Long-term outcome of 56 dogs with nasal tumours treated with four doses of radiation at intervals of seven days.

PubMed

Mellanby, R J; Stevenson, R K; Herrtage, M E; White, R A S; Dobson, J M

2002-08-31

A retrospective study was undertaken on 56 dogs treated for nasal tumours by megavoltage radiotherapy with a hypofractionated schedule consisting of four doses of 9 Gy given at intervals of seven days. The dogs were followed until they died or were euthanased. The clinical signs had improved in 53 of the 56 dogs by the end of the treatment schedule. Mild acute radiation side effects were observed in the majority of the dogs but late radiation side effects were rare. Kaplan-Meier survival analysis revealed a median survival time after the final dose of radiation of 212 days. The one- and two-year survival rates were 45 per cent and 15 per cent. Fifty of the dogs were euthanased because the initial clinical signs recurred.

Cerebrovascular Diseases in Childhood Cancer Survivors: Role of the Radiation Dose to Willis Circle Arteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

El-Fayech, Chiraz; Haddy, Nadia; Allodji, Rodrigue Sètchéou

Background and Purpose: The aim of this study was to investigate the role of radiation dose received to the circle of Willis (WC) during radiation therapy (RT) and of potential dose-response modifiers on the risk of stroke after treatment of childhood cancer. Methods: We evaluated the risk factors for stroke in a cohort of 3172 5-year survivors of childhood cancer who were followed up for a median time of 26 years. Radiation doses to the WC and brain structures were estimated for each of the 2202 children who received RT. Results: Fifty-four patients experienced a confirmed stroke; 39 were ischemic. Patientsmore » not receiving RT had a stroke risk similar to that of the general population, whereas those who received RT had an 8.5-fold increased risk (95% confidence interval [CI]: 6.3-11.0). The excess of incidence of stroke increased yearly. The dose of radiation to the WC, rather than to other brain structures, was found to be the best predictor of stroke. The relative risk was 15.7 (95% CI: 4.9-50.2) for doses of 40 Gy or more. At 45 years of age, the cumulative stroke incidence was 11.3% (95% CI: 7.1%-17.7%) in patients who received 10 Gy or more to the WC, compared with 1% expected from general population data. Radiation doses received to the heart and neck also increased the risk. Surgery for childhood brain cancer was linked to hemorrhagic strokes in these patients. Conclusion: The WC should be considered as a major organ at risk during RT for childhood brain cancers. The incidence of radiation-induced ischemic stroke strongly increases with long-term follow-up.« less

Techno-commercial aspects of food irradiation in India

NASA Astrophysics Data System (ADS)

Sharma, Arun; Madhusoodanan, P.

2012-08-01

Research and development work has been carried out at Food Technology Division of Bhabha Atomic Research Center for more than past fifty years. After establishing potential commercial applications, a lot of time and efforts were spent on proving the wholesomeness and nutritional adequacy of irradiated foods. The first approval from health authorities came in 1994 for processing potato, onion and spices. Additional commodities were approved in 1998 and 2001, bringing the list of commodities to more than 20. Two technology demonstration plants were set up by the government, one for high dose applications like microbial decontamination of spices and dry vegetables in 2000, and another for low dose applications, like sprout inhibition and insect disinfestation, in 2003. In 2004, irradiation was approved as a quarantine measure. This enabled export of mango to USA after a gap of 18 years in 2007. More than a dozen plants have now been set up by private entrepreneurs in the country.

Influence of radiotherapy treatment concept on the outcome of patients with localized ependymomas.

PubMed

Combs, Stephanie E; Kelter, Verena; Welzel, Thomas; Behnisch, Wolfgang; Kulozik, Andreas E; Bischof, Marc; Hof, Holger; Debus, Jürgen; Schulz-Ertner, Daniela

2008-07-15

To assess the outcome of 57 patients with localized ependymomas treated with radiotherapy (RT). Fifty-seven patients with localized ependymomas were treated with RT. Histology was myxopapillary ependymoma (n = 4), ependymoma (n = 23), and anaplastic ependymoma (n = 30). In 16 patients, irradiation of the craniospinal axis (CSI) was performed with a median dose of 20 Gy. Forty-one patients were treated with local RT, with a local dose of 45 Gy to the posterior fossa, including a boost to the tumor bed of 9 Gy. In 19 patients, the tumor bed was irradiated with a median dose of 54 Gy. Overall survival after primary diagnosis was 83% and 71% at 3 and 5 years. Five-year overall survival was 80% in low-grade and 79% in high-grade tumors. Survival from RT was 79% at 3 and 64% at 5 years. We could not show a significant difference in overall survival between CSI and local RT only. Freedom of local failure was 67% at 5 years in patients treated with CSI and 60% at 5 years after local RT. A rate of 83% for distant failure-free survival could be observed in the CSI group as opposed to 93% in the group receiving local RT only. Local RT in patients with localized tumors is equieffective to CSI. The radiation oncologist must keep in mind that patients with localized ependymomas benefit from local doses > or =45 Gy.

Cerebellar medulloblastoma: the importance of posterior fossa dose to survival and patterns of failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silverman, C.L.; Simpson, J.R.

1982-11-01

Fifty patients with biopsy-proven cerebellar medulloblastoma were retrospectively analyzed for prognostic factors, survival and patterns of failure. Five- and ten-year actuarial survivals for the entire group were 51% and 42%. Survival and local control were significantly better for the 21 patients who received doses greater than 5000 rad to the posterior fossa (85% and 80% respectively) than for the remaining patients (38% and 38%, respectively). Significant prognostic factors included achievement of local control in the posterior fossa (p = .0001) and dose to the posterior fossa (p = .0005). Sex, age, duration of symptoms, extent of surgery and initial T-stagemore » of disease were not significant. Posterior fossa was the predominant site of failure (71% of failures), but 10% of patients failed in the cerebrum and 12% outside the CNS. This experience confirms that survival rates of 70-80% are achievable with current treatment policies but accurate and consistent dose delivery to the posterior fossa is essential.« less

Cerebellar medulloblastoma: the importance of posterior fossa dose to survival and patterns of failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silverman, C.L.; Simpson, J.R.

1982-11-01

Fifty patients with biopsy-proven cerebellar medulloblastoma were retrospectively analyzed for prognostic factors, survival and patterns of failure. Five- and ten-year actuarial survivals for the entire group were 51% and 42%. Survival and local control were significantly better for the 21 patients who received doses greater that 5000 rad to the posterior fossa (85% and 80% respectively) than for the remaining patients (38% and 38%, respectively). Significant prognostic factors included achievement of local control in the posterior fossa (p = .0001) and dose to the posterior fossa (p = .0005). Sex, age, duration of symptoms, extent of surgery and initial T-stagemore » of disease were not significant. Posterior fossa was the predominant site of failure (71% of failures), but 10% of patients failed in the cerebrum and 12% outside the CNS. This experience confirms that survival rates of 70-80% are achievable with current treatment policies but accurate and consistent dose delivery to the posterior fossa is essential.« less

Teriparatide versus low-dose bisphosphonates before and after surgery for adult spinal deformity in female Japanese patients with osteoporosis.

PubMed

Seki, Shoji; Hirano, Norikazu; Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Suzuki, Kayo; Watanabe, Kenta; Makino, Hiroto; Kanamori, Masahiko; Kimura, Tomoatsu

2017-08-01

Complications of adult spinal deformity surgery are problematic in osteoporotic individuals. We compared outcomes between Japanese patients treated perioperatively with teriparatide vs. low-dose bisphosphonates. Fifty-eight osteoporotic adult Japanese female patients were enrolled and assigned to perioperative teriparatide (33 patients) and bisphosphonate (25 patients) groups in non-blinded fashion. Pre- and post-operative X-ray and computed tomography imaging were used to assess outcome, and rates were compared between the groups and according to age. Pain scores and Oswestry Disability Indices (ODI) were calculated before and 2 years after surgery. Adjacent vertebral fractures and implant failure, fusion failure, and poor pain and ODI outcomes were significantly more common in the bisphosphonates group than the teriparatide group. Perioperative administration of teriparatide is more effective than that of low-dose bisphosphonates in preventing complications and maintaining fusion rates in osteoporotic Japanese females with spinal deformities undergoing surgery.

The role of concomitant methotrexate dosage and maintenance over time in the therapy of rheumatoid arthritis patients treated with adalimumab or etanercept: retrospective analysis of a local registry.

PubMed

Favalli, Ennio Giulio; Becciolini, Andrea; Biggioggero, Martina; Bertoldi, Ilaria; Crotti, Chiara; Raimondo, Maria Gabriella; Marchesoni, Antonio

2018-01-01

To evaluate the pattern of prescription and maintenance over time of concomitant methotrexate (MTX), and its impact on a 2-year clinical response in a cohort of rheumatoid arthritis (RA) patients treated with a first-line tumor necrosis factor alpha inhibitor (TNFi). The study population included all RA patients receiving adalimumab or etanercept a as first-line biologic drug, extracted from a local registry. Enrolled patients were stratified into 3 subgroups according to baseline concomitant MTX: no MTX, low-dose MTX (≤10 mg/wk), and high-dose MTX (≥12.5 mg/wk). The 2-year persistence of the initial MTX regimen was computed by the Kaplan-Meier method, and a Cox proportional hazard model was developed to examine potential predictors of MTX withdrawal/change of dosage. European League Against Rheumatism remission and good-to-moderate response were evaluated according to baseline MTX regimen and MTX maintenance over time. A total of 330 patients (163 treated with adalimumab and 167 with etanercept) were included; 141 were prescribed TNFi without MTX and 112 received low-dose and 77 high-dose concomitant MTX. Male sex, younger age, and shorter mean disease duration were predictors of high-dose MTX use. Among MTX users (76.2% parenteral and 23.8% oral), initial MTX dose persisted over time in 79.9% at 1 year and 70.2% at 2 years. Fifty-one patients (27%) underwent MTX dose de-escalation/discontinuation because of intolerance/adverse events. The 2-year EULAR remission rate was higher in the patients receiving and maintaining high-dose MTX than in those receiving low-dose or no MTX (46.2% vs 29.5% and 23.4%, respectively; p =0.009). The same was true for good-to-moderate response rate (71.2% vs 52.6% and 50.4%, respectively; p =0.031). In a real-life setting, about one-third of RA patients treated with TNFis experienced dose reduction/discontinuation of concomitant MTX because of intolerance/adverse events over a 2-year follow-up period. Initial high-dose MTX and its maintenance over time are associated with better 2-year clinical response.

Safety of Single-Dose Primaquine in G6PD-Deficient and G6PD-Normal Males in Mali Without Malaria: An Open-Label, Phase 1, Dose-Adjustment Trial.

PubMed

Chen, Ingrid; Diawara, Halimatou; Mahamar, Almahamoudou; Sanogo, Koualy; Keita, Sekouba; Kone, Daouda; Diarra, Kalifa; Djimde, Moussa; Keita, Mohamed; Brown, Joelle; Roh, Michelle E; Hwang, Jimee; Pett, Helmi; Murphy, Maxwell; Niemi, Mikko; Greenhouse, Bryan; Bousema, Teun; Gosling, Roly; Dicko, Alassane

2018-03-28

The World Health Organization recommendation on the use of a single low dose of primaquine (SLD-PQ) to reduce Plasmodium falciparum malaria transmission requires more safety data. We conducted an open-label, nonrandomized, dose-adjustment trial of the safety of 3 single doses of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient adult males in Mali, followed by an assessment of safety in G6PD-deficient boys aged 11-17 years and those aged 5-10 years, including G6PD-normal control groups. The primary outcome was the greatest within-person percentage drop in hemoglobin concentration within 10 days after treatment. Fifty-one participants were included in analysis. G6PD-deficient adult males received 0.40, 0.45, or 0.50 mg/kg of SLD-PQ. G6PD-deficient boys received 0.40 mg/kg of SLD-PQ. There was no evidence of symptomatic hemolysis, and adverse events considered related to study drug (n = 4) were mild. The mean largest within-person percentage change in hemoglobin level between days 0 and 10 was -9.7% (95% confidence interval [CI], -13.5% to -5.90%) in G6PD-deficient adults receiving 0.50 mg/kg of SLD-PQ, -11.5% (95% CI, -16.1% to -6.96%) in G6PD-deficient boys aged 11-17 years, and -9.61% (95% CI, -7.59% to -13.9%) in G6PD-deficient boys aged 5-10 years. The lowest hemoglobin concentration at any point during the study was 92 g/L. SLD-PQ doses between 0.40 and 0.50 mg/kg were well tolerated in G6PD-deficient males in Mali. NCT02535767.

Long-term sequelae of autologous bone marrow or peripheral stem cell transplantation for lymphoid malignancies.

PubMed

Vose, J M; Kennedy, B C; Bierman, P J; Kessinger, A; Armitage, J O

1992-02-01

The study was made to evaluate the long-term physical and psychosocial changes after high-dose therapy and autologous bone marrow or peripheral stem transplantation for recurrent lymphoid malignancies. Patients who had undergone high dose therapy and autologous bone marrow or peripheral stem cell transplantation for recurrent lymphoid malignancies at least 1 year previously were contacted by phone interview regarding their status after the transplant. The patients' comments were confirmed by checking medical records when possible. Fifty patients who had undergone transplantation at the University of Nebraska Medical Center at least 1 year before the interview were available for interview and willing to answer questions. After transplant, many patients noticed temporary changes in their appearance, which usually returned to normal within 1 year. Few patients reported remarkable cardiovascular, gastrointestinal, or pulmonary changes after transplantation. However, up to one-third of the patients reported changes in sexual function or desire. The most common infectious problem after transplant was Herpes zoster, which occurred in 25% of the patients. Overall, the patients had a positive outlook after high-dose therapy and transplantation, with most being able to return to work and enjoy a normal life style. Ninety-six percent of the patients stated that they would be willing to undergo high-dose therapy and transplantation again under the same circumstances.

High-dose octreotide acetate for management of gastroenteropancreatic neuroendocrine tumors.

PubMed

Chadha, Manpreet K; Lombardo, Jeffrey; Mashtare, Terry; Wilding, Gregory E; Litwin, Alan; Raczyk, Cheryl; Gibbs, John F; Kuvshinoff, Boris; Javle, Milind M; Iyer, Renuka V

2009-10-01

Long-acting sandostatin (S-LAR; octreotide acetate) is well tolerated and effective for symptom control and possibly disease control in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We undertook a retrospective analysis to study the efficacy and tolerability of higher doses (more than 20-30 mg/month) of S-LAR in GEP-NETs. With IRB approval, charts of all patients with GEP-NET who received S-LAR between June 2002 to September 2007 at Roswell Park Cancer Institute were reviewed and their data analyzed. Fifty-four patients with GEP-NET received S-LAR; thirty required dose escalation. Patients received a median of 5 doses of S-LAR at conventional dose followed by up-titration of the dose for symptom control (20) and radiological progression (17). Median high dose of S-LAR was 40 mg (range: 40-90 mg) with a median of 8.5 high doses received. No treatment related toxicities were seen. The estimated 1-year survival for patients on conventional dose alone was 0.77 (95% CI of 0.50 to 0.91) and those on high-dose was 0.88 (95% CI of 0.68 to 0.96) (p=0.4777) while median time to any other intervention was 2.9 months versus 17.7 months (p=0.12). Dose escalation of S-LAR is well tolerated and may provide longer disease control.

PET Studies of CX-157

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, Joanna; Furey, Michael

We completed measuring Brain MAO A activity in 15 subjects at baseline and after different doses of CX157 and also at different times after each dose. Fifty five scans were completed. We determined that plasma levels of the drug are a surrogate marker for the degree of MAO A inhibition in the brain.

A prospective randomized study of the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in hyperthyroidism.

PubMed

Pusuwan, Pawana; Tuntawiroon, Malulee; Sritongkul, Nopamol; Chaudakshetrin, Pachee; Nopmaneejumruslers, Cherdchai; Komoltri, Chulalak; Thepamongkhol, Kullathorn; Khiewvan, Benjapa; Tuchinda, Pongpija; Sriussadaporn, Sutin

2011-03-01

To compare the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in patients with hyperthyroidism. One hundred fifty patients with proven hyperthyroidism were randomly allocated into the high (74 patients) and low (76 patients) dose regimen of I-131 treatment. Four patients of the high dose group and one patient of the low dose group were excluded because of lost follow-up. A gland-specific dosage was calculated on the estimated weight of thyroid gland and 24-hour I-131 uptake. The high and low I-131 dose regimens were 150 microCi/gm and 100 microCi/gm, respectively. The first mean radioiodine activity administered to the high and low dose group was 10.2 and 8 mCi, respectively. Repeated treatment was given to 25 patients of the high dose group and 40 patients of the low dose group. Clinical outcome and calculated costs for outpatient attendances, and laboratory tests together with initial and subsequent treatments were evaluated for one year after I-131 treatment. Elimination of hyperthyroidism that resulted in either euthyroidism or hypothyroidism was classified as therapeutic success. The cost effectiveness was also compared. At 6 months after treatment, 45 (64.3%) patients receiving high dose and 59 (78.7%) patients receiving low dose were hyperthyroidism. Clinical outcome at one year showed persistence of hyperthyroidism in 21 (30%) patients of the high dose regimen and 36 (48%) patients of the low dose regimen. At one year post treatment, it was demonstrated that the high dose regimen could eliminate hyperthyroidism in a significantly shorter time than the low dose regimen, i.e., 259.6 days and 305.5 days, respectively, p = 0.008). For the persistent hyperthyroid patients, the average total cost of treatment in the low dose group was significantly higher than that of the high dose group, i.e., 13,422.78 baht and 10,942.79 baht, respectively; p = 0.050). A high dose regimen of radioactive iodine treatment is more effective than the low dose regimen. The successful outcome of a high dose regimen occurred significantly earlier than that of the low dose regimen. For the persistent hyperthyroid patients, the average total cost in the low dose group was significantly higher than that of the high dose group.

Increasing incidence of hypothyroidism within one year after radioiodine therapy for toxic diffuse goiter. [/sup 131/I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Von Hofe, S.E.; Dorfman, S.G.; Carrette, R.F.

1978-02-01

Patients treated with 10 mCi of I-131 for toxic diffuse goiter in the period January 1974--June 1976 were evaluated for development of hypothyroidism. Fifty percent were hypothyroid within 3 months and 69 percent within 1 year of treatment. Our data suggest that there is a higher incidence of hypothyroidism after standard doses of I-131 in the 1970s as contrasted with treatment groups in the 1950s and 1960s. The pathophysiology of this increased incidence is not known with certainty; however, infrequent use of thionamide medication, together with recent increases in dietary iodine, may render the gland more radiosensitive.

Clinical experience with intravenous Augmentin in the treatment of paediatric infections.

PubMed

Ploechl, E; Huber, E G

1986-01-01

The clinical efficacy of intravenous Augmentin (a formulation containing amoxycillin plus clavulanic acid) was investigated in an open study in fifty-eight children with a mean age of 6 years (range 1-15 years). The normal dosage was in the range 100-200 mg/kg/day Augmentin, administered parenterally by short i.v. infusion in 3 or 4 divided doses. Most patients were hospitalised for lower respiratory tract infections. Complete clinical cure or distinct clinical improvement was achieved in all assessable cases. Bacteriological success was obtained in 92% of the assessable cases. In two patients, mild, transient exanthema was noted after i.v. Augmentin was replaced by oral Augmentin. No additional therapeutic measures were required.

Phase II study of erlotinib in patients with advanced biliary cancer.

PubMed

Philip, Philip A; Mahoney, Michelle R; Allmer, Cristine; Thomas, James; Pitot, Henry C; Kim, George; Donehower, Ross C; Fitch, Tom; Picus, Joel; Erlichman, Charles

2006-07-01

Epidermal growth factor receptor/human epidermal growth factor receptor 1 and ligand expression is common in biliary cancers (BILI) and may be associated with worse outcome. The primary objective of this study was to determine the proportion of patients with advanced BILI who were progression-free at 6 months. Patients with either unresectable or metastatic disease were studied. Only one prior systemic or locoregional therapy was allowed. Erlotinib was administered continuously at a dose of 150 mg per day orally. Forty-two patients with BILI were enrolled. The median age was 67 years (range, 33 to 82 years). Fifty-two percent of patients had Eastern Cooperative Oncology Group performance status of 1. Fifty-seven percent of patients had received prior chemotherapy for advanced BILI. HER1/EGFR expression by immunohistochemistry in tumor cells was detected in 29 (81%) of the 36 assessable patients. Seven of the patients (17%; 95% CI, 7% to 31%) were progression free at 6 months. Three patients had partial response by Response Evaluation Criteria in Solid Tumors Group classification of duration 4, 4, and 14 months, respectively. All responding patients had mild (grade 1/2) skin rash and two patients had positive tumoral HER1/EGFR expression. Three patients (7%) had toxicity-related dose reductions of erlotinib due to grade 2/3 skin rash. Results suggest a therapeutic benefit for EGFR blockade with erlotinib in patients with biliary cancer. Additional studies with erlotinib as a single agent and in combination with other targeted agents are warranted in this disease.

Clinical relevance of deferasirox trough levels in β-thalassemia patients.

PubMed

Allegra, Sarah; Massano, Davide; De Francia, Silvia; Longo, Filomena; Piccione, Francesca; Pirro, Elisa; Cusato, Jessica; D'Avolio, Antonio; Piga, Antonio

2018-02-01

We evaluated the role of deferasirox therapeutic drug monitoring in order to avoid toxicity or treatment failure. Plasma concentrations, measured between two consecutive liver iron determinations, were determined at the end of dosing interval. Fifty-four β-thalassemic adult patients were enrolled: 50% were males; median age was 32.3 years (IQR 19.1-41.7 years) and median body mass index was 22.25 kg/m 2 (IQR 20.24-23.75 kg/m 2 ). The mean deferasirox dose was 28.6 ± 6.3 mg/kg/d and mean plasma concentration was 17.3 ± 16.8 μg/mL. Drug levels showed lower results in males. Deferasirox concentration was significantly correlated with serum creatinine levels (P = .01) and serum ferritin (P < .0001). The assessment of deferasirox therapeutic drug monitoring could help clinicians to predict patient responses and to optimize the therapy. © 2017 John Wiley & Sons Australia, Ltd.

Comparative assessment of efficacy of two different pretreatment single oral doses of betamethasone on inter-appointment and postoperative discomfort: An in vivo clinical evaluation.

PubMed

Gyanani, Hitesh; Chhabra, Naveen; Parmar, Ghanshyam R

2016-01-01

Study aimed to evaluate the efficacy of two different pretreatment single oral doses of betamethasone on the incidence of inter-appointment flare up and postoperative discomfort. Fifty-four patients aged 18-59 years requiring endodontic treatment were selected and randomly assigned to three groups; single pretreatment oral dose of placebo or betamethasone in two different oral doses of 0.5 mg and 1 mg, respectively. Endodontic therapy was completed in two visits using triple antibiotic paste as intracanal medicament. Patients were given a questionnaire to record their pain at 1, 2, 3, and 7 days after treatment. In the second visit, obturation was done, and the patients were again instructed to record their pain scores after treatment and discharged. The verbal rating scale was used for recording the pain scores. Statistical analysis was done using ANOVA and the Friedman test. 0.5 mg betamethasone group showed least mean pain scores among all experimental groups; however, there was no statistically significant difference between any of the groups ( P > 0.05). Pretreatment single oral dose of betamethasone is an effective in managing endodontic flare-ups; however, the results were statistically insignificant.

Radiotherapy in the treatment of multiple myeloma.

PubMed

Bosch, A; Frias, Z

1988-12-01

Fifty-nine patients with multiple myeloma referred for treatment of painful bony lesions received irradiation to 95 local areas, and 16 of the 59 were irradiated using hemibody techniques. Pain relief was obtained in practically all of the irradiated regions. Most local areas were treated to doses of 3000 cGy in 10 to 15 fractions. Patients with generalized pain due to multiple site involvement were treated with single dose hemibody irradiation, to doses of 600 cGy to the upper hemibody, and of 800 cGy to the lower hemibody. This treatment was well tolerated and side effects minimal. Median survival from diagnosis was 30 months and the survival at 1, 3, and 5 years was 80%, 42%, and 12% respectively. Key articles on radiation therapy of multiple myeloma are reviewed and discussed. Since all patients eventually relapse after chemotherapy, the role of radiotherapy using present techniques should be fully evaluated and considered as an alternative in the primary treatment of multiple myeloma.

Radiation Dose-rate Reduction Pattern in Well-differentiated Thyroid Cancer Treated with I-131.

PubMed

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.

Long-term antibody response and immunologic memory in children immunized with hepatitis B vaccine at birth.

PubMed

Saffar, M J; Rezai, M S

2004-12-01

Four hundred and fifty three healthy children immunized with a course of hepatitis B vaccine beginning at birth were tested at 10-11 years of age for persistence of anti-hepatitis B-S antigen antibody (anti-HBs); and responses of children without protective antibody to different doses of hepatitis B vaccine booster were evaluated. Although nearly 42% of them were not seroprotected, but most of boosted subjects (87.3%) retained robust immunologic memory and rapidly retained a protective anti-HBs antibody titer of at least 10 IU/L after booster vaccination.

Hundred joules plasma focus device as a potential pulsed source for in vitro cancer cell irradiation

NASA Astrophysics Data System (ADS)

Jain, J.; Moreno, J.; Andaur, R.; Armisen, R.; Morales, D.; Marcelain, K.; Avaria, G.; Bora, B.; Davis, S.; Pavez, C.; Soto, L.

2017-08-01

Plasma focus devices may arise as useful source to perform experiments aimed to study the effects of pulsed radiation on human cells in vitro. In the present work, a table top hundred joules plasma focus device, namely "PF-400J", was adapted to irradiate colorectal cancer cell line, DLD-1. For pulsed x-rays, the doses (energy absorbed per unit mass, measured in Gy) were measured using thermoluminescence detectors (TLD-100 dosimeters). The neutron fluence and the average energy were used to estimate the pulsed neutron doses. Fifty pulses of x-rays (0.12 Gy) and fifty pulses of neutrons (3.5 μGy) were used to irradiate the cancer cells. Irradiation-induced DNA damage and cell death were assessed at different time points after irradiation. Cell death was observed using pulsed neutron irradiation, at ultralow doses. Our results indicate that the PF-400J can be used for in vitro assessment of the effect of pulsed radiation in cancer cell research.

In Vivo Differentiation of Uric Acid Versus Non-Uric Acid Urinary Calculi With Third-Generation Dual-Source Dual-Energy CT at Reduced Radiation Dose.

PubMed

Franken, Axelle; Gevenois, Pierre Alain; Muylem, Alain Van; Howarth, Nigel; Keyzer, Caroline

2018-02-01

The objective of our study was to evaluate in vivo urinary calculus characterization with third-generation dual-source dual-energy CT (DECT) at reduced versus standard radiation dose. One hundred fifty-three patients requiring unenhanced CT for suspected or known urolithiasis were prospectively included in our study. They underwent two acquisitions at reduced-dose CT (90 kV and 50 mAs ref ; Sn150 kV and 31 mAs ref , where Sn denotes the interposition of a tin filter in the high-energy beam) and standard-dose CT (90 kV and 50 mAs ref ; Sn150 kV and 94 mAs ref ). One radiologist interpreted the reduced-dose examinations before the standard-dose examinations during the same session. Among 103 patients (23 women, 80 men; mean age ± SD, 50 ± 15 years; age range, 18-82 years) with urolithiasis, dedicated DECT software measured the maximal diameter and CT numbers, calculated the DECT number ratio, and labeled with a color code each calculus visualized by the radiologist as uric acid (UA) or non-UA. Volume CT dose index (CTDI vol ) and dose-length product (DLP) were recorded. The radiologist visualized 279 calculi on standard-dose CT and 262 on reduced-dose CT; 17 calculi were missed on reduced-dose CT, all of which were ≤ 3 mm. Among the 262 calculi visualized at both doses, the CT number ratio was obtained with the software for 227 calculi and was not different between the doses (p = 0.093). Among these 262 calculi, 197 were labeled at both doses; 194 of the 197 labeled calculi were labeled with the same color code. Among the 65 remaining calculi, 48 and 61 (all ≤ 5 mm) were not labeled at standard-dose and reduced-dose CT (p = 0.005), respectively. At reduced-dose CT, the mean CTDI vol was 2.67 mGy and the mean DLP was 102.2 mGy × cm. With third-generation dual-source DECT, a larger proportion of calculi ≤ 5 mm are not characterized as UA or non-UA at a reduced dose.

[Cefamandole as prophylactic A.B. in abdominal surgery. Comparative study of cefamandole versus clindamycin/tobramycin (author's transl)].

PubMed

Iarchy, J

1980-01-01

A prospective, randomized and controlled study of prophylactic A.B. was made in 100 patients prior to abdominal surgery. Fifty patients received 3 x 2 g of cefamandole I.V. within 24 hrs, the first dose being given at the time of anesthetic induction. Postoperative infections occurred in 2% of this group. Fifty patients received the association Clindamycin-Tobramycin (clindamycin 600 mg - tobramycin 80 mg/8 hrs) for 24 hrs, the first dose also at the induction of anesthesia. The complication rate in this group was 18%. The difference between those 2 groups is statistically significant (p less than 0.01). Cefamandole used as a prophylactic antibiotic in abdominal surgery reduces the incidence of postoperative wound infections when compared to the association clindamycin-tobramycin.

Thyroid Radiation Dose and Other Risk Factors of Thyroid Carcinoma Following Childhood Cancer.

PubMed

de Vathaire, Florent; Haddy, Nadia; Allodji, Rodrigue S; Hawkins, Mike; Guibout, Catherine; El-Fayech, Chiraz; Teinturier, Cécile; Oberlin, Odile; Pacquement, Hélène; Diop, Fara; Kalhouche, Amar; Benadjaoud, Mohamedamine; Winter, David; Jackson, Angela; Bezin Mai-Quynh, Giao; Benabdennebi, Aymen; Llanas, Damien; Veres, Cristina; Munzer, Martine; Nguyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Deutsch, Eric; Lefkopoulos, Dimitri; Schlumberger, Martin; Diallo, Ibrahima; Rubino, Carole

2015-11-01

Thyroid carcinoma is a frequent complication of childhood cancer radiotherapy. The dose response to thyroid radiation dose is now well established, but the potential modifier effect of other factors requires additional investigation. This study aimed to investigate the role of potential modifiers of the dose response. We followed a cohort of 4338 5-year survivors of solid childhood cancer treated before 1986 over an average of 27 years. The dose received by the thyroid gland and some other anatomical sites during radiotherapy was estimated after reconstruction of the actual conditions in which irradiation was delivered. Fifty-five patients developed thyroid carcinoma. The risk of thyroid carcinoma increased with a radiation dose to the thyroid of up to two tenths of Gy, then leveled off for higher doses. When taking into account the thyroid radiation dose, a surgical or radiological splenectomy (>20 Gy to the spleen) increased thyroid cancer risk (relative risk [RR] = 2.3; 95% confidence interval [CI], 1.3-4.0), high radiation doses (>5 Gy) to pituitary gland lowered this risk (RR = 0.2; 95% CI, 0.1-0.6). Patients who received nitrosourea chemotherapy had a 6.6-fold (95% CI, 2.5-15.7) higher risk than those who did not. The excess RR per Gy of radiation to the thyroid was 4.7 (95% CI, 1.7-22.6). It was 7.6 (95% CI, 1.6-33.3) if body mass index at time of interview was equal or higher than 25 kg/m(2), and 4.1 (95% CI, 0.9-17.7) if not (P for interaction = .1). Predicting thyroid cancer risk following childhood cancer radiation therapy probably requires the assessment of more than just the radiation dose to the thyroid. Chemotherapy, splenectomy, radiation dose to pituitary gland, and obesity also play a role.

Attenuation-based automatic kilovolt (kV)-selection in computed tomography of the chest: effects on radiation exposure and image quality.

PubMed

Eller, Achim; Wuest, Wolfgang; Scharf, Michael; Brand, Michael; Achenbach, Stephan; Uder, Michael; Lell, Michael M

2013-12-01

To evaluate an automated attenuation-based kV-selection in computed tomography of the chest in respect to radiation dose and image quality, compared to a standard 120 kV protocol. 104 patients were examined using a 128-slice scanner. Fifty examinations (58 ± 15 years, study group) were performed using the automated adaption of tube potential (100-140 kV), based on the attenuation profile of the scout scan, 54 examinations (62 ± 14 years, control group) with fixed 120 kV. Estimated CT dose index (CTDI) of the software-proposed setting was compared with a 120 kV protocol. After the scan CTDI volume (CTDIvol) and dose length product (DLP) were recorded. Image quality was assessed by region of interest (ROI) measurements, subjective image quality by two observers with a 4-point scale (3--excellent, 0--not diagnostic). The algorithm selected 100 kV in 78% and 120 kV in 22%. Overall CTDIvol reduction was 26.6% (34% in 100 kV) overall DLP reduction was 22.8% (32.1% in 100 kV) (all p<0.001). Subjective image quality was excellent in both groups. The attenuation based kV-selection algorithm enables relevant dose reduction (~27%) in chest-CT while keeping image quality parameters at high levels. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[Post-exposure antirabies vaccination. Early serological response to vaccine cultivated on VERO cells using a reduced 2-1-1 schedule].

PubMed

Colnot, F; Sureau, P; Alexandre, J L; Arnaudo, J P; Hesse, J Y; Jeanmaire, H

1994-11-12

An abbreviated 2-1-1 schedule for post-exposure rabies vaccination would theoretically lead to more rapid production of specific antibodies than the classical schedule. We measured early serological response to the 2-1-1 schedule. Patients consulting the antirabies centre of the Epinal hospital from June 1992 to June 1993 who had never been vaccinated and whose exposure history justified antirabies vaccination were included in this study. Fifty subjects were vaccinated with PVRV (purified vero rabies vaccine, Pasteur Institute) cultured on VERO (vervet monkey origin) cells using the abbreviated 2-1-1 schedule of 2 doses (0.5 ml = 2.5 IU/dose) on day 0 and 1 dose on days 7 and 21. Antirabies antibodies were assayed using the Platelia Rage immunoenzyme method (Diagnostic Pasteur) on day 21. Titres above 0.5 IU were considered to give protection and non-protected subjects were seen again on day 28 for a supplementary dose. Only 34 subjects (68%) had protective antibody titres on day 21, but by day 28, 48 (96%) had acquired immunity. In this study population, the age range was from 1 to 83 years and age over 30 years appeared to delay antibody formation. These findings emphasize the importance of initial antirabies immunoglobulins if short incubation in suspected and the need for serological follow-up if delayed antibody formation is suspected (subjects over 30).

Hormone replacement therapy may reduce the return of endogenous lead from bone to the circulation.

PubMed Central

Webber, C E; Chettle, D R; Bowins, R J; Beaumont, L F; Gordon, C L; Song, X; Blake, J M; McNutt, R H

1995-01-01

Hormone replacement therapy (HRT) in postmenopausal women suppresses the increase in bone resorption expected as circulating levels of endogenous estrogen decline. We tested the hypothesis that bone lead content might remain elevated in women on HRT. Fifty six women who at recruitment were on average 35 years postmenopausal were placed on calcium supplementation. Six months later 33 of these women were prescribed either low dose or moderate dose hormone replacement in addition to the calcium supplementation. After approximately 4 years of hormone replacement, lead content was measured at the tibia and calcaneus by in vivo fluorescence excitation, and lead concentrations were measured in serum, whole blood, and urine. Women not taking hormones had significantly lower lead concentrations in cortical bone compared to all women on HRT (p = 0.007). Tibia lead content (mean +/- SD) for women on calcium only was 11.13 +/- 6.22 microgram/g bone mineral. For women on HRT, tibia bone lead was 19.37 +/- 8.62 micrograms/g bone mineral on low-dose HRT and 16.87 +/- 11.68 micrograms/g bone mineral on moderate-dose HRT. There were no differences between groups for lead concentrations measured in trabecular bone, whole blood, serum or urine. Hormone replacement maintains cortical bone lead content. In women not on HRT, there will be a perimenopausal release of lead from bone. Images Figure 1. PMID:8747022

Correlation of biologically effective dose and the tumor control in Stage I (<5 cm) non-small cell lung cancer with stereotactic ablative radiotherapy: a single institutional cohort study.

PubMed

Jeon, Wan; Ahn, Sung-Ja; Kim, Young-Chul; Oh, In-Jae; Park, Chul-Kyu; Jeong, Jae-Uk; Yoon, Mee Sun; Song, Ju-Young; Nam, Taek-Keun; Chung, Woong-Ki

2018-02-01

Stereotactic ablative radiotherapy (SABR) is one of the newly developed innovative radiotherapy and of which optimal dose prescription needs to be standardized. We aimed to investigate the dose-response relationship for patients with SABR. Fifty-three patients with Stage I non-small cell lung cancer patients, who underwent SABR between November 2006 and January 2015, were evaluated retrospectively. Thirteen patients (24.5%), who refused the surgery were included and 40 patients (75.5%) were medically inoperable at diagnosis. The median age was 74 years. The median SABR dose was 50 Gy in 3-8 fractions and the median biologically effective dose (BED;α/β = 10) was 105.6 Gy (range: 60-160.53 Gy). The median follow-up was 37.1 months. The 1 and 3 year local control rates were 91.7% and 85.1%. The 3 year overall and progression-free survival rate were 63.3% and 47.5%, respectively, and freedom from progression was 62.2%. Local control rate and 3-year overall survival according to tumor size was 100% and 79.4% in T1 tumors in a while 61.8% and 45% in T2a tumors. The 3-year local and regional control by BED10 was 79.4% and 69.4% in ≤100 Gy vs. 89.1% and 100% in >100 Gy (P = 0.526, 0.004). Dyspnea more than Grade 3 was reported in six (11.3%) patients and Grade 1 chest pain was shown in five (9.4%) patients. The excellent regional control was conferred with a prescription of more than BED10 of 100 Gy, which also might be needed to achieve better local tumor control in T2a patients with tolerable lung function. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Development and Prospective Federal State-Wide Evaluation of a Device for Height-Based Dose Recommendations in Prehospital Pediatric Emergencies: A Simple Tool to Prevent Most Severe Drug Errors.

PubMed

Kaufmann, Jost; Roth, Bernhard; Engelhardt, Thomas; Lechleuthner, Alex; Laschat, Michael; Hadamitzky, Christoph; Wappler, Frank; Hellmich, Martin

2018-01-01

Drug dosing errors pose a particular threat to children in prehospital emergency care. With the Pediatric emergency ruler (PaedER), we developed a simple height-based dose recommendation system and evaluated its effectiveness in a pre-post interventional trial as the Ethics Committee disapproved randomization due to the expected positive effect of the PaedER on outcome. Pre-interventional data were retrospectively retrieved from the electronic records and medical protocols of the Cologne Emergency Medical Service over a two-year period prior to the introduction of the PaedER. Post-interventional data were collected prospectively over a six-year period in a federal state-wide open trial. The administered doses of either intravenous or intraosseous fentanyl, midazolam, ketamine or epinephrine were recorded. Primary outcome measure was the number and severity of drug dose deviation from recommended dose (DRD) based on the patient's weight. Fifty-nine pre-interventional and 91 post-interventional prehospital drug administrations in children were analyzed. The rate of DRD > 300% overall medications were 22.0% in the pre- and 2.2% in the post-interventional group (p < 0.001). All administrations of epinephrine occurred excessive (DRD > 300%) in pre-interventional and none in post-interventional patients (p < 0.001). The use of the PaedER resulted in a 90% reduction of medication errors (95% CI: 57% to 98%; p < 0.001) and prevented all potentially life-threatening errors associated with epinephrine administration. There is an urgent need to increase the safety of emergency drug dosing in children during emergencies. A simple height-based system can support health care providers and helps to avoid life-threatening medication errors.

Clinical Outcomes and Prognostic Factors of High-Dose Proton Beam Therapy for Peripheral Stage I Non-Small-Cell Lung Cancer.

PubMed

Hatayama, Yoshiomi; Nakamura, Tatsuya; Suzuki, Motohisa; Azami, Yusuke; Ono, Takashi; Yabuuchi, Tomonori; Hayashi, Yuichiro; Kimura, Kanako; Hirose, Katsumi; Wada, Hitoshi; Hareyama, Masato; Kikuchi, Yasuhiro; Takai, Yoshihiro

2016-09-01

The efficacy, toxicity, and prognostic factors of high-dose proton beam therapy (PBT) for peripheral stage I non-small-cell lung cancer were assessed in this retrospective study. Fifty patients with peripheral stage I non-small-cell lung cancer, two of whom had heterochronic multiple lung cancers, underwent high-dose PBT between January 2009 and September 2014. The relative biological effectiveness of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned for the 90% isodose volume of the prescribed dosage to encompass the planning target volume. The cumulative survival curves were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events, version 4. The study included 35 males and 15 females with a median age of 72.5 years. The median follow-up period was 22.8 months. The clinical stage was IA in 44 (85%) and IB in eight (15%) tumors. The total dose of PBT was 66 GyE in 10 fractions in all tumors. Three-year overall survival rate among all patients was 87.9% (95% confidence interval [CI], 94.8%-73.2%). Forty-five patients were alive, and 5 were dead. Three-year local control and progression-free survival rates were 95.7% (95% CI, 98.9%-83.8%) and 76.3% (95% CI, 86.9%-59.3%), respectively. Only one patient experienced Grade 2 pneumonitis. High-dose PBT may be an effective and safe treatment option for patients with stage I non-small-cell lung cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Research and Operational Support for the Study of Militarily Relevant Infectious Diseases of Interest to the United States and Royal Thai Government

DTIC Science & Technology

2005-01-01

vaccine ( Varicella vaccine for dose 1 and Hemophilius B vaccine for dose 2). Fifty-one healthy male and female, flavivirus naive infants were enrolled...Bangkok, Thailand. 11th International Conference of Infectious Disease. Cancun, Mexico . 4-8 March 2004. 80. Zhang C, Klungthong C, Monkongdee P, Mammen MP

Reirradiation for second primary or recurrent cancers of the head and neck: Dosimetric and outcome analysis.

PubMed

Garg, Shivank; Kilburn, Jeremy M; Lucas, John T; Randolph, David; Urbanic, James J; Hinson, William H; Kearns, William T; Porosnicu, Mercedes; Greven, Kathryn

2016-04-01

The purpose of this study was to examine outcomes, toxicity, and dosimetric characteristics of patients treated with reirradiation for head and neck cancers. Fifty patients underwent ≥2 courses of radiation therapy (RT) postoperatively or definitively with or without chemotherapy. Composite dose volume histograms (DVHs) for selected anatomic structures were correlated with grade ≥3 late toxicity. Median initial and retreatment radiation dose was 64 and 60 Gy, respectively. Median overall survival (OS), progression-free survival (PFS), and 1-year PFS rates were 18 months, 11 months, and 45%, respectively, with 13 months median follow-up. Thirty-four percent of patients experienced grade ≥3 late toxicity with 1 death from carotid blowout. The DVH corresponding to the carotid blowout fell above the third quartile compared with other patients. Our analysis is the first to systematically evaluate the dose to the carotid artery using composite dosimetry in head and neck reirradiation patients, and demonstrates a promising technique for evaluating the dose to other normal tissue structures. © 2015 Wiley Periodicals, Inc. Head Neck 38: E961-E969, 2016. © 2015 Wiley Periodicals, Inc.

Comparative assessment of efficacy of two different pretreatment single oral doses of betamethasone on inter-appointment and postoperative discomfort: An in vivo clinical evaluation

PubMed Central

Gyanani, Hitesh; Chhabra, Naveen; Parmar, Ghanshyam R.

2016-01-01

Aim: Study aimed to evaluate the efficacy of two different pretreatment single oral doses of betamethasone on the incidence of inter-appointment flare up and postoperative discomfort. Materials and Methods: Fifty-four patients aged 18–59 years requiring endodontic treatment were selected and randomly assigned to three groups; single pretreatment oral dose of placebo or betamethasone in two different oral doses of 0.5 mg and 1 mg, respectively. Endodontic therapy was completed in two visits using triple antibiotic paste as intracanal medicament. Patients were given a questionnaire to record their pain at 1, 2, 3, and 7 days after treatment. In the second visit, obturation was done, and the patients were again instructed to record their pain scores after treatment and discharged. The verbal rating scale was used for recording the pain scores. Statistical analysis was done using ANOVA and the Friedman test. Results: 0.5 mg betamethasone group showed least mean pain scores among all experimental groups; however, there was no statistically significant difference between any of the groups (P > 0.05). Conclusion: Pretreatment single oral dose of betamethasone is an effective in managing endodontic flare-ups; however, the results were statistically insignificant. PMID:27994320

Flares in Biopsy-Proven Giant Cell Arteritis in Northern Italy

PubMed Central

Restuccia, Giovanna; Boiardi, Luigi; Cavazza, Alberto; Catanoso, Mariagrazia; Macchioni, Pierluigi; Muratore, Francesco; Cimino, Luca; Aldigeri, Raffaella; Crescentini, Filippo; Pipitone, Nicolò; Salvarani, Carlo

2016-01-01

Abstract This study evaluated the frequency, timing, and characteristics of flares in a large cohort of Italian patients with biopsy-proven giant cell arteritis (GCA) and to identify factors at diagnosis able to predict the occurrence of flares. We evaluated 157 patients with biopsy-proven transmural GCA diagnosed and followed at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for whom sufficient information was available from the time of diagnosis until at least 4 years of follow-up. Fifty-seven patients (36.5%) experienced ≥1 flares. Fifty-one (46.4%) of the 110 total flares (88 relapses and 22 recurrences) were experienced during the first 2 years after diagnosis. The majority of relapses occurred with doses of prednisone ≤ 10 mg/day (82.9%), whereas only 3.4% of relapses occurred for doses ≥ 25 mg/day. Polymyalgia rheumatica (46.5%) and cranial symptoms (41.9%) were the most frequent manifestations at the time of the first relapse. Cumulative prednisone dose during the first year and total cumulative prednisone dose were significantly higher in flaring patients compared with those without flares (7.8 ± 2.4 vs 6.7 ± 2.4 g, P = 0.02; 15.5 ± 8.9 vs 10.0 ± 9.2 g, P = 0.0001, respectively). The total duration of prednisone treatment was longer in flaring patients (58 ± 44 vs 30 ± 30 months, P = 0.0001). Patients with disease flares had at diagnosis more frequently systemic manifestations (P = 0.02) and fever ≥ 38°C (P = 0.02), significantly lower hemoglobin levels (P = 0.05), more frequent presence at temporal artery biopsy (TAB) specimens of giant cells (P = 0.04) and intraluminal acute thrombosis (P = 0.007), and more moderate/severe arterial inflammation (P = 0.009) compared with those without flares. In the multivariate model fever ≥ 38 °C (hazard ratio 2.14; 95% confidence interval, 1.06–4.32, P = 0.03) and the severity of inflammatory infiltrate (moderate/severe versus mild) (hazard ratio 5.41; 95% confidence interval, 1.64–17.87, P = 0.006) were significantly associated with an increased risk of flares. In conclusion, a flaring course is common in GCA and it is associated with prolonged GC requirements. Fever at diagnosis and severity of inflammation at TAB appear to predict the development of disease flares. PMID:27175649

One-Year Outcomes following Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in Japanese Patients: The APOLLO Study.

PubMed

Oshima, Yuji; Kimoto, Kenichi; Yoshida, Noriko; Fujisawa, Kimihiko; Sonoda, Shozo; Kubota, Toshiaki; Murata, Toshinori; Sakamoto, Taiji; Yoshida, Shigeo; Sonoda, Koh-Hei; Ishibashi, Tatsuro

2017-01-01

To evaluate 1-year outcomes of intravitreal injections of aflibercept (IVA) in Japanese polypoidal choroidal vasculopathy (PCV) patients. In this prospective, open-label, single-arm multicenter clinical trial, treatment-naïve PCV patients received IVA (2.0 mg) every 2 months, after 3 initial monthly doses. The primary endpoint assessed was the proportion of patients maintaining baseline best-corrected visual acuity (BCVA) at 1 year. Fifty eyes with PCV were included in the study. BCVA was maintained or improved in 97.6% of the patients. Mean logMAR BCVA at baseline was 0.33, and had improved to 0.12 logMAR 1 year after the initiation of aflibercept treatment (p < 0.001). Mean central foveal thickness decreased from 356 to 239 μm (p < 0.001). Complete regression of polypoidal lesions was seen in 72.5% after 1 year of treatment. One year of IVA resulted in stabilization of BCVA and anatomical improvement in Japanese PCV patients. © 2017 S. Karger AG, Basel.

Comparison of monovalent and trivalent live attenuated influenza vaccines in young children.

PubMed

Gruber, W C; Kirschner, K; Tollefson, S; Thompson, J; Reed, G; Edwards, K M; Wright, P F

1993-07-01

Fifty children, 6 months to 2 years of age, were vaccinated intranasally with a trivalent preparation containing 10(6) TCID50 each of H1N1 and H3N2 and 10(4) (n = 14) or 10(6) (n = 36) TCID50 of B live, attenuated, cold-adapted (ca) influenza strains. The same doses were administered as monovalent vaccines to 69 comparably aged children. Forty-five controls were given placebo. No clinically significant adverse reactions to vaccines were observed. Of children seronegative to H1N1 or H3N2, > or = 90% were infected by these vaccine strains. Trivalent vaccine containing 10(4) TCID50 of B infected only 27% of children seronegative to B (3/11), which was markedly reduced from the 88% infection rate (7/8) following monovalent B vaccine of the same dose (P = .02); increasing the B dose to 10(6) TCID50 increased the infection rate to 81% (21/26). Replication of ca influenza viruses in tissue culture matched vaccine responses. Trivalent ca influenza vaccines can be formulated that are safe and immunogenic in young children.

The hypertension of autonomic failure and its treatment

NASA Technical Reports Server (NTRS)

Shannon, J.; Jordan, J.; Costa, F.; Robertson, R. M.; Biaggioni, I.

1997-01-01

We studied the incidence and severity of supine hypertension in 117 patients with severe primary autonomic failure presenting to a referral center over a 9-year period. Patients were uniformly characterized by disabling orthostatic hypotension, lack of compensatory heart rate increase, abnormal autonomic function tests, and unresponsive plasma norepinephrine. Fifty-four patients had isolated autonomic impairment (pure autonomic failure). Sixty-three patients had central nervous system involvement in addition to autonomic impairment (multiple-system atrophy). Patients were studied off medications, in a metabolic ward, and on a controlled diet containing 150 mEq of sodium. Fifty-six percent of patients had supine diastolic blood pressure > or =90 mm Hg. The prevalence of hypertension was slightly greater in females (63%) than in males (52%). Potential mechanisms responsible for this hypertension were investigated. No correlation was found between blood volume and blood pressure. Similarly, plasma norepinephrine (92+/-15 pg/mL) and plasma renin activity (0.3+/-0.05 ng/mL per hour) were very low in the subset of patients with pure autonomic failure and supine hypertension (mean systolic/diastolic pressure, 177 +/- 6/108 +/- 2 mm Hg, range 167/97 to 219/121). Supine hypertension represents a challenge in the treatment of orthostatic hypotension. We found these patients to be particularly responsive to the hypotensive effects of transdermal nitroglycerin. Doses ranging from 0.025 to 0.1 mg/h decreased systolic blood pressure by 36+/-7 mm Hg and may effectively treat supine hypertension overnight, but the dose should be individualized and used with caution.

Assessment of the epidemiology and burden of measles in Southern Mozambique.

PubMed

Mandomando, Inácio; Naniche, Denise; Pasetti, Marcela F; Cuberos, Lilian; Sanz, Sergi; Vallès, Xavier; Sigauque, Betuel; Macete, Eusébio; Nhalungo, Delino; Kotloff, Karen L; Levine, Myron M; Alonso, Pedro L

2011-07-01

Measles has been a major killer among vaccine-preventable diseases in children < 5 years of age in developing countries. Despite progress in global efforts to reduce mortality, measles remains a public health problem. Hospital-based measles surveillance was conducted in Manhica, Mozambique (July 2001-September 2004). Suspected cases and community-based controls were enrolled, and blood was collected for immunoglobulin M (IgM) confirmation. Two hundred fifty-three suspected cases and 477 controls were enrolled, with 85% (216 of 253) cases reported during a measles outbreak. Measles-IgM confirmation was 30% among suspected cases and 5% in controls. Fifty-eight percent (14 of 24) of laboratory-confirmed cases had records indicating previous measles vaccination. Mortality was 3% (8 of 246) among cases and 1% among controls (6 of 426). Forty-five percent (33 of 74) of cases were < 24 months of age and 22% occurred in infants < 9 months of age and were associated with a high case-fatality rate (25%). Our data suggest that improved diagnostics, new tools to protect infants < 9 months of age, and a supplemental dose of measles vaccine could assist measles control.

Intrathecal treatment in cancer patients unresponsive to multiple trials of systemic opioids.

