor in women with post-term pregnancy of Shahid Akbarabadi hospital in Tehran in 2013. Patients and Methods This double-blind clinical trial study was performed in Iran on 80 post-term pregnant women with a gestational age of 40 weeks or more, a single pregnancy, 18 - 35 years old, cephalic presentation, an estimated fetal weight of 2500 - 4000 grams, an absence of uterine contraction, a cervical Bishop score of less than 4, the safety of the membrane, and low-risk pregnancy; they were randomly assigned to one of two groups of 40 women. Each of the participants was given a bottle containing 42 capsules (500 mg each) and took 2 capsules every 8 hours. The data were collected through the questionnaire of demographic observational, and examinal characteristics. Descriptive statistics, independent samples t-test, and Fisher’s exact test using SPSS (16/win) were used to determine and compare the effects of drugs on inducing labor in the groups. Results After a week of using the first dose, the results showed that in 92.5% of the chamomile group and 62.5% in the placebo group, delivery symptoms started after taking the oral capsules, and there were significant statistical differences between the two groups for the onset of labor (P = 0.003) There was a noticeable statistical difference between the two groups regarding the mean interval time to the onset of labor pain after taking the capsules (P = 0.000). Conclusions In this study
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Fixed Costs and Hours Constraints
ERIC Educational Resources Information Center
Johnson, William R.
2011-01-01
Hours constraints are typically identified by worker responses to questions asking whether they would prefer a job with more hours and more pay or fewer hours and less pay. Because jobs with different hours but the same rate of pay may be infeasible when there are fixed costs of employment or mandatory overtime premia, the constraint in those…
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Registrar working hours in Cape Town.
Vadia, S; Kahn, D
2005-08-01
The number of hours worked by general surgical registrars in Europe and the USA has been reduced so as to reduce fatigue and the possibility of errors. The impact of these restrictions on surgical training remains unresolved. To date there are no officially reported data on the number of hours worked by registrars in South Africa. The aim of this study was to document the hours worked by registrars in general surgery in Cape Town. Thirty-three general surgical registrars at the University of Cape Town were asked to complete a time sheet over a 2-week period, indicating hours spent in hospital as part of a normal working day, hours spent in hospital outside of a normal day, hours at home on 'cold call' and hours off duty. Of the 33 registrars, 25 completed the time sheet. Registrars at Groote Schuur Hospital worked an average of 105 hours per week (68 hours in hospital and 37 hours on call at home). Registrars at New Somerset Hospital worked 79 hours per week (70 hours on site), while registrars at Red Cross Children's Hospital, G. F. Jooste Hospital and the Trauma Unit worked 60 - 69 hours per week. In the Surgical Intensive Care Unit (SICU) registrars worked 75 hours per week. In conclusion, general surgical registrars at the University of Cape Town work hours in excess of European and American work-hour restrictions.
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Ng, Juki; Rogosheske, John; Barker, Juliet; Weisdorf, Daniel; Jacobson, Pamala A
2006-06-01
Renal transplant patients with suboptimal mycophenolic acid (MPA) areas under the curves (AUCs) are at greater risk of acute rejection. In hematopoietic cell transplantation, a low MPA AUC is also associated with a higher incidence of acute graft versus host disease. Therefore, a limited sampling model was developed and validated to simultaneously estimate total and unbound MPA AUC0-12 in hematopoietic cell transplantation patients. Intensive pharmacokinetic sampling was performed at steady state between days 3 to 7 posttransplant in 73 adult subjects while receiving prophylactic mycophenolate mofetil 1 g per 12 hours orally or intravenously plus cyclosporine. Total and unbound MPA plasma concentrations were measured, and total and unbound AUC0-12 was determined using noncompartmental analysis. Regression analysis was then performed to build IV and PO, total and unbound AUC0-12 models from the first 34 subjects. The predictive performance of these models was tested in the next 39 subjects. Trough concentrations poorly estimate observed total and unbound AUC0-12 (r<0.48). A model with 3 concentrations (2-, 4-, and 6-hour post start of infusion) best estimated observed total and unbound AUC0-12 after IV dosing (r>0.99). Oral total and unbound AUC0-12 was more difficult to estimate and required at least 4 concentrations (0-, 1-, 2-, and 6-hour post dose) in the model (r>0.85). The predictive performance of the final models was good. Eighty-three percent of IV and 70% of PO AUC0-12 predictions fell within +/-20% of the observed values without significant bias. Trough MPA concentrations do not accurately describe MPA AUC0-12. Three intravenous (2-, 4-, 6-hour post start of infusion) or 4 oral (0-, 1-, 2-, and 6-hour post dose) MPA plasma concentrations measured over a 12-hour dosing interval will estimate the total and unbound AUC0-12 nearly as well as intensive pharmacokinetic sampling with good precision and low bias. This approach simplifies AUC0-12 targeting of MPA
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Behavioral effects of microwaves: relationship of total dose and dose rate
DOE Office of Scientific and Technical Information (OSTI.GOV)
O'Connor, M.E.; Strattan, R.
1988-10-01
The goal of the research was to compare the relationship of whole-body averaged specific absorption rate (SAR) and specific absorption (SA) to determine whether dose rate or dose was the better predictor of biological effects. Sperm-positive Long-Evans female rats were exposed to 2450-MHz CW microwave radiation for 1-3 hours at approximately 10 W/kg. The maternal subjects were then observed for natural delivery of their litters. Sensitivity to thermally induced seizures and huddling were studied in the offspring. Analyses revealed that there were no statistically significant differences between exposed and control offspring on the behavioral indices. The behavior did not appearmore » to be affected by prenatal exposure to microwave radiation at this level. The huddle sizes became smaller as the pups aged both in exposed and control offspring.« less
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Work shift duration: a review comparing eight hour and 12 hour shift systems
Smith, L.; Folkard, S.; Tucker, P.; Macdonald, I.
1998-01-01
OBJECTIVES: Shiftwork is now a major feature of working life across a broad range of industries. The features of the shift systems operated can impact on the wellbeing, performance, and sleep of shiftworkers. This paper reviews the current state of knowledge on one major characteristic of shift rotas-namely, shift duration. Evidence comparing the relative effects of eight hour and 12 hour shifts on fatigue and job performance, safety, sleep, and physical and psychological health are considered. At the organisational level, factors such as the mode of system implementation, attitudes towards shift rotas, sickness absence and turnover, overtime, and moonlighting are discussed. METHODS: Manual and electronic searches of the shiftwork research literature were conducted to obtain information on comparisons between eight hour and 12 hour shifts. RESULTS: The research findings are largely equivocal. The bulk of the evidence suggests few differences between eight and 12 hour shifts in the way they affect people. There may even be advantages to 12 hour shifts in terms of lower stress levels, better physical and psychological wellbeing, improved durations and quality of off duty sleep as well as improvements in family relations. On the negative side, the main concerns are fatigue and safety. It is noted that a 12 hour shift does not equate with being active for only 12 hours. CONCLUSIONS: There can be considerable extension of the person's time awake either side of the shift. However, the effects of longer term exposure to extended work days have been relatively uncharted in any systematic way. Longitudinal comparative research into the chronic impact of the compressed working week is needed. PMID:9624275
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Jafarzadeh, Naser; Mani-Varnosfaderani, Ahmad; Gilany, Kambiz; Eynali, Samira; Ghaznavi, Habib; Shakeri-Zadeh, Ali
2018-03-01
Radiotherapy is one of the main modalities of cancer treatment. The utility of Raman spectroscopy (RS) for detecting the distinct radiobiological responses in human cancer cells is currently under investigation. RS holds great promises to provide good opportunities for personalizing radiotherapy treatments. Here, we report the effects of the radiation dose and post-irradiation time on the molecular changes in the human breast cancer SKBR3 cells, using RS. The SKBR3 cells were irradiated by gamma radiation with different doses of 0, 1, 2, 4, and 6 Gy. The Raman signals were acquired 24 and 48 h after the gamma radiation. The collected Raman spectra were analyzed by different statistical methods such as principal component analysis, linear discriminant analysis, and genetic algorithm. A thorough analysis of the obtained Raman signals revealed that 2 Gy of gamma radiation induces remarkable molecular and structural changes in the SKBR3 cells. We found that the wavenumbers in the range of 1000-1400 cm -1 in Raman spectra are selective for discriminating between the effects of the different doses of irradiation. The results also revealed that longer post-irradiation time leads to the relaxation of the cells to their initial state. The molecular changes that occurred in the 2Gy samples were mostly reversible. On the other hand, the exposure to doses higher than 4Gy induced serious irreversible changes, mainly seen in 2700-2800 cm -1 in Raman spectra. The classification models developed in this study would help to predict the radiation-based molecular changes induced in the cancer cells by only using RS. Also, this designed framework may facilitate the process of biodosimetry. Copyright © 2018 Elsevier B.V. All rights reserved.
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Dong, Xiang; Hu, Rong; Sun, Yu; Li, Qifang; Jiang, Hong
2013-09-01
Isoflurane (ISO) has been shown to attenuate acute lung injury (ALI). Induction of heme oxygenase-1 (HO-1) and suppression of inducible nitric oxide synthase (iNOS) expression provide cytoprotection in lung and vascular injury. The aim of this study was to investigate the effect of post-treatment with isoflurane on lung vascular permeability and the role of HO-1 in an ALI rat model induced by cecal ligation and puncture (CLP). Male Sprague-Dawley rats were randomly assigned to one of four groups: sham group, sham rats post-treated with vehicle (Sham); CLP group, CLP rats post-treated with vehicle (CLP); ISO group, CLP rats post-treated with isoflurane (ISO); and ZnPP group, CLP rats injected with zinc protoporphyrin IX (ZnPP), a competitive inhibitor of HO-1, 1 hour before the operation, and post-treated with isoflurane (ZnPP). Isoflurane (1.4%) was administered 2 hour after CLP. At 24 hour after CLP, the extent of ALI was evaluated by lung wet/dry ratio, Evans blue dye (EBD) extravasation, lung permeability index (LPI), as well as histological and immunohistochemical examinations. We also determined pulmonary iNOS and HO-1 expression. Compared with the CLP group, the isoflurane post-treatment group showed improved pulmonary microvascular permeability as detected by EBD extravasation, LPI, as well as histological and immunohistochemical examinations. Furthermore, isoflurane decreased iNOS and increased HO-1 expression in lung tissue. Pretreatment with ZnPP prevented the protective effects of isoflurane in rats. These findings indicate that the protective role of isoflurane post-conditioning against CLP-induced lung injury may be associated with its role in upregulating HO-1 in ALI.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hardin, M; Elson, H; Lamba, M
2014-06-01
Purpose: To quantify the clinically observed dose enhancement adjacent to cranial titanium fixation plates during post-operative radiotherapy. Methods: Irradiation of a titanium burr hole cover was simulated using Monte Carlo code MCNPX for a 6 MV photon spectrum to investigate backscatter dose enhancement due to increased production of secondary electrons within the titanium plate. The simulated plate was placed 3 mm deep in a water phantom, and dose deposition was tallied for 0.2 mm thick cells adjacent to the entrance and exit sides of the plate. These results were compared to a simulation excluding the presence of the titanium tomore » calculate relative dose enhancement on the entrance and exit sides of the plate. To verify simulated results, two titanium burr hole covers (Synthes, Inc. and Biomet, Inc.) were irradiated with 6 MV photons in a solid water phantom containing GafChromic MD-55 film. The phantom was irradiated on a Varian 21EX linear accelerator at multiple gantry angles (0–180 degrees) to analyze the angular dependence of the backscattered radiation. Relative dose enhancement was quantified using computer software. Results: Monte Carlo simulations indicate a relative difference of 26.4% and 7.1% on the entrance and exit sides of the plate respectively. Film dosimetry results using a similar geometry indicate a relative difference of 13% and -10% on the entrance and exit sides of the plate respectively. Relative dose enhancement on the entrance side of the plate decreased with increasing gantry angle from 0 to 180 degrees. Conclusion: Film and simulation results demonstrate an increase in dose to structures immediately adjacent to cranial titanium fixation plates. Increased beam obliquity has shown to alleviate dose enhancement to some extent. These results are consistent with clinically observed effects.« less
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Leeman-Neill, Rebecca J.; Brenner, Alina V.; Little, Mark P.; Bogdanova, Tetiana I.; Hatch, Maureen; Zurnadzy, Liudmyla Y.; Mabuchi, Kiyohiko; Tronko, Mykola D.; Nikiforov, Yuri E.
2012-01-01
Background Childhood exposure to I-131 from the 1986 Chernobyl accident led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited. Methods We performed mutational analysis of 62 PTCs diagnosed in a Ukrainian cohort of patients who were <18 y.o. in 1986 and received 0.008-8.6 Gy of I-131 to the thyroid and explored associations between mutation types and I-131 dose and other characteristics. Results RET/PTC rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ rearrangement were identified. We found a significant negative association with I-131 dose for BRAF and RAS point mutations and a significant concave association with I-131 dose, with an inflection point at 1.6 Gy and odds ratio 2.1, based on a linear-quadratic model for RET/PTC and PAX8/PPARγ rearrangements. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared to point mutations, rearrangements were associated with residence in the relatively iodine deficient Zhytomyr region, younger age at exposure or surgery, and male gender. Conclusions Our results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with I-131 dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and I-131 exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. PMID:23436219
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Barker, D P; Simpson, J; Pawula, M; Barrett, D A; Shaw, P N; Rutter, N
1995-07-01
To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective.
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Barker, D. P.; Simpson, J.; Pawula, M.; Barrett, D. A.; Shaw, P. N.; Rutter, N.
1995-01-01
AIMS--To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. METHODS--Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. RESULTS--Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. CONCLUSIONS--Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective. PMID:7552591
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See, Emily J; Hawley, Carmel M; Cho, Yeoungjee; Toussaint, Nigel D; Agar, John Wm; Pascoe, Elaine M; Lim, Wai H; Francis, Ross S; Collins, Michael G; Johnson, David W
2018-01-08
Differences in early graft function between kidney transplant recipients previously managed with either haemodialysis (HD) or peritoneal dialysis are well described. However, only two single-centre studies have compared graft and patient outcomes between extended hour and conventional HD patients, with conflicting results. This study compared the outcomes of all extended hour (≥24 hours/week) and conventional HD patients transplanted in Australia and New Zealand between 2000 and 2014. The primary outcome was delayed graft function (DGF), defined in an ordinal manner as either a spontaneous fall in serum creatinine of less than 10% within 24 hours, or the need for dialysis within 72 hours following transplantation. Secondary outcomes included the requirement for dialysis within 72 hours post-transplant, acute rejection, estimated glomerular filtration rate at 12 months, death-censored graft failure, all-cause and cardiovascular mortality, and a composite of graft failure and mortality. A total of 4,935 HD patients (378 extended hour HD, 4,557 conventional HD) received a kidney transplant during the study period. Extended hour HD was associated with an increased likelihood of DGF compared with conventional HD (adjusted proportional odds ratio 1.33; 95% confidence interval 1.06-1.67). There was no significant difference between extended hour and conventional HD in terms of any of the secondary outcomes. Compared to conventional HD, extended hour HD was associated with DGF, although long-term graft and patient outcomes were not different. This article is protected by copyright. All rights reserved.
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Sundberg, Kristina; Frydén, Hanna; Kihlström, Lars; Nordquist, Jonas
2014-01-01
The Swedish resident duty hour limit is regulated by Swedish and European legal frameworks. With a maximum average of 40 working hours per week, the Swedish duty hour regulation is one of the most restrictive in the world. At the same time, the effects of resident duty hour limits have been neither debated nor researched in the Swedish context. As a result, little is known about the Swedish conceptual framework for resident duty hours, their restriction, or their outcomes: we call this "the Swedish duty hour enigma." This situation poses a further question: How do Swedish residents themselves construct a conceptual framework for duty hour restrictions? A case study was conducted at Karolinska University Hospital, Stockholm--an urban, research-intensive hospital setting. Semi-structured interviews were carried out with 34 residents currently in training in 6 specialties. The empirical data analysis relied on theoretical propositions and was conducted thematically using a pattern-matching technique. The interview guide was based on four main topics: the perceived effect of duty hour restrictions on (1) patient care, (2) resident education, (3) resident well-being, and (4) research. The residents did not perceive the volume of duty hours to be the main determinant of success or failure in the four contextual domains of patient care, resident education, resident well-being, and research. Instead, they emphasized resident well-being and a desire for flexibility. According to Swedish residents' conceptual framework on duty hours, the amount of time spent on duty is not a proxy for the quality of resident training. Instead, flexibility, organization, and scheduling of duty hours are considered to be the factors that have the greatest influence on resident well-being, quality of learning, and opportunities to attain the competence needed for independent practice.
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2014-01-01
Background The Swedish resident duty hour limit is regulated by Swedish and European legal frameworks. With a maximum average of 40 working hours per week, the Swedish duty hour regulation is one of the most restrictive in the world. At the same time, the effects of resident duty hour limits have been neither debated nor researched in the Swedish context. As a result, little is known about the Swedish conceptual framework for resident duty hours, their restriction, or their outcomes: we call this “the Swedish duty hour enigma.” This situation poses a further question: How do Swedish residents themselves construct a conceptual framework for duty hour restrictions? Methods A case study was conducted at Karolinska University Hospital, Stockholm – an urban, research-intensive hospital setting. Semi-structured interviews were carried out with 34 residents currently in training in 6 specialties. The empirical data analysis relied on theoretical propositions and was conducted thematically using a pattern-matching technique. The interview guide was based on four main topics: the perceived effect of duty hour restrictions on (1) patient care, (2) resident education, (3) resident well-being, and (4) research. Results The residents did not perceive the volume of duty hours to be the main determinant of success or failure in the four contextual domains of patient care, resident education, resident well-being, and research. Instead, they emphasized resident well-being and a desire for flexibility. Conclusions According to Swedish residents’ conceptual framework on duty hours, the amount of time spent on duty is not a proxy for the quality of resident training. Instead, flexibility, organization, and scheduling of duty hours are considered to be the factors that have the greatest influence on resident well-being, quality of learning, and opportunities to attain the competence needed for independent practice. PMID:25559074
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Jung, Caroline; Greco, Santo; Nguyen, Hanh H T; Ho, Jui T; Lewis, John G; Torpy, David J; Inder, Warrick J
2014-11-26
Glucocorticoid replacement is essential in patients with primary and secondary adrenal insufficiency, but many patients remain on higher than recommended dose regimens. There is no uniformly accepted method to monitor the dose in individual patients. We have compared cortisol concentrations in plasma, saliva and urine achieved following "physiological" and "stress" doses of hydrocortisone as potential methods for monitoring glucocorticoid replacement. Cortisol profiles were measured in plasma, saliva and urine following "physiological" (20 mg oral) or "stress" (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to endogenous cortisol levels (12 subjects). Total plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5 h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5 h, and hourly from time 0 to 5 h following administration of oral or intravenous hydrocortisone. Plasma free cortisol was calculated using Coolens' equation. Plasma, salivary and urine cortisol at 2 h after oral hydrocortisone gave a good indication of peak cortisol concentrations, which were uniformly supraphysiological. Intravenous hydrocortisone administration achieved very high 30 minute cortisol concentrations. Total plasma cortisol correlated significantly with both saliva and urine cortisol after oral and intravenous hydrocortisone (P <0.0001, correlation coefficient between 0.61 and 0.94). There was no difference in CBG levels across the sampling period. An oral dose of hydrocortisone 20 mg is supraphysiological for routine maintenance, while stress doses above 50 mg 6-hourly would rarely be necessary in managing acute illness. Salivary cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in
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Recent research on the acute effects of volatile organic compounds (VQCs) suggests that extrapolation from short (~ 1 h) to long durations (up to 4 h) may be improved by using estimates of brain toluene concentration (Br[Tol]) instead of cumulative inhaled dose (C x t) as a metri...
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Morcos, Peter N; Leong, Ruby; Thommes, James A; DePamphilis, Jean; Grippo, Joseph F; Brennan, Barbara J
2015-01-01
PROGRESS randomized chronic hepatitis C genotype 1 patients with a baseline viral load ≥400,000 IU/mL weighing ≥85 kg to regimens of 180 μg/week for 48 weeks or 360 μg/week for 12 weeks followed by 180 μg/week for 36 weeks peginterferon alfa-2a plus ribavirin. This analysis explored pharmacokinetics and early viral kinetics (VK) and evaluates differences between groups. Blood samples for pharmacokinetic and VK analyses were collected from 51 patients enrolled in the PROGRESS study. Mean peginterferon alfa-2a trough concentration at week 12 was 11.7±4.3 ng/mL for 180 μg and 23.4±11.3 ng/mL for 360 μg. Early VK profiles suggested a trend towards an enhanced viral decline in the 360 μg groups with a mean decrease in HCV RNA at 48 hours post first dose of 1.04 log10 (IU/mL) compared with 0.76 log10 (IU/mL) in the 180 μg groups. Mean beta slope increased with dose, ranging from 0.38±0.26 log10 IU/week at 180 μg to 0.52±0.32 log10 IU/week at 360 μg. Early viral de clines may be enhanced with the 360 μg dose. These data may suggest the utility of high-dose peginterfer on alfa-2a plus direct-acting antivirals (DAA) in select difficult-to-treat populations.
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[The use of polymer gel dosimetry to measure dose distribution around metallic implants].
Nagahata, Tomomasa; Yamaguchi, Hajime; Monzen, Hajime; Nishimura, Yasumasa
2014-10-01
A semi-solid polymer dosimetry system using agar was developed to measure the dose distribution close to metallic implants. Dosimetry of heterogeneous fields where electron density markedly varies is often problematic. This prompted us to develop a polymer gel dosimetry technique using agar to measure the dose distribution near substance boundaries. Varying the concentration of an oxygen scavenger (tetra-hydroxymethyl phosphonium chloride) showed the absorbed dose and transverse relaxation rate of the magnetic resonance signal to be linear between 3 and 12 Gy. Although a change in the dosimeter due to oxidization was observed in room air after 24 hours, no such effects were observed in the first 4 hours. The dose distribution around the metal implants was measured using agar dosimetry. The metals tested were a lead rod, a titanium hip joint, and a metallic stent. A maximum 30% dose increase was observed near the lead rod, but only a 3% increase in the absorbed dose was noted near the surface of the titanium hip joint and metallic stent. Semi-solid polymer dosimetry using agar thus appears to be a useful method for dosimetry around metallic substances.
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Thompson, Gary A.; Solomon, Gail; Albrecht, Helmut H.; Reitberg, Donald P.
2016-01-01
Abstract This study characterized guaifenesin pharmacokinetics in children aged 2 to 17 years (n = 40) who received a single oral dose of guaifenesin (age‐based doses of 100‐400 mg) 2 hours after breakfast. Plasma samples were obtained before and for 8 hours after dosing and analyzed for guaifenesin using liquid chromatography‐tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods, relationships with age were assessed using linear regression, and dose proportionality was assessed on 95% confidence intervals. Based on the upper dose recommended in the monograph (for both children and adolescents), area under the curve from time zero to infinity and maximum plasma concentration both increased with age. However, when comparing the upper dose for children aged 2 to 11 years with the lower dose for adolescents aged 12 to 17 years, similar systemic exposure was observed. As expected due to increasing body size, oral clearance (CLo) and terminal volume of distribution (Vz/F) increased with age. Due to a larger increase in Vz/F than CLo, an increase in terminal exponential half‐life was also observed. Allometric scaling indicated no maturation‐related changes in CLo and Vz/F. PMID:26632082
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Kiernan, Michael; Civetta, Joseph; Bartus, Christine; Walsh, Stephen
2006-01-01
Studies in on-call residents have shown that mood is worsened by fatigue as indicated by increased scores on measures of depression, anxiety, confusion, and anger using the Profile of Mood States (POMS). In prior sleep deprivation studies, mood has been shown to be more affected than either cognitive or motor performances. The purpose of this study was to examine the effect of the 80-hour work week regulations on resident mood in general and in a post-call period (PC). Institutional Review Board approval was obtained to survey the residents and publish the results. POMS is a 65-item adjective questionnaire that includes subscales for measuring tension-anxiety, anger-hostility, depression-dejection, vigor-activity, fatigue-inertia, and confusion-bewilderment, with the summation of the scales forming a total mood disturbance score. Surgical residents were tested at a 9 am didactic curriculum session (9 am has been shown to correlate with the nadir of performance). Residents were tested after nights off call (NOC) or after PC. Time asleep in the preceding 24 hours and other demographic data were also collected. Acute fatigue (AF) was defined as <4 hours sleep. The two-sample t-test and linear regression were used to assess differences between groups. A total of 123 standardized POMS mood questionnaires were administered on 4 occasions to 51 surgical residents, 35 men and 16 women at levels PGY-1 through PGY-5. Overall, 33 tests (27%) were taken after PC and 90 (73%) were taken after NOC. Acute fatigue residents had a mean sleep time of 2.2 (+/-1.5) hours, whereas rested (R) residents had a mean sleep time of 6.7 (+/-2.2) hours (whether PC or NOC). No statistical differences in mean values of vigor, anger, depression, concentration, fatigue, tension, or total score were observed between PC and NOC or between AF and R residents. There was no significant relationship between acute sleep deprivation and total mood disturbance, whether PC or NOC. In linear relationships
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Effect of stress at dosing on organophosphate and heavy metal toxicity
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jortner, Bernard S.
2008-11-15
This paper reviews recent studies assessing the effect of well-defined, severe, transient stress at dosing on two classical models of toxicity. These are the acute (anticholinesterase) toxicity seen following exposure to the organophosphate insecticide chlorpyrifos, and the nephrotoxicity elicited by the heavy metal depleted uranium, in rats. Stress was induced by periods of restraint and forced swimming in days to weeks preceding toxicant exposure. Forced swimming was far more stressful, as measured by marked, if transient, elevation of plasma corticosterone. This form of stress was administered immediately prior to administration of chlorpyrifos or depleted uranium. Chlorpyrifos (single 60 mg/kg subcutaneously)more » elicited marked inhibition of brain acetylcholinesterase 4-day post-dosing. Depleted uranium (single intramuscular doses of 0.1, 0.3 or 1.0 mg/kg uranium) elicited dose-dependent increase in kidney concentration of the metal, with associated injury to proximal tubular epithelium and increases in serum blood urea nitrogen and creatinine during the 30-day post-dosing period. Stress at dosing had no effect on these toxicologic endpoints.« less
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A 2000-Hour Durability Test of a 5-Centimeter Diameter Mercury Bombardment Ion Thruster
NASA Technical Reports Server (NTRS)
Nakanishi, S.; Finke, R. G.
1972-01-01
A 2000-hour durability test of a modified Hughes SIT-5 (Structurally Integrated Thruster, 5 cm) was conducted at the Lewis Research Center. The thruster operated with a translating screen thrust vector grid locked in position for 10 deg beam deflection. The test was essentially continuous except for seven stoppages of beam current. The neutralizer keeper voltage and thruster floating potential increased slightly with time. Performance profiles and maps of thruster characteristics were obtained at 453 and 2023 hours into the test. Overall efficiency was nearly constant at 31 - 32 percent, and operating characteristics were similar at both points in the test. A post-shutdown inspection showed negligible erosion damage to the accelerator and cathode baffle. Some erosion was found in the aperture of the neutralizer cathode.
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Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults
Toms, Laurence; Derry, Sheena; Moore, R Andrew; McQuay, Henry J
2014-01-01
Background This is an updated version of the Cochrane review published in Issue 4, 1998. Combining drugs from different classes with different modes of action may offer opportunity to optimise efficacy and tolerability, using lower doses of each drug to achieve the same degree of pain relief. Previously we concluded that addition of codeine to paracetamol provided additional pain relief, but at expense of additional adverse events. New studies have been published since. This review sought to evaluate efficacy and safety of paracetamol plus codeine using current data, and compare findings with other analgesics evaluated similarly. Objectives Assess efficacy of single dose oral paracetamol plus codeine in acute postoperative pain, increase in efficacy due to the codeine component, and associated adverse events. Search methods We searched CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database in October 2008 for this update. Selection criteria Randomised, double-blind, placebo-controlled trials of paracetamol plus codeine, compared with placebo or the same dose of paracetamol alone, for relief of acute postoperative pain in adults. Data collection and analysis Two authors assessed trial quality and extracted data. The area under the “pain relief versus time” curve was used to derive proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over four-to-six hours, using validated equations. Number-needed-to-treat-to-benefit (NNT) was calculated using 95% confidence intervals (CIs). Proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Twenty-six studies, with 2295 participants, were included comparing paracetamol plus codeine with placebo. Significant dose response was seen for the outcome of at least 50% pain
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Galgani, Ilaria; Bunge, Eveline M; Hendriks, Lisa; Schludermann, Christopher; Marano, Cinzia; De Moerlooze, Laurence
2017-09-01
Tick-borne encephalitis (TBE), which is endemic across large regions of Europe and Asia, is most effectively prevented through vaccination. Three-dose primary TBE vaccination schedules are either rapid (0,7,21-days) or conventional (0,28-84-days, 9-12-months). The second dose can also be administered at 14 days for faster priming and sero-protection). Areas covered: We used a three-step selection process to identify 21 publications comparing the immunogenicity and/or safety of different schedules. Expert commentary: Priming with two or three TBE vaccine doses was highly immunogenic. After conventional priming (0-28 days), 95% adults and ≥95% children had neutralization test (NT) titers ≥10 at 14 days post-dose-2 compared with 92% adults and 99% children at 21 days post-dose-3 (rapid schedule). Most subjects retained NT titers ≥10 at day 300. A single booster dose induced a strong immune response in all subjects irrespective of primary vaccination schedule or elapsed time since priming. GMT peaked at 42 days post-dose-1 (i.e., 21 days post-dose 3 [rapid-schedule], or 14-28 days post-dose-2 [conventional-schedule]), and declined thereafter. Adverse events were generally rare and declined with increasing doses. In the absence of data to recommend one particular schedule, the regimen choice will remain at the physician's discretion, based on patient constraints and availability.
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Babalis, George A; Yiannakopoulos, Christos K; Karliaftis, Konstantinos; Antonogiannakis, Emmanuel
2004-03-01
The efficacy of a minimum dose of methylprednisolone for the prevention of posttraumatic hypoxaemia and fat embolism syndrome (FES) was prospectively studied in 87 patients with isolated, closed or grade I open, femoral and tibial fractures. On admission, the patients were randomly allocated either to a control group given placebo (40 patients) or to a methylprednisolone-treated group (47 patients). A total dose of 6 mg/kg BW methylprednisolone (SoluMedrol, Upjohn) was administered intravenously, divided in six equal doses at 8 h intervals. Six patients (12.8%) in the control group and one patient (2.5%) in the trial group developed FES (P = 0.079) but the difference is not statistically significant. Twenty-four hours after admission, the steroid-treated patients displayed statistically significant higher p(O2) values compared to the control group (P = 0.035) and this difference persisted on the second and the third post-admission day as well (P = 0.008). No corticosteroid-related side-effects were noticed in any of the patients during hospitalisation. Our results support the prophylactic administration of methylprednisolone in small dosage to prevent posttraumatic hypoxaemia and probably FES in patients with isolated lower limb long bone fractures, especially when early fracture stabilisation is not possible.
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Quantitation of 24-Hour Moisturization by Electrical Measurements of Skin Hydration.
Wickett, R Randall; Damjanovic, Bronson
The purpose of this study was to quantify the effects of several moisturizers on hydration of the stratum corneum by measuring their effect on electrical conductance over a 24-hour period. Double-blind, randomized controlled trial. Twenty-five healthy female volunteers aged 18 to 65 years with dry skin on the lower legs and no other known dermatologic pathology participated in the study. Additional exclusion criteria were pregnant or taking anti-inflammatory steroids. The study was carried out in a clinical research facility in Winnipeg, Manitoba, Canada. Subjects underwent a 3-day conditioning period using a natural soap bar on the lower legs and no application of moisturizer to the skin. Participants then came to the test site and equilibrated for at least 30 minutes under controlled conditions of temperature and humidity. After baseline hydration measurements on test sites on the lower legs of each subject, a single application of each of 5 test products at a dose of 2 mg/cm was made. Skin hydration was assessed by electrical conductance measurements with a specialized probe. The probe was briefly placed on the skin surface with light pressure, and the measurement recorded in units of microsiemens (μS). Conductance was measured at 2, 4, 6, 8, and 24 hours after product applications. Although all but 1 of the test products increased conductance at 2 hours, only 2 moisturizers containing high levels of glycerin (products C and E) maintained increased conductance relative to baseline at 24 hours, +37.8 (P < .001) and +103.5 (P < .001), respectively. Moisturizers containing high levels of glycerin can provide a measurable moisturization benefit as determined by skin conductance for at least 24 hours after a single application.
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Pons, Zara; Margalef, Maria; Bravo, Francisca I; Arola-Arnal, Anna; Muguerza, Begoña
2016-03-01
The aims of this study were to evaluate the antihypertensive effectiveness of different doses of grape seed polyphenols in cafeteria diet-fed hypertensive rats (CHRs) and to establish the mechanism involved in the blood pressure (BP) lowering effect of these compounds in this experimental model of metabolic syndrome (MS). Male 8-week-old Wistar rats were fed cafeteria or standard (ST) diet for 10 weeks. After this, the antihypertensive effect of a single oral administration of a polyphenol grape seed extract (GSPE) was tested at different doses (250, 375 and 500 mg/kg) in CHRs. BP was recorded before and 2, 4, 6, 8, 24 and 48 h post-administration. The hypotensive effect of GSPE was also proved in ST diet-fed rats. Additionally, in other experiment, CHRs were orally administered 375 mg/kg GSPE. Four hours post-administration, the rats were intraperitoneally administrated 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME) or 5 mg/kg indomethacin [inhibitors of nitric oxide (NO) and prostacyclin synthesis, respectively]. BP was recorded initially and 6 h post-administration. GSPE produced a decrease in SBP and DBP, the most effective dose (375 mg/kg) showing an antihypertensive effect in CHRs similar to the drug captopril, and did not affect BP of ST diet-fed rats. The antihypertensive effect was completely abolished by L-NAME and partially inhibited by indomethacin. GSPE acts as an antihypertensive agent in a rat model of hypertension associated with MS. The change in endothelium-derived NO availability is one of the mechanisms involved in the antihypertensive effect of GSPE in CHRs. Additionally, endothelial prostacyclin contributes to the effect of GSPE on arterial BP.
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Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs: A pilot study
Larson, Jeanne C.; Allstadt, Sara D.; Fan, Timothy M.; Khanna, Chand; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Legendre, Alfred M.; Galyon, Gina D.; LeBlanc, Amy K.; Martin-Jimenez, Tomas
2017-01-01
Objective To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. Animals 5 healthy purpose-bred hounds. Procedures The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and non-compartmental analyses. Results Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Conclusions and Clinical Relevance Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in ng/mL. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, needs to be determined. PMID:26709938
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hattori, Naoya; Gopal, Ajay K.; Shields, Andrew T.