PubMed

Mercadante, Sebastiano; Intravaia, Giuseppe; Villari, Patrizia; Ferrera, Patrizia; Riina, Salvatore; David, Fabrizio; Mangione, Salvatore

2007-01-01

The aim of this study was to evaluate the clinical response to a combination of intrathecal morphine and levobupivacaine in advanced cancer patients who were highly opioid-tolerant, being previously treated with multiple opioid trials unsuccessfully. Initial intrathecal morphine dose was calculated from the previous opioid consumption using a morphine oral-intrathecal ratio of 100:1. Then, doses of both drugs were modified during the treatment according to the clinical needs and balanced with adverse effects. Fifty-five patients were assessed during admission, before starting the intrathecal treatment, during the titration phase, and followed up to death, by frequent phone contacts or visits, as available. Pain and symptom intensities were recorded before starting the intrathecal treatment (T0), at time of hospital discharge (T dis), and then at 1 month (T1), 3 months (T3), 6 months (T6) intervals, and the last observation, at least 1 week before death (T death). Fifty-five patients were selected for starting an intrathecal treatment. Thirty-two patients were males. The mean age was 60 years (95% CI 57-63), and 65.4% of patients were under 65 years. The most frequent indication was the presence of adverse effects and poor pain control. Complete data with adequate follow-up until death were available in 45 patients. Statistical differences in pain intensity were found at the different time intervals examined until death. Statistical decreases in the intensity of drowsiness and confusion were found until 1 month after starting intrathecal therapy. Statistical differences were found in daily intrathecal morphine doses, with a 3-fold increase at time of hospital discharge. Subsequently, further increases in doses were not significant. Conversely, systemic opioids, expressed as oral morphine equivalents, significantly decreased at all the intervals examined until death. Early complications included mild bleeding in 2 patients, without consequences, headache in 4 patients, bladder catheterization in 6 patients, reoperation for bleeding or changes of catheter position in 4 patients, unrelated death in 1 patient, and stroke in another 1. Late complications included local infection in 2 patients, and discontinuation of intrathecal therapy due to spinal compression. In patients who had received multiple trial of opioids and routes of administration, the intrathecal treatment started with an oral-intrathecal morphine conversion ratio of 100:1, and local anesthetics at the most convenient clinical doses provided a long-term improvement of analgesia, with a decrease in adverse effects and opioid consumption until death.

Initial Dosing and Taper Complexity of Methadone and Morphine for Treatment of Neonatal Abstinence Syndrome

PubMed Central

Ibach, Bethany W.; Johnson, Peter N.; Ernst, Kimberly D.; Harrison, Donald; Miller, Jamie L.

2016-01-01

Background: Methadone and morphine are commonly used to treat neonatal abstinence syndrome (NAS). Limited data exist to describe the most appropriate initial doses and taper regimens of these agents. Objectives: Describe the median initial dose and frequency of methadone and morphine for NAS. Compare dose adjustments, time to symptom relief, and taper complexity between groups. Methods: Retrospective study of neonates receiving enteral methadone or morphine for NAS over a 4-year period. Data collection included medication regimen, abstinence scores based on the Modified Finnegan Neonatal Abstinence Scoring Tool, and adverse events. Planned home taper complexity was assessed using the Medication Taper Complexity Score–Revised (MTCS-R). The primary outcome was initial opioid dose. Secondary outcomes included number of dose adjustments, time to symptom relief, and MTCS-R score. Results: Fifty neonates were initially treated for NAS with methadone (n = 36) or morphine (n = 14). The median initial dose was 0.09 mg/kg (range = 0.03-0.2) for methadone and 0.04 mg/kg (range = 0.03-0.4) for morphine. The most common initial dosing interval was q8h for methadone versus q3h for morphine. Number of dose adjustments and time to symptom relief were similar between groups. Median MTCS-R scores were similar between groups. There was no difference in adverse events between groups. Limitations included small sample size, preference toward methadone use, and variability of initial opioid dosing and titration. Conclusions: There was significant variability in initial doses of both agents. Neonates receiving methadone required less frequent dosing than morphine, which may result in easier administration and may allow for safer outpatient administration.

A brief history of inhaled asthma therapy over the last fifty years.

PubMed

Crompton, Graham

2006-12-01

This year is the 50th anniversary of the introduction into clinical use of the first modern inhaler for the management of asthma--the pressurised metered-dose inhaler (pMDI). The pMDI was initially used for the administration of the non-selective beta-agonists adrenaline and isoprenaline. However, the epidemic of asthma deaths which occurred in the 1960s led to these drugs being superseded by the selective short-acting beta-agonist salbutamol, and the first inhaled corticosteroid (ICS) beclomethasone. At the same time, sodium cromoglycate was introduced, to be administered via the first dry-powder inhaler--the Spinhaler--but owing to its relatively weak anti-inflammatory action its use is now very limited. Over the last 10 years, the long-acting beta-agonists (LABAs) have become an important add-on therapy for the management of asthma, and they are now often used with ICS in a single ICS/LABA combination inhaler.

Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia

PubMed Central

Liebman, Howard A.; Saleh, Mansoor N.; Bussel, James B.; Negrea, O. George; Horne, Heather; Wegener, William A.; Goldenberg, David M.

2016-01-01

We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×109/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues. Forty-seven response-evaluable patients had 23 (49%) objective responses (platelet counts ≥30×109/L and ≥2 × baseline) including 15 (32%) complete responses (platelets ≥100×109/L). Responses (including complete responses) and bleeding reduction occurred in all dose groups and were not dose-dependent. In contrast, response duration increased progressively with total dose, reaching a median of 2.7 years with the four once-weekly 320-mg doses. Among nine responders retreated at relapse, three at higher dose levels responded again, including one patient who was retreated four times. In all dose groups, B-cell depletion occurred after the first dose until recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with dose group according to total dose administered, but terminal half-life and clearance were comparable. Human anti-veltuzumab antibody titers developed without apparent dose dependence in nine patients, of whom six responded including five who had complete responses. Subcutaneous veltuzumab was convenient, well-tolerated, and active, without causing significant safety concerns. Platelet responses and bleeding reduction occurred in all dose groups, and response durability appeared to improve with higher doses. Clinicaltrials.gov identifier: NCT00547066 PMID:27515248

Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the treatment of tinea versicolor: a randomized clinical trial.

PubMed

Wahab, M A; Ali, M E; Rahman, M H; Chowdhury, S A; Monamie, N S; Sultana, N; Khondoker, L

2010-01-01

Tinea (pityriasis) versicolor is a superficial fungal infection and one of the most commonly found pigmentary disorders of skin caused by the yeast Malassezia. Multiple topical as well as systemic therapies are available for treatment. Systemic therapies are used for extensive disease, frequent relapse or where topical agents have failed. The aim that translates the rationale of the study was to compare the efficacy, safety, tolerability and cost effectiveness of single dose 400mg versus 7 day 200 mg daily dose of itraconazole in the treatment of tinea versicolor. A clinical study was done to compare the efficacy of single dose (400 mg) of itraconazole and 7 day 200 mg daily dose of itraconazole in the treatment of extensive tinea versicolor. Total 60 patients (aged 18-50 years) were selected for the study during the period of June 2007 to May 2008 in the department of Dermatology of three different hospitals in Bangladesh. Cases having with extensive involvement, diagnosed clinically and confirmed by wood's lamp and KOH microscopy were taken. Patients were randomly allocated into equal groups. Group A was given single dose 400 mg itraconazole and Group B was given 7 day 200 mg daily itraconazole. Fifty three (88%) male and 7(12%) female were included in the study. The mean age of group A was 32.37+/-9 years and in group B 33.23+/-8 years. The mean duration of the disease in group A was 2.63+/-2 months and 2.76+/-2 months in group B. In group A clinical responders was found cure 22(73.33%) and improvement 5(16.33%) and in group B it was found cure 24(79.99%) and improvement 4(13.33%). The measure at the End point (EP1) equals to 90% response and in-group B it was found cure 24 (79.99%) and improvement 4(13.33%). (Here the End point EP2) equals to 93.33%. The EP clinical analysis however shows 91.66% response. Both single dose and 7 day daily dose of itraconazole can be effective in the treatment of tinea versicolor with extensive involvement but single dose appears to be better for improving compliance and decreasing the cost of treatment.

Radiation-Induced Cranial Nerve Palsy: A Cross-Sectional Study of Nasopharyngeal Cancer Patients After Definitive Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong, Lin, E-mail: konglinj@gmail.co; Lu, Jiade J.; Department of Radiation Oncology, National University Cancer Institute of Singapore

2011-04-01

Purpose: To address the characteristics and the causative factors of radiation-induced cranial nerve palsy (CNP) in nasopharyngeal carcinoma (NPC) patients with an extensive period of followed-up. Patients and Methods: A total of 317 consecutive and nonselected patients treated with definitive external-beam radiotherapy between November 1962 and February 1995 participated in this study. The median doses to the nasopharynx and upper neck were 71 Gy (range, 55-86 Gy) and 61 Gy (range, 34-72 Gy), respectively. Conventional fractionation was used in 287 patients (90.5%). Forty-five patients (14.2%) received chemotherapy. Results: The median follow-up was 11.4 years (range, 5.1-38.0 years). Ninety-eight patients (30.9%)more » developed CNP, with a median latent period of 7.6 years (range, 0.3-34 years). Patients had a higher rate of CNP (81 cases, 25.5%) in lower-group cranial nerves compared with upper group (44 cases, 13.9%) ({chi}{sup 2} = 34.444, p < 0.001). Fifty-nine cases experienced CNP in more than one cranial nerve. Twenty-two of 27 cases (68.8%) of intragroup CNP and 11 of 32 cases (40.7%) of intergroup CNP occurred synchronously ({chi}{sup 2} = 4.661, p = 0.031). The cumulative incidences of CNP were 10.4%, 22.4%, 35.5%, and 44.5% at 5, 10, 15, and 20 years, respectively. Multivariate analyses revealed that CNP at diagnosis, chemotherapy, total radiation dose to the nasopharynx, and upper neck fibrosis were independent risk factors for developing radiation-induced CNP. Conclusion: Radiation-induced fibrosis may play an important role in radiation-induced CNP. The incidence of CNP after definitive radiotherapy for NPC remains high after long-term follow-up and is dose and fractionation dependent.« less

Long-term subcutaneous pulsatile low dose LH-RH administration for treatment of infertile men with secondary hypogonadotrophic hypogonadism.

PubMed

Skarin, G; Nillius, S J; Wide, L

1984-01-01

Chronic pulsatile subcutaneous low dose LH-RH treatment was given to three infertile men with longstanding (2-4 years) secondary hypothalamic pituitary failure. Before the therapy they had very low serum concentrations of gonadotrophins and testosterone. They were impotent and could not produce any ejaculate for sperm analysis. The pulsatile LH-RH treatment, which was continued up to 250 days, was given by means of a small portable automatically-timed infusion pump. Fifty microliter of the LH-RH solution was infused during one min every 90 min. The LH-RH doses were 1, 5 and 20 micrograms. The serum concentrations of the gonadotrophins and testosterone were normalized in the three patients within 10 days of pulsatile low dose LH-RH therapy. Libido and potency returned. The first ejaculates contained no sperms. With continued LH-RH treatment spermatogenesis was induced and normalized. Two of the men fertilized their wives. The pregnancy tests were positive after 181 and 230 days of treatment, respectively. Two healthy girls have been born. Paternity tests were positive. The third man is still receiving pulsatile LH-RH therapy. He has up till now been treated for four months. Chronic pulsatile s.c. low dose LH-RH administration is a very promising new therapy for those hypogonadal men who previously have required human gonadotrophin treatment to restore fertility.

[Results of a multidisciplinary and intensified treatment program for type 1 Diabetes Mellitus in a Chilean Public Hospital].

PubMed

Codner, Ethel; Mericq, Verónica; García, Hernán; López, Claudia; Cáceres, Jeannette; Gaete, Ximena; Avila, Alejandra

2003-08-01

During the last decade, the importance of glycemic control in the prevention of the microvascular complications of type 1 Diabetes Mellitus (DM1) was clearly demonstrated. To evaluate the metabolic and anthropometric results of a multidisciplinary intensified treatment program of DMI in children and adolescents. Report of 54 patients treated during 2001. The intensified treatment consisted of: multiple daily doses of insulin, frequent glycemic control, nutritional, psychological and educational support, and permanent availability of a diabetes nurse for telephonic support. Thirty one patients were female, their mean age was 10.4 +/- 0.5 years old and 52% were experiencing puberty. Fifty three percent of the patients used 3 insulin doses per day, 95% changed rapid insulin dose based on glucose levels and 18% considered carbohydrates in their rapid insulin dosing. Mean glycosilated hemoglobin was 8.18 +/- 0.23% without differences by sex or pubertal status. Sex, pubertal stage and the number of insulin doses did not contribute to glycosilated hemoglobin changes. There were no differences in weight or BMI, but there was a decrease in height Z score from the admission to the program until the last control (0.1 +/- 0.1 vs--0.3 +/- 0.1 DS; p < 0.01). A modified intensified modality of DM1 therapy for pediatric patients in a public hospital in Chile is feasible, achieving similar metabolic control, compared to international large centers.

High-Dose Ursodeoxycholic Acid Is Associated With the Development of Colorectal Neoplasia in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

PubMed Central

Eaton, John E.; Silveira, Marina G.; Pardi, Darrell S.; Sinakos, Emmanouil; Kowdley, Kris V.; Luketic, Velimir A.C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Lindor, Keith D.

2011-01-01

OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28–30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30–20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC. PMID:21556038

False-Positive Tuberculin Skin Test Results Among Low-Risk Healthcare Workers Following Implementation of Fifty-Dose Vials of Purified Protein Derivative.

PubMed

Collins, Jeffrey M; Hunter, Mary; Gordon, Wanda; Kempker, Russell R; Blumberg, Henry M; Ray, Susan M

2018-06-01

Following large declines in tuberculosis transmission the United States, large-scale screening programs targeting low-risk healthcare workers are increasingly a source of false-positive results. We report a large cluster of presumed false-positive tuberculin skin test results in healthcare workers following a change to 50-dose vials of Tubersol tuberculin.Infect Control Hosp Epidemiol 2018;39:750-752.

High dose chemoradiation for unresectable hilar cholangiocarcinomas using intensity modulated external beam radiotherapy: a single tertiary care centre experience

PubMed Central

Mehta, Shaesta; Kalyani, Nikhil; Chaudhari, Suresh; Dharia, Tejas; Shetty, Nitin; Chopra, Supriya; Goel, Mahesh; Kulkarni, Suyash; Shrivastava, Shyam Kishore

2017-01-01

Background We present results of patients diagnosed with unresectable hilar cholangiocarcinomas treated with high dose radiotherapy and concurrent chemotherapy. Methods From Aug 2005 to Dec 2012, 68 consecutive patients were treated. Fifty patients (group 1) presenting to us with obstructive jaundice were planned for endobiliary brachytherapy (EBBT 14 Gy) followed external beam radiotherapy (EBRT 45 Gy). Twenty-two patients (group 2) who had previously undergone biliary drainage underwent EBRT (57 Gy). All patients received injection Gemcitabine 300 mg/m2/weekly along with EBRT. Results Twenty-nine patients in group 1 and 22 patients in group 2 completed the treatment. Twenty-six (55%) patients achieved complete radiological response, 16 (64%) belonging to group 1 and 8 (44%) of group 2 (P=0.05). The median overall survival (MOS) was 17.5 and 16 months for group 1 and 2 respectively (P=0.07). The 1- and 2-year survival was 63%, and 18% for group I and 61% and 22% for group II respectively. The MOS was 5 months and 1 year survival was 14% for patients receiving EBBT only. MOS was significantly better after complete response (P=0.001). Conclusions Intensity modulated radiotherapy (IMRT) modulated high dose radiotherapy used either alone or with brachytherapy demonstrates potential to prolonged overall survival in unresectable hilar cholangiocarcinomas. PMID:28280622

Long-term safety and efficacy of stereotactic radiosurgery for vestibular schwannomas: evaluation of 440 patients more than 10 years after treatment with Gamma Knife surgery.

PubMed

Hasegawa, Toshinori; Kida, Yoshihisa; Kato, Takenori; Iizuka, Hiroshi; Kuramitsu, Shunichiro; Yamamoto, Takashi

2013-03-01

Object Little is known about long-term outcomes, including tumor control and adverse radiation effects, in patients harboring vestibular schwannomas (VSs) treated with stereotactic radiosurgery > 10 years previously. The aim of this study was to confirm whether Gamma Knife surgery (GKS) for VSs continues to be safe and effective > 10 years after treatment. Methods A total of 440 patients with VS (including neurofibromatosis Type 2) treated with GKS between May 1991 and December 2000 were evaluable. Of these, 347 patients (79%) underwent GKS as an initial treatment and 93 (21%) had undergone prior resection. Three hundred fifty-eight patients (81%) had a solid tumor and 82 (19%) had a cystic tumor. The median tumor volume was 2.8 cm(3) and the median marginal dose was 12.8 Gy. Results The median follow-up period was 12.5 years. The actuarial 5- and ≥ 10-year progression-free survival was 93% and 92%, respectively. No patient developed treatment failure > 10 years after treatment. According to multivariate analysis, significant factors related to worse progression-free survival included brainstem compression with a deviation of the fourth ventricle (p < 0.0001), marginal dose ≤ 13 Gy (p = 0.01), prior treatment (p = 0.02), and female sex (p = 0.02). Of 287 patients treated at a recent optimum dose of ≤ 13 Gy, 3 (1%) developed facial palsy, including 2 with transient palsy and 1 with persistent palsy after a second GKS, and 3 (1%) developed facial numbness, including 2 with transient and 1 with persistent facial numbness. The actuarial 10-year facial nerve preservation rate was 97% in the high marginal dose group (> 13 Gy) and 100% in the low marginal dose group (≤ 13 Gy). Ten patients (2.3%) developed delayed cyst formation. One patient alone developed malignant transformation, indicating an incidence of 0.3%. Conclusions In this study GKS was a safe and effective treatment for the majority of patients followed > 10 years after treatment. Special attention should be paid to cyst formation and malignant transformation as late adverse radiation effects, although they appeared to be rare. However, it is necessary to collect further long-term follow-up data before making conclusions about the long-term safety and efficacy of GKS, especially for young patients with VSs.

Rationale and design of the Children's Oncology Group (COG) study ALTE1621: a randomized, placebo-controlled trial to determine if low-dose carvedilol can prevent anthracycline-related left ventricular remodeling in childhood cancer survivors at high risk for developing heart failure.

PubMed

Armenian, Saro H; Hudson, Melissa M; Chen, Ming Hui; Colan, Steven D; Lindenfeld, Lanie; Mills, George; Siyahian, Aida; Gelehrter, Sarah; Dang, Ha; Hein, Wendy; Green, Daniel M; Robison, Leslie L; Wong, F Lennie; Douglas, Pamela S; Bhatia, Smita

2016-10-04

Anthracyclines are widely used in the treatment of childhood cancer. One of the well-recognized side-effects of anthracycline therapy is dose-dependent cardiomyopathy that may progress to heart failure (HF) years after completion of cancer-directed therapy. This study will evaluate the efficacy of low-dose beta-blocker (carvedilol) for HF risk reduction in childhood cancer survivors at highest risk for HF. The proposed intervention has the potential to significantly reduce chronic cardiac injury via interruption of neurohormonal systems responsible for left ventricular (LV) remodeling, resulting in improved cardiac function and decreased risk of HF. The intervention is informed by previous studies demonstrating efficacy in pediatric and adult non-oncology populations, yet remains unstudied in the pediatric oncology population. The primary objective of the trial is to determine impact of the intervention on echocardiographic markers of cardiac remodeling and HF risk, including: LV wall thickness/ dimension ratio (LVWT/D; primary endpoint), as well as LV ejection fraction, volume, and blood biomarkers (natriuretic peptides, galectin-3) associated with HF risk. Secondary objectives are to establish safety and tolerability of the 2-year course of carvedilol using: 1) objective measures: hepatic and cardiovascular toxicity, treatment adherence, and 2) subjective measures: participant self-reported outcomes. Two hundred and fifty survivors of childhood cancer (diagnosed <21 years of age), and previously treated with high-dose (≥300 mg/m 2 ) anthracyclines will be enrolled in a randomized, double-blind, placebo controlled trial. After baseline assessments, participants will be randomized in a 1:1 ratio to low-dose carvedilol (maximum dose: 12.5 mg/day) or placebo. Carvedilol or placebo is up-titrated (starting dose: 3.125 mg/day) according to tolerability. When completed, this study will provide much-needed information regarding a physiologically plausible pharmacological risk-reduction strategy for childhood cancer survivors at high risk for developing anthracycline-related HF. ClinicalTrials.gov; NCT02717507.

Clinical and dosimetric factors of radiation-induced esophageal injury: radiation-induced esophageal toxicity.

PubMed

Qiao, Wen-Bo; Zhao, Yan-Hui; Zhao, Yan-Bin; Wang, Rui-Zhi

2005-05-07

To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during three-dimensional conformal radiotherapy (3D-CRT). We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria. Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus > or =60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, no grade 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P = 0.0001<0.01). Concurrent chemotherapy and the maximal esophageal point dose > or =60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT.

Preoperative Chemoradiotherapy for Rectal Cancer in Patients Aged 75 Years and Older: Acute Toxicity, Compliance with Treatment, and Early Results.

PubMed

Guimas, Valentine; Boustani, Jihane; Schipman, Benjamin; Lescut, Nicolas; Puyraveau, Marc; Bosset, Jean François; Servagi-Vernat, Stéphanie

2016-06-01

Treatment of locally advanced rectal cancer (T3-T4 or N+) is based on short-course radiotherapy (RT) or chemoradiotherapy (CRT) followed by surgery. It is estimated that 30-40 % of rectal cancer occurs in patients aged 75 years or more. Data on adherence to neoadjuvant CRT and its safety remain poor owing to the under-representation of older patients in randomized clinical trials and the discordance in the results from retrospective studies. The aim of this study was to assess adherence with preoperative CRT and tolerability in older patients with a stage II/III unresectable rectal cancer. Patients aged 75 years or more with stage II/III rectal cancer treated with preoperative CRT at the University Hospital of Besancon from 1993 to 2011 were included. Feasibility, toxicities, overall survival, and local recurrence rates were studied. Fifty-six patients with a Charlson score from 2 to 6 were included. The mean age was 78 years. The compliance rates for RT and chemotherapy were 91 and 41.1 %, respectively. Two patients stopped CRT; one for hemostatic surgery, and one for severe sepsis. For CRT, the rate of grade ≥3 toxicity was 14.29 %, mainly the digestive type. Fifty-two patients underwent tumor resection, including 76.79 % total mesorectal excision resection with 84.6 % complete resection, and a rate of postoperative complications of 39.6 %. At 2 years, the overall survival and local recurrences rates were 87.3 and 7.8 %, respectively. In older patients, selected preoperative CRT, with an adapted chemotherapy dose, is well tolerated. The main toxicity was gastrointestinal. Adherence to RT is comparable to that of younger patients.

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ben-Josef, Edgar, E-mail: edgar.ben-josef@uphs.upenn.edu; Schipper, Mathew; Francis, Isaac R.

2012-12-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of {>=}1500/mm{sup 3}, platelets {>=}100,000/mm{sup 3}, creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase {<=}2.5 Multiplication-Sign upper limit of normal. FDR-G (1000 mg/m{sup 2}/100 min intravenously) wasmore » given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) {>=}3, neutropenic fever, or deterioration in performance status to {>=}3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.« less

Beneficial effects of Korean red ginseng on lymphocyte DNA damage, antioxidant enzyme activity, and LDL oxidation in healthy participants: a randomized, double-blind, placebo-controlled trial.

PubMed

Kim, Ji Young; Park, Ju Yeon; Kang, Hee Jung; Kim, Oh Yoen; Lee, Jong Ho

2012-07-17

The reported health benefits of Korean red ginseng (KRG) include antioxidant, antitumor, antimutagenic, and immunomodulatory activities; however, the effects on oxidative stress have not yet been evaluated. Therefore, we assessed the effect of KRG on antioxidant enzymes and oxidative stress markers in humans. We conducted a randomized, double-blind, placebo-controlled study with three groups, including placebo, low-dose (3 g/day), and high-dose (6 g/day), which were randomly assigned to healthy subjects aged 20-65 years. Lymphocyte DNA damage, antioxidative enzyme activity, and lipid peroxidation were assessed before and after the 8-week supplementation. Fifty-seven subjects completed the protocol. Plasma superoxide dismutase (SOD) activity after the 8-week KRG supplementation was significantly higher in the low-and high-dose groups compared to baseline. Plasma glutathione peroxidase (GPx) and catalase activities were also increased after the high-dose supplementation. Furthermore, the DNA tail length and tail moment were significantly reduced after the supplementation (low-dose and high-dose), and plasma oxidized low-density lipoprotein (LDL) levels were reduced in low-dose and high-dose groups, but increased in the placebo group. The net changes in oxidized LDL after the supplementation differed significantly between both KRG supplementation groups and the placebo group. Net changes in GPx, SOD and catalase activities, and DNA tail length and tail moment were significantly different between the high-dose group and the placebo group. Additionally, the net changes in urinary 8-epi-PGF(2α) were significantly different between the KRG supplementation groups and the placebo group. KRG supplementation may attenuate lymphocyte DNA damage and LDL oxidation by upregulating antioxidant enzyme activity.

Beneficial effects of Korean red ginseng on lymphocyte DNA damage, antioxidant enzyme activity, and LDL oxidation in healthy participants: a randomized, double-blind, placebo-controlled trial

PubMed Central

2012-01-01

Background The reported health benefits of Korean red ginseng (KRG) include antioxidant, antitumor, antimutagenic, and immunomodulatory activities; however, the effects on oxidative stress have not yet been evaluated. Therefore, we assessed the effect of KRG on antioxidant enzymes and oxidative stress markers in humans. Methods We conducted a randomized, double-blind, placebo-controlled study with three groups, including placebo, low-dose (3 g/day), and high-dose (6 g/day), which were randomly assigned to healthy subjects aged 20–65 years. Lymphocyte DNA damage, antioxidative enzyme activity, and lipid peroxidation were assessed before and after the 8-week supplementation. Results Fifty-seven subjects completed the protocol. Plasma superoxide dismutase (SOD) activity after the 8-week KRG supplementation was significantly higher in the low-and high-dose groups compared to baseline. Plasma glutathione peroxidase (GPx) and catalase activities were also increased after the high-dose supplementation. Furthermore, the DNA tail length and tail moment were significantly reduced after the supplementation (low-dose and high-dose), and plasma oxidized low-density lipoprotein (LDL) levels were reduced in low-dose and high-dose groups, but increased in the placebo group. The net changes in oxidized LDL after the supplementation differed significantly between both KRG supplementation groups and the placebo group. Net changes in GPx, SOD and catalase activities, and DNA tail length and tail moment were significantly different between the high-dose group and the placebo group. Additionally, the net changes in urinary 8-epi-PGF2α were significantly different between the KRG supplementation groups and the placebo group. Conclusions KRG supplementation may attenuate lymphocyte DNA damage and LDL oxidation by upregulating antioxidant enzyme activity. PMID:22805313

Association of Low-Dose Aspirin and Survival of Women With Endometrial Cancer.

PubMed

Matsuo, Koji; Cahoon, Sigita S; Yoshihara, Kosuke; Shida, Masako; Kakuda, Mamoru; Adachi, Sosuke; Moeini, Aida; Machida, Hiroko; Garcia-Sayre, Jocelyn; Ueda, Yutaka; Enomoto, Takayuki; Mikami, Mikio; Roman, Lynda D; Sood, Anil K

2016-07-01

To examine the survival outcomes in women with endometrial cancer who were taking low-dose aspirin (81-100 mg/d). A multicenter retrospective study was conducted examining patients with stage I-IV endometrial cancer who underwent hysterectomy-based surgical staging between January 2000 and December 2013 (N=1,687). Patient demographics, medical comorbidities, medication types, tumor characteristics, and treatment patterns were correlated to survival outcomes. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio for disease-free and disease-specific overall survival. One hundred fifty-eight patients (9.4%, 95% confidence interval [CI] 8.8-11.9) were taking low-dose aspirin. Median follow-up time for the study cohort was 31.5 months. One hundred twenty-seven patients (7.5%) died of endometrial cancer. Low-dose aspirin use was significantly correlated with concurrent obesity, hypertension, diabetes mellitus, and hypercholesterolemia (all P<.001). Low-dose aspirin users were more likely to take other antihypertensive, antiglycemic, and anticholesterol agents (all P<.05). Low-dose aspirin use was not associated with histologic subtype, tumor grade, nodal metastasis, or cancer stage (all P>.05). On multivariable analysis, low-dose aspirin use remained an independent prognostic factor associated with an improved 5-year disease-free survival rate (90.6% compared with 80.9%, adjusted hazard ratio 0.46, 95% CI 0.25-0.86, P=.014) and disease-specific overall survival rate (96.4% compared with 87.3%, adjusted hazard ratio 0.23, 95% CI 0.08-0.64, P=.005). The increased survival effect noted with low-dose aspirin use was greatest in patients whose age was younger than 60 years (5-year disease-free survival rates, 93.9% compared with 84.0%, P=.013), body mass index was 30 or greater (92.2% compared with 81.4%, P=.027), who had type I cancer (96.5% compared with 88.6%, P=.029), and who received postoperative whole pelvic radiotherapy (88.2% compared with 61.5%, P=.014). These four factors remained significant for disease-specific overall survival (all P<.05). Our results suggest that low-dose aspirin use is associated with improved survival outcomes in women with endometrial cancer, especially in those who are young, obese, with low-grade disease, and who receive postoperative radiotherapy.

Current practice of antibiotic prophylaxis for surgical fixation of closed long bone fractures: a survey of 297 members of the Orthopaedic Trauma Association.

PubMed

Gans, Itai; Jain, Amit; Sirisreetreerux, Norachart; Haut, Elliott R; Hasenboehler, Erik A

2017-01-01

The risk of postoperative surgical site infection after long bone fracture fixation can be decreased with appropriate antibiotic use. However, there is no agreement on the superiority of a single- or multiple-dose perioperative regimen of antibiotic prophylaxis. The purpose of this study is to determine the following: 1) What are the current practice patterns of orthopaedic trauma surgeons in using perioperative antibiotics for closed long bone fractures? 2) What is the current knowledge of published antibiotic prophylaxis guidelines among orthopaedic trauma surgeons? 3) Are orthopaedic surgeons willing to change their current practices? A questionnaire was distributed via email between September and December 2015 to 955 Orthopaedic Trauma Association members, of whom 297 (31%) responded. Most surgeons (96%) use cefazolin as first-line infection prophylaxis. Fifty-nine percent used a multiple-dose antibiotic regimen, 39% used a single-dose regimen, and 2% varied this decision according to patient factors. Thirty-six percent said they were unfamiliar with Centers for Disease Control and Prevention (CDC) antibiotic prophylaxis guidelines; only 30% were able to select the correct CDC recommendation from a multiple-choice list. However, 44% of surgeons said they followed CDC recommendations. Fifty-six percent answered that a single-dose antibiotic prophylaxis regimen was not inferior to a multiple-dose regimen. If a level-I study comparing a single preoperative dose versus multiple perioperative antibiotic dosing regimen for treatment of closed long bone fractures were published, most respondents (64%) said they would fully follow these guidelines, and 22% said they would partially change their practice to follow these guidelines. There is heterogeneity in the use of single- versus multiple-dose antibiotic prophylaxis for surgical repair of closed long bone fractures. Many surgeons were unsure of current evidence-based recommendations regarding perioperative antibiotic use. Most respondents indicated they would be receptive to high-level evidence regarding the single- versus multiple-dose perioperative prophylactic antibiotics for the treatment of closed long bone fractures.

75 FR 3746 - Draft Program Comment for the Department of the Navy for the Disposition of Historic Vessels

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-22

... less than fifty years. Because naval vessels have a limited useful life, the Chief of Naval Operations undertakes a Ship Disposition Review (SDR) each year to determine whether any vessels should be... service for typically less than fifty years. Because naval vessels have a limited useful life, the Chief...

Tanzania Higher Education--Fifty Years after Independence

ERIC Educational Resources Information Center

Mnubi, Godfrey M.

2013-01-01

As Tanzania celebrates fifty years of independence at the crossroads of globalization, the country has experienced a changing landscape and a major transformation in higher learning education with spectacular expansion in student enrollment rates. This requires its higher education institutions, particularly universities, to function effectively…

Assessment of the Epidemiology and Burden of Measles in Southern Mozambique

PubMed Central

Mandomando, Inácio; Naniche, Denise; Pasetti, Marcela F.; Cuberos, Lilian; Sanz, Sergi; Vallès, Xavier; Sigauque, Betuel; Macete, Eusébio; Nhalungo, Delino; Kotloff, Karen L.; Levine, Myron M.; Alonso, Pedro L.

2011-01-01

Measles has been a major killer among vaccine-preventable diseases in children < 5 years of age in developing countries. Despite progress in global efforts to reduce mortality, measles remains a public health problem. Hospital-based measles surveillance was conducted in Manhica, Mozambique (July 2001–September 2004). Suspected cases and community-based controls were enrolled, and blood was collected for immunoglobulin M (IgM) confirmation. Two hundred fifty-three suspected cases and 477 controls were enrolled, with 85% (216 of 253) cases reported during a measles outbreak. Measles-IgM confirmation was 30% among suspected cases and 5% in controls. Fifty-eight percent (14 of 24) of laboratory-confirmed cases had records indicating previous measles vaccination. Mortality was 3% (8 of 246) among cases and 1% among controls (6 of 426). Forty-five percent (33 of 74) of cases were < 24 months of age and 22% occurred in infants < 9 months of age and were associated with a high case-fatality rate (25%). Our data suggest that improved diagnostics, new tools to protect infants < 9 months of age, and a supplemental dose of measles vaccine could assist measles control. PMID:21734140

Post-relapse survival in patients with Ewing sarcoma.

PubMed

Ferrari, Stefano; Luksch, Roberto; Hall, Kirsten Sundby; Fagioli, Franca; Prete, Arcangelo; Tamburini, Angela; Tienghi, Amelia; DiGirolamo, Stefania; Paioli, Anna; Abate, Massimo Eraldo; Podda, Marta; Cammelli, Silvia; Eriksson, Mikael; Brach del Prever, Adalberto

2015-06-01

Post-relapse survival (PRS) was evaluated in patients with Ewing sarcoma (EWS) enrolled in chemotherapy protocols based on the use of high-dose chemotherapy with busulfan and melfalan (HDT) as a first-line consolidation treatment in high-risk patients. EWS patients enrolled in ISG/SSG III and IV trials who relapsed after complete remission were included in the analysis. At recurrence, chemotherapy based on high-dose ifosfamide was foreseen, and patients who responded but had not received HDT underwent consolidation therapy with HDT. Data from 107 EWS patients were included in the analysis. Median time to recurrence (RFI) was 18 months, and 45 (42%) patients had multiple sites of recurrence. Patients who had previously been treated with HDT had a significantly (P = 0.02) shorter RFI and were less likely to achieve a second complete remission (CR2). CR2 status was achieved by 42 (39%) patients. Fifty patients received high-dose IFO (20 went to consolidation HDT). The 5-year PRS was 19% (95% CI 11 to 27%). With CR2, the 5-year PRS was 48% (95% CI 31 to 64%). Without CR2, median time to death was six months (range 1-45 months). According to the multivariate analysis, patients younger than 15 years, recurrence to the lung only, and RFI longer than 24 months significantly influenced the probability of PRS. Age, pattern of recurrence, RFI, and response to second-line chemotherapy influence post-relapse survival in patients with recurrent Ewing sarcoma. No survival advantage was observed from chemotherapy consolidation with HDT. © 2015 Wiley Periodicals, Inc.

A randomized controlled trial of conventional fraction and late course accelerated hyperfraction three-dimensional conformal radiotherapy for esophageal cancer.

PubMed

Wang, Jian-Hua; Lu, Xu-Jing; Zhou, Jian; Wang, Feng

2012-01-01

We compared the curative and side-effects in esophageal carcinoma treated by conventional fraction (CF) and late course accelerated hyperfraction (LCAF) three-dimensional conformal radiotherapy. Ninety-eight patients were randomly assigned to two different radiotherapy model groups. Fifty patients were treated using CF three-dimensional conformal radiotherapy at a total dose of 60-68 Gy; 2 Gy/F; 5 fractions/week (median 64 Gy), 48 patients were treated with LCAF (First CF-treated at the dose 40 Gy. Later, LCAF-treated 1.5 Gy/F; 2 fractions/day; 21-27 Gy; a total dose of 61-67 Gy; median 64 Gy). The data showed that the 1-, 2- and 3-year-survival rates in LCAF group were 79.2, 56.3, and 43.8%, compared to 74, 54, and 36% in CF group (P = 0.476). The 1-, 2- and 3-year-local control rates in LCAF group were 81.3, 62.5, and 50%, compared to 78, 58, and 42% in CF group (P = 0.454). In CF group, the incidence of radiation-induced esophagitis was lower than that in LCAF group (72 vs. 93.8%; P = 0.008) and there was no significant difference between rates of radiation-induced pneumonitis in CF and LCAF groups (10 vs. 6.25%; P = 0.498). It was concluded that the 1-, 2- and 3-year-local control and survival rates of esophageal carcinoma patients treated with LCAF were slightly better than CF radiotherapy; however, the radiation side-effects in LCAF group were greater than those in CF group.

Final report of the 70.2-Gy and 75.6-Gy dose levels of a phase I dose escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable non-small cell lung cancer.

PubMed

Rosenzweig, K E; Mychalczak, B; Fuks, Z; Hanley, J; Burman, C; Ling, C C; Armstrong, J; Ginsberg, R; Kris, M G; Raben, A; Leibel, S

2000-01-01

Three-dimensional conformal radiotherapy (3D-CRT) is a mode of high-precision radiotherapy designed to increase the tumor dose and decrease the dose to normal tissues. This study reports the final results of the first two dose levels (70.2 Gy and 75.6 Gy) of a phase I dose-escalation study using 3D-CRT for the treatment of non-small cell lung cancer. Fifty-two patients were treated with 3D-CRT without chemotherapy. The median age was 67 years (range, 39-82 years). The majority of patients had locally advanced cancer. Tumor was staged as I/II in 10%, IIIA in 40%, and IIIB in 50%. Radiation was delivered in daily fractions of 1.8 Gy, 5 days a week. A radiation dose level was considered complete when 10 patients received the intended dose without unacceptable acute morbidity. Toxicity was scored according to the Radiation Therapy Oncology Group grading scheme. Twenty patients were initially assigned to the 70.2-Gy level; 14 of them received the intended dose. Three patients experienced severe acute toxicity, two with grade 3 (requiring steroids or oxygen) and a third with grade 5 (fatal) acute radiation pneumonitis. Because of the grade 5 pulmonary toxicity, the protocol was modified, and only patients with a calculated risk of normal tissue complication of less than 25% were eligible for dose escalation. Patients who had a normal tissue complication probability (NTCP) of greater than 25% received a lower dose of radiation. An additional 18 patients were entered on the modified study; 11 of them received 70.2 Gy. One patient experienced grade 3 acute pneumonitis. Despite dose reduction in four patients because of an unacceptably high NTCP, two additional patients developed grade 3 pulmonary toxicity. Fourteen patients were accrued to the 75.6-Gy dose level, and 10 received the intended dose. One of the 10 patients experienced grade 3 pulmonary toxicity and one developed grade 3 esophageal toxicity. Three patients were treated to lower doses as a result of their calculated NTCP without toxicity, and one patient refused treatment. The 2-year local control, disease-free survival, and overall survival rates were 37%, 12%, and 24%, respectively. The median survival time was 11 months. Treatment to 70.2 Gy and 75.6 Gy using 3D-CRT was delivered with acceptable morbidity when NTCP constraints were observed. Local control was encouraging in these patients with locally advanced disease. Patients are currently being accrued to the 81-Gy level of the study.

Fifty Years after "Brown": Tarnished Gold, Broken Promises

ERIC Educational Resources Information Center

Gantz, Julie

2004-01-01

May 17, 2004 marked the fifty years that have passed since the United States Supreme Court handed down one of its most famous, compelling and iconic decisions, "Brown v. Board of Education of Topeka, Kansas." Certainly the decision itself, labeling the practice of "separate but equal" as unconstitutional, deserves the fanfare…

You Ain't Seen Nothin' Yet

ERIC Educational Resources Information Center

Strawn, George

2006-01-01

Information technology has been changing the academy for the past fifty years, but those changes are small compared with what can be expected in the next fifty years. Three relatively recent IT "subrevolutions" have had an increasing impact on research, scholarly communication, and education. These are namely: (1) "PC subrevolution" that began in…

Evaluating the Safety and Tolerability of Sacubitril/Valsartan for HFrEF Managed Within a Pharmacist Clinic.

PubMed

Pogge, Elizabeth K; Davis, Lindsay E

2018-04-01

The objective of this research was to describe the use of pharmacist-managed sacubitril/valsartan therapy in a multi-center, outpatient cardiac group. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNi), is a novel agent for the treatment of heart failure. An ARNi is recommended by national guidelines to be used in place of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy for patients who remain symptomatic. A retrospective chart review was performed to identify patients initiated and fully titrated on sacubitril/valsartan therapy from July 7, 2015 to March 7, 2017. Fifty-two of the 72 symptomatic heart failure with reduced ejection fraction (HFrEF) patients prescribed sacubitril/valsartan during the 21-month period were included in this analysis. The average ejection fraction was 26%. The average age was 69 years. At baseline, 26.9% of patients were not on ACEi/ARB therapy and 13.5% were on target-dose therapy. After completing the uptitration process, the maximally tolerated dose of sacubitril/valsartan was 5.8% low-dose, 7.7% mid-dose, and 86.5% target-dose. Loop and thiazide diuretic use decreased significantly. There was a significant mean reduction in systolic blood pressure of 6 mmHg with no significant changes in serum creatinine, blood urea nitrogen, or potassium levels. With close monitoring and follow-up, ARNi therapy was a safe alternative to ACEi/ARB therapy for chronic symptomatic HFrEF when initiated within a pharmacist clinic.

Epidural analgesia practices for labour: results of a 2005 national survey in Ireland.

PubMed

Fanning, Rebecca A; Briggs, Liam P; Carey, Michael F

2009-03-01

The last 25 years have seen changes in the management of epidural analgesia for labour, including the advent of low-dose epidural analgesia, the development of new local anaesthetic agents, various regimes for maintaining epidural analgesia and the practice of combined spinal-epidural analgesia. We conducted a survey of Irish obstetric anaesthetists to obtain information regarding the conduct and management of obstetric epidural analgesia in Ireland in 2005. The specific objective of this survey was to discover whether new developments in obstetric anaesthesia have been incorporated into clinical practice. A postal survey was sent to all anaesthetists with a clinical commitment for obstetric anaesthesia in the sites approved for training by the College of Anaesthetists, Ireland. Fifty-three per cent of anaesthetists surveyed responded. The majority of anaesthetists (98%) use low-dose epidural analgesia for the maintenance of analgesia. Only 11% use it for test-dosing and 32% for the induction of analgesia. The combined spinal-epidural analgesia method is used by 49%, but two-thirds of those who use it perform fewer than five per month. Patient-controlled epidural analgesia was in use at only one site. It appears that Irish obstetric anaesthetists have adopted the low-dose epidural analgesia trend for the maintenance of labour analgesia. This practice is not as widespread, however, for test dosing, the induction of analgesia dose or in the administration of intermittent epidural boluses to maintain analgesia when higher concentrations are used. Since its introduction in 2000, levobupivacaine has become the most popular local anaesthetic agent.

Gadolinium Enhanced MR Coronary Vessel Wall Imaging at 3.0 Tesla.

PubMed

Kelle, Sebastian; Schlendorf, Kelly; Hirsch, Glenn A; Gerstenblith, Gary; Fleck, Eckart; Weiss, Robert G; Stuber, Matthias

2010-10-11

Purpose. We evaluated the influence of the time between low-dose gadolinium (Gd) contrast administration and coronary vessel wall enhancement (LGE) detected by 3T magnetic resonance imaging (MRI) in healthy subjects and patients with coronary artery disease (CAD). Materials and Methods. Four healthy subjects (4 men, mean age 29 ± 3 years and eleven CAD patients (6 women, mean age 61 ± 10 years) were studied on a commercial 3.0 Tesla (T) whole-body MR imaging system (Achieva 3.0 T; Philips, Best, The Netherlands). T1-weighted inversion-recovery coronary magnetic resonance imaging (MRI) was repeated up to 75 minutes after administration of low-dose Gadolinium (Gd) (0.1 mmol/kg Gd-DTPA). Results. LGE was seen in none of the healthy subjects, however in all of the CAD patients. In CAD patients, fifty-six of 62 (90.3%) segments showed LGE of the coronary artery vessel wall at time-interval 1 after contrast. At time-interval 2, 34 of 42 (81.0%) and at time-interval 3, 29 of 39 evaluable segments (74.4%) were enhanced. Conclusion. In this work, we demonstrate LGE of the coronary artery vessel wall using 3.0 T MRI after a single, low-dose Gd contrast injection in CAD patients but not in healthy subjects. In the majority of the evaluated coronary segments in CAD patients, LGE of the coronary vessel wall was already detectable 30-45 minutes after administration of the contrast agent.

Fifty years of Cuba's medical diplomacy: from idealism to pragmatism.

PubMed

Feinsilver, Julie M

2010-01-01

Medical diplomacy, the collaboration between countries to simultaneously produce health benefits and improve relations, has been a cornerstone of Cuban foreign policy since the outset of the revolution fifty years ago. It has helped Cuba garner symbolic capital (goodwill, influence, and prestige) well beyond what would have been possible for a small, developing country, and it has contributed to making Cuba a player on the world stage. In recent years, medical diplomacy has been instrumental in providing considerable material capital (aid, credit, and trade), as the oil-for-doctors deals with Venezuela demonstrates. This has helped keep the revolution afloat in trying economic times. What began as the implementation of the one of the core values of the revolution, namely health as a basic human right for all peoples, has continued as both an idealistic and a pragmatic pursuit. This article examines the factors that enabled Cuba to conduct medical diplomacy over the past fifty years, the rationale behind the conduct of this type of soft power politics, the results of that effort, and the mix of idealism and pragmatism that has characterized the experience. Moreover, it presents a typology of medical diplomacy that Cuba has used over the past fifty years.

Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.

Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses ofmore » 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged {<=}7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.« less

Efficacy of granulocyte colony stimulating factor as a secondary prophylaxis along with full-dose chemotherapy following a prior cycle of febrile neutropenia.

PubMed

Gupta, Seema; Singh, Pankaj K; Bhatt, Madan L B; Pant, Mohan C; Gupta, Rajeev; Negi, Mahendra P S

2010-10-01

Secondary prophylaxis with recombinant human granulocyte colony stimulating factor (G-CSF) is recommended where patients have experienced febrile neutropenia in an earlier chemotherapy cycle and for whom the maintenance of chemotherapy dose intensity is important; or where febrile neutropenia has not occurred but prolonged neutropenia is causing excessive dose delay or reduction, where maintenance of dose intensity is important. The objective of this study was to determine the efficacy and feasibility of G-CSF as secondary prophylaxis when used along with full dose moderately myelotoxic chemotherapy following a prior cycle with febrile-neutropenia. Fifty-two patients aged 22-75 years with febrile neutropenia that required intravenous antibiotics following moderately myelotoxic chemotherapy were included. These patients received the next cycle of the same chemotherapy regime without dose modification but with support of filgrastim 24 h after completion of chemotherapy (300 μg/day/subcutaneously (s.c.) for weight < 60 kg, 480 μg/day/s.c. for weight > 60 kg, for at least 10 consecutive days), patients in whom neutropenia was associated with a life-threatening infection and those who developed prolonged myelosuppression were excluded. The use of the hematopoietic growth factor G-CSF was shown to shorten the neutrophil recovery time, resulting in significant reduction of incidence of febrile neutropenia, hospitalization and use of broad spectrum antibiotics. There was no drug related death or adverse events associated with either cycle. In conclusion, recombinant human G-CSF is effective and relatively safe as a secondary prophylaxis with full dose chemotherapy in patients who develop febrile neutropenia following prior cycles of moderately myelotoxic chemotherapy.

l-Carnosine as Adjunctive Therapy in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

PubMed

Ghajar, Alireza; Aghajan-Nashtaei, Farinaz; Afarideh, Mohsen; Mohammadi, Mohammad-Reza; Akhondzadeh, Shahin

2018-06-01

This study aimed to investigate the efficacy and tolerability of l-carnosine as an add-on to methylphenidate in management of children with attention-deficit/hyperactivity disorder (ADHD). This was an 8-week, randomized, double-blind placebo-controlled study. Fifty-six drug-free children and adolescents aged 6-17 years old with a diagnosis of ADHD entered the study. The patients were randomly assigned to l-carnosine (800 mg/d in two divided doses) or placebo plus methylphenidate (0.5-1.5 mg/kg/d) for 8 weeks. Children were assessed using the Teacher and Parent ADHD Rating Scale-IV (ADHD-RS-IV) at baseline and at weeks 4 and 8 postbaseline. Fifty patients completed the study, and all had two postbaseline measurements. Using the general linear model repeated measures, significant effect was observed for time × treatment interaction on total and inattention subscales of the Parent ADHD-RS (Greenhouse-Geisser corrected: F = 3.783, df = 1.444, p = 0.041 and F = 4.032, df = 1.600, p = 0.030). Improvements in the Teacher ADHD-RS were not significantly different between the two groups in total (Greenhouse-Geisser corrected: F = 0.200, df = 1.218, p = 0.705), as well as inattention and hyperactivity subscale scores (p = 0.956 and 0.281, respectively). The frequency of side effects was not significantly different between the two treatment arms. l-carnosine, as a supplementary medication, might be beneficial in treatment of children with ADHD. However, further investigations and different doses of l-carnosine are required to replicate these findings in children with ADHD.

Management of gout by UK rheumatologists: a British Society for Rheumatology national audit.

PubMed

Roddy, Edward; Packham, Jon; Obrenovic, Karen; Rivett, Ali; Ledingham, Joanna M

2018-05-01

To assess the concordance of gout management by UK rheumatologists with evidence-based best-practice recommendations. Data were collected on patients newly referred to UK rheumatology out-patient departments over an 8-week period. Baseline data included demographics, method of diagnosis, clinical features, comorbidities, urate-lowering therapy (ULT), prophylaxis and blood tests. Twelve months later, the most recent serum uric acid level was collected. Management was compared with audit standards derived from the 2006 EULAR recommendations, 2007 British Society for Rheumatology/British Health Professionals in Rheumatology guideline and the National Institute for Health and Care Excellence febuxostat technology appraisal. Data were collected for 434 patients from 91 rheumatology departments (mean age 59.8 years, 82% male). Diagnosis was crystal-proven in 13%. Of 106 taking a diuretic, this was reduced/stopped in 29%. ULT was continued/initiated in 76% of those with one or more indication for ULT. One hundred and fifty-eight patients started allopurinol: the starting dose was most commonly 100 mg daily (82%); in those with estimated glomerular filtration rate <60 ml/min the highest starting dose was 100 mg daily. Of 199 who started ULT, prophylaxis was co-prescribed for 94%. Fifty patients started a uricosuric or febuxostat: 84% had taken allopurinol previously. Of 44 commenced on febuxostat, 18% had a history of heart disease. By 12 months, serum uric acid levels ⩽360 and <300 μmol/l were achieved by 45 and 25%, respectively. Gout management by UK rheumatologists concords well with guidelines for most audit standards. However, fewer than half of patients achieved a target serum uric level over 12 months. Rheumatologists should help ensure that ULT is optimized to achieve target serum uric acid levels to benefit patients.

Parental beliefs and practices regarding childhood fever in Turkish primary care.

PubMed

Yavuz, E; Yayla, E; Cebeci, S E; Kırımlı, E; Gümüştakım, R Ş; Çakır, L; Doğan, S

2017-01-01

Fever is a very common problem in pediatric age and is one of the most common reasons parents seek medical attention. We aimed to investigate beliefs, habits, and concerns of Turkish parents regarding their children's fever. We performed a cross-sectional survey which was conducted as face-to-face interviews by family physicians from April to June 2014 in family healthcare centers in nine different cities in Turkey. Parents with a child with fever aged between 0 and 14 years were interviewed. The participants were asked questions about sociodemographic data, the definition and measurement of fever, antipyretics, and other interventions used to reduce fever before presenting to the primary care center. A total of 205 parents participated in this study. Ninety-four parents (45.8%) measured fever with a thermometer prior to presentation. Only 36 parents (38%) used the thermometer correctly. Thirty-eight parents (18.5%) knew the correct temperature definition of fever for the measured site. A mercury-in-glass thermometer was the choice for most parents (78%) and preferred site for measurement was axillary region (85%). The fever was treated prior to arrival by 171 parents (83.4%). Paracetamol was the most frequently used antipyretic. Fifty-four parents (31.5%) failed to administer the correct antipyretic dose, and 73 parents (42.6%) failed to give the antipyretics at proper intervals. One hundred and fifty-three parents (67%) believed that if not treated fever could cause convulsions. We conclude that parents share important misconceptions about definition, treatment, and consequences of childhood fever and tend to treat fever before seeking medical care with a substantial rate of wrong doses and wrong intervals.

The fifty-year-old woman and midlife stress.

PubMed

Campbell, S

It has been assumed that the fifties are a relatively stable decade; however, women in their fifties are susceptible to many stresses, internal and external. The possibilities of widowhood, divorce, or poverty, combined with intra- and interpersonal strains, make this a time of insecurity about aging for many women. Some suggestions as to why women nonetheless cope successfully with aging are considered.

Fifty Years Later: Comments on the Further Development of a Science of Verbal Behavior

ERIC Educational Resources Information Center

Leigland, Sam

2007-01-01

Fifty years after the publication of Skinner's "Verbal Behavior", some possibilities for the future of Skinner's "science of verbal behavior" are considered. Specifically, certain areas of development or advancement are examined which might be of special importance to the expansion and influence of the functional analysis of verbal behavior.…

Information Systems Curricula: A Fifty Year Journey

ERIC Educational Resources Information Center

Longenecker, Herbert E., Jr.; Feinstein, David; Clark, Jon D.

2013-01-01

This article presents the results of research to explore the nature of changes in skills over a fifty year period spanning the life of Information Systems model curricula. Work begun in 1999 was expanded both backwards in time, as well as forwards to 2012 to define skills relevant to Information Systems curricula. The work in 1999 was based on job…

Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents - An observational, longitudinal study.

PubMed

Hausman-Kedem, Moran; Menascu, Shay; Kramer, Uri

2018-04-16

The objective of this observational study was to evaluate the efficacy of medical cannabis for the treatment of refractory epilepsy. Fifty-seven patients (age 1-20 years) with epilepsy of various etiologies were treated with Cannabis oil extract (CBD/THC ratio of 20:1) for at least 3 months (Median follow up time-18 months). Forty-Six Patients were included in the efficacy analysis. Average CBD dose was11.4 mg/kg/d. Twenty-six patients (56%) had ≤50% reduction in mean monthly seizure frequency. There was no statistically significant difference in response rate among various epilepsy etiologies, and cannabis strain used. Younger age at treatment onset (<10 years) and higher CBD dose (>11 mg/kg/d) were associated with better response to treatment. Adverse reactions were reported in 46% of patients and were the main reason for treatment cessation. Our results suggest that adding CBD-enriched cannabis extract to the treatment regimen of patients with refractory epilepsy may result in a significant reduction in seizure frequency according to parental reports. Randomized controlled trials are necessary to assess its true efficacy. Copyright © 2018 Elsevier B.V. All rights reserved.

Fifty years of entomological publications in the Revista de Biología Tropical.

PubMed

Hanson, Paul

2002-01-01

Over its fifty year history nearly twenty percent of the papers published in the Revista de Biología Tropical have been about insects and arachnids. In the 1950's papers on arthropods of medical importance were dominant, in the 1960's there was a poliferation of papers on bees, and in more recent years the subjects have become increasingly diverse. In terms of nationality of contributing authors, the journal appears to have become increasingly international in later years.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Vishal; Mychalczak, Borys; Krug, Lee

Purpose: To evaluate pleurectomy/decortication (P/D) and adjuvant radiotherapy (RT) in the treatment of malignant pleural mesothelioma (MPM). Methods and Materials: In a retrospective review, we included MPM patients treated with P/D and adjuvant RT at Memorial Sloan-Kettering Cancer Center from 1974 to 2003. When indicated, patients received intraoperative brachytherapy to residual tumor. Results: All 123 patients received external beam RT (median dose, 42.5 Gy; range, 7.2-67.8 Gy) to the ipsilateral hemithorax postoperatively. Fifty-four patients underwent brachytherapy (matched peripheral dose, 160 Gy). The median and 2-year overall survival for all patients was 13.5 months (range, 1-199 months) and 23%, respectively. One-yearmore » actuarial local control for all patients was 42%. Multivariate analysis for overall survival revealed radiation dose <40 Gy (p = 0.001), nonepithelioid histology (p = 0.002), left-sided disease (p = 0.01), and the use of an implant (p = 0.02) to be unfavorable. Two patients (1.6%) died from Grade 5 toxicity within 1 month of treatment. Conclusions: Pleurectomy/decortication with adjuvant radiotherapy is not an effective treatment option for patients with MPM. Our results imply that residual disease cannot be eradicated with external RT with or without brachytherapy and that a more extensive surgery followed by external RT might be required to improve local control and overall survival.« less

[Safinamide from daily clinical practice: first clinical steps].

PubMed

Pagonabarraga, J; Kulisevsky, J

2017-11-16

The management of motor complications in Parkinson's disease (PD) is still limited. Safinamide, a new drug that has MAO-B inhibition and antiglutamatergic effects through inhibition of sodium channels, has shown efficacy for the treatment of fluctuations at doses of 50-100 mg/day. From daily clinical practice, we describe the efficacy and tolerability of safinamide at three months in PD patients with motor complications. Efficacy was assessed by the Clinical Global Impression of Change scale and change in 'off' time during the daytime. All reported adverse events were recorded. Fifty patients were recruited. 57.4% reported to be much better or moderately better at three months, improving both motor and non-motor fluctuations. Significant decrease of 0.9 ± 0.6 h/day was achieved at three months. In 13 patients (27.6%), levodopa equivalent daily dose was reduced in 132 mg/day. In patients with dyskinesias, safinamide 100 mg/day was better for controlling fluctuations and dyskinesias. 19% of patients had mild adverse events. Seven patients stopped treatment after development of confusional syndrome. The dopaminergic and non-dopaminergic action of safinamide exerts a good control of motor fluctuations. In patients with fluctuations and dyskinesias the dose of 100 mg/day of safinamide is preferred. Tolerability was good, except for patients older than 75 years or in advanced stages of the disease.

Evaluation of the effectiveness of Haemophilus influenzae type b conjugate vaccine introduction against radiologically-confirmed hospitalized pneumonia in young children in Ukraine.

PubMed

Pilishvili, Tamara; Chernyshova, Liudmyla; Bondarenko, Anastasia; Lapiy, Fedir; Sychova, Irina; Cohen, Adam; Flannery, Brendan; Hajjeh, Rana

2013-07-01

Haemophilus influenzae type b (Hib) conjugate vaccine was included into the national vaccination schedule of Ukraine in 2006. The objective of this study was to demonstrate the effectiveness of Hib conjugate vaccine against radiologically-confirmed hospitalized pneumonia in children. Children <2 years old with radiologically confirmed pneumonia admitted to 11 participating hospitals in Kiev and Dnepropetrovsk between April 2007 and June 2009 were included in a case-control evaluation. Four controls were matched to each case by date of birth (within 14 days) and outpatient clinic. We estimated ORs for vaccination and vaccine effectiveness ((1 - OR)*100%) using conditional logistic regression, adjusting for comorbid conditions and contraindications for vaccination. We enrolled 188 case-children and 735 controls. Median age was 16 months (range 4-24 months). Fifty-one percent of cases and 67% of controls received ≥1 doses of Hib conjugate vaccine; 26% of cases and 37% of controls received ≥3 doses. The effectiveness of ≥1 dose Hib conjugate vaccine was estimated at 45% (95% CI 18%-63%). Our study showed that Hib infections are important causes of hospitalized radiologically confirmed pneumonia in young children in Ukraine. Copyright © 2013. Published by Mosby, Inc.

Results of a prospective multicentre myeloablative double-unit cord blood transplantation trial in adult patients with acute leukaemia and myelodysplasia.

PubMed

Barker, Juliet N; Fei, Mingwei; Karanes, Chatchada; Horwitz, Mitchell; Devine, Steven; Kindwall-Keller, Tamila L; Holter, Jennifer; Adams, Alexia; Logan, Brent; Navarro, Willis H; Riches, Marcie

2015-02-01

Double-unit cord blood (CB) grafts may improve engraftment and relapse risk in adults with haematological malignancies. We performed a prospective high-dose myeloablative double-unit CB transplantation (CBT) trial in adults with high-risk acute leukaemia or myelodysplasia (MDS) between 2007 and 2011. The primary aim was to establish the 1-year overall survival in a multi-centre setting. Fifty-six patients (31 acute myeloid leukaemia, 19 acute lymphoblastic leukaemia, 4 other acute leukaemias, 2 myelodysplastic syndrome [MDS]) were transplanted at 10 centres. The median infused total nucleated cell doses were 2·62 (larger unit) and 2·02 (smaller unit) x 10(7) /kg. The cumulative incidence of day 100 neutrophil engraftment was 89% (95% confidence interval [CI]: 80-96). Day 180 grade II-IV acute graft-versus-host disease (GVHD) incidence was 64% (95%CI: 51-76) and 36% (95%CI: 24-49) of patients had chronic GVHD by 3-years. At 3-years post-transplant, the transplant-related mortality (TRM) was 39% (95%CI: 26-52), and the 3-year relapse incidence was 11% (95%CI: 4-21). With a median 37-month (range 23-71) follow-up of survivors, the 3-year disease-free survival was 50% (95%CI: 37-63). Double-unit CBT is a viable alternative therapy for high-risk acute leukaemia/ MDS in patients lacking a matched unrelated donor. This is especially important for minority patients. The relapse incidence was low but strategies to ameliorate TRM are needed. © 2014 John Wiley & Sons Ltd.

Onabotulinum toxin A dosage trends over time for adductor spasmodic dysphonia: A 15-year experience.

PubMed

Tang, Christopher G; Novakovic, Daniel; Mor, Niv; Blitzer, Andrew

2016-03-01

Although onabotulinum neurotoxin A (BoNTA) has been used for over three decades for the treatment of adductor spasmodic dysphonia, no study has been performed to look at the trend of BoNTA dosages across time. The goal of this study is to evaluate the dosage trends to determine if the dosage necessary for voice improvement in patients increases over time. Charts were reviewed for patients with 15 years or more of experience. Linear regression analysis was performed to determine correlation coefficients and trends. Fifty-five patients receiving BoNTA injections by the senior author (a.b.) for over 15 years were evaluated. Thirty-nine patients (82% female) met inclusion criteria. Patients received injections over an average of 18.6 years ± 1.36 years, with the longest follow-up of 21.5 years. Of 39 patients, 16 (41%) had a negative correlation coefficient (Pearson's r) suggesting a decrease over time, whereas 23 (59%) had a positive correlation coefficient suggesting an increase over time. The mean correlation coefficient was 0.139 ± 0.534 and P < 0.05 in 19 patients and P > 0.05 in 20 patients. R(2) for all patients were less than 0.75. Onabotulinum neurotoxin A injection dosage trends vary depending on the individual over time. Overall, the dose range appears to be stable in the majority of patients, suggesting that tolerance does not play a significant part in dose variation over time. 4. Laryngoscope, 126:678-681, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Why we prefer levetiracetam over phenytoin for treatment of status epilepticus.

PubMed

Zaccara, G; Giorgi, F S; Amantini, A; Giannasi, G; Campostrini, R; Giovannelli, F; Paganini, M; Nazerian, P

2018-06-01

Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine-resistant convulsive status epilepticus and several guidelines recommended this treatment regimen with simultaneous iv diazepam. Clinical studies have never shown a better efficacy of PHT over other antiepileptic drugs. In addition, iv PHT loading dose is a complex and time-consuming procedure which may expose patients to several risks, such as local cutaneous reactions (purple glove syndrome), severe hypotension and cardiac arrhythmias up to ventricular fibrillation and death, and increased risk of severe allergic reactions. A further disadvantage of PHT is that it is a strong enzymatic inducer and it may make ineffective several drugs that need to be used simultaneously with antiepileptic treatment. In patients with a benzodiazepine-resistant status epilepticus, we suggest iv administration of levetiracetam as soon as possible. If levetiracetam would be ineffective, a further antiepileptic drug among those currently available for iv use (valproate, lacosamide, or phenytoin) can be added before starting third line treatment. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Breast surface radiation dose during coronary CT angiography: reduction by breast displacement and lead shielding.

PubMed

Foley, Shane J; McEntee, Mark F; Achenbach, Stephan; Brennan, Patrick C; Rainford, Louise S; Dodd, Jonathan D

2011-08-01

The purpose of this study was to prospectively evaluate the effect of cranial breast displacement and lead shielding on in vivo breast surface radiation dose in women undergoing coronary CT angiography. Fifty-four women (mean age, 59.2 ± 9.8 years) prospectively underwent coronary 64-MDCT angiography for evaluation of chest pain. The patients were randomly assigned to a control group (n = 16), breast displacement group (n = 22), or breast displacement plus lead shielding group (n = 16). Thermoluminescent dosimeters (TLDs) were placed superficially on each breast quadrant and the areolar region of both breasts. Breast surface radiation doses, the degree of breast displacement, and coronary image quality were compared between groups. A phantom dose study was conducted to compare breast doses with z-axis positioning on the chest wall. A total of 1620 TLD dose measurements were recorded. Compared with control values, the mean breast surface dose was reduced 23% in the breast displacement group (24.3 vs 18.6 mGy, p = 0.015) and 36% in the displacement plus lead shielding group (24.3 vs 15.6 mGy, p = 0.0001). Surface dose reductions were greatest in the upper outer (displacement alone, 66%; displacement plus shielding, 63%), upper inner (65%, 58%), and areolar quadrants (44%, 53%). The smallest surface dose reductions were recorded for A-cup breasts: 7% for the displacement group and 3% for the displacement plus lead group (p = 0.741). Larger reductions in surface dose were recorded for B-cup (25% and 56%, p = 0.273), C-cup (38% and 60%, p = 0.001), and D-cup (31% and 25%, p = 0.095) sizes. Most of the patients (79%) had either good (< 50% of breast above scan range) or excellent (< 75% of breast above the scan range) breast displacement. No significant difference in coronary image quality was detected between groups. The phantom dose study showed that surface TLD measurements were underestimates of absorbed tissue dose by a mean of 9% and that a strong negative correlation exists between the amount of cranial displacement and breast dose. Use of breast displacement during coronary CTA substantially reduces the radiation dose to the breast surface.

Intervention Efficacy and Intensity for Children with Speech Sound Disorder

ERIC Educational Resources Information Center

Allen, Melissa M.

2013-01-01

Purpose: Clinicians do not have an evidence base they can use to recommend optimum intervention intensity for preschool children who present with speech sound disorder (SSD). This study examined the effect of dose frequency on phonological performance and the efficacy of the multiple oppositions approach. Method: Fifty-four preschool children with…

Law as a Teacher of Society: Reflections on Title VII after Fifty Years

ERIC Educational Resources Information Center

Little, Andrew

2016-01-01

The Civil Rights Act of 1964 has worked to reshape American society for more than fifty years through arguably its most important subpart, Title VII, which prohibits discrimination in employment. This article is not so much an attempt to join the chorus of scholars offering reflections on the statute after five decades, as it is an attempt to…

Historical Doses from Tritiated Water and Tritiated Hydrogen Gas Released to the Atmosphere from Lawrence Livermore National Laboratory (LLNL). Part 5. Accidental Releases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, S

2007-08-15

Over the course of fifty-three years, LLNL had six acute releases of tritiated hydrogen gas (HT) and one acute release of tritiated water vapor (HTO) that were too large relative to the annual releases to be included as part of the annual releases from normal operations detailed in Parts 3 and 4 of the Tritium Dose Reconstruction (TDR). Sandia National Laboratories/California (SNL/CA) had one such release of HT and one of HTO. Doses to the maximally exposed individual (MEI) for these accidents have been modeled using an equation derived from the time-dependent tritium model, UFOTRI, and parameter values based onmore » expert judgment. All of these acute releases are described in this report. Doses that could not have been exceeded from the large HT releases of 1965 and 1970 were calculated to be 43 {micro}Sv (4.3 mrem) and 120 {micro}Sv (12 mrem) to an adult, respectively. Two published sets of dose predictions for the accidental HT release in 1970 are compared with the dose predictions of this TDR. The highest predicted dose was for an acute release of HTO in 1954. For this release, the dose that could not have been exceeded was estimated to have been 2 mSv (200 mrem), although, because of the high uncertainty about the predictions, the likely dose may have been as low as 360 {micro}Sv (36 mrem) or less. The estimated maximum exposures from the accidental releases were such that no adverse health effects would be expected. Appendix A lists all accidents and large routine puff releases that have occurred at LLNL and SNL/CA between 1953 and 2005. Appendix B describes the processes unique to tritium that must be modeled after an acute release, some of the time-dependent tritium models being used today, and the results of tests of these models.« less

Phase I Pharmacokinetic and Pharmacodynamic Study of Pazopanib in Children With Soft Tissue Sarcoma and Other Refractory Solid Tumors: A Children's Oncology Group Phase I Consortium Report

PubMed Central

Glade Bender, Julia L.; Lee, Alice; Reid, Joel M.; Baruchel, Sylvain; Roberts, Timothy; Voss, Stephan D.; Wu, Bing; Ahern, Charlotte H.; Ingle, Ashish M.; Harris, Pamela; Weigel, Brenda J.; Blaney, Susan M.

2013-01-01

Purpose Pazopanib, an oral multikinase angiogenesis inhibitor, prolongs progression-free survival in adults with soft tissue sarcoma (STS). A phase I pharmacokinetic and pharmacodynamic study of two formulations of pazopanib was performed in children with STS or other refractory solid tumors. Patients and Methods Pazopanib (tablet formulation) was administered once daily in 28-day cycles at four dose levels (275 to 600 mg/m2) using the rolling-six design. Dose determination for a powder suspension was initiated at 50% of the maximum-tolerated dose (MTD) for the intact tablet. Ten patients with STS underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scanning at baseline and 15 ± 2 days after initiation of pazopanib at the tablet MTD. Results Fifty-three patients were enrolled; 51 were eligible (26 males; median age, 12.9 years; range, 3.8 to 23.9 years). Hematologic and nonhematologic toxicities were generally mild, with dose-limiting lipase, amylase, and ALT elevation, proteinuria, and hypertension. One patient with occult brain metastasis had grade 4 intracranial hemorrhage. The MTD was 450 mg/m2 for tablet and 160 mg/m2 for suspension. Steady-state trough concentrations were reached by day 15 and did not seem to be dose dependent. One patient each with hepatoblastoma or desmoplastic small round cell tumor achieved a partial response; eight patients had stable disease for ≥ six cycles, seven of whom had sarcoma. All patients with evaluable DCE-MRI (n = 8) experienced decreases in tumor blood volume and permeability (P < .01). Placental growth factor increased, whereas endoglin and soluble vascular endothelial growth factor receptor-2 decreased (P < .01; n = 41). Conclusion Pazopanib is well tolerated in children, with evidence of antiangiogenic effect and potential clinical benefit in pediatric sarcoma. PMID:23857966

[A case report of early-onset Alzheimer's disease with multiple psychotic symptoms, finally diagnosed as APPV717I mutation by genetic testing].

PubMed

Ishimaru, Takashi; Ochi, Shinichiro; Matsumoto, Teruhisa; Yoshida, Taku; Abe, Masao; Toyota, Yasutaka; Fukuhara, Ryuji; Tanimukai, Satoshi; Ueno, Shu-ichi

2013-01-01

It is difficult to confirm a diagnosis of early-onset Alzheimer's disease (EOAD) because patients sometimes have non-specific cortical features, such as psychiatric symptoms, executive functional impairment, and pyramidal symptoms, along with typical symptoms, such as recent memory impairment and disorientation. We encountered a patient with multiple psychotic symptoms, finally diagnosed with EOAD on genetic testing. A right-handed sixty-year-old man, whose mother was suspected of having dementia, developed memory impairment at the age of fifty, disorientation at the age of fifty-six, and both visual hallucination and dressing apraxia at the age of fifty-nine. After admission to a psychiatric hospital for treatment, his symptoms disappeared with antipsychotic medication. However, his ADL were declining and so he was referred to our university hospital. He had frontal lobe symptoms, pyramidal signs, and extrapyramidal signs with severe dementia. Neuropsychological examinations were not possible because of sedation. On brain MRI, he showed diffuse atrophy of the cerebral cortex and hippocampus. HMPO-SPECT showed hypoperfusion of cerebral cortices diffusely. We decided to perform genetic testing because he had both family and alcohol abuse histories. He showed EOAD with V717I mutation of the amyloid precursor protein gene. After the discontinuation of antipsychotics, excessive sedation and extrapyramidal signs disappeared. A dose of 10 mg of donepezil was effective to improve motivation and activity, and his mini mental examination score was calculable after recovery. The case supports usefulness of applying genetic testing for Alzheimer's disease to patients with early onset dementia, even when they do not have a family history.

Cediranib in patients with malignant mesothelioma: A phase II trial of the University of Chicago Phase II Consortium

PubMed Central

Campbell, Nicholas P.; Kunnavakkam, Rangesh; Leighl, Natasha; Vincent, Mark D.; Gandara, David R.; Koczywas, Marianna; Gitlitz, Barbara J.; Agamah, Edem; Thomas, Sachdev P.; Stadler, Walter M.; Vokes, Everett E.; Kindler, Hedy L.

2013-01-01

Introduction Malignant mesothelioma (MM) is an aggressive disease with limited therapeutic options. In preclinical models, vascular endothelial growth factor (VEGF) stimulates MM proliferation. In MM patients, higher plasma VEGF levels correlate inversely with survival. Cediranib is an orally administered tyrosine kinase inhibitor of VEGF receptors -1, -2, and -3. Methods We conducted a multi-center phase II trial of cediranib in patients with unresectable, histologically-confirmed MM who had received ≤1 prior regimen of chemotherapy. The primary endpoint was objective response rate. Initial cediranib dosing was 45 mg daily during a 28-day cycle. Due to substantial toxicity, the starting dose was subsequently lowered to 30 mg daily. Results Fifty-one patients enrolled at 9 centers; 50 were evaluable for response. Partial responses were observed in 10% of patients; stable disease was seen in 34%. Disease control (PR + SD) was higher at the 45 mg cediranib dose level (67% vs. 34%, p=0.04). Median progression-free survival was 1.8 months (95% CI 0.1, 14.2); median overall survival (OS) was 4.4 months (95% CI 0.9, 41.7). The 1-year survival rate was 15%. Grade 3/4 toxicities were more frequent in the 45 mg dose level group (87% vs. 43%, p=0.002). These included fatigue, hypertension, pulmonary embolism, angioedema, and reversible posterior leukoencephalopathy. Median OS was superior in patients who developed ≥ grade 3 hypertension (8.5 vs. 4.1 months, p=0.024). Conclusion This trial did not meet its pre-specified response endpoint. A higher cediranib dose level was associated with improved disease control, but this dose was poorly tolerated. PMID:22831987

Brachial Plexus-Associated Neuropathy After High-Dose Radiation Therapy for Head-and-Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.edu; Hall, William H.; Li, Judy

2012-09-01

Purpose: To identify clinical and treatment-related predictors of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer. Methods and Materials: Three hundred thirty patients who had previously completed radiation therapy for head-and-neck cancer were prospectively screened using a standardized instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from completion of radiation therapy was 56 months (range, 6-135 months). One-hundred fifty-five patients (47%) were treated by definitive radiation therapy, and 175 (53%) were treated postoperatively. Radiation doses ranged from 50 to 74 Gy (median,more » 66 Gy). Intensity-modulated radiation therapy was used in 62% of cases, and 133 patients (40%) received concurrent chemotherapy. Results: Forty patients (12%) reported neuropathic symptoms, with the most common being ipsilateral pain (50%), numbness/tingling (40%), motor weakness, and/or muscle atrophy (25%). When patients with <5 years of follow-up were excluded, the rate of positive symptoms increased to 22%. On univariate analysis, the following factors were significantly associated with brachial plexus symptoms: prior neck dissection (p = 0.01), concurrent chemotherapy (p = 0.01), and radiation maximum dose (p < 0.001). Cox regression analysis confirmed that both neck dissection (p < 0.001) and radiation maximum dose (p < 0.001) were independently predictive of symptoms. Conclusion: The incidence of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer may be underreported. In view of the dose-response relationship identified, limiting radiation dose to the brachial plexus should be considered when possible.« less

Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jebsen, Nina L., E-mail: nina.louise.jebsen@helse-bergen.no; Department of Oncology, Haukeland University Hospital, Bergen; Engellau, Jacob

2013-08-01

Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence intervalmore » [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.« less

Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis.

PubMed

Cuffari, Carmen; Pierce, David; Korczowski, Bartosz; Fyderek, Krzysztof; Van Heusen, Heather; Hossack, Stuart; Wan, Hong; Edwards, Alena Y Z; Martin, Patrick

2016-01-01

Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC). To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC. Participants (5-17 years of age; 18-82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model. Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%-45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified. Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844.

Fifty Year Canon of Lunar Eclipses: 1986-2035

NASA Technical Reports Server (NTRS)

Espenak, Fred

1989-01-01

A complete catalog is presented, listing the general circumstances of every lunar eclipse from 1901 through 2100. To compliment this catalog, a set of figures illustrate the basic Moon-shadow geometry and global visibility for every lunar eclipse over the 200 year interval. Focusing in on the next fifty years, 114 detailed diagrams show the Moon's path through Earth's shadow during every eclipse, including contact times at each phase. The accompanying cylindrical projection maps of Earth show regions of hemispheric visibility for all phases. The appendices discuss eclipse geometry, eclipse frequency and recurrence, enlargement of Earth's shadow, crater timings, eclipse brightness and time determination. Finally, a simple FORTRAN program is provided which can be used to predict the occurrence and general characteristics of lunar eclipses. This work is a companion volume to NASA Reference Publication 1178: Fifty Year Canon of Solar Eclipses: 1986-2035.

An Ode to Stuart Hall's "The Supply of Demand": The Case of Post-Secondary Education in Ontario Fifty Years Later

ERIC Educational Resources Information Center

FitzGerald Murphy, Maggie

2016-01-01

Despite the fact that over fifty years have passed since its publication, Stuart Hall's article "The Supply of Demand" (1960), is remarkably relevant today. The central message that society must not be blinded by "prosperity" such that it no longer envisions and demands a better world is especially pertinent in light of the…

Through the Looking Glass: Adult Education through the Lens of the Australian Journal of Adult Learning over Fifty Years

ERIC Educational Resources Information Center

Harris, Roger; Morrison, Anne

2011-01-01

In this paper we review fifty years of articles published in Australian Journal of Adult Learning in its various iterations. We examine the different roles of the journal: to illuminate the history and trends of adult education authors; to be the flagship of the adult education profession in Australia; to reflect on significant national events;…

From the Scientistic to the Humanistic in the Construction of Contemporary Educational Knowledge

ERIC Educational Resources Information Center

Bridges, David

2011-01-01

The starting point for this article is a lecture given fifty years ago by C.P. Snow under the title "The Two Cultures and the Scientific Revolution", in which Snow critiques what he sees as the damaging intellectual division between the arts and humanities on the one side and the sciences on the other. Fifty years later this problem is, perhaps,…

Long-term exposure and safety of lacosamide monotherapy for the treatment of partial-onset (focal) seizures: Results from a multicenter, open-label trial.

PubMed

Vossler, David G; Wechsler, Robert T; Williams, Paulette; Byrnes, William; Therriault, Sheila

2016-10-01

To assess long-term use and safety of lacosamide (LCM) ≤800 mg/day monotherapy in patients with partial-onset seizures (POS) enrolled previously in a historical-controlled, conversion-to-monotherapy study (SP902; NCT00520741). Patients completing or exiting SP902 with LCM as monotherapy or as adjunctive therapy were eligible to enter this 2-year open-label extension (OLE) trial (SP904; NCT00530855) at a starting dose ±100 mg/day of their final SP902 dose. Investigators could adjust the LCM dose to 100-800 mg/day and add up to two antiepileptic drugs to optimize tolerability and seizure reduction. Three hundred twenty-two patients received LCM: 210 patients (65.2%) completed and 112 (34.8%) discontinued, most commonly owing to withdrawal of consent (9.3%). Two hundred fifty-eight patients (80.1%) had ≥1 year of and 216 (67.1%) had ≥2 years of LCM exposure, of whom 179/258 (69.4%) achieved LCM monotherapy lasting for any 12-month period, and 126/216 (58.3%) patients exposed for ≥24 months achieved LCM monotherapy for any 24-month period. Total exposure = 525.5 patient-years. The median modal dose was 500 mg/day. Two hundred ninety-two patients (90.7%) achieved LCM monotherapy at some point during the study. Sixty-five of 87 patients who exited and 193/235 who completed SP902 were exposed for ≥12 months, and 43.1% and 78.2%, respectively, achieved LCM monotherapy for ≥12 months. Median LCM monotherapy duration was 587.0 days (2-791 days); 91.0% of patients reported treatment-emergent adverse events, of which the most common were dizziness (27.3%), headache (17.1%), and nausea (14.3%). Compared with the SP902 study baseline, 74.2% of patients had a ≥50% seizure reduction and 5.6% were seizure-free at 24 months. The majority of patients were receiving LCM monotherapy at 0, 12, and 24 months in this OLE. Lacosamide monotherapy (median dose of 500 mg/day) had a safety profile similar to that of adjunctive therapy studies. These results support the use of lacosamide as long-term monotherapy treatment for adults with POS. © 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Extracorporeal shock wave therapy without local anesthesia for chronic lateral epicondylitis.

PubMed

Pettrone, Frank A; McCall, Brian R

2005-06-01

The use of extracorporeal shock wave therapy for the treatment of lateral epicondylitis is controversial. The purpose of this study was to evaluate the use of extracorporeal shock wave therapy without local anesthesia to treat chronic lateral epicondylitis. One hundred and fourteen patients with a minimum six-month history of lateral epicondylitis that was unresponsive to conventional therapy were randomized into double-blind active treatment and placebo groups. The protocol consisted of three weekly treatments of either low-dose shock wave therapy without anesthetic or a sham treatment. Patients had a physical examination, including provocation testing and dynamometry, at one, four, eight, and twelve weeks and at six and twelve months after treatment. Radiographs, laboratory studies, and electrocardiograms were also evaluated prior to participation and at twelve weeks. A visual analog scale was used to evaluate pain, and an upper extremity functional scale was used to assess function. Crossover to active treatment was initiated for nonresponsive patients who had received the placebo and met the inclusion criteria after twelve weeks. A total of 108 of the 114 randomized patients completed all treatments and the twelve weeks of follow-up required by the protocol. Sixty-one patients completed one year of follow-up, whereas thirty-four patients crossed over to receive active treatment. A significant difference (p = 0.001) in pain reduction was observed at twelve weeks in the intent-to-treat cohort, with an improvement in the pain score of at least 50% seen in 61% (thirty-four) of the fifty-six patients in the active treatment group who were treated according to protocol compared with 29% (seventeen) of the fifty-eight subjects in the placebo group. This improvement persisted in those followed to one year. Functional activity scores, activity-specific evaluation, and the overall impression of the disease state all showed significant improvement as well (p < 0.05). Crossover patients also showed significant improvement after twelve weeks of active treatment, with 56% (nineteen of thirty-four) achieving an improvement in the pain score of at least 50% (p < 0.0001). These results demonstrate that low-dose shock wave therapy without anesthetic is a safe and effective treatment for chronic lateral epicondylitis.

Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.

PubMed

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.

Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.

PubMed Central

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

Allogeneic hematopoietic cell transplantation after conditioning with I-131-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pagel, John M.; Gooley, T. A.; Rajendran, Joseph G.

2009-12-24

We conducted a study to estimate the maximum tolerated dose (MTD) of I-131-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the bloodmore » by day 28 after the transplantation. The MTD of I-131-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.« less

Effects of Surgery and Proton Therapy on Cerebral White Matter of Craniopharyngioma Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uh, Jinsoo, E-mail: jinsoo.uh@stjude.org; Merchant, Thomas E.; Li, Yimei

Purpose: The purpose of this study was to determine radiation dose effect on the structural integrity of cerebral white matter in craniopharyngioma patients receiving surgery and proton therapy. Methods and Materials: Fifty-one patients (2.1-19.3 years of age) with craniopharyngioma underwent surgery and proton therapy in a prospective therapeutic trial. Anatomical magnetic resonance images acquired after surgery but before proton therapy were inspected to identify white matter structures intersected by surgical corridors and catheter tracks. Longitudinal diffusion tensor imaging (DTI) was performed to measure microstructural integrity changes in cerebral white matter. Fractional anisotropy (FA) derived from DTI was statistically analyzed for 51more » atlas-based white matter structures of the brain to determine radiation dose effect. FA in surgery-affected regions in the corpus callosum was compared to that in its intact counterpart to determine whether surgical defects affect radiation dose effect. Results: Surgical defects were seen most frequently in the corpus callosum because of transcallosal resection of tumors and insertion of ventricular or cyst catheters. Longitudinal DTI data indicated reductions in FA 3 months after therapy, which was followed by a recovery in most white matter structures. A greater FA reduction was correlated with a higher radiation dose in 20 white matter structures, indicating a radiation dose effect. The average FA in the surgery-affected regions before proton therapy was smaller (P=.0001) than that in their non–surgery-affected counterparts with more intensified subsequent reduction of FA (P=.0083) after therapy, suggesting that surgery accentuated the radiation dose effect. Conclusions: DTI data suggest that mild radiation dose effects occur in patients with craniopharyngioma receiving surgery and proton therapy. Surgical defects present at the time of proton therapy appear to accentuate the radiation dose effect longitudinally. This study supports consideration of pre-existing surgical defects and their locations in proton therapy planning and studies of treatment effect.« less

Evaluation of an every-other-day palonosetron schedule to control emesis in multiple-day high-dose chemotherapy.

PubMed

Mirabile, Aurora; Celio, Luigi; Magni, Michele; Bonizzoni, Erminio; Gianni, Alessandro Massimo; Di Nicola, Massimo

2014-12-01

Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.

Effect of image-guided hypofractionated stereotactic radiotherapy on peripheral non-small-cell lung cancer

PubMed Central

Wang, Shu-wen; Ren, Juan; Yan, Yan-li; Xue, Chao-fan; Tan, Li; Ma, Xiao-wei

2016-01-01

The objective of this study was to compare the effects of image-guided hypofractionated radiotherapy and conventional fractionated radiotherapy on non-small-cell lung cancer (NSCLC). Fifty stage- and age-matched cases with NSCLC were randomly divided into two groups (A and B). There were 23 cases in group A and 27 cases in group B. Image-guided radiotherapy (IGRT) and stereotactic radiotherapy were conjugately applied to the patients in group A. Group A patients underwent hypofractionated radiotherapy (6–8 Gy/time) three times per week, with a total dose of 64–66 Gy; group B received conventional fractionated radiotherapy, with a total dose of 68–70 Gy five times per week. In group A, 1-year and 2-year local failure survival rate and 1-year local failure-free survival rate were significantly higher than in group B (P<0.05). The local failure rate (P<0.05) and distant metastasis rate (P>0.05) were lower in group A than in group B. The overall survival rate of group A was significantly higher than that of group B (P=0.03), and the survival rate at 1 year was 87% vs 63%, (P<0.05). The median survival time of group A was longer than that of group B. There was no significant difference in the incidence of complications between the two groups (P>0.05). Compared with conventional fractionated radiation therapy, image-guided hypofractionated stereotactic radiotherapy in NSCLC received better treatment efficacy and showed good tolerability. PMID:27574441

Long-term outcome for immune suppression and immune related lymphoproliferative disorder: prospective data from the United Kingdom Children's Leukaemia and Cancer Group registry 1994-2004.

PubMed

Taj, Mary M; Hadzic, Nedim; Height, Susan E; Wotherspoon, Andrew; Burke, Margaret; Hobson, Rachel; Viskaduraki, Maria; Pinkerton, C Ross

2012-05-01

Prospective national registry data on 98 patients were studied to determine the long-term outcome of immune related lymphoproliferative disease (LPD) and define prognostic factors. Seventy-three developed LPD following organ transplant (26 liver, 21 heart, 15 kidney, nine bone marrow [BM], two bowel). Twenty-five had non-transplant related immunosuppression. Age was 1.1-17 years (median 8.6). Fifty-eight patients had lymphomatous, 21 systemic and 17 lymphadenopathic disease. Sixty (73%) were disseminated and 22 (27%) localized. Thirty-three (54%) were monoclonal. Seventy-three (83%) were Epstein-Barr virus (EBV) positive. Median follow-up was 7.6 years. LPD developed earlier after liver and BM as compared to heart or kidney transplant. Five-year overall survival (OS) was 58%. Prognosis was best after liver and kidney transplant (OS >77%). Mortality was higher following heart (2.5 times) and BM transplant (5 times). Adverse prognostic factors were disseminated or lymphomatous disease and lack of reduction of immunosuppression. With appropriate reduction of immunosuppression, rituximab and low-dose chemotherapy, long-term survival is high.

Initial effects from re-introducing fire in Alabama montane longleaf stands: fifty years since last burn

Treesearch

Sharon M. Hermann; John S. Kush

2010-01-01

In 2006, after more than fifty years with no burns, the National Park Service reintroduced fire in montane longleaf pine stands at Horseshoe Bend National Military Park in central AL. Residual longleaf pine stands indicates that this tree once dominated many slopes. The prolonged period of fire exclusion resulted in accumulation of duff and litter that exceeds 4 to 5...

Effectiveness of an organized bowel management program in the management of severe chronic constipation in children.

PubMed

Russell, Katie W; Barnhart, Douglas C; Zobell, Sarah; Scaife, Eric R; Rollins, Michael D

2015-03-01

Chronic constipation is a common problem in children. The cause of constipation is often idiopathic, when no anatomic or physiologic etiology can be identified. In severe cases, low dose laxatives, stool softeners and small volume enemas are ineffective. The purpose of this study was to assess the effectiveness of a structured bowel management program in these children. We retrospectively reviewed children with chronic constipation without a history of anorectal malformation, Hirschsprung's disease or other anatomical lesions seen in our pediatric colorectal center. Our bowel management program consists of an intensive week where treatment is assessed and tailored based on clinical response and daily radiographs. Once a successful treatment plan is established, children are followed longitudinally. The number of patients requiring hospital admission during the year prior to and year after initiation of bowel management was compared using Fisher's exact test. Forty-four children with refractory constipation have been followed in our colorectal center for greater than a year. Fifty percent had at least one hospitalization the year prior to treatment for obstructive symptoms. Children were treated with either high-dose laxatives starting at 2mg/kg of senna or enemas starting at 20ml/kg of normal saline. Treatment regimens were adjusted based on response to therapy. The admission rate one-year after enrollment was 9% including both adherent and nonadherent patients. This represents an 82% reduction in hospital admissions (p<0.001). Implementation of a structured bowel management program similar to that used for children with anorectal malformations, is effective and reduces hospital admissions in children with severe chronic constipation. Copyright © 2015 Elsevier Inc. All rights reserved.

The combined approach to lysis utilizing eptifibatide and rt-PA in acute ischemic stroke: the CLEAR stroke trial.

PubMed

Pancioli, Arthur M; Broderick, Joseph; Brott, Thomas; Tomsick, Thomas; Khoury, Jane; Bean, Judy; del Zoppo, Gregory; Kleindorfer, Dawn; Woo, Daniel; Khatri, Pooja; Castaldo, John; Frey, James; Gebel, James; Kasner, Scott; Kidwell, Chelsea; Kwiatkowski, Thomas; Libman, Richard; Mackenzie, Richard; Scott, Phillip; Starkman, Sidney; Thurman, R Jason

2008-12-01

Multiple approaches are being studied to enhance the rate of thrombolysis for acute ischemic stroke. Treatment of myocardial infarction with a combination of a reduced-dose fibrinolytic agent and a glycoprotein (GP) IIb/IIIa receptor antagonist has been shown to improve the rate of recanalization versus fibrinolysis alone. The combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator (rt-PA) (CLEAR) stroke trial assessed the safety of treating acute ischemic stroke patients within 3 hours of symptom onset with this combination. The CLEAR trial was a National Institutes of Health/National Institute of Neurological Disorders and Stroke-funded multicenter, double-blind, randomized, dose-escalation and safety study. Patients were randomized 3:1 to either low-dose rt-PA (tier 1=0.3 mg/kg, tier 2=0.45 mg/kg) plus eptifibatide (75 microg/kg bolus followed by 0.75 microg/kg per min infusion for 2 hours) or standard-dose rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracerebral hemorrhage within 36 hours. Secondary analyses were performed regarding clinical efficacy. Ninety-four patients (40 in tier 1 and 54 in tier 2) were enrolled. The combination group of the 2 dose tiers (n=69) had a median age of 71 years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 14, and the standard-dose rt-PA group (n=25) had a median age of 61 years and a median baseline NIHSS score of 10 (P=0.01 for NIHSS score). Fifty-two (75%) of the combination treatment group and 24 (96%) of the standard treatment group had a baseline modified Rankin scale score of 0 (P=0.04). There was 1 (1.4%; 95% CI, 0% to 4.3%) symptomatic intracranial hemorrhage in the combination group and 2 (8.0%; 95% CI, 0% to 19.2%) in the rt-PA-only arm (P=0.17). During randomization in tier 2, a review by the independent data safety monitoring board demonstrated that the safety profile of combination therapy at the tier 2 doses was such that further enrollment was statistically unlikely to indicate inadequate safety for the combination treatment group, the ultimate outcome of the study. Thus, the study was halted. There was a trend toward increased clinical efficacy of standard-dose rt-PA compared with the combination treatment group. The safety of the combination of reduced-dose rt-PA plus eptifibatide justifies further dose-ranging trials in acute ischemic stroke.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, David W., E-mail: David.Chang@petermac.org; Marvelde, Luc te; Chua, Boon H.

Purpose: To report the local recurrence rate and late toxicity of intraoperative radiation therapy (IORT) boost to the tumor bed using the Intrabeam System followed by external-beam whole-breast irradiation (WBI) in women with early-stage breast cancer in a prospective single-institution study. Methods and Materials: Women with breast cancer ≤3 cm were recruited between February 2003 and May 2005. After breast-conserving surgery, a single dose of 5 Gy IORT boost was delivered using 50-kV x-rays to a depth of 10 mm from the applicator surface. This was followed by WBI to a total dose of 50 Gy in 25 fractions. Patientsmore » were reviewed at regular, predefined intervals. Late toxicities were recorded using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring systems. Results: Fifty-five patients completed both IORT boost and external-beam WBI. Median follow-up was 3.3 years (range, 1.4-4.1 years). There was no reported locoregional recurrence or death. One patient developed distant metastases. Grade 2 and 3 subcutaneous fibrosis was detected in 29 (53%) and 8 patients (15%), respectively. Conclusions: The use of IORT as a tumor bed boost using kV x-rays in breast-conserving therapy was associated with good local control but a clinically significant rate of grade 2 and 3 subcutaneous fibrosis.« less

1961-2011: Fifty years of Hayashi tracks

NASA Astrophysics Data System (ADS)

Palla, Francesco

2012-09-01

Fifty years after the seminal paper by Prof. C. Hayashi, the field of pre-main sequence (PMS) evolution still plays a fundamental role in observational and theoretical astrophysics. In this contribution, I highlight the contribution made by Hayashi in establishing the theoretical foundation of early stellar evolution. Then, I discuss the changes of the classical theory introduced by the inclusion of protostellar evolution in PMS models and present selected results on young stars.

Fifty Years of Learning: A History of Adult & Community Education in Aotearoa from the 1960s to the Present Day

ERIC Educational Resources Information Center

Tobias, Robert Michael

2016-01-01

This monograph aims to provide a brief but critical history of adult and community education in Aotearoa over the past fifty years. It draws on primary and secondary sources as well as a substantial body of previous research much of which has yet to be published. The focus of this work is on changing policy environments and their impact on adult…

L'etat, c'est moi. Fifty years of history and philosophy of evolutionary biology.

PubMed

Ruse, Michael

2016-01-01

I reflect on my fifty-year history as a philosopher of biology, showing how it has taken me from rather narrow analytic studies, through the history of ideas, and now on to issues to do with science and religion. I argue that moral concerns were and still are a major motivation behind what I do and write. Copyright: © 2016 by Fabrizio Serra editore, Pisa · Roma.

Human space exploration the next fifty years.

PubMed

Williams, David R; Turnock, Matthew

2011-06-01

Preparation for the fiftieth anniversary of human spaceflight in the spring of 2011 provides the space faring nations with an opportunity to reflect on past achievements as well as consider the next fifty years of human spaceflight. The International Space Station is a unique platform for long duration life science research that will play a critical role in preparing for future human space exploration beyond low earth orbit. Some feel the future path back to the Moon and on to Mars may be delayed with the current commitment of the United States to support the development of human-rated commercial spacecraft. Others see this as a unique opportunity to leverage the capability of the private sector in expanding access to space exploration. This article provides an overview of the past achievements in human spaceflight and discusses future missions over the next fifty years and the role space medicine will play in extending the time-distance constant of human space exploration.

Coenzyme Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy.

PubMed

Cooper, J M; Korlipara, L V P; Hart, P E; Bradley, J L; Schapira, A H V

2008-12-01

A pilot study of high dose coenzyme Q(10) (CoQ(10))/vitamin E therapy in Friedreich's ataxia (FRDA) patients resulted in significant clinical improvements in most patients. This study investigated the potential for this treatment to modify clinical progression in FRDA in a randomized double blind trial. Fifty FRDA patients were randomly divided into high or low dose CoQ(10)/ vitamin E groups. The change in International Co-operative Ataxia Ratings Scale (ICARS) was assessed over 2 years as the primary end-point. A post hoc analysis was made using cross-sectional data. At baseline serum CoQ(10) and vitamin E levels were significantly decreased in the FRDA patients (P < 0.001). During the trial CoQ(10) and vitamin E levels significantly increased in both groups (P < 0.01). The primary and secondary end-points were not significantly different between the therapy groups. When compared to cross-sectional data 49% of all patients demonstrated improved ICARS scores. This responder group had significantly lower baseline serum CoQ(10) levels. A high proportion of FRDA patients have a decreased serum CoQ(10) level which was the best predictor of a positive clinical response to CoQ(10)/vitamin E therapy. Low and high dose CoQ(10)/vitamin E therapies were equally effective in improving ICARS scores.

Nasopharyngeal Pneumococcal Colonization and Impact of a Single Dose of 13-Valent Pneumococcal Conjugate Vaccine in Indian Children With HIV and Their Unvaccinated Parents.

PubMed

Arya, Bikas K; Bhattacharya, Sangeeta Das; Sutcliffe, Catherine G; Ganaie, Feroze; Bhaskar, Arun; Bhattacharyya, Subhasish; Niyogi, Swapan Kumar; Moss, William J; Panda, Samiran; Ravikumar, Kadahalli Lingegowda; Das, Ranjan Saurav; Mandal, Sutapa

2018-05-01

Human immunodeficiency virus (HIV) infection increases risk of invasive disease from Streptococcus pneumoniae. Pneumococcal conjugate vaccines (PCV) prevent invasive disease and acquisition of vaccine type (VT) pneumococcus in the nasopharynx. To look at the safety and impact of one dose of PCV13 on acquisition of VT pneumococcal carriage in Indian children with HIV. We conducted a cohort study in families of HIV-infected children (CLH) and families of HIV-uninfected children (HUC) in West Bengal. All children received one dose of PCV13. Nasopharyngeal swabs were collected from children and parents at baseline and 2 months after vaccination. One hundred and fifteen CLH and 47 HUC received one dose of PCV13. Fifty-eight percent of CLH were on antiretroviral therapy (ART), and the median nadir CD4 count was 287. There were no significant adverse events in either group. HUC had more VT colonization than CLH-55% versus 23% of all pneumococcal isolates. HIV infection doubled the risk of nonvaccine serotype colonization (P = 0.03). There was no difference in acquisition of VT isolates in CLH (4.4%) and HUC (4.5%) post-PCV13; however, older CLH (>5 years) had decreased clearance of VT strains. ART made no difference in pneumococcal colonization at baseline or after PCV13; however, CLH with higher nadir CD4 counts before starting ART were less likely to have VT colonization post-PCV13 (prevalence ratio, 0.2; 95% confidence interval: 0.1-0.5). While there was no difference in acquisition of VT nasopharyngeal carriage of pneumococcus in CLH and HUC after one dose of PCV13, earlier access to ART may impact response to PCV13 in CLH.

Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial†

PubMed Central

Skorupski, K. A.; Uhl, J. M.; Szivek, A; Allstadt Frazier, S. D.; Rebhun, R. B.; Rodriguez, C. O.

2016-01-01

Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. PMID:24118677

Higher Dose Imatinib for Children With De Novo Chronic Phase Chronic Myelogenous Leukemia: A Report From the Children’s Oncology Group

PubMed Central

Champagne, Martin A.; Fu, Cecilia H.; Chang, Myron; Chen, Helen; Gerbing, Robert B.; Alonzo, Todd A.; Cooley, Linda D.; Heerema, Nyla A.; Oehler, Vivian; Wood, Charlotte; French, Mary Ellen; Arceci, Robert J.; Smith, Franklin O.; Bernstein, Mark L.

2016-01-01

Purpose To determine the efficacy of imatinib in children with newly diagnosed chronic phase (CP) chronic myelogenous leukemia (CML). Methods This was an open label, multi-center phase II clinical trial. Courses were defined as consecutive 28-day intervals. Oral imatinib was administered daily at 340 mg/m2 without interruption in the absence of toxicity. Results Fifty-one children received 978 28-day courses of imatinib. The most common toxicities encountered were hematologic. Forty-one patients (80%) achieved a complete hematologic response by the end of course 2. Nineteen children (38%) obtained a complete cytogenetic response (CCyR) at the end of course 3. Overall, 72% achieved CCyR at a median time of 5.6 months. The rate of complete molecular response (>3 log reduction) was 27%. Progression-free and overall survival at 3 years were 72% ± 6.4% and 92% ± 3.9%, respectively. Conclusions Daily oral imatinib at a dose of 340 mg/m2 is well tolerated in children. In addition, imatinib therapy is effective in inducing a high percent of hematologic, cytogenetic and molecular responses, comparable to adults with CML. PMID:21465636

Kawasaki disease in Sicily: clinical description and markers of disease severity.

PubMed

Maggio, Maria Cristina; Corsello, Giovanni; Prinzi, Eugenia; Cimaz, Rolando

2016-11-02

Kawasaki disease (KD) is an acute systemic vasculitis of small and middle size arteries; 15-25 % of untreated patients and 5 % of patients treated with intravenous immunoglobulin (IVIG) develop coronary artery lesions (CAL). Many studies tried to find the most effective treatment in the management of resistant KD and to select the risk factors for CAL. Our data are assessed on children from west Sicily, characterized by a genetic heterogeneity. We studied the clinical data of 70 KD Sicilian children (36 males: 51 %; 34 females: 49 %), analysed retrospectively, including: demographic and laboratory parameters; echocardiographic findings at diagnosis, at 2, 6 and 8 weeks, and at 1 year after the onset of the illness. Forty-seven had Typical KD, three Atypical KD and twenty Incomplete KD. Age at the disease onset ranged from 0.1 to 8.9 years. IVIG were administered 5 ± 2 days after the fever started. Defervescence occurred 39 ± 26 hours after the first IVIG infusion. Fifty-six patients (80 %) received 1 dose of IVIG (responders); 14 patients (20 %) had a resistant KD, with persistent fever after the first IVIG dose (non responders). Ten (14 %) non responders responded to the second dose, 4 (5 %) responded to three doses; one needed treatment with high doses of steroids and Infliximab. Cardiac involvement was documented in twenty-two cases (eighteen with transient dilatation/ectasia, fifteen with aneurysms). Pericardial effusion, documented in eleven, was associated with coronaritis and aneurysms, and was present earlier than coronary involvement in seven. Hypoalbuminemia, D-dimer pre-IVIG, gamma-GT pre-IVIG showed a statistically significant direct correlation with IVIG doses, highlighting the role of these parameters as predictor markers of refractory disease. The persistence of elevated CRP, AST, ALT levels, a persistent hyponatremia and hypoalbuminemia after IVIG therapy, also had a statistical significant correlation with IVIG doses. Non responders showed higher levels of D-dimer and gamma-GT pre-IVIG, persistent high levels of D-dimer, CRP, AST, ALT, hypoalbuminemia and hyponatremia after IVIG. This is the first study on KD in Sicily. We suggest some laboratory parameters as predictive criteria for resistant KD. Patients who show early pericarditis need careful surveillance for coronary lesions.

The Fifty-Year-Old Woman and Midlife Stress.