Purpose: To investigate radiation doses to the testes delivered by a radiolabeled anti-CD20 antibody and its effects on male sex hormone levels. Materials and methods: Testicular uptake and retention of 131I-tositumomab were measured, and testicular absorbed doses were calculated for 67 male patients (54+/-11 years of age) with non-Hodgkin's lymphoma who had undergone myeloablative radioimmunotherapy (RIT) using 131I-tositumomab. Time-activity curves for the major organs, testes, and whole body were generated from planar imaging studies. In a subset of patients, male sex hormones were measured before and 1 year after the therapy. Results: The absorbed dose to the testes showed considerablemore » variability (range=4.4-70.2 Gy). Pretherapy levels of total testosterone were below the lower limit of the reference range, and post-therapy evaluation demonstrated further reduction [4.6+/-1.8 nmol/l (pre-RIT) vs. 3.8+/-2.9 nmol/l (post-RIT), P<0.05]. Patients receiving higher radiation doses to the testes (>=25 Gy) showed a greater reduction [4.7+/-1.6 nmol/l (pre-RIT) vs. 3.3+/-2.7 nmol/l (post-RIT), P<0.05] compared with patients receiving lower doses (<25 Gy), who showed no significant change in total testosterone levels. Conclusion: The testicular radiation absorbed dose varied highly among individual patients. Finally, patients receiving higher doses to the testes were more likely to show post-RIT suppression of testosterone levels.« less
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Can we safely administer the recommended dose of phenobarbital in very low birth weight infants?
Oztekin, Osman; Kalay, Salih; Tezel, Gonul; Akcakus, Mustafa; Oygur, Nihal
2013-08-01
We investigated whether the recommended phenobarbital loading dose of 15-20 mg/kg with maintenance of 3-4 mg/kg/day can safely be administered to very low birth weight preterm newborns with seizures. Twenty-four convulsive preterms of <1,500 g were enrolled in the study. Phenobarbital was administered intravenously with a loading dose of 15 mg/kg in approximately 10-15 min. After 24 h, the maintenance dose of 3 mg/kg/day was administered as a single injection. Blood samples were obtained 2, 24, 48, 72, and 96 h after the phenobarbital loading dose was administered, immediately before the next phenobarbital dose was injected. None of the cases had plasma phenobarbital concentrations above the therapeutic upper limit of 40 μg/mL on the 2nd hour; one case (4.7%), on the 24th; 11 cases (45.8%), on the 48th; 15 cases (62.5%), on the 72nd; and 17 cases (70.8%), on the 96th hour. A negative correlation was detected between the serum concentrations of phenobarbital and gestational age on the 72th (p, 0.036; r, -0.608) and 96th hour (p, 0.043; r, -0.769). We suggest that particular attention should be done while administering phenobarbital in preterms, as blood levels of phenobarbital are higher than the reference ranges that those are often reached with the recommended doses in these groups of babies.
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A Systematic Review of the Effects of Resident Duty Hour Restrictions in Surgery
Devitt, Katharine S.; Keshet, Itay; Spicer, Jonathan; Imrie, Kevin; Feldman, Liane; Cools-Lartigue, Jonathan; Kayssi, Ahmed; Lipsman, Nir; Elmi, Maryam; Kulkarni, Abhaya V.; Parshuram, Chris; Mainprize, Todd; Warren, Richard J.; Fata, Paola; Gorman, M. Sean; Feinberg, Stan; Rutka, James
2014-01-01
Background: In 2003, the Accreditation Council for Graduate Medical Education (ACGME) mandated 80-hour resident duty limits. In 2011 the ACGME mandated 16-hour duty maximums for PGY1 (post graduate year) residents. The stated goals were to improve patient safety, resident well-being, and education. A systematic review and meta-analysis were performed to evaluate the impact of resident duty hours (RDH) on clinical and educational outcomes in surgery. Methods: A systematic review (1980–2013) was executed on CINAHL, Cochrane Database, Embase, Medline, and Scopus. Quality of articles was assessed using the GRADE guidelines. Sixteen-hour shifts and night float systems were analyzed separately. Articles that examined mortality data were combined in a random-effects meta-analysis to evaluate the impact of RDH on patient mortality. Results: A total of 135 articles met the inclusion criteria. Among these, 42% (N = 57) were considered moderate-high quality. There was no overall improvement in patient outcomes as a result of RDH; however, some studies suggest increased complication rates in high-acuity patients. There was no improvement in education related to RDH restrictions, and performance on certification examinations has declined in some specialties. Survey studies revealed a perception of worsened education and patient safety. There were improvements in resident wellness after the 80-hour workweek, but there was little improvement or negative effects on wellness after 16-hour duty maximums were implemented. Conclusions: Recent RDH changes are not consistently associated with improvements in resident well-being, and have negative impacts on patient outcomes and performance on certification examinations. Greater flexibility to accommodate resident training needs is required. Further erosion of training time should be considered with great caution. PMID:24662409
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Krishna, Rajesh; Gheyas, Ferdous; Liu, Yang; Cote, Josee; Laterza, Omar; Ruckle, Jon L; Wagner, John A; Denker, Andrew E
2018-02-01
Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor being developed for the treatment of mixed dyslipidemia. The aim of the study was to evaluate the pharmacokinetic, pharmacodynamic, and safety characteristics of anacetrapib following single doses in healthy, young Japanese men. In a double-blind, randomized, placebo-controlled, 3-panel, single-rising-dose study, 6 healthy young Japanese male or white male subjects (aged 19 to 44 years) received single oral doses of 5 to 500 mg anacetrapib, and 2 received placebo. Plasma and urine drug concentrations were measured 0-168 hours postdose, and plasma CETP inhibition was measured 0-24 hours postdose. Urinary anacetrapib levels were all below quantitation limits. Plasma concentrations of anacetrapib increased approximately less than dose-proportionally. Consumption of a traditional Japanese breakfast prior to dosing increased the plasma pharmacokinetics of anacetrapib in Japanese subjects compared with fasted conditions, to a similar extent as in white subjects. CETP activity measured over 0-24 hours postdose resulted in significant inhibition. Anacetrapib was generally well tolerated, and there were no serious adverse experiences. No clinically meaningful differences in PK and CETP inhibition parameters were found between Japanese and white subjects. © 2017, The American College of Clinical Pharmacology.
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Duty hours restriction for our surgical trainees: An ethical obligation or a bad idea?
Adin, Christopher A; Fogle, Callie A; Marks, Steven L
2018-04-01
To ensure patient safety and protect the well-being of interns and residents, the Accreditation Council for Graduate Medical Education (ACGME) issued guidelines in 2003 limiting the working hours of physician trainees. Although many supported the goals of the ACGME, institutions struggled to restructure their programs and hire staff required by this unfunded mandate. Numerous studies have analyzed the effects of duty hours restrictions on patient outcomes and physician training over the past 15 years. Most agree that duty hours restrictions improved well-being of house officers, but these improvements came at the expense of continuity, and patient hand-offs led to medical errors. Effects on resident training are program specific, with duty hours restrictions having the most deleterious effects on surgical disciplines. Because veterinary specialists assume a similar role in providing 24-hour patient care, interns and residents face work-related stress as a result of extended working hours, on-call duty, and an increasingly complex caseload. The North Carolina State Veterinary Hospital is staffed by approximately 100 house officers representing almost every veterinary specialty group. We surveyed departing house officers regarding their quality of life and training experience. Sixty-six percent of interns and residents reported that they do not have time to take care of personal needs, and 57%-62% felt neutral or dissatisfied with their mental and physical well-being. Most trainees believed that decreased duty hours would improve learning, but 42% believed that decreased caseload would be detrimental to training. Veterinary educators must consider post-DVM veterinary training guidelines that maintain patient care with a good learning environment for interns and residents. © 2018 The American College of Veterinary Surgeons.
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The effect of IVPCA morphine on post-hysterectomy bowel function.
Chan, Kuang-Cheng; Cheng, Ya-Jung; Huang, Guang-Ta; Wen, Yuan-Jui; Lin, Chen-Jung; Chen, Li-Kuei; Sun, Wei-Zen
2002-06-01
Although morphine has been shown to induce bowel dysfunction in a dose-dependent fashion, in most relevant studies it was investigated in single bolus injection. Recently, intravenous morphine via patient-controlled analgesia (IVPCA) has been widely used to provide analgesia by divided bolus doses on patients' demand with satisfactory effects. This approach, by reducing the peak serum surge, largely resembles the pharmacokinetic and pharmacodynamic advantage of continuous infusion. There is yet no report on the investigation of its effect on post-operative bowel dysfunction. Fifty-one women who underwent abdominal total hysterectomy (ATH) due to uterine myoma were enrolled to investigate the association between the doses of morphine consumption by PCA and the time of first passage of flatus. In all patients morphine was administered intravenously via a PCA pump immediately after recovery from general anesthesia. We found that 49 out of 51 patients (96%) exhibited mild pain with IVPCA morphine. They had consumed an average dose of 16.9 mg morphine (range, 0-46 mg) upon the first passage of flatus which occurred 2036.4 min (average) post-operatively. There was no correlation between the dose of morphine and the time of first passage of flatus (r = 0.053, P > 0.05). The absence of suppression of bowel movement by IVPCA morphine for post-operative pain control suggests that favorable pharmacokinetic profile of IVPCA can help reduce the morphine-induced bowel dysfunction at its therapeutic level.
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The biobehavioral and neuroimmune impact of low-dose ionizing radiation
York, Jason M; Blevins, Neil A; Meling, Daryl D; Peterlin, Molly B; Gridley, Daila S; Cengel, Keith A; Freund, Gregory G
2011-01-01
In the clinical setting, repeated exposures (10–30) to low-doses of ionizing radiation (≤ 200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation was found to reduce spontaneous locomotor activity by 35% and 36%, respectively, 6 h post irradiation. In contrast, the motivated behavior of social exploration was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene transcripts in the brain demonstrated that gamma radiation increased hippocampal TNF-α expression as early as 4 h post-irradiation. This was coupled to subsequent increases in IL-1RA (8 h and 12 h post irradiation) in the cortex and hippocampus and reductions in activity-regulated cytoskeleton-associated protein (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a significant modulator of the neuroimmune response to radiation blocking the ability of 200 cGy gamma radiation from impairing locomotor activity and altering the brain-based inflammatory response to irradiation. Taken together, these findings indicate that low-dose ionizing radiation rapidly activates the neuroimmune system potentially causing early onset fatigue-like symptoms in mice. PMID:21958477
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Single dose oral flurbiprofen for acute postoperative pain in adults
Sultan, Asquad; McQuay, Henry J; Moore, R Andrew; Derry, Sheena
2014-01-01
Background Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic painful conditions. There is no systematic review of its use in acute postoperative pain. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered flurbiprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Eleven studies compared flurbiprofen (699 participants) with placebo (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate reporting quality, and most participants had pain following dental extractions. The dose of flurbiprofen used was 25 mg to 100 mg, with most information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to 6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7 (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50% pain relief, compared with 25% to 30% with placebo. Rescue medication was used by 25
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Leeman-Neill, Rebecca J; Brenner, Alina V; Little, Mark P; Bogdanova, Tetiana I; Hatch, Maureen; Zurnadzy, Liudmyla Y; Mabuchi, Kiyohiko; Tronko, Mykola D; Nikiforov, Yuri E
2013-05-15
Childhood exposure to iodine-131 from the 1986 nuclear accident in Chernobyl, Ukraine, led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited. Mutational analysis was performed on 62 PTCs diagnosed in a Ukrainian cohort of patients who were < 18 years old in 1986 and received 0.008 to 8.6 Gy of (131) I to the thyroid. Associations between mutation types and (131) I dose and other characteristics were explored. RET/PTC (ret proto-oncogene/papillary thyroid carcinoma) rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ (paired box 8/peroxisome proliferator-activated receptor gamma) rearrangement were identified. A significant negative association with (131) I dose for BRAF and RAS point mutations and a significant concave association with (131) I dose, with an inflection point at 1.6 Gy and odds ratio of 2.1, based on a linear-quadratic model for RET/PTC and PAX8/PPARγ rearrangements were found. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared with point mutations, rearrangements were associated with residence in the relatively iodine-deficient Zhytomyr region, younger age at exposure or surgery, and male sex. These results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with (131) I dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and (131) I exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. Copyright © 2013 American Cancer Society.
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SU-F-T-130: [18F]-FDG Uptake Dose Response in Lung Correlates Linearly with Proton Therapy Dose
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, D; Titt, U; Mirkovic, D
2016-06-15
Purpose: Analysis of clinical outcomes in lung cancer patients treated with protons using 18F-FDG uptake in lung as a measure of dose response. Methods: A test case lung cancer patient was selected in an unbiased way. The test patient’s treatment planning and post treatment positron emission tomography (PET) were collected from picture archiving and communication system at the UT M.D. Anderson Cancer Center. Average computerized tomography scan was registered with post PET/CT through both rigid and deformable registrations for selected region of interest (ROI) via VelocityAI imaging informatics software. For the voxels in the ROI, a system that extracts themore » Standard Uptake Value (SUV) from PET was developed, and the corresponding relative biological effectiveness (RBE) weighted (both variable and constant) dose was computed using the Monte Carlo (MC) methods. The treatment planning system (TPS) dose was also obtained. Using histogram analysis, the voxel average normalized SUV vs. 3 different doses was obtained and linear regression fit was performed. Results: From the registration process, there were some regions that showed significant artifacts near the diaphragm and heart region, which yielded poor r-squared values when the linear regression fit was performed on normalized SUV vs. dose. Excluding these values, TPS fit yielded mean r-squared value of 0.79 (range 0.61–0.95), constant RBE fit yielded 0.79 (range 0.52–0.94), and variable RBE fit yielded 0.80 (range 0.52–0.94). Conclusion: A system that extracts SUV from PET to correlate between normalized SUV and various dose calculations was developed. A linear relation between normalized SUV and all three different doses was found.« less
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Martin, David E; Blum, Robert; Doto, Judy; Galbraith, Hal; Ballow, Charles
2007-01-01
Bevirimat [3-O-(3',3'-dimethylsuccinyl)-betulinic acid] is a novel inhibitor of HIV-1 maturation. This study was performed to investigate the pharmacokinetics and safety of bevirimat during repeated dosing in healthy volunteers. The study was a 10-day, randomised, double-blind, placebo-controlled, dose escalation study. A total of 48 healthy male volunteers, aged 19-54 years, took part in the study. Treatment was administered for 10 days in six escalating dose cohorts (n = 8 in each cohort; 6 bevirimat, 2 placebo). The doses of bevirimat given in each successive cohort were 25 mg, 50 mg, 75 mg (with 150 mg loading dose), 100 mg, 150 mg and 200mg. Safety follow-up was performed 28 days after the first dose. PHARMACOKINETIC AND STATISTICAL ANALYSIS: Plasma bevirimat levels were measured from blood samples collected pre-dose on days 1-10 and then at approximately 48-hour intervals until 21 days after dosing started. On days 1 and 10, further blood samples were obtained at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours after dosing. Urine samples were collected in the morning on days 1, 5 and 11 and at the end of the study for the measurement of cortisol and 6beta-hydroxycortisol. The pharmacokinetic parameters of bevirimat were estimated using non-compartmental methods. Dose proportionality of exposure to bevirimat, assessed by the maximum plasma concentration and the area under the plasma concentration-time curve. The mean terminal elimination half-life of bevirimat ranged from 56.3 to 69.5 hours, and the mean clearance ranged from 173.9 to 185.8 mL/hour. Bevirimat showed approximately 4-fold greater accumulation on day 10 compared with day 1, and the degree of accumulation was similar with all doses. Maximum plasma concentrations ranged from 8 to 58 microg/mL at day 10. Testing for dose-proportionality showed that exposure to bevirimat was proportional to the dose, both after a single dose and after repeat dosing for 10 days. Measurement of the urinary 6beta
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Sundaram, Arun; Alshaikh, Belal; Dersch-Mills, Deonne; Dobry, Jenna; Akierman, Albert R; Yusuf, Kamran
2017-06-01
Extended-interval dosing (EID) regimens of gentamicin have been validated for treating confirmed or suspected early- and late-onset sepsis in preterm infants in the first week of life. Despite the marked changes in volume of distribution and renal clearance in preterm infants after the first few days of life, few studies have validated EID regimens of gentamicin in this population. The objective of the study was to evaluate an EID regimen of gentamicin in infants born at <32 weeks' gestational age and aged >7 days. This observational study of an EID regimen was conducted in 39 infants. Dosing interval was based on the serum drug concentration at 22 hours after the administration of the first dose of 5 mg/kg. Gentamicin peak (5-12 µg/mL) and trough (<2 µg/mL) levels were compared to those in a historical control group of 39 infants who received traditional-interval dosing (TID) of 2.5 mg/kg of gentamicin with dosing intervals of 8, 12, or 24 hours. There were no differences in birthweight, gestational age at birth, postmenstrual age, weight at the start of gentamicin administration, postnatal age, small for gestational age status, antenatal corticosteroid use, or postnatal indomethacin exposure between the 2 groups. In the EID group, dosing intervals were 24 hours in 30 infants, 36 hours in 6 infants, and 48 hours in 3 infants. Compared with the TID group (n = 39), the EID group had a significantly higher peak level (median, 9.0 vs 4.7 µg/mL) and a significantly lower trough level (median, 0.7 vs 1.1 µg/mL) (both, P < 0.001). On regression analysis, the postmenstrual age was correlated significantly with trough levels in the EID group. There was no adverse effect on renal function in either group. On follow-up, 1 infant in the EID group and 2 infants in the TID group had evidence of sensorineural hearing loss. In infants born at <32 weeks' gestation and >7 days of age, an EID gentamicin regimen, with a dosing interval based on a single concentration measurement
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Liposomal Bupivacaine as a Single-Injection Peripheral Nerve Block: A Dose-Response Study
Ilfeld, Brian M.; Malhotra, Nisha; Furnish, Timothy J.; Donohue, Michael C.; Madison, Sarah J.
2013-01-01
Background Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration less than 24 hours. A liposomal bupivacaine formulation (EXPAREL®, Pacira Pharmaceuticals, Inc., San Diego, California), releasing bupivacaine over 96 hours, recently gained Food and Drug Administration approval exclusively for wound infiltration, but not peripheral nerve blocks. Methods Bilateral single-injection femoral nerve blocks were administered in healthy volunteers (n=14). For each block, liposomal bupivacaine (0–80 mg) was mixed with normal saline to produce 30 mL of study fluid. Each subject received two different doses, one on each side, applied randomly in a double-masked fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. Results There were statistically significant dose responses in MVIC (0.09% / mg, SE = 0.03, 95% CI 0.04 to 0.14, p = 0.002) and tolerance to cutaneous current (−0.03 mA / mg, SE = 0.01, 95% CI −0.04 to 0.02, p < 0.001), however, in the opposite direction than expected (the higher the dose, the lower the observed effect). This inverse relationship is biologically implausible, and most likely due to the limited sample size and the subjective nature of the measurement instruments. While peak effects occurred within 24 hours after block administration in 75% of cases (95% CI 43 to 93%), block duration usually lasted much longer: for bupivacaine doses above 40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 h in 100% of subjects (95% CI 56 to 100). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI 54 to 100%). Motor block duration was not correlated with
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NASA Technical Reports Server (NTRS)
Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.
2001-01-01
The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.
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Kugelman, Tara; Zuloaga, Damian G.; Weber, Sydney; Raber, Jacob
2015-01-01
The brain might be exposed to irradiation under a variety of situations, including clinical treatments, nuclear accidents, dirty bomb scenarios, and military and space missions. Correctly recalling tasks learned prior to irradiation is important but little is known about post-learning effects of irradiation. It is not clear whether exposure to X-ray irradiation during memory consolidation, a few hours following training, is associated with altered contextual fear conditioning 24 hours after irradiation and which brain region(s) might be involved in these effects. Brain immunoreactivity patterns of the immediately early gene c-Fos, a marker of cellular activity was used to determine which brain areas might be altered in post-training irradiation memory retention tasks. In this study, we show that post-training gamma irradiation exposure (1 Gy) enhanced contextual fear memory 24 hours later and is associated with reduced cellular activation in the infralimbic cortex. Reduced GABA-ergic neurotransmission in parvalbumin-positive cells in the infralimbic cortex might play a role in this post-training radiation-enhanced contextual fear memory. PMID:26522840
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Jena, Anupam B.; Schoemaker, Lena; Bhattacharya, Jayanta
2014-01-01
In 2003, work hours for physicians in training (residents) were mandatorily reduced to be no more than 80 hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000–2009 which were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and length of stay for internists varied according to the number of years an internist was exposed to the 2003 duty hour regulations during their own residency. Using a difference-in-difference analysis which compared trends in outcomes of junior physicians pre- and post-2003 to a control group of senior physicians who were not exposed to these reforms during their own residency, we found that the 2003 reforms did not affect the quality of physician training reflected by hospital mortality and length of stay. PMID:25288430
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Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke.
Anderson, Craig S; Robinson, Thompson; Lindley, Richard I; Arima, Hisatomi; Lavados, Pablo M; Lee, Tsong-Hai; Broderick, Joseph P; Chen, Xiaoying; Chen, Guofang; Sharma, Vijay K; Kim, Jong S; Thang, Nguyen H; Cao, Yongjun; Parsons, Mark W; Levi, Christopher; Huang, Yining; Olavarría, Verónica V; Demchuk, Andrew M; Bath, Philip M; Donnan, Geoffrey A; Martins, Sheila; Pontes-Neto, Octavio M; Silva, Federico; Ricci, Stefano; Roffe, Christine; Pandian, Jeyaraj; Billot, Laurent; Woodward, Mark; Li, Qiang; Wang, Xia; Wang, Jiguang; Chalmers, John
2016-06-16
Thrombolytic therapy for acute ischemic stroke with a lower-than-standard dose of intravenous alteplase may improve recovery along with a reduced risk of intracerebral hemorrhage. Using a 2-by-2 quasi-factorial open-label design, we randomly assigned 3310 patients who were eligible for thrombolytic therapy (median age, 67 years; 63% Asian) to low-dose intravenous alteplase (0.6 mg per kilogram of body weight) or the standard dose (0.9 mg per kilogram); patients underwent randomization within 4.5 hours after the onset of stroke. The primary objective was to determine whether the low dose would be noninferior to the standard dose with respect to the primary outcome of death or disability at 90 days, which was defined by scores of 2 to 6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]). Secondary objectives were to determine whether the low dose would be superior to the standard dose with respect to centrally adjudicated symptomatic intracerebral hemorrhage and whether the low dose would be noninferior in an ordinal analysis of modified Rankin scale scores (testing for an improvement in the distribution of scores). The trial included 935 patients who were also randomly assigned to intensive or guideline-recommended blood-pressure control. The primary outcome occurred in 855 of 1607 participants (53.2%) in the low-dose group and in 817 of 1599 participants (51.1%) in the standard-dose group (odds ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; the upper boundary exceeded the noninferiority margin of 1.14; P=0.51 for noninferiority). Low-dose alteplase was noninferior in the ordinal analysis of modified Rankin scale scores (unadjusted common odds ratio, 1.00; 95% CI, 0.89 to 1.13; P=0.04 for noninferiority). Major symptomatic intracerebral hemorrhage occurred in 1.0% of the participants in the low-dose group and in 2.1% of the participants in the standard-dose group (P=0.01); fatal events occurred within 7 days in 0.5% and 1.5%, respectively
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Herlitz, Georg N.; Sanders, Renee L.; Cheung, Nora H.; Coyle, Susette M.; Griffel, Benjamin; Macor, Marie A.; Lowry, Stephen F.; Calvano, Steve E.; Gale, Stephen C.
2014-01-01
Introduction Human injury or infection induces systemic inflammation with characteristic neuro-endocrine responses. Fluctuations in autonomic function during inflammation are reflected by beat-to-beat variation in heart rate, termed heart rate variability (HRV). In the present study, we determine threshold doses of endotoxin needed to induce observable changes in markers of systemic inflammation, we investigate whether metrics of HRV exhibit a differing threshold dose from other inflammatory markers, and we investigate the size of data sets required for meaningful use of multi-scale entropy (MSE) analysis of HRV. Methods Healthy human volunteers (n=25) were randomized to receive placebo (normal saline) or endotoxin/lipopolysaccharide (LPS): 0.1, 0.25, 0.5, 1.0, or 2.0 ng/kg administered intravenously. Vital signs were recorded every 30 minutes for 6 hours and then at 9, 12, and 24 hours after LPS. Blood samples were drawn at specific time points for cytokine measurements. HRV analysis was performed using EKG epochs of 5 minutes. MSE for HRV was calculated for all dose groups to scale factor 40. Results The lowest significant threshold dose was noted in core temperature at 0.25ng/kg. Endogenous TNF-α and IL-6 were significantly responsive at the next dosage level (0.5ng/kg) along with elevations in circulating leukocytes and heart rate. Responses were exaggerated at higher doses (1 and 2 ng/kg). Time domain and frequency domain HRV metrics similarly suggested a threshold dose, differing from placebo at 1.0 and 2.0 ng/kg, below which no clear pattern in response was evident. By applying repeated-measures ANOVA across scale factors, a significant decrease in MSE was seen at 1.0 and 2.0 ng/kg by 2 hours post exposure to LPS. While not statistically significant below 1.0 ng/kg, MSE unexpectedly decreased across all groups in an orderly dose-response pattern not seen in the other outcomes. Conclusions By usingrANOVA across scale factors, MSE can detect autonomic change
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Dose Response of Endotoxin on Hepatocyte and Muscle Mitochondrial Respiration In Vitro
Brandt, Sebastian; Porta, Francesca; Jakob, Stephan M.; Takala, Jukka; Djafarzadeh, Siamak
2015-01-01
Introduction. Results on mitochondrial dysfunction in sepsis are controversial. We aimed to assess effects of LPS at wide dose and time ranges on hepatocytes and isolated skeletal muscle mitochondria. Methods. Human hepatocellular carcinoma cells (HepG2) were exposed to placebo or LPS (0.1, 1, and 10 μg/mL) for 4, 8, 16, and 24 hours and primary human hepatocytes to 1 μg/mL LPS or placebo (4, 8, and 16 hours). Mitochondria from porcine skeletal muscle samples were exposed to increasing doses of LPS (0.1–100 μg/mg) for 2 and 4 hours. Respiration rates of intact and permeabilized cells and isolated mitochondria were measured by high-resolution respirometry. Results. In HepG2 cells, LPS reduced mitochondrial membrane potential and cellular ATP content but did not modify basal respiration. Stimulated complex II respiration was reduced time-dependently using 1 μg/mL LPS. In primary human hepatocytes, stimulated mitochondrial complex II respiration was reduced time-dependently using 1 μg/mL LPS. In isolated porcine skeletal muscle mitochondria, stimulated respiration decreased at high doses (50 and 100 μg/mL LPS). Conclusion. LPS reduced cellular ATP content of HepG2 cells, most likely as a result of the induced decrease in membrane potential. LPS decreased cellular and isolated mitochondrial respiration in a time-dependent, dose-dependent and complex-dependent manner. PMID:25649304
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Development of CER-001: Preclinical Dose Selection Through to Phase I Clinical Findings.
Keyserling, Constance H; Barbaras, Ronald; Benghozi, Renee; Dasseux, Jean-Louis
2017-05-01
CER-001 comprises recombinant human apolipoprotein A-I complexed with phospholipids that mimics natural, nascent, pre-β high-density lipoprotein (HDL). We present animal model data showing dose-dependent increases in cholesterol efflux with CER-001 and its subsequent elimination by reverse lipid transport, together with inhibition of atherosclerotic plaque progression. We report the first phase I study results with CER-001 in humans, starting at 0.25 mg/kg, which is 1/80th of the safe dose (20 mg/kg) established in 4-week multiple-dose animal studies dosed every second day. Healthy volunteers, 18-55 years old with a low-density lipoprotein-cholesterol:HDL-cholesterol ratio greater than 3.0, received single intravenous escalating doses of CER-001 (0.25-45.0 mg/kg) and placebo in a double-blind randomised cross-over fashion. Subjects were followed up for 3 weeks post-dose. Assessments included adverse event monitoring, blood sampling, and clinical laboratory measurements. Thirty-two subjects were enrolled. All CER-001 doses (0.25-45 mg/kg) were safe and well tolerated, with an adverse event profile similar to placebo. Effects on clinical chemistry, haematology and coagulation parameters were comparable to placebo. No adverse effects of CER-001 on electrocardiograms were observed. No antibodies to apolipoprotein A-I were detected following single-dose administration of CER-001. Plasma apolipoprotein A-I levels increased in a dose-related manner and returned to baseline by 24 h post-dose for doses up to 10 mg/kg but remained in circulation for >72 h post-dose for doses >10 mg/kg. CER-001 caused elevations in plasma cholesterol and total and unesterified cholesterol in the HDL fraction. Mobilisation of unesterified cholesterol in the HDL fraction was seen with CER-001 at doses as low as 2 mg/kg. CER-001 is well tolerated when administered to humans as single doses up to 45 mg/kg and mobilises and eliminates cholesterol via reverse lipid transport.
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Bordman, Risa; Wheler, David; Drummond, Neil; White, David; Crighton, Eric
2005-01-01
OBJECTIVE To determine the prevalence and content of existing or developing policies and guidelines of medical associations and colleges regarding after-hours care by family physicians and general practitioners, especially legal requirements. DESIGN Telephone survey in fall 2002, updated in fall 2004. SETTING Canada. PARTICIPANTS All national and provincial medical associations, Colleges of Family Physicians, Colleges of Physicians and Surgeons, local government offices for the north, and the Canadian Medical Protective Association (CMPA). MAIN OUTCOME MEASURE Response to the question: “Does your agency have a policy in place regarding after-hours health care coverage by FPs/GPs, or are there active discussions regarding such a policy?” RESULTS The College of Physicians and Surgeons of British Columbia was the first to institute a policy, in 1995, requiring physicians to make “specific arrangements” for after-hours care of their patients. The College of Physicians and Surgeons of Alberta adopted a similar policy in 1996 along with a guideline to aid implementation. In 2002, the College of Physicians and Surgeons of Nova Scotia approved a guideline on the Availability of Physicians After Hours. The Saskatchewan Medical Association and the College of Physicians and Surgeons of Saskatchewan formulated a joint policy on medical practice coverage that was released in 2003. Many agencies actively discussed the topic. Provincial and national Colleges of Family Physicians did not have any policies in place. The CMPA does not generate guidelines but released in an information letter in May 2000 a section entitled “Reducing your risk when you’re not available.” CONCLUSION There is increasing interest Canada-wide in setting policy for after-hours care. While provincial Colleges of Physicians and Surgeons have traditionally led the way, a trend toward more collaboration between associations was identified. The effect of policy implementation on physicians
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Lo, Siu-Fai; Spurgeon, Peter
2007-01-01
The Accreditation Council for Graduate Medical Education and European working time directive have restricted residents' workweek to 80 and 48 hours, respectively. Impacts on resident's training and health services are under evaluation in western countries. However, relevant studies are deficient in Hong Kong. Surgeons in a regional hospital of Hong Kong were recruited. Opinions were collected by semi-structured questionnaire. Response rate was 82%. Most respondents agreed that residents' work hours should be limited. Seventy-two percent thought that the addition of physician assistants, nurse practitioners and ancillary staff could help decrease the workload of residents. More than 60% thought that residents should have post-call afternoon off. Seventy-two percent worried that the number of operations residents performed would decrease. Only half agreed that long work hours was part of resident training and 56.3% agreed that the training period should be lengthened because of limiting work hours. Ninety-four percent agreed that sleep-deprived residents would create more medical errors; 72% thought that long work hours would impair quality of care. Surprisingly, only 28% thought that limiting work hours would compromise continued patient care. Most respondents opine that resident work hours should be regulated and welcome minor rescheduling of residents' workflow. The impacts on residents' training and patient care require further evaluation.
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Dunphy, F R; Boyd, J H; Kim, H J; Dunphy, C H; Harrison, B R; Dunleavy, T L; Rodriguez, J J; McDonough, E M; Minster, J R; Hilton, J G
1997-05-15
Standard therapy for advanced head and neck carcinoma is surgery and radiation, and the subsequent 5-year survival with this treatment has been less than 50%. New combined modality treatment strategies are being tested to improve survival. New chemotherapy combinations are being developed and administered simultaneously with, or sequenced with, radiation and surgery. This article reports the Phase I results of administering paclitaxel and carboplatin preoperatively. The authors' objective was to develop an outpatient chemotherapy that would downstage tumors and allow organ preservation with equal or improved survival as compared with standard therapy. Thirty-six patients with untreated Stage III/IV head and neck carcinoma were treated and were evaluable for toxicity. All patients had lesions that were measurable in perpendicular planes. A nonrandomized, Phase I design was used, according to which cohorts of patients were treated every 21 days with escalating doses of paclitaxel (150-265 mg/m2) given as a 3-hour infusion immediately preceding carboplatin. Premedication was used to avoid acute hypersensitivity reactions. Carboplatin was administered intravenously over 1 hour at a constant dose calculated with the Calvert formula (area under the curve, 7.5). The dose-limiting toxicities were neuropathy and thrombocytopenia at a paclitaxel dose of 265 mg/m2. Neutropenic fever was observed in 30% of patients at a paclitaxel dose of 250-265 mg/m2. Other observed adverse effects included pruritus, myalgia, arthralgia, alopecia, nausea, and vomiting. Toxicity was acceptable. The maximum tolerated dose of paclitaxel was 230 mg/m2 without hematopoietic growth factor, or 250 mg/m2 with hematopoietic growth factor, the carboplatin dose held constant, calculated at area under the curve of 7.5. Phase II studies of this combination are warranted in the treatment of these carcinomas.
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Wang, Heyang; Liang, Zhenyang; Li, Yi; Li, Bin; Liu, Junming; Hong, Xueyi; Lu, Xin; Wu, Jiansheng; Zhao, Wei; Liu, Qiang; An, Jian; Li, Linfeng; Pu, Fanli; Ming, Qiang; Han, Yaling
2017-06-01
This study aimed to evaluate the effect of prolonged full-dose bivalirudin infusion in real-world population with ST-elevation myocardial infarction (STEMI). Subgroup data as well as meta-analysis from randomized clinical trials have shown the potency of postprocedural full-dose infusion (1.75 mg/kg/h) of bivalirudin on attenuating acute stent thrombosis (ST) after primary percutaneous coronary intervention (PCI). In this multicenter retrospective observational study, 2047 consecutive STEMI patients treated with bivalirudin during primary PCI were enrolled in 65 Chinese centers between July 2013 and May 2016. The primary outcome was acute ST defined as ARC definite/probable within 24 hours after the index procedure, and the secondary endpoints included total ST, major adverse cardiac or cerebral events (MACCE, defined as death, reinfarction, stroke, and target vessel revascularization), and any bleeding at 30 days. Among 2047 STEMI patients, 1123 (54.9%) were treated with postprocedural bivalirudin full-dose infusion (median 120 minutes) while the other 924 (45.1%) received low-dose (0.25 mg/kg/h) or null postprocedural infusion. A total of three acute ST (0.3%) occurred in STEMI patients with none or low-dose prolonged infusion of bivalirudin, but none was observed in those treated with post-PCI full-dose infusion (0.3% vs 0.0%, P=.092). Outcomes on MACCE (2.1% vs 2.7%, P=.402) and total bleeding (2.1% vs 1.4%, P=.217) at 30 days showed no significant difference between the two groups, and no subacute ST was observed. Post-PCI full-dose bivalirudin infusion is safe and has a trend to protect against acute ST in STEMI patients undergoing primary PCI in real-world settings. © 2017 John Wiley & Sons Ltd.