ERIC Educational Resources Information Center

Campbell, Shirley

1984-01-01

Suggests that women in their fifties are susceptible to many stresses. The possibilities of widowhood, divorce, or poverty, combined with intra- and interpersonal strains, make this a time of insecurity about aging for many women. Some suggestions as to why women nonetheless cope successfully with aging are considered. (Author/JAC)

Current Dosing Paradigm for Stereotactic Radiosurgery Alone After Surgical Resection of Brain Metastases Needs to Be Optimized for Improved Local Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prabhu, Roshan; Shu, Hui-Kuo; Winship Cancer Institute, Emory University, Atlanta, GA

2012-05-01

Purpose: To describe the use of radiosurgery (RS) alone to the resection cavity after resection of brain metastases as an alternative to adjuvant whole-brain radiotherapy (WBRT). Methods and Materials: Sixty-two patients with 64 cavities were treated with linear accelerator-based RS alone to the resection cavity after surgical removal of brain metastases between March 2007 and August 2010. Fifty-two patients (81%) had a gross total resection. Median cavity volume was 8.5 cm{sup 3}. Forty-four patients (71%) had a single metastasis. Median marginal and maximum doses were 18 Gy and 20.4 Gy, respectively. Sixty-one cavities (95%) had gross tumor volume to planningmore » target volume expansion of {>=}1 mm. Results: Six-month and 1-year actuarial local recurrence rates were 14% and 22%, respectively, with a median follow-up period of 9.7 months. Six-month and 1-year actuarial distant brain recurrence, total intracranial recurrence, and freedom from WBRT rates were 31% and 51%, 41% and 63%, and 91% and 74%, respectively. The symptomatic cavity radiation necrosis rate was 8%, with 2 patients (3%) undergoing surgery. Of the 11 local failures, 8 were in-field, 1 was marginal, and 2 were both (defined as in-field if {>=}90% of recurrence within the prescription isodose and marginal if {>=}90% outside of the prescription isodose). Conclusions: The high rate of in-field cavity failure suggests that geographic misses with highly conformal RS are not a major contributor to local recurrence. The current dosing regimen derived from Radiation Therapy Oncology Group protocol 90-05 should be optimized in this patient population before any direct comparison with WBRT.« less

The efficacy of concurrent cisplatin and 5-flurouracil chemotherapy and radiation therapy for locally advanced cancer of the uterine cervix

PubMed Central

Choi, Il Jung; Park, Eunku Seul; Han, Myung Seok; Choi, Youngmin; Je, Goo Hwa; Kim, Hyun Ho

2008-01-01

Objective To evaluate the efficacy of concurrent chemoradiation (CCRT) using 5-flurouracil (5-FU) and cisplatin for locally advanced cervical cancer. Methods We reviewed the medical records of 57 patients with locally advanced cervical cancer (stage IIB-IVA and bulky IB2-IIA tumor) who underwent the CCRT at Dong-A University Hospital from January 1997 to June 2007. The CCRT consisted of 5-FU, cisplatin and pelvic radiation. Every three weeks, 75 mg/m2 cisplatin was administered on the first day of each cycle and 5-FU was infused at the dose of 1,000 mg/m2/d from the second day to the fifth day of each cycle. Radiation was administered to the pelvis at a daily dose of 1.8 Gy for five days per week until a medium accumulated dose reached to 50.4 Gy. If necessary, the radiation field was extended to include paraaortic lymph nodes. Consolidation chemotherapy was performed using 5-FU and cisplatin. Results Fifty-seven patients were enrolled and the median follow-up duration was 53 months (range 7-120 months). The overall response rate was 91.5% (74% complete response and 17.5% partial response). The 5-year overall survival and 3-year progression free survival rates were 69.4% and 74.9%, respectively. During the follow-up period (median 23 months, range 7-60 months), fourteen patients were diagnosed as recurrent disease. Conclusion CCRT with 5-FU and cisplatin which is the primary treatment for patients with locally advanced cervical cancer was effective and well tolerated. PMID:19471554

Safety and effectiveness of long-term growth hormone therapy in Japanese patients with adult growth hormone deficiency: a postmarketing, multicenter, observational study.

PubMed

Shimatsu, Akira; Ishii, Hitoshi; Nishinaga, Hiromi; Murai, Osamu; Chihara, Kazuo

2017-07-28

We aimed to evaluate the long-term safety and effectiveness of growth hormone (GH) therapy in Japanese patients with adult growth hormone deficiency (AGHD). In this observational, multicenter study, Norditropin ® (Novo Nordisk A/S, Bagsvaerd, Denmark) was administered as injections of 0.021 mg/kg/week as a starting dose divided into 6-7 doses/week. The dose was increased according to clinical response. Patients' data were obtained from medical records. Measurements (lipids, glucose metabolism, and body composition) taken at baseline; 3, 6, and 12 months; and yearly until the end of the study were collected. Adverse drug reactions (ADRs), serious ADRs, and serious adverse events (SAEs) were evaluated. Of 387 registered patients, 334 were eligible for safety. After GH treatment initiation, a marked decrease in total cholesterol was observed earlier in the child-onset group than in the adult-onset group. LDL-cholesterol also decreased, but no significant differences in changes in LDL-cholesterol between adult-onset and child-onset groups were found. A significant increase in HDL-cholesterol starting 1 year after GH treatment initiation was found in the adult-onset group. There was no effect of GH treatment on glucose metabolism. Because of the small number of dual-energy X-ray absorptiometry data, the overall assessment of changes of body composition was difficult. Fifty-six (16.8%), 12 (3.6%), and 35 (10.5%) patients experienced ADRs, serious ADRs, and SAEs, respectively. This study demonstrated a favorable long-term safety and effectiveness profile of GH therapy in AGHD patients in the real-life Japanese clinical practice setting.

HYDROCORTISONE THERAPY AND GROWTH TRAJECTORY IN CHILDREN WITH CLASSICAL CONGENITAL ADRENAL HYPERPLASIA.

PubMed

Bizzarri, Carla; Improda, Nicola; Maggioli, Chiara; Capalbo, Donatella; Roma, Silvia; Porzio, Ottavia; Salerno, Mariacarolina; Cappa, Marco

2017-05-01

Poor linear growth is one of the main concerns in children with congenital adrenal hyperplasia (CAH). We aimed to analyze factors affecting growth trajectory in children with classical CAH. Clinical records of children followed from infancy up to the end of growth at two Italian tertiary referral hospitals were reviewed. Fifty-seven patients (31 males), treated with hydrocortisone and fludrocortisone only, were included. Clinical observations were divided into three groups: 0 to 2 years, 172 observations; from 2 years to puberty onset, 813 observations; after puberty onset, 527 observations. Height velocity, pubertal growth spurt, and final height were evaluated as outcomes. Final height standard deviation score (SDS) was lower than target height SDS (-0.74 ± 1.1 versus -0.31 ± 1.01; P<.001). Target-adjusted final height SDS was -0.44 ± 1.8 in males and -0.13 ± 1.1 in females (P = .001). Total pubertal growth was 21.9 ± 7.3 cm in males and 19.2 ± 8.2 cm in females (P = .19). Hydrocortisone dose increased and height-velocity SDS decreased during puberty. At multivariable analysis, height-velocity SDS was adversely affected by hydrocortisone dose (P = .038) and directly related to adrenocorticotropic hormone (ACTH) levels (P = .023). Target-adjusted final-height SDS was adversely affected by hydrocortisone dose (P<.001) and positively related to mineralocorticoid therapy (P = .001) and ACTH levels (P = .02). Total pubertal growth (cm) was positively related to ACTH levels (P = .01). Height outcome of CAH patients is now better than previously reported. During puberty, the lowest effective dose of hydrocortisone should be used to optimize pubertal growth spurt and final height. 17-OHP = 17-alpha-hydroxyprogesterone ACTH = adrenocorticotropic hormone BMI = body mass index CAH = congenital adrenal hyperplasia GH = growth hormone HPA = hypothalamus-pituitary-adrenal PRA = plasma renin activity SDS = standard deviation score SV = simple virilizing SW = salt-wasting.

Assessment of olfactory threshold in patients undergoing radiotherapy for head and neck malignancies.

PubMed

Jalali, Mir Mohammad; Gerami, Hooshang; Rahimi, Abbas; Jafari, Manizheh

2014-10-01

Radiotherapy is a common treatment modality for patients with head and neck malignancies. As the nose lies within the field of radiotherapy of the head and neck, the olfactory fibers and olfactory receptors may be affected by radiation. The aim of this study was to evaluate changes in olfactory threshold in patients with head and neck malignancies who have received radiation to the head and neck. The olfactory threshold of patients with head and neck malignancies was assessed prospectively before radiation therapy and serially for up to 6 months after radiotherapy using sniff bottles. In vivo dosimetry was performed using 82 LiF (MCP) chips and a thermoluminescent dosimeter (TLD) system. Sixty-one patients were recruited before radiotherapy was commenced. Seven patients did not return for evaluation after radiation. Fifty-four patients were available for follow-up assessment (28 women, 26 men; age, 22-86 years; median, 49 years). Total radiation dose was 50.1 Gy (range, 30-66 Gy). Mean olfactory threshold scores were found to deteriorate significantly at various timepoints after radiotherapy (11.7 before radiotherapy versus 4.0 at Month 6, general linear model, P<0.0001). With in vivo dosimetry, we found that the median measured dose to the olfactory area was 334 µC. We also identified a cutoff point according to the dose to the olfactory epithelium. Olfactory threshold was significantly decreased 2-6 weeks after initiation of therapy, with cumulative local radiation >135 µC (Mann-Whitney U test, P=0.01). Deterioration in olfactory threshold scores was found at 6 months after initiation of radiation therapy. Provided that these results are reproducible, an evaluation of olfactory functioning in patients with head and neck malignancies using in vivo dosimetry may be useful for determining the optimal dose for patients treated with conformal radiotherapy techniques while avoiding the side effects of radiation.

Retreatment with interferon plus ribavirin of chronic hepatitis C non-responders to interferon monotherapy: a meta-analysis of individual patient data

PubMed Central

Cammà, C; Bruno, S; Schepis, F; Lo Iacono, O; Andreone, P; Gramenzi, A G; Mangia, A; Andriulli, A; Puoti, M; Spadaro, A; Freni, M; Di Marco, V; Cino, L; Saracco, G; Chiesa, A; Crosignani, A; Caporaso, N; Morisco, F; Rumi, M G; Craxì, A

2002-01-01

Background and aims: Retreatment with a combination of α interferon (IFN) plus ribavirin of patients with chronic hepatitis C who did not respond to IFN monotherapy has not been assessed in large controlled studies. Methods: To assess the effectiveness and tolerability of IFN/ribavirin retreatment of non-responders to IFN and to identify predictors of complete (biochemical and virological) sustained response, we performed a meta-analysis of individual data on 581 patients from 10 centres. Retreatment with various IFN schedules (mean total dose 544 mega units) and a fixed ribavirin dose (1000–1200 mg/daily depending on body weight) was given for 24–60 (mean 39.5) weeks. Results: Biochemical end of treatment and sustained responses were observed in 271/581 (46.6%; 95% confidence interval (CI) 42.6–50.7%) and in 109/581 (18.7%; 95% CI 15.6–22.0%) cases, respectively. Two hundred and six of 532 patients (38.7%; 95% CI 34.6–42.9%) had an end of treatment complete response to retreatment while a complete sustained response occurred in 88 of 559 (15.7%; 95% CI 12.8–18.8%). Fifty four of 581 patients (9.2%; 95% CI 7.0–11.7%) stopped retreatment due to adverse effects. By logistic regression, complete sustained response was predicted independently by age <45 years (p=0.04), by normal pretreatment γ-glutamyltransferase levels (p=0.01), and by a second course total IFN dose of at least 432 mega units (p=0.008). Conclusions: The overall low probability of effectiveness argues against indiscriminate retreatment of all IFN monotherapy non-responders with IFN/ribavirin. Patients less than 45 years old with normal γ-glutamyltransferase levels who were retreated with high dose long course combination therapy had a complete sustained response rate of 30%. PMID:12427791

Optimization of initial propofol bolus dose for EEG Narcotrend Index-guided transition from sevoflurane induction to intravenous anesthesia in children.

PubMed

Dennhardt, Nils; Boethig, Dietmar; Beck, Christiane; Heiderich, Sebastian; Boehne, Martin; Leffler, Andreas; Schultz, Barbara; Sümpelmann, Robert

2017-04-01

Sevoflurane induction followed by intravenous anesthesia is a widely used technique to combine the benefits of an easier and less traumatic venipuncture after sevoflurane inhalation with a recovery with less agitation, nausea, and vomiting after total intravenous anesthesia (TIVA). Combination of two different anesthetics may lead to unwanted burst suppression in the electroencephalogram (EEG) during the transition phase. The objective of this prospective clinical observational study was to identify the optimal initial propofol bolus dose for a smooth transition from sevoflurane induction to TIVA using the EEG Narcotrend Index (NI). Fifty children aged 1-8 years scheduled for elective pediatric surgery were studied. After sevoflurane induction and establishing of an intravenous access, a propofol bolus dose range 0-5 mg·kg -1 was administered at the attending anesthetist's discretion to maintain a NI between 20 and 64, and sevoflurane was stopped. Anesthesia was continued as TIVA with a propofol infusion dose of 15 mg·kg -1 ·h -1 for the first 15 min, followed by stepwise reduction according to McFarlan's pediatric infusion regime, and remifentanil 0.25 μg·kg -1 ·min -1 . Endtidal concentration of sevoflurane, NI, and hemodynamic data were recorded during the whole study period using a standardized case report form. Propofol plasma concentrations were calculated using the paedfusor dataset and a TIVA simulation program. Median endtidal concentration of sevoflurane at the time of administration of the propofol bolus was 5.1 [IQR 4.7-5.9] Vol%. The median propofol bolus dose was 1.2 [IQR 0.9-2.5] mg·kg -1 and median NI thereafter was 33 [IQR 23-40]. Nine children presented with a NI 13-20 and three children with burst suppression in the EEG (NI 0-12); all of them received an initial propofol bolus dose >2 mg·kg -1 . Regression equation demonstrated that NI 20-64 was achieved with a 95% probability when using a propofol bolus dose of 1 mg·kg -1 after sevoflurane induction. Decrease in mean arterial blood pressure correlated significantly with propofol bolus dose (P = 0.038). After 25 min of TIVA, children younger than 2 years had a higher NI (median difference 14.0, 95%CI: 6.0-20.0, P = 0.001), higher deviations from the expected Narcotend Index (median difference 4.1, 95%CI: 3.9-4.2, P < 0.001) and lower calculated propofol plasma concentrations (median difference 0.2 μg·ml -1 , 95% CI: 0.1-0.3 μg·ml -1 , P < 0.001) than older children. After sevoflurane induction, a reduced propofol bolus dose of 1 mg·kg -1 followed by TIVA according to McFarlan's regime resulted in a NI within the recommended range in children aged 1-8 years. During the course of TIVA, children younger than 2 years displayed higher NI values and more pronounced interindividual variation. Processed EEG monitoring is recommended to find adequate individual age-dependent doses. © 2017 John Wiley & Sons Ltd.

Patient and Regimen Characteristics Associated with Self-Reported Nonadherence to Antiretroviral Therapy

PubMed Central

Sullivan, Patrick S.; Campsmith, Michael L.; Nakamura, Glenn V.; Begley, Elin B.; Schulden, Jeffrey; Nakashima, Allyn K.

2007-01-01

Background Nonadherence to antiretroviral therapy (ARVT) is an important behavioral determinant of the success of ARVT. Nonadherence may lead to virological failure, and increases the risk of development of drug resistance. Understanding the prevalence of nonadherence and associated factors is important to inform secondary HIV prevention efforts. Methodology/Principal Findings We used data from a cross-sectional interview study of persons with HIV conducted in 18 U.S. states from 2000–2004. We calculated the proportion of nonadherent respondents (took <95% of prescribed doses in the past 48 hours), and the proportion of doses missed. We used multivariate logistic regression to describe factors associated with nonadherence. Nine hundred and fifty-eight (16%) of 5,887 respondents reported nonadherence. Nonadherence was significantly (p<0.05) associated with black race and Hispanic ethnicity; age <40 years; alcohol or crack use in the prior 12 months; being prescribed ≥4 medications; living in a shelter or on the street; and feeling “blue” ≥14 of the past 30 days. We found weaker associations with having both male-male sex and injection drug use risks for HIV acquisition; being prescribed ARVT for ≥21 months; and being prescribed a protease inhibitor (PI)-based regimen not boosted with ritonavir. The median proportion of doses missed was 50%. The most common reasons for missing doses were forgetting and side effects. Conclusions/Significance Self-reported recent nonadherence was high in our study. Our data support increased emphasis on adherence in clinical settings, and additional research on how providers and patients can overcome barriers to adherence. PMID:17579723

The standard treatment protocol for paracetamol poisoning may be inadequate following overdose with modified release formulation: a pharmacokinetic and clinical analysis of 53 cases.

PubMed

Salmonson, Heléne; Sjöberg, Gunilla; Brogren, Jacob

2018-01-01

The use of the standard procedure for managing overdoses with immediate release (IR) paracetamol is questionable when applied to overdoses with modified release (MR) formulations. This study describes the pharmacokinetics of paracetamol and the clinical outcomes following overdoses with a MR formulation. Medical records including laboratory analyses concerning overdoses of MR paracetamol from 2009 to 2015 were collected retrospectively. Inclusion criteria were ingestion of a toxic dose, known time of intake and documented measurements of serum paracetamol and liver function tests. Graphical analysis, descriptive statistics and population pharmacokinetic modelling were used to describe data. Fifty-three cases were identified. Median age was 26 years (range 13-68), median dose was 20 g (range 10-166) and 74% were females. The pharmacokinetic analysis showed a complex, dose dependent serum versus time profile with prolonged absorption and delayed serum peak concentrations with increasing dose. Ten patients had persistently high serum levels for 24 h or more, six of them had a second peak 8-19 h after ingestion. Seven of 34 patients receiving N-acetylcysteine (NAC) within 8 h had alanine aminotransferase (ALT) above reference range. Three of them developed hepatotoxicity (ALT >1000 IU/l). The pharmacokinetic and clinical analysis showed that the standard treatment protocol, including risk assessment and NAC regimen, used for IR paracetamol poisoning not appear suitable for MR formulation. Individual and tailored treatment may be valuable but further studies are warranted to determine optimal regimen of overdoses with MR formulation.

The effects of metformin in type 1 diabetes mellitus.

PubMed

Beysel, Selvihan; Unsal, Ilknur Ozturk; Kizilgul, Muhammed; Caliskan, Mustafa; Ucan, Bekir; Cakal, Erman

2018-01-16

This retrospective study investigated the effect of adding metformin to pharmacologic insulin dosing in type 1 diabetics on insulin therapy 1 year after treatment compared with patients on insulin therapy alone. Twenty-nine adults with type 1 diabetes who had metformin added to their insulin therapy for 12 months were compared with 29 adults with type 1 diabetes who remained on insulin-alone therapy. Fifty-eight patients with C peptide negative-type 1 diabetics (26 females, mean age: 29.01 ± 7.03 years, BMI: 24.18 ± 3.16 kg/m2) were analyzed. Age, sex, body weight, insulin dose requirement, plasma glucose (PG), blood pressure (BP), and lipids did not differ between groups before treatment (p > 0.05). Metabolic syndrome (44.8 vs 41.4%, p > 0.05) did not differ between the metformin-insulin and insulin alone groups before treatment. Metabolic syndrome was more decreased in the metformin-insulin group than in the insulin alone group after treatment (-8.9 ± 1.3 vs. 2.5 ± 0.6%, p = 0.028). Insulin dose requirement was lower in the metformin-insulin group than in the insulin alone group (-0.03 vs. 0.11 IU/kg/d, p = 0.006). Fasting PG (-26.9 ± 54.2 vs. 0.7 ± 29.5 mg/dL, p = 0.022) and postprandial PG (-43.1 ± 61.8 mg/dL vs. -3.1 ± 40.1 mg/dL, p = 0.010) was more decreased in the metformin-insulin group than in the insulin alone group. Body weight, lipids, and HbA1c did not differ between the groups (p > 0.05). Metformin decreased glucose concentrations, reduced metabolic syndrome, as well as insulin dose requirement more than insulin therapy alone, 1 year after treatment. These results were independent of blood lipid improvement or weight loss, although on average weight remained decreased with metformin-insulin therapy, whereas the average weight increased with insulin therapy alone.

A single-item self-report medication adherence question predicts hospitalisation and death in patients with heart failure.

PubMed

Wu, Jia-Rong; DeWalt, Darren A; Baker, David W; Schillinger, Dean; Ruo, Bernice; Bibbins-Domingo, Kristen; Macabasco-O'Connell, Aurelia; Holmes, George M; Broucksou, Kimberly A; Erman, Brian; Hawk, Victoria; Cene, Crystal W; Jones, Christine DeLong; Pignone, Michael

2014-09-01

To determine whether a single-item self-report medication adherence question predicts hospitalisation and death in patients with heart failure. Poor medication adherence is associated with increased morbidity and mortality. Having a simple means of identifying suboptimal medication adherence could help identify at-risk patients for interventions. We performed a prospective cohort study in 592 participants with heart failure within a four-site randomised trial. Self-report medication adherence was assessed at baseline using a single-item question: 'Over the past seven days, how many times did you miss a dose of any of your heart medication?' Participants who reported no missing doses were defined as fully adherent, and those missing more than one dose were considered less than fully adherent. The primary outcome was combined all-cause hospitalisation or death over one year and the secondary endpoint was heart failure hospitalisation. Outcomes were assessed with blinded chart reviews, and heart failure outcomes were determined by a blinded adjudication committee. We used negative binomial regression to examine the relationship between medication adherence and outcomes. Fifty-two percent of participants were 52% male, mean age was 61 years, and 31% were of New York Heart Association class III/IV at enrolment; 72% of participants reported full adherence to their heart medicine at baseline. Participants with full medication adherence had a lower rate of all-cause hospitalisation and death (0·71 events/year) compared with those with any nonadherence (0·86 events/year): adjusted-for-site incidence rate ratio was 0·83, fully adjusted incidence rate ratio 0·68. Incidence rate ratios were similar for heart failure hospitalisations. A single medication adherence question at baseline predicts hospitalisation and death over one year in heart failure patients. Medication adherence is associated with all-cause and heart failure-related hospitalisation and death in heart failure. It is important for clinicians to assess patients' medication adherence on a regular basis at their clinical follow-ups. © 2013 John Wiley & Sons Ltd.

A Long-Acting Human Growth Hormone With Delayed Clearance (VRS-317): Results of a Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Growth Hormone–Deficient Adults

PubMed Central

Yuen, Kevin C. J.; Conway, Gerard S.; Popovic, Vera; Merriam, George R.; Bailey, Timothy; Hamrahian, Amir H.; Biller, Beverly M. K.; Kipnes, Mark; Moore, Jerome A.; Humphriss, Eric; Cleland, Jeffrey L.

2013-01-01

Background: Administration of daily recombinant human GH (rhGH) poses a considerable challenge to patient compliance. Reduced dosing frequency may improve treatment adherence and potentially overall treatment outcomes. Objectives: This study assessed the safety and tolerability and the potential for achieving IGF-I levels within the target range in adults with GH deficiency after a single dose of the long-acting rhGH analog, VRS-317. Design: This was a randomized, double-blind, placebo-controlled, single ascending dose study. Patients: Fifty adults with growth hormone deficiency (mean age, 45 years) were studied in 5 treatment groups of 10 subjects each (8 active drug and 2 placebo). Setting: The study was conducted in 17 adult endocrinology centers in North America and Europe. Main Outcome Measures: Adverse events, laboratory safety assessments, and VRS-317 pharmacokinetics and pharmacodynamics (IGF-I and IGF binding protein-3) were analyzed. Results: At 0.80 mg/kg, VRS-317 had a mean terminal elimination half-life of 131 hours. Single VRS-317 doses of 0.05, 0.10, 0.20, 0.40, and 0.80 mg/kg (approximately equivalent to daily rhGH doses of 0.3–5.0 μg/kg over 30 d) safely increased the amplitude and duration of IGF-I responses in a dose-dependent manner. After a single 0.80 mg/kg dose, serum IGF-I was maintained in the normal range between −1.5 and 1.5 SD values for a mean of 3 weeks. No unexpected or serious adverse events were observed. Conclusions: The elimination half-life for VRS-317 is 30- to 60-fold longer and stimulates more durable IGF-I responses than previously studied rhGH products. Prolonged IGF-I responses do not come at the expense of overexposure to high IGF-I levels. The pharmacokinetics and pharmacodynamics combined with the observed safety profile indicate the potential for safe and effective monthly dosing. PMID:23585663

Scheduled versus Pro Re Nata Dosing in the VIEW Trials.

PubMed

Richard, Gisbert; Monés, Jordi; Wolf, Sebastian; Korobelnik, Jean François; Guymer, Robyn; Goldstein, Michaella; Norenberg, Christiane; Sandbrink, Rupert; Zeitz, Oliver

2015-12-01

To analyze visual acuity (VA) outcomes before and after preplanned treatment regimen change in the VIEW studies at week 52 (W52). Multiple post hoc analyses for retrospectively defined subgroups in 2 multicenter, multinational, double-masked trials. Two thousand four hundred fifty-seven neovascular age-related macular degeneration (AMD) patients. Patients were randomized to treatment with 0.5 mg ranibizumab given monthly, a 0.5-mg or 2-mg intravitreal aflibercept injection given monthly, or 2 mg intravitreal aflibercept given every other month, after 3 initial monthly doses, up to W52. From W52 through W96, patients received their original dosing assignment using a capped pro re nata (PRN) regimen, with defined retreatment criteria based on VA and morphologic signs of disease activity and mandatory dosing at least every 12 weeks. Best-corrected VA (BCVA) and optical coherence tomography assessments were mandatory at all visits from baseline to W96. Outcomes were changes in BCVA and central retinal thickness. Outcomes were evaluated in all patients who completed 2 years of the VIEW studies using the last observation carried forward method for missing data at interim visits. After W52, approximately 20% of patients lost 5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more across all treatment arms with PRN treatment. Patients who met the retreatment criterion of loss of 5 ETDRS letters or more in the first quarter of the PRN dosing phase did not recover; mean final VA loss across the 4 study arms was -4.4 to -5.8 letters. Outcomes of these patients up to W52 were indistinguishable from those of the overall population. There were no differences between groups in serious ocular adverse events or Anti-Platelet Trialists' Collaboration arterial thromboembolic events through W96. These analyses suggest that there are subgroups of patients for whom VA outcomes in the second year of the VIEW studies were less stable than in the first year and for whom W52 seems to be an important inflection point. Although alternate reasons specific to the nature of the underlying AMD cannot be fully excluded, the switch in treatment regimen at W52 is a plausible explanation. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Safety and immunogenicity of a Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar-TCV) in healthy infants, children, and adults in typhoid endemic areas: a multicenter, 2-cohort, open-label, double-blind, randomized controlled phase 3 study.

PubMed

Mohan, Vadrevu Krishna; Varanasi, Vineeth; Singh, Anit; Pasetti, Marcela F; Levine, Myron M; Venkatesan, Ramasamy; Ella, Krishna M

2015-08-01

Enteric fever caused by Salmonella Typhi remains a major public health problem in developing countries. Typbar-TCV is a single-dose typhoid Vi polysaccharide-tetanus toxoid conjugate vaccine for persons ≥6 months of age. Six hundred fifty-four healthy subjects aged 2-45 years enrolled in a double-blind, randomized controlled trial (RCT) received a single dose of Typbar-TCV or comparator "Vi polysaccharide" (Typbar), and 327 healthy subjects aged 6-23 months received a single dose of Typbar-TCV in an open-label trial (OLT); both received single- or multidose presentations from different lots. After 2 years, subsets in each group received a booster dose. The primary objective included analysis of geometric mean titer (GMTs) and 4-fold rise of anti-Vi serum immunoglobulin G (IgG) enzyme-linked immunosorbent assay titers over baseline (seroconversion [SCN]) 42 days after immunization. Typbar-TCV recipients in the RCT attained higher anti-Vi IgG GMTs 42 days after immunization (SCN, 97%; GMT, 1293 [95% confidence interval {CI}, 1153-1449]) than recipients of Typbar (SCN, 93%; GMT, 411 [95% CI, 359-471]) (P < .001). Typbar-TCV was highly immunogenic in the OLT (SCN, 98%; GMT, 1937 [95% CI, 1785-2103]). Two years after vaccination, anti-Vi titers remained higher in Typbar-TCV subjects (GMT, 82 [95% CI, 73-92]); and exhibited higher avidity (geometric mean avidity index [GMAI], 60%) than in Typbar recipients (GMT, 46 [95% CI, 40-53]; GMAI 46%) in the RCT (P < .001). OLT Typbar-TCV recipients achieved GMT of 48 (95% CI, 42-55) and GMAI of 57%. Typbar-TCV induced multiple IgG subclasses and strong booster responses in all ages. No serious vaccine-attributable adverse events were observed. Single-dose Typbar-TCV is well tolerated and induces robust and long-lasting serum anti-Vi IgG across age groups. CTRI/2011/08/001957, CTRI/2014/01/004341. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Fractionated Conformal Radiotherapy in the Management of Cavernous Sinus Meningiomas: Long-Term Functional Outcome and Tumor Control at a Single Institution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Metellus, Philippe; Batra, Sachin; Karkar, Siddharth

2010-11-01

Purpose: To evaluate long-term outcome of cavernous sinus meningioma (CSM) treated with fractionated conformal radiotherapy (FCR). Patients and Methods: Fifty-three patients with CSMs (16 men [30.2%], 37 women [69.8%], aged 53 {+-} 13.0 years [mean {+-} SD]) were treated by FCR. In 28 patients (52.8%) FCR was performed as first-line treatment and in 25 patients (47.2%) as adjuvant treatment. All patients received FCR with a dose of 52.9 {+-} 1.8 Gy in 29.4 {+-} 1.0 fractions over 6 weeks. Dose per fraction was 1.9 {+-} 0.1 Gy. Radiotherapy was delivered stereotactically in 47 cases (88.7%) and conformally in 6 (11.3%)more » Results: The median follow-up was 6.9 years (range, 3-19 years). According to Sekhar's classification, 19 patients (35.8%) were Grade 1-2, 30 patients (56.6%) were Grade 3-4, and 4 patients (7.6%) were Grade 5. Pretreatment tumor volume was determined in 46 patients, and tumor volume was 12.6 {+-} 8.2 cm{sup 3}. In these patients, the distance between tumor and optic apparatus was 1.62 {+-} 1.2 mm. Actuarial 5- and 10-year progression-free survival rates were 98.1% and 95.8%, respectively. Clinical improvement was observed in 31 patients (58.5%), and 20 patients (37.7%) remained unchanged. Radiologic response was observed in 18 patients (30.2%), and 35 patients (66.0%) showed stable lesions. Two patients (3.8%) showed tumor progression during follow-up. Transient morbidity was observed in 3 patients (5.7%) and permanent morbidity in 1 (1.9%). Conclusion: Fractionated conformal radiotherapy affords satisfactory long-term tumor control and low treatment morbidity.« less

Skeletal sequelae of radiation therapy for malignant childhood tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Butler, M.S.; Robertson, W.W. Jr.; Rate, W.

1990-02-01

One hundred forty-three patients who received radiation therapy for childhood tumors, and survived to the age of skeletal maturity, were studied by retrospective review of oncology records and roentgenograms. Diagnoses for the patients were the following: Hodgkin's lymphoma (44), Wilms's tumor (30), acute lymphocytic leukemia (26), non-Hodgkin's lymphoma (18), Ewing's sarcoma (nine), rhabdomyosarcoma (six), neuroblastoma (six), and others (four). Age at the follow-up examination averaged 18 years (range, 14-28 years). Average length of follow-up study was 9.9 years (range, two to 18 years). Asymmetry of the chest and ribs was seen in 51 (36%) of these children. Fifty (35%) hadmore » scoliosis; 14 had kyphosis. In two children, the scoliosis was treated with a brace, while one developed significant kyphosing scoliosis after laminectomy and had spinal fusion. Twenty-three (16%) patients complained of significant pain at the radiation sites. Twelve of the patients developed leg-length inequality; eight of those were symptomatic. Three patients developed second primary tumors. Currently, the incidence of significant skeletal sequelae is lower and the manifestations are less severe than reported in the years from 1940 to 1970. The reduction in skeletal complications may be attributed to shielding of growth centers, symmetric field selection, decreased total radiation doses, and sequence changes in chemotherapy.« less

New World Vistas: New Models of Computation Lattice Based Quantum Computation

DTIC Science & Technology

1996-07-25

ro ns Eniac (18,000 vacuum tubes) UNIVAC II (core memory) Digital Devices magnetostrictive delay line Intel 1103 integrated circuit IBM 3340 disk...in areal size of a bit for the last fifty years since the 1946 Eniac computer. 1 Planned Research I propose to consider the feasibility of implement...tech- nology. Fiqure 1 is a log-linear plot of data for the areal size of a bit over the last fifty years (from 18,000 bits in the 1946 Eniac computer

Werner Heisenberg and Carl Friedrich Freiherr von Weizsäcker: A Fifty-Year Friendship*

NASA Astrophysics Data System (ADS)

Cassidy, David C.

2015-03-01

This paper follows Werner Heisenberg and Carl Friedrich von Weizsäcker during their fifty-year friendship from 1926, when they first met in Copenhagen, to Heisenberg's death in Munich in 1976. The relationship underwent profound changes during that period, as did physics, philosophy, and German society and politics, all of which exerted important influences on their lives, work, and interactions with each other. The nature of these developments and their impact are explored in this paper.

Fifty years of accelerator based physics at Chalk River

DOE Office of Scientific and Technical Information (OSTI.GOV)

McKay, John W.

1999-04-26

The Chalk River Laboratories of Atomic Energy of Canada Ltd. was a major centre for Accelerator based physics for the last fifty years. As early as 1946, nuclear structure studies were started on Cockroft-Walton accelerators. A series of accelerators followed, including the world's first Tandem, and the MP Tandem, Superconducting Cyclotron (TASCC) facility that was opened in 1986. The nuclear physics program was shut down in 1996. This paper will describe some of the highlights of the accelerators and the research of the laboratory.

26 CFR 1.1348-2 - Computation of the fifty-percent maximum tax on earned income.

Code of Federal Regulations, 2011 CFR

2011-04-01

... earned income. 1.1348-2 Section 1.1348-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Other Limitations § 1.1348-2 Computation of the fifty-percent maximum tax on earned income. (a) Computation of tax for taxable years...

Vaginal dose de-escalation in image guided adaptive brachytherapy for locally advanced cervical cancer.

PubMed

Mohamed, Sandy; Lindegaard, Jacob Christian; de Leeuw, Astrid A C; Jürgenliemk-Schulz, Ina; Kirchheiner, Kathrin; Kirisits, Christian; Pötter, Richard; Tanderup, Kari

2016-09-01

Vaginal stenosis is a major problem following radiotherapy in cervical cancer. We investigated a new dose planning strategy for vaginal dose de-escalation (VDD). Fifty consecutive locally advanced cervical cancer patients without lower or middle vaginal involvement at diagnosis from 3 institutions were analysed. External beam radiotherapy was combined with MRI-guided brachytherapy. VDD was obtained by decreasing dwell times in ovoid/ring and increasing dwell times in tandem/needles. The aim was to maintain the target dose (D90 of HR-CTV⩾85Gy EQD2) while reducing the dose to the surface of the vagina to <140% of the physical fractional brachytherapy dose corresponding to a total EQD2 of 85Gy. The mean vaginal loading (ovoid/ring) was reduced from 51% to 33% of the total loading with VDD, which significantly reduced the dose to the vaginal dose points (p<0.001) without compromising the target dose. The dose to the ICRU recto-vaginal point was reduced by a mean of 4±4Gy EQD2 (p<0.001), while doses to bladder and rectum (D 2cm 3 ) were reduced by 2±2Gy and 3±2Gy, respectively (p<0.001). VDD significantly reduces dose to the upper vagina which is expected to result in reduction of vaginal stenosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Infection after injury: association with blood transfusion.

PubMed

Rosemurgy, A S; Hart, M B; Murphy, C G; Albrink, M H; Piazza, A; Leparc, G F; Harris, R E

1992-02-01

This study was undertaken to evaluate the association between red blood cell transfusions and infections in an easily stratified, homogenous group of injured adults. All received their initial transfusions upon arrival to the emergency department. Over 5 years, 390 uncross-matched trauma patients received type "O" red blood cells (RBCs) during initial resuscitation. One hundred fifty-four (39%) died within 7 days because of injuries sustained: 236 (61%) survived at least 7 days. Of these 236, clear differences could be seen between those receiving 6 or fewer or 7 or more units of RBCs. When adjusted for age, sex, and severity of injury (Champion Trauma Score, Injury Severity Score, TRISS), the risk of infection was higher in those receiving 7 or more units of RBCs. Similarly, risk of infection was related to units of RBCs transfused in a dose-related fashion. Blood transfusions should be avoided, if possible. Arbitrary "trigger points" for transfusions should be abandoned.

Daily Physical Activity and Cognitive Function Variability in Older Adults.

PubMed

Phillips, Christine B; Edwards, Jerri D; Andel, Ross; Kilpatrick, Marcus

2016-04-01

Physical activity (PA) is believed to preserve cognitive function in older adulthood, though little is known about these relationships within the context of daily life. The present microlongitudinal pilot study explored within- and between-person relationships between daily PA and cognitive function and also examined within-person effect sizes in a sample of community-dwelling older adults. Fifty-one healthy participants (mean age = 70.1 years) wore an accelerometer and completed a cognitive assessment battery for five days. There were no significant associations between cognitive task performance and participants' daily or average PA over the study period. Effect size estimates indicated that PA explained 0-24% of within-person variability in cognitive function, depending on cognitive task and PA dose. Results indicate that PA may have near-term cognitive effects and should be explored as a possible strategy to enhance older adults' ability to perform cognitively complex activities within the context of daily living.

Haemoglobin concentrations and infection by Giardia intestinalis in children: effect of treatment with secnidazole.

PubMed

Jiménez, J C; Rodríguez, N; Di Prisco, M C; Lynch, N R; Costa, V

1999-12-01

The blood concentrations of haemoglobin were investigated in 82 children aged 2-9 years. Fifty-seven (31 boys and 26 girls) were stool-positive for Giardia intestinalis but the other 25, used as controls, were negative. The mean (S.D.) haemoglobin concentration among the infected children was significantly lower pre-treatment than that for the control group [11.6 (1.2) v. 12.6 (1.5) g/dl; P < 0.05]. Treatment of the infected children with a single oral dose of secnidazole (30 mg/kg) led to a significant increase in their mean haemoglobin level 15 days later, from 11.6 (1.2) g/dl pre-treatment to 12.4 (1.2) g/dl post-treatment (P < 0.05). The results indicate that the therapeutic control of giardiasis could be important in programmes to combat anaemia in children living in endemic areas.

Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial.

PubMed

Pop, L C; Sukumar, D; Schneider, S H; Schlussel, Y; Stahl, T; Gordon, C; Wang, X; Papathomas, T V; Shapses, S A

2017-01-01

The effects of higher than recommended vitamin D doses on bone mineral density (BMD) and quality are not known. In this study, higher intakes, in postmenopausal women undergoing weight control over 1 year, had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry. Studies examining how bone responds to a standard dose of vitamin D supplementation have been inconsistent. In addition, the effects of higher doses on BMD and quality are not known. Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance. This 1-year-long, randomized, double-blind controlled study addresses whether vitamin D supplementation, in healthy overweight/obese older women, affects BMD and bone structural parameters. In addition, bone turnover and serum total, free, and bioavailable 25-hydroxyvitamin D (25OHD) responses to one of three daily levels of vitamin D 3 (600, 2000, 4000 IU) with 1.2 Ca g/day during weight control were examined. Fifty-eight women (age, 58 ± 6 years; body mass index, 30.2 ± 3.8 kg/m 2 , serum 25OHD, 27.3 ± 4.4 ng/mL) were randomized to treatment. After 1 year, serum 25OHD concentrations increased to 26.5 ± 4.4, 35.9 ± 4.5, and 41.5 ± 6.9 ng/mL, in groups 600, 2000, and 4000 IU, respectively, and differed between groups (p < 0.01). Weight change was similar between groups (-3.0 ± 4.1 %). Cortical (Ct) thickness of the tibia changed by -1.5 ± 5.1 %, +0.6 ± 3.2 %, and +2.0 ± 4.5 % in groups 600, 2000, and 4000 IU, respectively, and each group was significantly different from each other (p < 0.05). The decline in Ct thickness was prevented with higher vitamin D 3 supplementation, but there were no other significant changes due to treatment over 1 year. Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies.

Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis

PubMed Central

Cuffari, Carmen; Pierce, David; Korczowski, Bartosz; Fyderek, Krzysztof; Van Heusen, Heather; Hossack, Stuart; Wan, Hong; Edwards, Alena YZ; Martin, Patrick

2016-01-01

Background Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC). Aim To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC. Methods Participants (5–17 years of age; 18–82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model. Results Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%–45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified. Conclusion Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844. PMID:26893546

The "Journal of the Experimental Analysis of Behavior" at Fifty

ERIC Educational Resources Information Center

Laties, Victor G.

2008-01-01

The "Journal of the Experimental Analysis of Behavior" was founded in 1958 by a group of male psychologists, mainly from the northeastern USA and connected with either Harvard or Columbia. Fifty years later about 20% of both editors and authors reside outside this country and almost the same proportion is women. Other changes in the…

Blended Families in Conflict: Essentials a Pastor Must Know

ERIC Educational Resources Information Center

Perry, William J.

2013-01-01

The rise of blended families is becoming a prevalent dynamic in our society. According to the United States Census Bureau: American Community Survey, 2009 report, the U.S. is approaching a fifty percent divorce rate. Fifty percent will remarry within three and half years of their divorce. Of these, sixty-five percent will have children from their…

Pelvis Ewing sarcoma: Local control and survival in the modern era.

PubMed

Ahmed, Safia K; Robinson, Steven I; Arndt, Carola A S; Petersen, Ivy A; Haddock, Michael G; Rose, Peter S; Issa Laack, Nadia N

2017-09-01

Local control for Ewing sarcoma (ES) has improved in modern studies. However, it is unclear if these gains have also been achieved for pelvis tumors. The purpose of this study is to evaluate local control and survival in pelvis ES patients treated in the modern era. All pelvis ES patients diagnosed from 1990 to 2012 and seen at Mayo Clinic were identified. Factors relevant to survival and local control were analyzed. The cohort consisted of 48 patients. Fifty-two percent had metastatic disease at diagnosis. The 5-year overall survival and event-free survival was 73% and 65%, respectively, for localized disease. The 5-year cumulative incidence of local recurrence was 19%, with a 26% incidence for radiation, 13% for surgery, and 0% for surgery + radiation (P = 0.54). All local failures occurred in-field. Sacral involvement by tumor trended toward a higher incidence of local recurrence (hazard ratio 3.06, P = 0.09). Patients treated with definitive radiation doses ≥5,600 cGy had a lower incidence of local recurrence (17% vs. 28%, P = 0.61). Our study demonstrates excellent survival for localized tumors in the modern era. Anatomical localization within the pelvis likely correlates with outcomes. Local control remains problematic, especially for patients treated with definitive radiation. Though statistically not significant, surgery + radiation and definitive radiation dose ≥5,600 cGy were associated with the lowest incidence of local failure, suggesting treatment intensification may improve local control for pelvis ES. © 2017 Wiley Periodicals, Inc.

Six steps to a successful dose-reduction strategy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bennett, M.

1995-03-01

The increased importance of demonstrating achievement of the ALARA principle has helped produce a proliferation of dose-reduction ideas. Across a company there may be many dose-reduction items being pursued in a variety of areas. However, companies have a limited amount of resource and, therefore, to ensure funding is directed to those items which will produce the most benefit and that all areas apply a common policy, requires the presence of a dose-reduction strategy. Six steps were identified in formulating the dose-reduction strategy for Rolls-Royce and Associates (RRA): (1) collating the ideas; (2) quantitatively evaluating them on a common basis; (3)more » prioritizing the ideas in terms of cost benefit, (4) implementation of the highest priority items; (5) monitoring their success; (6) periodically reviewing the strategy. Inherent in producing the dose-reduction strategy has been a comprehensive dose database and the RRA-developed dose management computer code DOMAIN, which allows prediction of dose rates and dose. The database enabled high task dose items to be identified, assisted in evaluating dose benefits, and monitored dose trends once items had been implemented. The DOMAIN code was used both in quantifying some of the project dose benefits and its results, such as dose contours, used in some of the dose-reduction items themselves. In all, over fifty dose-reduction items were evaluated in the strategy process and the items which will give greatest benefit are being implemented. The strategy has been successful in giving renewed impetus and direction to dose-reduction management.« less

Results of the 2013-2015 Association of Residents in Radiation Oncology Survey of Chief Residents in the United States.

PubMed

Nabavizadeh, Nima; Burt, Lindsay M; Mancini, Brandon R; Morris, Zachary S; Walker, Amanda J; Miller, Seth M; Bhavsar, Shripal; Mohindra, Pranshu; Kim, Miranda B; Kharofa, Jordan

2016-02-01

The purpose of this project was to survey radiation oncology chief residents to define their residency experience and readiness for independent practice. During the academic years 2013 to 2014 and 2014 to 2015, the Association of Residents in Radiation Oncology (ARRO) conducted an electronic survey of post-graduate year-5 radiation oncology residents in the United States during the final 3 months of training. Descriptive statistics are reported. Sixty-six chief residents completed the survey in 2013 to 2014 (53% response rate), and 69 completed the survey in 2014 to 2015 (64% response rate). Forty to 85% percent of residents reported inadequate exposure to high-dose rate and low-dose rate brachytherapy. Nearly all residents in both years (>90%) reported adequate clinical experience for the following disease sites: breast, central nervous system, gastrointestinal, genitourinary, head and neck, and lung. However, as few as 56% reported adequate experience in lymphoma or pediatric malignancies. More than 90% of residents had participated in retrospective research projects, with 20% conducting resident-led prospective clinical trials and 50% conducting basic science or translational projects. Most chief residents reported working 60 or fewer hours per week in the clinical/hospital setting and performing fewer than 15 hours per week tasks that were considered to have little or no educational value. There was more than 80% compliance with Accreditation Council for Graduate Medical Education (ACGME) work hour limits. Fifty-five percent of graduating residents intended to join an established private practice group, compared to 25% who headed for academia. Residents perceive the job market to be more competitive than previous years. This first update of the ARRO chief resident survey since the 2007 to 2008 academic year documents US radiation oncology residents' experiences and conditions over a 2-year period. This analysis may serve as a valuable tool for those seeking to improve training of the next generation of oncology leaders. Copyright © 2016 Elsevier Inc. All rights reserved.

Sexist Attitudes Among Emerging Adult Women Readers of Fifty Shades Fiction.

PubMed

Altenburger, Lauren E; Carotta, Christin L; Bonomi, Amy E; Snyder, Anastasia

2017-02-01

Stereotypical sexist representations of men and women in popular culture reinforce rigid views of masculinity (e.g., males as being strong, in control, masterful, and aggressive) and femininity (e.g., women as being fragile and weak, unassertive, peaceful, irrational, and driven by emotions). The present study examined associations between the fictional series Fifty Shades-one popular culture mechanism that includes pervasive traditional gender role representations-and underlying sexist beliefs among a sample of 715 women ages 18-24 years. Analyses revealed associations between Fifty Shades readership and sexism, as measured through the Ambivalent Sexism Inventory. Namely women who reported reading Fifty Shades had higher levels of ambivalent, benevolent, and hostile sexism. Further, those who interpreted Fifty Shades as "romantic" had higher levels of ambivalent and benevolent sexism. Our findings support prior empirical studies noting associations between interacting with aspects of popular culture, such as television and video games, and individual beliefs and behaviors.

Fifty-year old and still ticking.... an interview with Emile Zuckerkandl on the 50th anniversary of the molecular clock. Interview by Giacomo Bernardi.

PubMed

Zuckerkandl, Emile

2012-06-01

In 1962, a young post-doctoral fellow and a prominent Nobel Prize winner, Emile Zuckerkandl and Linus Pauling, published a seminal paper that described the relationship between the average number of aminoacid replacements and divergence time, known as the molecular clock (Zuckerkandl and Pauling 1962). Fifty years after the original publication, I was fortunate enough to interview Emile Zuckerkandl. We shared thoughts on his life and the historical events that led to the discovery of the molecular clock.

Fifty years of sociological leadership at Social Science and Medicine.

PubMed

Timmermans, Stefan; Tietbohl, Caroline

2018-01-01

In this review article, we examine some of the conceptual contributions of sociology of health and illness over the past fifty years. Specifically, we focus on research dealing with medicalization, the management of stigma, research on adherence and compliance, and patient-doctor interaction. We show how these themes that originated within sociology, diffused in other disciplines. Sociology in Social Science and Medicine started as an applied research tradition but morphed into a robust, stand-alone social science tradition. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treatment of tumor-bearing dogs with actinomycin D.

PubMed

Hammer, A S; Couto, C G; Ayl, R D; Shank, K A

1994-01-01

Fifty dogs with advanced malignancies were treated with actinomycin D at doses ranging from 0.5 to 1.1 mg/m2 every 3 weeks. The greatest number of responses was noted in dogs with lymphoma, including dogs that had received prior chemotherapy. Other responding tumor types included anal sac adenocarcinoma, perianal adenocarcinoma, squamous cell carcinoma, thyroid carcinoma, and transitional cell carcinoma. The median time to maximum response for dogs with lymphoma was 7 days, with a median duration of 42 days. Gastrointestinal toxicity was the most frequently observed side effect. A dose of 0.6 to 0.7 mg/m2 appears to be appropriate for treating various malignancies in dogs.

Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial.

PubMed

Skorupski, K A; Uhl, J M; Szivek, A; Allstadt Frazier, S D; Rebhun, R B; Rodriguez, C O

2016-03-01

Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease-free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin. © 2013 John Wiley & Sons Ltd.

A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities.

PubMed

Wasdell, Michael B; Jan, James E; Bomben, Melissa M; Freeman, Roger D; Rietveld, Wop J; Tai, Joseph; Hamilton, Donald; Weiss, Margaret D

2008-01-01

The purpose of this study was to determine the efficacy of controlled-release (CR) melatonin in the treatment of delayed sleep phase syndrome and impaired sleep maintenance of children with neurodevelopmental disabilities including autistic spectrum disorders. A randomized double-blind, placebo-controlled crossover trial of CR melatonin (5 mg) followed by a 3-month open-label study was conducted during which the dose was gradually increased until the therapy showed optimal beneficial effects. Sleep characteristics were measured by caregiver who completed somnologs and wrist actigraphs. Clinician rating of severity of the sleep disorder and improvement from baseline, along with caregiver ratings of global functioning and family stress were also obtained. Fifty-one children (age range 2-18 years) who did not respond to sleep hygiene intervention were enrolled. Fifty patients completed the crossover trial and 47 completed the open-label phase. Recordings of total night-time sleep and sleep latency showed significant improvement of approximately 30 min. Similarly, significant improvement was observed in clinician and parent ratings. There was additional improvement in the open-label somnolog measures of sleep efficiency and the longest sleep episode in the open-label phase. Overall, the therapy improved the sleep of 47 children and was effective in reducing family stress. Children with neurodevelopmental disabilities, who had treatment resistant chronic delayed sleep phase syndrome and impaired sleep maintenance, showed improvement in melatonin therapy.

Impact of reduced dose limits on NRC licensed activities. Major issues in the implementation of ICRP/NCRP dose limit recommendations: Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meinhold, C.B.

This report summarizes information required to estimate, at least qualitatively, the potential impacts of reducing occupational dose limits below those given in 10 CFR 20 (Revised). For this study, a questionnaire was developed and widely distributed to the radiation protection community. The resulting data together with data from existing surveys and sources were used to estimate the impact of three dose-limit options; 10 mSv yr{sup {minus}1} (1 rem yr{sup {minus}1}), 20 mSv yr{sup {minus}1} (2 rem yr{sup {minus}1}), and a combination of an annual limit of 50 mSv yr{sup {minus}1} (5 rem yr{sup {minus}1}) coupled with a cumulative limit, inmore » rem, equal to age in years. Due to the somewhat small number of responses and the lack of data in some specific areas, a working committee of radiation protection experts from a variety of licensees was employed to ensure the exposure data were representative. The following overall conclusions were reached: (1) although 10 mSv yr{sup {minus}1} is a reasonable limit for many licensees, such a limit could be extraordinarily difficult to achieve and potentially destructive to the continued operation of some licensees, such as nuclear power, fuel fabrication, and medicine; (2) twenty mSv yr{sup {minus}1} as a limit is possible for some of these groups, but for others it would prove difficult. (3) fifty mSv yr{sup {minus}1} and age in 10s of mSv appear reasonable for all licensees, both in terms of the lifetime risk of cancer and severe genetic effects to the most highly exposed workers, and the practicality of operation.« less

A Phase I Study of Hepatic Arterial Infusion of Nab-Paclitaxel in Combination with Intravenous Gemcitabine and Bevacizumab for Patients with Advanced Cancers and Predominant Liver Metastases

PubMed Central

Tsimberidou, Apostolia M.; Ye, Yang; Wheler, Jennifer; Naing, Aung; Hong, David; Nwosu, Uchechi; Hess, Kenneth R.; Wolff, Robert A.