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[Once-daily gentamicin dosing versus thrice-daily dosing in infants with acute pyelonephritis].
Calvo Rey, C; García Díaz, B; Nebreda Pérez, V; García García, M L; Maderuelo Sánchez, A I; Cilleruelo Pascual, M L; García Lacalle, C
2003-03-01
Once-daily dosing (ODD) of gentamicin is advocated as an effective and safe treatment of Gram-negative bacterial infections in adults. There are insufficient data in the literature to justify its use in infants. To compare the efficacy of ODD of gentamicin with that of classical thrice-daily (t.i.d.) administration in infants with acute pyelonephritis. We performed a quasi-experimental study comparing 33 infants who received ODD of gentamicin with a historical control group of 25 infants treated with gentamicin t.i.d. Leukocytosis, C-reactive protein, creatinine, gentamicin dose, peak and trough values, time required for disappearance of fever, and outcome were analyzed. The mean doses of gentamicin (mg/kg/day) were higher in the t.i.d. group (6.4 1.14) than in the ODD group (5.06 0.22; p < 0.001). Peak serum gentamicin concentrations (micro g/ml) were significantly higher in the ODD group (9.32 1.4) than in the t.i.d. group (5.09 1.15; p < 0.001). Mean trough gentamicin concentrations (micro g/ml) were lower in the ODD group than in the t.i.d. group (0.23 0.26 vs 0.78 0.45; p 0.001). There were no significant differences in the duration of fever between the groups (30.64 32 hours in the t.i.d. group vs. 28.57 32 hours in the ODD group). Serum creatinine levels were normal during treatment in both groups. In all patients outcome was good and no adverse effects were noted. Treatment with ODD of gentamicin in our population of infants with acute pyelonephritis was as effective as traditional administration t.i.d. and possibly was equally safe or safer.
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Thompson, Gary A; Solomon, Gail; Albrecht, Helmut H; Reitberg, Donald P; Guenin, Eric
2016-07-01
This study characterized guaifenesin pharmacokinetics in children aged 2 to 17 years (n = 40) who received a single oral dose of guaifenesin (age-based doses of 100-400 mg) 2 hours after breakfast. Plasma samples were obtained before and for 8 hours after dosing and analyzed for guaifenesin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods, relationships with age were assessed using linear regression, and dose proportionality was assessed on 95% confidence intervals. Based on the upper dose recommended in the monograph (for both children and adolescents), area under the curve from time zero to infinity and maximum plasma concentration both increased with age. However, when comparing the upper dose for children aged 2 to 11 years with the lower dose for adolescents aged 12 to 17 years, similar systemic exposure was observed. As expected due to increasing body size, oral clearance (CLo ) and terminal volume of distribution (Vz /F) increased with age. Due to a larger increase in Vz /F than CLo , an increase in terminal exponential half-life was also observed. Allometric scaling indicated no maturation-related changes in CLo and Vz /F. © 2016, The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.
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A 9700-hour durability test of a five centimeter diameter ion thruster
NASA Technical Reports Server (NTRS)
Nakanishi, S.; Finke, R. C.
1973-01-01
A modified Hughes SIT-5 thruster was life-tested at the Lewis Research Center. The final 2700 hours of the test are described with a charted history of thruster operating parameters and off-normal events. Performance and operating characteristics were nearly constant throughout the test except for neutralizer heater power requirements and accelerator drain current. A post-shutdown inspection revealed sputter erosion of ion chamber components and component flaking of sputtered metal. Several flakes caused beamlet divergence and anomalous grid erosion, causing the test to be terminated. All sputter erosion sources were identified.
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Repeated Post- or Presession Cocaine Administration: Roles of Dose and Fixed-Ratio Schedule
ERIC Educational Resources Information Center
Pinkston, Jonathan W.; Branch, Marc N.
2004-01-01
Effects of repeated administration of cocaine to animals behaving under operant contingencies have depended on when the drug is given. Moderate doses given presession have generally led to a decrease in the drug's effect, an outcome usually referred to as tolerance. When these same doses have been given after sessions, the usual result has been no…
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NASA Astrophysics Data System (ADS)
Ejiri, A.
The second questionnaire for scientists and engineers was carried out in 2007, and status of Japanese scientists and engineers were analyzed and reported. A part of the data was reanalyzed from the viewpoint of work life balance. In particular, office/laboratory staying hour and home working hour were analyzed and dependences on various factors were investigated. It was found that these hours depend on gender, marital status, number of child, employment status and age. In addition, the total hours tend to be kept constant regardless of various factors.
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Jenkins, A P; Ghatei, M A; Bloom, S R; Thompson, R P
1992-01-01
To investigate the enterotrophic effects of bolus doses of long chain triglycerides, two groups of eight female Wistar rats were fed identical diets with 48.2% total calories as the essential fatty acid rich oil Efamol. To one group the oil was given in twice daily bolus doses by gavage, while for the other group the oil was mixed with the remainder of the feed and thus consumed over 24 hours. The animals were killed after 20 to 22 days. Bolus dosing significantly increased parameters of mucosal mass along the length of the small intestine in association with an increase in two hour accumulation of vincristine arrested metaphases in small intestinal crypts. In a second experiment, four replicate studies were carried out, each involving two groups of 12 rats respectively fed as described above. After 21 days one animal from each group was killed every two hours, providing regular plasma samples over 24 hours for measurement of gastrin, cholecystokinin, peptide tyrosine-tyrosine and enteroglucagon. Bolus dosing markedly enhanced release of peptide tyrosine-tyrosine and enteroglucagon, but not of gastrin or cholecystokinin. Thus, the enhanced enterotrophic effects of bolus doses of long chain triglycerides could be mediated by release of a distally located gut peptide, perhaps enteroglucagon. PMID:1541417
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Lee, Banghyun; Kim, Kidong; Suh, Dong Hoon; Shin, Hyun-Jung; No, Jae Hong; Lee, Jung Ryeol; Jee, Byung Chul; Hwang, Jung Won; Do, Sang Hwan; Kim, Yong Beom
2017-06-01
This randomized trial investigated whether a 2-dose administration of intravenous ramosetron (5-hydroxytryptamine type 3 receptor antagonist) is more effective than a single-dose administration in preventing postoperative nausea and vomiting (PONV) in 89 patients who were scheduled to undergo laparoscopic operation for benign gynecologic diseases and to receive intravenous patient-controlled analgesia for relief of postoperative pain. After assignment at a ratio of 1:1, intravenous ramosetron (0.3 mg) was initially administered at the end of skin closure in all patients. Thereafter, ramosetron (0.3 mg) and placebo were administered to the study and control groups, respectively, at 4 hours after the operation. The baseline and operative characteristics were similar between the groups. The incidence of PONV during the 24-hour period after operation which was assessed as the primary endpoint did not differ between the groups. No serious adverse events occurred in either group. A 2-dose administration of intravenous ramosetron may not be superior to a single-dose administration in preventing PONV in patients undergoing laparoscopic operation for benign gynecologic diseases.
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Active immunity induced by passive IgG post-exposure protection against ricin.
Hu, Charles Chen; Yin, Junfei; Chau, Damon; Cherwonogrodzky, John W; Hu, Wei-Gang
2014-01-21
Therapeutic antibodies can confer an instant protection against biothreat agents when administered. In this study, intact IgG and F(ab')2 from goat anti-ricin hyperimmune sera were compared for the protection against lethal ricin mediated intoxication. Similar ricin-binding affinities and neutralizing activities in vitro were observed between IgG and F(ab')2 when compared at the same molar concentration. In a murine ricin intoxication model, both IgG and F(ab')2 could rescue 100% of the mice by one dose (3 nmol) administration of antibodies 1 hour after 5 × LD50 ricin challenge. Nine days later, when the rescued mice received a second ricin challenge (5 × LD50), only the IgG-treated mice survived; the F(ab')2-treated mice did not. The experimental design excluded the possibility of residual goat IgG responsible for the protection against the second ricin challenge. Results confirmed that the active immunity against ricin in mice was induced quickly following the passive delivery of a single dose of goat IgG post-exposure. Furthermore, it was demonstrated that the induced active immunity against ricin in mice lasted at least 5 months. Therefore, passive IgG therapy not only provides immediate protection to the victim after ricin exposure, but also elicits an active immunity against ricin that subsequently results in long term protection.
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Active Immunity Induced by Passive IgG Post-Exposure Protection against Ricin
Hu, Charles Chen; Yin, Junfei; Chau, Damon; Cherwonogrodzky, John W.; Hu, Wei-Gang
2014-01-01
Therapeutic antibodies can confer an instant protection against biothreat agents when administered. In this study, intact IgG and F(ab’)2 from goat anti-ricin hyperimmune sera were compared for the protection against lethal ricin mediated intoxication. Similar ricin-binding affinities and neutralizing activities in vitro were observed between IgG and F(ab’)2 when compared at the same molar concentration. In a murine ricin intoxication model, both IgG and F(ab’)2 could rescue 100% of the mice by one dose (3 nmol) administration of antibodies 1 hour after 5 × LD50 ricin challenge. Nine days later, when the rescued mice received a second ricin challenge (5 × LD50), only the IgG-treated mice survived; the F(ab’)2-treated mice did not. The experimental design excluded the possibility of residual goat IgG responsible for the protection against the second ricin challenge. Results confirmed that the active immunity against ricin in mice was induced quickly following the passive delivery of a single dose of goat IgG post-exposure. Furthermore, it was demonstrated that the induced active immunity against ricin in mice lasted at least 5 months. Therefore, passive IgG therapy not only provides immediate protection to the victim after ricin exposure, but also elicits an active immunity against ricin that subsequently results in long term protection. PMID:24451844
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A dose ranging study of ibuprofen suspension as an antipyretic.
Marriott, S C; Stephenson, T J; Hull, D; Pownall, R; Smith, C M; Butler, A
1991-01-01
A double blind trial was conducted to determine the dose of ibuprofen suspension, which is effective in reducing the body temperature. The principal measure of efficacy was a reduction in axillary temperature of 1 degree C or more three hours after dosing. A second objective of the trial was to compare the incidence and severity of side effects and the palatability of a range of ibuprofen doses. Ninety three children were included in the analysis. All four doses of ibuprofen studied (0.625 mg/kg-5 mg/kg) were associated with temperature reduction and only the lowest dose failed to satisfy the principal measure of efficacy. The influence of dose on the magnitude of the body temperature reduction was significant and the 5 mg/kg dose achieved the largest mean reduction in body temperature (2 degrees C). The tolerability and palatability of all doses studied were excellent. These findings suggest that ibuprofen is a good alternative to paracetamol as an antipyretic. PMID:1929509
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Piruzan, Elham; Haghighatafshar, Mahdi; Faghihi, Reza; Entezarmahdi, Seyed Mohammad
2016-03-01
Radioiodine therapy is known as the most effective treatment of differentiated thyroid carcinoma (DTC) to ablate remnant thyroid tissue after surgery. In patients with DTC treated with radioiodine, internal radiation dosimetry of radioiodine is useful for radiation risk assessment. The aim of this study is to describe a method to estimate the absorbed dose to the blood using medical internal radiation dosimetry methods. In this study, 23 patients with DTC with different administrated activities, 3.7, 4.62, and 5.55 GBq after thyroidectomy, were randomly selected. Blood dosimetry of treated patients was performed with external whole body counting using a dual-head gamma camera imaging device and also with blood sample activity measurements using a dose calibrator. Absorbed dose to the blood was measured at 2, 6, 12, 24, 48, and 96 hours after the administration of radioiodine with the 2 methods. Based on the results of whole body counting and blood sample activity dose rate measurements, 96 hours after administration of 3.7, 4.62, and 5.55 GBq of radioiodine, absorbed doses to patients' blood were 0.65 ± 0.20, 0.67 ± 0.18, 0.79 ± 0.51 Gy, respectively. Increasing radioiodine activity from 3.7 to 5.55 GBq increased blood dose significantly, while there was no significant difference in blood dose between radioiodine dosages of 3.7 and 4.62 GBq. Our results revealed a significant correlation between the blood absorbed dose and blood sample activity and between the blood absorbed dose and whole body counts 24 to 48 hours after the administration of radioiodine.
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Single dose oral analgesics for acute postoperative pain in adults
Moore, R Andrew; Derry, Sheena; McQuay, Henry J; Wiffen, Philip J
2014-01-01
Background Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This overview brings together the results of all those reviews and assesses the reliability of available data. Objectives To summarise data from all Cochrane Reviews that have assessed the effects of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery, who have been given a single dose of oral analgesic taken alone. Methods We identified systematic reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single Review Group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews we extracted the number needed to treat (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, the percentage of participants remedicating by 6, 8, 12, or 24 hours, and results for participants experiencing at least one adverse event. Main results The overview included 35 separate Cochrane Reviews with 38 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 45,000 participants studied in approximately 350 individual studies. The individual reviews included only high-quality trials of standardised design and outcome reporting. The reviews used standardised methods and reporting for both efficacy and harm. Event rates with placebo were consistent in larger data sets. No statistical comparison was undertaken. There were reviews but no trial data were available for acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for dexibuprofen, dextropropoxyphene 130
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Radiation dose effect of DNA repair-related gene expression in mouse white blood cells.
Li, Ming-juan; Wang, Wei-wei; Chen, Shi-wei; Shen, Qian; Min, Rui
2011-10-01
The aim of this study was to screen molecular biomarkers for biodosimetry from DNA repair-related gene expression profiles. Mice were subjected to whole-body exposure with 60Co gamma rays with a dose range of 0-8 Gy at a dose rate of 0.80 Gy/min. RNA was extracted from the peripheral blood of irradiated mice at 4, 8, 12, 24 and 48hrs post-irradiation. The mRNA transcriptional changes of 11 genes related to DNA damage and repair were detected using real-time quantitative polymerase chain reaction (RT-PCR). Of the 11 genes examined, CDKN1A (cyclin-dependent kinase inhibitor 1A or p21, Cip1) and ATM (ataxia telangiectasia mutated) expression levels were found to be heavily up- and down-regulated, respectively, with exposure dose increasing at different post-irradiation times. RAD50 (RAD50 homolog), PLK3 (polo-like kinase 3), GADD45A (growth arrest and DNA damage-inducible, alpha), DDB2 (damage-specific DNA-binding protein 2), BBC3 (BCL2-binding component 3) and IER5 (immediate early response 5) gene expression levels were found to undergo significant oscillating changes over a broad dose range of 2-8 Gy at post-exposure time points observed. Three of the genes were found not to change within the observed exposure dose and post-radiation time ranges. The results of this study add to the biodosimetry with biomarker data pool and will be helpful for constructing appropriate gene expression biomarker systems to evaluate radiation exposure doses.
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Five-year Experience With Arterial Switch Operation in the First Hours of Life.
Chasovskyi, Kyrylo; Mykychak, Yaroslav; Rudenko, Nadiia; Vorobyova, Hanna; Yemets, Illya
2017-01-01
We assessed morbidity after 2 management strategies for arterial switch operation (ASO) in a single institution: first hours of life surgery and conventional approach. From September 2009 to September 2014, 346 consecutive patients who underwent ASO were enrolled. The study group included 92 patients who underwent ASO in the first 24 hours after birth (group I). The control group consisted of 254 patients who underwent ASO after 24 hours of life in the conventional way (group II). Three outcomes were analyzed: postoperative ventilation time (VT), post-extubation hospital length of stay (peLOS), and a composite morbidity index, defined as postoperative VT + peLOS + occurrence of selected major complications. Overall 30-day survival was 98% (2 [2%] group I vs 5 [2%] group II, P = 1.000). Fifty (13.3%) major complications were observed: 14 (15%) in group I and 36 (15%) in group II (P = 0.635). Although peLOS and morbidity index did not differ significantly between groups, postoperative VT (42 hours [24, 67] vs 27 hours [22, 47], P = 0.008) and total hospital stay were significantly longer in group II (18 days [10, 19] vs 14 days [12, 18]). A median volume of 80 mL (60-100 mL) of autologous umbilical cord blood was collected (80 mL, group 1 vs 60 mL, group II; P = 0.090). Homologous blood cell transfusion was avoided in 70 patients (78%) in group I and in 13 patients (6%) in group II (P < 0.001). Arterial switch operation during the initial 24 hours of life has similar outcomes in view of morbidity and mortality to the conventional approach. Copyright © 2017 Elsevier Inc. All rights reserved.
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Zhou, Huili; Xu, Wei; Wu, Guolan; Wu, Lihua; Shentu, Jianzhong; Pan, Zhengfei; Hu, Shuai; Liu, Yang
2016-11-01
Recently a formulation of intravenous (IV) ibuprofen was developed in China for management of mild to moderate pain in patients who could not take oral medications or where intravenous administration was preferable. The aim of this study was to evaluate the pharmacokinetic properties and tolerability of single and multiple doses of ibuprofen injection in healthy Chinese volunteers. This open-label, single- and multiple-dose study was conducted in healthy Chinese volunteers. In the single-dose phase, subjects were randomized to receive a single dose of ibuprofen injection 0.2, 0.4, or 0.8 g administered as a 30-minute IV infusion with a 1-week washout between periods. Blood samples were collected at regular intervals from 0 to 12.5 hours after drug administration and were analyzed using a validated LC-MS/MS method. In the multiple-dose phase, subjects received 0.4 g ibuprofen every 6 hours for 9 doses. Blood samples were obtained before the 7th, 8th, and 9th administration to determine the Cmin at steady state; on the 9th intravenous administration, blood samples were also collected for 12.5 hours after drug administration. Pharmacokinetic parameters were estimated using a noncompartmental model. Tolerability was determined using clinical evaluation and monitoring of adverse events (AEs). A total of 12 healthy male (n = 6) and female (n = 6) Chinese volunteers were enrolled and completed the trial. After IV administration of single dose, the mean (SD) Cmax value increased from 35.77 (6.98) to 117.12 (19.78) µg/mL, and the mean (SD) AUC0-t value increased from 67.63 (10.30) to 230.50 (33.55) µg×h/mL in the range of 0.2-g to 0.8-g dose. The terminal half-life in plasma was ~ 2.0 hours. After IV administration of 9 doses of ibuprofen 400 mg every 6 hours, the mean (SD) Cmax was 66.49 (8.49) µg/mL, the AUC0-t was 135.65 (26.91) µg×h/mL, the t1
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-15
... many hours per day and per week would be safe and healthy for a truck driver to work? 4. Would an hours... given scheduling flexibility--the ability to borrow an hour from another driving day once a week, for... No. FMCSA-2004-19608] RIN 2126-AB26 Hours of Service AGENCY: Federal Motor Carrier Safety...
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-02
... or adversely impact driver health? 3. How many hours per day and per week would be safe and healthy for a truck driver to work? 4. Would an hours-of-service rule that allows drivers to drive an hour... No. FMCSA-2004-19608] RIN 2126-AB26 Hours of Service AGENCY: Federal Motor Carrier Safety...
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Every three-hour versus every six-hour oral feeding in preterm infants: a randomised clinical trial.
Gray, Megan M; Medoff-Cooper, Barbara; Enlow, Elizabeth M; Mukhopadhyay, Sagori; DeMauro, Sara B
2017-02-01
This trial compares two oral feeding schedules, every three-hour and every six-hour oral feeding attempts, to determine which schedule allows for more rapid attainment of full oral feeding in preterm infants. Infants born at ≤33-week gestation were randomly assigned to receive oral feeding every three hours or every six hours if feeding cues were present. The primary outcome was time to full oral feeding; secondary outcomes include respiratory and apnoea rates, growth and length of stay. A total of 55 infants were recruited. There was no difference between the groups in the primary or secondary outcomes. For preterm infants fed when oral feeding cues are present, an every six-hour schedule did not alter the time to full oral feeding and had no effect on rates of tachypnoea, apnoea or length of hospital stay compared to every three-hour feeding schedule. An every six-hour oral feeding schedule led to only small reductions in number of oral feeding attempts per day. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.
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Single dose dipyrone for acute postoperative pain
Derry, Sheena; Faura, Clara; Edwards, Jayne; McQuay, Henry J; Moore, R Andrew
2014-01-01
Background Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought. Objectives To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain. Search methods The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010. Selection criteria Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs. Data collection and analysis Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls. Over 70% of participants
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The biobehavioral and neuroimmune impact of low-dose ionizing radiation.
York, Jason M; Blevins, Neil A; Meling, Daryl D; Peterlin, Molly B; Gridley, Daila S; Cengel, Keith A; Freund, Gregory G
2012-02-01
In the clinical setting, repeated exposures (10-30) to low-doses of ionizing radiation (≤200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation was found to reduce spontaneous locomotor activity by 35% and 36%, respectively, 6 h post irradiation. In contrast, the motivated behavior of social exploration was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene transcripts in the brain demonstrated that gamma radiation increased hippocampal TNF-α expression as early as 4 h post-irradiation. This was coupled to subsequent increases in IL-1RA (8 and 12 h post irradiation) in the cortex and hippocampus and reductions in activity-regulated cytoskeleton-associated protein (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a significant modulator of the neuroimmune response to radiation blocking the ability of 200 cGy gamma radiation from impairing locomotor activity and altering the brain-based inflammatory response to irradiation. Taken together, these findings indicate that low-dose ionizing radiation rapidly activates the neuroimmune system potentially causing early onset fatigue-like symptoms in mice. Copyright © 2011 Elsevier Inc. All rights reserved.
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Dose-time relationships for post-irradiation cutaneous telangiectasia
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cohen, L.; Ubaldi, S.E.
1977-01-01
Seventy-five patients who had received electron beam radiation a year or more previously were studied. The irradiated skin portals were photographed and late reactions graded in terms of the number and severity of telangiectatic lesions observed. The skin dose, number of fractions, overall treatment time and irradiated volume were recorded in each case. A Strandqvist-type iso-effect line was derived for this response. A multi-probit search program also was used to derive best-fitting cell population kinetic parameters for the same data. From these parameters a comprehensive iso-effect table could be computed for a wide range of treatment schedules including daily treatmentmore » as well as fractionation at shorter and longer intervals; this provided a useful set of normal tissue tolerance limits for late effects.« less
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Psychiatric Emergency Services - Can Duty-Hour Changes Help Residents and Patients?
Brainch, Navjot; Schule, Patrick; Laurel, Faith; Bodic, Maria; Jacob, Theresa
2018-04-14
Limitations on resident duty hours have been widely introduced with the intention of decreasing resident fatigue and improving patient outcomes. While there is evidence of improvement in resident well-being and education following such initiatives, they have inadvertently resulted in increased number of hand-offs between clinicians leading to potential errors in patient care. Current literature emphasizes need for more specialty/setting-specific scheduling, while considering residents' opinions when implementing duty-hour reforms. There are no reports examining the impact of duty-hour changes on residents or patients in psychiatric emergency service (PES) settings. Our purpose was to assess the impact of a recent scheduling change and decrease in overall duty hours, on resident well-being and sense of burnout, while also evaluating changes to patient wait-time and length of stay (LOS) in PES. Residents completed Maslach Burnout Inventory and anonymous surveys focusing on: fatigue, sleep, life outside work for shifts - regular (8 am-8 pm) and swing shifts (12 pm-10 pm). Data from the electronic medical records were collected for 6 months pre- and post-schedule change (January 2016-February 2017), for LOS and patient wait-time. Residents' preference for shifts was split. However, 86% reported getting enough sleep during swing shifts, while 83% reported lack of sleep during regular shifts. The average patient wait-time and LOS significantly decreased from 169 to 147 and 690 to 515 min, respectively. The change to swing shifts significantly impacts LOS and patient wait-time. The short shifts demonstrated an improvement in well-being for residents, but were not the singular factor for overall resident satisfaction.
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Wang, Xia; Robinson, Thompson G; Lee, Tsong-Hai; Li, Qiang; Arima, Hisatomi; Bath, Philip M; Billot, Laurent; Broderick, Joseph; Demchuk, Andrew M; Donnan, Geoffrey; Kim, Jong S; Lavados, Pablo; Lindley, Richard I; Martins, Sheila O; Olavarria, Veronica V; Pandian, Jeyaraj D; Parsons, Mark W; Pontes-Neto, Octavio M; Ricci, Stefano; Sharma, Vijay K; Thang, Nguyen H; Wang, Ji-Guang; Woodward, Mark; Anderson, Craig S; Chalmers, John
2017-11-01
A lower dose of intravenous alteplase appears to be a safer treatment option than the standard dose, reducing the risk of symptomatic intracerebral hemorrhage. There is uncertainty, however, over how this effect translates into an overall clinical benefit for patients with acute ischemic stroke (AIS). To assess whether older, Asian, or severely affected patients with AIS who are considered at high risk of thrombolysis may benefit more from low-dose rather than standard-dose alteplase treatment. This study is a prespecified secondary analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded, end-point clinical trial of low-dose vs standard-dose intravenous alteplase for patients with AIS. From March 1, 2012, to August 31, 2015, a total of 3310 patients who had a clinical diagnosis of AIS as confirmed by brain imaging and who fulfilled the local criteria for thrombolysis treatment were included in the alteplase-dose arms. Patients were randomly assigned to receive low-dose (0.6 mg/kg; 15% as bolus and 85% as infusion over 1 hour) or standard-dose (0.9 mg/kg; 10% as bolus and 90% as infusion over 1 hour) alteplase. Of the 3310 randomized patients, 13 patients were excluded for missing consent, mistaken randomization, and duplicate randomization numbers. This secondary analysis was conducted between May 1, 2016, and April 28, 2017. The primary end point was a poor outcome defined by the combination of death and any disability as scored by the modified Rankin Scale (scores range from 2 to 6, with the highest score indicating death) at 90 days. Of the 3297 patients included in the analysis, 1248 (37.9%) were women, and the mean (SD) age was 67 (13) years. No significant differences in the treatment effects were observed between low- and standard-dose alteplase for poor outcomes (death or disability) by age, ethnicity, or severity (all P > .37 for interaction). Similarly, the treatment
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NASA Technical Reports Server (NTRS)
Nakanishi, S.
1976-01-01
A laboratory model 8 cm thruster with improvements to minimize ion chamber erosion and peeling of sputtered metal was subjected to a cyclic endurance test for 15,040 hours and 460 restarts. A charted history of several thruster operating variables and off-normal events are shown in 600-hour segments at three points in the test. The transient behavior of these variables during a typical start-stop cycle is presented. Finding of the post-test inspection confirmed most of the expected results. Charge exchange ions caused normal accelerator grid erosion. The workability of the various design features was substantiated, and attainable improvements in propellant utilization efficiency should significantly reduce accelerator erosion.
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Ilic, S; Drmic, D; Zarkovic, K; Kolenc, D; Coric, M; Brcic, L; Klicek, R; Radic, B; Sever, M; Djuzel, V; Ivica, M; Boban Blagaic, A; Zoricic, Z; Anic, T; Zoricic, I; Djidic, S; Romic, Z; Seiwerth, S; Sikiric, P
2010-04-01
We focused on stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported) because of its hepatoprotective effects. We investigate a particular aspect of the sudden onset of encephalopathy with extreme paracetamol overdose (5 g/kg intraperitoneally) so far not reported: rapidly induced progressive hepatic encephalopathy with generalized convulsions in rats. BPC 157 therapy (10 microg, 10 ng, 10 pg/kg, intraperitoneally or intragastrically) was effective (microg-ng range) against paracetamol toxicity, given in early (BPC 157 immediately after paracetamol, prophylactically) or advanced stage (BPC 157 at 3 hours after paracetamol, therapeutically). At 25 min post-paracetamol increased ALT, AST and ammonium serum values precede liver lesion while in several brain areas, significant damage became apparent, accompanied by generalized convulsions. Through the next 5 hour seizure period and thereafter, the brain damage, liver damage enzyme values and hyperammonemia increased, particularly throughout the 3-24 h post-paracetamol period. BPC 157 demonstrated clinical (no convulsions (prophylactic application) or convulsions rapidly disappeared (therapeutic effect within 25 min)), microscopical (markedly less liver and brain lesions) and biochemical (enzyme and ammonium serum levels decreased) counteraction. Both, the prophylactic and therapeutic benefits (intraperitoneally and intragastrically) clearly imply BPC 157 (microg-ng range) as a highly effective paracetamol antidote even against highly advanced damaging processes induced by an extreme paracetamol over-dose.
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The pharmacokinetics of commonly used antiepileptic drugs in immature CD1 mice
Markowitz, Geoffrey J.; Kadam, Shilpa D.; Boothe, Dawn M.; Irving, Natasha D.; Comi, Anne M.
2010-01-01
Rodents eliminate antiepileptic drugs (AEDs) faster than humans, creating challenges for designing clinically-relevant protocols. Half-lives of AEDs in immature mice are unknown. The pharmacokinetics of commonly-used AEDs were examined in CD1 mice using a single-dose protocol at post-natal day 19. Following intraperitoneal therapeutic dosing, blood serum concentrations spanning 1–48 hours post-administration and corresponding brain tissue concentrations at 4 hours were analyzed. Half-lives of valproate, phenobarbital, diazepam (and metabolites), phenytoin, and levetiracetam were 2.6, 15.8, 22.3, 16.3, and 3.2 hours respectively, compared to 0.8, 7.5, 7.7, 16.0, and 1.5 hours reported for adult mice. Brain-to-blood ratios were comparable to adult ratios. AEDs tested had longer half-lives and maintained therapeutic plasma concentrations longer than reported in mature mice, making clinically-relevant protocols feasible. PMID:20848732
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Huang, Alison J; Cummings, Steven R; Schembri, Michael; Vittinghoff, Eric; Ganz, Peter; Grady, Deborah
2016-03-01
To describe the efficacy and tolerability of continuous nitroglycerin for treatment of hot flashes. Perimenopausal and postmenopausal women reporting at least seven hot flashes per day were recruited into a single-arm, dose-escalation trial of continuous transdermal nitroglycerin. Participants were started on a generic 0.1 mg/hour nitroglycerin patch applied daily without patch-free periods. During 4 weeks, participants escalated dosage weekly to 0.2, 0.4, or 0.6 mg/hour as tolerated, then discontinued nitroglycerin during the final week. Changes in hot flash frequency and severity were assessed using symptom diaries. Paired t tests examined change in outcomes between baseline and maximal-dose therapy and after discontinuation of nitroglycerin. Of the 19 participants, mean age was 51.4 (±4.3) years. Women reported an average 10.6 (±3.0) hot flashes and 7.1 (±3.8) moderate-to-severe hot flashes per day at baseline. Eleven women escalated to 0.6 mg/hour, three to 0.4 mg/hour, two to 0.2 mg/hour, and one remained on 0.1 mg/hour nitroglycerin. Two discontinued nitroglycerin before the first outcomes assessment. Among the remaining 17 women, the average daily frequency of hot flashes decreased by 54% and the average frequency of moderate-to-severe hot flashes decreased by 69% from baseline to maximum-dose therapy (P < 0.001 for both). After discontinuing nitroglycerin, participants reported an average 23% increase in frequency of any hot flashes (P = 0.041) and 96% increase in moderate-to-severe hot flashes (P < 0.001). Continuous nitroglycerin may substantially and reversibly decrease hot flash frequency and severity. If confirmed in a randomized blinded trial, it may offer a novel nonhormonal hot flash treatment.
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Post-Mating Sexual Behaviors of Oriental Storks (Ciconia boyciana) in Captivity.
Yoon, Jongmin; Ha, Hae-Sook; Jung, Jung-Shim; Park, Shi-Ryong
2015-08-01
Parental behaviors that vary by sex and breeding stage facilitate the survival of offspring in birds. Females invest in reproducing according to the level of direct and/or indirect benefits provided by males. Males face trade-offs from defending territories or nests, providing for the young, and seeking additional mating opportunities. We examined whether post-mating sexual behaviors such as courtship display and nest-building were associated with reproductive investments made by males and females in the current study. The oriental stork (Ciconia boyciana) is known as a solitary breeder that nests in tall trees and provides biparental care with long post-hatching development. We filmed parental behaviors in seven stork pairs in captivity for 655 hours (245 hours during nest-building, 218 hours during incubation, 328 hours during nestling, and 192 hours during the fledgling period). We found that paired mating behaviors such as synchronous allopreening and bill-clattering were highly skewed to the pre-incubation period. Males participated in nest-building more than females although both sexes shared similar parental care during the incubation and nestling period. Male nest-building was negatively correlated with male nest attentiveness only during the nestling period. Our results suggest that male oriental storks with higher nest-building effort might spend more time taking precautions against conspecific intruders or nest predators near the nests with chicks while the females were attending the nests in the form of biparental care.
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Ludäscher, Petra; Schmahl, Christian; Feldmann, Robert E; Kleindienst, Nikolaus; Schneider, Miriam; Bohus, Martin
2015-10-01
Post-traumatic stress disorder is characterized by intrusive traumatic memories. Presently, a controversial debate is ongoing regarding whether reduced cortisol secretion in post-traumatic stress disorder promotes an automatic retrieval of trauma-associated memories. Hence, a pharmacological elevation of cortisol was proposed to decrease post-traumatic stress disorder symptoms, particularly intrusions. The present study investigated the impact of two different doses of hydrocortisone on automatic memory retrieval using a randomized, double-blind, placebo-controlled, crossover study in 30 inpatients with post-traumatic stress disorder. All participants were female and received various psychotropic medications. They were randomly assigned to one of two groups within a crossover design: they received either 1 week placebo followed by 1 week hydrocortisone 10/d, followed by 1 week placebo, followed by hydrocortisone 30 mg/d (15 participants) or 1 week hydrocortisone 30 mg/d, followed by 1 week placebo, followed by 1 week hydrocortisone 10 mg/d, followed by 1 week placebo (15 participants). The outcome measures were the frequency and the intensity of intrusions, the overall symptomatology of post-traumatic stress disorder and the general psychopathology. We did not find any differences in the frequency and the intensity of post-traumatic stress disorder-related intrusions between the 10 mg hydrocortisone, the 30 mg hydrocortisone and the placebo condition. All effect sizes for the hydrocortisone condition vs. placebo were very small. Additionally, the overall symptomatology of post-traumatic stress disorder and the general psychopathology did not differ between the hydrocortisone therapies and placebo. Our results do not show any effect of the hydrocortisone administration on intrusions in complex post-traumatic stress disorder. © The Author(s) 2015.