2014-01-01

PURPOSE We conducted a Phase I clinical trial for patients with advanced cancer and predominant liver disease. EXPERIMENTAL DESIGN Patients were treated with HAI nab-paclitaxel (120-210 mg/m2; day 1); intravenous bevacizumab (10 mg/kg; day 1); and intravenous gemcitabine (600-800 mg/m2; days 1 and 8). A conventional “3 + 3” study design was used. RESULTS Fifty patients with advanced cancer and predominant liver metastases were treated (median age, 58 years; 27 women, 23 men; median number of prior therapies, 3 [range, 0-12]). The most common cancers were breast (n=9) and pancreatic (n=9). Overall, 264 cycles were administered (median/patient, 4; range, 1-17). No dose-limiting toxicities were noted during the escalation phase. On dose level 4, 3 patients were unable to receive gemcitabine on day 8 because of severe thrombocytopenia. Dose level 3 was selected as the maximum tolerated dose (HAI nab-paclitaxel 180 mg/m2 and intravenous gemcitabine 800 mg/m2 and bevacizumab 10 mg/kg); Thirty-two patients were treated in the expansion phase. The most common treatment-related toxicities were thrombocytopenia (n=17), neutropenia (n=10), and fatigue (n=12). Of 46 patients evaluable for response, 9 (20%) had a partial response [1] and 9 (20%) had stable disease for {greater than or equal to} 6 months. The median overall survival duration was 7.0 months (95% CI: 4, 22 months) and the median progression-free survival duration was 4.2 months (95% CI: 2.7, 8.6 months). CONCLUSIONS HAI nab-paclitaxel in combination with gemcitabine and bevacizumab was well tolerated and had antitumor activity in selected patients with advanced cancer and liver metastases. PMID:23377373

Single-Dose Versus Fractionated Stereotactic Radiotherapy for Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Yeon-Joo; Cho, Kwan Ho, E-mail: kwancho@ncc.re.kr; Kim, Joo-Young

2011-10-01

Purpose: To evaluate the efficacy of stereotactic radiotherapy in patients with brain metastases by comparing two different treatment regimens, single-dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Between November 2003 and December 2008, 98 patients with brain metastases were included. Fifty-eight patients were treated with SRS, and forty were treated with FSRT. Fractionated stereotactic radiotherapy was used for large lesions or lesions located near critical structures. The median doses were 20 Gy for the SRS group and 36 Gy in 6 fractions for the FSRT group. Results: With a median follow-up period of 7 months, the medianmore » survival was 7 months for all patients, with a median of 6 months for the SRS group and 8 months for the FSRT group (p = 0.89). Local progression-free survival (LPFS) rates at 6 months and 1 year were 81% and 71%, respectively, for the SRS group and 97% and 69%, respectively, for the FSRT group (p = 0.31). Despite the fact that FSRT was used for large lesions and lesions in adverse locations, LPFS was not inferior to SRS. Toxicity was more frequently observed in the SRS group than in the FSRT group (17% vs. 5%, p = 0.05). Conclusions: Because patients treated with FSRT exhibited similar survival times and LPFS rates with a lower risk of toxicity in comparison to those treated with SRS, despite the fact that FSRT was used for large lesions and lesions in adverse locations, we find that FSRT can particularly be beneficial for patients with large lesions or lesions located near critical structures. Further investigation is warranted to determine the optimal dose/fractionation.« less

Efficacy of transfusion with granulocytes from G-CSF/dexamethasone–treated donors in neutropenic patients with infection

PubMed Central

Boeckh, Michael; Harrison, Ryan W.; McCullough, Jeffrey; Ness, Paul M.; Strauss, Ronald G.; Nichols, W. Garrett; Hamza, Taye H.; Cushing, Melissa M.; King, Karen E.; Young, Jo-Anne H.; Williams, Eliot; McFarland, Janice; Holter Chakrabarty, Jennifer; Sloan, Steven R.; Friedman, David; Parekh, Samir; Sachais, Bruce S.; Kiss, Joseph E.; Assmann, Susan F.

2015-01-01

High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count <500/μL) and proven/probable/presumed infection. Subjects were randomized to receive either (1) standard antimicrobial therapy or (2) standard antimicrobial therapy plus daily granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. The primary end point was a composite of survival plus microbial response, at 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Fifty-six subjects were randomized to the granulocyte arm and 58 to the control arm. Transfused subjects received a median of 5 transfusions. Mean transfusion dose was 54.9 × 109 granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (P > .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 109 granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393. PMID:26333778

Intensity-Modulated Radiation Therapy in the Salvage of Locally Recurrent Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu Sufang; Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore; Lin Shaojun

2012-06-01

Purpose: Local recurrences of nasopharyngeal carcinoma (NPC) may be salvaged by reirradiation with conventional techniques, but with significant morbidity. Intensity-modulated radiation therapy (IMRT) may improve the therapeutic ratio by reducing doses to normal tissue. The aim of this study was to address the efficacy and toxicity profile of IMRT for a cohort of patients with locally recurrent NPC. Methods and Materials: Between August 2003 and June 2009, 70 patients with radiologic or pathologically proven locally recurrent NPC were treated with IMRT. The median time to recurrence was 30 months after the completion of conventional radiation to definitive dose. Fifty-seven percentmore » of the tumors were classified asrT3-4. The minimum planned doses were 59.4 to 60 Gy in 1.8- to 2-Gy fractions per day to the gross disease with margins, with or without chemotherapy. Results: The median dose to the recurrent tumor was 70 Gy (range, 50-77.4 Gy). Sixty-five patients received the planned radiation therapy; 5 patients received between 50 and 60 Gy because of acute side effects. With a median follow-up time of 25 months, the rates of 2-year locoregional recurrence-free survival, disease-free survival, and overall survival were 65.8%, 65.8%, and 67.4%, respectively. Moderate to severe late toxicities were noted in 25 patients (35.7%). Eleven patients (15.7%) had posterior nasal space ulceration, 17 (24.3%) experienced cranial nerve palsies, 12 (17.1%) had trismus, and 12 (17.1%) experienced deafness. Extended disease-free interval (relative risk 2.049) and advanced T classification (relative risk 3.895) at presentation were adverse prognostic factors. Conclusion: Reirradiation with IMRT provides reasonable long-term control in patients with locally recurrent NPC.« less

Penile brachytherapy: Results for 49 patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crook, Juanita M.; Jezioranski, John; Grimard, Laval

2005-06-01

Purpose: To report results for 49 men with squamous cell carcinoma (SCC) of the penis treated with primary penile interstitial brachytherapy at one of two institutions: the Ottawa Regional Cancer Center, Ottawa, and the Princess Margaret Hospital, Toronto, Ontario, Canada. Methods and Materials: From September 1989 to September 2003, 49 men (mean age, 58 years; range, 22-93 years) had brachytherapy for penile SCC. Fifty-one percent of tumors were T1, 33% T2, and 8% T3; 4% were in situ and 4% Tx. Grade was well differentiated in 31%, moderate in 45%, and poor in 2%; grade was unspecified for 20%. Onemore » tumor was verrucous. All tumors in Toronto had pulsed dose rate (PDR) brachytherapy (n = 23), whereas those in Ottawa had either Iridium wire (n 22) or seeds (n = 4). Four patients had a single plane implant with a plastic tube technique, and all others had a volume implant with predrilled acrylic templates and two or three parallel planes of needles (median, six needles). Mean needle spacing was 13.5 mm (range, 10-18 mm), mean dose rate was 65 cGy/h (range, 33-160 cGy/h), and mean duration was 98.8 h (range, 36-188 h). Dose rates for PDR brachytherapy were 50-61.2 cGy/h, with no correction in total dose, which was 60 Gy in all cases. Results: Median follow-up was 33.4 months (range, 4-140 months). At 5 years, actuarial overall survival was 78.3% and cause-specific survival 90.0%. Four men died of penile cancer, and 6 died of other causes with no evidence of recurrence. The cumulative incidence rate for never having experienced any type of failure at 5 years was 64.4% and for local failure was 85.3%. All 5 patients with local failure were successfully salvaged by surgery; 2 other men required penectomy for necrosis. The soft tissue necrosis rate was 16% and the urethral stenosis rate 12%. Of 8 men with regional failure, 5 were salvaged by lymph node dissection with or without external radiation. All 4 men with distant failure died of disease. Of 49 men, 42 had an intact and tumor-free penis at last follow-up or death. The actuarial penile preservation rate at 5 years was 86.5%. Conclusions: Brachytherapy is an effective treatment for T1, T2, and selected T3 SCC of the penis. Close follow-up is mandatory because local failures and many regional failures can be salvaged by surgery.« less

Oxaliplatin-related neuropathy in Indian patients - no difference between generic and original molecules.

PubMed

Sirohi, Bhawna; Ostwal, Vikas; Dawood, Shaheenah; Lopes, Gilberto; Talole, Sanjay; Nashikkar, Chaitali; Shrikhande, Shailesh

2016-01-01

Oxaliplatin-induced neuropathy is a dose-limiting toxicity that significantly affects patients' quality of life. The aim of this study was to compare its occurrence between a generic versus the original molecule in Indian patients. Between August 2012 and July 2013, 163 patients receiving oxaliplatin were prospectively enrolled. A data recording form was used in the clinic to record detailed information. The median age of patients was 55 years (range, 19-79). Chemotherapy regimens used included: capecitabine, oxaliplatin (59), epirubicin, oxaliplatin, and capecitabine (20), docetaxel, oxaliplatin, and capecitabine (11), 5-FU, leucovorin, oxaliplatin (9), and gemcitabine-oxaliplatin (64). The median cumulative dose of oxaliplatin was 780 mg/m 2 . Eighty patients received the original version and 83 the generic one. Overall, 63 patients (38%) developed neuropathy. There was no significant difference in the incidence of neuropathy between the two forms of oxaliplatin used ( P = 0.50). Forty-nine percent of female patients had neuropathy as compared to 30% of male patients ( P = 0.014). Older patients had a trend toward a higher incidence of neuropathy: 44% of patients above age fifty developed neuropathy compared to 30% of patients younger than 50 ( P = 0.06). This is the first study to specifically show that neuropathy rates do not vary with the use of generic versus original oxaliplatin.

Clinical Management of ADHD in a Family Medicine Residency Program: Comparison with AAP Guidelines.

PubMed

Skelley, Jessica W; Carpenter, P Chase; Morehead, M Shawn; Murphy, Patrick L

2016-06-01

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder. Research has shown that even with the growing incidence of children diagnosed as having ADHD, physicians may find providing optimal care to these patients challenging. Our objective was to contrast existing clinical management of ADHD in a family medicine setting with published American Academy of Pediatrics guidelines and review the literature pertinent to differences. A report was generated for all visits with "ADHD" or "ADD" (attention-deficit disorder) as a current or past medical problem that had been addressed at the family medicine clinic from July 2012 to June 2014. A total of 60 pediatric patients were identified. A retrospective chart review of clinical practice and management patterns for these patients was completed using a standardized data collection form based on the 2011 ADHD treatment guidelines set by the American Academy of Pediatrics. Fifty-seven (95%) patients had documentation of at least one core symptom of ADHD, and 27 (45%) patients had documentation of these symptoms in more than one setting (clinic/school/home). Only 30 (50%) patients were assessed at the initial ADHD visit for coexisting conditions. Coexisting conditions were found to be present in 20 (33.3%) patients. Of these 20 patients, coexisting conditions were not addressed during the visit in 12 (60%) patients before drug therapy for ADHD was initially prescribed. Behavioral therapy was initiated as first-line monotherapy in one of the nine preschool-age patients (4-5 years old). Fifty-two (86.7%) patients received a preferred initial medication as identified by guidelines, and 41 (78.8%) of those patients received an appropriate initial dose. Fifty-one (85%) patients were assessed for improvement of symptoms, and 39 (65%) were assessed for adverse events. Of 62 documented medication adjustments, 54 (87.1%) adjustments coincided with current practice guidelines. Sixteen (26.7%) patients were referred to mental health specialists. This retrospective review identified areas of strength and weakness for attending physicians and medical residents in the diagnosis, evaluation, and treatment of children with ADHD. A significant need was identified for more physician-focused education on the evaluation of coexisting conditions and long-term management associated with ADHD therapy. Further training in the initiation of behavioral therapy as a first-line treatment above drug therapy and proper medication selection in children aged 4 to 5 years also are recommended.

Utilization of Subcutaneous Methotrexate in Rheumatoid Arthritis Patients After Failure or Intolerance to Oral Methotrexate: A Multicenter Cohort Study.

PubMed

Branco, Jaime C; Barcelos, Anabela; de Araújo, Filipe Pombo; Sequeira, Graça; Cunha, Inês; Patto, José Vaz; Oliveira, Margarida; Mateus, Margarida Pratas; Couto, Maura; Nero, Patrícia; Pinto, Patrícia; Monteiro, Paulo; Castelão, Walter; Félix, Jorge; Ferreira, Diana; Almeida, João; Silva, Maria João

2016-01-01

Low-dose weekly methotrexate (MTX) is the mainstay in the therapy of rheumatoid arthritis (RA). It can be given via oral, intramuscular or subcutaneous (SC) route. This study sought to determine the real-world pattern of treatment with SC MTX in Portuguese adult patients with active RA. Utilization of Metoject(®) in Rheumatoid Arthritis (UMAR) was a non-interventional, cohort multicenter study with retrospective data collection. Eligible patients had active RA, at least 18 years of age, and started SC MTX treatment in 2009 or 2010 after failure or intolerance to oral MTX. Data were collected from patient's clinical records. Both non-parametric and parametric survival methods were used to obtain a detailed understanding of SC MTX treatment duration. Fifty patients were included, of which only 9 discontinued SC MTX during the study follow-up period. The probability of discontinuation after 1, 2, and 3 years of treatment of SC MTX treatment is expected to be 6.10%, 8.50%, and 23.20%, respectively. The extrapolated median duration of SC MTX using an exponential model was 106.4 months/8.87 years. Mean dose of SC MTX was 18.36 mg. The reasons for treatment discontinuation were occurrence of adverse events in six patients and lack of efficacy in three. The long treatment duration of SC MTX highlights its excellent tolerability compared to oral MTX, especially concerning the frequent adverse gastrointestinal events of MTX. Furthermore, long MTX treatment duration provides the opportunity to postpone or even avoid expensive therapies with biologics. The results obtained from the UMAR study provide important information for the utilization and public financing of SC MTX in Portugal.

Long-term outcomes of Gamma Knife radiosurgery in patients with vestibular schwannomas.

PubMed

Murphy, Erin S; Barnett, Gene H; Vogelbaum, Michael A; Neyman, Gennady; Stevens, Glen H J; Cohen, Bruce H; Elson, Paul; Vassil, Andrew D; Suh, John H

2011-02-01

The authors sought to determine the long-term tumor control and side effects of Gamma Knife radiosurgery (GKRS) in patients with vestibular schwannomas (VS). One hundred seventeen patients with VS underwent GKRS between January 1997 and February 2003. At the time of analysis, at least 5 years had passed since GKRS in all patients. The mean patient age was 60.9 years. The mean maximal tumor diameter was 1.77 ± 0.71 cm. The mean tumor volume was 1.95 ± 2.42 ml. Eighty-two percent of lesions received 1300 cGy and 14% received 1200 cGy. The median dose homogeneity ratio was 1.97 and the median dose conformality ratio was 1.78. Follow-up included MR imaging or CT scanning approximately every 6-12 months. Rates of progression to surgery were calculated using the Kaplan-Meier method. Of the 117 patients in whom data were analyzed, 103 had follow-up MR or CT images and 14 patients were lost to follow-up. Fifty-three percent of patients had stable tumors and 37.9% had a radiographically documented response. Imaging-documented tumor progression was present in 8 patients (7.8%), but in 3 of these the lesion eventually stabilized. Only 5 patients required a neurosurgical intervention. The estimated 1-, 3-, and 5-year rates of progression to surgery were 1, 4.6, and 8.9%, respectively. One patient (1%) developed trigeminal neuropathy, 4 patients (5%) developed permanent facial neuropathy, 3 patients (4%) reported vertigo, and 7 patients (18%) had new gait imbalance following GKRS. Gamma Knife radiosurgery results in excellent local control rates with minimal toxicity for patients with VS. The authors recommend standardized follow-up to gain a better understanding of the long-term effects of GKRS.

Stereotactic Ablative Radiotherapy for stage I histologically proven non-small cell lung cancer: an Italian multicenter observational study.

PubMed

Ricardi, Umberto; Frezza, Giovanni; Filippi, Andrea Riccardo; Badellino, Serena; Levis, Mario; Navarria, Piera; Salvi, Fabrizio; Marcenaro, Michela; Trovò, Marco; Guarneri, Alessia; Corvò, Renzo; Scorsetti, Marta

2014-06-01

Aim of this retrospective multicenter observational study was to provide data on outcomes and prognostic factors in patients affected with stage I histologically confirmed NSCLC treated with Stereotactic Ablative Radiotherapy (SABR, or Stereotactic Body Radiotherapy, SBRT) outside clinical trials. We analyzed a cohort of 196 patients with histological/cytological diagnosis of NSCLC. Median age at treatment was 75 years old; median tumor diameter was 2.48 cm, and median GTV 13.3 cc. One hundred fifty-five patients had stage IA disease (79.1%) and 41 patients stage IB disease (20.9%). Total doses ranged from 48 to 60 Gy in 3-8 fractions. Primary endpoints of the study were safety (acute and late toxicity) and efficacy (Local Control, Disease-Free Survival, Overall and Cancer-Specific Survival). Median follow-up time was 30 months. The percentage of grade ≥2 pulmonary toxicity was 3%, and the 30 and 60 days mortality rate was 0%. Local Recurrence-Free Survival was 89.7% at 3 years. Fifty-nine patients (30.1%) had at least one failure (local and/or nodal and/or distant), with a Disease-Free Survival (DFS) rate at 3 years of 65.5%. Overall Survival (OS) and Cancer-Specific Survival (CSS) rates were 68% and 82.1% at 3 years, respectively. Median time to any recurrence was 15 months, while median overall survival time was 54 months. At multivariate analysis, stage IB was the only variable associated to a decrease in DFS, OS and CSS (HR 2.77, p = 0.006; HR 2.38, p = 0.009; HR 4.06, p ≤ 0.001, respectively). A difference in survival according to stage was also evident at the log-rank test (p ≤ 0.0001 for CSS and OS). The results of the present study support the routine use of SABR for stage I NSCLC in a daily practice environment. The only prognostic factor that has been confirmed by our analysis was tumor stage (IA vs. IB). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Monitoring medication errors in personalised dispensing using the Sentinel Surveillance System method].

PubMed

Pérez-Cebrián, M; Font-Noguera, I; Doménech-Moral, L; Bosó-Ribelles, V; Romero-Boyero, P; Poveda-Andrés, J L

2011-01-01

To assess the efficacy of a new quality control strategy based on daily randomised sampling and monitoring a Sentinel Surveillance System (SSS) medication cart, in order to identify medication errors and their origin at different levels of the process. Prospective quality control study with one year follow-up. A SSS medication cart was randomly selected once a week and double-checked before dispensing medication. Medication errors were recorded before it was taken to the relevant hospital ward. Information concerning complaints after receiving medication and 24-hour monitoring were also noted. Type and origin error data were assessed by a Unit Dose Quality Control Group, which proposed relevant improvement measures. Thirty-four SSS carts were assessed, including 5130 medication lines and 9952 dispensed doses, corresponding to 753 patients. Ninety erroneous lines (1.8%) and 142 mistaken doses (1.4%) were identified at the Pharmacy Department. The most frequent error was dose duplication (38%) and its main cause inappropriate management and forgetfulness (69%). Fifty medication complaints (6.6% of patients) were mainly due to new treatment at admission (52%), and 41 (0.8% of all medication lines), did not completely match the prescription (0.6% lines) as recorded by the Pharmacy Department. Thirty-seven (4.9% of patients) medication complaints due to changes at admission and 32 matching errors (0.6% medication lines) were recorded. The main cause also was inappropriate management and forgetfulness (24%). The simultaneous recording of incidences due to complaints and new medication coincided in 33.3%. In addition, 433 (4.3%) of dispensed doses were returned to the Pharmacy Department. After the Unit Dose Quality Control Group conducted their feedback analysis, 64 improvement measures for Pharmacy Department nurses, 37 for pharmacists, and 24 for the hospital ward were introduced. The SSS programme has proven to be useful as a quality control strategy to identify Unit Dose Distribution System errors at initial, intermediate and final stages of the process, improving the involvement of the Pharmacy Department and ward nurses. Copyright © 2009 SEFH. Published by Elsevier Espana. All rights reserved.

High-quality low-dose cardiovascular computed tomography (CCT) in pediatric patients using a 64-slice scanner.

PubMed

Cannaò, Paola Maria; Secchi, Francesco; Alì, Marco; D'Angelo, Ida Daniela; Scarabello, Marco; Di Leo, Giovanni; Sardanelli, Francesco

2018-01-01

Background Cardiovascular computed tomography (CCT) technology is rapidly advancing allowing to perform good quality examinations with a radiation dose as low as 1.2 mSv. However, latest generation scanners are not available in all centers. Purpose To estimate radiation dose and image quality in pediatric CCT using a standard 64-slice scanner. Material and Methods A total of 100 patients aged 6.9 ± 5.4 years (mean ± standard deviation) who underwent a 64-slice CCT scan using 80, 100, or 120 kVp, were retrospectively evaluated. Radiation effective dose was calculated on the basis of the dose length product. Two independent readers assessed the image quality through signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and a qualitative score (3 = very good, 2 = good, 1 = poor). Non-parametric tests were used. Results Fifty-five exams were not electrocardiographically (ECG) triggered, 20 had a prospective ECG triggering, and 25 had retrospective ECG triggering. The median effective dose was 1.3 mSv (interquartile range [IQR] = 0.8-2.7 mSv). Median SNR was 30.6 (IQR = 23.4-33.6) at 120 kVp, 29.4 (IQR = 23.7-34.8) at 100 kVp, and 24.7 (IQR = 19.4-34.3) at 80 kVp. Median CNR was 21.0 (IQR = 14.8-24.4), 19.1 (IQR = 15.6-23.9), and 25.3 (IQR = 19.4-33.4), respectively. Image quality was very good, good, and poor in 56, 39, and 5 patients, respectively. No significant differences were found among voltage groups for SNR ( P = 0.486), CNR ( P = 0.336), and subjective image quality ( P = 0.296). The inter-observer reproducibility was almost perfect (κ = 0.880). Conclusion High-quality pediatric CCT can be performed using a 64-slice scanner, with a radiation effective dose close to 2 mSv in about 50% of the cases.

Low-voltage chest CT: another way to reduce the radiation dose in asbestos-exposed patients.

PubMed

Macía-Suárez, D; Sánchez-Rodríguez, E; Lopez-Calviño, B; Diego, C; Pombar, M

2017-09-01

To assess whether low voltage chest computed tomography (CT) can be used to successfully diagnose disease in patients with asbestos exposure. Fifty-six former employees of the shipbuilding industry, who were candidates to receive a standard-dose chest CT due to their occupational exposure to asbestos, underwent a routine CT. Immediately after this initial CT, they underwent a second acquisition using low-dose chest CT parameters, based on a low potential (80 kV) and limited tube current. The findings of the two CT protocols were compared based on typical diseases associated with asbestos exposure. The kappa coefficient for each parameter and for an overall rating (grouping them based on mediastinal, pleural, and pulmonary findings) were calculated in order to test for correlations between the two protocols. A good correlation between routine and low-dose CT was demonstrated for most parameters with a mean radiation dose reduction of up to 83% of the effective dose based on the dose-length product between protocols. Low-dose chest CT, based on a limited tube potential, is useful for patients with an asbestos exposure background. Low-dose chest CT can be successfully used to minimise the radiation dose received by patients, as this protocol produced an estimated mean effective dose similar to that of an abdominal or pelvis plain film. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Fifty-Year Record of Glacier Change Reveals Shifting Climate in the Pacific Northwest and Alaska, USA

USGS Publications Warehouse

,

2009-01-01

Fifty years of U.S. Geological Survey (USGS) research on glacier change shows recent dramatic shrinkage of glaciers in three climatic regions of the United States. These long periods of record provide clues to the climate shifts that may be driving glacier change. The USGS Benchmark Glacier Program began in 1957 as a result of research efforts during the International Geophysical Year (Meier and others, 1971). Annual data collection occurs at three glaciers that represent three climatic regions in the United States: South Cascade Glacier in the Cascade Mountains of Washington State; Wolverine Glacier on the Kenai Peninsula near Anchorage, Alaska; and Gulkana Glacier in the interior of Alaska (fig. 1).

PHYSICIANS' KNOWLEDGE ABOUT RADIATION DOSE AND POSSIBLE RISKS OF COMMON MEDICAL TESTS: A SURVEY IN IRAN.

PubMed

Zakeri, Farideh; Shakeri, Mahsa; Rajabpour, Mohammad Reza; Farshidpour, Mohammad Reza; Mianji, Fereidoun

2016-12-01

Recent data suggest that knowledge of radiation exposures among physicians is inadequate. This study, therefore, aimed to evaluate their knowledge of the radiation doses their patients received and awareness of associated biological risks of radiation exposure. A questionnaire in multiple-choice format consisted of four sections with a total of 10 questions based on the literature review. A total of 136 questionnaires were returned from 69 general practitioners and 67 physicians in various specialties from 10 different hospitals in the capital city of Tehran, Iran. Fifty-four percent of general practitioners and twenty-five percent of specialties declared that they are not aware of biological risks of radiation exposure. Fifty-six percent of physicians did not know the correct definition of absorbed dose. Only 33% of physicians knew the dose exposure of a chest X-ray and only 31% knew the approximate doses of various procedures relative to a chest X-ray. Forty-seven percent of physicians incorrectly distinguished the stochastic effects of radiation from the deterministic effects, and thirty-eight of physicians did not know the organs of the body that are most sensitive to ionizing radiation. Only 23.5% of physicians were aware of the one in 2000 risk of induction of fatal carcinoma from computed tomography of the abdomen. Seventy-nine percent of physicians incorrectly underestimated the contribution of nuclear and radiological tests in exposure of an average person. The mean score of the specialties trended toward being more accurate than general practitioners (4.18 ± 1.28 vs. 3.89 ± 1.46, respectively, from a potential accurate total score of 9), but these differences were not statistically significant. Among specialists, orthopedics had the highest scores. The present study demonstrated the limited knowledge of radiation exposures among general practitioners and specialists and a need to improve their knowledge by means of targeted training and re-education. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Analysis of clinical efficacy, side effects, and laboratory changes among patients with acne vulgaris receiving single versus twice daily dose of oral isotretinoin.

PubMed

Ahmad, Hesham M

2015-01-01

Acne vulgaris is a debilitating disorder and requires proper treatment. This work evaluates the clinical efficacy, side effects, and laboratory changes of serum lipids and liver function during oral isotretinoin therapy for acne vulgaris, comparing single versus twice daily dose. Fifty-eight patients with acne vulgaris were included and randomized into group I (26 patients), who received once daily dose, and group II (32 patients), who received twice daily dose of oral isotretinoin. Global acne scoring system was used to evaluate acne severity and post-treatment improvement. Both regimens resulted in highly significant clinical improvement of acne with no significant difference. However, side effects were significantly more common among patients of group I. Both regimens caused mild rise of serum cholesterol, alanine transaminase (ALT), and aspartate aminotransferase (AST) with more prominent rise of triglycerides especially with twice daily dose. Oral isotretinoin is a very effective treatment for acne vulgaris with no statistically significant difference in clinical efficacy between once and twice daily doses. However, dividing dose to twice per day might cause fewer incidence of side effects without reducing clinical efficacy. The drug causes mild clinically insignificant rise of serum cholesterol, triglycerides, AST, and ALT. © 2015 Wiley Periodicals, Inc.

Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer?

PubMed

George, Rani; Haywood, Alison; Good, Phillip; Hennig, Stefanie; Khan, Sohil; Norris, Ross; Hardy, Janet

2017-09-01

Methadone is a potent analgesic used to treat refractory cancer pain. It is administered as a racemic mixture, with the l-enantiomer being primarily a μ-receptor agonist, whereas the d-enantiomer is an N-methyl-d-aspartate antagonist and inhibits serotonin and norepinephrine reuptake. Dose requirements vary greatly among patients to achieve optimal pain control and to avoid the risk of adverse effects. The relationship between plasma and saliva methadone enantiomer concentrations was investigated to determine if saliva could be a substitute for plasma in pharmacodynamic and pharmacokinetic studies for clinical monitoring and dose optimization of methadone in patients with advanced cancer. Patients with advanced cancer who were prescribed varying doses of oral methadone for pain management were recruited to obtain paired plasma and saliva samples. Pain scores were recorded at the time of sampling. The total and unbound plasma and saliva concentrations of the l- and d-enantiomers of methadone were quantified by using an HPLC-MS/MS method. The relationship between plasma (total and unbound) and saliva concentrations were compared. The saliva-to-plasma concentration ratio was compared versus the dose administered and the time after dosing for both enantiomers. The association of methadone concentrations with reported pain scores was compared by using a Mann-Whitney U test for significance. Fifty patients receiving a mean dose of 11mg/d of methadone provided 151 paired plasma and saliva samples. The median age of the population was 61 years with an interquartile range of 53-71 years with total body weight ranging from 59-88 kg. Median (interquartile) total plasma concentrations for l- and d-methadone were 50.78 ng/mL (30.6-113.0 ng/mL) and 62.0 ng/mL (28.7-116.0 ng/mL), respectively. Median (interquartile range) saliva concentrations for l- and d-methadone were 81.5 ng/mL (28.0-203.2 ng/mL) and 44.2 (16.2-149.7 ng/mL). No relationship could be established between plasma and saliva concentrations for l- and d-methadone (r 2 = 0.35 and 0.25). The saliva-to-plasma concentration analyzed with the methadone dose showed higher saliva concentrations at lower doses. Dose-normalized saliva concentrations followed a similar pattern over time compared with plasma concentrations. No correlation was found between l-methadone plasma, d-methadone plasma, l-methadone saliva, d-methadone saliva concentrations, and pain score. Saliva concentration was not a better predictor of pain control than plasma concentration for dose optimization and monitoring studies of methadone in patients with cancer. Although the saliva-to-plasma ratio of the concentration of methadone enantiomers was stable across the dosing range, due to the variability in individual saliva-to-plasma ratios, saliva sampling may not be a valid substitute in pharmacokinetic studies of methadone in cancer. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willegaignon, J., E-mail: j.willegaignon@gmail.com; Sapienza, M. T.; Coura-Filho, G. B.

Purpose: The precise determination of organ mass (m{sub th}) and total number of disintegrations within the thyroid gland (A{sup ~}) are essential for thyroid absorbed-dose calculations for radioiodine therapy. Nevertheless, these parameters may vary according to the method employed for their estimation, thus introducing uncertainty in the estimated thyroid absorbed dose and in any dose–response relationship derived using such estimates. In consideration of these points, thyroid absorbed doses for Graves’ disease (GD) treatment planning were calculated using different approaches to estimating the m{sub th} and the A{sup ~}. Methods: Fifty patients were included in the study. Thyroid{sup 131}I uptake measurementsmore » were performed at 2, 6, 24, 48, 96, and 220 h postadministration of a tracer activity in order to estimate the effective half-time (T{sub eff}) of {sup 131}I in the thyroid; the thyroid cumulated activity was then estimated using the T{sub eff} thus determined or, alternatively, calculated by numeric integration of the measured time-activity data. Thyroid mass was estimated by ultrasonography (USG) and scintigraphy (SCTG). Absorbed doses were calculated with the OLINDA/EXM software. The relationships between thyroid absorbed dose and therapy response were evaluated at 3 months and 1 year after therapy. Results: The average ratio (±1 standard deviation) betweenm{sub th} estimated by SCTG and USG was 1.74 (±0.64) and that between A{sup ~} obtained by T{sub eff} and the integration of measured activity in the gland was 1.71 (±0.14). These differences affect the calculated absorbed dose. Overall, therapeutic success, corresponding to induction of durable hypothyroidism or euthyroidism, was achieved in 72% of all patients at 3 months and in 90% at 1 year. A therapeutic success rate of at least 95% was found in the group of patients receiving doses of 200 Gy (p = 0.0483) and 330 Gy (p = 0.0131) when m{sub th} was measured by either USG or SCTG and A{sup ~} was determined by the integration of measured {sup 131}I activity in the thyroid gland and based on T{sub eff}, respectively. No statistically significant relationship was found between therapeutic response and patients’ age, administered {sup 131}I activity (MBq), 24-h thyroid {sup 131}I uptake (%) or T{sub eff} (p ≥ 0.064); nonetheless, a good relationship was found between the therapeutic response and m{sub th} (p ≤ 0.035). Conclusions: According to the results of this study, the most effective thyroid absorbed dose to be targeted in GD therapy should not be based on a fixed dose but rather should be individualized based on the patient'sm{sub th} and A{sup ~}. To achieve a therapeutic success (i.e., durable euthyroidism or hypothyroidism) rate of at least 95%, a thyroid absorbed dose of 200 or 330 Gy is required depending on the methodology used for estimating m{sub th} and A{sup ~}.« less

Graves' disease radioiodine-therapy: Choosing target absorbed doses for therapy planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willegaignon, J., E-mail: j.willegaignon@gmail.com; Sapienza, M. T.; Coura-Filho, G. B.

2014-01-15

Purpose: The precise determination of organ mass (m{sub th}) and total number of disintegrations within the thyroid gland (A{sup ~}) are essential for thyroid absorbed-dose calculations for radioiodine therapy. Nevertheless, these parameters may vary according to the method employed for their estimation, thus introducing uncertainty in the estimated thyroid absorbed dose and in any dose–response relationship derived using such estimates. In consideration of these points, thyroid absorbed doses for Graves’ disease (GD) treatment planning were calculated using different approaches to estimating the m{sub th} and the A{sup ~}. Methods: Fifty patients were included in the study. Thyroid{sup 131}I uptake measurementsmore » were performed at 2, 6, 24, 48, 96, and 220 h postadministration of a tracer activity in order to estimate the effective half-time (T{sub eff}) of {sup 131}I in the thyroid; the thyroid cumulated activity was then estimated using the T{sub eff} thus determined or, alternatively, calculated by numeric integration of the measured time-activity data. Thyroid mass was estimated by ultrasonography (USG) and scintigraphy (SCTG). Absorbed doses were calculated with the OLINDA/EXM software. The relationships between thyroid absorbed dose and therapy response were evaluated at 3 months and 1 year after therapy. Results: The average ratio (±1 standard deviation) betweenm{sub th} estimated by SCTG and USG was 1.74 (±0.64) and that between A{sup ~} obtained by T{sub eff} and the integration of measured activity in the gland was 1.71 (±0.14). These differences affect the calculated absorbed dose. Overall, therapeutic success, corresponding to induction of durable hypothyroidism or euthyroidism, was achieved in 72% of all patients at 3 months and in 90% at 1 year. A therapeutic success rate of at least 95% was found in the group of patients receiving doses of 200 Gy (p = 0.0483) and 330 Gy (p = 0.0131) when m{sub th} was measured by either USG or SCTG and A{sup ~} was determined by the integration of measured {sup 131}I activity in the thyroid gland and based on T{sub eff}, respectively. No statistically significant relationship was found between therapeutic response and patients’ age, administered {sup 131}I activity (MBq), 24-h thyroid {sup 131}I uptake (%) or T{sub eff} (p ≥ 0.064); nonetheless, a good relationship was found between the therapeutic response and m{sub th} (p ≤ 0.035). Conclusions: According to the results of this study, the most effective thyroid absorbed dose to be targeted in GD therapy should not be based on a fixed dose but rather should be individualized based on the patient'sm{sub th} and A{sup ~}. To achieve a therapeutic success (i.e., durable euthyroidism or hypothyroidism) rate of at least 95%, a thyroid absorbed dose of 200 or 330 Gy is required depending on the methodology used for estimating m{sub th} and A{sup ~}.« less

Organ dose conversion coefficients for tube current modulated CT protocols for an adult population

NASA Astrophysics Data System (ADS)

Fu, Wanyi; Tian, Xiaoyu; Sahbaee, Pooyan; Zhang, Yakun; Segars, William Paul; Samei, Ehsan

2016-03-01

In computed tomography (CT), patient-specific organ dose can be estimated using pre-calculated organ dose conversion coefficients (organ dose normalized by CTDIvol, h factor) database, taking into account patient size and scan coverage. The conversion coefficients have been previously estimated for routine body protocol classes, grouped by scan coverage, across an adult population for fixed tube current modulated CT. The coefficients, however, do not include the widely utilized tube current (mA) modulation scheme, which significantly impacts organ dose. This study aims to extend the h factors and the corresponding dose length product (DLP) to create effective dose conversion coefficients (k factor) database incorporating various tube current modulation strengths. Fifty-eight extended cardiac-torso (XCAT) phantoms were included in this study representing population anatomy variation in clinical practice. Four mA profiles, representing weak to strong mA dependency on body attenuation, were generated for each phantom and protocol class. A validated Monte Carlo program was used to simulate the organ dose. The organ dose and effective dose was further normalized by CTDIvol and DLP to derive the h factors and k factors, respectively. The h factors and k factors were summarized in an exponential regression model as a function of body size. Such a population-based mathematical model can provide a comprehensive organ dose estimation given body size and CTDIvol. The model was integrated into an iPhone app XCATdose version 2, enhancing the 1st version based upon fixed tube current modulation. With the organ dose calculator, physicists, physicians, and patients can conveniently estimate organ dose.

Effectiveness of a direct-to-consumer written health education program in the reduction of benzodiazepine and sedative-hypnotic use in an elderly population at a single Veterans Affairs medical center

PubMed Central

2018-01-01

Introduction: The use of benzodiazepines and sedative-hypnotics in the elderly is associated with a significant risk of delirium, falls, fractures, cognitive impairment, and motor vehicle accidents. This quality improvement project applies a direct-to-consumer intervention to an elderly veteran population to reduce the use of these medications. Methods: Patients aged 75 and older currently taking a benzodiazepine and/or a sedative-hypnotic were included in the project. Direct-to-consumer education intervention letters were mailed to patients within 30 days of their next appointment. Their providers were emailed a questionnaire after the patient's appointment. Providers were asked if the letter prompted a conversation regarding medication use, whether the provider initiated discussion regarding a taper, and whether a specific taper plan was developed. Medical records were reviewed to determine if a reduction in dose or discontinuation occurred. Results: Fifty-nine direct-to-consumer education letters were mailed to the patients. Follow-up questionnaires were e-mailed to 44 providers, and 27 providers responded. Twenty-two percent of patients had their benzodiazepine and/or sedative hypnotic dose reduced or discontinued after their follow-up appointment. Sixty-seven percent of veterans initiated a conversation with their provider regarding their medication with 74% of providers discussing dose reduction. Fifty-six percent of recipients developed a specific taper plan with their provider. Discussion: The data from this project suggests that direct-to-consumer patient education can reduce the exposure to benzodiazepines and sedative-hypnotics in an elderly veteran population. More data is needed on larger populations to further explore the benefit of direct-to-consumer interventions.

Pharmacokinetic Dashboard-Recommended Dosing Is Different than Standard of Care Dosing in Infliximab-Treated Pediatric IBD Patients.

PubMed

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.

High-versus standard-dose filgrastim (rhG-CSF) for mobilization of peripheral-blood progenitor cells from allogeneic donors and CD34(+) immunoselection.

PubMed

Engelhardt, M; Bertz, H; Afting, M; Waller, C F; Finke, J

1999-07-01

The efficacy of a high- versus a standard-dose filgrastim (recombinant human granulocyte colony-stimulating factor, or rhG-CSF) regimen to mobilize peripheral-blood progenitor cells (PBPCs) for allogeneic transplantation was investigated in 75 healthy donors. From December 1994 to December 1997, 75 consecutive donors (median age, 38 years; range, 17 to 67 years) were assigned to two different schedules of rhG-CSF for PBPC mobilization. Fifty donors received 24 microg rhG-CSF/kg body weight (BW) divided into two daily subcutaneous injections (two doses of 12 microg, group A), whereas 25 were treated with 10 microg rhG-CSF once daily (group B). Apheresis was started on day 4 in group A and on day 5 in group B. Target CD34(+) cell numbers in apheresis products were >/= 4 x 10(6)/kg recipient BW. Cytokine priming and collection of PBPCs were equally well tolerated in both groups. Significantly higher CD34(+) cell numbers in group A with 3. 7 x 10(6)/kg recipient BW/apheresis (0.47 x 10(6)/L apheresis) compared with 2 x 10(6)/kg recipient BW/apheresis (0.25 x 10(6)/L apharesis) in group B were obtained (P <.05). Using standard aphereses (median, 9 L), two doses of 12 microg rhG-CSF/kg allowed collection of >/= 4 x 10(6)/kg CD34(+) cells with two aphereses (range, one to three) in group A versus three aphereses (range, one to six) in group B (P <.015). Donor age, sex, and BW influenced the collection of CD34(+) cell numbers: in particular, significantly higher apheresis results were obtained in donors younger than 40 years compared with donors older than 40 years of age (P <.05). In 65 CD34(+) selection procedures using avidin-biotin immunoabsorption columns (Ceprate SC System, CellPro, Bothell, WA), a median CD34(+) purity of 53%, CD34(+) recovery of 40%, and the collection of 2 x 10(6)/kg CD34(+) cells/selection were achieved. In group A with higher CD34(+) cells/kg/apheresis, CD34(+) purity, recovery, and cell yields were 60%, 45%, and 2.3 x 10(6)/kg/selection, respectively, as compared with 48%, 31%, and 0.7 x 10(6)/kg in group B (P <.05). Our results demonstrate that twice daily rhG-CSF (two doses of 12 microg/kg BM) compared with once daily rhG-CSF (10 microg/kg BW), in addition to being well tolerated, significantly improves PBPC mobilization, allows the collection of higher numbers of CD34(+) cells with one or two standard aphereses, and facilitates subsequent selection procedures in healthy allogeneic donors.

Comparison of lornoxicam and low-dose tramadol for management of post-thyroidectomy pain.

PubMed

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.

The influence of residual apixaban on bleeding complications during and after catheter ablation of atrial fibrillation.

PubMed

Mukai, Yutaro; Wada, Kyoichi; Miyamoto, Koji; Nakagita, Kazuki; Fujimoto, Mai; Hosomi, Kouichi; Kuwahara, Takeshi; Takada, Mitsutaka; Kusano, Kengo; Oita, Akira

2017-10-01

The periprocedural protocol for atrial fibrillation (AF) ablation commonly includes anticoagulation therapy. Apixaban, a direct oral anticoagulant, is currently approved for clinical use; however, little is known about the effects of residual apixaban concentration on bleeding complications during/after AF ablation. Therefore, we measured residual apixaban concentration by using mass spectrometry and examined the anticoagulant's residual effects on bleeding complications. Fifty-eight patients (Mean age of 64.7±12.5 years; 31 males, 27 females) were enrolled and administered apixaban twice daily. We analyzed trough apixaban concentration, activated clotting time (ACT), heparin dose, and bleeding complications during/after AF ablation. Apixaban concentrations were directly measured using mass spectrometry. Bleeding complications were observed in 19 patients (delayed hemostasis at the puncture site, 16; hematuria, 3; hemosputum, 1). No patient required blood transfusion. The mean trough apixaban concentration was significantly lower in patients with bleeding complications than without (152.4±73.1 vs. 206.8±98.8 ng/mL respectively, P =0.037), while the heparin dose to achieve ACT>300 s was significantly higher in patients with bleeding complications (9368.4±2929.0 vs. 7987.2±2135.2 U/body respectively, P =0.046). Interestingly, a negative correlation was found between the trough apixaban concentration and the heparin dose to achieve ACT>300 s ( P =0.033, R=-0.281). Low residual plasma apixaban is associated with a higher incidence of bleeding complications during/after AF ablation, potentially because of a greater heparin requirement during AF ablation.

Prevention and treatment of venous thromboembolism in patients with solid brain neoplasms: results of a survey among Italian physicians.

PubMed

Mumoli, Nicola; Barco, Stefano; Cei, Marco; Giorgi-Pierfranceschi, Matteo; Campanini, Mauro; Fontanella, Andrea; Ageno, Walter; Dentali, Francesco

2017-06-01

The decision concerning the introduction of primary and secondary prophylaxis of venous thromboembolism (VTE) in patients with solid brain neoplasms and brain metastases is often challenging due to the concomitant increased risk of intracranial hemorrhage and to limited evidence from available literature. A standardized questionnaire composed of nine multiple-choice questions regarding primary VTE prevention in non-surgical patients during high-risk conditions and VTE secondary prevention in patients with a solid brain neoplasm or cerebral metastases was sent via electronic mail to all the members (n = 2420) of the Italian Federation of the Internal Medicine Hospital Executives' Associations (FADOI) in June 2015. Three hundred and fifty two physicians (14.5%) returned it (participants' median age 51 years; females 46.9%). The majority of respondents prescribe primary thromboprophylaxis (usually with heparin) in non-surgical patients with solid brain neoplasms and brain metastases in concomitance with high-risk conditions. Full-dose anticoagulation with either low-molecular-weight heparin or fondaparinux is the preferred option for acute VTE (69.6%), while a reduced dose is chosen by 21.0% of physicians. The presence of a highly vascular brain neoplasm histotype mandates the prescription of a reduced-dose antithrombotic regimen in a minority of respondents. Vena cava filter placement is an option for the treatment of acute VTE in more than 6% of respondents. Anticoagulants are often prescribed for both VTE primary prevention and treatment. In conclusion, physicians' managements are partially in contrast to recent guidelines, reinforcing the need for educational programs and other studies in this setting.

Reduced-Intensity Conditioning Combined with (188)Rhenium Radioimmunotherapy before Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia: The Role of In Vivo T Cell Depletion.

PubMed

Schneider, Sebastian; Strumpf, Annette; Schetelig, Johannes; Wunderlich, Gerd; Ehninger, Gerhard; Kotzerke, Jörg; Bornhäuser, Martin

2015-10-01

The combination of reduced-intensity conditioning, (188)rhenium anti-CD66 radioimmunotherapy, and in vivo T cell depletion was successfully applied in elderly patients with acute myeloid leukemia or myelodysplastic syndrome. Within a prospective phase II protocol, we investigated whether a dose reduction of alemtuzumab (from 75 mg to 50 mg MabCampath) would improve leukemia-free survival by reducing the incidence of relapse. Fifty-eight patients (median age, 67 years; range, 54 to 76) received radioimmunotherapy followed by fludarabine 150 mg/m(2) and busulfan 8 mg/kg combined with either 75 mg (n = 26) or 50 mg (n = 32) alemtuzumab. Although we observed a trend towards a shorter duration of neutropenia in the 50 mg group (median, 19 versus 21 days; P = .07), the time from transplantation to neutrophil and platelet engraftment as well as the overall incidence of engraftment did not differ. The incidence of severe acute graft-versus-host disease tended to be higher after the lower alemtuzumab dose (17% versus 4%; P = .15). No significant differences in the cumulative incidences of relapse (38% versus 35%; P = .81) or nonrelapse mortality (46% versus 27%; P = .31) were observed. Accordingly, disease-free and overall survival were not significantly different between groups. Although the feasibility of radioimmunotherapy plus reduced-intensity conditioning could be demonstrated in elderly patients, the dose reduction of alemtuzumab had no positive impact on overall outcome. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.

PubMed

Nash, Richard A; Dansey, Roger; Storek, Jan; Georges, George E; Bowen, James D; Holmberg, Leona A; Kraft, George H; Mayes, Maureen D; McDonagh, Kevin T; Chen, Chien-Shing; Dipersio, John; Lemaistre, C Fred; Pavletic, Steven; Sullivan, Keith M; Sunderhaus, Julie; Furst, Daniel E; McSweeney, Peter A

2003-09-01

High-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated for the control of severe autoimmune diseases. The addition of antithymocyte globulin (ATG) to high-dose chemoradiotherapy in the high-dose immunosuppressive therapy regimen and CD34 selection of the autologous graft may induce a higher degree of immunosuppression compared with conventional autologous HSCT for malignant diseases. Patients may be at higher risk of transplant-related complications secondary to the immunosuppressed state, including Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD), but this is an unusual complication after autologous HSCT. Fifty-six patients (median age, 42 years; range, 23-61 years) with either multiple sclerosis (n = 26) or systemic sclerosis (n = 30) have been treated. The median follow-up has been 24 months (range, 2-60 months). Two patients (multiple sclerosis, n = 1; systemic sclerosis, n = 1) had significant reactivations of herpesvirus infections early after HSCT and then developed aggressive EBV-PTLD and died on days +53 and +64. Multiorgan clonal B-cell infiltrates that were EBV positive by molecular studies or immunohistology were identified at both autopsies. Both patients had positive screening skin tests for equine ATG (Atgam) and had been converted to rabbit ATG (Thymoglobulin) from the first dose. Of the other 54 patients, 2 of whom had partial courses of rabbit ATG because of a reaction to the intravenous infusion of equine ATG, only 1 patient had a significant clinical reactivation of a herpesvirus infection (herpes simplex virus 2) early after HSCT, and none developed EBV-PTLD. The T-cell count in the peripheral blood on day 28 was 0/microL in all 4 patients who received rabbit ATG; this was significantly less than in patients who received equine ATG (median, 174/microL; P =.001; Mann-Whitney ranked sum test). Although the numbers are limited, the time course and similarity of the 2 cases of EBV-PTLD and the effect on day 28 T-cell counts support a relationship between the development of EBV-PTLD and the administration of rabbit ATG. The differences between equine and rabbit ATG are not yet clearly defined, and they should not be considered interchangeable in this regimen without further study.

Extended Infusion of Piperacillin/Tazobactam in Children.

PubMed

Knoderer, Chad A; Karmire, Lauren C; Andricopulos, Katie L; Nichols, Kristen R

2017-01-01

Extended-infusion piperacillin/tazobactam (TZP) has been associated with positive clinical outcomes in adults, but similar data in children are lacking. The objective of this study was to describe efficacy outcomes with pediatric patients receiving extended-infusion TZP. This was a retrospective case series of children aged 1 month to 17 years who had documented Gram-negative infection and received extended-infusion TZP between April 2011 and March 2012. The primary outcome was 21-day clinical cure defined as negative follow-up cultures, where available, and infection resolution. Fifty children with a median (interquartile range [IQR]) age of 5 (2-9) years were included in the study. Patients received a median (IQR) TZP dose of 111.4 (100-112.5) mg/kg administered every 8 hours over 4 hours. Clinical and microbiologic cure were observed in 74% and 100% of patients, respectively. Patients not meeting criterial for 21-day clinical cure were younger (1 vs 7 years, p = 0.087) and had a longer length of hospital stay (23 vs 11 days, p = 0.037). The majority of children in this cohort achieved 21-day clinical cure with extended-interval TZP. Those without clinical cure tended to be younger and critically ill. Additional comparative studies evaluating traditional and extended-infusion TZP in children are needed.

Effect of aspirin on acute changes in peripheral arterial stiffness and endothelial function following exertional heat stress in firefighters: The factorial group results of the Enhanced Firefighter Rehab Trial.

PubMed

Olafiranye, Oladipupo; Hostler, David; Winger, Daniel G; Wang, Li; Reis, Steven E

2015-06-01

Peripheral arterial stiffness and endothelial function, which are independent predictors of cardiac events, are abnormal in firefighters. We examined the effects of aspirin on peripheral arterial stiffness and endothelial function in firefighters. Fifty-two firefighters were randomized to receive daily 81 mg aspirin or placebo for 14 days before treadmill exercise in thermal protection clothing, and a single dose of 325 mg aspirin or placebo immediately following exertion. Peripheral arterial augmentation index adjusted for a heart rate of 75 (AI75) and reactive hyperemia index (RHI) were determined immediately before, and 30, 60, and 90 minutes after exertion. Low-dose aspirin was associated with lower AI75 (-15.25±9.25 vs -8.08±10.70, p=0.014) but not RHI. On repeated measures analysis, treatment with low-dose aspirin before, but not single-dose aspirin after exertion, was associated with lower AI75 following exertional heat stress (p=0.018). Low-dose aspirin improved peripheral arterial stiffness and wave reflection but not endothelial function in firefighters. © The Author(s) 2015.

Feasibility of Chlamydia trachomatis screening and treatment in pregnant women in Lima, Peru: a prospective study in two large urban hospitals.

PubMed

Cabeza, Jeanne; García, Patricia J; Segura, Eddy; García, Pedro; Escudero, Francisco; La Rosa, Sayda; León, Segundo; Klausner, Jeffrey D

2015-02-01

Chlamydia trachomatis, which is asymptomatic in most women, causes significant adverse effects for pregnant women and neonates. No programmes conduct antenatal screening in Latin America. We determined chlamydia prevalence, feasibility and acceptability of chlamydia screening, and adherence to treatment in pregnant women in two urban public hospitals in Lima, Peru. We offered chlamydia screening using self-collected vaginal swabs to pregnant women ≥ 16 years of age during their first antenatal visit. Chlamydia-infected women were contacted within 14 days and asked to bring partners for counselling and directly observed therapy with oral azithromycin. Unaccompanied women received counselling, directly observed therapy, and azithromycin to take to partners. Test of cure was performed ≥ 3 weeks after treatment. We approached 640 women for the study and enrolled 600 (93.8%). Median age was 27.3 years (range 16-47), median lifetime partners 2.3 (range 1-50), and median gestational age 26.1 weeks (range 4-41). Chlamydia prevalence was 10% (95% CI 7.7% to 12.7%). Of 60 infected patients, 59 (98%) were treated with one dose of azithromycin. Fifty-two of 59 (88%) returned for test of cure, all of whom were treated successfully, with 46 (86%) achieving negative test of cure with one dose of azithromycin, and 6 (12%) after retreatment with a second dose. C. trachomatis screening and treatment in pregnancy was feasible and highly acceptable in two urban hospitals in Peru. Chlamydia prevalence was high. Clinical trials to evaluate efficacy and cost-effectiveness of chlamydia screening, and treatment of pregnant women to prevent adverse pregnancy outcomes in low-resource settings, are warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Metacognition deficits as a risk factor for prospective motivation deficits in schizophrenia spectrum disorders.