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Bravo, Lulu; Chitraka, Amarjeet; Liu, Aixue; Choudhury, Jaydeep; Kumar, Kishore; Berezo, Lennie; Cimafranca, Leonard; Chatterjee, Pallab; Garg, Pankaj; Siriwardene, Prasanna; Bernardo, Rommel; Mehta, Shailesh; Balasubramanian, Sundaram; Karkada, Naveen; Htay Han, Htay
2014-01-01
Regulatory bodies in The Philippines, Sri Lanka, and India require post-marketing surveillance to provide additional safety data on Rotarix™ in real-life settings. In such studies conducted in The Philippines (November 2006 to July 2012; NCT00353366), Sri Lanka (November 2008 to August 2009; NCT00779779), and India (August 2009 to April 2010; NCT00938327), 2 doses of Rotarix™ were administered according to the local prescribing information (PI). The occurrence of at least Grade "2"/"3" solicited adverse event (AE) (fever, vomiting, or diarrhea), within 15 days in The Philippines or 8 days in Sri Lanka and India; unsolicited AEs within 31 days and serious adverse events (SAEs) throughout the study were recorded. Of the 1494, 522, and 332 infants enrolled in The Philippines, Sri Lanka, and India, 14.7% 14.9% and 12.7% infants, respectively recorded at least Grade "2"/"3" solicited AEs. The most commonly reported solicited AEs were irritability in The Philippines (32.2% post-Dose-1; 23.5% post-Dose-2) and India (23.0% post-Dose-1; 13.2% post-Dose-2), and fever (18.0% post-Dose-1; 20.2% post-Dose-2) in Sri Lanka. Unsolicited AEs were recorded in 24.5% (The Philippines), 4.8% (Sri Lanka), and 6.9% (India) of infants. Forty-one SAEs were recorded in the Philippines of which 6 (decreased oral intake with increased sleeping time and constipation; pneumonia, urinary tract infection, and intussusception) were considered by the investigators as causally related to vaccination. One vaccine-unrelated SAE occurred in a Sri Lankan infant. All SAEs resolved and the infants recovered. Two doses of Rotarix™, administered to healthy infants according to local PI, were well tolerated in The Philippines, Sri Lanka, and India.
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Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain
Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee
2013-01-01
We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736
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Kollias, Anastasios; Destounis, Antonios; Kalogeropoulos, Petros; Kyriakoulis, Konstantinos G; Ntineri, Angeliki; Stergiou, George S
2018-07-01
This study assessed the diagnostic accuracy of a novel 24-hour ambulatory blood pressure (ABP) monitor (Microlife WatchBP O3 Afib) with implemented algorithm for automated atrial fibrillation (AF) detection during each ABP measurement. One hundred subjects (mean age 70.6±8.2 [SD] years; men 53%; hypertensives 85%; 17 with permanent AF; 4 paroxysmal AF; and 79 non-AF) had simultaneous 24-hour ABP monitoring and 24-hour Holter monitoring. Among a total of 6410 valid ABP readings, 1091 (17%) were taken in ECG AF rhythm. In reading-to-reading ABP analysis, the sensitivity, specificity, and accuracy of ABP monitoring in detecting AF were 93%, 87%, and 88%, respectively. In non-AF subjects, 12.8% of the 24-hour ABP readings indicated false-positive AF, of whom 27% were taken during supraventricular premature beats. There was a strong association between the proportion of false-positive AF readings and that of supraventricular premature beats ( r =0.67; P <0.001). Receiver operating characteristic curve revealed that in paroxysmal AF and non-AF subjects, AF-positive readings at 26% during 24-hour ABP monitoring had 100%/85% sensitivity/specificity (area under the curve 0.91; P <0.01) for detecting paroxysmal AF. These findings suggest that in elderly hypertensives, a novel 24-hour ABP monitor with AF detector has high sensitivity and moderate specificity for AF screening during routine ABP monitoring. Thus, in elderly hypertensives, a 24-hour ABP recording with at least 26% of the readings suggesting AF indicates a high probability for AF diagnosis and should be regarded as an indication for performing 24-hour Holter monitoring. © 2018 American Heart Association, Inc.
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ERIC Educational Resources Information Center
Laitinen, Amy
2012-01-01
The basic currency of higher education--the credit hour--represents the root of many problems plaguing America's higher education system: the practice of measuring time rather than learning. "Cracking the Credit Hour" traces the history of this time-based unit, from the days of Andrew Carnegie to recent federal efforts to define a credit…
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The financial and service implications of splitting fixed-dose antiretroviral drugs - a case study.
Taylor, R; Carlin, E; Sadique, Z; Ahmed, I; Adams, E J
2015-02-01
In 2010/2011, regional commissioners withdrew payment for the fixed-dose combination Combivir, forcing a switch to component drugs. This was deemed clinically acceptable and annual savings of £44 k expected. We estimated the true costs of switching and examined patient outcomes. Information for 46 patients using Combivir was extracted from case notes for each clinical contact in the 12 months pre- and post-switch (clinician seen, tests, antiretrovirals). Post-switch care costs £93/patient more annually versus pre-switch (95% CI £424 to £609), yielding £4278/year more post-switch for all patients. Drug and pathology costs were more expensive post-switch and extra clinical visits required. None of these results were statistically significant. Forty-two per cent of patients switched directly or in the subsequent year to an alternative fixed-dose combination rather than generics. Costs in this group were significantly higher post-switch driven by drug cost. Six patients (13%) reported problems with the switch including confusion around dosing and new side effects. As less-expensive generic antiretroviral drugs become available, it may appear cheaper to switch from fixed-dose combinations to component drugs. However, the additional clinical costs involved may outweigh the initial cost savings of the drugs and switching may cause confusion for some patients, risking loss of adherence. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
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Time related neutralization of two doses acetyl salicylic acid.
Aguejouf, O; Malfatti, E; Belon, P; Doutremepuich, C
2000-11-15
Aspirin has a well established role in the prevention of arterial thrombosis. Discussion on the efficacy and safety of aspirin in the treatment and prophylaxis of thrombosis has become an important issue. In fact, hemorrhage complications are often associated with its use. On the other hand, previous studies showed unexpected thrombotic potencies associated with the presence of this drug at ultra low doses (ULD) in the circulation. In this study, we aimed to evaluate the effect of aspirin at ULD, injected 1, 2, or 3 hours after the administration of aspirin at 100 mg/kg, on hemostasis and bleeding in rats. We used an experimental model of thrombosis induced by laser beams to evaluate these effects. Platelet aggregation was determined by Cardinal and Flower method. Results from this investigation demonstrate that the neutralizing effect of aspirin at ULD did not operate significantly 1 hour after the injection of aspirin at 100 mg/kg. This effect was observed 2 and 3 hours after. The use of aspirin at ULD to neutralize the side effects of aspirin at high doses will reduce the hemorrhagic risk during extra corporeal circulation. The therapeutic benefit and safety of aspirin therapy in the treatment of cardiovascular diseases can be obtained.
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HUMAN ACTIVITIES THAT MAY LEAD TO HIGH INHALED INTAKE DOSES IN CHILDREN AGED 6-13
The paper focuses on possible activities of children aged 6-13 that may make them susceptible to high hourly intake doses of ozone (O3) air pollution. Data from an O3 exposure modeling exercise indicates that a relatively few hours can account for a significant amount of the t...
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Asundi, Krishna; Johnson, Peter W; Dennerlein, Jack T
2012-01-01
To determine the number of direct measurements needed to obtain a representative estimate of typing force and wrist kinematics, continuous measures of keyboard reaction force and wrist joint angle were collected at the workstation of 22 office workers while they completed their own work over three days, six hours per day. Typing force and wrist kinematics during keyboard, mouse and idle activities were calculated for each hour of measurement along with variance in measurements between subjects and between day and hour within subjects. Variance in measurements between subjects was significantly greater than variance in measurements between days and hours within subjects. Therefore, we concluded a single, one-hour period of continuous measures is sufficient to identify differences in typing force and wrist kinematics between subjects. Within subjects, day and hour of measurement had a significant effect on some measures and thus should be accounted for when comparing measures within a subject. The dose response relationship between exposure to computer related biomechanical risk factors and musculoskeletal disorders is poorly understood due to the difficulty and cost of direct measures. This study demonstrates a single hour of direct continuous measures is sufficient to identify differences in wrist kinematics and typing force between individuals.
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Farhang, Borzoo; Grondin, Lydia
2018-01-01
Postoperative sore throat (POST) is commonly seen after endotracheal intubation, and oral zinc prevents oral mucositis associated with chemotherapy. This study is designed to evaluate the effects of administration of zinc lozenges on POST. Seventy-nine patients undergoing low- or moderate-risk surgery with endotracheal intubation were randomly assigned into 2 groups: Control group received placebo and zinc group received 40-mg zinc lozenges 30 minutes preoperatively. Patients were assessed for incidence and severity (4-point scale, 0-3) of POST at 0, 2, 4, and 24 hours postoperatively. The primary outcome was incidence of POST at 4 hours after surgery. The secondary outcomes were the incidence of POST at 0, 2, and 24 hours and the severity of POST. At 4 hours, there was a significantly lower incidence of POST in the zinc group, 7%, than the control group, 29% (P = .046). The incidence of POST at 0 hour was 0% in zinc group and 24% in control group (P = .004). The highest incidence of POST occurred at the second hour after surgery, with the rate of 10% in the zinc group and 34% in the control group (P = .0495). The incidence of POST at 24 hours was 13% in zinc group and 24% in control group (not significant). The severity of POST was significantly lower in the zinc group for mild (P = .003) and moderate (P = .004) POST. The administration of a single dose of 40-mg zinc lozenge 30 minutes preoperatively is effective to reduce both incidence of POST in the first 4 hours and severity of mild and moderate POST in the immediate postoperative period.
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An alternative method for immediate dose estimation using CaSO4:Dy based TLD badges
NASA Astrophysics Data System (ADS)
Singh, A. K.; Menon, S. N.; Dhabekar, Bhushan; Kadam, Sonal; Chougaonkar, M. P.; Babu, D. A. R.
2014-11-01
CaSO4:Dy based Thermoluminescence dosimeters (TLDs) are being used in country wide personnel monitoring program in India. The TL glow curve of CaSO4:Dy consists of a dosimetric peak at 220 °C and a low temperature peak at 120 °C which is unstable at room temperature. The TL integral counts in CaSO4:Dy reduces by 15% in seven days after irradiation due to the thermal fading of 120 °C TL peak. As the dosimetric procedure involves total integrated counts for dose conversion, the dosimeters are typically read about a week after receiving. However in the event of a suspected over exposure, where urgent processing is expected, this poses limitation. Post irradiation annealing treatment is used in such cases of immediate readout of cards. In this paper we report a new and easier to use technique based on optical bleaching for the urgent processing of TLD cards. Optical bleaching with green LED (∼555 nm photons) of 25,000 lux for one and half hour removes the low temperature TL peak without affecting the dosimetric peak. This method can be used for immediate dose estimation using CaSO4:Dy based TLD badges.
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Fujita, Mitsue; Sato, Katsuaki; Nishioka, Hiroshi; Sakai, Fumihiko
2014-04-01
The objective of this article is to evaluate the efficacy and tolerability of two doses of oral sumatriptan vs placebo in the acute treatment of migraine in children and adolescents. Currently, there is no approved prescription medication in Japan for the treatment of migraine in children and adolescents. This was a multicenter, outpatient, single-attack, double-blind, randomized, placebo-controlled, parallel-group study. Eligible patients were children and adolescents aged 10 to 17 years diagnosed with migraine with or without aura (ICHD-II criteria 1.1 or 1.2) from 17 centers. They were randomized to receive sumatriptan 25 mg, 50 mg or placebo (1:1:2). The primary efficacy endpoint was headache relief by two grades on a five-grade scale at two hours post-dose. A total of 178 patients from 17 centers in Japan were enrolled and randomized to an investigational product in double-blind fashion. Of these, 144 patients self-treated a single migraine attack, and all provided a post-dose efficacy assessment and completed the study. The percentage of patients in the full analysis set (FAS) population who report pain relief at two hours post-treatment for the primary endpoint was higher in the placebo group than in the pooled sumatriptan group (38.6% vs 31.1%, 95% CI: -23.02 to 8.04, P = 0.345). The percentage of patients in the FAS population who reported pain relief at four hours post-dose was higher in the pooled sumatriptan group (63.5%) than in the placebo group (51.4%) but failed to achieve statistical significance ( P = 0.142). At four hours post-dose, percentages of patients who were pain free or had complete relief of photophobia or phonophobia were numerically higher in the sumatriptan pooled group compared to placebo. Both doses of oral sumatriptan were well tolerated. No adverse events (AEs) were serious or led to study withdrawal. The most common AEs were somnolence in 6% (two patients) in the sumatriptan 25 mg treatment group and chest
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Dubinsky, Marla C; Phan, Becky L; Singh, Namita; Rabizadeh, Shervin; Mould, Diane R
2017-01-01
Standard of care (SOC; combination of 5-10 mg/kg and an interval every 6-8 weeks) dosing of infliximab (IFX) is associated with significant loss of response. Dashboards using covariates that influence IFX pharmacokinetics (PK) may be a more precise way of optimizing anti-TNF dosing. We tested a prototype dashboard to compare forecasted dosing regimens with actual administered regimens and SOC. Fifty IBD patients completing IFX induction were monitored during maintenance (weeks 14-54). Clinical and laboratory data were collected at each infusion; serum was analyzed for IFX concentrations and anti-drug antibodies (ADA) at weeks 14 and 54 (Prometheus Labs, San Diego). Dosing was blinded to PK data. Dashboard-based assessments were conducted on de-identified clinical, laboratory, and PK data. Bayesian algorithms were used to forecast individualized troughs and determine optimal dosing to maintain target trough concentrations (3 μg/mL). Dashboard forecasted dosing post-week 14 was compared to actual administered dose and frequency and SOC. Using week 14 clinical data only, the dashboard recommended either a dose or an interval change (<0.5 mg/kg or <1 week difference) in 43/50 patients; only 44% recommended to have SOC dosing. When IFX14 concentration and ADA status were added to clinical data, dose and/or interval changes based on actual dosing were recommended in 48/50 (96%) patients; SOC dosing was recommended in only 11/50 (22%). Dashboard recommended SOC IFX dosing in a minority of patients. Dashboards will be an important tool to individualize IFX dosing to improve treatment durability.
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Riddle, Mark S; Connor, Patrick; Fraser, Jamie; Porter, Chad K; Swierczewski, Brett; Hutley, Emma J; Danboise, Brook; Simons, Mark P; Hulseberg, Christine; Lalani, Tahaniyat; Gutierrez, Ramiro L; Tribble, David R
2017-11-29
Recommended treatment for travelers' diarrhea includes the combination of an antibiotic, usually a fluoroquinolone or azithromycin, and loperamide for rapid resolution of symptoms. However, adverse events, postdose nausea with high-dose azithromycin, effectiveness of single-dose rifaximin, and emerging resistance to front-line agents are evidence gaps underlying current recommendations. A randomized, double-blind trial was conducted in 4 countries (Afghanistan, Djibouti, Kenya, and Honduras) between September 2012 and July 2015. US and UK service members with acute watery diarrhea were randomized and received single-dose azithromycin (500 mg; 106 persons), levofloxacin (500 mg; 111 persons), or rifaximin (1650 mg; 107 persons), in combination with loperamide (labeled dosing). The efficacy outcomes included clinical cure at 24 hours and time to last unformed stool. Clinical cure at 24 hours occurred in 81.4%, 78.3%, and 74.8% of the levofloxacin, azithromycin, and rifaximin arms, respectively. Compared with levofloxacin, azithromycin was not inferior (P = .01). Noninferiority could not be shown with rifaximin (P = .07). At 48 and 72 hours, efficacy among regimens was equivalent (approximately 91% at 48 and 96% at 72 hours). The median time to last unformed stool did not differ between treatment arms (azithromycin, 3.8 hours; levofloxacin, 6.4 hours; rifaximin, 5.6 hours). Treatment failures were uncommon (3.8%, 4.4%, and 1.9% in azithromycin, levofloxacin, and rifaximin arms, respectively) (P = .55). There were no differences between treatment arms with postdose nausea, vomiting, or other adverse events. Single-dose azithromycin, levofloxacin, and rifaximin with loperamide were comparable for treatment of acute watery diarrhea. NCT01618591. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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12 hour shifts the Nambour Hospital experience.
2007-08-01
Union members have a lengthy history of campaigning for fair working hours and conditions. The success of such campaigns has led to the implementation of the eight hour working day and the 40 hour and then 38 hour week as industrial standards. More recently though, calls for greater flexibility in their shift arrangements by nurses at Nambour Hospital have led to a voluntary 12 hour shift being implemented in their Intensive Care Unit. While union members are protective of their hard won gains in achieving reduced working hours through the 8 hour day--ICU nurses at Nambour Hospital say the voluntary 12 hour shift initiative goes a way in addressing their work/life balance issues.
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Gilca, Vladimir; Sauvageau, Chantal; Boulianne, Nicole; De Serres, Gatson; Crajden, Mel; Ouakki, Manale; Trevisan, Andrea; Dionne, Marc
2015-01-01
This randomized, blinded study evaluated the immunogenicity and safety of a booster dose of Gardasil (qHPV) or Cervarix (bHPV) when administered to 12-13 year-old girls who were vaccinated at the age of 9-10 with 2 doses of qHPV (0-6 months). 366 out of 416 eligible girls participated in this follow-up study. Antibody titers were measured just before and one month post-booster. A Luminex Total IgG assay was used for antibody assessment and results are presented in Liminex Units (LU). Three years post-primary vaccination, 99-100% of subjects had detectable antibodies to 4HPV genotypes included in the qHPV with GMTs varying from 50 to 322 LU depending on genotype. After a booster dose of qHPV, a ≥4 fold increase of antibody titers to genotypes included in the vaccine was observed in 88-98% of subjects. Post-booster GMTs varied from 1666 to 4536 LU depending on genotype. These GMTs were 1.1 to 1.8-fold higher when compared to those observed one month post-second dose. After a booster of bHPV, a ≥4 fold increase of antibody titers to HPV16 and HPV18 was observed in 93-99% of subjects. The anti-HPV16 and HPV18 GMTs were 5458 and 2665 LU, respectively. These GMTs were 1.2 and 1.8 higher than those observed in the qHPV group (both P < 0.01). In bHPV group a 1.4-1.6-fold increase of antibody GMTs to HPV6 and HPV11was also observed (P < 0.001). The safety profile was acceptable for both vaccines. Both qHPV and bHPV increase antibody titers when given as a booster to girls previously vaccinated with 2 doses of qHPV. The magnitude of the immune response after booster is vaccine-dependent and has the same pattern as that reported after primary vaccination with qHPV or bHPV. When given as a booster, both vaccines have an acceptable safety profile. Longer follow-up studies are warranted to assess the need of booster doses.
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Ghaleb, Ahmed; Khorasani, Arjang; Mangar, Devanand
2012-01-01
Since August Bier reported the first case in 1898, post-dural puncture headache (PDPH) has been a problem for patients following dural puncture. Clinical and laboratory research over the last 30 years has shown that use of smaller-gauge needles, particularly of the pencil-point design, are associated with a lower risk of PDPH than traditional cutting point needle tips (Quincke-point needle). A careful history can rule out other causes of headache. A postural component of headache is the sine qua non of PDPH. In high-risk patients < 50 years, post-partum, in the event a large-gauge needle puncture is initiated, an epidural blood patch should be performed within 24–48 hours of dural puncture. The optimum volume of blood has been shown to be 12–20 mL for adult patients. Complications caused by autologous epidural blood patching (AEBP) are rare. PMID:22287846
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Piruzan, Elham; Haghighatafshar, Mahdi; Faghihi, Reza; Entezarmahdi, Seyed Mohammad
2016-01-01
Abstract Radioiodine therapy is known as the most effective treatment of differentiated thyroid carcinoma (DTC) to ablate remnant thyroid tissue after surgery. In patients with DTC treated with radioiodine, internal radiation dosimetry of radioiodine is useful for radiation risk assessment. The aim of this study is to describe a method to estimate the absorbed dose to the blood using medical internal radiation dosimetry methods. In this study, 23 patients with DTC with different administrated activities, 3.7, 4.62, and 5.55 GBq after thyroidectomy, were randomly selected. Blood dosimetry of treated patients was performed with external whole body counting using a dual-head gamma camera imaging device and also with blood sample activity measurements using a dose calibrator. Absorbed dose to the blood was measured at 2, 6, 12, 24, 48, and 96 hours after the administration of radioiodine with the 2 methods. Based on the results of whole body counting and blood sample activity dose rate measurements, 96 hours after administration of 3.7, 4.62, and 5.55 GBq of radioiodine, absorbed doses to patients’ blood were 0.65 ± 0.20, 0.67 ± 0.18, 0.79 ± 0.51 Gy, respectively. Increasing radioiodine activity from 3.7 to 5.55 GBq increased blood dose significantly, while there was no significant difference in blood dose between radioiodine dosages of 3.7 and 4.62 GBq. Our results revealed a significant correlation between the blood absorbed dose and blood sample activity and between the blood absorbed dose and whole body counts 24 to 48 hours after the administration of radioiodine. PMID:26986171
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Economic and microbiologic evaluation of single-dose vial extension for hazardous drugs.
Rowe, Erinn C; Savage, Scott W; Rutala, William A; Weber, David J; Gergen-Teague, Maria; Eckel, Stephen F
2012-07-01
The update of US Pharmacopeia Chapter <797> in 2008 included guidelines stating that single-dose vials (SDVs) opened and maintained in an International Organization for Standardization Class 5 environment can be used for up to 6 hours after initial puncture. A study was conducted to evaluate the cost of discarding vials after 6 hours and to further test sterility of vials beyond this time point, subsequently defined as the beyond-use date (BUD). Financial determination of SDV waste included 2 months of retrospective review of all doses prescribed. Additionally, actual waste log data were collected. Active and control vials (prepared using sterilized trypticase soy broth) were recovered, instead of discarded, at the defined 6-hour BUD. The institution-specific waste of 19 selected SDV medications discarded at 6 hours was calculated at $766,000 annually, and tracking waste logs for these same medications was recorded at $770,000 annually. Microbiologic testing of vial extension beyond 6 hours showed that 11 (1.86%) of 592 samples had one colony-forming unit on one of two plates. Positive plates were negative at subsequent time points, and all positives were single isolates most likely introduced during the plating process. The cost of discarding vials at 6 hours was significant for hazardous medications in a large academic medical center. On the basis of microbiologic data, vial BUD extension demonstrated a contamination frequency of 1.86%, which likely represented exogenous contamination; vial BUD extension for the tested drugs showed no growth at subsequent time points and could provide an annual cost savings of more than $600,000.
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Kong, Eva Yi; Cheng, Shuk Han; Yu, Kwan Ngok
2016-07-01
The in vivo low-dose responses of zebrafish (Danio rerio) embryos to 150 kV X-rays with different levels of hardness were examined through the number of apoptotic events revealed at 24 h post fertilization by vital dye acridine orange staining. Our results suggested that a triphasic dose response was likely a common phenomenon in living organisms irradiated by X-rays, which comprised an ultra-low-dose inhibition, low-dose stimulation and high-dose inhibition. Our results also suggested that the hormetic zone (or the stimulation zone) was shifted towards lower doses with application of filters. The non-detection of a triphasic dose response in previous experiments could likely be attributed to the use of hard X-rays, which shifted the hormetic zone into an unmonitored ultra-low-dose region. In such cases where the subhormetic zone was missed, a biphasic dose response would be reported instead. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.
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Kang, Woo Youl; Seong, Sook Jin; Ohk, Boram; Gwon, Mi-Ri; Kim, Bo Kyung; La, Sookie; Kim, Hyun-Ju; Cho, Seungil; Yoon, Young-Ran; Yang, Dong Heon; Lee, Hae Won
2018-01-01
A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance. The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography-tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period. Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (C max ) and the area under the plasma concentration-time curve from time 0 to the last measurement (AUC 0-t ) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean C max and AUC 0-t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan C max and AUC 0-t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353-0.9846) and 0.9431 (0.8698-1.0226), respectively. The GMR and 90% CI for the S-amlodipine C max and AUC 0-t (FDC/concomitant administration) were 0.9829 (0.9143-1.0567) and 0.9632 (0.8798-1.0546), respectively. As the intrasubject variability of the C max for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. CKD-828 FDC tablets were shown to
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Fabritius, Maria Louise; Wetterslev, Jørn; Mathiesen, Ole; Dahl, Jørgen B
2017-01-01
Background During the last 15 years, gabapentin has become an established component of postoperative pain treatment. Gabapentin has been employed in a wide range of doses, but little is known about the optimal dose, providing the best balance between benefit and harm. This systematic review with meta-analyses aimed to explore the beneficial and harmful effects of various doses of gabapentin administered to surgical patients. Materials and methods Data in this paper were derived from an original review, and the subgroup analyses were predefined in an International Prospective Register of Systematic Reviews published protocol: PROSPERO (ID: CRD42013006538). The methods followed Cochrane guidelines. The Cochrane Library’s CENTRAL, PubMed, EMBASE, Science Citation Index Expanded, Google Scholar, and FDA database were searched for relevant trials. Randomized clinical trials comparing gabapentin versus placebo were included. Four different dose intervals were investigated: 0–350, 351–700, 701–1050, and >1050 mg. Primary co-outcomes were 24-hour morphine consumption and serious adverse events (SAEs), with emphasis put on trials with low risk of bias. Results One hundred and twenty-two randomized clinical trials, with 8466 patients, were included. Sixteen were overall low risk of bias. No consistent increase in morphine-sparing effect was observed with increasing doses of gabapentin from the trials with low risk of bias. Analyzing all trials, the smallest and the highest dose subgroups demonstrated numerically the most prominent reduction in morphine consumption. Twenty-seven trials reported 72 SAEs, of which 83% were reported in the >1050 mg subgroup. No systematic increase in SAEs was observed with increasing doses of gabapentin. Conclusion Data were sparse, and the small number of trials with low risk of bias is a major limitation for firm conclusions. Taking these limitations into account, we were not able to demonstrate a clear relationship between the dosage
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Low-dose aspirin use and survival in breast cancer patients: A nationwide cohort study.
Mc Menamin, Úna C; Cardwell, Chris R; Hughes, Carmel M; Murray, Liam J
2017-04-01
Preclinical evidence from breast cancer cell lines and animal models suggest that aspirin could have anti-cancer properties. In a large breast cancer patient cohort, we investigated whether post-diagnostic low-dose aspirin use was associated with a reduction in the risk of breast cancer-specific mortality. We identified 15,140 newly diagnosed breast cancer patients within the Scottish Cancer Registry. Linkages to the Scottish Prescribing Information System provided data on dispensed medications and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% CIs for breast cancer-specific and all-cause mortality by post-diagnostic low-dose aspirin use. HRs were adjusted for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of statins. Secondary analysis investigated the association between pre-diagnostic low-dose aspirin use and breast cancer-specific and all-cause mortality. Post-diagnostic users of low-dose aspirin appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.44, 95% CI 1.26, 1.65) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.92, 95% CI 0.75, 1.14). Findings were similar in analysis by increasing duration of use and in analysis of pre-diagnostic low-dose aspirin use. In this large nationwide study of breast cancer patients, we found little evidence of an association between post-diagnostic low-dose aspirin use and cancer-specific mortality. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Brennan, Alana T; Thea, Donald M; Semrau, Katherine; Goggin, Caitlin; Scott, Nancy; Pilingana, Portipher; Botha, Belinda; Mazimba, Arthur; Hamomba, Leoda; Seidenberg, Phil
2014-01-01
Access to lifesaving prevention of mother-to-child transmission (PMTCT) services is problematic in rural Zambia. The simplest intervention used in Zambia has been 2-dose nevirapine (NVP) administration in the peripartum period, a regimen of 1 NVP tablet to the mother at the onset of labor and 1 dose in the form of syrup to the newborn within 4 to 72 hours after birth. This 2-dose regimen has been shown to reduce MTCT by nearly 50%. We set out to demonstrate that in-home HIV testing and NVP dosing by traditional birth attendants (TBAs) is feasible and acceptable by women in rural Zambia. This was a pilot program using TBAs to perform rapid saliva-based HIV testing and administer single-dose NVP in tablet form to the mother at the onset of labor and syrup to the infant after birth. A total of 280 pregnant women were consented and enrolled into the program, of whom 124 (44.3%) gave birth at home with the assistance of a trained TBA. Of those, 16 (12.9%) were known to be HIV positive, and 101 of the remaining 108 (93.5%) accepted a rapid HIV test. All these women tested HIV negative. In the subset of 16 mothers who were HIV positive, 13 (81.3%) took single-dose NVP administered by a TBA between 1 and 24 hours prior to birth and 100% of exposed newborns (16 of 16) received NVP syrup within 72 hours after birth, 80% of whom were dosed in the first 24 hours of life. With the substantial shortage of human resources in public health care throughout sub-Saharan Africa, it is extremely valuable to utilize lay health care workers to help extended services beyond the level of the facility. Given the high uptake of PMTCT services we believe that TBAs with proper training and support can successfully provide country-approved PMTCT. © 2013 by the American College of Nurse-Midwives.
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Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J
2013-06-01
To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.
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Ultra-low dose naltrexone enhances cannabinoid-induced antinociception.
Paquette, Jay; Olmstead, Mary C; Olmstead, Mary
2005-12-01
Both opioids and cannabinoids have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to Gi/o-proteins. Surprisingly, the analgesic effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist, naltrexone. As opioid and cannabinoid systems interact, this study investigated whether ultra-low dose naltrexone also influences cannabinoid-induced antinociception. Separate groups of Long-Evans rats were tested for antinociception following an injection of vehicle, a sub-maximal dose of the cannabinoid agonist WIN 55 212-2, naltrexone (an ultra-low or a high dose) or a combination of WIN 55 212-2 and naltrexone doses. Tail-flick latencies were recorded for 3 h, at 10-min intervals for the first hour, and at 15-min intervals thereafter. Ultra-low dose naltrexone elevated WIN 55 212-2-induced tail flick thresholds without extending its duration of action. This enhancement was replicated in animals receiving intraperitoneal or intravenous injections. A high dose of naltrexone had no effect on WIN 55 212-2-induced tail flick latencies, but a high dose of the cannabinoid 1 receptor antagonist SR 141716 blocked the elevated tail-flick thresholds produced by WIN 55 212-2+ultra-low dose naltrexone. These data suggest a mechanism of cannabinoid-opioid interaction whereby activated opioid receptors that couple to Gs-proteins may attenuate cannabinoid-induced antinociception and/or motor functioning.
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van der Brempt, X; Ledent, C; Mairesse, M
1997-06-01
In this study, we performed 150 desensitizations in 139 Hymenoptera venom allergic patients (109 Yellow jacket allergic patients, 19 Honey bee allergic patients and 11 patients sensitized to both insects, who received a dual desensitization). We used a rush protocol, allowing injection of a total cumulated dose of 125,1 (Honey bee) to 175,1 (Yellow jacket) microgram of venom in 30 hours. Patients were hospitalized, with all emergency precautions for treating systemic reactions. The protocol was well tolerated in 147/150 cases; 3 patients had a benign systemic reaction. Patients received monthly maintenance doses of 100 micrograms venom. 39 patients experienced a field sting during immunotherapy; 2 of them (5%) had a benign systemic reaction. Thus, our rush desensitization protocol seems to be safe and effective.
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Low dose mTHPC photodynamic therapy for cholangiocarcinoma
NASA Astrophysics Data System (ADS)
Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg
2013-06-01
Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.
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Schachtel, Bernard; Aspley, Sue; Shephard, Adrian; Shea, Timothy; Smith, Gary; Schachtel, Emily
2014-07-03
The sore throat pain model has been conducted by different clinical investigators to demonstrate the efficacy of acute analgesic drugs in single-dose randomized clinical trials. The model used here was designed to study the multiple-dose safety and efficacy of lozenges containing flurbiprofen at 8.75 mg. Adults (n=198) with moderate or severe acute sore throat and findings of pharyngitis on a Tonsillo-Pharyngitis Assessment (TPA) were randomly assigned to use either flurbiprofen 8.75 mg lozenges (n=101) or matching placebo lozenges (n=97) under double-blind conditions. Patients sucked one lozenge every three to six hours as needed, up to five lozenges per day, and rated symptoms on 100-mm scales: the Sore Throat Pain Intensity Scale (STPIS), the Difficulty Swallowing Scale (DSS), and the Swollen Throat Scale (SwoTS). Reductions in pain (lasting for three hours) and in difficulty swallowing and throat swelling (for four hours) were observed after a single dose of the flurbiprofen 8.75 mg lozenge (P<0.05 compared with placebo). After using multiple doses over 24 hours, flurbiprofen-treated patients experienced a 59% greater reduction in throat pain, 45% less difficulty swallowing, and 44% less throat swelling than placebo-treated patients (all P<0.01). There were no serious adverse events. Utilizing the sore throat pain model with multiple doses over 24 hours, flurbiprofen 8.75 mg lozenges were shown to be an effective, well-tolerated treatment for sore throat pain. Other pharmacologic actions (reduced difficulty swallowing and reduced throat swelling) and overall patient satisfaction from the flurbiprofen lozenges were also demonstrated in this multiple-dose implementation of the sore throat pain model. This trial was registered with ClinicalTrials.gov, registration number: NCT01048866, registration date: January 13, 2010.
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2014-01-01
Background The sore throat pain model has been conducted by different clinical investigators to demonstrate the efficacy of acute analgesic drugs in single-dose randomized clinical trials. The model used here was designed to study the multiple-dose safety and efficacy of lozenges containing flurbiprofen at 8.75 mg. Methods Adults (n = 198) with moderate or severe acute sore throat and findings of pharyngitis on a Tonsillo-Pharyngitis Assessment (TPA) were randomly assigned to use either flurbiprofen 8.75 mg lozenges (n = 101) or matching placebo lozenges (n = 97) under double-blind conditions. Patients sucked one lozenge every three to six hours as needed, up to five lozenges per day, and rated symptoms on 100-mm scales: the Sore Throat Pain Intensity Scale (STPIS), the Difficulty Swallowing Scale (DSS), and the Swollen Throat Scale (SwoTS). Results Reductions in pain (lasting for three hours) and in difficulty swallowing and throat swelling (for four hours) were observed after a single dose of the flurbiprofen 8.75 mg lozenge (P <0.05 compared with placebo). After using multiple doses over 24 hours, flurbiprofen-treated patients experienced a 59% greater reduction in throat pain, 45% less difficulty swallowing, and 44% less throat swelling than placebo-treated patients (all P <0.01). There were no serious adverse events. Conclusions Utilizing the sore throat pain model with multiple doses over 24 hours, flurbiprofen 8.75 mg lozenges were shown to be an effective, well-tolerated treatment for sore throat pain. Other pharmacologic actions (reduced difficulty swallowing and reduced throat swelling) and overall patient satisfaction from the flurbiprofen lozenges were also demonstrated in this multiple-dose implementation of the sore throat pain model. Trial registration This trial was registered with ClinicalTrials.gov, registration number: NCT01048866, registration date: January 13, 2010. PMID:24988909
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Teh, Daniel Boon Loong; Chua, Soo Min; Prasad, Ankshita; Kakkos, Ioannis; Jiang, Wenxuan; Yue, Mu; Liu, Xiaogang; All, Angelo Homayoun
2018-03-01
Although general hypothermia is recognized as a clinically applicable neuroprotective intervention, acute moderate local hypothermia post contusive spinal cord injury (SCI) is being considered a more effective approach. Previously, we have investigated the feasibility and safety of inducing prolonged local hypothermia in the central nervous system of a rodent model. Here, we aimed to verify the efficacy and neuroprotective effects of 5 and 8 hours of local moderate hypothermia (30±0.5°C) induced 2 hours after moderate thoracic contusive SCI in rats. Rats were induced with moderate SCI (12.5 mm) at its T8 section. Local hypothermia (30±0.5°C) was induced 2 hours after injury induction with an M-shaped copper tube with flow of cold water (12°C), from the T6 to the T10 region. Experiment groups were divided into 5-hour and 8-hour hypothermia treatment groups, respectively, whereas the normothermia control group underwent no hypothermia treatment. The neuroprotective effects were assessed through objective weekly somatosensory evoked potential (SSEP) and motor behavior (basso, beattie and bresnahan Basso, Beattie and Bresnahan (BBB) scoring) monitoring. Histology on spinal cord was performed until at the end of day 56. All authors declared no conflict of interest. This work was supported by the Singapore Institute for Neurotechnology Seed Fund (R-175-000-121-733), National University of Singapore, Ministry of Education, Tier 1 (R-172-000-414-112.). Our results show significant SSEP amplitudes recovery in local hypothermia groups starting from day 14 post-injury onward for the 8-hour treatment group, which persisted up to days 28 and 42, whereas the 5-hour group showed significant improvement only at day 42. The functional improvement plateaued after day 42 as compared with control group of SCI with normothermia. This was supported by both 5-hour and 8-hour improvement in locomotion as measured by BBB scores. Local hypothermia also observed insignificant changes
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Hakim, Hana; Allison, Kim J; Van de Velde, Lee-Ann; Tang, Li; Sun, Yilun; Flynn, Patricia M; McCullers, Jonathan A
2016-06-08
Approaches to improve the immune response of immunocompromised patients to influenza vaccination are needed. Children and young adults (3-21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine. Eighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p=0.27 and 0.09 after dose 1 and 2, respectively). HD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Vilos, Angelos G; Vilos, George A; Hollett-Caines, Jackie; Garvin, Greg; Kozak, Roman; Abu-Rafea, Basim
2014-11-01
To evaluate the efficacy and post-procedural pain associated with uterine artery embolization (UAE) using Gelfoam alone versus Embospheres plus Gelfoam in women with symptomatic uterine fibroids. We conducted a prospective, non-randomized pilot study. Fluoroscopy-guided trans-femoral artery UAE was performed using Gelfoam pledgets alone or Embospheres (500 to 700 mg) plus Gelfoam under conscious sedation and local anaesthesia. This was followed by patient-controlled analgesia (PCA) using a morphine pump overnight. Post-procedural pain was assessed by the mean amount of self-administered morphine delivered by PCA pump (mL) from 0 to 19 hours in each group. The mean volumes of the uterus and the dominant fibroid were calculated by ultrasound at baseline, three months, six months, and 12 months. A total of 17 women participated in the study. Bilateral uterine artery occlusion was performed in eight women using Gelfoam alone, and in nine women using Embosphere + Gelfoam. One woman in the Embosphere + Gelfoam group developed a puncture-site hematoma requiring further intervention one week later. The mean (SD) amount of morphine self-administered by PCA pump at time 0, 1, and 2 hours was 3.4 mg (3.1), 2.9 mg (2.2), and 2.4 mg (3.3) in the Gelfoam-only group and 6.1 mg (3.0), 9.6 mg (7.1), and 5.3 mg (4.4) in the Embosphere + Gelfoam group, respectively. After three hours, the amount of morphine used was equal in both groups. The mean (SD) total dose of morphine used was 29.5 mg (18.6) in the Gelfoam group and 41.1 mg (19.3) in the Embosphere + Gelfoam group (P = 0.228). At 12 months, the reduction in median total uterine volume and median dominant fibroid volume in each group was equal. Clinical outcomes were equivalent after uterine artery embolization using Gelfoam alone versus Gelfoam + Embospheres. Although the amount of immediate post-procedure pain may be less with Gelfoam alone, we could not demonstrate this objectively using morphine use as a measure of pain.
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Vogl, T J; Friebe, C E; Balzer, T; Mack, M G; Steiner, S; Schedel, H; Pegios, W; Lanksch, W; Banzer, D; Felix, R
1995-08-01
To assess the effectiveness and safety of normal and high doses of Gadobutrol versus a standard dose of Gadolinium DTPA in the MR evaluation of patients with brain metastases. In a clinical phase-II study 20 patients who had been diagnosed as having brain metastases with CT or MRT were studied prospectively with Gadobutrol, a new nonionic, low osmolality contrast agent. Each patient received an initial injection of 0.1 mmol/kg body weight and an additional dose of 0.2 mmol/kg Gadobutrol 10 min later. Spin-echo images were obtained before and after the two applications of Gadobutrol. Dynamic scanning (Turbo-FLASH) was performed for 3 min after each injection of the contrast agent. Both quantitative and qualitative data were intraindividually evaluated. The primary tumor was a bronchial carcinoma in 11 cases; in 9 other cases there were different primary tumors. Forty-eight hours after the use of Gadobutrol there were no adverse signs in the clinical examination, vital signs or blood and urine chemistry. Statistical analysis (Friedman test and Wilcoxon test) of the C/N ratios between tumor and white matter, percentage enhancement, and visual assessment rating revealed statistically significant superiority of high-dose Gadobutrol injection in comparison to the standard dose. The percentage enhancement increased on average from 104% after 0.1 mmol/kg to 162% after 0.3 mmol/kg Gadobutrol. Qualitative delineation and contrast of the lesions increased significantly. The use of high-dose Gadobutrol improved the detection of 36 additional lesions in 6 patients. The first in vivo results prove the excellent contrast capacity of the nonionic contrast agent Gadobutrol for the diagnosis of intracerebral metastases.
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Effects of high doses of oxytetracycline on metacarpophalangeal joint kinematics in neonatal foals.
Kasper, C A; Clayton, H M; Wright, A K; Skuba, E V; Petrie, L
1995-07-01
Thirteen clinically normal Belgian-type foals were used to study the effects of high doses of oxytetracycline on metacarpophalangeal joint kinematics. Seven foals (treatment group) received 2 doses of oxytetracycline (3 g, IV). The first dose was given when foals were 4 days old; the second dose was given 24 hours later. Six foals (control group) received 2 doses of saline (0.9% NaCl) solution (15 ml, IV) at equivalent time periods. All foals were videotaped at a walk twice: immediately prior to the first treatment and 24 hours after the second treatment. The tapes were digitized, and metacarpophalangeal joint angle was measured along the palmar surface of the limb during 3 strides. The angular data were normalized for time, and data from the 3 strides were averaged to describe a representative stride. Repeated measures ANOVA was used to test for differences between groups and within groups over time. Values for stride duration, stance phase percentage, and minimum metacarpophalangeal joint angle obtained before treatment were not significantly different from values obtained after treatment. Maximum metacarpophalangeal joint angle, which occurred during the stance phase of the stride, and range of joint motion were significantly increased for foals in the treatment group, compared with foals in the control group.
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Endocrine response to an ultra-marathon in pre- and post-menopausal women.
Copeland, J L; Verzosa, M L S
2014-06-01
Ultra-endurance competitions are becoming increasingly popular but there is limited research on female participants. The purpose of this study was to examine changes in estrogen and the IGF-I system in women after an ultra-marathon. Six pairs of pre- and post- menopausal women were matched for race finish times;mean finish time was 20 hours. Blood samples were drawn 24 hours before the race, at the finish, and 24 hours into recovery. Samples were analysed for estradiol, total IGF-I, IGFBP-1, and intact IGFBP-3. There was a significant increase in estradiol following the race in both groups (P < 0.05). Total IGF-I decreased after the race (P < 0.01) and remained lower in recovery. IGFBP-1 increased after the race (P < 0.001) but returned to pre-race levels after 24 hours, while intact IGFBP-3 was significantly lower post-race and in recovery (P < 0.001). Postmenopausal women had significantly lower estradiol at baseline, but there were no other group differences. These results demonstrate that among recreational female runners, an ultra-marathon is associated with IGF system changes that are consistent with an energy-deficient, catabolic state. Further research is needed to confirm the effect of these endocrine changes on health and performance.
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Samuels, Ronald C; Chi, Grace W; Rauch, Daniel A; Palfrey, Judith S; Shelov, Steven P
2005-05-01
To evaluate the impact of residency work hour limitations on pediatrics residency programs in New York State, and to learn lessons that can be used nationally with the implementation of the Accreditation Council of Graduate Medical Education's similar rules. A three-page questionnaire was mailed to all pediatrics residency program directors in New York. The questionnaire assessed methods used to accommodate the work hour limitations and perceptions of the limitations' effects. Twenty-one program directors responded (68%). Only large programs used night floats and night teams to meet work hour requirements. Programs of all sizes and in all settings used cross coverage and sent residents home immediately post call. About half of the programs hired additional nonresident staff, usually nurse practitioners, physician assistants, and/or attendings. The most frequently reported effects were decreases in the amount of time residents spent in inpatient settings, patient continuity in inpatient settings, flexibility of residents' scheduling, and increased logistical work needed to maintain continuity clinic. A summary of advice to other program directors was "be creative" and "be flexible." New York's pediatrics residency programs used a variety of mechanisms to meet work hour restrictions. Smaller programs had fewer methods available to them to meet such restrictions. Although the logistical work needed to maintain continuity clinic increased greatly, continuity and outpatient settings themselves were not greatly affected by work hour limitations. Inpatient settings were more affected and experienced much more in the way of change.
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The Effects of Dinner-to-Bed Time and Post-Dinner Walk on Gastric Cancer Across Different Age Groups
Xu, Le; Zhang, Xi; Lu, Jun; Dai, Jia-Xi; Lin, Ren-Qin; Tian, Fang-Xi; Liang, Bing; Guo, Yi-Nan; Luo, Hui-Yu; Li, Ni; Fang, Dong-Ping; Zhao, Ruo-Hua; Huang, Chang-Ming
2016-01-01
Abstract Gastric cancer (GC) remains a major killer throughout the world. Despite the dramatic decrease in GC over the last century, its etiology has not yet been well characterized. This study investigated the possible independent and combined effects of the dinner-to-bed time and post-dinner walk on the risk for GC across different age groups. A population-based, case–control study was conducted in southeast China, including 452 patients with GC and 465 age-, race-, and gender-matched controls. A self-designed questionnaire was used to collect information on demographic characteristics, dinner-to-bed time, post-dinner walk, and other behavioral factors. Conditional logistic regression models were used to estimate the effects of the dinner-to-bed time and post-dinner walk as well as their joint effect on the risk for GC across different age groups. Individuals with dinner-to-bed time <3 hours were more prone to have GC (P < 0.001), and the shorter the dinner-to-bed time was, the higher was the risk for GC (Ptrend < 0.001). Post-dinner nonwalk was associated with a 2.9-fold increased risk for GC compared with post-dinner walk (adjusted odds ratio [AOR] = 2.942, 95% confidence intervals [95% CIs] = 2.072–4.179). The interaction effect of dinner-to-bed time and post-dinner walk on GC risk was detected (AOR = 1.862, 95% CIs = 1.584–3.885, synergy index [SI] = 2.654, 95% CIs = 2.27–3.912). Participants with dinner-to-bed time <3 hours who did not walk after dinner were 7.4 times likely to suffer from GC (AOR = 7.401, 95% CIs = 4.523–13.16) than those with dinner-to-bed time ≥4 hours who took such walk. The risk of GC due to dinner-to-bed time <3 hours, post-dinner nonwalk and their interaction was positively correlated with age. The strongest risk was observed among people ≥70 years old, but the effects were not significant for people ≤55 years old. Dinner-to-bed time <3 hours and post-dinner nonwalk are
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Dominicus, Rolf; Galtier, Florence; Richard, Patrick; Baudin, Martine
2014-06-30
The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years. This open-label, multicentre study was conducted in adults aged ≥ 40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥ 0.1IU/mL by seroneutralization assay [SNA]); tetanus (≥ 0.1IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥ 8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥ 5EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥ 0.01IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose. Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5-96.8); tetanus and poliomyelitis, 100% (CI: 98.8-100). Percentage of participants with an antibody titre ≥ 5EU/mL against pertussis antigens was ≥ 95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8-100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%). This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an
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Carrera, Marinete Pinheiro; Carey, Robert J; Dias, Flávia Regina Cruz; de Matos, Liana Wermelinger
2011-07-01
Sensitization is a common feature of psychostimulants and sensitization effects are generally considered to be linked to the addictive properties of these drugs. We used a conventional paired/unpaired Pavlovian protocol to induce a context specific sensitization to the locomotor stimulant effect of a high dose of apomorphine (2.0mg/kg). Two days following a 5 session sensitization induction phase, a brief 5min non-drug test for conditioning was conducted. Only the paired groups exhibited locomotor stimulant conditioned response effects. Immediately following this brief test for conditioning, the paired and the unpaired groups received injections of 0.05mg/kg apomorphine, 2.0mg/kg apomorphine or vehicle designed to differentially impact memory re-consolidation of the conditioning. Two days later, all groups received a sensitization challenge test with 2.0mg/kg apomorphine. The 2.0mg/kg apomorphine post-trial treatment potentiated sensitization while the 0.05mg/kg eliminated sensitization. These effects were only observed in the paired groups. The activation of dopaminergic systems by the high dose of apomorphine strengthened the drug/environment association whereas the inhibition of dopamine activity by the low auto-receptor dose eliminated this association. The results point to the importance of conditioning to context specific sensitization and targeting memory re-consolidation of conditioning as a paradigm to modify sensitization. Copyright © 2011 Elsevier Inc. All rights reserved.
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Cavalca, V; Rocca, B; Veglia, F; Petrucci, G; Porro, B; Myasoedova, V; De Cristofaro, R; Turnu, L; Bonomi, A; Songia, P; Cavallotti, L; Zanobini, M; Camera, M; Alamanni, F; Parolari, A; Patrono, C; Tremoli, E
2017-11-01
On-pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase-1 renewal, thereby modifying low-dose aspirin pharmacodynamics. Thirty-seven patients on standard aspirin 100 mg once-daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once-daily, 100 mg twice-daily, or 200 mg once-daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C-reactive protein, and interleukin-6 significantly increased. Interleukin-6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once-daily showed a significant increase in serum thromboxane (TX)B 2 within the 24-hour dosing interval and urinary TXA 2 metabolite (TXM) excretion. Aspirin 100 mg twice-daily lowered serum TXB 2 and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once-daily dose, rescues the impaired antiplatelet effect of low-dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover. © 2017 American Society for Clinical Pharmacology and Therapeutics.
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de Menezes Martins, Reinaldo; Maia, Maria de Lourdes S; de Lima, Sheila Maria Barbosa; de Noronha, Tatiana Guimarães; Xavier, Janaina Reis; Camacho, Luiz Antonio Bastos; de Albuquerque, Elizabeth Maciel; Farias, Roberto Henrique Guedes; da Matta de Castro, Thalita; Homma, Akira
2018-06-27
In 2009, Bio-Manguinhos conducted a dose-response study with the yellow fever vaccine, administering the vaccine in the usual mean dose of 27,476 IU (full dose, reference) and in tapered doses (10,447 IU, 3013 IU, 587 IU, 158 IU, and 31 IU) by the usual subcutaneous route and usual volume (0.5 mL). Tapered doses were obtained by dilution in the manufacturer's laboratory, and the test batches presented industrial quality. Doses down to 587 IU showed similar immunogenicity to the full dose (27,476, reference), while the 158 IU and 31 IU doses displayed lower immunogenicity. Seropositivity was maintained at 10 months, except in the group that received the 31 IU dose. The current study aims to determine whether yellow fever seropositivity was maintained eight years after YF vaccination in non-revaccinated individuals. According to the current study's results, seropositivity was maintained in 85% of 318 participants and was similar across groups. The findings support the use of the yellow fever vaccine in fractional doses during outbreaks, but each fractional dose should have at least 587 IU. This study also supports the minimum dose required by WHO, 1000 IU. Clinicaltrials.gov NCT 03338231. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Use of high-dose nandrolone aggravates septic shock in a mouse model.
Lin, Che; Chen, Shou-Tung; Chien, Su-Yu; Kuo, Shou-Jen; Chen, Dar-Ren
2011-06-01
Nandrolone, an anabolic-androgenic steroid, is widely misused by athletes who wish to rapidly increase muscle mass and performance. An increasing number of reports have indicated that nandrolone may affect and modulate the immune system. This study aimed to investigate the effects of nandrolone on septic shock-caused immune responses and the cellular mechanism of action using a sepsis murine model. Before septic shock induction, BALB/c mice were given a high dose of nandrolone or peanut oil only. After septic shock induction, mice were sacrificed at different time points. Their blood and tissue specimens were analyzed. It was found that the high-dose nandrolone group had significantly increased mortality compared with the control group (p<0.001). The serum malondialdehyde level was significantly increased in the high-dose group compared with the control group. Animals administered a high dose of nandrolone had significantly increased hepatic tumor necrosis factor-α or splenic interferon-γ at 0 and 6 hours. In lung tissue, insulin-like growth factor-1, insulin-like growth factor binding proteins (IGFBPs) and insulin-like growth factor-1 receptor, and IGFBP1 and IGFBP2 mRNA expression were increased in the high-dose nandrolone group at 6 hours. Nandrolone abuse may hasten the death of patients with septic shock and may aggravate septic shock in mice. Copyright © 2011. Published by Elsevier B.V.
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Pharmacokinetic profile of Mitoguazone (MGBG) in patients with AIDS related non-Hodgkin's lymphoma.
Rizzo, J; Levine, A M; Weiss, G R; Pearce, T; Kraynak, M; Mueck, R; Smith, S; Von Hoff, D D; Kuhn, J G
1996-01-01
Mitoguazone is a unique chemotherapeutic agent whose activity is believed to result primarily from the competitive inhibition of S-adenosyl-methionine decarboxylase leading to a disruption in polyamine biosynthesis. Initial clinical trials demonstrated that the dose-limiting toxicities (mucositis and myelosuppression) of Mitoguazone were both dose and schedule dependent. Early pharmacokinetic studies of Mitoguazone in man revealed a prolonged half-life. Concurrent with a recent Phase II trial of Mitoguazone in patients with AIDS related non-Hodgkin's lymphoma, the single dose pharmacokinetics of Mitoguazone were characterized. Twelve patients received 600 mg/m2 of intravenous Mitoguazone over 30 minutes on an intermittent every 2 week schedule. Blood, urine, cerebrospinal fluid (CSF), pleural fluid and tissue samples were collected and analyzed by HPLC. Mitoguazone was cleared from the plasma triexponentially with a harmonic mean terminal half-life of 175 hours and a mean residence time of 192 hours. Peak plasma levels occurred immediately post-infusion, ranged from 6.47 to 42.8 micrograms/ml, and remained (for an extended period) well above the reported concentration for inhibition of polyamine biosynthesis. Plasma clearance averaged 4.73 l/hr/m2 with a relatively large apparent volume of distribution at steady-state of 1012 l/m2 indicating tissue sequestration. Renal excretion of unchanged Mitoguazone accounted for an average of 15.8% of the dose within 48 to 72 hours post-administration. Detectable levels of drug were present in random voided samples eight days post-dose. Mitoguazone levels in CSF ranged from 22 to 186 ng/ml post-dose with CSF/plasma ratios ranging from 0.6% to 7%. The pleural fluid/plasma ratio was approximately 1. Tissue levels of Mitoguazone were highest in the liver followed by lymph node, spleen and the brain.
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Kim, Inah; Kim, Hyunjoo; Lim, Sinye; Lee, Mira; Bahk, Jinwook; June, Kyung Ja; Kim, Soyeon; Chang, Won Joon
2013-09-01
This study aimed to examine the distribution of working hours and the association between working hours and depressive symptomatology using representative data from a national, population-based survey. Data came from the fourth Korean National Health and Nutrition Examination Survey (2007-2009), which employed a systematic, stratified cluster-sampling method. We used logistic regression procedures to estimate the importance of weekly working hours as a predictor of depressive symptomatology. The prevalence of depressive symptomatology was 10.2%. The work week, which averaged 48.3 hours for the sample as a whole, was longer for men (49.8 hours) than women (45.3 hours), and 12.1% of respondents were engaged in shift work. In logistic regression analyses, compared to those working < 52 hours per week, the odds ratios (OR) of working hours as a predictor of depressive symptomatology were 1.19 [95% confidence interval (95% CI) 0.77-1.85] for those working 52-59 hours per week and 1.62 (95% CI 1.20-2.18) for those working ≥ 60 hours per week, after adjustment for demographic characteristics, health behaviors, socioeconomic status, employment status, and work schedules. It showed a positive dose-response relationship between working hours and depressive symptomatology (P = 0.0059). Working hours in Korea are long. There is an association between working hours and depressive symptomatology, and there seems be a trend in working hours and depressive symptomatology.
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Ala-Mursula, L; Vahtera, J; Kouvonen, A; Väänänen, A; Linna, A; Pentti, J; Kivimäki, M
2006-09-01
To explore the associations of working hours (paid, domestic, commuting, and total) with sickness absence, and to examine whether these associations vary according to the level of employee control over daily working hours. Prospective cohort study among 25 703 full-time public sector employees in 10 towns in Finland. A survey of working hours and control over working hours was carried out in 2000-01. The survey responses were linked with register data on the number of self-certified (< or =3 days) and medically certified (>3 days) sickness absences until the end of 2003. Poisson regression analyses with generalised estimating equations were used to take into account the fact that the employees were nested within work units. Adjustments were made for work and family characteristics and health behaviour. The mean follow-up period was 28.1 (SD 8.1) months. Long domestic and total working hours were associated with higher rates of medically certified sickness absences among both genders. In contrast, long paid working hours were associated with lower rates of subsequent self-certified sickness absences. Long commuting hours were related to increased rates of sickness absence of both types. Low control over daily working hours predicted medically certified sickness absences for both the women and men and self-certified absences for the men. In combinations, high control over working hours reduced the adverse associations of long domestic and total working hours with medically certified absences. Employee control over daily working hours may protect health and help workers successfully combine a full-time job with the demands of domestic work.
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... medlineplus.gov/ency/article/003604.htm 24-hour urine copper test To use the sharing features on this page, please enable JavaScript. The 24-hour urine copper test measures the amount of copper in ...
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Long Working Hours and Cognitive Function
Singh-Manoux, Archana; Ferrie, Jane E.; Gimeno, David; Marmot, Michael G.; Elovainio, Marko; Jokela, Markus; Vahtera, Jussi; Kivimäki, Mika
2009-01-01
This study examined the association between long working hours and cognitive function in middle age. Data were collected in 1997–1999 (baseline) and 2002–2004 (follow-up) from a prospective study of 2,214 British civil servants who were in full-time employment at baseline and had data on cognitive tests and covariates. A battery of cognitive tests (short-term memory, Alice Heim 4-I, Mill Hill vocabulary, phonemic fluency, and semantic fluency) were measured at baseline and at follow-up. Compared with working 40 hours per week at most, working more than 55 hours per week was associated with lower scores in the vocabulary test at both baseline and follow-up. Long working hours also predicted decline in performance on the reasoning test (Alice Heim 4-I). Similar results were obtained by using working hours as a continuous variable; the associations between working hours and cognitive function were robust to adjustments for several potential confounding factors including age, sex, marital status, education, occupation, income, physical diseases, psychosocial factors, sleep disturbances, and health risk behaviors. This study shows that long working hours may have a negative effect on cognitive performance in middle age. PMID:19126590
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Galantamine is a novel post-exposure therapeutic against lethal VX challenge.
Hilmas, Corey J; Poole, Melissa J; Finneran, Kathryn; Clark, Matthew G; Williams, Patrick T
2009-10-15
The ability of galantamine hydrobromide (GAL HBr) treatment to antagonize O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX)-induced lethality, impairment of muscle tension, and electroencephalographic (EEG) changes was assessed in guinea pigs. Guinea pigs were challenged with 16.8 microg/kg VX (2LD50). One min after challenge, animals were administered 0.5 mg/kg atropine sulfate (ATR) and 25 mg/kg pyridine-2-aldoxime methochloride (2-PAM). In addition, guinea pigs were given 0, 1, 2, 4, 8 or 10 mg/kg GAL as a post-exposure treatment immediately prior to ATR and 2-PAM. Animals were either monitored for 24-h survival, scheduled for electroencephalography (EEG) recording, or euthanized 60 min later for measurement of indirectly-elicited muscle tension in the hemidiaphragm. Post-exposure GAL therapy produced a dose-dependent increase in survival from lethal VX challenge. Optimal clinical benefits were observed in the presence of 10 mg/kg GAL, which led to 100% survival of VX-challenged guinea pigs. Based on muscle physiology studies, GAL post-exposure treatment protected the guinea pig diaphragm, the major effector muscle of respiration, from fatigue, tetanic fade, and muscular paralysis. Protection against the paralyzing effects of VX was dose-dependent. In EEG studies, GAL did not alter seizure onset for all doses tested. At the highest dose tested (10 mg/kg), GAL decreased seizure duration when administered as a post-exposure treatment 1 min after VX. GAL also reduced the high correlation associated between seizure activity and lethality after 2LD50 VX challenge. GAL may have additional benefits both centrally and peripherally that are unrelated to its established mechanism as a reversible acetylcholinesterase inhibitor (AChEI).
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Intravenous Sedation with Low-Dose Dexmedetomidine: Its Potential for Use in Dentistry
Ogawa, Sachie; Seino, Hiroaki; Ito, Hiroshi; Yamazaki, Shinya; Ganzberg, Steven; Kawaai, Hiroyoshi
2008-01-01
This study investigated the physiologic and sedative parameters associated with a low-dose infusion of dexmedetomidine (Dex). Thirteen healthy volunteers were sedated with Dex at a loading dose of 6 mcg/kg/h for 5 minutes and a continuous infusion dose of 0.2 mcg/kg/h for 25 minutes. The recovery process was observed for 60 minutes post infusion. The tidal volume decreased significantly despite nonsignificant changes in respiratory rate, minute ventilation, oxygen saturation, and end-tidal carbon dioxide. The mean arterial pressure and heart rate also decreased significantly but within clinically acceptable levels. Amnesia to pin prick was present in 69% of subjects. A Trieger dot test plot error ratio did not show a significant change at 30 minutes post infusion despite a continued significant decrease in bispectral index. We conclude that sedation with a low dose of Dex appears to be safe and potentially efficacious for young healthy patients undergoing dental procedures. PMID:18788843
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Jani, Ashish; Shaikh, Fauzia; Barton, Sunjay
Purpose: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis ofmore » tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.« less
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Zafar, Mohammad Urooj; Vorchheimer, David A; Gaztanaga, Juan; Velez, Mauricio; Yadegar, Daniel; Moreno, Pedro R; Kunitada, Satoshi; Pagan, Juan; Fuster, Valentin; Badimon, Juan J
2007-10-01
Direct and specific inhibition of factor Xa is an emerging therapeutic strategy for atherothrombotic disease. Parenteral factor Xa inhibitors promise efficacy comparable to standard therapies, which could be extended to ambulatory patients with oral agents. We evaluated the antithrombotic effect of the oral, direct factor Xa inhibitor DU-176b in a phase-I study. Healthy subjects (n = 12) received a single, 60 mg dose of DU-176b. Antithrombotic effects were assessed by comparing ex-vivo thrombus formation at 1.5, 5, and 12 hours post-dose versus baseline, along with factor Xa activity, thrombin generation and clotting parameters. Under venous flow after 1.5 and 5 hours, the thrombus was 28% and 21% smaller versus baseline, respectively (p < 0.05). Under arterial condition, the reduction was 26% and 17% (p < 0.05). Thrombin generation decreased by 28% at 1.5 hours and 10% at 5 hours. Changes in PT and INR correlated well with plasma drug concentrations (R2 = 0.79 and 0.78). Direct and specific inhibition of factor Xa by DU-176b significantly reduced ex-vivo thrombus formation at both venous and arterial rheologies, up to 5 hours post-dose. The effects mirrored changes in clotting parameters, suggesting their potential usefulness for monitoring in a clinical setting.
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29 CFR 825.402 - Violations of the posting requirement.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 29 Labor 3 2010-07-01 2010-07-01 false Violations of the posting requirement. 825.402 Section 825.402 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR OTHER LAWS THE FAMILY AND MEDICAL LEAVE ACT OF 1993 Enforcement Mechanisms § 825.402 Violations of the...
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Moore, R Andrew; Derry, Sheena; Aldington, Dominic; Wiffen, Philip J
2015-09-28
This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events are now dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews and assesses the reliability of available data. To summarise the efficacy of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery who have been given a single dose of oral analgesic. We identified systematic reviews in the Cochrane Database of Systematic Reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome the number of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews, we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, and the percentage of participants remedicating by six, eight, 12, or 24 hours. Where there was adequate information for pairs of drug and dose (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable. The overview included 39 separate Cochrane Reviews with 41 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 50,000 participants in approximately 460 individual studies. The individual reviews included only high-quality trials of standardised design
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Suh, Yang-Gun; Lee, Ik Jae; Koom, Wong Sub; Cha, Jihye; Lee, Jong Young; Kim, Soo Kon; Lee, Chang Geol
2014-06-01
In this study, we investigated the effects of radiotherapy ≥60 Gy in the setting of concurrent chemo-radiotherapy for treating patients with Stages II-III esophageal cancer. A total of 126 patients treated with 5-fluorouracilbased concurrent chemo-radiotherapy between January 1998 and February 2008 were retrospectively reviewed. Among these patients, 49 received a total radiation dose of <60 Gy (standard-dose group), while 77 received a total radiation dose of ≥60 Gy (high-dose group). The median doses in the standard- and high-dose groups were 54 Gy (range, 45-59.4 Gy) and 63 Gy (range, 60-81 Gy), respectively. The high-dose group showed significantly improved locoregional control (2-year locoregional control rate, 69 versus 32%, P < 0.01) and progression-free survival (2-year progression-free survival, 47 versus 20%, P = 0.01) than the standard-dose group. Median overall survival in the high- and the standard-dose groups was 28 and 18 months, respectively (P = 0.26). In multivariate analysis, 60 Gy or higher radiotherapy was a significant prognostic factor for improved locoregional control, progression-free survival and overall survival. No significant differences were found in frequencies of late radiation pneumonitis, post-treatment esophageal stricture or treatment-related mortality between the two groups. High-dose radiotherapy of 60 Gy or higher with concurrent chemotherapy improved locoregional control and progression-free survival without a significant increase of in treatment-related toxicity in patients with Stages II-III esophageal cancer. Our study could provide the basis for future randomized clinical trials. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-05
... period long enough to provide restorative sleep regardless of the number of hours worked prior to the... No. FMCSA-2004-19608] RIN 2126-AB26 Hours of Service AGENCY: Federal Motor Carrier Safety... hold three public listening sessions to solicit comments and information on potential hours-of- service...
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Barkay, Hadas; Rasamoelisolo, Michele; Butler, Kathleen; Yamada, Kazumasa; Bassan, Merav; Yoon, Esther; Spiegelstein, Ofer
2016-01-01
Abstract TV‐1106 is a human serum albumin genetically fused to recombinant human growth hormone, designed to provide a long‐acting alternative to daily growth hormone (GH) injections in patients with GH deficiency. This study investigated the pharmacokinetics, pharmacodynamics, and safety of single subcutaneous doses of TV‐1106 (7.5, 15, 50, and 100 mg) in Japanese (n = 44) and caucasian (n = 44) healthy subjects. TV‐1106 pharmacokinetics and pharmacodynamics were comparable in Japanese and caucasian populations. TV‐1106 demonstrated relatively slow absorption (median tmax, 10–30 hours) and a mean elimination half‐life of 26–36 hours. Apparent clearance and volume of distribution decreased with increasing TV‐1106 doses in both populations and appeared to increase more than dose proportionality across the tested doses. Insulin‐like growth factor‐1 (IGF‐1) and IGF binding protein‐3 (IGFBP‐3) increased in a dose‐related manner, with maximum responses observed at 33–96 and 42–109 hours, respectively. IGF‐1 and IGFBP‐3 returned to baseline values at 168 hours following 7.5 and 15 mg of TV‐1106, and 336 hours following 50 and 100 mg of TV‐1106. TV‐1106 appeared safe in both populations. There was no evidence of differences in pharmacokinetics, pharmacodynamics, or safety of TV‐1106 between Japanese and caucasian populations. The data also demonstrate long‐acting growth hormone properties of TV‐1106 and support its potential for once‐weekly dosing. PMID:27489211
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Patel, Gita Wasan; Duquaine, Susan M; McKinnon, Peggy S
2007-12-01
To compare outcomes and cost for the traditional United States Food and Drug Administration-approved dosing regimen for meropenem versus an alternative dosing regimen providing similar pharmacodynamic exposure with a lower total daily dose. Retrospective cohort study with a cost-minimization analysis. A 417-bed, privately owned community hospital. One hundred patients who received meropenem 1 g every 8 or 12 hours (traditional dosing regimen) between January 1 and September 30, 2004 (historical controls), and 192 patients who received meropenem 500 mg every 6 or 8 hours (alternative dosing regimen) between October 1, 2004, and September 30, 2005. Demographic and clinical data were collected for all patients. Cost-minimization analysis was performed by using the drug acquisition cost for meropenem. Demographics, sources of infection, distributions of organisms, and Charlson Comorbidity Index scores were similar between patients in the traditionally and alternatively dosed groups. Concomitant therapy, duration of therapy, success rates, lengths of stay, and in-hospital mortality rates were also similar between groups. Median time to the resolution of symptoms was 3 days for traditional dosing and 1.5 days for alternative dosing (p<0.0001). A logistic regression model including the dosing strategy showed that only polymicrobial infections and sepsis were associated with increased failure rates. The median cost for antibiotics was $439.05/patient for traditional dosing and $234.08/patient for alternative dosing (p<0.0001). An alternative dosing regimen for meropenem with a lower total daily dose yielded patient outcomes, including success rates and duration of therapy, equivalent to those of the traditional dosing regimen. Alternative dosing decreased total drug exposure, costs for antibiotics, and time to the resolution of infections.