PubMed

Luther, Lauren; Firmin, Ruth L; Minor, Kyle S; Vohs, Jenifer L; Buck, Benjamin; Buck, Kelly D; Lysaker, Paul H

2016-11-30

Although motivation deficits are key determinants of functional outcomes, little is known about factors that contribute to prospective motivation in people with schizophrenia. One candidate factor is metacognition, or the ability to form complex representations about oneself, others, and the world. This study aimed to assess whether metacognition deficits were a significant predictor of reduced prospective motivation, after controlling for the effects of baseline motivation, anticipatory pleasure, and antipsychotic medication dose. Fifty-one participants with a schizophrenia spectrum disorder completed measures of metacognition and anticipatory pleasure at baseline; participants also completed a measure of motivation at baseline and six months after the initial assessment. Baseline antipsychotic dose was obtained from medical charts. Hierarchical regression analysis revealed that lower levels of baseline metacognition significantly predicted reduced levels of motivation assessed six months later, after controlling for baseline levels of motivation, anticipatory pleasure, and antipsychotic dose. Higher baseline antipsychotic dose was also a significant predictor of reduced six month motivation. Results suggest that metacognition deficits and higher antipsychotic dose may be risk factors for the development of motivation deficits in schizophrenia. Implications include utilizing interventions to improve metacognition in conjunction with evaluating and possibly lowering antipsychotic dose for people struggling with motivation deficits. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Feasibility of Preoperative Chemotherapy With or Without Radiation Therapy in Localized Soft Tissue Sarcomas of Limbs and Superficial Trunk in the Italian Sarcoma Group/Grupo Español de Investigación en Sarcomas Randomized Clinical Trial: Three Versus Five Cycles of Full-Dose Epirubicin Plus Ifosfamide.

PubMed

Palassini, Elena; Ferrari, Stefano; Verderio, Paolo; De Paoli, Antonino; Martin Broto, Javier; Quagliuolo, Vittorio; Comandone, Alessandro; Sangalli, Claudia; Palmerini, Emanuela; Lopez-Pousa, Antonio; De Sanctis, Rita; Bottelli, Stefano; Libertini, Michela; Picci, Piero; Casali, Paolo G; Gronchi, Alessandro

2015-11-01

We report on feasibility of preoperative chemotherapy with or without radiation therapy (RT) in the context of a phase III randomized clinical trial involving localized, high-risk, soft tissue sarcomas. Of 321 eligible patients, 161 were randomly assigned to three preoperative cycles of epirubicin 120 mg/m(2) plus ifosfamide 9 g/m(2), and 160 were randomly assigned to three preoperative plus two postoperative cycles. Among them, 303 patients were included in this analysis; 169 were male and 134 were female, with a median age of 48 years (range, 15 to 79 years). One hundred fifty-two patients received concurrent RT preoperatively at a total dose of 44 to 50 Gy. Preoperative chemotherapy-related hematologic toxicity and early postoperative complications were reported. The influence of RT, age, and sex on hematologic grade 3 or 4 toxicities and wound complications was analyzed. Chemotherapeutic dose intensity (DI) was analyzed. Among the patients, 61.4%, 22.4%, and 23.8% experienced, grade 4 leucopenia, grade 3 or 4 anemia, and grade 3 or 4 thrombocytopenia, respectively. Respective rates were 66.4%, 24.3%, and 31.6% when RT was added preoperatively, and 56.3%, 20.5%, and 15.9% when preoperative chemotherapy was administered alone. Patient age affected grade 3 or 4 thrombocytopenia. Grade 4 leucopenia and grade 3 or 4 anemia presented 2.5 times more frequently in female patients than in male patients. Wound complications were observed in 13.5% of patients: 17% with preoperative RT and 10% without. Chemotherapeutic DI was greater than 90%, even in patients receiving preoperative RT and in patients age 65 years or older. This preoperative chemotherapy is feasible and can also be proposed for selected elderly patients. Grade 3 or 4 hematologic toxicity was common, but DI was excellent. Concurrent preoperative RT is safe, although an increased rate of grade 4 thrombocytopenia and limited increase in wound complications may be observed. © 2015 by American Society of Clinical Oncology.

Comparison of ambulatory blood pressure-lowering effects of higher doses of different calcium antagonists in uncontrolled hypertension: the Calcium Antagonist Controlled-Release High-Dose Therapy in Uncontrolled Refractory Hypertensive Patients (CARILLON) Study.

PubMed

Mizuno, Hiroyuki; Hoshide, Satoshi; Tomitani, Naoko; Kario, Kazuomi

2017-10-01

Data are sparse regarding ambulatory blood pressure (BP) reduction of up-titration from a standard dose to a high dose in both nifedipine controlled-release (CR) and amlodipine. This was a prospective, randomized, multicenter, open-label trial. Fifty-one uncontrolled hypertensives medicated by two or more antihypertensive drugs including a renin-angiotensin system inhibitor and a calcium antagonist were randomly assigned to either the nifedipine CR (80 mg)/candesartan (8 mg) group or the amlodipine (10 mg)/candesartan (8 mg) group. The changes in 24-hr BP were comparable between the groups. The nifedipine group demonstrated a significant decrease in their urinary albumin creatinine ratio, whereas the amlodipine group demonstrated a significant decrease in their NTproBNP level. However, there was no significant difference in any biomarkers between the two groups. Nifedipine showed an almost equal effect on ambulatory blood pressure as amlodipine. Their potentially differential effects on renal protection and NTproBNP should be tested in larger samples.

Nutrition intervention for high-risk auto workers: results of the Next Step Trial.

PubMed

Tilley, B C; Glanz, K; Kristal, A R; Hirst, K; Li, S; Vernon, S W; Myers, R

1999-03-01

The Next Step Trial tested interventions encouraging prevention and early detection practices in automotive-industry employees at increased colorectal cancer risk. This article describes results of the nutrition intervention promoting low-fat, high-fiber eating patterns. Twenty-eight worksites (5,042 employees at baseline) were randomized to a 2-year nutrition intervention including classes, mailed self-help materials, and personalized dietary feedback. Control worksites received no intervention. Nutrition outcomes were assessed by mailed food frequency questionnaires (FFQs) Primary nutrition outcomes included percentage energy from fat and fiber density (g/1,000 kcal) at 1 year postrandomization. Secondary outcomes included servings of fruits/vegetables and dietary measures at 2 years postrandomization. Analyses were adjusted for within worksite correlations and baseline covariates. Fifty-eight percent of employees returned FFQs. At 1 year, there were modest but statistically significant intervention effects for fat (-0.9 %en), fiber (+0.5 g/1,000 kcal), and fruits/vegetables (+0.2 servings/day) (all P < 0.007). At 2 years, due to significant positive changes in control worksites, intervention effects were smaller, significant for fiber only. Intervention effects were larger in younger (<50 years), active employees and class attendees. The nutrition intervention produced significant but modest effects on dietary fat and fiber and fruits/vegetables in these high-risk employees. Age and dose effects suggest younger employees may be more responsive to this intervention. Copyright 1999 American Health Foundation and Academic Press.

Is the fluoride intake by diet and toothpaste in children living in tropical semi-arid city safe?

PubMed

Oliveira, Priscila Ferreira Torres de; Cury, Jaime Aparecido; Lima, Carolina Veloso; Vale, Glauber Campos; Lima, Marina de Deus Moura de; Moura, Lúcia de Fátima Almeida de Deus; Moura, Marcoeli Silva de

2018-01-01

Data about total fluoride intake in children living in a tropical semi-arid climate city is scarce, thus we conducted this study. Fifty-eight children aged two to five years, living in a Brazilian tropical city with optimally fluoridated water were selected. Dietary samples were collected using the duplicate diet method on two non-consecutive days in the children's home toothpaste was determined by subtracting the amount of fluoride recovered after brushing from the amount placed on the toothbrush. The mean total dose (SD) of fluoride intake was 0.043(0.016) mg F·kg-1·d-1, with the major (60.6%) contribution from water. The factors associated with the ingestion of fluoride from toothpaste were fluoride concentration of the toothpaste (p = 0.03) and the use of kids toothpaste (p = 0.02). The findings suggest that children have a low fluoride intake, measured by at-home meals and use of fluoride toothpaste; drinking water is the main source of fluoride ingestion.

Development of scale inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gill, J.S.

1996-12-01

During the last fifty years, scale inhibition has gone from an art to a science. Scale inhibition has changed from simple pH adjustment to the use of optimized dose of designer polymers from multiple monomers. The water-treatment industry faces many challenges due to the need to conserve water, availability of only low quality water, increasing environmental regulations of the water discharge, and concern for human safety when using acid. Natural materials such as starch, lignin, tannin, etc., have been replaced with hydrolytically stable organic phosphates and synthetic polymers. Most progress in scale inhibition has come from the use of synergisticmore » mixtures and copolymerizing different functionalities to achieve specific goals. Development of scale inhibitors requires an understanding of the mechanism of crystal growth and its inhibition. This paper discusses the historic perspective of scale inhibition and the development of new inhibitors based on the understanding of the mechanism of crystal growth and the use of powerful tools like molecular modeling to visualize crystal-inhibitor interactions.« less

Strategy aimed at reduction of sputum eosinophils decreases exacerbation rate in patients with asthma.

PubMed

Chlumský, J; Striz, I; Terl, M; Vondracek, J

2006-01-01

Under Global Initiative for Asthma guidelines, the clinical control of disease activity and the adjustment of treatment in patients with asthma are based on symptoms, use of rescue medication, lung function and peak expiratory flow measurement (standard strategy). We investigated whether a strategy to reduce the number of sputum eosinophils (EOS strategy) gives better clinical control and a lower exacerbation rate compared with the standard strategy. Fifty-five patients with moderate to severe asthma entered this open, randomized, parallel-group study and visited the out-patient department every 3 months for 18 months. The dose of corticosteroids was adjusted according to the standard strategy or the percentage of sputum eosinophils (EOS strategy). During the study period, the EOS strategy led to a significantly lower incidence of asthma exacerbations compared with the standard strategy group (0.22 and 0.78 exacerbations per year per patient, respectively). There were significant differences between the strategies in time to first exacerbation.

Is omphalocele a non-specific malformation in New Zealand White rabbits?

PubMed

Daston, George P; Beekhuijzen, Manon

2018-06-01

We evaluated the incidence of omphalocele, a malformation that occurs sporadically in many studies. We assembled data on external malformations using all treatment groups from every study published in three major journals over the past 35 years using New Zealand White rabbits. Fifty-eight papers were included: 4905 litters and 36,977 fetuses. Omphalocele was reported in 43% and was among the most common defects, occurring at a rate of 1.10% (litter) and 0.16% (fetus). The defect did not appear to be treatment-related, although it may have been in two studies, based on rate and dose-responsiveness. Removing these two studies from the analysis, the defect was still prevalent (0.77% litter, 0.11% fetal incidence). Three studies evaluated the effects of food restriction and omphalocele was observed with food restriction in two of them, suggesting that decreased maternal weight gain or food consumption may be causal. Otherwise, it appears to be spontaneous and common. Copyright © 2018 Elsevier Inc. All rights reserved.

A Different Laboratory Tale: Fifty Years of Mössbauer Spectroscopy

NASA Astrophysics Data System (ADS)

Westfall, Catherine

2006-05-01

I explore the fifty-year development of Mössbauer spectroscopy by focusing on three episodes in its development at Argonne National Laboratory: work by nuclear physicists using radioactive sources in the early 1960s, work by solid-state physicists using radioactive resources from the mid- 1960s through the 1970s,and work by solid-state physicists using the Advanced Photon Source from the 1980s to 2005. These episodes show how knowledge about the properties of matter was produced in a national-laboratory context and highlights the web of connections that allow nationallaboratory scientists working at a variety of scales to produce both technological and scientific innovations.

Cruelty in Maternity Wards: Fifty Years Later

PubMed Central

Goer, Henci

2010-01-01

Fifty years have passed since a scandal broke over inhumane treatment of laboring women in U.S. hospitals, yet first-person and eyewitness reports document that medical care providers continue to subject childbearing women to verbal and physical abuse and even to what would constitute sexual assault in any other context. Women frequently are denied their right to make informed decisions about care and may be punished for attempting to assert their right to refusal. Mistreatment is not uncommon and persists because of factors inherent to hospital social culture. Concerted action on the part of all stakeholders will be required to bring about systemic reform. PMID:21629381

Selected clinical aspects of acute intoxication with baclofen.

PubMed

Sein Anand, Jacek; Chodorowski, Zygmunt; Burda, Piotr

2005-01-01

Baclofen is a lipophilic analogue of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in central nervous system. The aim of the study was to evaluate some clinical aspects of acute intoxication with baclofen. Fifty two patients (37 females and 15 males) aged from 14 to 58 (mean 30.6 +/- 13.7) years were analyzed. Patients were admitted to the Clinic of Internal Diseases and Acute Poisonings Medical University of Gdańsk and the Centre of Acute Poisonings of Praski Hospital in Warszawa during the years 1996-2004 because of suicidal intoxication with baclofen. The doses of baclofen varied from 100 to 1500 (mean 444.8 +/- 317.8) mg. There were twenty eight patients (53.8%) in deep coma (III and IV grade of Matthew scale). Acute respiratory failure which required mechanical ventilation was observed in 18 cases (34.6%). Cardiac abnormalities included bradycardia (36.5%), hypertension (32.7%) and hypotension (3.8%). Toxic psychoses were observed in 6 cases (11.5%). The dosage of baclofen in patients with acute respiratory failure (ARF) was significantly higher than in patients without ARF. Treatment of patients with acute baclofen intoxication should take place in hospitals appropriately equipped which can provide artificial respiration.

Using Quality of Life Measures in a Phase I Clinical Trial of Noni in Patients with Advanced Cancer to Select a Phase II Dose

PubMed Central

Issell, Brian F.; Gotay, Carolyn C.; Pagano, Ian; Franke, A. Adrian

2015-01-01

Purpose We conducted a Phase I study of noni in patients with advanced cancer. Quality of life measures were examined as an alternate way to select a Phase II dose of this popular dietary supplement. Patients and Methods Starting at two capsules twice daily (2 grams), the dose suggested for marketed products, dose levels were escalated by 2 grams daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed QLQ-C30 Quality of Life, and the Brief Fatigue Inventory (BFI), questionnaires at baseline and at four week intervals. Scopoletin was measured in blood and urine collected at baseline and at approximately four week intervals. Results Fifty-one patients were enrolled at seven dose levels. Seven capsules four times daily (14 grams) was the maximum tolerated dose. No dose limiting toxicity was found but four of eight patients at this level withdrew from the study due to the challenges of ingesting so many capsules. There was a dose response for self reported physical functioning and the control of pain and fatigue. Patients taking four capsules four times daily experienced less fatigue than patients taking lower or higher doses. A relationship between noni dose and blood and urinary scopoletin concentrations was found. Conclusion Measuring quality of life to determine a dose for subsequent Phase II testing is feasible. A noni dose of four capsules four times daily (8 grams) is recommended for Phase II testing where controlling fatigue and maintaining physical function is the efficacy of interest. Scopoletin is a measurable noni ingredient for pharmacokinetic studies in patients with cancer. PMID:22435516

Retrospective dosimetry related to chronic environmental exposure

NASA Technical Reports Server (NTRS)

Degteva, M. O.; Kozheurov, V. P.; Tolstykh, E. I.; Neta, R. (Principal Investigator)

1998-01-01

Radioactive contamination of the environment occurred in the early fifties as a result of the releases from the Mayak plutonium production complex (Southern Urals, Russia). The releases of liquid wastes into the Techa river resulted in chronic exposure of 30,000 residents of the riverside communities. Since 1951 90Sr body burdens have been measured for over half of this cohort. This paper presents the analysis of data on 90Sr in humans and describes the reconstruction of internal doses for these people.

Double-Blind Comparison of Iodamide and Diatrizoate for Excretory Urography 1

PubMed Central

Rosenfield, Arthur T.; Putman, Charles E.; Ulreich, Sidney; Koss, Neal

1977-01-01

A double-blind comparison of meglumine iodamide and Renografin 60 (52% meglumine diatrizoate and 8% sodium diatrizoate) for bolus excretory urography was performed. Doses of 0.8 cc/kg. to a maximum of 55 cc were administered to fifty patients, twenty-five receiving each drug. There is a suggestion that iodamide may be superior to diatrizoate in pyelocalyceal opacification while being equal to diatrizoate in parenchymal opacification and in types and severity of side-effects. PMID:345632

Retrospective dosimetry related to chronic environmental exposure.

PubMed

Degteva, M O; Kozheurov, V P; Tolstykh, E I

1998-01-01

Radioactive contamination of the environment occurred in the early fifties as a result of the releases from the Mayak plutonium production complex (Southern Urals, Russia). The releases of liquid wastes into the Techa river resulted in chronic exposure of 30,000 residents of the riverside communities. Since 1951 90Sr body burdens have been measured for over half of this cohort. This paper presents the analysis of data on 90Sr in humans and describes the reconstruction of internal doses for these people.

Effectiveness of amoxicillin/clavulanate potassium in the treatment of acute bacterial sinusitis in children.

PubMed

Wald, Ellen R; Nash, David; Eickhoff, Jens

2009-07-01

The role of antibiotic therapy in managing acute bacterial sinusitis (ABS) in children is controversial. The purpose of this study was to determine the effectiveness of high-dose amoxicillin/potassium clavulanate in the treatment of children diagnosed with ABS. This was a randomized, double-blind, placebo-controlled study. Children 1 to 10 years of age with a clinical presentation compatible with ABS were eligible for participation. Patients were stratified according to age (<6 or >or=6 years) and clinical severity and randomly assigned to receive either amoxicillin (90 mg/kg) with potassium clavulanate (6.4 mg/kg) or placebo. A symptom survey was performed on days 0, 1, 2, 3, 5, 7, 10, 20, and 30. Patients were examined on day 14. Children's conditions were rated as cured, improved, or failed according to scoring rules. Two thousand one hundred thirty-five children with respiratory complaints were screened for enrollment; 139 (6.5%) had ABS. Fifty-eight patients were enrolled, and 56 were randomly assigned. The mean age was 66 +/- 30 months. Fifty (89%) patients presented with persistent symptoms, and 6 (11%) presented with nonpersistent symptoms. In 24 (43%) children, the illness was classified as mild, whereas in the remaining 32 (57%) children it was severe. Of the 28 children who received the antibiotic, 14 (50%) were cured, 4 (14%) were improved, 4 (14%) experienced treatment failure, and 6 (21%) withdrew. Of the 28 children who received placebo, 4 (14%) were cured, 5 (18%) improved, and 19 (68%) experienced treatment failure. Children receiving the antibiotic were more likely to be cured (50% vs 14%) and less likely to have treatment failure (14% vs 68%) than children receiving the placebo. ABS is a common complication of viral upper respiratory infections. Amoxicillin/potassium clavulanate results in significantly more cures and fewer failures than placebo, according to parental report of time to resolution of clinical symptoms.

Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease

PubMed Central

Penagini, Roberto; Sweis, Rami; Mauro, Aurelio; Domingues, Gerson; Vales, Andres; Sifrim, Daniel

2015-01-01

Background/Aims The diagnosis of functional heartburn is important for management, however it stands on fragile pH monitoring variables, ie, acid exposure time varies from day to day and symptoms are often few or absent. Aim of this study was to investigate consistency of the diagnosis of functional heartburn in subsequent days using prolonged wireless pH monitoring and its impact on patients’ outcome. Methods Fifty proton pump inhibitotor refractory patients (11 male, 48 years [range, 38–57 years]) with a diagnosis of functional heart-burn according to Rome III in the first 24 hours of wireless pH monitoring were reviewed. pH variables were analysed in the following 24-hour periods to determine if tracings were indicative of diagnosis of non-erosive reflux disease (either acid exposure time > 5% or normal acid exposure time and symptom index ≥ 50%). Outcome was assessed by review of hospital files and/or telephone interview. Results Fifteen out of 50 patients had a pathological acid exposure time after the first day of monitoring (10 in the second day and 5 in subsequent days), which changed their diagnosis from functional heartburn to non-erosive reflux disease. Fifty-four percent of non-erosive reflux disease vs 11% of functional heartburn patients (P < 0.003) increased the dose of proton pump inhibitors or underwent fundoplication after the pH test. Outcome was positive in 77% of non-erosive reflux disease vs 43% of functional heartburn patients (P < 0.05). Conclusions One-third of patients classified as functional heartburn at 24-hour pH-monitoring can be re-classified as non-erosive reflux disease after a more prolonged pH recording period. This observation has a positive impact on patients’ management. PMID:25843078

The immunizing effect and reactogenicity of two live attenuated mumps virus vaccines in Swedish schoolchildren.

PubMed

Christenson, B; Heller, L; Böttiger, M

1983-10-01

An evaluation of the seroconversion and booster effects after vaccination with two different mumps vaccines, the Urabe Am 9 strain and the Jeryl Lynn strain, was carried out in schoolchildren. Four hundred and fifty-four schoolchildren aged 11 to 12 years with no previous history of mumps or mumps vaccination were enrolled for the study. The antibody responses were measured by serum neutralization (SN) and haemolysis-in-gel (HIG) tests. Of the 454 subjects, 130 were found to be initially seronegative. Two lots of different strengths of each vaccine were used to evaluate the relationships. The Urabe Am 9 vaccine lots had infectivity titres of 100 000 and 19 000 TCID50 per dose and the Jeryl Lynn vaccine titres of 59 000 and 28 000 TCID50 per dose. Only slight differences in seroconversion rates were seen between the lots. The overall seroconversion rate, measured by SN, was 94% for the Urabe Am 9 vaccine and 91% for the Jeryl Lynn vaccine, whereas the geometric mean titre for virus-neutralizing antibody in seroconverting children was 7.4 with the Urabe Am 9 vaccine and 10.7 with the Jeryl Lynn vaccine. In children who were seropositive prior to vaccination, a marked rise in antibody titre was found 8 weeks after vaccine injection indicating a booster effect. The miscellaneous post-vaccination side-effects were mild and inconsequential.

[Effect of low-dose focused ultrasound pre-irradiation versus microbubbles for enhancing high-intensity focused ultrasound ablation of VX2 hepatic tumor in rabbits].

PubMed

Zhang, Yi; Yang, Chao; Zou, Jian-Zhong; Chen, Fei; Ou, Xia; Zou, Hai-Rong; Wang, Yan

2016-10-20

To compare the effect of low-dose focused ultrasound pre-irradiation and microbubbles for enhancing the ablation effect of high intensity focused ultrasound (HIFU) on VX 2 hepatic tumor in rabbits. Fifty-five rabbits bearing VX 2 hepatic tumor were randomly divided into low-dose pre-irradiation + HIFU ablation group, microbubbles+HIFU ablation group, and HIFU ablation group for corresponding treatments. The pathological changes in the tumors after low-dose irradiation, time for HIFU ablation, tumor volume with coagulative necrosis, energy efficiency factor (EEF), pathological changes in the ablated tumor, and sound channel of HIFU ablation were observed. Tumor cell edema, vacuolar changes in the cytoplasm and tumor interstitial vascular congestion were observed 24 h after low-dose pre-irradiation. The ablation time were significantly shorter, coagulative necrosis volume was larger, and EEF was lower in low-dose irradiation + HIFU ablation group and microbubbles+HIFU ablation group than in simple HIFU ablation group (P<0.05), but the differences between the former two groups were not significant. The effectiveness and stability of the synergistic effect of low-dose pre-irradiation were inferior to microbubbles, but the former ensured a better safety of the sound channel. Low-dose irradiation has comparable synergistic effect in HIFU with microbubbles with such advantages as non-invasiveness, high concentration and good safety, and can be a potentially new method to enhance the efficiency of HIFU.

Neurotoxicity of subarachnoid hyperbaric bupivacaine in dogs.

PubMed

Ganem, E M; Vianna, P T; Marques, M; Castiglia, Y M; Vane, L A

1996-01-01

The study investigated possible neurotoxic effects of increasing concentrations and doses of bupivacaine administered into the subarachnoid space in dogs. Fifty animals were allocated to five experimental groups: G1, control; G2, 5 mg 0.5 bupivacaine in 10% glucose solution; G3, 10 mg of 1% bupivacaine in 10% glucose solution; G4, 20 mg 2% bupivacaine in 10% glucose solution, and G5, 20 mg 2% bupivacaine in water. After 72 hours of observation, the animals were killed and the spinal cords removed for histologic examination by light microscopy. None of the animals showed any neurologic clinical disturbance following recovery from spinal anesthesia. One case of necrosis of nerve tissue was observed in G3 and four in G4. Increasing concentrations and doses of hyperbaric bupivacaine solutions increased the incidence of nerve tissue damage, which did not occur with hypobaric solutions. These results should contribute to the further understanding of neurologic complications following spinal anesthesia when large doses of local anesthetics in hyperbaric solutions are used.

RESULTS OF THE MEGAVERTEBRATE ANALGESIA SURVEY: ELEPHANTS AND RHINO.

PubMed

Kottwitz, Jack; Boothe, Matthew; Harmon, Roy; Citino, Scott B; Zuba, Jeffery R; Boothe, Dawn M

2016-03-01

An online survey utilizing Survey Monkey linked through the American Association of Zoo Veterinarians listserve examined current practices in megavertebrate analgesia. Data collected included drugs administered, dosing regimens, ease of administration, efficacy, and adverse events. Fifty-nine facilities (38 housing elephants, 33 housing rhinoceroses) responded. All facilities administered nonsteroidal anti-inflammatory drugs (NSAIDs), with phenylbutazone (0.25-10 mg/kg) and flunixin meglumine (0.2-4 mg/kg) being most common. Efficacy was reported as "good" to "excellent" for these medications. Opioids were administered to elephants (11 of 38) and rhinoceroses (7 of 33), with tramadol (0.5-3.0 mg/kg) and butorphanol (0.05-1.0 mg/kg) being most common. Tramadol efficacy scores were highly variable in both elephants and rhinoceroses. While drug choices were similar among institutions, substantial variability in dosing regimens and reported efficacy between and within facilities indicates the need for pharmacokinetic studies and standardized methods of analyzing response to treatment to establish dosing regimens and clinical trials to establish efficacy and safety.

Results of the 2013-2015 Association of Residents in Radiation Oncology Survey of Chief Residents in the United States

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nabavizadeh, Nima, E-mail: nabaviza@ohsu.edu; Burt, Lindsay M.; Mancini, Brandon R.

Purpose: The purpose of this project was to survey radiation oncology chief residents to define their residency experience and readiness for independent practice. Methods and Materials: During the academic years 2013 to 2014 and 2014 to 2015, the Association of Residents in Radiation Oncology (ARRO) conducted an electronic survey of post-graduate year-5 radiation oncology residents in the United States during the final 3 months of training. Descriptive statistics are reported. Results: Sixty-six chief residents completed the survey in 2013 to 2014 (53% response rate), and 69 completed the survey in 2014 to 2015 (64% response rate). Forty to 85% percent ofmore » residents reported inadequate exposure to high-dose rate and low-dose rate brachytherapy. Nearly all residents in both years (>90%) reported adequate clinical experience for the following disease sites: breast, central nervous system, gastrointestinal, genitourinary, head and neck, and lung. However, as few as 56% reported adequate experience in lymphoma or pediatric malignancies. More than 90% of residents had participated in retrospective research projects, with 20% conducting resident-led prospective clinical trials and 50% conducting basic science or translational projects. Most chief residents reported working 60 or fewer hours per week in the clinical/hospital setting and performing fewer than 15 hours per week tasks that were considered to have little or no educational value. There was more than 80% compliance with Accreditation Council for Graduate Medical Education (ACGME) work hour limits. Fifty-five percent of graduating residents intended to join an established private practice group, compared to 25% who headed for academia. Residents perceive the job market to be more competitive than previous years. Conclusions: This first update of the ARRO chief resident survey since the 2007 to 2008 academic year documents US radiation oncology residents' experiences and conditions over a 2-year period. This analysis may serve as a valuable tool for those seeking to improve training of the next generation of oncology leaders.« less

Neonatal morphine exposure in very preterm infants-cerebral development and outcomes.

PubMed

Steinhorn, Rachel; McPherson, Christopher; Anderson, Peter J; Neil, Jeffrey; Doyle, Lex W; Inder, Terrie

2015-05-01

To investigate the association of morphine exposure in very preterm infants with cerebral volumes and neurodevelopmental outcome from birth through middle childhood. Observational study of very preterm infants in the Victorian Infant Brain Study cohort. A total of 230 infants born <30 weeks' gestational age or <1250 g were recruited from all admissions to the neonatal intensive care unit of the Royal Women's Hospital. Fifty-seven (25%) infants received morphine analgesia during their neonatal intensive care unit stay at the attending physician's discretion. Primary outcomes were regional brain volumes at term and 7 years; neurobehavioral performance at term; and cognitive, motor, emotional, behavioral, communication, and executive function scores at age 2 and 7 years. Linear regressions were used to compare outcomes between participants who did and did not receive morphine. At term, preterm infants who received morphine had similar rates of gray matter injury to no-morphine infants, but a trend toward smaller cortical volumes in the orbitofrontal (Pleft=.002, Pright=.01) and subgenual (Pleft=.01) regions. At 7 years, cortical volumes did not differ between groups. At 2 years, morphine-exposed children were more likely to show behavioral dysregulation (P=.007) than no-morphine children, but at 7 years no detrimental impacts of morphine on neurobehavioral outcome were observed. Low-dose morphine analgesia received during neonatal intensive care was associated with early alterations in cerebral structure and short-term neurobehavioral problems that did not persist into childhood. Copyright © 2015 Elsevier Inc. All rights reserved.

[Efficacy of vaccination against hepatitis B in adult with HIV infection].

PubMed

Kalinowska-Nowak, Anna; Bociaga-Jasik, Monika; Garlicki, Aleksander; Mach, Tomasz

2007-01-01

The aim of the study was to evaluate the efficacy of vaccination against hepatitis B in HIV infected individuals and the influence of the stage of HIV infection and antiretroviral therapy (HAART). Response for additional doses of hepatitis B vaccine among the patients who do not develop protective anti-HBs level after routine vaccination schedule was analysed. Fifty-four HIV infected individuals, 20 women (37%) and 34 men (63%), 20 to 64 years old (mean age 32 years) were analysed. 32 patients (59.6%), 22 men and 10 women were treated with antiretroviral drugs. Stage of HIV infection was assessed on the basis of data derived from medical records (lowest CD4 cells count, highest viral load), and immunological status at the moment of introduction of vaccination (CD4 cells count, viral load). Efficacy of vaccination was compared with control group, which consisted of 56 healthy volunteers. In both groups hepatitis B virus infection was excluded by serologic tests. HBvaxPro vaccine produced by Merck Sharp & Dohme Company, dose registered for adults (10 ug) was injected at month 0-1-6. Patients with anti-HBs <10 IU/l have received booster doses of vaccine month intervals, no more then three. Protective level of antibodies was found in 52 (92.9%) persons from control group and 32 (63%) HIV infected individuals. Anti-HBs > 100 IU/l was twice more common in control group (80%) than in investigated group (46.3%) (p < 0.001). Protective level of anti-HBs had 14.3% patients with CD4 below 200 cells/pl, none of them had anti-HBs > 100 IU/l. Patients with higher CD4 cell count had better response for vaccination (p = 0.015). Differences between patients with high and low viral load were not statistically significant (p = 0.015). Patients with viral load below 10,000 copies/ml had slightly better response then those with higher viral load. Efficacy of vaccination was also associated with the level of distraction of immunological system before introduction of HAART. Patients with CD4 < 200 cells/microl or HIV-RNA > 50,000 copies/ml had worst immunological response for vaccination. After the fist additional dose of vaccine anti-HBs >10 IU/l had 79.7% patients, 87.1% after the second dose and 90.7% after the third dose. Anti-HBs >100 IU/l had subsequently 57.4%, 66.7%, 79.6% patients. We concluded that efficacy of the routine vaccination schedule was lower among HIV individuals in comparison with healthy volunteers. Influence of the progression of HIV infection on the response for vaccination was detected. Additional vaccine's doses have improved efficacy of immunisation which was comparable with general population.

No evidence found for an association between prednisone dose and FVC change in newly-treated pulmonary sarcoidosis.

PubMed

Broos, Caroline E; Poell, Linda H C; Looman, Caspar W N; In 't Veen, Johannes C C M; Grootenboers, Marco J J H; Heller, Roxane; van den Toorn, Leon M; Wapenaar, Monique; Hoogsteden, Henk C; Kool, Mirjam; Wijsenbeek, Marlies S; van den Blink, Bernt

2018-05-01

Prednisone is used as first-line therapy for pulmonary sarcoidosis. What dosing strategy has the best balance between effect and side-effects is largely unknown. We analyzed change in forced vital capacity (FVC) and weight during different prednisone doses used in daily practice for treatment naïve pulmonary sarcoidosis patients. Multilevel models were used to describe FVC and weight change over time. Correlations were calculated using linear regression models. Fifty-four patients were included. FVC changed over time (p < 0.001), with an average increase of 9.6% predicted (95% CI: 7.2 to 12.1) at 12 months. Weight changed significantly over time (p < 0.001), with an average increase of 4.3 kg (95% CI: 3.0 to 5.6) at 12 months. Although FVC and weight changed significantly over time, there was little correlation between prednisone dose and FVC change, while weight increase correlated significantly with cumulative prednisone dose at 24 months. In patients treated with a high cumulative prednisone dose, baseline FVC was on average lower (p = 0.001) compared to low dose treated patients, while no significant differences were observed in need for second/third-line therapy or number of exacerbations. A strategy leading to a low cumulative dose at 12 months was defined by rapid dose tapering to 10 mg/day within 3.5 months. These results suggest that prednisone therapy aimed at improving or preserving FVC in newly- treated pulmonary sarcoidosis can often be reduced in dose, using a treatment regimen that is characterized by early dose tapering. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fifty Years of "Comparative Education Review" Bibliographies: Reflections on the Field

ERIC Educational Resources Information Center

Raby, Rosalind Latiner

2007-01-01

For the past three years, the "Comparative Education Review" ("CER") has published annual bibliographic essays reflecting the changes in the field over the previous year. This year, to mark the 50th anniversary of the Comparative and International Education Society (CIES), the author analyzed "CER" bibliographies since 1959, in addition to…

Influence of Renal Impairment on Outcome for Thrombolysis-Treated Acute Ischemic Stroke: ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) Post Hoc Analysis.

PubMed

Carr, Susan J; Wang, Xia; Olavarria, Veronica V; Lavados, Pablo M; Rodriguez, Jorge A; Kim, Jong S; Lee, Tsong-Hai; Lindley, Richard I; Pontes-Neto, Octavio M; Ricci, Stefano; Sato, Shoichiro; Sharma, Vijay K; Woodward, Mark; Chalmers, John; Anderson, Craig S; Robinson, Thompson G

2017-09-01

Renal dysfunction (RD) is associated with poor prognosis after stroke. We assessed the effects of RD on outcomes and interaction with low- versus standard-dose alteplase in a post hoc subgroup analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). A total of 3220 thrombolysis-eligible patients with acute ischemic stroke (mean age, 66.5 years; 37.8% women) were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset. Six hundred and fifty-nine (19.8%) patients had moderate-to-severe RD (estimated glomerular filtration rate, <60 mL/min per 1.73 m 2 ) at baseline. The impact of RD on death or disability (modified Rankin Scale scores, 2-6) at 90 days, and symptomatic intracerebral hemorrhage, was assessed in logistic regression models. Compared with patients with normal renal function (>90 mL/min per 1.73 m 2 ), those with severe RD (<30 mL/min per 1.73 m 2 ) had increased mortality (adjusted odds ratio, 2.07; 95% confidence interval, 0.89-4.82; P =0.04 for trend); every 10 mL/min per 1.73 m 2 lower estimated glomerular filtration rate was associated with an adjusted 9% increased odds of death from thrombolysis-treated acute ischemic stroke. There was no significant association with modified Rankin Scale scores 2 to 6 (adjusted odds ratio, 1.03; 95% confidence interval, 0.62-1.70; P =0.81 for trend), modified Rankin Scale 3 to 6 (adjusted odds ratio, 1.20; 95% confidence interval, 0.72-2.01; P =0.44 for trend), or symptomatic intracerebral hemorrhage, or any heterogeneity in comparative treatment effects between low-dose and standard-dose alteplase by RD grades. RD is associated with increased mortality but not disability or symptomatic intracerebral hemorrhage in thrombolysis-eligible and treated acute ischemic stroke patients. Uncertainty persists as to whether low-dose alteplase confers benefits over standard-dose alteplase in acute ischemic stroke patients with RD. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616. © 2017 American Heart Association, Inc.

Radiation dose does not influence anastomotic complications in patients with esophageal cancer treated with neoadjuvant chemoradiation and transhiatal esophagectomy.

PubMed

Koëter, Marijn; van der Sangen, Maurice J C; Hurkmans, Coen W; Luyer, Misha D P; Rutten, Harm J T; Nieuwenhuijzen, Grard A P

2015-03-06

Neoadjuvant chemoradiation might increase anastomotic leakage and stenosis in patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. The aim of this study was to determine the influence of radiation dose on the incidence of leakage and stenosis. Fifty-three patients with esophageal cancer received neoadjuvant chemoradiation (23 × 1.8 Gy) (combined with Paclitaxel and Carboplatin) followed by a transhiatal esophagectomy between 2009 and 2011. On planning CT, the future anastomotic region was determined and the mean radiation dose, V20, V25, V30, V35 and V40 were calculated. Logistic regression analysis was conducted to examine determinants of anastomotic leakage and stenosis. Anastomotic leaks occurred in 13 of 53 patients (25.5%) and anastomotic stenosis occurred in 24 of 53 patients (45.3%). Median follow-up was 20 months. Logistic regression analysis showed that mean dose, V20-V40, age, co-morbidity, method of anastomosis, operating time and interval between last radiotherapy treatment and surgery were not predictors of anastomotic leakage and stenosis. A radiation dose of 23 × 1.8 Gy on the future anastomotic region has no influence on the occurrence of anastomotic leakage and stenosis in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by transhiatal esophagectomy.

Overview of the INPRO Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kupitz, J.; Depisch, F.; Zou, Y.

2004-10-03

During the last fifty years remarkable results are achieved in the application of nuclear technology for the production of electricity. Looking ahead to the next fifty years it is clear that the demand for energy will grow considerably and also the requirements for the way the energy will be supplied. Within the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO), the future of the energy demand and supply was explored and several scenario's identified. A leading requirement for energy supply is coming up and will play a crucial role: sustainability of the way the energy supply will bemore » realized. Fulfilling the growing need for energy in developing countries is as well an important issue. Based on these scenario's for the next fifty years, an inventory of requirements for the future of nuclear energy systems has been collected as well a methodology developed by INPRO to assess innovative nuclear systems and fuel cycles. On the base of this assessment, the need for innovations and breakthroughs in existing technology can be defined. To facilitate the deployment of innovative nuclear systems also the infrastructure, technical as well as institutional has to be adjusted to the anticipated changes in the world such as the globalization. As a contribution to the conference the main messages of INPRO will be presented.« less

Risk of therapy-related secondary leukemia in Hodgkin lymphoma: the Stanford University experience over three generations of clinical trials.

PubMed

Koontz, Michael Zach; Horning, Sandra J; Balise, Raymond; Greenberg, Peter L; Rosenberg, Saul A; Hoppe, Richard T; Advani, Ranjana H

2013-02-10

To assess therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) risk in patients treated for Hodgkin lymphoma (HL) on successive generations of Stanford clinical trials. Patients with HL treated at Stanford with at least 5 years of follow-up after completing therapy were identified from our database. Records were reviewed for outcome and development of t-AML/MDS. Seven hundred fifty-four patients treated from 1974 to 2003 were identified. Therapy varied across studies. Radiotherapy evolved from extended fields (S and C studies) to involved fields (G studies). Primary chemotherapy was mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or procarbazine, mechlorethamine, and vinblastine (PAVe) in S studies; MOPP, PAVe, vinblastine, bleomycin, and methotrexate (VBM), or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in C studies; and VbM (reduced dose of bleomycin compared with VBM) or mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) in G studies. Cumulative exposure to alkylating agent (AA) was notably lower in the G studies compared with the S and C studies, with a 75% to 83% lower dose of nitrogen mustard in addition to omission of procarbazine and melphalan. Twenty-four (3.2%) of 754 patients developed t-AML/MDS, 15 after primary chemotherapy and nine after salvage chemotherapy for relapsed HL. The incidence of t-AML/MDS was significantly lower in the G studies (0.3%) compared with the S (5.7%) or C (5.2%) studies (P < .001). Additionally, in the G studies, no t-AML/MDS was noted after primary therapy, and the only patient who developed t-AML/MDS did so after second-line therapy. Our data demonstrate the relationship between the cumulative AA dose and t-AML/MDS. Limiting the dose of AA and decreased need for secondary treatments have significantly reduced the incidence of t-AML/MDS, which was extremely rare in the G studies (Stanford V era).

Subcutaneous Injection of Testosterone Is an Effective and Preferred Alternative to Intramuscular Injection: Demonstration in Female-to-Male Transgender Patients.

PubMed

Spratt, Daniel I; Stewart, India I; Savage, Clara; Craig, Wendy; Spack, Norman P; Chandler, Donald Walt; Spratt, Lindsey V; Eimicke, Toni; Olshan, Jerrold S

2017-07-01

Testosterone (T) is commonly administered intramuscularly to treat hypogonadal males and female-to-male (FTM) transgender patients. However, these injections can involve significant discomfort and may require arrangements for administration by others. We assessed whether T could be administered effectively and safely subcutaneously as an alternative to intramuscular (IM) injections. Retrospective cohort study. Outpatient reproductive endocrinology clinic at an academic medical center. Sixty-three FTM transgender patients aged >18 years electing to receive subcutaneous (SC) T therapy for sex transition were included. Fifty-three patients were premenopausal. Patients were administered T cypionate or enanthate weekly at an initial dose of 50 mg. Dose was adjusted if needed to achieve serum total T levels within the normal male range. Serum concentrations of free and total T and total estradiol (E2), masculinization, and surveillance for reactions at injection sites. Serum T levels within the normal male range were achieved in all 63 patients with doses of 50 to 150 mg (median, 75/80 mg). Therapy was effective across a wide range of body mass index (19.0 to 49.9 kg/m2). Minor and transient local reactions were reported in 9 out of 63 patients. Among 53 premenopausal patients, 51 achieved amenorrhea and 35 achieved serum E2 concentrations <50 pg/mL. Twenty-two patients were originally receiving IM and switched to SC therapy. All 22 had a mild (n = 2) or marked (n = 20) preference for SC injections; none preferred IM injections. Our observations indicate that SC T injections are an effective, safe, and well-accepted alternative to IM T injections. Copyright © 2017 Endocrine Society

Stereotactic radiosurgery of World Health Organization grade II and III intracranial meningiomas: treatment results on the basis of a 22-year experience.

PubMed

Pollock, Bruce E; Stafford, Scott L; Link, Michael J; Garces, Yolanda I; Foote, Robert L

2012-02-15

A study was undertaken to define the variables associated with tumor control and survival after single-session stereotactic radiosurgery (SRS) for patients with atypical and malignant intracranial meningiomas. Fifty patients with World Health Organization (WHO) grade II (n = 37) or grade III (n = 13) meningiomas underwent SRS from 1990 to 2008. Most tumors were located in the falx/parasagittal region or cerebral convexities (n = 35, 70%). Twenty patients (40%) had progressing tumors despite prior external beam radiation therapy (EBRT) (median dose, 54.0 grays [Gy]). The median treatment volume was 14.6 cm(3) ; the median tumor margin dose was 15.0 Gy. Seven patients (14%) received concurrent EBRT (median dose, 50.4 Gy). Follow-up (median, 38 months) was censored at last evaluation (n = 28) or death (n = 22). Tumor grade correlated with disease-specific survival (DSS) (hazard ratio [HR], 3.4; P = .008), local tumor control (HR, 2.4; P = .02), and progression-free survival (PFS) (HR, 2.6; P = .02) on univariate analysis, but not on multivariate analysis. Multivariate analysis showed that having failed EBRT and tumor volume >14.6 cm(3) were negative predictors of DSS and local control (HR, 3.0; P = .02 and HR, 4.4; P = .01; HR, 3.3; P = .001 and HR, 2.3; P = .02;, respectively). Having failed EBRT was a negative predictor of PFS (HR, 3.5; P = .002). Thirteen patients (26%) had radiation-related complications at a median of 6 months after radiosurgery. Tumor progression despite prior EBRT and larger tumor volume are negative predictors of tumor control and survival for patients having SRS for WHO grade II and III intracranial meningiomas. Copyright © 2011 American Cancer Society.

Methylphenidate side effects in advanced cancer: a retrospective analysis.

PubMed

Lasheen, Wael; Walsh, Declan; Mahmoud, Fade; Davis, Mellar P; Rivera, Nilo; Khoshknabi, Dilara Seyidova

2010-02-01

Methylphenidate (MP) is often recommended for symptom control in advanced cancer. Little is known about its side effects in frail adults. To evaluate MP-associated symptoms or side effects (S/E). Data was collected from 2 published prospective cohort series and a phase 2 study of MP for symptom control in advanced cancer. All 3 reports had identical dosing schedules and symptom assessments. Initial MP doses were 10 mg/d (5 mg at 8 AM and at 12 noon) titrated up to a maximum of 30 mg/d. Depression, fatigue, and symptoms identified as possible MP S/E were evaluated for presence (prevalence) and for severity (using categorical scales) before MP (day 0) and on days 3, 5, and 7 thereafter. The categorical scale used was none, mild, moderate, and severe. 62 patients were enrolled. Fifty completed 7 days of MP with a median age of 69 (range 30-90) years. Thirty-five received MP 10 mg/day. Most (96%) had improvement in depression and/or fatigue. Among the 62 patients, new symptom prevalence throughout the study was agitation (16%), insomnia (16%), dry mouth (15%), nausea (10%), tremors (6%), anorexia (5%), headache (3%), palpitations (2%), and vomiting (2%). Patients could have more than 1 symptom simultaneously. Seven (11%) withdrew due to MP S/E. Some symptoms present before MP showed significant improvement during MP therapy. (1) Treatment with MP (10-20 mg/d) in advanced cancer is well tolerated. (2) S/E symptoms with MP appeared to improve spontaneously despite continued MP therapy. (3) Depression and fatigue improved at doses lower than those recommended in other clinical conditions. (4) MP improved depression and fatigue, and some secondary symptoms associated with them. Methylphenidate (MP) appears safe when used in the treatment of depression and fatigue in advanced cancer.

Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia.

PubMed

Warris, Lidewij T; van den Akker, Erica L T; Aarsen, Femke K; Bierings, Marc B; van den Bos, Cor; Tissing, Wim J E; Sassen, Sebastiaan D T; Veening, Margreet A; Zwaan, Christian M; Pieters, Rob; van den Heuvel-Eibrink, Marry M

2016-10-01

Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied whether we could predict the occurrence of these side effects using the very low-dose dexamethasone suppression test (DST) or by measuring trough levels of dexamethasone. Fifty pediatric patients (3-16 years of age) with acute lymphoblastic leukemia (ALL) were initially included during the maintenance phase (with dexamethasone) of the Dutch ALL treatment protocol. As a marker of glucocorticoid sensitivity, the salivary very low-dose DST was used. A post-dexamethasone cortisol level <2.0nmol/L was considered a hypersensitive response. The neurobehavioral endpoints consisted of questionnaires regarding psychosocial and sleeping problems administered before and during the course of dexamethasone (6mg/m(2)), and dexamethasone trough levels were measured during dexamethasone treatment. Patients with a hypersensitive response to dexamethasone had more behavioral problems (N=11), sleeping problems, and/or somnolence (N=12) (P<0.05 for all three endpoints). The positive predictive values of the DST for psychosocial problems and sleeping problems were 50% and 30%, respectively. Dexamethasone levels were not associated with neurobehavioral side effects. We conclude that neither the very low-dose DST nor measuring dexamethasone trough levels can accurately predict dexamethasone-induced neurobehavioral side effects. However, patients with glucocorticoid hypersensitivity experienced significantly more symptoms associated with dexamethasone-induced depression. Future studies should elucidate further the mechanisms by which neurobehavioral side effects are influenced by glucocorticoid sensitivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Directly observed therapy of sofosbuvir/ribavirin +/- peginterferon with minimal monitoring for the treatment of chronic hepatitis C in people with a history of drug use in Chennai, India (C-DOT).

PubMed

Solomon, S S; Sulkowski, M S; Amrose, P; Srikrishnan, A K; McFall, A M; Ramasamy, B; Kumar, M S; Anand, S; Thomas, D L; Mehta, S H

2018-01-01

We assessed the feasibility of field-based directly observed therapy (DOT) with minimal monitoring to deliver HCV treatment to people with a history of drug use in Chennai, India. Fifty participants were randomized 1:1 to sofosbuvir+peginterferon alfa 2a+ribavirin (SOF+PR) for 12 weeks (Arm 1) vs sofosbuvir+ribavirin (SOF+R) for 24 weeks (Arm 2). SOF+R was delivered daily at participant chosen venues and weekly peginterferon injections at the study clinic. HCV RNA testing was performed to confirm active HCV infection and sustained virologic response 12 weeks after treatment completion (SVR12). No baseline genotyping or on-treatment viral loads were performed. Median age was 46 years. All were male and 20% had significant fibrosis/cirrhosis. All self-reported history of injection drug use, 18% recent noninjection drug use and 38% alcohol dependence. Six discontinued treatment (88% completed treatment in each arm). Of 22 who completed SOF+PR, all achieved SVR12 (22/25=88%); 15 of 22 who completed SOF+R achieved SVR12 (15/25=60%; P=.05). Among those completing SOF+R, SVR12 was significantly less common in participants reporting ongoing substance use (36% vs 100%) and missed doses. Active substance use and missed doses did not impact SVR with SOF+PR. Field-based DOT of HCV therapy without real-time HCV RNA monitoring was feasible; however, achieving 100% adherence was challenging. SOF+PR appeared superior to SOF+R in achieving SVR12, even when doses were missed with no discontinuations due to side effects. Further exploration of short duration treatment with peginterferon plus direct-acting antivirals is warranted. © 2017 John Wiley & Sons Ltd.

A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism.

PubMed

Page, S R; Sheard, C E; Herbert, M; Hopton, M; Jeffcoate, W J

1996-11-01

The optimal dosage regimen for carbimazole (CBZ) in the treatment of hyperthyroidism remains uncertain, despite clinical use of the drug for approximately fifty years. We have compared the early clinical and biochemical responses to 20 or 40 mg/day of CBZ given as initial treatment for hyperthyroidism. Prospective open multicentre trial. Sixty-three patients presenting with hyperthyroidism. Serum total and free thyroid hormones, serum TSH and SHBG were measured at baseline and at 4 and 10 weeks after start of therapy. Weight, pulse and a symptom questionnaire were also monitored at 6 and 12 weeks. Patients randomized to a starting dose of 40 mg/day CBZ had lower total (98 +/- 10 vs 158 +/- 11 nmol/l, P < 0.001) and free T4 (19.4 +/- 2.6 vs 35.2 +/- 3.7 pmol/l, P < 0.001) and total (2.6 +/- 0.3 vs 4.3 +/- 0.4 nmol/l, P < 0.001) and free T3 (8.3 +/- 1.0 vs 13.7 +/- 1.2 pmol/l, P < 0.01) at 4 weeks than those receiving 20 mg/day. Clinical responses at 6 and 12 weeks (weight, pulse, symptom score) and SHBG concentrations were similar. Drug-related hypothyroidism was less likely to occur at 4 and 10 weeks in those patient who initially received 20 mg CBZ/day, but this dose was less effective at controlling hyperthyroidism in those with more severe hyperthyroidism with baseline TT4 > 260 nmol/l. In treating hyperthyroidism, 20 mg/day carbimazole is effective, convenient and has a lower risk than 40 mg/day of iatrogenic hypothyroidism in patients with mild or moderate hyperthyroidism. Higher doses are required for those with severe hyperthyroidism.

High- and low-dose-rate intraoperative radiotherapy for thoracic malignancies resected with close or positive margins.

PubMed

Fleming, Christopher; Rimner, Andreas; Cohen, Gil'ad N; Woo, Kaitlin M; Zhang, Zhigang; Rosenzweig, Kenneth E; Alektiar, Kaled M; Zelefsky, Michael J; Bains, Manjit S; Wu, Abraham J

2016-01-01

Local recurrence is a significant problem after surgical resection of thoracic tumors. As intraoperative radiotherapy (IORT) can deliver radiation directly to the threatened margin, we have used this therapy in an attempt to reduce local recurrence, using high-dose-rate (HDR) as well as low-dose-rate (LDR) techniques. We performed a retrospective review of patients undergoing LDR ((125)I) mesh placement or HDR ((192)Ir) afterloading therapy during lung tumor resection between 2001 and 2013 at our institution. Competing risks methods were used to estimate the cumulative incidence of local failure. We also assessed possible predictive factors of local failure. Fifty-nine procedures (41 LDR and 18 HDR) were performed on 58 patients. Median follow-up was 55.1 months. Cumulative incidence of local failure at 1, 2, and 3 years was 28.5%, 34.2%, and 34.2%, respectively. Median overall survival was 39.9 months. There was no significant difference in local failure according to margin status, HDR vs. LDR, use of adjuvant external beam radiotherapy, or metastatic vs. primary tumor. Two patients (3.4%) experienced Grade 3+ toxicities likely related to brachytherapy. Additionally, 7 patients experienced Grade 3+ postsurgical complications unlikely related to brachytherapy. IORT is associated with good local control after resection of thoracic tumors otherwise at very high risk for local recurrence. There is a low incidence of severe toxicity attributable to brachytherapy. HDR-IORT appears to have equivalent outcomes to LDR-IORT. HDR or LDR-IORT can, therefore, be considered in situations where the oncologic completeness of thoracic tumor resection is in doubt. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Phase I Trial of Aflibercept (VEGF Trap) with Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients with High-Grade Gliomas

PubMed Central

Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred WK; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

2017-01-01

Background Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor (PlGF), depleting circulating levels of these growth factors. Methods The Adult Brain Tumor Consortium (ABTC) conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed high-grade gliomas (HGG) with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Results Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4mg/kg every 2 weeks. Dose limiting toxicities (DLTs) at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. Conclusions This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4mg/kg every 2 weeks. PMID:28116649

Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas.

PubMed

Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred W K; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

2017-03-01

Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor, depleting circulating levels of these growth factors. The Adult Brain Tumor Consortium conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed HGG with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4 mg/kg every 2 weeks. Dose limiting toxicities at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients) (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4 mg/kg every 2 weeks.

Management of testosterone therapy in adolescents and young men with hypogonadism: are we following adult clinical practice guidelines?

PubMed

Nahata, Leena; Yu, Richard N; Bhasin, Shalender; Cohen, Laurie E

2015-05-01

Male hypogonadism is a common disorder that is associated with low bone density, poor muscle mass, anemia, and sexual dysfunction. The Endocrine Society recently published a Clinical Practice Guideline for testosterone therapy in androgen-deficient men. Because treatment is frequently initiated in adolescence, the goal of this quality improvement initiative was to assess whether pediatric endocrinologists at a large tertiary care center follow these guidelines and to identify opportunities for improvement. We performed a retrospective chart review at Boston Children's Hospital. Inclusion criteria were as follows: current age ≥16 years, diagnosis of hypogonadism, and testosterone replacement therapy. Data were collected about current age, age at treatment initiation, diagnoses, pre- and on-treatment testosterone levels, route of testosterone administration and dose, bone density, hematocrit levels, and adherence with therapy. Fifty-nine patients were included. Fourteen (24%) were prescribed lower testosterone doses than those recommended in the Clinical Practice Guideline. Seven (12%) had no pre-treatment testosterone levels, and 10 (17%) had no on-treatment levels. In 49 patients with on-treatment testosterone levels, 36 had at least one value that was lower than the adult reference range. Ten (28%) of the 36 men with low testosterone levels had no dose adjustments. Thirty-seven (63%) of the 59 patients had no dual-energy X-ray absorptiometry scans, and 18 (31%) did not have hematocrit levels. Pediatric endocrinologists in this review did not consistently follow the Clinical Practice Guideline for testosterone therapy in hypogonadal adult males. Strategies that improve adherence to guidelines could help maximize the benefits of therapy and minimize treatment-associated risks.

Postoperative pain after haemorrhoidectomy: role of impaired evacuation.

PubMed

Puigdollers, A; Cisternas, D; Azpiroz, F

2011-08-01

We hypothesized that obstructive defaecation is associated with more postoperative pain after haemorrhoidectomy. Fifty patients with grade IV haemorrhoids were included in a prospective study. Impaired evacuation was defined as the inability to evacuate a rectal balloon. Perianal sensitivity was evaluated by means of an algometer, and anxiety and depression were assessed by the hospital anxiety and depression (HAD) scale. Over the first 10 days after a Milligan-Morgan haemorrhoidectomy, the following parameters were measured on daily questionnaires: pain (associated with and unrelated to defaecation by means of visual analogue scales), number of bowel movements, faecal consistency and analgesic requirement on demand (tramadol 50 mg p.o., number of doses). Results are expressed as median and interquartile range or mean ± SE. Patients with impaired evacuation (14 women, eight men; age range 28-61 years) experienced more postoperative pain than patients with nonimpaired evacuation (eight women, 20 men; age range 24-70 years): 3.2 (2.1) vs 2.1 (1.8) defaecatory pain, respectively (P = 0.045), and 2.4 (2.3) vs 1.7 (2.3) nondefecatory pain, respectively (P = 0.048). There was no difference between the groups regarding stool consistency, number of bowel movements [12.5 (7.3) vs 15.5 (7.2), respectively; NS] and analgesic requirement [1.0 (6.1) vs 1.0 (5.2) extra doses on demand, respectively; NS] during the 10 postoperative days. No differences related to age, sex, HAD scores or perianal sensitivity were found. Impaired anal evacuation is predictive of postoperative pain after haemorrhoidectomy. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

Megavoltage irradiation of neoplasms of the nasal and paranasal cavities in 77 dogs.

PubMed

Théon, A P; Madewell, B R; Harb, M F; Dungworth, D L

1993-05-01

Seventy-seven dogs with malignant tumors of the nasal and paranasal cavities were treated by use of radiotherapy. The tumors included carcinomas (58) and sarcomas (19). Radiographic findings, including site of involvement and tumor extension, were the basis of clinical staging. Staging was performed according to the tumor, node, metastasis staging of the World Health Organization, and a modified staging scheme based on prognostic factors that seemed to correlate best with response to treatment. All irradiations were done with a telecobalt 60 unit. Fifty-six dogs were treated with irradiation alone, and 21 had partial tumor resection prior to radiotherapy. Treatment dose was 48 Gy (minimal tumor dose) administered on a Monday-Wednesday-Friday basis at 4 Gy/fraction over 4 weeks. The irradiation technique emphasized rostral field with a generous treatment volume. Duration of follow-up after irradiation ranged from 1 month to 61 months. The 1- and 2-year overall survival rates were 60.3% and 25%, respectively, and the 1- and 2-year relapse-free survival rates were 38.2% and 17.6%, respectively. Results of histologic examination and our modified staging scheme were significant (P = 0.02 and P = 0.04, respectively) prognostic factors of relapse-free survival. Conversely, tumor site, tumor extension, World Health Organization clinical stage, and cytoreductive surgery prior to irradiation did not affect the outcome of treatment. According to our modified staging scheme, dogs with stage-2- disease have a poorer prognosis than dogs with stage-1 disease, with a relative risk of relapse 2.3-fold higher. Dogs with carcinoma had a poorer prognosis than dogs with sarcoma (predominantly chondrosarcoma) with a relative risk of relapse 3.3-fold higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Venom immunotherapy in patients with clonal mast cell disorders: efficacy, safety, and practical considerations.

PubMed

Bonadonna, Patrizia; Gonzalez-de-Olano, David; Zanotti, Roberta; Riccio, Annamaria; De Ferrari, Laura; Lombardo, Carla; Rogkakou, Anthi; Escribano, Luis; Alvarez-Twose, Ivan; Matito, Almudena; Vega, Arantza; Passalacqua, Giovanni

2013-01-01

A preferential association between systemic mastocytosis (SM) and hymenoptera allergy (HVA) has been observed. Patients with both diseases are at risk for more severe reactions, and venom immunotherapy (VIT) may represent a life-saving treatment, but the use of VIT in such patients raised concerns about its safety. We evaluated a large population of patients with SM and HVA who received VIT. This prospective study was performed in Italy and Spain. A diagnosis of SM and HVA and a VIT prescription were made according to international recommendations. The patients were carefully followed up during VIT, with special attention to field stings. A total of 84 patients (70 men, 14 women; mean age 52.1 years) were included, 81% with grade IV reaction, 91% with indolent SM. No difference was seen between the Italian and Spanish patients. There were 10 adverse reactions during the induction phase: 3 with the conventional induction and 7 with the rush-modified induction, none resulted in epinephrine administration and/or hospitalization. Fifty patients had one or more field re-sting (95 episodes), none during induction. The time elapsed from starting VIT and first re-sting was 2 months to 7 years, and the number of re-stings per patient was 1-6. Of the 50 patients who were re-stung, 43 (86%) resulted in being fully protected. Seven patients had reactions, and the maintenance dose was safely increased to 200 mcg. The maintenance dose interval was not different between patients with and those without reactions at re-stings. VIT is well tolerated, safe, and effective in patients with SM. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Angiotensin-converting enzyme inhibitor and statin use and incident mobility limitation in community-dwelling older adults: the Health, Aging and Body Composition study.

PubMed

Gray, Shelly L; Boudreau, Robert M; Newman, Anne B; Studenski, Stephanie A; Shorr, Ronald I; Bauer, Douglas C; Simonsick, Eleanor M; Hanlon, Joseph T

2011-12-01

To evaluate whether the use of angiotensin-converting enzyme (ACE) inhibitors and statins is associated with a lower risk of incident mobility limitation in older community dwelling adults. Longitudinal cohort study. Health, Aging and Body Composition (Health ABC) study. Three thousand fifty-five participants who were well functioning at baseline (no mobility limitations). Summated standardized daily doses (low, medium, high) and duration of ACE inhibitor and statin use were computed. Mobility limitation (two consecutive self-reports of having any difficulty walking one-quarter of a mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazards analyses were conducted, adjusting for demographics, health status, and health behaviors. At baseline, 15.2% used ACE inhibitors and 12.9% used statins; use of both was greater than 25% by Year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio (HR) = 0.95, 95% confidence interval (CI) = 0.82-1.09) nor statin use (multivariate HR = 1.02, 95% CI = 0.87-1.17) was associated with lower risk of mobility limitation. Similar findings were seen in analyses examining dose-response and duration-response relationships and a sensitivity analysis restricted to those with hypertension. ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively, do not lower risk of mobility limitation, an important indicator of quality of life. © 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.

Fifty years of fat: news coverage of trends that predate obesity prevalence.

PubMed

Davis, Brennan; Wansink, Brian

2015-07-10

Obesity prevalence has risen in fifty years. While people generally expect media mentions of health risks like obesity prevalence to follow health risk trends, food consumption trends may precede obesity prevalence trends. Therefore, this research investigates whether media mentions of food predate obesity prevalence. Fifty years of non-advertising articles in the New York Times (and 17 years for the London Times) are coded for the mention of less healthy (5 salty and 5 sweet snacks) and healthy (5 fruits and 5 vegetables) food items by year and then associated with annual obesity prevalence in subsequent years. Time-series generalized linear models test whether food-related mentions predate or postdate obesity prevalence in each country. United States obesity prevalence is positively associated with New York Times mentions of sweet snacks (b = 55.2, CI = 42.4 to 68.1, p = .000) and negatively associated with mentions of fruits (b = -71.28, CI -91.5 to -51.1, p = .000) and vegetables (b = -13.6, CI = -17.5 to -9.6, p = .000). Similar results are found for the United Kingdom and The London Times. Importantly, the "obesity followed mentions" models are stronger than the "obesity preceded mentions" models. It may be possible to estimate a nation's future obesity prevalence (e.g., three years from now) based on how frequently national media mention sweet snacks (positively related) and vegetables or fruits (negatively related) today. This may provide public health officials and epidemiologists with new tools to more quickly assess the effectiveness of current obesity interventions based on what is mentioned in the media today.

Attenuating the defibrillation dosage decreases postresuscitation myocardial dysfunction in a swine model of pediatric ventricular fibrillation

PubMed Central

Berg, Marc D.; Banville, Isabelle L.; Chapman, Fred W.; Walker, Robert G.; Gaballa, Mohammed A.; Hilwig, Ronald W.; Samson, Ricardo A.; Kern, Karl B.; Berg, Robert A.

2009-01-01

Objective The optimal biphasic defibrillation dose for children is unknown. Postresuscitation myocardial dysfunction is common and may be worsened by higher defibrillation doses. Adult-dose automated external defibrillators are commonly available; pediatric doses can be delivered by attenuating the adult defibrillation dose through a pediatric pads/cable system. The objective was to investigate whether unattenuated (adult) dose biphasic defibrillation results in greater postresuscitation myocardial dysfunction and damage than attenuated (pediatric) defibrillation. Design Laboratory animal experiment. Setting University animal laboratory. Subjects Domestic swine weighing 19 ± 3.6 kg. Interventions Fifty-two piglets were randomized to receive biphasic defibrillation using either adult-dose shocks of 200, 300, and 360 J or pediatric-dose shocks of ~50, 75, and 85 J after 7 mins of untreated ventricular fibrillation. Contrast left ventriculograms were obtained at baseline and then at 1, 2, 3, and 4 hrs postresuscitation. Postresuscitation left ventricular ejection fraction and cardiac troponins were evaluated. Measurements and Main Results By design, piglets in the adult-dose group received shocks with more energy (261 ± 65 J vs. 72 ± 12 J, p < .001) and higher peak current (37 ± 8 A vs. 13 ± 2 A, p < .001) at the largest defibrillation dose needed. In both groups, left ventricular ejection fraction was reduced significantly at 1, 2, and 4 hrs from baseline and improved during the 4 hrs postresuscitation. The decrease in left ventricular ejection fraction from baseline was greater after adult-dose defibrillation. Plasma cardiac troponin levels were elevated 4 hrs postresuscitation in 11 of 19 adult-dose piglets vs. four of 20 pediatric-dose piglets (p = .02). Conclusions Unattenuated adult-dose defibrillation results in a greater frequency of myocardial damage and worse postresuscitation myocardial function than pediatric doses in a swine model of prolonged out-of-hospital pediatric ventricular fibrillation cardiac arrest. These data support the use of pediatric attenuating electrodes with adult biphasic automated external defibrillators to defibrillate children. PMID:18496405

Estimation of immunization providers' activities cost, medication cost, and immunization dose errors cost in Iraq.

PubMed

Al-lela, Omer Qutaiba B; Bahari, Mohd Baidi; Al-abbassi, Mustafa G; Salih, Muhannad R M; Basher, Amena Y

2012-06-06

The immunization status of children is improved by interventions that increase community demand for compulsory and non-compulsory vaccines, one of the most important interventions related to immunization providers. The aim of this study is to evaluate the activities of immunization providers in terms of activities time and cost, to calculate the immunization doses cost, and to determine the immunization dose errors cost. Time-motion and cost analysis study design was used. Five public health clinics in Mosul-Iraq participated in the study. Fifty (50) vaccine doses were required to estimate activities time and cost. Micro-costing method was used; time and cost data were collected for each immunization-related activity performed by the clinic staff. A stopwatch was used to measure the duration of activity interactions between the parents and clinic staff. The immunization service cost was calculated by multiplying the average salary/min by activity time per minute. 528 immunization cards of Iraqi children were scanned to determine the number and the cost of immunization doses errors (extraimmunization doses and invalid doses). The average time for child registration was 6.7 min per each immunization dose, and the physician spent more than 10 min per dose. Nurses needed more than 5 min to complete child vaccination. The total cost of immunization activities was 1.67 US$ per each immunization dose. Measles vaccine (fifth dose) has a lower price (0.42 US$) than all other immunization doses. The cost of a total of 288 invalid doses was 744.55 US$ and the cost of a total of 195 extra immunization doses was 503.85 US$. The time spent on physicians' activities was longer than that spent on registrars' and nurses' activities. Physician total cost was higher than registrar cost and nurse cost. The total immunization cost will increase by about 13.3% owing to dose errors. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Impact of AUC-Based Monitoring on Pharmacist-Directed Vancomycin Dose Adjustments in Complicated Methicillin-Resistant Staphylococcus aureus Infection.

PubMed

Stoessel, Andrew M; Hale, Cory M; Seabury, Robert W; Miller, Christopher D; Steele, Jeffrey M

2018-01-01

This study aimed to assess the impact of area under the curve (AUC)-based vancomycin monitoring on pharmacist-initiated dose adjustments after transitioning from a trough-only to an AUC-based monitoring method at our institution. A retrospective cohort study of patients treated with vancomycin for complicated methicillin-resistant Staphylococcus aureus (MRSA) infection between November 2013 and December 2016 was conducted. The frequency of pharmacist-initiated dose adjustments was assessed for patients monitored via trough-only and AUC-based approaches for trough ranges: 10 to 14.9 mg/L and 15 to 20 mg/L. Fifty patients were included: 36 in the trough-based monitoring and 14 in the AUC-based-monitoring group. The vancomycin dose was increased in 71.4% of patients when troughs were 10 to 14.9 mg/L when a trough-only approach was used and in only 25% of patients when using AUC estimation ( P = .048). In the AUC group, the dose was increased only when AUC/minimum inhibitory concentration (MIC) <400; unchanged regimens had an estimated AUC/MIC ≥400. The AUC-based monitoring did not significantly increase the frequency of dose reductions when trough concentrations were 15 to 20 mg/L (AUC: 33.3% vs trough: 4.6%; P = .107). The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation.

Toxicity studies on agents Gb and Gd (Phase 2): Delayed neuropathy study of soman in SPF white leghorn chickens. Final technical report, July 1985-August 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bucci, T.J.; Parker, R.M.; Gosnell, P.A.

1992-05-01

A dose rangefinding study, a delayed neuropathy study, and a neurotoxic esterase study, were performed in White Leghorn chickens using the organophosphate ester Soman. The hens used for the Rangefinding study were dosed once orally with 500, 250, 100, 50, 25, or 0 microns g/Kg GD, on Day 1. They were pretreated and protected daily through Day 7 with atropine. Surviving hens were euthanized with sodium pentobarbital on Day 21. The maximum tolerated dose (MTD) to be used in the Delayed Neuropathy Study was chosen based upon the rangefinding data. Fifty hens were assigned to a Single Dose Delayed Neuropathymore » study. Groups of ten hens were given 14.2 (MTD), 7.1 (MTD/2), 3.5 (MTD/4), 0 (negative control) microns/Kg GD or 51 0 mg/Kg tri-ortho-cresyl phosphate (TOCP) (positive control). Rangefinding study. They were evaluated for signs of neurologic toxicity/ataxia. Necropsy examination was performed on all animals. Sections of cerebellum, medulla, spinal cord (cervical, thoracic, and lumbar), both sciatic nerves and their tibial branch were examined microscopically.... Delayed neuropathy; Agents; Soman; Chickens.« less

Effectiveness and acceptability of intravenous sedation in child and adolescent dental patients: report of a case series at King's College Hospital, London.

PubMed

Lourenço-Matharu, L; Roberts, G J

2011-06-24

Conscious sedation for young patients continues to be challenging. Few studies have shown positive results using intravenous midazolam when sedating young patients. This case series reports an investigation of conscious sedation using intravenous midazolam for young patients receiving dental treatment. To determine acceptance, safety and efficacy of intravenous midazolam for conscious sedation in children and adolescent patients undergoing dental treatment.Patients and methods Patients from seven to 16 years of age, ASA I, II and III, opted to have extractions, minor oral surgery and/or conservative treatment with IV midazolam and local anaesthesia. A pulse oximeter was used to monitor vital signs and the Houpt scale to assess overall behaviour. A total of 552 patients, 234 boys and 318 girls with mean ages of 13.3 years and 13.5 years respectively, were included. Three hundred and sixty-five patients (66%) claimed to be anxious or very anxious before treatment. The average dose given was 5.7 mg and dosage ranged from 2 to 10 mg. Four hundred and fifty-seven patients (83%) scored 'very good' and 'excellent' for overall behaviour. Side-effects included crying, drowsiness and amnesia. Intravenous midazolam is accepted by patients and is a safe and effective method of sedation for use in children and adolescents, producing some level of tearfulness.

Hypofractionated Proton Boost Combined with External Beam Radiotherapy for Treatment of Localized Prostate Cancer

PubMed Central

Johansson, Silvia; Åström, Lennart; Sandin, Fredrik; Isacsson, Ulf; Montelius, Anders; Turesson, Ingela

2012-01-01

Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity. PMID:22848840

Young Maltese Children's Ideas about Plants

ERIC Educational Resources Information Center

Gatt, Suzanne; Tunnicliffe, Sue Dale; Borg, Kurtsten; Lautier, Katya

2007-01-01

Fifty Maltese children, 25 in the second year of pre-school (4 years olds) and 25 in the first year of compulsory education (5 years old), were interviewed about their knowledge of plants. Analysis showed that they had a restricted understanding of the term, meaning something small, with a thin stalk, leaves and a flower. Trees, cacti and nettles…

N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study.

PubMed

Grant, Jon E; Odlaug, Brian L; Kim, Suck Won

2009-07-01

Trichotillomania is characterized by repetitive hair pulling that causes noticeable hair loss. Data on the pharmacologic treatment of trichotillomania are limited to conflicting studies of serotonergic medications. N-acetylcysteine, an amino acid, seems to restore the extracellular glutamate concentration in the nucleus accumbens and, therefore, offers promise in the reduction of compulsive behavior. To determine the efficacy and tolerability of N-acetylcysteine in adults with trichotillomania. Twelve-week, double-blind, placebo-controlled trial. Ambulatory care center. Fifty individuals with trichotillomania (45 women and 5 men; mean [SD] age, 34.3 [12.1] years). N-acetylcysteine (dosing range, 1200-2400 mg/d) or placebo was administered for 12 weeks. Patients were assessed using the Massachusetts General Hospital Hair Pulling Scale, the Clinical Global Impression scale, the Psychiatric Institute Trichotillomania Scale, and measures of depression, anxiety, and psychosocial functioning. Outcomes were examined using analysis of variance modeling analyses and linear regression in an intention-to-treat population. Patients assigned to receive N-acetylcysteine had significantly greater reductions in hair-pulling symptoms as measured using the Massachusetts General Hospital Hair Pulling Scale (P < .001) and the Psychiatric Institute Trichotillomania Scale (P = .001). Fifty-six percent of patients "much or very much improved" with N-acetylcysteine use compared with 16% taking placebo (P = .003). Significant improvement was initially noted after 9 weeks of treatment. This study, the first to our knowledge that examines the efficacy of a glutamatergic agent in the treatment of trichotillomania, found that N-acetylcysteine demonstrated statistically significant reductions in trichotillomania symptoms. No adverse events occurred in the N-acetylcysteine group, and N-acetylcysteine was well tolerated. Pharmacologic modulation of the glutamate system may prove to be useful in the control of a range of compulsive behaviors. clinicaltrials.gov Identifier: NCT00354770.

Dose–Volume Modeling of Brachial Plexus-Associated Neuropathy After Radiation Therapy for Head-and-Neck Cancer: Findings From a Prospective Screening Protocol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Allen M., E-mail: amchen@mednet.ucla.edu; Wang, Pin-Chieh; Daly, Megan E.

2014-03-15

Purpose: Data from a prospective screening protocol administered for patients previously irradiated for head-and-neck cancer was analyzed to identify dosimetric predictors of brachial plexus-associated neuropathy. Methods and Materials: Three hundred fifty-two patients who had previously completed radiation therapy for squamous cell carcinoma of the head and neck were prospectively screened from August 2007 to April 2013 using a standardized self-administered instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from radiation therapy was 40 months (range, 6-111 months). A total of 177 patients (50%)more » underwent neck dissection. Two hundred twenty-one patients (63%) received concurrent chemotherapy. Results: Fifty-one patients (14%) reported brachial plexus-related neuropathic symptoms with the most common being ipsilateral pain (50%), numbness/tingling (40%), and motor weakness and/or muscle atrophy (25%). The 3- and 5-year estimates of freedom from brachial plexus-associated neuropathy were 86% and 81%, respectively. Clinical/pathological N3 disease (P<.001) and maximum radiation dose to the ipsilateral brachial plexus (P=.01) were significantly associated with neuropathic symptoms. Cox regression analysis revealed significant dose–volume effects for brachial plexus-associated neuropathy. The volume of the ipsilateral brachial plexus receiving >70 Gy (V70) predicted for symptoms, with the incidence increasing with V70 >10% (P<.001). A correlation was also observed for the volume receiving >74 Gy (V74) among patients treated without neck dissection, with a cutoff of 4% predictive of symptoms (P=.038). Conclusions: Dose–volume guidelines were developed for radiation planning that may limit brachial plexus-related neuropathies.« less

Clinical Study of Senna Administration to Nursing Mothers

PubMed Central

Baldwin, William F.

1963-01-01

Fifty nursing mothers were given regular doses of a senna compound (Senokot Granules) and 50 received mineral oil or magnesia (Magnolax) to determine whether senna was an effective laxative and whether senna affected the bowel habits of infants of nursing mothers. Senna laxative was effective in 49 of 50 mothers. Infant bowel habits were not affected by senna administration to nursing mothers. The evidence suggests that the active principles of senna if they are transmitted in breast milk have no effect on the evacuation patterns of nursed infants. PMID:14045350

Decreased Lung Perfusion After Breast/Chest Wall Irradiation: Quantitative Results From a Prospective Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liss, Adam L., E-mail: adamliss68@gmail.com; Marsh, Robin B.; Kapadia, Nirav S.

Purpose: To quantify lung perfusion changes after breast/chest wall radiation therapy (RT) using pre- and post-RT single photon emission computed tomography/computed tomography (SPECT/CT) attenuation-corrected perfusion scans; and correlate decreased perfusion with adjuvant RT dose for breast cancer in a prospective clinical trial. Methods and Materials: As part of an institutional review board–approved trial studying the impact of RT technique on lung function in node-positive breast cancer, patients received breast/chest wall and regional nodal irradiation including superior internal mammary node RT to 50 to 52.2 Gy with a boost to the tumor bed/mastectomy scar. All patients underwent quantitative SPECT/CT lung perfusion scanningmore » before RT and 1 year after RT. The SPECT/CT scans were co-registered, and the ratio of decreased perfusion after RT relative to the pre-RT perfusion scan was calculated to allow for direct comparison of SPECT/CT perfusion changes with delivered RT dose. The average ratio of decreased perfusion was calculated in 10-Gy dose increments from 0 to 60 Gy. Results: Fifty patients had complete lung SPECT/CT perfusion data available. No patient developed symptoms consistent with pulmonary toxicity. Nearly all patients demonstrated decreased perfusion in the left lung according to voxel-based analyses. The average ratio of lung perfusion deficits increased for each 10-Gy increment in radiation dose to the lung, with the largest changes in regions of lung that received 50 to 60 Gy (ratio 0.72 [95% confidence interval 0.64-0.79], P<.001) compared with the 0- to 10-Gy region. For each increase in 10 Gy to the left lung, the lung perfusion ratio decreased by 0.06 (P<.001). Conclusions: In the assessment of 50 patients with node-positive breast cancer treated with RT in a prospective clinical trial, decreased lung perfusion by SPECT/CT was demonstrated. Our study allowed for quantification of lung perfusion defects in a prospective cohort of breast cancer patients for whom attenuation-corrected SPECT/CT scans could be registered directly to RT treatment fields for precise dose estimates.« less

Using quality of life measures in a Phase I clinical trial of noni in patients with advanced cancer to select a Phase II dose.

PubMed

Issell, Brian F; Gotay, Carolyn C; Pagano, Ian; Franke, Adrian A

2009-01-01

ABSTRACT. The purpose of this study was to determine a maximum tolerated dose of noni in cancer patients and whether an optimal quality of life-sustaining dose could be identified as an alternative way to select a dose for subsequent Phase II efficacy trials. Dose levels started at two capsules twice daily (2 g), the suggested dose for the marketed product, and were escalated by 2 g daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed subscales of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life (physical functioning, pain, and fatigue) the brief fatigue inventory (BFI), questionnaires at baseline and at approximately 4-week intervals. Blood and urine were collected at baseline and at approximately 4-week intervals for measurement of scopoletin. Fifty-one patients were enrolled at seven dose levels. The maximum tolerated dose was six capsules four times daily (12 g). Although no dose-limiting toxicity was found, seven of eight patients at the next level (14 g), withdrew due to the challenges of ingesting so many capsules. There were dose-related differences in self-reported physical functioning and pain and fatigue control. Overall, patients taking three or four capsules four times daily experienced better outcomes than patients taking lower or higher doses. Blood and urinary scopoletin concentrations related to noni dose. We concluded that it is feasible to use quality of life measures to select a Phase II dose. Three or four capsules four times daily (6-8 g) is recommended when controlling fatigue, pain, and maintaining physical function are the efficacies of interest. Scopoletin, a bioactive component of noni fruit extract, is measurable in blood and urine following noni ingestion and can be used to study the pharmacokinetics of noni in cancer patients.

Low-power-laser therapy used in tendon damage

NASA Astrophysics Data System (ADS)

Strupinska, Ewa

1996-03-01

The following paper covers evaluation of low-power laser therapy results in chronic Achilles tendon damage and external Epicondylalia (tennis elbow). Fifty patients with Achilles damage (18 women and 32 men, age average 30, 24 plus or minus 10, 39 years) and fifty patients having external Epicondyalgiae (31 women and 19 men, age average 44, 36 plus or minus 10, 88 years) have been examined. The patients were irradiated by semiconductor infrared laser wavelength 904 nm separately or together with helium-neon laser wavelength 632.8 nm. The results of therapy have been based on the patient's interviews and examinations of patients as well as on the Laitinen pain questionnaire. The results prove analgesic effects in usage of low- power laser radiation therapy can be obtained.

Fifty Years of Progress, 1937-1987 [Lawrence Berkeley Laboratory (LBL, LBNL)

DOE R&D Accomplishments Database

Budinger, T. F. (ed.)

1987-01-01

This booklet was prepared for the 50th anniversary of medical and biological research at the Donner Laboratory and the Lawrence Berkeley Laboratory of the University of California. The intent is to present historical facts and to highlight important facets of fifty years of accomplishments in medical and biological sciences. A list of selected scientific publications from 1937 to 1960 is included to demonstrate the character and lasting importance of early pioneering work. The organizational concept is to show the research themes starting with the history, then discoveries of medically important radionuclides, then the use of accelerated charged particles in therapy, next human physiology studies then sequentially studies of biology from tissues to macromolecules; and finally studies of the genetic code.

200 Years of Vocational Education, 1776-1976; The Awakening, 1776-1826

ERIC Educational Resources Information Center

Barlow, Melvin L.

1976-01-01

Vocational education in the first fifty years of independence (1776-1826) was not perceived as a basic necessity in the education and training of the people. Rather, the focus was on expanding education and bringing it to the youth. (EC)

Long-Term Follow-Up of a Prospective Trial of Trimodality Therapy of Weekly Paclitaxel, Radiation, and Androgen Deprivation in High-Risk Prostate Cancer With or Without Prior Prostatectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hussain, Arif, E-mail: ahussain@som.umaryland.edu; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD; Baltimore VA Medical Center, Baltimore, MD

2012-01-01

Purpose: Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). Methods and Materials: Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) {>=}0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8-10; 3) GS 7 + PSA 10-20 ng/mL; or 4) PSA 20-150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m{sup 2}/wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). Results: Fifty-ninemore » patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45-86 years), PSA 5.9 (0.1-92.1 ng/mL), GS 8 (6-9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8-82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. Conclusions: In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m{sup 2}/week in RP patients and 60 mg/m{sup 2}/week in LAPC patients is feasible and well-tolerated.« less

Magnetic bearings: Fifty years of progress

NASA Technical Reports Server (NTRS)

Swann, Michael K.

1993-01-01

Magnetic bearings are just beginning to be flown in spacecraft systems, but their development spans more than 50 years. The promise of completely noncontacting, unlubricated rotating systems operating at speeds substantially beyond the range of conventional bearings, and with no wear and virtually no vibration, has provided the incentive to develop magnetic bearing technology for many diverse applications. Earnshaw theorized in 1842 that stable magnetic suspension is not possible in all three spatial directions unless the magnetic field is actively controlled. Since that time, researchers have attempted to successfully support spinning rotors in a stable manner. Development of magnetic suspension systems over the past fifty years has included progress on both passive (permanent magnet) and active (electromagnet) systems. The improvements in bearing load capacity, stiffness, and damping characteristics are traced. The trends in rotor size, rotational kinetic energy, and improvements in active control systems capabilities are also reviewed. Implications of superconductivity on suspension system design and performance are discussed.

Efficacy and toxicity profiles of two chemoradiotherapies for stage II laryngeal cancer - a comparison between late course accelerated hyperfractionation (LCAHF) and conventional fractionation (CF).

PubMed

Okazaki, Eiichiro; Matsushita, Naoki; Tashiro, Mari; Shimatani, Yasuhiko; Ishii, Kentaro; Hosono, Masako; Oishi, Masahiro; Teranishi, Yuichi; Iguchi, Hiroyoshi; Miki, Yukio

2017-08-01

To evaluate the treatment results of late course accelerated hyperfractionation (LCAHF) compared with conventional fractionation (CF) for stage II laryngeal cancer. Fifty-nine consecutive patients treated for stage II laryngeal cancer were retrospectively reviewed. Thirty-two patients underwent LCAHF, twice-daily fractions during the latter half with a total dose of 69 Gy. Twenty-seven patients received CF of 70 Gy. The local control rates (LCRs), overall survival (OS), and disease-specific survival (DSS) at 5 years were 80.6%, 74.0%, and 90.4%, respectively, after LCAHF and 64.7%, 68.2%, and 90.5%, respectively, after CF. There were no significant differences in LCR, OS, and DSS (p = .11, 0.68, and 0.69, respectively). In a small number of patients with supraglottic cancer, LCAHF was associated with a significantly higher LCR at 5 years compared with CF (100% vs. 41.7%; p = .02). This is the first report that compared the results of LCAHF and CF for stage II laryngeal cancer. We could not find significant differences in LCR, DSS, and OS rates between LCAHF and CF groups. Although in a small number of patients with supraglottic cancer, LCAHF may improve the LCR compared with CF.

Effect of Pretreatment Anemia on Treatment Outcome of Concurrent Radiochemotherapy in Patients With Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fortin, Andre; Wang Changshu; Vigneault, Eric

2008-09-01

Purpose: To investigate the effect of anemia on outcome of treatment with radiochemotherapy in patients with head-and-neck cancer. Methods and Materials: The data of 196 patients with Stage II-IV head-and-neck cancer treated with concomitant cisplatin-based radiochemotherapy were retrospectively reviewed. Anemia was defined according to World Health Organization criteria as hemoglobin <130 g/L in men and <120 g/L in women. Results: Fifty-three patients were classified as anemic, 143 as nonanemic. The 3-year local control rate of anemic and nonanemic patients was 72% and 85%, respectively (p = 0.01). The 3-year overall survival rate of anemic and nonanemic patients was 52% andmore » 77%, respectively (p = 0.004). In multivariate analysis, anemia was the most significant predictor of local control (hazard ratio, 0.37, p = 0.009) and survival (hazard ratio, 0.47, p = 0.007). A dose-effect relationship was also found for local control (p = .04) and survival (0.04) when grouping by hemoglobin concentration: <120, 120-140, and >140 g/L. Conclusions: Anemia was strongly associated with local control and survival in this cohort of patients with head-and-neck cancer receiving radiochemotherapy.« less

The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia.

PubMed

Stein, Eytan M; Garcia-Manero, Guillermo; Rizzieri, David A; Tibes, Raoul; Berdeja, Jesus G; Savona, Michael R; Jongen-Lavrenic, Mojca; Altman, Jessica K; Thomson, Blythe; Blakemore, Stephen J; Daigle, Scott R; Waters, Nigel J; Suttle, A Benjamin; Clawson, Alicia; Pollock, Roy; Krivtsov, Andrei; Armstrong, Scott A; DiMartino, Jorge; Hedrick, Eric; Löwenberg, Bob; Tallman, Martin S

2018-05-03

Pinometostat (EPZ-5676) is a first-in-class, small-molecule inhibitor of the histone methyltransferase DOT1L. In this phase 1 study, pinometostat was evaluated for safety and efficacy in adult patients with advanced acute leukemias, particularly those involving MLL rearrangements ( MLL-r ) resulting from 11q23 translocations. Fifty-one patients were enrolled into 6 dose escalation cohorts (n=26) and 2 expansion cohorts (n=25) at pinometostat doses of 54 and 90 mg/m 2 /day by continuous intravenous infusion in 28-day cycles. As a maximum tolerated dose was not established in the dose escalation phase, the expansion doses were selected based upon safety and clinical response data combined with pharmacodynamic evidence of reduction in H3K79 methylation during dose escalation. Across all dose levels, plasma pinometostat concentrations increased in an approximately dose-proportional fashion, reaching an apparent steady state by 4-8 hours after infusion, and rapidly decreased following treatment cessation. The most common adverse events, of any cause, were fatigue (39%), nausea (39%), constipation (35%), and febrile neutropenia (35%). Overall, 2 patients, both with t(11;19), experienced complete remissions at 54 mg/m 2 /day by continuous intravenous infusion, demonstrating proof of concept for delivering clinically meaningful responses through targeting DOT1L using single agent pinometostat in MLL-r leukemia patients. Administration of pinometostat was generally safe with the maximum tolerated dose not being reached, although efficacy as a single agent was modest. This study demonstrates the therapeutic potential for targeting DOT1L in MLL-r leukemia and lays the groundwork for future combination approaches in this patient population. This clinical trial is registered at www.clinicaltrials.gov as no. NCT01684150. Copyright © 2018 American Society of Hematology.

Thiazides diuretics in the treatment of nephrolithiasis: are we using them in an evidence-based fashion?

PubMed

Vigen, Rebecca; Weideman, Rick A; Reilly, Robert F

2011-09-01

In the 1980s a change occurred in hydrochlorothiazide prescribing practices for hypertension from high-dose (50 mg/day) to low-dose (12.5-25 mg/day) therapy. However, randomized controlled trials (RCT) for prevention of calcium-containing kidney stones (CCKS) employed only high doses (≥ 50 mg/day). We hypothesized that these practices have resulted in underdosing of hydrochlorothiazide for prevention of CCKS. Patients with a filled prescription for thiazide diuretics that underwent a 24-h urine stone risk factor analysis were eligible. Those with evidence that thiazide was prescribed for CCKS were further analyzed. Of 107 patients, 102 were treated with hydrochlorothiazide, 4 with indapamide, and one with chlorthalidone. Only 35% of hydrochlorothiazide-treated patients received 50 mg/day; a dose previously shown to reduce stone recurrence. Fifty-two percent were prescribed 25 mg and 13% 12.5 mg daily, doses that were not studied in RCT. Evidence-based hydrochlorothiazide use was suboptimal regardless of where the patient received care (Nephrology or Endocrinology clinic). In a small subset of patients (n = 6) with 24-h urinary calcium excretion measured at baseline and after 2 hydrochlorothiazide doses (25 and ≥ 50 mg), there was a trend toward decreased urinary calcium excretion as the dose was increased from 25 to ≥ 50 mg/day (p = 0.051). Low-dose hydrochlorothiazide was often used for prevention of CCKS despite the fact that there is no evidence that it is effective in this setting. This may have resulted from a practice pattern of using lower doses for hypertension therapy or a lack of knowledge of RCT results in treatment of CCKS.

The continuous time random walk, still trendy: fifty-year history, state of art and outlook

NASA Astrophysics Data System (ADS)

Kutner, Ryszard; Masoliver, Jaume

2017-03-01

In this article we demonstrate the very inspiring role of the continuous-time random walk (CTRW) formalism, the numerous modifications permitted by its flexibility, its various applications, and the promising perspectives in the various fields of knowledge. A short review of significant achievements and possibilities is given. However, this review is still far from completeness. We focused on a pivotal role of CTRWs mainly in anomalous stochastic processes discovered in physics and beyond. This article plays the role of an extended announcement of the Eur. Phys. J. B Special Issue [http://epjb.epj.org/open-calls-for-papers/123-epj-b/1090-ctrw-50-years-on] containing articles which show incredible possibilities of the CTRWs. Contribution to the Topical Issue "Continuous Time Random Walk Still Trendy: Fifty-year History, Current State and Outlook", edited by Ryszard Kutner and Jaume Masoliver.

Remembering the laser diode

NASA Astrophysics Data System (ADS)

2012-12-01

Fifty years ago, researchers at a handful of laboratories around the world were reporting lasing from the first semiconductor lasers. Our IT infrastructure today relies on their diligence and success.

[Immunohistochemistry of matrix metalloproteinases in different morphologic types of the lung cancer developed in the inhabitants of the Semipalatinsk Region].

PubMed

Sagindikova, G E; Kogan, E A; Satbaeva, E B

2008-01-01

The immunohistochemical characteristics of matrix metalloproteinases and their association with angiogenesis in different histological types of the lung cancer developed in the inhabitants of the Semipalatinsk Region (Kazakhstan) were investigated. The surgical and biopsy specimens from 87 patients with lung cancer, including 33 patients who had lived near the Semipalatinsk polygon from childhood to 2002 year and had been long exposed to radiation (annual radiation dose had been more than 0.1 Rem), were examined. Fifty-four control patients had lived in other Kazakhstan regions with the unchanged ionizing radiation background (n = 14) and in Moscow (n = 40). MMP-1, MMP-2, MMP-9, TIMP-1, VEGF, CD34, chromogranin, and CD68 were immunohistochemically detected. The increased expression of MMP-1, MMP-2, and MMP-9 in the cancer cells was ascertained in the study group as compared with the control one. Angiogenesis in the stroma of Semipalatinsk lung cancer was generally more pronounced, as judged by the expression of VEGF and the density of newly formed vessels.

Factors affecting outcome of treatment of chronic hepatitis C: result of an open label study from eastern India.

PubMed

Ray, Gautam

2016-01-01

Standard treatment of hepatitis C involves the use of pegylated interferon (PEGIFN) and ribavirin but directly acting antiviral agents (DAA) with seemingly greater efficacy have now appeared on the market. Thus closer detail needs to be given to optimise the use of the former. Fifty-two chronic hepatitis C patients (Child class A) were administered PEGIFN and ribavirin in a prospective, open label study in standard dose and duration. Complete therapy was ensured for the best chance of achieving a sustained viral response (SVR) and delineating its controlling factors. Seventy-five percent had genotype 3 virus. Compensated cirrhosis was present in 38.5%. Response overall and in cirrhotics were 65.4% and 30%, respectively, without difference between genotypes 1 and 3. Non-cirrhotics had higher response in all groups, especially genotype 1 (83.3%). The factors associated with positive response were age less than 50 years, absence of cirrhosis and presence of risk factors for transmission. Treatment outcome and factors affecting it are similar to studies from Europe and America. © The Author(s) 2015.

Fifty years of advances in sarcoma treatment: moving the needle from conventional chemotherapy to targeted therapy.

PubMed

Patel, Shreyaskumar R

2014-01-01

Much of the progress in systemic therapy for sarcomas was accomplished in the first half of the last 5 decades. Various chemotherapeutic agents were tested in the 70s through the 80s and became part of the standard of care for this patient population. During the decade of the 90s, dose intensification became feasible as a result of improved supportive care and the availability of growth factors, thus maximizing the therapeutic potential of this class of agents. However, response rates and survival plateaued and it became obvious that newer and mechanistically different agents were needed to improve the therapeutic index and gain further enhancement of outcomes. Since early 2000, primarily inspired by the experience with imatinib in gastrointestinal stromal tumors (GISTs), several targeted therapies have been tested in sarcomas with modest success. The major limitations encountered include the lack of drivers and actionable targets for bone and soft tissue sarcomas with complex genomic profiles. Continued investigations and sequencing of larger numbers of these rare and heterogeneous malignancies could shed some light on a path toward improved outcomes.

Serum Acetaminophen Protein Adduct Concentrations in Pediatric Emergency Department Patients.

PubMed

Heard, Kennon; Anderson, Victoria; Dart, Richard C; Kile, Deidre; Lavonas, Eric J; Green, Jody L

2017-04-01

Acetaminophen toxicity is a common cause of pediatric liver failure. The diagnosis may be limited by the short window of detection of acetaminophen in serum. Recently acetaminophen protein adducts (APAP-CYS) have been used as a biomarker with a longer duration of detection. The objective of this study was to describe the serum concentrations of APAP-CYS in pediatric patients with and without reported therapeutic acetaminophen exposure. A cross-sectional study of children age 1 to <12 years presenting to a pediatric emergency department. Subjects were stratified by recent acetaminophen use and had serum APAP-CYS measured using LC/MS. One hundred patients were enrolled. All of the patients whose caregivers denied acetaminophen exposure had nondetectable APAP-CYS. Fifty-two percent of subjects who were reported to have taken acetaminophen in the preceding 2 weeks had detectable serum APAP-CYS. The APAP-CYS concentrations were positively correlated with higher overall dose and more recent ingestion. APAP-CYS is detectable in the majority of children taking acetaminophen and not detected in the majority of children who are not exposed to acetaminophen.

Hydroxycarbamide treatment and brain MRI/MRA findings in children with sickle cell anaemia.

PubMed

Nottage, Kerri A; Ware, Russell E; Aygun, Banu; Smeltzer, Matthew; Kang, Guolian; Moen, Joseph; Wang, Winfred C; Hankins, Jane S; Helton, Kathleen J

2016-10-01

Silent cerebral infarction (SCI) is the most common neurological abnormality among children with sickle cell anaemia (SCA). The effect of hydroxycarbamide (also termed hydroxyurea) on the development and progression of SCI is unclear. We evaluated brain magnetic resonance imaging/angiography (MRI/MRA) in children with SCA receiving long-term hydroxycarbamide therapy. Fifty participants (median 9·4 years, range 1·1-17·3) enrolled in the Hydroxyurea Study of Long-Term Effects (HUSTLE; NCT00305175) underwent brain MRI/MRA and laboratory evaluations before hydroxycarbamide initiation and after 3 and 6 years of treatment to maximum tolerated dose. SCI and vascular stenosis were evaluated. At baseline, 3 and 6 years, SCI were present in 19/50 (38%), 20/49 (41%), and 7/17 (41%), respectively. At 3 years, one child developed a SCI lesion, and another progressed (single lesion to multiple). Lower haemoglobin (Hb) (80 g/l vs. 86 g/l, P = 0·049), fetal Hb (5·0% vs. 10·4%, P < 0·001) and oxygen saturation (97% vs. 98%, P = 0·027) before hydroxycarbamide initiation were associated with SCI. No patients had vascular stenosis identified on MRA, transient ischaemic attack or stroke. Our data indicate that children receiving hydroxycarbamide over a 3- to 6-year period have a low rate of new or worsening cerebrovascular disease. Further studies are needed to confirm that hydroxycarbamide can prevent the onset and progression of SCI. © 2016 John Wiley & Sons Ltd.

Estimating brain age using high-resolution pattern recognition: Younger brains in long-term meditation practitioners.

PubMed

Luders, Eileen; Cherbuin, Nicolas; Gaser, Christian

2016-07-01

Normal aging is known to be accompanied by loss of brain substance. The present study was designed to examine whether the practice of meditation is associated with a reduced brain age. Specific focus was directed at age fifty and beyond, as mid-life is a time when aging processes are known to become more prominent. We applied a recently developed machine learning algorithm trained to identify anatomical correlates of age in the brain translating those into one single score: the BrainAGE index (in years). Using this validated approach based on high-dimensional pattern recognition, we re-analyzed a large sample of 50 long-term meditators and 50 control subjects estimating and comparing their brain ages. We observed that, at age fifty, brains of meditators were estimated to be 7.5years younger than those of controls. In addition, we examined if the brain age estimates change with increasing age. While brain age estimates varied only little in controls, significant changes were detected in meditators: for every additional year over fifty, meditators' brains were estimated to be an additional 1month and 22days younger than their chronological age. Altogether, these findings seem to suggest that meditation is beneficial for brain preservation, effectively protecting against age-related atrophy with a consistently slower rate of brain aging throughout life. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy of preoperative injection versus intraoperative application of mitomycin in recurrent pterygium surgery

PubMed Central

Zaky, Khaled S; Khalifa, Yasser M

2012-01-01

Purpose: To determine the efficacy of preoperative subconjunctival injection of mitomycin C a day before surgery in the management of recurrent pterygium. Materials and Methods: Randomized comparative case series. Fifty eyes with recurrent pterygium were randomly divided into two groups; the mitomycin injection group (25 eyes) and the mitomycin application group (25 eyes). The mitomycin injection group underwent preoperative subconjunctival injection of mitomycin C in low dose (0.1 ml of 0.15 mg/ml) a day before bare sclera pterygium excision surgery. The mitomycin application group underwent bare sclera pterygium excision with topical application of mitomycin C (same concentration). Results: At one year of follow-up, 24 of 25 eyes (96%) in the mitomycin injection group and 23 of 25 (92%) eyes in the mitomycin application group were free of recurrence. The difference was statistically insignificant. As regards postoperative complications, delayed epithelization (more than two weeks) occurred in two eyes (8%) in the mitomycin injection group and in one eye (4%) in the mitomycin application group. Scleral thinning was reported in one eye (4%) in the mitomycin application group which resolved within three weeks after surgery, no other serious postoperative complications were reported. Conclusion: Preoperative subconjunctival injection of mitomycin C in low dose (0.1 ml of 0.15 mg/ml) a day before pterygium surgery is a simple and effective modality for management of recurrent pterygium. It has the advantage of low recurrence and complications’ rate. PMID:22824595

Citation measures in stereotactic radiosurgery: publication across a discipline.

PubMed

Kondziolka, Douglas

2011-01-01

It is possible to judge the impact of scientific research by the number of citations a publication has received. We identified the most cited works in the field of stereotactic radiosurgery to study the evolution of this field from the perspective of publication. A Web of Science search was performed for articles that included the word 'radiosurgery' in the title. We studied the reports with >100 citations. A total of 5,532 published works were available for study between 1951 and 2010. Eighty-five articles had ≥ 100 citations, and these were published in 19 separate journals. The majority were published in the International Journal of Radiation Oncology, Biology and Physics, the Journal of Neurosurgery and Neurosurgery. The most common topics included brain metastasis management (n = 20), arteriovenous malformations (n = 17), vestibular schwannomas (n = 9), technologies (n = 9), meningiomas (n = 8) and dose response/radiobiology (n = 6). Fifty-seven percent of the articles were published in the last 10 years. The first radiosurgery report by Leksell (1951) initiated the field. The 1980s were a period of new technology development followed in the 1990s by introductory articles on specific indications that consisted mainly of retrospective case series. More sophisticated higher level evidence reports were published in the last decade. The most significant works in radiosurgery include initial technology descriptions, multicenter studies with large numbers of patients, randomized clinical trials and reports that provide dose prescription guidelines. Copyright © 2011 S. Karger AG, Basel.

The effectiveness of the mumps component of the MMR vaccine: a case control study.

PubMed

Harling, Richard; White, Joanne M; Ramsay, Mary E; Macsween, Karen F; van den Bosch, Corry

2005-07-01

In 1998/1999, an outbreak of mumps occurred among children of a religious community in North East London. A case control study was conducted to assess the effectiveness of the mumps component of the MMR vaccine. One hundred and sixty-one cases of mumps were identified and 192 controls were selected. Fifty-one percent of cases and 77% of controls had a history at least one MMR vaccination. The observed effectiveness of any MMR vaccination adjusted for age, sex and general practice was 69% (95% CI: 41-84%). This is consistent with the results of other observational studies of mumps containing vaccines, but lower than the immunogenicity of mumps vaccines reported by clinical trials. This discrepancy is because observational studies tend to underestimate vaccine effectiveness, and because immunogenicity is not necessarily an accurate biological marker of vaccine effectiveness. Two doses of vaccine were more effective (88% (95% CI: 62-96%)) than a single dose (64% (95% CI: 40-78%)). The current two-dose vaccination programme remains the best method for controlling mumps infection in the community.

News

NASA Astrophysics Data System (ADS)

Davenhall, Clive

2010-07-01

Webb-Share update; Astro-cymru update; Copernicus reburied; Tycho to be exhumed; Caledonian anniversary 1: chair of astronomy at Glasgow; Caledonian anniversary II: James Ferguson: Fifty years of weather satellites; H.G. Wells remembered.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ben-David, Merav A.; Griffith, Kent A.; Abu-Isa, Eyad

Purpose: The role of radiation therapy (RT) in extrahepatic cholangiocarcinoma (EHCC) is not clear and only limited reports exist on the use of this modality. We have reviewed our institutional experience to determine the pattern of failure in patients after potentially curative resection and the expected outcomes after adjuvant RT and in unresectable patients. Methods and Materials: After institutional review board approval, 81 patients diagnosed with EHCC (gallbladder 28, distal bile duct 24, hilar 29) between June 1986 and December 2004 were identified and their records reviewed. Twenty-eight patients (35%) underwent potentially curative resection with R0/R1 margins. Fifty-two patients (64%)more » were unresectable or underwent resection with macroscopic residual disease (R2). All patients received three-dimensional planned megavoltage RT. The dose for each patient was converted to the equivalent total dose in a 2 Gy/fraction, using the linear-quadratic formalism and {alpha}/{beta} ratio of 10. The median dose delivered was 58.4 Gy (range, 23-88.2 Gy). 54% received concomitant chemotherapy. Results: With a median follow-up time of 1.2 years (range, 0.1-9.8 years) 75 patients (93%) have died. Median overall survival (OS) and progression-free survival (PFS) were 14.7 (95% CI, 13.1-16.3) and 11 (95% CI, 7.6-13.2) months, respectively. There was no difference among the three disease sites in OS (p = 0.70) or PFS (p = 0.80). Complete resection (R0) was the only predictive factor significantly associated with increase in both OS and PFS (p = 0.002), and there was no difference in outcomes between R1 and R2 resections. The first site of failure was predominantly locoregional (68.8% of all failures). Conclusion: Local failure is a major problem in EHCC, suggesting the need for more intense radiation schedules and better radiosensitizing strategies. Because R1 resection appears to convey no benefit, it appears that surgery should be contemplated only when an R0 resection is likely. Borderline-resectable patients might be better served by neoadjuvant therapy.« less

Rescue Pharmacotherapy With Duloxetine for Selective Serotonin Reuptake Inhibitor Nonresponders in Late-Life Depression: Outcome and Tolerability

PubMed Central

Karp, Jordan F.; Whyte, Ellen M.; Lenze, Eric J.; Dew, Mary A.; Begley, Amy; Miller, Mark D.; Reynolds, Charles F.