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Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency
Archin, Nancie M.; Kirchherr, Jennifer L.; Sung, Julia A.M.; Clutton, Genevieve; Sholtis, Katherine; Xu, Yinyan; Allard, Brigitte; Stuelke, Erin; Kashuba, Angela D.; Kuruc, Joann D.; Gay, Cynthia L.; Goonetilleke, Nilu
2017-01-01
BACKGROUND. The histone deacetylase (HDAC) inhibitor vorinostat (VOR) can increase HIV RNA expression in vivo within resting CD4+ T cells of aviremic HIV+ individuals. However, while studies of VOR or other HDAC inhibitors have reported reversal of latency, none has demonstrated clearance of latent infection. We sought to identify the optimal dosing of VOR for effective serial reversal of HIV latency. METHODS. In a study of 16 HIV-infected, aviremic individuals, we measured resting CD4+ T cell–associated HIV RNA ex vivo and in vivo following a single exposure to VOR, and then in vivo after a pair of doses separated by 48 or 72 hours, and finally following a series of 10 doses given at 72-hour intervals. RESULTS. Serial VOR exposures separated by 72 hours most often resulted in an increase in cell-associated HIV RNA within circulating resting CD4+ T cells. VOR was well tolerated by all participants. However, despite serial reversal of latency over 1 month of VOR dosing, we did not observe a measurable decrease (>0.3 log10) in the frequency of latent infection within resting CD4+ T cells. CONCLUSIONS. These findings outline parameters for the experimental use of VOR to clear latent infection. Latency reversal can be achieved by VOR safely and repeatedly, but effective depletion of persistent HIV infection will require additional advances. In addition to improvements in latency reversal, these advances may include the sustained induction of potent antiviral immune responses capable of recognizing and clearing the rare cells in which HIV latency has been reversed. TRIAL REGISTRATION. Clinicaltrials.gov NCT01319383. FUNDING. NIH grants U01 AI095052, AI50410, and P30 CA016086 and National Center for Advancing Translational Sciences grant KL2 TR001109. PMID:28714868
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Duty Hour Reporting: Conflicting Values in Professionalism.
Byrne, John M; Loo, Lawrence K; Giang, Dan W
2015-09-01
Duty hour limits challenge professional values, sometimes forcing residents to choose between patient care and regulatory compliance. This may affect truthfulness in duty hour reporting. We assessed residents' reasons for falsifying duty hour reports. We surveyed residents in 1 sponsoring institution to explore the reasons for noncompliance, frequency of violations, falsification of reports, and the residents' awareness of the option to extend hours to care for a single patient. The analysis used descriptive statistics. Linear regression was used to explore falsification of duty hour reports by year of training. The response rate was 88% (572 of 650). Primary reasons for duty hour violations were number of patients (19%) and individual patient acuity/complexity (19%). Junior residents were significantly more likely to falsify duty hours (R = -0.966). Of 124 residents who acknowledged falsification, 51 (41%) identified the primary reason as concern that the program will be in jeopardy of violating the Accreditation Council for Graduate Medical Education (ACGME) duty hour limits followed by fear of punishment (34, 27%). This accounted for more than two-thirds of the primary reasons for falsification. Residents' falsification of duty hour data appears to be motivated by concerns about adverse actions from the ACGME, and fear they might be punished. To foster professionalism, we recommend that sponsoring institutions educate residents about professionalism in duty hour reporting. The ACGME should also convey the message that duty hour limits be applied in a no-blame systems-based approach, and allow junior residents to extend duty hours for the care of individual patients.
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Ala‐Mursula, L; Vahtera, J; Kouvonen, A; Väänänen, A; Linna, A; Pentti, J; Kivimäki, M
2006-01-01
Objectives To explore the associations of working hours (paid, domestic, commuting, and total) with sickness absence, and to examine whether these associations vary according to the level of employee control over daily working hours. Methods Prospective cohort study among 25 703 full‐time public sector employees in 10 towns in Finland. A survey of working hours and control over working hours was carried out in 2000–01. The survey responses were linked with register data on the number of self‐certified (⩽3 days) and medically certified (>3 days) sickness absences until the end of 2003. Poisson regression analyses with generalised estimating equations were used to take into account the fact that the employees were nested within work units. Adjustments were made for work and family characteristics and health behaviour. The mean follow‐up period was 28.1 (SD 8.1) months. Results Long domestic and total working hours were associated with higher rates of medically certified sickness absences among both genders. In contrast, long paid working hours were associated with lower rates of subsequent self‐certified sickness absences. Long commuting hours were related to increased rates of sickness absence of both types. Low control over daily working hours predicted medically certified sickness absences for both the women and men and self‐certified absences for the men. In combinations, high control over working hours reduced the adverse associations of long domestic and total working hours with medically certified absences. Conclusions Employee control over daily working hours may protect health and help workers successfully combine a full‐time job with the demands of domestic work. PMID:16728502
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Vaughan, David; Speed, Joanne; Medve, Robert; Andrews, John S
2010-01-01
NXN-188 is a dual-action oral therapeutic being developed for the treatment of acute migraine. The mechanism of action of NXN-188 involves inhibition of both the neuronal nitric oxide synthase enzyme isoform and affinity for serotonin (5-hydroxytryptamine1B/D) receptors. The aims of the initial Phase I clinical studies were to compare the pharmacokinetic (PK) properties of NXN-188 administered as a single dose or multiple twice-daily doses to healthy adult volunteers and to determine the tolerability of NXN-188 in these individuals. Healthy adult male and female subjects were enrolled in 5 Phase I, randomized, double-blind studies, all of which (except for a fed/fasted trial) were placebo controlled. In the 4 single-dose studies, which differed with respect to feeding status and the formulation used (capsules or solution), subjects received NXN-188 at doses of 2 to 800 mg (0.027-11.2 mg/kg). In the repeat-dose study, subjects received 50-mg (0.71 mg/kg) doses twice daily for 4 days. Serum samples were analyzed for NXN-188 using validated HPLC-MS/MS methods. Standard clinical laboratory analyses (chemistry, hematology, and urinalysis) and measurements of serum creatine kinase and myoglobin levels were conducted at screening, admission, discharge, and follow-up. Baseline and postexposure values were compared to assess tolerability. Electrocardiography and physical examination were conducted at screening and at discharge and follow-up if any negative change occurred from the previous findings. Vital signs (heart rate, blood pressure, respiration), including assessment for orthostatic changes, were measured at screening, check-in, and follow-up visits (1 hour before dosing, every 30 minutes for the first 4 hours, then every hour for the next 4 hours, then every 4 hours for the remainder of the 24-hour study). Adverse events were recorded, reviewed, and monitored throughout the study. Two hundred three subjects (102 women, 101 men) 18 to 50 years of age were enrolled in
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Tracking and Explaining Credit-Hour Completion
ERIC Educational Resources Information Center
Kwenda, Maxwell Ndigume
2014-01-01
This study highlights factors associated with changes in earned hours for two cohorts of incoming freshmen during their first year. The objectives of this study are twofold: (a) to derive model(s) regressing the cumulative hours earned and differential hours earned on student demographic, socioeconomic, and academic characteristics; and (b) to…
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Carpenter, Robert O; Spooner, John; Arbogast, Patrick G; Tarpley, John L; Griffin, Marie R; Lomis, Kimberly D
2006-01-01
-reporting violations. These results support the previous findings of 80% and 49%, respectively. Of the various requirements, the "24+6" rule was most frequently violated. Of those in violation of the "24+6" requirement, the majority (90%) exceeded limits by no more than 3 hours. Of those in violation of the 80-hour weekly average requirement, the majority (57%) exceeded limits by no more than 5 hours. Per the ACGME website, "an RRC may grant exceptions for up to 10% of the 80-hour limit, to individual programs based on a sound educational rationale." Although the overall percent of residents reporting violation remains high, the number of excess hours worked is small relative to established standards (within 10%). The authors propose that systems adaptations could be developed to improve compliance. Special attention is warranted to investigate the activities of residents in the post-call period.
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Franks, Amy M; Schmidt, Julia M; McCain, Keith R; Fraer, Mony
2012-02-01
Cardiovascular events associated with energy drink consumption have been reported, but few data exist to delineate the hemodynamic effects of energy drinks. To compare the effects of an energy drink versus caffeine supplementation on blood pressure (BP) indices as measured by 24-hour ambulatory BP monitoring (ABPM). Healthy, nonsmoking, normotensive volunteers (aged 18-45 years) taking no medications were enrolled in a single-center, open-label, 2-period crossover pilot study. During each study period, subjects received either an energy drink (Red Bull Energy Drink, each dose containing 80 mg of caffeine and 1000 mg of taurine in an 8.3-oz serving) or a control (compounded caffeine solution, each dose containing 80 mg of caffeine solution in 8 oz of bottled water) at 0800, 1100, 1500, and 1900 hours and underwent 24-hour ABPM. The study periods were separated by a washout period (4-30 days). Mean 24-hour, daytime, and nighttime systolic (SBP), diastolic (DBP), and mean arterial (MAP) BP; BP load; and percent nocturnal dipping were compared between study periods. Nine subjects (5 females, mean [SD] age 27.7 [5.0] years) completed the study. Mean 24-hour SBP (123.2 vs 117.4 mm Hg, p = 0.04), DBP (73.6 vs 68.2 mm Hg, p = 0.02), and MAP (90.1 vs 84.8 mm Hg, p = 0.03) were significantly higher during energy drink supplementation versus caffeine supplementation. Daytime DBP (77.0 vs 72.0 mm Hg, p = 0.04) also was significantly higher with the energy drink versus caffeine supplementation. Trends in higher daytime SBP (127.0 vs 121.9 mm Hg, p = 0.05) and MAP (93.6 vs 88.6 mm Hg, p = 0.05) were recorded with energy drink supplementation versus caffeine supplementation. Nighttime SBP and DBP loads were significantly higher with the energy drink, but nocturnal dipping did not differ significantly between study periods. Single-day energy drink supplementation increased mean 24-hour and daytime BP compared to caffeine control in this pilot study. Additional research is
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Hatami, Maryam; Mirjalili, Mahdieh; Ayatollahi, Vida; Vaziribozorg, Sedighe; Zand, Vahid
2018-06-01
The authors investigated the effect of honey on post-tonsillectomy pain and compare its efficacy with tramadol. This clinical trial was performed on 60 patients with American Society of Anesthesia I and II aged between 18 and 55 years and underwent tonsillectomy. Induction of anesthesia was carried out using 2 mg/kg propofol and 0.5 atracurium following 1.5 μg/kg fentanyl administration. Group B was given tramadol at dose of 2 mg/kg and with volume of 4 mL and Group A was given normal saline with the same volume 2 mL of medications were injected using needle (25) into tonsil bed and anterior old of each tonsil by an anesthesiologist. Three minutes after injection, the surgery was performed by the same ENT residents for all patients. In the recovery room Group B received antibiotics and oral acetaminophen. Group A was given antibiotics, oral acetaminophen, and honey dissolved in 40 mL warm water every 6 hours from when the patient was fully awake. Patients in Group A were told to eat honey 3 times a day 7 days postoperatively. Pain was scored using Numeric Rating Scale at the time points of 2, 6, 12, and 24 hours as well as 3 and 7 days postoperatively. Moreover, the healing status and epithelialization degree of tonsillar bed were considered on 1 and 7 days after the surgery by ENT specialist. The mean of pain score was significantly higher in Group A within 24 hours postoperatively as compared with Group B (P < 0.01). The mean of pain score was lower in Group B after 3 and 7 days but this difference was not statistically significant (P > 0.05). Considering restoration status and epithelialization degree of tonsillar bed on the 1st and 7th days, there was no statistically significant difference between 2 groups; however, tonsillar bed healing process was better in Group B on the 7th day. The current investigation confirmed the positive impact of tramadol on post-tonsillectomy pain relief in adults. The authors also found that honey can be used as a complementary
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Single Enteral Loading Dose of Phenobarbital for Achieving Its Therapeutic Serum Levels in Neonates
Turhan, Ali H.; Atici, Aytug; Okuyaz, Cetin; Uysal, Sercan
2010-01-01
Aim To investigate whether therapeutic serum drug levels may be achieved with a single enteral loading dose of phenobarbital. Methods The study was performed at the Mersin University Hospital in Turkey between April 2004 and August 2006, and included 29 newborn babies with seizure. After the acute treatment of the seizure with midazolam at a dose of 0.1 mg/kg, phenobarbital was administered by orogastric route at a loading dose of 20 mg/kg. Serum phenobarbital concentrations were measured at 0.5, 3, 6, and 12 hours after the loading. Serum phenobarbital levels between 10-30 μg/mL were considered as the therapeutic range. Results The serum phenobarbital levels reached therapeutic values in 9 (31%), 19 (66%), 21 (72%), and 23 (79%) patients at 0.5, 3, 6, and 12 hours after loading, respectively, while they did not reach therapeutic values in 6 patients (21%) after 12 hours. Four of the patients in whom there was no increase in serum phenobarbital levels had hypoxic-ischemic encephalopathy. Conclusion Enteral loading of phenobarbital can achieve therapeutic serum levels in the large majority of newborn babies with seizure and may be safely used in babies with the intact gastrointestinal tract. PMID:20564764
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Code of Federal Regulations, 2013 CFR
2013-01-01
... REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Managing Fatigue § 26.205 Work hours. (a) Individuals subject to work hour controls. Any individual who performs duties identified in § 26.4(a)(1) through (a)(5... paragraphs (b)(1) through (b)(5) of this section, the calculated work hours must include all time performing...
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Code of Federal Regulations, 2014 CFR
2014-01-01
... REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Managing Fatigue § 26.205 Work hours. (a) Individuals subject to work hour controls. Any individual who performs duties identified in § 26.4(a)(1) through (a)(5... paragraphs (b)(1) through (b)(5) of this section, the calculated work hours must include all time performing...
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Code of Federal Regulations, 2012 CFR
2012-01-01
... REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Managing Fatigue § 26.205 Work hours. (a) Individuals subject to work hour controls. Any individual who performs duties identified in § 26.4(a)(1) through (a)(5... paragraphs (b)(1) through (b)(5) of this section, the calculated work hours must include all time performing...
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Brunet, Salut; Esteve, Jordi; Berlanga, Joan; Ribera, Josep M; Bueno, Javier; Martí, Josep M; Bargay, Joan; Guardia, Ramon; Juliá, Antoni; Granena, Albert; Montserrat, Emili; Sierra, Jorge
2004-08-01
To evaluate a regimen of induction and consolidation chemotherapy, followed by a post-remission therapy which depended on age and cytogenetics, in patients with primary acute myeloid leukemia. Two hundred patients up to 60 years old received idarubicin, standard dose cytarabine and etoposide as induction chemotherapy and one consolidation course including intermediate dose cytarabine and mitoxantrone. Subsequently, patients with favorable cytogenetics, [i.e., t(8;21), inv(16)] were scheduled to receive 2 courses of high-dose cytarabine. The remainder were scheduled for allogeneic stem cell transplantation (SCT), if
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Cocci, Emiliano; Sacchetti, Giampiero; Rocculi, Pietro; Dalla Rosa, Marco
2014-10-01
1-Methylcyclopropene (1-MCP) is an inhibitor of ethylene reception used in post-harvest treatments to delay fruit ripening. Several factors affect the efficacy of 1-MCP treatments. The effect of a post-harvest treatment with 1-MCP on the quality of Pink Lady® apples as a function of 1-MCP dose, storage time and maturity at harvest was investigated. 1-MCP treatment was further tested in combination with controlled atmosphere (CA) storage. 1-MCP limited fruit respiration and softening during storage and was more effective on partially matured fruits and at prolonged storage times. The delaying of 1-MCP on the increase of ripening index was greater on matured fruits at prolonged storage times. The combination of 1-MCP and CA treatments positively affected quality indices of mature apples during 6 months of storage and 7 days of commercial life, with 1-MCP being more effective than CA. 1-MCP and CA showed positive combined effects on firmness and ripening index after 6 months of storage, and on firmness and CO₂ production after a further 7 days of commercial life. By knowing fruit maturity at harvest and expected storage time it is possible to choose the most suitable 1-MCP dose to meet the market requirements by applying a simple polynomial model. © 2014 Society of Chemical Industry.
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Stahlman, Jodi; Britto, Margaret; Fitzpatrick, Sherahe; McWhirter, Cecilia; Testino, Samuel A; Brennan, John J; Zumbrunnen, Troy L
2012-02-01
To evaluate secondary exposure of testosterone transferred to females from a male partner, dosed with 1.62% testosterone gel after direct skin-to-skin contact with the application site, and to investigate the effect of wearing a t-shirt on testosterone transfer. Across three studies, a total of 72 healthy males applied 5.0 g 1.62% testosterone gel to their abdomen alone, upper arms/shoulders alone, or a combination of their upper arms/shoulders and abdomen (single dose or once daily for 7 days). Male-female contact occurred 2 or 12 hours after testosterone gel application, with males either wearing or not wearing a t-shirt. There were 15 minutes of supervised contact with the application site between the male and his female partner. Blood samples were collected over a 24 hour period in females for assessment of serum testosterone levels at baseline and after contact. Pharmacokinetic parameters included C(max) (maximum serum concentration), AUC(0-24) (area under the serum concentration-time curve from 0-24 hours), and C(av) (time-averaged concentration over the 24-hour period post-contact). Subjects were monitored for adverse events. CLINICAL TRIAL REGISTRATION NCT NUMBERS: Study 1 was not registered (first subject enrolled 8 March 2007); Study 2: 00998933; Study 3, 01130298. Testosterone levels (C(av) and C(max)) in females increased 86-185% from baseline after direct abdominal skin contact, although C(av) levels remained within female eugonadal range. Testosterone concentrations returned to baseline within 48 hours after last skin contact. A t-shirt barrier reduced testosterone transfer by approximately 40-48% when 5.0 g of testosterone gel was applied to the abdomen alone. A t-shirt barrier prevented transfer when 5.0 g of testosterone gel was applied to the upper arms and shoulders or to a combination of the upper arms and shoulders and the abdomen (C(max) and C(av) increased by approximately 5-11%). No major safety events were observed during the studies
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Sayah, N; Weiss, E; Watkins, W
Purpose: To evaluate the dose-mapping error (DME) inherent to conventional dose-mapping algorithms as a function of dose-matrix resolution. Methods: As DME has been reported to be greatest where dose-gradients overlap tissue-density gradients, non-clinical 66 Gy IMRT plans were generated for 11 lung patients with the target edge defined as the maximum 3D density gradient on the 0% (end of inhale) breathing phase. Post-optimization, Beams were copied to 9 breathing phases. Monte Carlo dose computed (with 2*2*2 mm{sup 3} resolution) on all 10 breathing phases was deformably mapped to phase 0% using the Monte Carlo energy-transfer method with congruent mass-mapping (EMCM);more » an externally implemented tri-linear interpolation method with voxel sub-division; Pinnacle’s internal (tri-linear) method; and a post-processing energy-mass voxel-warping method (dTransform). All methods used the same base displacement-vector-field (or it’s pseudo-inverse as appropriate) for the dose mapping. Mapping was also performed at 4*4*4 mm{sup 3} by merging adjacent dose voxels. Results: Using EMCM as the reference standard, no clinically significant (>1 Gy) DMEs were found for the mean lung dose (MLD), lung V20Gy, or esophagus dose-volume indices, although MLD and V20Gy were statistically different (2*2*2 mm{sup 3}). Pinnacle-to-EMCM target D98% DMEs of 4.4 and 1.2 Gy were observed ( 2*2*2 mm{sup 3}). However dTransform, which like EMCM conserves integral dose, had DME >1 Gy for one case. The root mean square RMS of the DME for the tri-linear-to- EMCM methods was lower for the smaller voxel volume for the tumor 4D-D98%, lung V20Gy, and cord D1%. Conclusion: When tissue gradients overlap with dose gradients, organs-at-risk DME was statistically significant but not clinically significant. Target-D98%-DME was deemed clinically significant for 2/11 patients (2*2*2 mm{sup 3}). Since tri-linear RMS-DME between EMCM and tri-linear was reduced at 2*2*2 mm{sup 3}, use of this resolution
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Glue, Paul; Cape, Gavin; Tunnicliff, Donna; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, C Tak; Harland, Sarah; Devane, Jane; Crockett, R S; Howes, John; Darpo, Borje; Zhou, Meijian; Weis, Holger; Friedhoff, Lawrence
2016-11-01
Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and C max and was slowly eliminated (mean t 1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues. © 2016, The American College of Clinical Pharmacology.
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NASA Technical Reports Server (NTRS)
Pecaut, Michael J.; Gridley, Daila S.; Smith, Anna L.; Nelson, Gregory A.
2002-01-01
The goal of part II of this study was to evaluate functional characteristics of leukocytes and circulating blood cell parameters after whole-body proton irradiation at varying doses and at low- and high-dose-rates (LDR and HDR, respectively). C57BL/6 mice (n=51) were irradiated and euthanized at 4 days post-exposure for assay. Significant radiation dose- (but not dose-rate-) dependent decreases were observed in splenocyte responses to T and B cell mitogens when compared to sham-irradiated controls (P<0.001). Spontaneous blastogenesis, also significantly dose-dependent, was increased in both blood and spleen (P<0.001). Red blood cell counts, hemoglobin concentration, and hematocrit were decreased in a dose-dependent manner (P<0.05), whereas thrombocyte numbers were only slightly affected. Comparison of proton- and gamma-irradiated groups (both receiving 3 Gy at HDR) showed a higher level of spontaneous blastogenesis in blood leukocytes and a lower splenocyte response to concanavalin A following proton irradiation (P<0.05). There were no dose rate effects. Collectively, the data demonstrate that the measurements in blood and spleen were largely dependent upon the total dose of proton radiation and that an 80-fold difference in the dose rate was not a significant factor. A difference, however, was found between protons and gamma-rays in the degree of change induced in some of the measurements.
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Seki, N
2001-07-01
The purpose of this study was to determine lifestyle factors in the elderly that affected longevity, using a population-based prospective study. The participants were 440 men and 625 women aged 60 to 74 living in a rural Japanese community. The baseline data such as age, sex, present illness, walking hours per day, sleeping hours per day, alcohol consumption, a history of smoking, and "ikigai" (meaningfulness of life) were collected in July 1990. During 90 months of follow-up from July 1990 to December 31 1997, there were 123 deaths. By Cox's multivariate hazard model adjusted age, sex, and medical histories, walking > or = 1 hour/day (HR = 0.63, 95% CI 0.44-0.91) and an "ikigai" (HR = 0.66, 95% CI 0.44-0.99) lowered the risk for all-cause mortality independently. In regard to hours of sleep, the cumulative survival curve showed that 7 hours/day was the border and sleeping > or = 7 hours/day lowered the risk (HR = 0.49 95% CI 0.33-0.74). Based on the findings in this study, walking > or = 1 hour/day, sleeping > or = 7 hours/day, and "ikigai" are important factors for longevity in the elderly.
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Economic and Microbiologic Evaluation of Single-Dose Vial Extension for Hazardous Drugs
Rowe, Erinn C.; Savage, Scott W.; Rutala, William A.; Weber, David J.; Gergen-Teague, Maria; Eckel, Stephen F.
2012-01-01
Purpose: The update of US Pharmacopeia Chapter <797> in 2008 included guidelines stating that single-dose vials (SDVs) opened and maintained in an International Organization for Standardization Class 5 environment can be used for up to 6 hours after initial puncture. A study was conducted to evaluate the cost of discarding vials after 6 hours and to further test sterility of vials beyond this time point, subsequently defined as the beyond-use date (BUD). Methods: Financial determination of SDV waste included 2 months of retrospective review of all doses prescribed. Additionally, actual waste log data were collected. Active and control vials (prepared using sterilized trypticase soy broth) were recovered, instead of discarded, at the defined 6-hour BUD. Results: The institution-specific waste of 19 selected SDV medications discarded at 6 hours was calculated at $766,000 annually, and tracking waste logs for these same medications was recorded at $770,000 annually. Microbiologic testing of vial extension beyond 6 hours showed that 11 (1.86%) of 592 samples had one colony-forming unit on one of two plates. Positive plates were negative at subsequent time points, and all positives were single isolates most likely introduced during the plating process. Conclusion: The cost of discarding vials at 6 hours was significant for hazardous medications in a large academic medical center. On the basis of microbiologic data, vial BUD extension demonstrated a contamination frequency of 1.86%, which likely represented exogenous contamination; vial BUD extension for the tested drugs showed no growth at subsequent time points and could provide an annual cost savings of more than $600,000. PMID:23180998
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Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.
Derry, Christopher J; Derry, Sheena; Moore, R Andrew
2013-06-24
Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations. To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543
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Duty Hour Reporting: Conflicting Values in Professionalism
Byrne, John M.; Loo, Lawrence K.; Giang, Dan W.
2015-01-01
Background Duty hour limits challenge professional values, sometimes forcing residents to choose between patient care and regulatory compliance. This may affect truthfulness in duty hour reporting. Objective We assessed residents' reasons for falsifying duty hour reports. Methods We surveyed residents in 1 sponsoring institution to explore the reasons for noncompliance, frequency of violations, falsification of reports, and the residents' awareness of the option to extend hours to care for a single patient. The analysis used descriptive statistics. Linear regression was used to explore falsification of duty hour reports by year of training. Results The response rate was 88% (572 of 650). Primary reasons for duty hour violations were number of patients (19%) and individual patient acuity/complexity (19%). Junior residents were significantly more likely to falsify duty hours (R = −0.966). Of 124 residents who acknowledged falsification, 51 (41%) identified the primary reason as concern that the program will be in jeopardy of violating the Accreditation Council for Graduate Medical Education (ACGME) duty hour limits followed by fear of punishment (34, 27%). This accounted for more than two-thirds of the primary reasons for falsification. Conclusions Residents' falsification of duty hour data appears to be motivated by concerns about adverse actions from the ACGME, and fear they might be punished. To foster professionalism, we recommend that sponsoring institutions educate residents about professionalism in duty hour reporting. The ACGME should also convey the message that duty hour limits be applied in a no-blame systems-based approach, and allow junior residents to extend duty hours for the care of individual patients. PMID:26457145
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[Low-dose desmopressin (DDAVP) and blood levels of FSH, LH and testosterone in men].
García-Pascual, I J; Rozán Flores, M A
1996-03-01
The effect of desmopressin (DDAVP) administration (2.5 micrograms/12 hours) on serum concentrations of FSH, LH and testosterone was studied in six men. No significant changes were observed in serum concentrations of FSH and LH after 9 days with DDAVP therapy. Nevertheless, serum concentrations of testosterone after 12 hours of DDAVP administration were significantly higher than basal concentrations. Three hours after the administration of DDAVP, serum testosterone concentrations decreased significantly. The conclusion reached was that low doses of desmopressin do not change serum concentrations of FSH and LH, but serum concentration of testosterone is decreased within three hours after the administration, although an increase is observed 12 hours later possibly due to a "rebound effect". Desmopressin would therefore directly act upon human testicle.
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Code of Federal Regulations, 2011 CFR
2011-01-01
... 10 Energy 1 2011-01-01 2011-01-01 false Work hours. 26.205 Section 26.205 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Managing Fatigue § 26.205 Work hours. (a) Individuals subject to work hour controls. Any individual who performs duties identified in § 26.4(a)(1) through (a)(5...
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Code of Federal Regulations, 2010 CFR
2010-01-01
... 10 Energy 1 2010-01-01 2010-01-01 false Work hours. 26.205 Section 26.205 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Managing Fatigue § 26.205 Work hours. (a) Individuals subject to work hour controls. Any individual who performs duties identified in § 26.4(a)(1) through (a)(5...
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Trotman, Melissa; Vermehren, Philipp; Gibson, Claire L; Fern, Robert
2015-01-01
Excitotoxicity is a major contributor to cell death during the acute phase of ischemic stroke but aggressive pharmacological targeting of excitotoxicity has failed clinically. Here we investigated whether pretreatment with low doses of memantine, within the range currently used and well tolerated for the treatment of Alzheimer's disease, produce a protective effect in stroke. A coculture preparation exposed to modeled ischemia showed cell death associated with rapid glutamate rises and cytotoxic Ca2+ influx. Cell death was significantly enhanced in the presence of high memantine concentrations. However, low memantine concentrations significantly protected neurons and glia via excitotoxic cascade interruption. Mice were systemically administered a range of memantine doses (0.02, 0.2, 2, 10, and 20 mg/kg/day) starting 24 hours before 60 minutes reversible focal cerebral ischemia and continuing for a 48-hour recovery period. Low dose (0.2 mg/kg/day) memantine treatment significantly reduced lesion volume (by 30% to 50%) and improved behavioral outcomes in stroke lesions that had been separated into either small/striatal or large/striatocortical infarcts. However, higher doses of memantine (20 mg/kg/day) significantly increased injury. These results show that clinically established low doses of memantine should be considered for patients ‘at risk' of stroke, while higher doses are contraindicated. PMID:25407270
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48 CFR 16.602 - Labor-hour contracts.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Labor-hour contracts. 16... METHODS AND CONTRACT TYPES TYPES OF CONTRACTS Time-and-Materials, Labor-Hour, and Letter Contracts 16.602 Labor-hour contracts. Description. A labor-hour contract is a variation of the time-and-materials...
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Extended working hours and health.
Raediker, Britta; Janssen, Daniela; Schomann, Carsten; Nachreiner, Friedhelm
2006-01-01
Statistical analyses of the relation between the amount of working hours and impairments to health, based on data from a European survey on working conditions in 2000, clearly reveal that there is a substantial correlation between the number of working hours per week and the frequencies of health complaints. This applies to both musculo-skeletal disorders as well as to psycho-vegetative complaints. The relationship of the duration of the exposure to working conditions to health impairments is moderated by a great number of individual (e.g., age) and situational (e.g., shift-work) variables, showing additive or interactive effects for which selected examples have been presented. In general, however, there is a consistent functional relationship between the number or working hours and their effects on the workers that holds over a great variety of conditions. It is argued that requests for extending working hours should thus be handled with care.
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Ke, Sally; Lai, Joshua; Sun, Terri; Yang, Michael M. H.; Wang, Jay Ching Chieh; Austin, Jehannine
2014-01-01
Background This study aimed to test the effects of a one-hour classroom-based workshop, led by medical students, on mental illness stigma amongst secondary school students. Method Students (aged 14–17) from three public secondary schools in British Columbia participated in the workshop. A questionnaire measuring stigma (including stereotype endorsement and desire for social distance) was administered immediately before (T1), immediately after (T2), and 1-month post-workshop (T3). Results A total of 279 students met the study inclusion criteria. Total scores on the stigma scale decreased by 23% between T1 and T2 (p<0.01). This was sustained 1-month post-workshop with a 21% stigma reduction compared to pre-intervention (p<0.01). This effect was primarily due to improvements in scores that measured desire for social distance. There were no significant changes in scores that measured stereotype endorsement. Conclusion Adolescents’ stigmatizing attitudes can be effectively reduced through a one-hour easily implementable and cost-effective classroom-based workshop led by medical students. PMID:25017811
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Kushioka, Junichi; Yamashita, Tomoya; Okuda, Shinya; Maeno, Takafumi; Matsumoto, Tomiya; Yamasaki, Ryoji; Iwasaki, Motoki
2017-03-01
OBJECTIVE Tranexamic acid (TXA), a synthetic antifibrinolytic drug, has been reported to reduce blood loss in orthopedic surgery, but there have been few reports of its use in spine surgery. Previous studies included limitations in terms of different TXA dose regimens, different levels and numbers of fused segments, and different surgical techniques. Therefore, the authors decided to strictly limit TXA dose regimens, surgical techniques, and fused segments in this study. There have been no reports of using TXA for prevention of intraoperative and postoperative blood loss in posterior lumbar interbody fusion (PLIF). The purpose of the study was to evaluate the efficacy of high-dose TXA in reducing blood loss and its safety during single-level PLIF. METHODS The study was a nonrandomized, case-controlled trial. Sixty consecutive patients underwent single-level PLIF at a single institution. The first 30 patients did not receive TXA. The next 30 patients received 2000 mg of intravenous TXA 15 minutes before the skin incision was performed and received the same dose again 16 hours after the surgery. Intra- and postoperative blood loss was compared between the groups. RESULTS There were no statistically significant differences in preoperative parameters of age, sex, body mass index, preoperative diagnosis, or operating time. The TXA group experienced significantly less intraoperative blood loss (mean 253 ml) compared with the control group (mean 415 ml; p < 0.01). The TXA group also had significantly less postoperative blood loss over 40 hours (mean 321 ml) compared with the control group (mean 668 ml; p < 0.01). Total blood loss in the TXA group (mean 574 ml) was significantly lower than in the control group (mean 1080 ml; p < 0.01). From 2 hours to 40 hours, postoperative blood loss in the TXA group was consistently significantly lower. There were no perioperative complications, including thromboembolic events. CONCLUSIONS High-dose TXA significantly reduced both intra
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48 CFR 552.236-74 - Working Hours.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Working Hours. 552.236-74... Hours. As prescribed in 536.570-5, insert the following clause: Working Hours (APR 1984) (a) It is contemplated that all work will be performed during the customary working hours of the trades involved unless...
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Roychowdhury, D F; Desai, P; Zhu, Y W
1997-08-01
This phase II study was performed to investigate the efficacy of a 3-hour 225 mg/m2 paclitaxel infusion (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) followed 24 hours later by a 30-minute infusion of carboplatin (dosed to an area under the concentration-time curve of 6) in patients with stage IIIA, IIIB, or IV non-small cell lung cancer. Patients received chemotherapy and were monitored for toxicity, response, quality of life, and survival. Paclitaxel and carboplatin pharmacokinetics were also determined with the first cycle of chemotherapy. Eleven men have been treated to date. Eight were white and three black, with a median age of 65 years. All patients had a performance status of 0 or 1. The regimen was well tolerated, with no deaths or grade 4 toxicities noted. The most common grade 3 toxicity was neutropenia, thrombocytopenia, and parasthesias (observed in <10% of cycles). The overall response rate was 57% (14% complete and 43% partial responses). Quality of life improved in most patients. Physical and emotional well-being improved in 57%, functional well-being in 43%, and social/family well-being in 14% of patients. Pharmacokinetic data are being analyzed by limited sampling technique to predict the paclitaxel area under the concentration-time curve. This unique schedule of paclitaxel and carboplatin is well tolerated and active, and is associated with improvements in various aspects of quality of life.
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Acute toxicity evaluation of proliferol: a dose-escalating, placebo-controlled study in swine.
Dagenais, Simon; Wooley, James; Hite, Mark; Green, Robert; Mayer, John
2009-01-01
Prolotherapy is one of the many treatments available for chronic musculoskeletal disorders. A commonly used drug contains dextrose 12.5%, glycerin 12.5%, phenol 1.0%, and lidocaine hydrochloride 0.25% in aqueous solution (recently termed Proliferol). For chronic low back pain, this is injected into lumbosacral ligaments to stimulate connective tissue repair. Despite generally positive clinical results, the toxicity of this drug is not well characterized and was assessed in 48 (24 male, 24 female) Yucatan miniature swine randomly assigned to low (1x), medium (5x), or high (10x) dose or saline placebo. Outcomes included clinical observations, clinical chemistry, hematology, coagulation, urinalysis, toxicokinetics, and full gross and microscopic histopathology after 24 hours or 14 days. Findings attributable to Proliferol after 24 hours included dose-response elevations in alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase, which returned to normal after 14 days. There were no remarkable findings in hematology, coagulation, or urinalysis. Urine concentrations of lidocaine and phenol both peaked after 8 hours. Histopathology findings after 24 hours included hemorrhage, inflammation, necrosis, and vascular changes in the ligaments and adjacent soft tissues at the sites of injection. After 14 days, there was evidence of repair under way, with fibrosis and skeletal muscle regeneration at the injection sites.
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Control of hypertension with single daily doses of sotalol hydrochloride.
Gabriel, R
A study was carried out in 12 previously untreated hypertensive patients to assess the efficacy of sotalol given in a once-daily dosage regimen. After an initial dosage titration period (mean 3 weeks) during which diastolic pressure was stabilized at less than 100 mmHg, all patients were satisfactorily maintained on a constant once-daily dose of sotalol for 3 months. Eight of the 12 patients required 320 mg or less daily (mean dose 190 mg). Whilst blood pressure remained controlled for at least 26 hours after daily doses the pulse rate, counted at the same time, showed escape from beta-blockade. Side-effects (vivid dreams) were reported in only 1 patient.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Yu, Victoria; Kishan, Amar U.; Cao, Minsong
2014-03-15
Purpose: To demonstrate a new method of evaluating dose response of treatment-induced lung radiographic injury post-SBRT (stereotactic body radiotherapy) treatment and the discovery of bimodal dose behavior within clinically identified injury volumes. Methods: Follow-up CT scans at 3, 6, and 12 months were acquired from 24 patients treated with SBRT for stage-1 primary lung cancers or oligometastic lesions. Injury regions in these scans were propagated to the planning CT coordinates by performing deformable registration of the follow-ups to the planning CTs. A bimodal behavior was repeatedly observed from the probability distribution for dose values within the deformed injury regions. Basedmore » on a mixture-Gaussian assumption, an Expectation-Maximization (EM) algorithm was used to obtain characteristic parameters for such distribution. Geometric analysis was performed to interpret such parameters and infer the critical dose level that is potentially inductive of post-SBRT lung injury. Results: The Gaussian mixture obtained from the EM algorithm closely approximates the empirical dose histogram within the injury volume with good consistency. The average Kullback-Leibler divergence values between the empirical differential dose volume histogram and the EM-obtained Gaussian mixture distribution were calculated to be 0.069, 0.063, and 0.092 for the 3, 6, and 12 month follow-up groups, respectively. The lower Gaussian component was located at approximately 70% prescription dose (35 Gy) for all three follow-up time points. The higher Gaussian component, contributed by the dose received by planning target volume, was located at around 107% of the prescription dose. Geometrical analysis suggests the mean of the lower Gaussian component, located at 35 Gy, as a possible indicator for a critical dose that induces lung injury after SBRT. Conclusions: An innovative and improved method for analyzing the correspondence between lung radiographic injury and SBRT treatment dose
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Respiratory health effects associated with restoration work in post-Hurricane Katrina New Orleans.
Rando, Roy J; Lefante, John J; Freyder, Laurie M; Jones, Robert N
2012-01-01
This study examines prevalence of respiratory conditions in New Orleans-area restoration workers after Hurricane Katrina. Between 2007 and 2010, spirometry and respiratory health and occupational questionnaire were administered to 791 New Orleans-area adults who mostly worked in the building construction and maintenance trades or custodial services. The associations between restoration work hours and lung function and prevalence of respiratory symptoms were examined by multiple linear regression, χ², or multiple logistic regression. 74% of participants performed post-Katrina restoration work (median time: 620 hours). Symptoms reported include episodes of transient fever/cough (29%), sinus symptoms (48%), pneumonia (3.7%), and new onset asthma (4.5%). Prevalence rate ratios for post-Katrina sinus symptoms (PRR = 1.3; CI: 1.1, 1.7) and fever and cough (PRR = 1.7; CI: 1.3, 2.4) were significantly elevated overall for those who did restoration work and prevalence increased with restoration work hours. Prevalence rate ratios with restoration work were also elevated for new onset asthma (PRR = 2.2; CI: 0.8, 6.2) and pneumonia (PRR = 1.3; CI: 0.5, 3.2) but were not statistically significant. Overall, lung function was slightly depressed but was not significantly different between those with and without restoration work exposure. Post-Katrina restoration work is associated with moderate adverse effects on respiratory health, including sinusitis and toxic pneumonitis.
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Increased Academic Productivity of Orthopaedic Surgery Residents Following 2011 Duty Hour Reform.
Johnson, Joey P; Savage, Kevin; Gil, Joseph A; Eberson, Craig P; Mulcahey, Mary K
2017-12-19
In 2003 and again in 2011, the Accreditation Council for Graduate Medical Education (ACGME) mandated increasingly stringent resident duty hour restrictions. With less time required at the hospital, residents theoretically have more time for other academic activities, such as research. Our study seeks to examine whether the number of research publications by orthopaedic residents increased following implementation of the 2011 ACGME duty hour restrictions. Pubmed was queried using publicly available alumni lists from programs across the United States. The years 2008 to 2011 were included to assess pre-2011 productivity. The years 2012 to 2015 were included in the post 2011 group. Paired t tests were used to assess differences between groups. Statistical significance was set to p < 0.05 a priori. A total of 10 orthopedic surgery residency programs across the United States. The study group was composed of 5 of the 2015 top 20 National Institutes of Health (NIH) funded programs and 5 programs without NIH funding. When corrected for number of residents per year, there were 0.290 publications per resident/year from 2008 to 2011 increasing to 0.528 publications per resident/year from 2012 to 2015 following implementation of the 2011 work hour restrictions (p = 0.033). When corrected for number of residents per year, there remained no difference in publications per resident from 2008 to 2011 (p = 0.81) or from 2012 to 2015 (p = 0.10) between NIH and non-NIH funded programs. There has been little data to support the theory that resident work hour restrictions have improved education or patient care in any meaningful way. In our study, there was a statistically significant increase in publications after 2011; however, the number of publications between NIH funded and non-NIH funded programs did not differ. Our study is the first to demonstrate that with increasing duty hour restrictions, orthopaedic surgery residents may be using more of their free time to conduct research
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Extended working hours: Impacts on workers
D. Mitchell; T. Gallagher
2010-01-01
Some logging business owners are trying to manage their equipment assets by increasing the scheduled machine hours. The intent is to maximize the total tons produced by a set of equipment. This practice is referred to as multi-shifting, double-shifting, or extended working hours. One area often overlooked is the impact that working non-traditional hours can have on...
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Baum, S.J.; Young, R.W.; Anno, G.H.
1984-08-31
This report distills from available data descriptions of typical human symptoms in reaction to prompt ionizing radiation in the dose range 75 to 4500 rads (cGy) free-in-air. The descriptions correlate symptoms with dose and time over the acute post-exposure period of six weeks. Their purpose is to provide an empirical base for estimating combat troop performance after a nuclear weapon attack. The dose range of interest is subdivided into eight subranges associated with important pathophysiological events. For each subrange, the signs and symptoms manifested by an exposed population are estimated--symptom onset, severity, duration, and incidence. The early or prodromal phasemore » of radiation sickness begins about 2 to 4 hrs after doses of 300 to 530 rads (cGy). Onset time diminishes with dose, occurring within minutes of exposure to 4500 rads (cGy). Characteristic prodromal symptoms are nausea, vomiting, anorexia, and diarrhea. The prodromal phase lasts from several days to a matter of hours, depending on dose. Symptoms of the hemopoietic syndrome are bleeding, fever, infection, and ulceration. Symptoms of the gastrointestinal syndrome are fluid loss, electrolyte imbalance, severe diarrhea, and septicemia.« less
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A 9700-hour durability test of a five centimeter diameter ion thruster
NASA Technical Reports Server (NTRS)
Nakanishi, S.; Finke, R. C.
1973-01-01
A modified Hughes SIT-5 thrustor has been life-tested at the Lewis Research Center. The final 2700 hours of the test are described with a charted history of thrustor operating parameters and off-normal events. Performance and operating characteristics were nearly constant throughout the test except for neutralizer heater power requirements and accelerator drain current. A post-shutdown inspection revealed sputter erosion of ion chamber components and component flaking of sputtered metal. Several flakes caused beamlet divergence and anomalous grid erosion, causing the test to be terminated. All sputter erosion sources have been identified and promising sputter resistant components are currently being evaluated.
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Galantamine is a novel post-exposure therapeutic against lethal VX challenge
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hilmas, Corey J.; Poole, Melissa J.; Finneran, Kathryn
2009-10-15
The ability of galantamine hydrobromide (GAL HBr) treatment to antagonize O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX)-induced lethality, impairment of muscle tension, and electroencephalographic (EEG) changes was assessed in guinea pigs. Guinea pigs were challenged with 16.8 {mu}g/kg VX (2LD50). One min after challenge, animals were administered 0.5 mg/kg atropine sulfate (ATR) and 25 mg/kg pyridine-2-aldoxime methochloride (2-PAM). In addition, guinea pigs were given 0, 1, 2, 4, 8 or 10 mg/kg GAL as a post-exposure treatment immediately prior to ATR and 2-PAM. Animals were either monitored for 24-h survival, scheduled for electroencephalography (EEG) recording, or euthanized 60 min later for measurement of indirectly-elicitedmore » muscle tension in the hemidiaphragm. Post-exposure GAL therapy produced a dose-dependent increase in survival from lethal VX challenge. Optimal clinical benefits were observed in the presence of 10 mg/kg GAL, which led to 100% survival of VX-challenged guinea pigs. Based on muscle physiology studies, GAL post-exposure treatment protected the guinea pig diaphragm, the major effector muscle of respiration, from fatigue, tetanic fade, and muscular paralysis. Protection against the paralyzing effects of VX was dose-dependent. In EEG studies, GAL did not alter seizure onset for all doses tested. At the highest dose tested (10 mg/kg), GAL decreased seizure duration when administered as a post-exposure treatment 1 min after VX. GAL also reduced the high correlation associated between seizure activity and lethality after 2LD50 VX challenge. GAL may have additional benefits both centrally and peripherally that are unrelated to its established mechanism as a reversible acetylcholinesterase inhibitor (AChEI)« less
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Diaz, Maria Cristina B; Rosales, Raymond L
2015-08-01
Current reports on movement disorder adverse effects of acetylcholinesterase inhibitors only include extrapyramidal symptoms and myoclonus.Here is a case of an 81-year-old female Filipino with dementia who presented with first-onset generalized choreiform movements.The etiology of the clinical finding of dyskinesia was investigated through laboratories, neuroimaging, and electroencephalogram, all of which yielded negative results. Review of her medications included the rivastigmine (Exelon) patch, which had just been increased to 13.3 mg/24-hour-dose 3 months prior. With all other possible causes excluded, a trial discontinuation of rivastigmine, showed decreased frequency of the dyskinesia 48 hours after, with complete resolution after 6 days, and no recurrence since then.This case thus presents a probable association or causality between the choreiform movement and rivastigmine at 13.3 mg/24-hour-dose patch because of clear temporal proximity, lack of alternative explanations, and a reversal of the dyskinesia upon medicament discontinuation.
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2009-04-12
circle all that apply) a. None b. Sedatives/Tranquilizers c. Aspirin/ Tylenol /any analgesic 31 d. Antihistamines e. Decongestants f. Other (please specify...4. Do you take any over the counter medications (e.g., antacids, Benadryl, Tylenol , etc.) two (2) or more times a month
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Mixed martial arts induces significant fatigue and muscle damage up to 24 hours post-combat.
Ghoul, Nihel; Tabben, Montassar; Miarka, Bianca; Tourny, Claire; Chamari, Karim; Coquart, Jeremy
2017-06-22
This study investigates the physiological/physical responses to a simulated mixed martial arts (MMA) competition over 24 hr. Twelve fighters performed a simulated MMA competition, consisting of three 5-min MMA matches. Physiological/physical data were assessed before (Trest), directly after round 1 (Trd1), round 2 (Trd2) and round 3 (Trd3), and then 30-min (Trecovery30min) and/or 24-hr (Trecovery24h) post-competition. Heart rate (HR), rating of perceived exertion (RPE) and blood lactate concentration ([La]) were assessed at Trest, Trd1, Trd2 and Trd3. Biological data were collected at Trest, Trd3, Trecovery30min and Trecovery24h. Physical tests were performed at Trest, Trecovery30min and Trecovery24h. HR, RPE and [La] were high during competition. Leukocytes, hemoglobin, total protein and glycemia were increased at Trd3 compared with all other time points (p<0.05). Cortisol was increased at Trd3 compared with Trest and Trecovery24h (p<0.05). Testosterone was higher at Trd3 and Trecovery30min than Trest (p<0.001). Higher values of uric acid were noted during recovery periods (p<0.001). Lactate dehydrogenase was lower at Trest compared with Trd3, Trecovery30min and Trecovery24h (p<0.05). Countermovement jump was higher at Trest than Trecovery30min (p=0.020). Consequently, MMA is a high-intensity intermittent combat sport that induces significant fatigue and muscle damage, both of which are still present 24-hr post-competition.
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Low-dose vaporized cannabis significantly improves neuropathic pain.
Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee
2013-02-01
We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.
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Kilciler, Guldem; Musabak, Ugur; Bagci, Sait; Yesilova, Zeki; Tuzun, Ahmet; Uygun, Ahmet; Gulsen, Mustafa; Oren, Sema; Oktenli, Cagatay; Karaeren, Necmettin
2008-01-01
Background. Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP) procedure and there are some reports showing cytokine changes in ERCP-induced pancreatits. Goals. To investigate the association between early changes (within 24 hours) in the serum interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)α, and IL-6 levels and the development of post-ERCP pancreatitis. Study. Forty five consecutive patients who underwent therapeutic ERCP and 10 patients with acute pancreatitis without ERCP were enrolled to the study. Serum concentrations of IL-2, IL-4, TNFα, and IL-6 were determined immediately before, 12 hours and 24 hours after ERCP. Results. Seven of the 45 patients (15.5%) developed post-ERCP pancreatitis. The levels of IL-4 at 24 hours after ERCP were significantly lower in the patients with post-ERCP pancreatitis than in those without pancreatitis, while TNFα levels at 12 hours after ERCP were higher in the complicated group than those of the uncomplicated group. The ratios of TNFα/IL-4 at 12 and 24 hours after ERCP were found significantly higher in the patients with post-ERCP pancreatitis than in those without pancreatitis. IL-6 in the complicated patients was found significantly increased at 24 hours after ERCP. Conclusions. The enhancement of serum TNFα and IL-6 levels in the patients with ERCP-induced pancreatitis reflects the inflammatory activity. Additionally, these cytokines together with IL-4 can be used in clinical laboratory monitoring of ERCP. PMID:18670651
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de Oliveira, Adriano Rodrigues; Vanin, Adriane Aver; De Marchi, Thiago; Antonialli, Fernanda Colella; Grandinetti, Vanessa dos Santos; de Paiva, Paulo Roberto Vicente; Albuquerque Pontes, Gianna Móes; Santos, Larissa Aline; Aleixo Junior, Ivo de Oliveira; de Carvalho, Paulo de Tarso Camillo; Bjordal, Jan Magnus; Leal-Junior, Ernesto Cesar Pinto
2014-02-27
Recent studies involving phototherapy applied prior to exercise have demonstrated positive results regarding the attenuation of muscle fatigue and the expression of biochemical markers associated with recovery. However, a number of factors remain unknown, such as the ideal dose and application parameters, mechanisms of action and long-term effects on muscle recovery. The aims of the proposed project are to evaluate the long-term effects of low-level laser therapy on post-exercise musculoskeletal recovery and identify the best dose andapplication power/irradiation time. A double-blind, randomized, placebo-controlled clinical trial with be conducted. After fulfilling the eligibility criteria, 28 high-performance athletes will be allocated to four groups of seven volunteers each. In phase 1, the laser power will be 200 mW and different doses will be tested: Group A (2 J), Group B (6 J), Group C (10 J) and Group D (0 J). In phase 2, the best dose obtained in phase 1 will be used with the same distribution of the volunteers, but with different powers: Group A (100 mW), Group B (200 mW), Group C (400 mW) and Group D (0 mW). The isokinetic test will be performed based on maximum voluntary contraction prior to the application of the laser and after the eccentric contraction protocol, which will also be performed using the isokinetic dynamometer. The following variables related to physical performance will be analyzed: peak torque/maximum voluntary contraction, delayed onset muscle soreness (algometer), biochemical markers of muscle damage, inflammation and oxidative stress. Our intention, is to determine optimal laser therapy application parameters capable of slowing down the physiological muscle fatigue process, reducing injuries or micro-injuries in skeletal muscle stemming from physical exertion and accelerating post-exercise muscle recovery. We believe that, unlike drug therapy, LLLT has a biphasic dose-response pattern. The protocol for this study is registered with
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Khorasani, Mohammad S; Diko, Sindi; Hsia, Allison W; Anderson, Matthew J; Genetos, Damian C; Haudenschild, Dominik R; Christiansen, Blaine A
2015-02-16
Previous studies in animal models of osteoarthritis suggest that alendronate (ALN) has antiresorptive and chondroprotective effects, and can reduce osteophyte formation. However, these studies used non-physiologic injury methods, and did not investigate early time points during which bone is rapidly remodeled prior to cartilage degeneration. The current study utilized a non-invasive model of knee injury in mice to investigate the effect of ALN treatment on subchondral bone changes, articular cartilage degeneration, and osteophyte formation following injury. Non-invasive knee injury via tibial compression overload or sham injury was performed on a total of 90 mice. Mice were treated with twice weekly subcutaneous injections of low-dose ALN (40 μg/kg/dose), high-dose ALN (1,000 μg/kg/dose), or vehicle, starting immediately after injury until sacrifice at 7, 14 or 56 days. Trabecular bone of the femoral epiphysis, subchondral cortical bone, and osteophyte volume were quantified using micro-computed tomography (μCT). Whole-joint histology was performed at all time points to analyze articular cartilage and joint degeneration. Blood was collected at sacrifice, and serum was analyzed for biomarkers of bone formation and resorption. μCT analysis revealed significant loss of trabecular bone from the femoral epiphysis 7 and 14 days post-injury, which was effectively prevented by high-dose ALN treatment. High-dose ALN treatment was also able to reduce subchondral bone thickening 56 days post-injury, and was able to partially preserve articular cartilage 14 days post-injury. However, ALN treatment was not able to reduce osteophyte formation at 56 days post-injury, nor was it able to prevent articular cartilage and joint degeneration at this time point. Analysis of serum biomarkers revealed an increase in bone resorption at 7 and 14 days post-injury, with no change in bone formation at any time points. High-dose ALN treatment was able to prevent early trabecular
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Mansi, Ishak A
2011-03-01
In a recent report, the Institute of Medicine recommended more restrictions on residents' working hours. Several problems exist with a system that places a weekly limit on resident duty hours: (1) it assumes the presence of a linear relationship between hours of work and patient safety; (2) it fails to consider differences in intensity among programs; and (3) it does not address increases in the scientific content of medicine, and it places the burden of enforcing the duty hour limits on the Accreditation Council for Graduate Medical Education. An innovative method of calculating credit hours for graduate medical education would shift the focus from "years of residency" to "hours of residency." For example, internal medicine residents would be requested to spend 8640 hours of total training hours (assuming 60 hours per week for 48 weeks annually) instead of the traditional 3 years. This method of counting training hours is used by other professions, such as the Intern Development Program of the National Council of Architectural Registration Boards. The proposed approach would allow residents and program directors to pace training based on individual capabilities. Standards for resident education should include the average number of patients treated in each setting (inpatient or outpatient). A possible set of "multipliers" based on these parameters, and possibly others such as resident evaluation, is devised to calculate the "final adjusted accredited hours" that count toward graduation. Substituting "years of training" with "hours of training" may resolve many of the concerns with the current residency education model, as well as adapt to the demands of residents' personal lives. It also may allow residents to pace their training according to their capabilities and learning styles, and contribute to reflective learning and better quality education.
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Mahajan, Vidushi; Arora, Sumant; Kaur, Tarundeep; Gupta, Sorab; Guglani, Vishal
2013-01-01
Background: The 23-hour Observation Unit (OU) is a novel and an effective means for tackling overcrowding in busy Paediatric Emergency Departments (PED) worldwide. However, unexpected hospitalisations in the OU involve transfer of care and they reduce the efficiency of the OU. Hence, we aimed to study the presenting diagnoses which were responsible for the unexpected hospitalisations in a 23-hour OU. Methods and Design: A prospective cohort study Setting: The PED at a tertiary care teaching hospital. Duration: 15th Feb-15th March 2011. Protocol: Consecutive children were triaged at presentation to the PED, according to the WHO paediatric emergency triage algorithm. Those who were transferred to the 23-hour OU, were further followed up for duration of the stay, the hospital course, and the outcome (discharge/hospitalisation). Results: Three hundred (228 males, 72 females) consecutive children who attended the PED over one month were enrolled. All the children, at presentation, were triaged by the medical intern/s who was/were posted in the PED, and they were crosschecked by a PED consultant. A majority (55%, n=165) of the children were triaged as non-urgent, 32% (n=97) as priority and 13% (n=38) as emergent. Out of the 300 children, 173(58%) were transferred to the 23-hour OU. Of these, 16 (9.1%) required unexpected hospitalisations. The children who required hospitalisations had the following diagnoses: bronchiolitis (4), bronchopneumonia (4), seizure (2), viral hepatitis (2), high fever (1), bronchial asthma (1), severe anaemia (1), and urticaria (1). The mean duration of the stay in the OU was 19 hours for those who needed hospitalisation, as against 13 hours for those who were discharged from the OU. Conclusion: The children with respiratory complaints (bronchiolitis and bronchopneumonia) need frequent monitoring in the 23-hour OU, as they have high hospitalisation rates in the OU. PMID:23998079
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Drapkin, Jefferson; Likourezos, Antonios; Beals, Tyler; Monfort, Ralph; Fromm, Christian; Marshall, John
2018-01-01
Introduction Our objective was to describe dosing, duration, and pre- and post-infusion analgesic administration of continuous intravenous sub-dissociative dose ketamine (SDK) infusion for managing a variety of painful conditions in the emergency department (ED). Methods We conducted a retrospective chart review of patients aged 18 and older presenting to the ED with acute and chronic painful conditions who received continuous SDK infusion in the ED for a period over six years (2010–2016). Primary data analyses included dosing and duration of infusion, rates of pre- and post-infusion analgesic administration, and final diagnoses. Secondary data included pre- and post-infusion pain scores and rates of side effects. Results A total of 104 patients were enrolled in the study. Average dosing of SDK infusion was 11.26 mg/hr, and the mean duration of infusion was 135.87 minutes. There was a 38% increase in patients not requiring post-infusion analgesia. The average decrease in pain score was 5.04. There were 12 reported adverse effects, with nausea being the most prevalent. Conclusion Continuous intravenous SDK infusion has a role in controlling pain of various etiologies in the ED with a potential to reduce the need for co-analgesics or rescue analgesic administration. There is a need for more robust, prospective, randomized trials that will further evaluate the analgesic efficacy and safety of this modality across a wide range of pain syndromes and different age groups in the ED. PMID:29760856
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Long Hours and Premium Pay, May 1979.
ERIC Educational Resources Information Center
Stamas, George D.
1980-01-01
From 1978-79 incidence of long hours among full-time wage and salary workers dropped for the first time since the 1974-75 recession. Of those who worked long hours, about 43% received premium pay (time and one-half the regular wage for hours worked in excess of forty per week). Employers used overtime hours to cope with disequilibrium phenomena…
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Yue, Yong; Collaku, Agron; Liu, Dongzhou J
2018-01-01
Acetaminophen (paracetamol) is a first-line treatment for mild and moderate pain. A twice-daily sustained-release (SR) formulation may be more convenient for chronic users than standard immediate-release (IR) acetaminophen. This randomized, 3-way crossover study evaluated pharmacokinetics and safety of single-dose 1500- and 2000-mg SR acetaminophen formulations and 2 doses of IR acetaminophen 1000 mg given 6 hours apart in healthy adults (n = 14). Primary outcome was time that plasma acetaminophen concentration was ≥4 μg/mL (T C≥4μg/mL ). Key secondary outcomes were area under the plasma concentration-time curve (AUC) from time 0 to time t, when plasma acetaminophen was detectable (AUC 0-t ), AUC from 0 to infinity (AUC 0-inf ), and maximum plasma acetaminophen concentration (C max ). T C≥4μg/mL from 2000-mg SR acetaminophen was similar to that from 2 doses of IR acetaminophen, whereas T C≥4μg/mL for 1500-mg SR acetaminophen was significantly shorter than that for IR acetaminophen (P = .004). The extent of acetaminophen absorption from 2000-mg SR and 2 doses of the IR formulation was similar and within bioequivalence limits with regard to AUC 0-12 , AUC 0-t , and AUC 0-inf . The extent of acetaminophen absorption from 1500-mg SR was significantly lower than that from IR acetaminophen. The 2000-mg SR represents a potential candidate formulation for 12-hour dosing with acetaminophen. © 2017, The American College of Clinical Pharmacology.
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Kinetic Post-match Fatigue in Professional and Youth Soccer Players During the Competitive Period
Djaoui, Leo; Diaz-Cidoncha Garcia, Jorge; Hautier, Christophe; Dellal, Alexandre
2016-01-01
Background No previous research has analysed kinetic fatigue of elite adult players and elite youth players during the competitive period. Objectives The aim of the present study was to analyse kinetic post-match fatigue in professional and youth soccer players during the competitive period. Materials and Methods resting heart rate (HRrest), post-effort recovery heart rate (HRrecovery), rate of perceived exertion fatigue (RPEf), muscle soreness and blood samples with creatine kinase (CK) and resting lactate (La) from nine professional soccer players were measured immediately before, 24 hour and 48 hour after two official French first league matches (Ligue 1) whereas RPEf, HRrest, and 20m speed performance (speed-20 m) were measured in ten U-17 elite players immediately before, 24 hour and 48h after a friendly match. Results for professionals, a soccer match elevated all physiological markers during the next 24 hours (P < 0.05); only HRrecovery remained significantly different 48 hours after the match (P < 0.05) whereas there was no variation of HRrest, RPEf, and speed-20m, which were elevated until 24h and got back to reference values 48 hours after the match (P < 0.05) for the U17 players. Comparing the two groups, HRrest results remained lower all the time for professionals, and RPEf was lower for U-17, 24 hours after the match (P < 0.05). Conclusions Independent of their level, professional soccer players, need 48 hours to recover after an official match. Professionals gain more fatigue than young players after a match, but recover as fast. Thus, they recover more efficiently especially due to a better physical condition and fitness training. It is expected that the results showed in the study help elite soccer and fitness coaches to manage the training load of the team according to the match. PMID:27217927
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Single dose oral aspirin for acute postoperative pain in adults.
Derry, Sheena; Moore, R Andrew
2012-04-18
This review is an update of a previously published review in the Cochrane Database of Systematic Reviews on 'Single dose oral aspirin for acute pain'. Aspirin has been known for many years to be an effective analgesic for many different pain conditions. Although its use as an analgesic is now limited in developed countries, it is widely available, inexpensive, and remains commonly used throughout the world. To assess the analgesic efficacy and associated adverse events of single dose oral aspirin in acute postoperative pain. For the earlier review, we identified randomised trials by searching CENTRAL (The Cochrane Library) (1998, Issue 1), MEDLINE (1966 to March 1998), EMBASE (1980 to January 1998), and the Oxford Pain Relief Database (1950 to 1994). We updated searches of CENTRAL, MEDLINE, and EMBASE to January 2012. Single oral dose, randomised, double-blind, placebo-controlled trials of aspirin for relief of established moderate to severe postoperative pain in adults. We assessed studies for methodological quality and two review authors extracted the data independently. We used summed total pain relief (TOTPAR) over four to six hours to calculate the number of participants achieving at least 50% pain relief. We used these derived results to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over four to six hours. We sought numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, as additional measures of efficacy. We collected information on adverse events and withdrawals. We included 68 studies in which aspirin was used at doses from 300 mg to 1200 mg, but the vast majority of participants received either 600/650 mg (2409 participants, 64 studies) or 990/1000 mg (380 participants, eight studies). There was only one new study.Studies were overwhelmingly of adequate or good
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ERIC Educational Resources Information Center
Cox, Daniel J.; Merkel, R. Lawrence; Penberthy, Jennifer Kim; Kovatchev, Boris; Hankin, Cheryl S.
2004-01-01
Objective: Adolescents with attention-deficit/hyperactivity disorder (ADHD) are at high risk for driving accidents. One dose of methylphenidate (MPH) improves simulator driving performances of ADHD-diagnosed adolescents at 1.5 hours post-dose. However, little is known about the effects of different MPH delivery profiles on driving performance…
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Clinical Decision Support Improves Initial Dosing and Monitoring of Tobramycin and Amikacin
Cox, Zachary L.; Nelsen, Cori L.; Waitman, Lemuel R.; McCoy, Jacob A.; Peterson, Josh F.
2010-01-01
Purpose Clinical decision support (CDS) systems could be valuable tools in reducing aminoglycoside prescribing errors. We evaluated the impact of CDS on initial dosing, interval, and pharmacokinetic outcomes of amikacin and tobramycin therapy. Methods A complex CDS advisor to provide guidance on initial dosing and monitoring, using both traditional and extended interval dosing strategies, was integrated into computerized provider order entry (CPOE) and compared to a control group which featured close pharmacy monitoring of all aminoglycoside orders. A random sample of 118 patients from an academic, tertiary care medical center prescribed amikacin and tobramycin prior to advisor implementation was compared to 98 patients admitted following advisor implementation. Primary outcome was an initial dose within 10% of a dose calculated to be adherent to published dose guidelines. Secondary outcomes were a guideline-adherent interval, trough and peak concentrations in goal range, and incidence of nephrotoxicity. Results Of 216 patients studied, 97 were prescribed amikacin and 119 were prescribed tobramycin. The primary outcome of initial dosing consistent with guideline-based care increased from 40% in the pre-advisor arm to 80% in the post-advisor arm (p<0.001), with a number needed to treat of 3 patients to prevent one incorrect dose. Correct initial interval based on renal function also increased from 63% to 87% (p<0.001). The changes in initial dosing and interval resulted in an increase of trough concentrations in the goal range from 59% pre-advisor to 89% post-advisor implementation (p=0.0004). There was no significant difference in peak concentrations in goal range or incidence of nephrotoxicity (25% vs. 17%, p=0.2). Conclusion An advisor for aminoglycoside dosing and monitoring integrated into CPOE significantly improves initial dosing, selection of interval, and trough concentrations at goal compared to unassisted physician dosing. PMID:21411805
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Felici, Roberta; Buonvicino, Daniela; Muzzi, Mirko; Cavone, Leonardo; Guasti, Daniele; Lapucci, Andrea; Pratesi, Sara; De Cesaris, Francesco; Luceri, Francesca; Chiarugi, Alberto
2017-05-01
Mitochondrial encephalopathies are fatal, infantile neurodegenerative disorders caused by a deficit of mitochondrial functioning, for which there is urgent need to identify efficacious pharmacological treatments. Recent evidence shows that rapamycin administered both intraperitoneally or in the diet delays disease onset and enhances survival in the Ndufs4 null mouse model of mitochondrial encephalopathy. To delineate the clinical translatability of rapamycin in treatment of mitochondrial encephalopathy, we evaluated the drug's effects on disease evolution and mitochondrial parameters adopting treatment paradigms with fixed daily, oral doses starting at symptom onset in Ndufs4 knockout mice. Molecular mechanisms responsible for the pharmacodynamic effects of rapamycin were also evaluated. We found that rapamycin did not affect disease development at clinically-relevant doses (0.5 mg kg -1 ). Conversely, an oral dose previously adopted for intraperitoneal administration (8 mg kg -1 ) delayed development of neurological symptoms and increased median survival by 25%. Neurological improvement and lifespan were not further increased when the dose raised to 20 mg kg -1 . Notably, rapamycin at 8 mg kg -1 did not affect the reduced expression of respiratory complex subunits, as well as mitochondrial number and mtDNA content. This treatment regimen however significantly ameliorated architecture of mitochondria cristae in motor cortex and cerebellum. However, reduction of mTOR activity by rapamycin was not consistently found within the brain of knockout mice. Overall, data show the ability of rapamycin to improve ultrastructure of dysfunctional mitochondria and corroborate its therapeutic potential in mitochondrial disorders. The non-clinical standard doses required, however, raise concerns about its rapid and safe clinical transferability. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Sanzari, Jenine K; Cengel, Keith A; Wan, X Steven; Rusek, Adam; Kennedy, Ann R
2014-07-01
NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure.
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Sanzari, Jenine K.; Cengel, Keith A.; Wan, X. Steven; Rusek, Adam; Kennedy, Ann R.
2014-01-01
NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure. PMID:25202654
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Code of Federal Regulations, 2010 CFR
2010-01-01
... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Hours. 0.3 Section 0.3 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE ORGANIZATION § 0.3 Hours. Principal and field offices are open on each business day from 8:30 a.m. to 5 p.m. ...
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48 CFR 1316.602 - Labor-hour contracts.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Labor-hour contracts. 1316... AND CONTRACT TYPES TYPES OF CONTRACTS Time-and-Materials, Labor-Hour, and Letter Contracts 1316.602 Labor-hour contracts. ...
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Hourly Updated GNSS Orbit and Clock
NASA Astrophysics Data System (ADS)
Song, S.; Xue, J.
2016-12-01
With the development of the performance of GNSS, the hourly updated orbit and clock of GNSS are paid much more attention and used by more and more users because of the timeliness and high accuracy. The hourly GNSS orbit and clock are produced routinely in Shanghai Analysis Center(AC) of the International GNSS Monitoring and Assessment Service (iGMAS).In this article, the accuracy of hourly and 6-hourly updated ultra-rapid GPS,GLONASS,GALILEO,BDS orbit and clock (SHU1 and SHU6) are analyzed relative to the final production in detail. The analysis show that, in calculation session, there's no much difference between the mean SHU1 and SHU6 RMS and STD for GNSS orbit and clock. However, for BDS clock in prediction session, the RMS and STD of BDS SHU1 are 2.6ns and 0.5ns respectively, the RMS of BDS SHU6 increase from 2.7ns to 4.5ns from the 1st to the 6th hour prediction session, but there's no much changes of STD. For GPS clock in prediction session, the RMS and STD of GPS SHU1 is quite stable with 0.5ns and 0.2ns.The RMS of GPS SHU6 clock increase from 0.6ns to 1.0ns from the 1st to the 6th hour, but STD is stable at about 0.2ns.For the orbit in calculate session, the RMS of BDS SHU1 is a little less than that of SHU6,the RMS of GPS SHU1 and SHU6 orbit are approximately at the same level. In prediction session, the RMS of IGSO/MEO for BDS SHU1 is relative stable, but the RMS of SHU6 1st-6th hour prediction session increase from about 26.5cm to 32.7cm. The RMS of GPS SHU1 orbit's prediction session is about 3.4cm,but which increase from 3.3cm to 4.3cm for GPS SHU6 1st-6th hour prediction session.The comparison of GLONASS and GALILEO orbit and clock also will be described.The results show that the hourly update is more important for BDS at this stage.Moreover,some problems appearing in satellites and stations can be found earlier by 1 hourly updated frequency.
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Le, Wei; Qi, Lixin; Li, Jiaxuan; Wu, DengIong; Xu, Jun; Zhang, Jinfu
2016-01-01
The present study aims to examine the effect of low-dose ionizing irradiation on DNA double strand breaks (DSB) in mouse spermatogonial stem cells (SSCs) and reveal the underlying pathways for the DNA repair for DSB in SSCs. Eighteen one-month-old mice were divided into 6 groups and sacrificed separately at 45 minutes, 2 hours, 24 hours, 48 hours, and 72 hours after 0.1Gy X-ray irradiation (mice without receiving ionizing irradiation served as control). After perfusion fixation, testes were removed, sectioned, and followed by staining of γH2AX, 53BP1, Caspase 3, and promyelocytic leukemia zinc-finger (PLZF) for analysis among the different groups. The staining was observed by immunofluorescence visualized by confocal laser scanning. After low-dose irradiation, only 53BP1, but not Caspase3 or γH2AX was upregulated in PLZF positive SSCs within 45 minutes. The expression level of 53BP1 gradually decreased 24 hours after irradiation. Moreover, low-dose irradiation had no effect on the cell number and apoptotic status of SSCs. However other spermatogenic cells highly expressed γH2AX shortly after irradiation which was dramatically reduced following the events of DNA repair. It appears that low-dose ionizing irradiation may cause the DNA DSB of mouse spermatogenic cells. 53BP1, but not γH2AX, is involved in the DNA repair for DSB in SSCs. Our data indicates that 53BP1 plays an important role in the pathophysiological repair of DNA DSB in SSCs. This may open a new avenue to understanding the mechanisms of DNA repair of SSCs and male infertility.
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Nakajima, Makoto; Inatomi, Yuichiro; Yonehara, Toshiro; Watanabe, Masaki; Ando, Yukio
2015-01-01
The aim of this study was to investigate whether stratifying patients according to the time period from admission to the start of regular working hours would help detect a weekend effect in acute stroke patients. Ischemic stroke patients admitted between October 2002 and March 2012 were analyzed. Working hours were defined as 9:00-17:00 on weekdays. Patients were divided into those admitted during working hours (no-wait group) and three other groups according to the time from admission to working hours: ≤24 h (short-wait group), 24-48 h (medium-wait group), and >48 h (long-wait group). The modified Rankin Scale score and mortality at three-months were compared among the groups. Of 5625 patients, 3323 (59%) were admitted outside working hours. The proportion of patients with an mRS score 0-1 at three-months showed a decreasing trend with the time period before working hours: 47% (no-wait group), 42% (short-wait group), 42% (medium-wait group), and 38% (long-wait group), respectively (P < 0·001). When the no-wait group was used as a reference, the odds ratio for modified Rankin Scale score 0-1 was 0·88 (95% confidence interval, 0·75-1·04) in the short-wait group, 0·86 (0·69-1·07) in the medium-wait group, and 0·67 (0·53-0·85) in the long-wait group after adjusting for sex, age, premorbid mRS score, previous morbidity, stroke severity, and vascular risk factors. Mortality at three-months was not different between the no-wait group and the other groups. A weekend effect might be evident if patients were stratified according to the time period from admission until working hours. © 2014 World Stroke Organization.
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Kim, Sung R; Chae, Hyun S; Yoon, Mi J; Han, Jung H; Cho, Kwang J; Chung, Sun J
2012-01-30
Supine recumbence has been widely performed to prevent post-lumbar puncture headache (PLPH). However, the optimal duration of supine recumbence is controversial. The aim of the study is to compare the occurrence of PLPH according to the duration of supine recumbence in patients with neurological disorders. A non-equivalent control/experimental pre-/post-test study design was used. Seventy consecutive patients were prospectively enrolled between July 2007 and July 2008. Thirty-five patients underwent supine recumbence for four hours after lumbar puncture (Group 1) and 35 patients underwent supine recumbence for one hour (Group 2). The overall frequency of PLPH was 31.4%. The frequency of PLPH was not significantly different between the Group 1 (28.6%) and Group 2 (34.3%) (P = 0.607). In patients with PLPH, the median severity (P = 0.203) and median onset time of PLPH (P = 0.582) were not significantly different between the two groups. In a logistic regression analysis, the previous history of post-lumbar puncture headache was a significant risk factor for the occurrence of PLPH (OR = 11.250, 95% CI: 1.10-114.369, P = 0.041). Our study suggests that short duration (one hour) of supine recumbence may be as efficient as long duration (four hours) of supine recumbence to prevent PLPH.
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Ionizing radiation post-curing of objects produced by stereolithography and other methods
Howell, David H.; Eberle, Claude C.; Janke, Christopher J.
2000-01-01
An object comprised of a curable material and formed by stereolithography or another three-dimensional prototyping method, in which the object has undergone initial curing, is subjected to post-curing by ionizing radiation, such as an electron beam having a predetermined beam output energy, which is applied in a predetermined dosage and at a predetermined dose rate. The post-cured object exhibits a property profile which is superior to that which existed prior to the ionizing radiation post-curing.
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Customized fiber glass posts. Fatigue and fracture resistance.
Costa, Rogério Goulart; De Morais, Eduardo Christiano Caregnatto; Campos, Edson Alves; Michel, Milton Domingos; Gonzaga, Carla Castiglia; Correr, Gisele Maria
2012-02-01
To evaluate the root fracture strength of human single-rooted premolars restored with customized fiberglass post-core systems after fatigue simulation. 40 human premolars had their crowns cut and the root length was standardized to 13 mm. The teeth were endodontically treated and embedded in acrylic resin. The specimens were distributed into four groups (n=10) according to the restorative material used: prefabricated fiber post (PFP), PFP+accessory fiber posts (PFPa), PFP+unidirectional fiberglass (PFPf), and unidirectional fiberglass customized post (CP). All posts were luted using resin cement and the cores were built up with a resin composite. The samples were stored for 24 hours at 37 degrees C and 100% relative humidity and then submitted to mechanical cycling. The specimens were then compressive-loaded in a universal testing machine at a crosshead speed of 0.5 mm/minute until fracture. The failure patterns were analyzed and classified. Data was submitted to one-way ANOVA and Tukey's test (alpha = 0.05). The mean values of maximum load (N) were: PFP - 811.4 +/- 124.3; PFPa - 729.2 +/- 157.2; PFPf- 747.5 +/- 204.7; CP - 762.4 +/- 110. Statistical differences were not observed among the groups. All groups showed favorable restorable failures. Fiberglass customized post did not show improved fracture resistance or differences in failure patterns when compared to prefabricated glass fiber posts.
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Nimmaanrat, Sasikaan; Oofuvong, Maliwan
2015-01-01
Medical practitioners' attitudes have a significant impact on quality of care for cancer pain patients. This study was conducted to determine if being given a lecture concerning cancer pain and its management could improve the attitudes of medical students. A comparative study was conducted in 126 fifth-year medical students. Each student completed a pretest consisting of 3 questions about attitudes toward the optimal use of analgesics and 5 questions about attitudes toward prescribing opioids. Then they were given a 1.5-hour lecture, immediately following which they completed a post-test with the same questions. Analysis with either comparison between groups or by matching, the post-test showed significantly more positive attitudes (p<0.05) of the medical students in all 3 questions about optimal use of analgesics and 4 out of 5 questions about prescription of opioids. The post-test results showed significantly more negative attitudes concerning the most appropriate stage for patients with severe pain to receive maximal doses of analgesics. Conservative attitudes, especially concerns about addiction, have been associated with a reluctance in many physicians to prescribe opioids. This study found that cancer pain education can help to improve medical student attitudes. However, fear of addiction and tolerance was still evident so emphasis of this particular issue during a lecture is essential. Providing appropriate information by means of a lecture can improve the attitudes of medical students regarding cancer pain management. However, more information should be given to lessen fear of addiction and tolerance.
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Breaking the Long Hours Culture.
ERIC Educational Resources Information Center
Kodz, J.; Kersley, B.; Strebler, M. T.; O'Regan, S.
Case studies of 12 leading British employers were driven by employers' interest in issues related to working long hours in light of introduction of the Working Time Directive, a European Community initiative enacted into British law that sets limits on working hours per week. Data showed over one-fourth of full-time employees worked over 48 hours…
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The impact of Ontario’s extended drinking hours on cross-border cities of Windsor and Detroit
Vingilis, E.; McLeod, A.I.; Seeley, J.; Mann, R.; Voas, R.; Compton, C.
2008-01-01
Purpose This study evaluated the cross-border safety impact of extended drinking hours from 1:00 to 2:00 a.m., in licensed establishments in Ontario, Canada. Methods This study examined patterns in total and alcohol-related casualties in: (1) Windsor, Ontario, Canada compared to Detroit, Michigan, US with a 2:00 a.m. closing time, and (2) Ontario compared to Michigan for overall trends. The criterion outcome indicators were: (1) monthly motor vehicle casualties (major injuries and fatalities) for the city-regions of Windsor and Detroit and (2) Ontario and Michigan monthly motor vehicle fatalities occurring between 11:00 p.m. and 3:00 a.m. for 4 years pre- and 3 years post-policy change. In order to examine cross-border drinking consequences, data were disaggregated to assess trends of motor vehicle injury collisions involving vehicles with US licence plates and with US drivers aged 16–20 in the Windsor region; similarly trends were assessed for motor vehicle injury collisions involving vehicles with Ontario licence plates in the Detroit region. Results The Windsor region total motor vehicle casualty data showed a non-significant pre–post increase, while the Detroit region showed a statistically significant decrease for total motor vehicle casualties. In the Windsor region, a significant increase was found for alcohol-related motor vehicle casualties after the drinking hours were extended. However, the Detroit region showed a statistically significant decrease in alcohol-related motor vehicle casualties concomitant with Ontario’s drinking hour extension. No similar trends were found for the province of Ontario and the state of Michigan as a whole. Moreover, a significant decrease was found for injury collisions involving vehicles with Ontario licence plates in the Detroit region but no similar pattern was found for injury collisions involving vehicles with US licence plates and with 16–20-year-old US drivers in the Windsor region. Discussion These data seem
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Richardson, Paul G; Soiffer, Robert J; Antin, Joseph H; Uno, Hajime; Jin, Zhezhen; Kurtzberg, Joanne; Martin, Paul L; Steinbach, Gideon; Murray, Karen F; Vogelsang, Georgia B; Chen, Allen R; Krishnan, Amrita; Kernan, Nancy A; Avigan, David E; Spitzer, Thomas R; Shulman, Howard M; Di Salvo, Donald N; Revta, Carolyn; Warren, Diane; Momtaz, Parisa; Bradwin, Gary; Wei, L J; Iacobelli, Massimo; McDonald, George B; Guinan, Eva C
2010-07-01
Therapeutic options for severe hepatic veno-occlusive disease (VOD) are limited and outcomes are dismal, but early phase I/II studies have suggested promising activity and acceptable toxicity using the novel polydisperse oligonucleotide defibrotide. This randomized phase II dose-finding trial determined the efficacy of defibrotide in patients with severe VOD following hematopoietic stem cell transplantation (HSCT) and identified an appropriate dose for future trials. Adult and pediatric patients received either lower-dose (arm A: 25 mg/kg/day; n = 75) or higher-dose (arm B: 40 mg/kg/day; n = 74) i.v. defibrotide administered in divided doses every 6 hours for > or =14 days or until complete response, VOD progression, or any unacceptable toxicity occurred. Overall complete response and day +100 post-HSCT survival rates were 46% and 42%, respectively, with no significant difference between treatment arms. The incidence of treatment-related adverse events was low (8% overall; 7% in arm A, 10% in arm B); there was no significant difference in the overall rate of adverse events between treatment arms. Early stabilization or decreased bilirubin was associated with better response and day +100 survival, and decreased plasminogen activator inhibitor type 1 (PAI-1) during treatment was associated with better outcome; changes were similar in both treatment arms. Defibrotide 25 or 40 mg/kg/day also appears effective in treating severe VOD following HSCT. In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD.
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Richardson, Paul G.; Soiffer, Robert J.; Antin, Joseph H.; Uno, Hajime; Jin, Zhezhen; Kurtzberg, Joanne; Martin, Paul L.; Steinbach, Gideon; Murray, Karen F.; Vogelsang, Georgia B.; Chen, Allen R.; Krishnan, Amrita; Kernan, Nancy A.; Avigan, David E.; Spitzer, Thomas R.; Shulman, Howard M.; Di Salvo, Donald N.; Revta, Carolyn; Warren, Diane; Momtaz, Parisa; Bradwin, Gary; Wei, L. J.; Iacobelli, Massimo; McDonald, George B.; Guinan, Eva C.
2010-01-01
Therapeutic options for severe hepatic veno-occlusive disease (VOD) are limited and outcomes are dismal, but early phase I/II studies have suggested promising activity and acceptable toxicity using the novel polydisperse oligonucleotide defibrotide. This randomized phase II dose-finding trial determined the efficacy of defibrotide in patients with severe VOD following hematopoietic stem cell transplantation (HSCT) and identified an appropriate dose for future trials. Adult and pediatric patients received either lower-dose (arm A: 25 mg/kg/day; n = 75) or higher-dose (arm B: 40 mg/kg/day; n = 74) i.v. defibrotide administered in divided doses every 6 hours for ≥ 14 days or until complete response, VOD progression, or any unacceptable toxicity occurred. Overall complete response and day + 100 post-HSCT survival rates were 46% and 42%, respectively, with no significant difference between treatment arms. The incidence of treatment-related adverse events was low (8% overall; 7% in arm A, 10% in arm B); there was no significant difference in the overall rate of adverse events between treatment arms. Early stabilization or decreased bilirubin was associated with better response and day + 100 survival, and decreased plasminogen activator inhibitor type 1 (PAI-1) during treatment was associated with better outcome; changes were similar in both treatment arms. Defibrotide 25 or 40 mg/kg/day also appears effective in treating severe VOD following HSCT. In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD. PMID:20167278
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Gulzar, Z; Jana, S; Young, I; Bukberg, P; Yen, V; Naddaf, S; Abdel-Dayem, H M
2001-01-01
To determine whether a 5-mCi dose of 123I can be used as an effective radiotracer for assessing the presence of remnant thyroid tissue and for searching for metastatic lesions in patients with well-differentiated thyroid cancer as well as to attempt to ascertain whether a scan performed only at 4 hours is sufficient for accurate diagnosis and might replace the conventional protocol of scanning at both 4 hours and 24 hours. We prospectively studied 27 patients who had undergone near-total thyroidectomy and had a documented diagnosis of well-differentiated thyroid carcinoma. Patients underwent scanning after receiving a 5-mCi dose of 123I, at a time when they had discontinued thyroid replacement therapy and had a thyrotropin level in excess of 30 mIU/mL. Whole-body images at 4 hours and 24 hours were obtained and were compared with posttherapy scans obtained 5 to 7 days after administration of 131I. Scans were interpreted by two board-certified nuclear medicine physicians. Of the 27 patients, 2 (7.4%) showed discordance between the 123I scan performed at 24 hours and the posttherapy 131I scan. When 4-hour images after administration of 123I were compared with the posttherapy 131I scans, a discordance rate of 14.8% (4 of 27 patients) was noted. In addition, two of these four patients showed lesions on the 24-hour images that were not seen on the 4-hour images (one with new lung metastatic involvement and the other with a local recurrence in the lower neck area). The prognosis and treatment of these two patients were substantially changed by the result of the 24-hour images. On comparison of scans obtained after administration of a 5-mCi dose of 123I with those obtained after 131I therapy, we conclude that 5 mCi of 123I produces images that have excellent quality and resolution and also compare favorably with those obtained after 131I therapy. Furthermore, a decrease in the dose of 123I from 10 mCi to 5 mCi lowered the cost of the study without compromising the
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Choi, Peter; Farouk, Mourad; Manamley, Nick; Addison, Janet
2013-11-01
There is limited information published on switching erythropoiesis-stimulating agent (ESA) treatment for anemia associated with chronic kidney disease (CKD) from darbepoetin alfa (DA) to methoxy polyethylene glycol-epoetin beta (PEG-Epo) outside the protocol of interventional clinical studies. AFFIRM (Aranesp Efficiency Relative to Mircera) was a retrospective, multi-site, observational study designed to estimate the population mean maintenance dose conversion ratio [DCR; dose ratio achieving comparable hemoglobin level (Hb) between two evaluation periods] in European hemodialysis patients whose treatment was switched from DA to PEG-Epo. Eligible patients had received hemodialysis for ≥ 12 months and DA for ≥ 7 months. Data were collected from 7 months before until 7 months after switching treatment. DCR was calculated for patients with Hb and ESA data available in both evaluation periods (EP; Months 1 and 2 were defined as the pre-switch EP, and Months 6 and 7 as the post-switch EP). Red blood cell transfusions pre- and post-switch were quantified. Of 302 patients enrolled, 206 had data available for DCR analysis. The geometric mean DCR was 1.17 (95% CI 1.05, 1.29). Regression analysis indicated a non-linear relationship between pre- and post-switch ESA doses; DCR decreased with increasing pre-switch DA dose. The geometric mean weekly ESA doses were 24.1 μg DA in the pre-switch EP and 28.6 μg PEG-Epo in the post-switch EP. Mean Hb was 11.5 g/dL in the pre-switch EP and 11.4 g/dL in the post-switch EP. There were 16 transfusions and 34 units transfused in the pre-switch period, versus 48 transfusions and 95 units transfused post-switch. Excluding patients receiving a transfusion within 90 days of or during either EP, the DCR was 1.21 (95% CI 1.09, 1.35). In these hemodialysis patients switched from DA to PEG-Epo the DCR was 1.17 and 1.21 after accounting for the effect of transfusions. The number of transfusions and units transfused increased approximately
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Ali, Kishwar; Latif, Humera; Ahmad, Sajjad
2015-01-01
Antibiotics are used both pre and post-operatively in acute appendicitis for preventing wound infection. It has been observed that the routine use of post-operative antibiotics is not necessary in cases of non-perforated appendicitis as only prophylactic antibiotics are sufficient to prevent wound infection. The aim of this study was to see the frequency of wound infection in non-perforated appendicitis with single dose preoperative antibiotics only. This observational study was conducted at the Department of Surgery, Ayub Medical College, Abbottabad from May to November 2014. A total of 121 patients with non-perforated appendicitis were included in the study. Only single dose preoperative antibiotics were used. The patients were followed for wound infection till 8th post-operative day. 121 patients, 56 (46.28%) male and 65 (53.72%) female were included in the study. The mean age of patients was 27.41 +/- 7.12 years with an age range of 18 to 45 years. In the entire series, 7 (5.78%) patients developed wound infection. The infection was minor which settled with conservative therapy. Prophylactic antibiotics were found efficacious in 114 (94.21%) patients. There was no significant association between wound infection and age and gender. Single dose preoperative antibiotics were found effective in controlling post-operative wound infection without the need of extending the antibiotics to post-operative period in cases of non-perforated appendicitis.
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Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson’s disease: a dose-finding study
Rosenblad, Carl; af Edholm Arvidsson, Karolina; Wictorin, Klas; Keywood, Charlotte; Shankar, Bavani; Lowe, David A.; Björklund, Anders; Widner, Håkan
2015-01-01
In advanced stages of Parkinson’s disease, serotonergic terminals take up l-DOPA and convert it to dopamine. Abnormally released dopamine may participate in the development of l-DOPA-induced dyskinesias. Simultaneous activation of 5-HT1A and 5-HT1B receptors effectively blocks l-DOPA-induced dyskinesias in animal models of dopamine depletion, justifying a clinical study with eltoprazine, a 5-HT1A/B receptor agonist, against l-DOPA-induced dyskinesias in patients with Parkinson’s disease. A double-blind, randomized, placebo-controlled and dose-finding phase I/IIa study was conducted. Single oral treatment with placebo or eltoprazine, at 2.5, 5 and 7.5 mg, was tested in combination with a suprathreshold dose of l-DOPA (Sinemet®) in 22 patients with Parkinson’s disease (16 male/six female; 66.6 ± 8.8 years old) with l-DOPA-induced dyskinesias. A Wilcoxon Signed Ranked Test was used to compare each eltoprazine dose level to paired randomized placebo on the prespecified primary efficacy variables; area under the curve scores on Clinical Dyskinesia Rating Scale for 3 h post-dose and maximum change of Unified Parkinson’s Disease Rating Scale part III for 3 h post-dose. Secondary objectives included effects on maximum Clinical Dyskinesia Rating Scale score, area under the curve of Rush Dyskinesia Rating Scale score for 3 h post-dose, mood parameters measured by Hospital Anxiety Depression Scale and Montgomery Asberg Depression Rating Scale along with the pharmacokinetics, safety and tolerability profile of eltoprazine. A mixed model repeated measures was used for post hoc analyses of the area under the curve and peak Clinical Dyskinesia Rating Scale scores. It was found that serum concentrations of eltoprazine increased in a dose-proportional manner. Following levodopa challenge, 5 mg eltoprazine caused a significant reduction of l-DOPA-induced dyskinesias on area under the curves of Clinical Dyskinesia Rating Scale [–1.02(1.49); P = 0.004] and Rush Dyskinesia
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NASA Technical Reports Server (NTRS)
Nakanishi, S.
1976-01-01
A laboratory model 8-cm thruster with improvements to minimize ion chamber erosion and peeling of sputtered metal was subjected to a cyclic endurance test for 15,040 hours and 460 restarts. A charted history of several thruster operating variables and off-normal events are shown in 600-hour segments at three points in the test. The transient behavior of these variables during a typical start-stop cycle is presented. Performance and operating characteristics were nearly constant throughout the test except for a change in the accelerator back-streaming limit. Findings of the post-test inspection confirmed most of the expected results. Charge-exchange ions caused normal accelerator grid erosion. The workability of the various design features have been substantiated, and attainable improvements in propellant utilization efficiency should significantly reduce accelerator erosion.
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Making residency work hour rules work.
Cohen, I Glenn; Czeisler, Charles A; Landrigan, Christopher P
2013-01-01
In July 2011, the ACGME implemented new rules that limit interns to 16 hours of work in a row, but continue to allow 2nd-year and higher resident physicians to work for up to 28 consecutive hours. Whether the ACGME's 2011 work hour limits went too far or did not go far enough has been hotly debated. In this article, we do not seek to re-open the debate about whether these standards get matters exactly right. Instead, we wish to address the issue of effective enforcement. That is, now that new work hour limits have been established, and given that the ACGME has been unable to enforce work hour limits effectively on its own, what is the best way to make sure the new limits are followed in order to reduce harm to residents, patients, and others due to sleep-deprived residents? We focus on three possible national approaches to the problem, one rooted in funding, one rooted in disclosure, and one rooted in tort law. © 2013 American Society of Law, Medicine & Ethics, Inc.
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24-hour urinary aldosterone excretion test
Aldosterone - urine; Addison disease - urine aldosterone; Cirrhosis - serum aldosterone ... A 24-hour urine sample is needed. You will need to collect your urine over 24 hours . Your health care provider will tell ...
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2,445 Hours of Code: What I Learned from Facilitating Hour of Code Events in High School Libraries
ERIC Educational Resources Information Center
Colby, Jennifer
2015-01-01
This article describes a school librarian's experience with initiating an Hour of Code event for her school's student body. Hadi Partovi of Code.org conceived the Hour of Code "to get ten million students to try one hour of computer science" (Partovi, 2013a), which is implemented during Computer Science Education Week with a goal of…
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Respiratory Health Effects Associated with Restoration Work in Post-Hurricane Katrina New Orleans
Rando, Roy J.; Lefante, John J.; Freyder, Laurie M.; Jones, Robert N.
2012-01-01
Background. This study examines prevalence of respiratory conditions in New Orleans-area restoration workers after Hurricane Katrina. Methods. Between 2007 and 2010, spirometry and respiratory health and occupational questionnaire were administered to 791 New Orleans-area adults who mostly worked in the building construction and maintenance trades or custodial services. The associations between restoration work hours and lung function and prevalence of respiratory symptoms were examined by multiple linear regression, χ 2, or multiple logistic regression. Results. 74% of participants performed post-Katrina restoration work (median time: 620 hours). Symptoms reported include episodes of transient fever/cough (29%), sinus symptoms (48%), pneumonia (3.7%), and new onset asthma (4.5%). Prevalence rate ratios for post-Katrina sinus symptoms (PRR = 1.3; CI: 1.1, 1.7) and fever and cough (PRR = 1.7; CI: 1.3, 2.4) were significantly elevated overall for those who did restoration work and prevalence increased with restoration work hours. Prevalence rate ratios with restoration work were also elevated for new onset asthma (PRR = 2.2; CI: 0.8, 6.2) and pneumonia (PRR = 1.3; CI: 0.5, 3.2) but were not statistically significant. Overall, lung function was slightly depressed but was not significantly different between those with and without restoration work exposure. Conclusions. Post-Katrina restoration work is associated with moderate adverse effects on respiratory health, including sinusitis and toxic pneumonitis. PMID:23365586
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Probabilistic Analysis of Radiation Doses for Shore-Based Individuals in Operation Tomodachi
2013-05-01
Based Upon Oxygen Consumption Rates. EPA/600/R-06/129F, U.S. Environmental Protection Agency, Washington, D.C. May. USEPA (U.S. Environmental...pascal (Pa) pound-force per square inch (psi) 6.894 757 × 103 pascal (Pa) Angle/ Temperature /Time hour (h) 3.6 × 103 second (s) degree of arc (o...equivalent and effective dose is the sievert (Sv). (1 Sv = 1 J kg–1). 1 DTRA-TR-12-002: Probabilistic Analysis of Radiation Doses for Shore-Based
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Pietrzak, R H; Maruff, P; Snyder, P J
2009-03-01
Change in cognitive function in response to a pharmacologic challenge can be observed with greater sensitivity by employing cognitive tests with optimal psychometric properties and a statistical approach that more accurately accounts for individual variability in performance. To demonstrate this approach we examined the cognitive effects of a single acute dose administration of an acetylcholinesterase inhibitor, donepezil, in healthy older adults and in older adults with mild Alzheimer's disease (AD). Placebo-controlled crossover study with three separate testing days: baseline, placebo, and donepezil, with assessments at baseline, and 1-, 2-, 3-, 6-, and 8-hrs post-dosing on each day. Early phase I clinical trial. 15 healthy older adults; 14 older adults with mild Alzheimer's disease. Single acute dose of 5mg donepezil. Performance on the Groton Maze Learning Test (GMLT), a computerized neuropsychological measure of spatial working memory and error monitoring. A single acute dose of donepezil improved GMLT performance in healthy older adults (effect size: 0.83 at 6 hrs post-dosing) and older adults with mild AD (effect size: 0.58 at 3 hrs post-dosing). The GMLT detected cognitive improvement following a single, acute dose administration of donepezil in healthy older adults and older adults with mild AD. The choice of cognitive tests designed for repeated administration, as well as an analytic approach that emphasizes individual-level change in cognitive function, provides a sensitive approach to detecting central nervous system drug penetration and activity of cognitive-enhancing agents.
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Bastian, Jaime R; Chen, Huijun; Zhang, Hongfei; Rothenberger, Scott; Tarter, Ralph; English, Dennis; Venkataramanan, Raman; Caritis, Steve N
2017-01-01
Buprenorphine is a Food and Drug Administration-approved maintenance therapy for opioid use disorders and is increasingly being used in pregnant women with opioid use disorders as an alternative to methadone. Dosing of buprenorphine in pregnant women is based on the regimen recommended for nonpregnant females and males. Limited data are available defining the pharmacokinetic properties of sublingual buprenorphine administered during pregnancy. This study evaluated the impact of physiological changes associated with pregnancy on the pharmacokinetics of sublingual buprenorphine during and after pregnancy. Pregnant women (n = 13), between 18 0/7 and 37 6/7 weeks' singleton gestation, receiving sublingual buprenorphine twice daily for opioid use disorders were studied. Pharmacokinetic-2 studies were performed between 18 and 25 weeks (n = 7), pharmacokinetic-3 studies were performed between 31 and 37 weeks (n = 11), and pharmacokinetic-P was performed 4-18 weeks postpartum (n = 10). On the day of the study, blood was withdrawn prior to the daily morning dose of buprenorphine and at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, and 12 hours after the dose. Buprenorphine plasma concentrations were analyzed by liquid chromatography tandem mass spectrometric detection. All pharmacokinetic parameters were observed or estimated using Microsoft Excel. Statistical analyses were performed to identify significant changes in study participants' buprenorphine pharmacokinetic parameter estimates over the duration of the study. Univariate linear and generalized linear mixed models were used to investigate changes in these measures over time, some of which were log transformed for normality. Dose-normalized (plasma concentration per dose) buprenorphine plasma concentrations were significantly lower during pregnancy (pharmacokinetic-2 plus pharmacokinetic-3) than during the postpartum period (pharmacokinetic-P). Specific pharmacokinetic parameters (and level of significance) were as follows
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Raghubar, Kimberly P; Lamba, Michael; Cecil, Kim M; Yeates, Keith Owen; Mahone, E Mark; Limke, Christina; Grosshans, David; Beckwith, Travis J; Ris, M Douglas
2018-06-01
Advances in radiation treatment (RT), specifically volumetric planning with detailed dose and volumetric data for specific brain structures, have provided new opportunities to study neurobehavioral outcomes of RT in children treated for brain tumor. The present study examined the relationship between biophysical and physical dose metrics and neurocognitive ability, namely learning and memory, 2 years post-RT in pediatric brain tumor patients. The sample consisted of 26 pediatric patients with brain tumor, 14 of whom completed neuropsychological evaluations on average 24 months post-RT. Prescribed dose and dose-volume metrics for specific brain regions were calculated including physical metrics (i.e., mean dose and maximum dose) and biophysical metrics (i.e., integral biological effective dose and generalized equivalent uniform dose). We examined the associations between dose-volume metrics (whole brain, right and left hippocampus), and performance on measures of learning and memory (Children's Memory Scale). Biophysical dose metrics were highly correlated with the physical metric of mean dose but not with prescribed dose. Biophysical metrics and mean dose, but not prescribed dose, correlated with measures of learning and memory. These preliminary findings call into question the value of prescribed dose for characterizing treatment intensity; they also suggest that biophysical dose has only a limited advantage compared to physical dose when calculated for specific regions of the brain. We discuss the implications of the findings for evaluating and understanding the relation between RT and neurocognitive functioning. © 2018 Wiley Periodicals, Inc.
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Change from an 8-hour shift to a 12-hour shift, attitudes, sleep, sleepiness and performance.
Lowden, A; Kecklund, G; Axelsson, J; Akerstedt, T
1998-01-01
The present study sought to evaluate the effect of a change from a rotating 3-shift (8-hour) to a 2-shift shift (12 hour) schedule on sleep, sleepiness, performance, perceived health, and well-being. Thirty-two shift workers at a chemical plant (control room operators) responded to a questionnaire a few months before a change was made in their shift schedule and 10 months after the change. Fourteen workers also filled out a diary, carried activity loggers, and carried out reaction-time tests (beginning and end of shift). Fourteen day workers served as a reference group for the questionnaires and 9 were intensively studied during a week with workdays and a free weekend. The questionnaire data showed that the shift change increased satisfaction with workhours, sleep, and time for social activities. Health, perceived accident risk, and reaction-time performance were not negatively affected. Alertness improved and subjective recovery time after night work decreased. The quick changes in the 8-hour schedule greatly increased sleep problems and fatigue. Sleepiness integrated across the entire shift cycle showed that the shift workers were less alert than the day workers, across workdays and days off (although alertness increased with the 12-hour shift). The change from 8-hour to 12-hour shifts was positive in most respects, possibly due to the shorter sequences of the workdays, the longer sequences of consecutive days off, the fewer types of shifts (easier planning), and the elimination of quick changes. The results may differ in groups with a higher work load.
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6.6-hour inhalation of ozone concentrations from 60 to 87 parts per billion in healthy humans.
Schelegle, Edward S; Morales, Christopher A; Walby, William F; Marion, Susan; Allen, Roblee P
2009-08-01
Identification of the minimal ozone (O(3)) concentration and/or dose that induces measurable lung function decrements in humans is considered in the risk assessment leading to establishing an appropriate National Ambient Air Quality Standard for O(3) that protects public health. To identify and/or predict the minimal mean O(3) concentration that produces a decrement in FEV(1) and symptoms in healthy individuals completing 6.6-hour exposure protocols. Pulmonary function and subjective symptoms were measured in 31 healthy adults (18-25 yr, male and female, nonsmokers) who completed five 6.6-hour chamber exposures: filtered air and four variable hourly patterns with mean O(3) concentrations of 60, 70, 80, and 87 parts per billion (ppb). Compared with filtered air, statistically significant decrements in FEV(1) and increases in total subjective symptoms scores (P < 0.05) were measured after exposure to mean concentrations of 70, 80, and 87 ppb O(3). The mean percent change in FEV(1) (+/-standard error) at the end of each protocol was 0.80 +/- 0.90, -2.72 +/- 1.48, -5.34 +/- 1.42, -7.02 +/- 1.60, and -11.42 +/- 2.20% for exposure to filtered air and 60, 70, 80, and 87 ppb O(3), respectively. Inhalation of 70 ppb O(3) for 6.6 hours, a concentration below the current 8-hour National Ambient Air Quality Standard of 75 ppb, is sufficient to induce statistically significant decrements in FEV(1) in healthy young adults.
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The role of intercostal cryoanalgesia in post-thoracotomy analgesia
Sepsas, Evangelos; Misthos, Panagiotis; Anagnostopulu, Maria; Toparlaki, Olga; Voyagis, Gregorios; Kakaris, Stamatios
2013-01-01
OBJECTIVES Patients undergoing thoracotomy were studied to compare the effects of cryoanalgesia, combined with intravenous patient-controlled analgesia (IVPCA), against IVPCA alone during the four days following surgery. METHODS Fifty patients were randomized into two groups: an IVPCA group (n = 25) and an IVPCA-cryo group (n = 25). Subjective pain intensity was assessed on a verbal analogue scale at rest and during coughing. The intensity and the incidence of post-thoracotomy pain, numbness, epigastric distension and/or back pain, the analgesic requirements, as well as the blood gas values and respiratory function tests were evaluated up to the second postoperative (postop) month. Haemodynamic data and episodes of nausea and/or vomiting were recorded over the four postop days. RESULTS In the cryo group there was a statistically significant improvement in postop pain scores (P = 10–4), reduction in consumption of morphine (P = 10–4) and other analgesics (P = 10–4), optimization (less acidosis) of the pH values of blood gases (P < 0.015 over 72 hours postop and P < 0.03 on the first and second postop months), increase in systolic blood pressure (P < 0.05 over 96 hours postop), reduction in heart rate (P < 0.05 over 96 hours postop), increase in values of FEV1 (P < 0.02) and FVC (P < 0.05) at the first and second postop months, reduction in the incidence of nausea (0.05 < P < 0.1 over 18 hours postop), numbness, epigastric distension and back pain (P < 0.05 at days 5, 6, 7, 14, 30 and 60 following surgery). CONCLUSIONS We suggest that cryoanalgesia be considered as a simple, safe, inexpensive, long-term form of post-thoracotomy pain relief. Cryoanalgesia effectively restores FEV1 values at the second postop month. PMID:23424242