2010-01-01

Background Up to 50% of depressed older adults either do not adequately respond to or are unable to tolerate treatment with a serotonin-specific reuptake inhibitor. On the basis of previous experience with serotonin-norepinephrine reuptake inhibitors, we predicted at least a 50% response rate to open-label treatment with duloxetine in subjects who were resistant to treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram. Method Community-dwelling subjects aged 65 years or older with current nonpsychotic major depressive disorder as established by the Structured Clinical Interview for DSM-IV received escitalopram under protocolized conditions between April 2004 and September 2006. Subjects who failed to meet response criteria or relapsed after achieving an initial response were subsequently switched to open treatment with duloxetine up to 120 mg/day. Side effects were assessed at every visit. Results Subjects (N = 40) switched to duloxetine had a mean (SD) age of 74.4 (7.0) years and a baseline (before escitalopram) 17-item Hamilton Rating Scale for Depression (HAM-D-17) score of 20.0 (3.5) and were predominantly female (65.0%) and white (82.5%). The mean (SD) maximum dose of duloxetine was 93.0 (27.8) mg/day. Subjects received this maximum dose for a median duration of 6.9 weeks. Fifty percent of subjects (N = 20) met criteria for full response, 17.5% (N = 7) were partial responders, and 32.5% (N = 13) did not respond. The median time to response was 12.0 weeks (95% CI = 8.4 to 14.6). Five of the subjects (12.5%) discontinued duloxetine because of intolerable side effects. Discussion These open-label data suggest that duloxetine at doses up to 120 mg/day is a well-tolerated and potentially effective treatment for older adults who fail to respond to an adequate trial of an SSRI. These results are preliminary, and future controlled studies are required to test the efficacy of rescue pharmacotherapy with duloxetine. Trial Registration clinicaltrials.gov Identifier: NCT00177671 PMID:18251622

A knowledge-based approach to automated planning for hepatocellular carcinoma.

PubMed

Zhang, Yujie; Li, Tingting; Xiao, Han; Ji, Weixing; Guo, Ming; Zeng, Zhaochong; Zhang, Jianying

2018-01-01

To build a knowledge-based model of liver cancer for Auto-Planning, a function in Pinnacle, which is used as an automated inverse intensity modulated radiation therapy (IMRT) planning system. Fifty Tomotherapy patients were enrolled to extract the dose-volume histograms (DVHs) information and construct the protocol for Auto-Planning model. Twenty more patients were chosen additionally to test the model. Manual planning and automatic planning were performed blindly for all twenty test patients with the same machine and treatment planning system. The dose distributions of target and organs at risks (OARs), along with the working time for planning, were evaluated. Statistically significant results showed that automated plans performed better in target conformity index (CI) while mean target dose was 0.5 Gy higher than manual plans. The differences between target homogeneity indexes (HI) of the two methods were not statistically significant. Additionally, the doses of normal liver, left kidney, and small bowel were significantly reduced with automated plan. Particularly, mean dose and V15 of normal liver were 1.4 Gy and 40.5 cc lower with automated plans respectively. Mean doses of left kidney and small bowel were reduced with automated plans by 1.2 Gy and 2.1 Gy respectively. In contrast, working time was also significantly reduced with automated planning. Auto-Planning shows availability and effectiveness in our knowledge-based model for liver cancer. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Fifty years of forestry research: annotated bibliography of the Pacific Southwest Forest and Range Experiment Station, 1926-1975

Treesearch

Vincent P. Aitro

1977-01-01

Lists 2905 publications, with annotations and subject and author indexes, issued during the first 50 years of the Pacific Southwest Forest and Range Experiment Station (formerly the California Forest and Range Experiment Station), headquartered at Berkeley, California.

An Evaluation of the Preschool PATHS Curriculum on the Development of Preschool Children

ERIC Educational Resources Information Center

Hughes, Cerian; Cline, Tony

2015-01-01

This study evaluated the efficacy of preschool Promoting Alternative Thinking Strategies (PATHS), an early years curriculum designed to improve children's social and emotional competence, and reduce problem behaviour. Fifty-seven children aged three to four years took part in the study over one academic year. The control group (Group 1) received…

Fostering First-Year Students' Engagement and Well-Being through Visual Narratives

ERIC Educational Resources Information Center

Everett, Michele C.

2017-01-01

This article reports on a qualitative study that explored the learning outcomes from an innovative instructional method, visual narratives, used in a first-year seminar. Fifty-three students enrolled in a mandatory first semester student success course were instructed to use visual images to tell the story of the first-year experience. Data…

The effect of IVPCA morphine on post-hysterectomy bowel function.

PubMed

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.

A phase 2 study of the safety, tolerability, and pharmacodynamics of FBS0701, a novel oral iron chelator, in transfusional iron overload.

PubMed

Neufeld, Ellis J; Galanello, Renzo; Viprakasit, Vip; Aydinok, Yesim; Piga, Antonio; Harmatz, Paul; Forni, Gian Luca; Shah, Farrukh T; Grace, Rachael F; Porter, John B; Wood, John C; Peppe, Jennifer; Jones, Amber; Rienhoff, Hugh Young

2012-04-05

This was a 24-week, multicenter phase-2 study designed to assess safety, tolerability, and pharmacodynamics of FBS0701, a novel oral chelator, in adults with transfusional iron overload. Fifty-one patients, stratified by transfusional iron intake, were randomized to FBS0701 at either 14.5 or 29 mg/kg/d (16 and 32 mg/kg/d salt form). FBS0701 was generally well tolerated at both doses. Forty-nine patients (96%) completed the study. There were no drug-related serious adverse events. No adverse events (AEs) showed dose-dependency in frequency or severity. Treatment-related nausea, vomiting, abdominal pain, and diarrhea were each noted in < 5% of patients. Mean serum creatinine did not change significantly from Baseline or between dose groups. Transaminases wer increased in 8 (16%), three of whom acquired HCV on-study from a single blood bank while five had an abnormal baseline ALT. The 24 week mean change in liver iron concentration (ΔLIC) at 14.5 mg/kg/d was +3.1 mg/g (dw); 29% achieved a decrease in LIC. Mean ΔLIC at 29 mg/kg/d was -0.3 mg/g (dw); 44% achieved a decrease in LIC (P < .03 for ΔLIC between doses). The safety and tolerability profile at therapeutic doses compare favorably to other oral chelators.

Quercetin dose affects the fate of hepatic ischemia and reperfusion injury in rats: An experimental research.

PubMed

Uylaş, Mustafa Ufuk; Şahin, Adnan; Şahintürk, Varol; Alataş, İbrahim Özkan

2018-05-01

Quercetin found in fruits and vegetables has an antioxidative effect. We aimed to investigate the protective effects of quercetin according to different doses on hepatic and ischemia-reperfusion (I/R) injury. Fifty mature male Sprague-Dawley rats were randomly divided into five groups (n = 10 for each). All the animal groups underwent laparotomy. Group 1 rats served as a sham-operated group. Groups 2-5 underwent 1 h hepatic ischemia and were followed by 2 h reperfusion. Group 3-5 animals received an additional intraperitoneal dose of 25, 50 or 100 mg/kg quercetin respectively before I/R operation. Blood samples were collected for determining serum aspartate transaminase (AST), alanine transaminase (ALT) and malondialdehyde (MDA) levels. Also, liver tissue samples were taken for measuring of liver MDA concentration and for histopathology assessment. The highest levels of biochemical parameters were observed in group 2. In quercetin-treated groups, serum AST, ALT, MDA levels, and tissue MDA concentration were decreased as inversely with increasing quercetin dose. Microscopic evaluation revealed that most conspicuous histological improvement was observed in 50 mg/kg quercetin co-treated rats. 25 and 100 mg/kg quercetin co-treatment could not protect completely against hepatic I/R injury. Quercetin can be effective in preventing of hepatic I/R injury when the correct dose was used. Copyright © 2018. Published by Elsevier Ltd.

Dual-energy CT for the characterization of urinary calculi: In vitro and in vivo evaluation of a low-dose scanning protocol.

PubMed

Thomas, C; Patschan, O; Ketelsen, D; Tsiflikas, I; Reimann, A; Brodoefel, H; Buchgeister, M; Nagele, U; Stenzl, A; Claussen, C; Kopp, A; Heuschmid, M; Schlemmer, H-P

2009-06-01

The efficiency and radiation dose of a low-dose dual-energy (DE) CT protocol for the evaluation of urinary calculus disease were evaluated. A low-dose dual-source DE-CT renal calculi protocol (140 kV, 46 mAs; 80 kV, 210 mAs) was derived from the single-energy (SE) CT protocol used in our institution for the detection of renal calculi (120 kV, 75 mAs). An Alderson-Rando phantom was equipped with thermoluminescence dosimeters and examined by CT with both protocols. The effective doses were calculated. Fifty-one patients with suspected or known urinary calculus disease underwent DE-CT. DE analysis was performed if calculi were detected using a dedicated software tool. Results were compared to chemical analysis after invasive calculus extraction. An effective dose of 3.43 mSv (male) and 5.30 mSv (female) was measured in the phantom for the DE protocol (vs. 3.17/4.57 mSv for the SE protocol). Urinary calculi were found in 34 patients; in 28 patients, calculi were removed and analyzed (23 patients with calcified calculi, three with uric acid calculi, one with 2,8-dihyxdroxyadenine-calculi, one patient with a mixed struvite calculus). DE analysis was able to distinguish between calcified and non-calcified calculi in all cases. In conclusion, dual-energy urinary calculus analysis is effective also with a low-dose protocol. The protocol tested in this study reliably identified calcified urinary calculi in vivo.

Use of Arginine Hydrochloride in the Treatment of Metabolic Alkalosis or Hypochloremia in Pediatric Patients

PubMed Central

Hernandez, Elvin A.; Parbuoni, Kristine A.

2018-01-01

OBJECTIVES Dosing of arginine for treatment of hypochloremia or metabolic alkalosis is laborious and has inherent variability in dose selection. The primary objective of this study was to determine the efficacy of arginine in the treatment of metabolic alkalosis and hypochloremia. Secondary objectives were to determine an optimal dose, route, and frequency for arginine administration in the treatment of these conditions. METHODS This single center, retrospective, descriptive study was conducted in children who received arginine for treatment of hypochloremia or metabolic alkalosis. Treatment success was assessed by measuring serum chloride and bicarbonate concentrations after arginine administration. RESULTS Of the 464 orders analyzed, 177 met inclusion criteria in 82 unique patients. Fifty percent (n = 81) of arginine administrations used to manage hypochloremia saw normalization of abnormal chloride levels, and 83% (n = 62) of arginine administrations used to treat metabolic alkalosis saw normalization of abnormal bicarbonate levels. Patients who received arginine to resolve hypochloremia were statistically significantly more likely to have their hypochloremia resolve if they used alternative dosing methods compared to established dosing methods (76 vs. 5, p = 0.001). However, this relationship was not seen for patients with metabolic alkalosis (11 vs. 51, p = 1.000). The median percentage of calculated daily dose of arginine needed for resolution of hypochloremia was 59% and was 35% for metabolic alkalosis. CONCLUSIONS Arginine is effective to improve metabolic alkalosis and hypochloremia. Established dosing methods are not more effective than other methods in resolving metabolic alkalosis or hypochloremia. Further prospective studies are warranted to validate these results. PMID:29720912

Compliance with occlusion therapy for childhood amblyopia.

PubMed

Wallace, Michael P; Stewart, Catherine E; Moseley, Merrick J; Stephens, David A; Fielder, Alistair R

2013-09-17

Explore compliance with occlusion treatment of amblyopia in the Monitored and Randomized Occlusion Treatment of Amblyopia Studies (MOTAS and ROTAS), using objective monitoring. Both studies had a three-phase protocol: initial assessment, refractive adaptation, and occlusion. In the occlusion phase, participants were instructed to dose for 6 hours/day (MOTAS) or randomized to 6 or 12 hour/day (ROTAS). Dose was monitored continuously using an occlusion dose monitor (ODM). One hundred and fifty-two patients (71 male, 81 female; 122 Caucasian, 30 non-Caucasian) of mean ± SD age 68 ± 18 months participated. Amblyopia was defined as an interocular acuity difference of at least 0.1 logMAR and was associated with anisometropia in 50, strabismus in 44, and both (mixed) in 58. Median duration of occlusion was 99 days (interquartile range 72 days). Mean compliance was 44%, mean proportion of days with no patch worn was 42%. Compliance was lower (39%) on weekends compared with weekdays (46%, P = 0.04), as was the likelihood of dosing at all (52% vs. 60%, P = 0.028). Compliance was lower when attendance was less frequent (P < 0.001) and with prolonged treatment duration (P < 0.001). Age, sex, amblyopia type, and severity were not associated with compliance. Mixture modeling suggested three subpopulations of patch day doses: less than 30 minutes; doses that achieve 30% to 80% compliance; and doses that achieve around 100% compliance. This study shows that compliance with patching treatment averages less than 50% and is influenced by several factors. A greater understanding of these influences should improve treatment outcome. (ClinicalTrials.gov number, NCT00274664).

Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia.

PubMed

Akdim, Fatima; Tribble, Diane L; Flaim, JoAnn D; Yu, Rosie; Su, John; Geary, Richard S; Baker, Brenda F; Fuhr, Rainard; Wedel, Mark K; Kastelein, John J P

2011-11-01

Mipomersen, an apolipoprotein (apo) B synthesis inhibitor, has been shown to produce potent reductions in apoB and LDL-cholesterol levels in animal models as well as healthy human volunteers. A randomized, double-blind, placebo-controlled, dose-escalation study was designed to evaluate the efficacy and safety of mipomersen monotherapy with or without dose loading in subjects with mild-to-moderate hyperlipidaemia. Fifty subjects with LDL-cholesterol levels between 119 and 266 mg/dL were enrolled into five cohorts at a 4:1 randomization ratio of active to placebo. Two 13-week dose regimens were evaluated at doses ranging from 50 to 400 mg/week. Mipomersen produced dose-dependent reductions in all apoB containing lipoproteins. In the 200 and 300 mg/week dose cohorts, mean reductions from baseline in LDL cholesterol were -45 ± 10% (P= 0.000) and -61 ± 8% (P= 0.000), corresponding to a -46 ± 11% (P= 0.000) and -61 ± 7% (P= 0.000) decrease in apoB levels. Triglyceride levels were also lowered with median reductions up to 53% (P= 0.021). The most common adverse events were injection site reactions. Seven of 40 subjects (18%) showed consecutive transaminase elevations >3× upper limit of normal. Five of these subjects received 400 mg/week, four of whom had apoB levels below the limit of detection. As a consequence, the 400 mg/week cohort was discontinued. Mipomersen administered as monotherapy in subjects with mild-to-moderate hyperlipidaemia produced potent reductions in all apoB-containing lipoproteins. Higher doses were associated with hepatic transaminase increases.

Emulsification and demulsification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lissant, K.J.

1986-01-01

The origins and the field of emulsification and demulsification and early studies are reviewed with particular emphasis on the last fifty years. Trends and causes of the current revival in interest are indicated.

Risk of ionising radiation to trainee orthopaedic surgeons.

PubMed

Khan, Ishrat A; Kamalasekaran, Senthil; Fazal, M Ali

2012-02-01

We undertook this study to determine the amount of scattered radiation received by the primary surgeon, assistant and patient during dynamic hip screw fixation for proximal femoral fractures. Data was collected from fifty patients. Five registrars were included as operating surgeon and four senior house officers as assistant surgeon. Radiation was monitored by thermo luminescent dosimeters placed on the surgeon and assistant. The approximate distance of surgeon and assistant from the operative site was measured. A dosimeter on the unaffected hip of patients measured the radiation to the patient. The results show that the surgeon's dominant hand receives the highest dose of radiation and radiation exposure is dependent on the experience of the operator. Our study concludes that exposure to radiation during this procedure is well below the toxic levels; however greater awareness is needed for harmful effects of exposure to long term low dose radiation.

Are two doses of human papillomavirus vaccine sufficient for girls aged 15-18 years? Results from a cohort study in India.

PubMed

Bhatla, Neerja; Nene, Bhagwan M; Joshi, Smita; Esmy, Pulikottil O; Poli, Usha Rani Reddy; Joshi, Geeta; Verma, Yogesh; Zomawia, Eric; Pimple, Sharmila; Prabhu, Priya R; Basu, Partha; Muwonge, Richard; Hingmire, Sanjay; Sauvaget, Catherine; Lucas, Eric; Pawlita, Michael; Gheit, Tarik; Jayant, Kasturi; Malvi, Sylla G; Siddiqi, Maqsood; Michel, Angelika; Butt, Julia; Sankaran, Subha; Kannan, Thiraviam Pillai Rameshwari Ammal; Varghese, Rintu; Divate, Uma; Willhauck-Fleckenstein, Martina; Waterboer, Tim; Müller, Martin; Sehr, Peter; Kriplani, Alka; Mishra, Gauravi; Jadhav, Radhika; Thorat, Ranjit; Tommasino, Massimo; Pillai, M Radhakrishna; Sankaranarayanan, Rengaswamy

2018-06-01

Extending two-dose recommendations of HPV vaccine to girls between 15 and 18 years will reduce program cost and improve compliance. Immunogenicity and vaccine targeted HPV infection outcomes were compared between 1795 girls aged 15-18 years receiving two (1-180 days) and 1515 girls of same age receiving three (1-60-180 days) doses. Immunogenicity outcomes in 15-18 year old two-dose recipients were also compared with the 10-14 year old three-dose (N = 2833) and two-dose (N = 3184) recipients. The 15-18 year old two-dose recipients had non-inferior L1-binding antibody titres at seven months against vaccine-targeted HPV types compared to three-dose recipients at 15-18 years and three-dose recipients at 10-14 years of age. Neutralizing antibody titres at 18 months in 15-18 year old two-dose recipients were non-inferior to same age three-dose recipients for all except HPV 18. The titres were inferior to those in the 10-14 year old three-dose recipients for all targeted types. Frequency of incident infections from vaccine-targeted HPV types in the 15-18 year old two-dose recipients was similar to the three dose recipients. None of the girls receiving two or three doses had persistent infection from vaccine-targeted types. These findings support that two doses of HPV vaccine can be extended to girls aged 15-18 years. Copyright © 2018. Published by Elsevier B.V.

Bruton Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Has Significant Activity in Patients With Relapsed/Refractory B-Cell Malignancies

PubMed Central

Buggy, Joseph J.; Sharman, Jeff P.; Smith, Sonali M.; Boyd, Thomas E.; Grant, Barbara; Kolibaba, Kathryn S.; Furman, Richard R.; Rodriguez, Sara; Chang, Betty Y.; Sukbuntherng, Juthamas; Izumi, Raquel; Hamdy, Ahmed; Hedrick, Eric; Fowler, Nathan H.

2013-01-01

Purpose Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies. Patients and Methods Patients with relapsed or refractory B-cell lymphoma and chronic lymphocytic leukemia received escalating oral doses of ibrutinib. Two schedules were evaluated: one, 28 days on, 7 days off; and two, once-daily continuous dosing. Occupancy of BTK by ibrutinib in peripheral blood was monitored using a fluorescent affinity probe. Dose escalation proceeded until either the maximum-tolerated dose (MTD) was achieved or, in the absence of MTD, until three dose levels above full BTK occupancy by ibrutinib. Response was evaluated every two cycles. Results Fifty-six patients with a variety of B-cell malignancies were treated over seven cohorts. Most adverse events were grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without reaching MTD. Pharmacokinetic data indicated rapid absorption and elimination, yet BTK occupancy was maintained for at least 24 hours, consistent with the irreversible mechanism. Objective response rate in 50 evaluable patients was 60%, including complete response of 16%. Median progression-free survival in all patients was 13.6 months. Conclusion Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies. PMID:23045577

Doxycycline shows dose-dependent changes in hernia repair strength after mesh repair.

PubMed

Tharappel, Job C; Harris, Jennifer W; Zwischenberger, Brittany A; Levy, Salomon M; Puleo, David A; Roth, J Scott

2016-05-01

Ventral hernia is a commonly occurring surgical problem. Our earlier studies have shown that a 30 mg/kg dose of doxycycline can significantly impact the strength of polypropylene (PP) mesh in a rat hernia repair model at 6 and 12 weeks. The objective of the present study was to investigate the dose dependence of doxycycline treatment on hernia repair strengths in rats. Fifty-six Sprague-Dawley rats underwent hernia repair with either PP mesh (n = 28) or sutures only (primary; n = 28); both groups were further divided into four doxycycline groups of seven animals each: control (0 mg/kg), low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg). One day before hernia repair surgery, animals received doxycycline doses by gavage and continued receiving daily until euthanasia. After 8 weeks, rats were euthanized and tissue samples from hernia repaired area were collected and analyzed for tensile strength using a tensiometer (Instron, Canton, MA, USA), while MMPs 2, 3, and 9, and collagen type 1 and 3 were analyzed by western blotting. In mesh-repaired animals, medium and high doxycycline dose repaired mesh fascia interface (MFI) showed significant increase in tensile strength when compared to control. In the primary repaired animals, there was no significant difference in MFI tensile strength in any dose group. In medium-dose MFI, there was a significant reduction in MMPs 2, 3, and 9. In this animal group, MFI showed significant increase in collagen 1 and significant reduction in collagen type 3 when compared to control. It is possible to improve the strength of mesh-repaired tissue by administering a significantly lower dose of the drug, which has implications for translation of the findings.

Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies.

PubMed

Advani, Ranjana H; Buggy, Joseph J; Sharman, Jeff P; Smith, Sonali M; Boyd, Thomas E; Grant, Barbara; Kolibaba, Kathryn S; Furman, Richard R; Rodriguez, Sara; Chang, Betty Y; Sukbuntherng, Juthamas; Izumi, Raquel; Hamdy, Ahmed; Hedrick, Eric; Fowler, Nathan H

2013-01-01

Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies. Patients with relapsed or refractory B-cell lymphoma and chronic lymphocytic leukemia received escalating oral doses of ibrutinib. Two schedules were evaluated: one, 28 days on, 7 days off; and two, once-daily continuous dosing. Occupancy of BTK by ibrutinib in peripheral blood was monitored using a fluorescent affinity probe. Dose escalation proceeded until either the maximum-tolerated dose (MTD) was achieved or, in the absence of MTD, until three dose levels above full BTK occupancy by ibrutinib. Response was evaluated every two cycles. Fifty-six patients with a variety of B-cell malignancies were treated over seven cohorts. Most adverse events were grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without reaching MTD. Pharmacokinetic data indicated rapid absorption and elimination, yet BTK occupancy was maintained for at least 24 hours, consistent with the irreversible mechanism. Objective response rate in 50 evaluable patients was 60%, including complete response of 16%. Median progression-free survival in all patients was 13.6 months. Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies.

Lessons Drawn from Sputnik 50 Years Later

ERIC Educational Resources Information Center

Cavanagh, Sean

2007-01-01

Fifty years ago, with the Soviet Union's launch of the Sputnik satellite, millions of Americans found themselves peering anxiously into the night sky--and also looking inward, as they reconsidered previously cozy assumptions about their nation's technological and educational superiority. The 184-pound, unmanned aluminum beacon lasted just three…

50 Years after "Brown": Segregation in the Miami-Dade County Public Schools

ERIC Educational Resources Information Center

Moore, James

2004-01-01

Fifty years after the "Brown v. Board of Education" decision outlawed de jure segregation in American schools, many school districts remain segregated. Despite numerous efforts aimed at desegregation, residential segregation--the primary barrier to significant school desegregation--remains entrenched throughout the United States. The Miami-Dade…

Selected Characteristics of Beginning Science and Mathematics Teachers in Georgia.

ERIC Educational Resources Information Center

Carter, Jack Caldwell

One hundred fifty-seven first year science and mathematics teachers were randomly selected from the population of beginning teachers in Georgia for the school years 1965-66 and 1966-67. Instruments used for data collection were the "Classroom Observation Record (COR),""Pupil Observation Survey (POSR),""Bills Index of…

Fish Stories

ERIC Educational Resources Information Center

Hinshaw, Craig

2007-01-01

Every year, the Parent-Teacher Organization of Hiller Elementary School gives every teacher a fifty dollar bill to help offset classroom expenses. This year the author, a second grade teacher, knew exactly how he would spend the money. He bought thirty-eight perfect, clear, two-quart plastic, lidded containers for each of his students and three…

Tax Wealth in Fifty States.

ERIC Educational Resources Information Center

Halstead, D. Kent

This study presents a scheme for yearly, comparative, computation of state and local government tax capacity and effort. Figures for all states for fiscal year 1975 are presented in extensive tables. The system used is a simplified version of the Representative Tax System, which identifies tax bases, determines national average tax rates for those…

Enhancing English Language Planning Strategy Using a WebQuest Model

ERIC Educational Resources Information Center

Al-Sayed, Rania Kamal Muhammad; Abdel-Haq, Eman Muhammad; El-Deeb, Mervat Abou-Bakr; Ali, Mahsoub Abdel-Sadeq

2016-01-01

The present study aimed at developing English language planning strategy of second year distinguished governmental language preparatory school pupils using the a WebQuest model. Fifty participants from second year at Hassan Abu-Bakr Distinguished Governmental Language School at Al-Qanater Al-Khairia (Qalubia Governorate) were randomly assigned…

Salvage Chemoimmunotherapy With Inotuzumab Ozogamicin Combined With Mini-Hyper-CVD for Patients With Relapsed or Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: A Phase 2 Clinical Trial.

PubMed

Jabbour, Elias; Ravandi, Farhad; Kebriaei, Partow; Huang, Xuelin; Short, Nicholas J; Thomas, Deborah; Sasaki, Koji; Rytting, Michael; Jain, Nitin; Konopleva, Marina; Garcia-Manero, Guillermo; Champlin, Richard; Marin, David; Kadia, Tapan; Cortes, Jorge; Estrov, Zeev; Takahashi, Koichi; Patel, Yogin; Khouri, Maria R; Jacob, Jovitta; Garris, Rebecca; O'Brien, Susan; Kantarjian, Hagop

2018-02-01

The outcome of patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has single-agent activity in R/R ALL. To evaluate the efficacy and safety of inotuzumab ozogamicin plus low-intensity chemotherapy in patients with R/R ALL. A single-arm, phase 2 study of adults with R/R B-cell ALL conducted at The University of Texas MD Anderson Cancer Center, Houston. The chemotherapy used was lower intensity than hyper-CVAD (cyclophosphamide, vincristine, doxorubicin [trade name, Adriamycin; Pfizer], and dexamethasone) and is referred to as mini-hyper-CVD (mini-HCVD: cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine at 0.5 g/m2 × 4 doses). Inotuzumab was given on day 3 of the first 4 courses at 1.8 to 1.3 mg/m2 for cycle 1 followed by 1.3 to 1.0 mg/m2 for subsequent cycles. The primary end points were the overall response rate and overall survival (OS). Secondary end points included safety, relapse-free survival (RFS), the rate of allogeneic stem cell transplantation (ASCT), and the minimal residual disease (MRD) negativity rate. Fifty-nine patients (30 women and 29 men) with a median age of 35 years (range, 18-87 years) were treated. Overall, 46 patients (78%) responded, 35 of them (59%) achieving complete response. The overall MRD negativity rate among responders was 82%. Twenty-six patients (44%) received ASCT. Grade 3 to 4 toxic effects included prolonged thrombocytopenia (81%; n = 48), infections (73%; n = 43), and hyperbilirubinemia (14%; n = 8). Veno-occlusive disease (VOD) occurred in 9 patients (15%). With a median follow-up of 24 months, the median RFS and OS were 8 and 11 months, respectively. The 1-year RFS and OS rates were 40% and 46%, respectively. The 1-year OS rates for patients treated in salvage 1, salvage 2, and salvage 3 or beyond were 57%, 26%, and 39%, respectively (P = .03). The combination of inotuzumab with low-intensity mini-HCVD chemotherapy shows encouraging results in R/R ALL. The risk of VOD should be considered carefully in patients with previous liver damage and among transplant candidates. clinicaltrials.gov Identifier: NCT01371630.

[Minamata disease: a neuropathological viewpoint].

PubMed

Eto, Komyo

2006-01-01

Minamata disease (methylmercury poisoning) was first officially discovered around Minamata Bay in the Kumamoto Prefecture on May 1st, 1956. This year, a commemoration marking fifty years since this discovery of Minamata disease will be held in Minamata City. Over the years, new facts have gradually surfaced, especially after 1995, with the resolution of the political problems surrounding Minamata disease. For example, it was recently reported that large amounts of methylmercury were generated by the chemical processes of the Chisso acetaldehyde plant and later dumped directly into Minamata Bay. This report revealed the August 1951 switch from using manganese dioxide to ferric sulfide as a reaction promoter to maintain the activity of the Hg catalyst. As a result of this switch, the amount of methylmercury generated in the process rapidly increased. Thus, the true cause of the acute onset of Minamata disease in patients with a high-dose contamination of methylmercury was made clear. The severe contamination by methylmercury continued until 1968, when the plant finally stopped discharging its waste water into Minamata Bay. In 1996, the National Institute for Minamata Disease started an experimental study of methylmercury poisoning using the common marmoset. Results from this study showed that the lesions characteristic of the central nervous system in cases of acute methylmercury poisoning were promoted by brain edema, while those of the peripheral nerves were caused by axonal degeneration. Peripheral nerves were regenerated in two animals after two and a half years. Lesions characteristic of Minamata disease are systematically found throughout the nervous system. These lesions are found in the calcarine areas of occipital lobes, the pre- and post-central lobes, and the temporal transverse gyri. Milder and more diffuse lesions are also found in the cerebrum, where secondary degeneration of the central parts of white matter and internal sagittal stratum are due to primary damage of neurons. Purkinje and granular cells decrease in number in the cerebellum depending on the dose of methylmercury and the duration of methylmercury exposure. In the spinal cord, there is no primary change, but secondary degeneration is found on pyramidal tracts due to damage of the motor neurons of the precentral cortices. Additionally, secondary degeneration of Goll's tract is seen due to the primary degeneration of sensory nerve fibers including ganglion cells, sciatic nerves, and sural nerves. The experiments on the methylmercury-treated common marmosets provided every feature of pathological change found in the nervous system in human autopsy cases, depending on the dose of methylmercury.

Evaluation of warfarin management with international normalized ratio self-testing and online remote monitoring and management plus low-dose vitamin k with genomic considerations: a pilot study.

PubMed

Bussey, Henry I; Bussey, Marie; Bussey-Smith, Kristin L; Frei, Christopher R

2013-11-01

As better international normalized ratio (INR) control and self-testing reduce events in warfarin-treated patients, and vitamin K supplementation may improve INR control, our primary objective was to evaluate the effect of a system combining frequent INR self-testing with online remote monitoring and management (STORM₂) and low-dose vitamin K supplementation on INR control; our secondary objectives were to assess the impact of STORM₂ on clinician time and to evaluate the influence of pharmacogenomics on INR stability and warfarin dose after vitamin K supplementation. Prospective pre- and postintervention study. Freestanding clinical research center. Fifty-five patients treated with long-term warfarin therapy who were referred from four anticoagulation clinics and seven medical practices. All patients performed weekly INR self-testing and received vitamin K 100 µg/day and online anticoagulation management for 1 year. INR control and time required for anticoagulation management were assessed, and an analysis of warfarin dosing and INR stability by genetic polymorphism subgroup (vitamin K epoxide reductase complex 1 [VKORC1] and cytochrome P450 2C9 isoenzyme) was performed; vitamin K product content was also analyzed. The percentage of time that the INR is within the time in therapeutic range (TTR) improved from 56% before the intervention to 81% after the intervention (p<0.0001), and time spent at extreme INR values of lower than 1.5 or higher than 5 was reduced from 3.1% to 0.4% (p=0.01). Clinician time was less than 10 minutes per four patient visits per month. Genetic polymorphisms did not correlate with INR stability or the increase in warfarin dose after vitamin K supplementation. The content of the vitamin K product, however, was only 34-76% of the labeled amount. Patients with the GG VKORC1 genotype required a higher warfarin dose than predicted by the genomic-based dosing chart in the warfarin package insert. The 25% point improvement in TTR with STORM₂ is a greater improvement than reported previously with other efforts to improve TTR. STORM₂ required a minimum amount of clinician time. Pharmacogenomics were not predictive of improved INR control or the magnitude of the warfarin dose after vitamin K supplementation, although the content of the product was unreliable. Patients with the GG VKORC1 genotype required a higher warfarin dose than predicted by the product information. The potential clinical impact of improved INR control with this method warrants comparisons with conventionally managed warfarin and with the new oral anticoagulants. © 2013 Pharmacotherapy Publications, Inc.

SU-F-T-378: Evaluation of Dose-Volume Variability and Parameters Between Prostate IMRT and VMAT Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chow, J; Jiang, R; Kiciak, A

2016-06-15

Purpose: This study compared the rectal dose-volume consistency, equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) in prostate intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). Methods: For forty prostate IMRT and fifty VMAT patients treated using the same dose prescription (78 Gy/39 fraction) and dose-volume criteria in inverse planning optimization, the rectal EUD and NTCP were calculated for each patient. The rectal dose-volume consistency, showing the variability of dose-volume histogram (DVH) among patients, was defined and calculated based on the deviation between the mean and corresponding rectal DVH. Results: From both the prostate IMRT andmore » VMAT plans, the rectal EUD and NTCP were found decreasing with the rectal volume. The decrease rates for the IMRT plans (EUD = 0.47 × 10{sup −3} Gy cm{sup −3} and NTCP = 3.94 × 10{sup −2} % cm{sup −3}) were higher than those for the VMAT (EUD = 0.28 × 10{sup −3} Gy cm{sup −3} and NTCP = 2.61 × 10{sup −2} % cm{sup −3}). In addition, the dependences of the rectal EUD and NTCP on the dose-volume consistency were found very similar between the prostate IMRT and VMAT plans. This shows that both delivery techniques have similar variations of the rectal EUD and NTCP on the dose-volume consistency. Conclusion: Dependences of the dose-volume consistency on the rectal EUD and NTCP were compared between the prostate IMRT and VMAT plans. It is concluded that both rectal EUD and NTCP decreased with an increase of the rectal volume. The variation rates of the rectal EUD and NTCP on the rectal volume were higher for the IMRT plans than VMAT. However, variations of the rectal dose-volume consistency on the rectal EUD and NTCP were found not significant for both delivery techniques.« less

Methylphenidate reduces mental fatigue and improves processing speed in persons suffered a traumatic brain injury.

PubMed

Johansson, B; Wentzel, A-P; Andréll, P; Mannheimer, C; Rönnbäck, L

2015-01-01

Post-traumatic brain injury symptoms, such as mental fatigue, have considerable negative impacts on quality-of-life. In the present study the effects of methylphenidate in two different dosages were assessed with regard to mental fatigue, pain and cognitive functions in persons who had suffered a traumatic brain injury. Fifty-one subjects were included and 44 completed the study. The treatment continued for 12 weeks, including three treatment periods with no medication for 4 weeks, administration of low dose methylphenidate (up to 5 mg × 3) for 4 weeks and normal dose methylphenidate (up to 20 mg × 3) for a further 4 weeks. The patients were randomized into three groups where all groups were given all treatments. Significantly reduced mental fatigue, assessed with the Mental Fatigue Scale (MFS) and increased information processing speed (coding, WAIS-III), were detected. The SF-36 vitality and social functioning scales were also improved significantly. Pain was not reduced by methylphenidate. The positive effects of treatment were dose-dependent, with the most prominent effects being at 60 mg methylphenidate/day spread over three doses. Observed side-effects were increased blood pressure and increased heart rate. Methylphenidate was generally well-tolerated and it improved long-lasting mental fatigue and processing speed after traumatic brain injury.

Efficacy of oral single dose therapy with artemisinin-naphthoquine phosphate in uncomplicated falciparum malaria.

PubMed

Tun, Thein; Tint, Hla Soe; Lin, Khin; Kyaw, Thar Tun; Myint, Moe Kyaw; Khaing, Win; Tun, Zaw Win

2009-09-01

All artemisinin-based combination therapies (ACTs), recommended by the World Health Organization, are 3-day regimens. A considerable level of non-compliance on ACTs has been reported from some countries. The study aimed to assess the therapeutic efficacy of single dose treatment with new generation ACT containing artemisinin plus naphthoquine. An oral single dose of eight tablets (400 mg of naphthoquine+1000 mg artemisinin) of the combination drug was administered to adult uncomplicated falciparum malaria patients. Observations of fever, parasite clearance and reappearance, and other clinical manifestations were made on Days 0, 1, 2, 3, 7, 14, 21 and 28. Fifty-three adult falciparum positive cases, with fever or history of fever within the previous 24 h, were included in the final evaluation of the study. Mean fever clearance time, parasite clearance time were 18.2+/-8.6 h and 34.6+/-14.3 h, respectively. Adequate clinical and parasitological response was achieved in 52 cases, the rate being 98.1% (95% CI, 91.1-99.9). One patient was classified as late parasitological failure because of the reappearance of falciparum parasite on Day 14. The drug was well tolerated and no adverse reactions were detected in the patients. Since it is a single dose therapy, health workers can administer the drug as directly observed treatment.

Changing anthropology, changing society.

PubMed

Varughese, Heather

2009-12-01

Fifty years after the founding of the field of medical anthropology, the Society for Medical Anthropology of the American Anthropological Association held its first independent meeting on September 24-27, 2009, at Yale University.

Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agbahiwe, Harold C.; Wharam, Moody; Batra, Sachin

2013-02-01

Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves andmore » descriptive statistics were used for analysis. Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.« less

ASPREE-NEURO study protocol: A randomized controlled trial to determine the effect of low-dose aspirin on cerebral microbleeds, white matter hyperintensities, cognition, and stroke in the healthy elderly.

PubMed

Ward, Stephanie A; Raniga, Parnesh; Ferris, Nicholas J; Woods, Robyn L; Storey, Elsdon; Bailey, Michael J; Brodtmann, Amy; Yates, Paul A; Donnan, Geoffrey A; Trevaks, Ruth E; Wolfe, Rory; Egan, Gary F; McNeil, John J

2017-01-01

Rationale Cerebral microbleeds seen on brain magnetic resonance imaging are markers of small vessel disease, linked to cognitive dysfunction and increased ischemic and hemorrhagic stroke risk. Observational studies suggest that aspirin use may induce cerebral microbleeds, and associated overt intracranial hemorrhage, but this has not been definitively resolved. Aims ASPREE-NEURO will determine the effect of aspirin on cerebral microbleed development over three years in healthy adults aged 70 years and over, participating in the larger 'ASPirin in Reducing Events in the Elderly (ASPREE)' primary prevention study of aspirin. Sample size Five hundred and fifty-nine participants provide 75% power (two-sided p value of 0.05) to determine an average difference of 0.5 cerebral microbleed per person after three years. Methods and design A multi-center, randomized placebo-controlled trial of 100 mg daily aspirin in participants who have brain magnetic resonance imaging at study entry, one and three years after randomization and who undergo cognitive testing at the same time points. Study outcomes The primary outcome is the number of new cerebral microbleeds on magnetic resonance imaging after three years. Secondary outcomes are the number of new cerebral microbleeds after one year, change in volume of white matter hyperintensity, cognitive function, and stroke. Discussion ASPREE-NEURO will resolve whether aspirin affects the presence and number of cerebral microbleeds, their relationship with cognitive performance, and indicate whether consideration of cerebral microbleeds alters the risk-benefit profile of aspirin in primary prevention for older people. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613001313729.

Impact of tumour motion compensation and delineation methods on FDG PET-based dose painting plan quality for NSCLC radiation therapy.

PubMed

Thomas, Hannah Mary; Kinahan, Paul E; Samuel, James Jebaseelan E; Bowen, Stephen R

2018-02-01

To quantitatively estimate the impact of different methods for both boost volume delineation and respiratory motion compensation of [18F] FDG PET/CT images on the fidelity of planned non-uniform 'dose painting' plans to the prescribed boost dose distribution. Six locally advanced non-small cell lung cancer (NSCLC) patients were retrospectively reviewed. To assess the impact of respiratory motion, time-averaged (3D AVG), respiratory phase-gated (4D GATED) and motion-encompassing (4D MIP) PET images were used. The boost volumes were defined using manual contour (MANUAL), fixed threshold (FIXED) and gradient search algorithm (GRADIENT). The dose painting prescription of 60 Gy base dose to the planning target volume and an integral dose of 14 Gy (total 74 Gy) was discretized into seven treatment planning substructures and linearly redistributed according to the relative SUV at every voxel in the boost volume. Fifty-four dose painting plan combinations were generated and conformity was evaluated using quality index VQ0.95-1.05, which represents the sum of planned dose voxels within 5% deviation from the prescribed dose. Trends in plan quality and magnitude of achievable dose escalation were recorded. Different segmentation techniques produced statistically significant variations in maximum planned dose (P < 0.02), as well as plan quality between segmentation methods for 4D GATED and 4D MIP PET images (P < 0.05). No statistically significant differences in plan quality and maximum dose were observed between motion-compensated PET-based plans (P > 0.75). Low variability in plan quality was observed for FIXED threshold plans, while MANUAL and GRADIENT plans achieved higher dose with lower plan quality indices. The dose painting plans were more sensitive to segmentation of boost volumes than PET motion compensation in this study sample. Careful consideration of boost target delineation and motion compensation strategies should guide the design of NSCLC dose painting trials. © 2017 The Royal Australian and New Zealand College of Radiologists.

75 FR 12245 - Program Comment for the Department of the Navy for the Disposition of Historic Vessels

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-15

... way and remain in active service for typically less than fifty years. Because naval vessels have a limited useful life, the Chief of Naval Operations undertakes a Ship Disposition Review (SDR) each year to... decommissioned in the following year and when the Navy would strike those historic vessels from the Naval Vessel...

Results of a Two-Year Longitudinal Study of Beverage-Specific Alcohol Use among Adolescents

ERIC Educational Resources Information Center

Moore, Michele Johnson; Werch, Chudley

2007-01-01

This study explored beverage-specific alcohol consumption patterns among a sample of high school students over a two-year period. Four hundred fifty-five students completed the validated questionnaire at all three time points (2002, 2003, 2004). Variables of interest included five use measures (past year use, 30-day frequency, quantity, heavy use,…

Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders 20 Years after Initial Diagnosis

ERIC Educational Resources Information Center

Gillberg, I. Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher

2016-01-01

We examined comorbid psychiatric and neurodevelopmental disorders in fifty adult males (mean age 30 years) with Asperger syndrome (AS) diagnosed in childhood and followed up prospectively for almost two decades (13-26 years). Only three of the 50 men had "never" met criteria for an additional psychiatric/neurodevelopmental diagnosis and…

Causes of Mortality among American College Students: A Pilot Study

ERIC Educational Resources Information Center

Turner, James C.; Leno, E. Victor; Keller, Adrienne

2013-01-01

This pilot study from self-selected institutions of higher education provides an estimate of the causes and rates of mortality among college students between the ages of 18 and 24 years old. One hundred fifty-seven 4-year colleges participated in an online survey of student deaths during one academic year. A total of 254 deaths were reported. The…

A prospective, within-patient, crossover study of continuous intravenous and subcutaneous morphine for chronic cancer pain.

PubMed

Nelson, K A; Glare, P A; Walsh, D; Groh, E S

1997-05-01

The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

[Sexual hormone and traditional Chinese patent medicine for early postmenopausal women: effect on quality of life and cost-utility analysis].

PubMed

Zhou, Ling-Ling; Xu, Liang-Zhi; Liu, Hong-Wei; Zhang, Jing; Liu, Ying; Liu, Xiao-Fang; Tang, Liu-Lin; Zhuang, Jing; Liu, Xiao-Xian; Qiao, Lin

2009-11-01

To evaluate the effect of Premarin and Kuntai capsule (a traditional Chinese patent medicine) on the quality of life (QOL) and their cost-utility in early postmenopausal women. Fifty-seven women with menopausal syndrome in the early postmenopausal stage were randomly allocated into Premarin group (0.3 mg/day and 0.6 mg/day alternately, n=29) and Kuntai group (4 g/day, n=28). The therapies lasted for one year and the patients were followed up every 3 months. The QOL of the patients was evaluated and the utility scores were obtained from rating scale to conduct a cost-utility analysis (CUA). At each follow-up examination, no significant difference was found in the QOL between the two groups (P>0.05). The QOL obviously increased after the 1-year-long therapy in both the groups, and Kuntai required longer treatment time than Premarin to take effect. The cost-utility ratio of Premarin and Kuntai were 13581.45 yuan/QALY (quality adjusted life year) and 25105.12 yuan/QALY, respectively. Both incremental cost analysis and sensitivity analysis showed that Kuntai was more costly than Premarin. The result of per-protocol analysis was consistent with that of intention-to-treat analysis. At early stage of menopause, the QOL of women with menopausal syndrome can be significantly improved by low-dose Premarin and Kuntai capsule, but the latter is more costly.

Clinical Experience and Evaluation of Patient Treatment Verification With a Transit Dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ricketts, Kate, E-mail: k.ricketts@ucl.ac.uk; Department of Radiotherapy Physics, Royal Berkshire NHS Foundation Trust, Reading; Navarro, Clara

2016-08-01

Purpose: To prospectively evaluate a protocol for transit dosimetry on a patient population undergoing intensity modulated radiation therapy (IMRT) and to assess the issues in clinical implementation of electronic portal imaging devices (EPIDs) for treatment verification. Methods and Materials: Fifty-eight patients were enrolled in the study. Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. Measured EPID dose maps were back-projected using the planning computed tomographic (CT) images to calculate dose at prespecified points within the patient and compared with treatment planning system dose offline using point dose difference and point γ analysis. Themore » deviation of the results was used to inform future action levels. Results: Two hundred twenty-five transit images were analyzed, composed of breast, prostate, and head and neck IMRT fields. Patient measurements demonstrated the potential of the dose verification protocol to model dose well under complex conditions: 83.8% of all delivered beams achieved the initial set tolerance level of Δ{sub D} of 0 ± 5 cGy or %Δ{sub D} of 0% ± 5%. Importantly, the protocol was also sensitive to anatomic changes and spotted that 3 patients from 20 measured prostate patients had undergone anatomic change in comparison with the planning CT. Patient data suggested an EPID-reconstructed versus treatment planning system dose difference action level of 0% ± 7% for breast fields. Asymmetric action levels were more appropriate for inversed IMRT fields, using absolute dose difference (−2 ± 5 cGy) or summed field percentage dose difference (−6% ± 7%). Conclusions: The in vivo dose verification method was easy to use and simple to implement, and it could detect patient anatomic changes that impacted dose delivery. The system required no extra dose to the patient or treatment time delay and so could be used throughout the course of treatment to identify and limit systematic and random errors in dose delivery for patient groups.« less

Clinical Experience and Evaluation of Patient Treatment Verification With a Transit Dosimeter.

PubMed

Ricketts, Kate; Navarro, Clara; Lane, Katherine; Blowfield, Claire; Cotten, Gary; Tomala, Dee; Lord, Christine; Jones, Joanne; Adeyemi, Abiodun

2016-08-01

To prospectively evaluate a protocol for transit dosimetry on a patient population undergoing intensity modulated radiation therapy (IMRT) and to assess the issues in clinical implementation of electronic portal imaging devices (EPIDs) for treatment verification. Fifty-eight patients were enrolled in the study. Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. Measured EPID dose maps were back-projected using the planning computed tomographic (CT) images to calculate dose at prespecified points within the patient and compared with treatment planning system dose offline using point dose difference and point γ analysis. The deviation of the results was used to inform future action levels. Two hundred twenty-five transit images were analyzed, composed of breast, prostate, and head and neck IMRT fields. Patient measurements demonstrated the potential of the dose verification protocol to model dose well under complex conditions: 83.8% of all delivered beams achieved the initial set tolerance level of ΔD of 0 ± 5 cGy or %ΔD of 0% ± 5%. Importantly, the protocol was also sensitive to anatomic changes and spotted that 3 patients from 20 measured prostate patients had undergone anatomic change in comparison with the planning CT. Patient data suggested an EPID-reconstructed versus treatment planning system dose difference action level of 0% ± 7% for breast fields. Asymmetric action levels were more appropriate for inversed IMRT fields, using absolute dose difference (-2 ± 5 cGy) or summed field percentage dose difference (-6% ± 7%). The in vivo dose verification method was easy to use and simple to implement, and it could detect patient anatomic changes that impacted dose delivery. The system required no extra dose to the patient or treatment time delay and so could be used throughout the course of treatment to identify and limit systematic and random errors in dose delivery for patient groups. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of adjuvant external beam radiation therapy for papillary thyroid carcinoma invading the trachea

PubMed Central

Kim, Young Suk; Choi, Jae Hyuck; Kim, Kwang Sik; Lim, Gil Chae; Kim, Jeong Hong; Kang, Ju Wan; Song, Hee-Sung; Lee, Sang Ah; Hyun, Chang Lim; Choi, Yunseon; Kim, Gwi Eon

2017-01-01

Purpose To evaluate the effect of adjuvant external beam radiation therapy (EBRT) on local failure-free survival rate (LFFS) for papillary thyroid cancer (PTC) invading the trachea. Materials and Methods Fifty-six patients with locally advanced PTC invading the trachea were treated with surgical resection. After surgery, 21 patients received adjuvant EBRT and radioactive iodine therapy (EBRT group) and 35 patients were treated with radioactive iodine therapy (control group). Results The age range was 26–87 years (median, 56 years). The median follow-up period was 43 months (range, 4 to 145 months). EBRT doses ranged from 50.4 to 66 Gy (median, 60 Gy). Esophagus invasion and gross residual disease was more frequent in the EBRT group. In the control group, local recurrence developed in 9 (9/35, 26%) and new distant metastasis in 2 (2/35, 6%) patients, occurring 4 to 68 months (median, 37 months) and 53 to 68 months (median, 60 months) after surgery, respectively. Two patients had simultaneous local recurrence and new distant metastasis. There was one local failure in the EBRT group at 18 months after surgery (1/21, 5%). The 5-year LFFS was 95% in the EBRT group and 63% in the control group (p = 0.103). In the EBRT group, one late grade 2 xerostomia was developed. Conclusion Although, EBRT group had a higher incidence of esophagus invasion and gross residual disease, EBRT group showed a better 5-year LFFS. Adjuvant EBRT may have contributed to the better LFFS in these patients. PMID:28712279

Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.

PubMed

Lee, DaHae; Keymeulen, Bart; Hilbrands, Robert; Ling, Zhidong; Van de Velde, Ursule; Jacobs-Tulleneers-Thevissen, Daniel; Maleux, Geert; Lapauw, Bruno; Crenier, Laurent; De Block, Christophe; Mathieu, Chantal; Pipeleers, Daniel; Gillard, Pieter

2017-09-01

Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

Changing Anthropology, Changing Society

PubMed Central

Varughese, Heather

2009-01-01

Fifty years after the founding of the field of medical anthropology, the Society for Medical Anthropology of the American Anthropological Association held its first independent meeting on September 24-27, 2009, at Yale University. PMID:20027281

Triz in Mems

NASA Astrophysics Data System (ADS)

Apte, Prakash R.

1999-11-01

TRIZ is a Russian abbreviation. Genrich Altshuller developed it fifty years ago in the former Soviet Union. He examined thousands of inventions made in different technological systems and formulated a 'Theory of Inventive problem solving' (TRIZ). Altshuller's research of over fifty years on Creativity and Inventive Problem Solving has led to many different classifications, methods and tools of invention. Some of these are, Contradictions table, Level of inventions, Patterns in evolution of technological systems, ARIZ-Algorithm for Inventive Problem Solving, Diagnostic problem solving and Anticipatory Failure Determination. MEMS research consists of conceptual design, process technology and including of various Mechanical, ELectrical, Thermal, Magnetic, Acoustic and other effects. MEMS system s are now rapidly growing in complexity. Each system will thus follow one or more 'patterns of evolution' as given by Altshuller. This paper attempts to indicate how various TRIZ tools can be used in MEMS research activities.

The Research of Dr. Joanne Simpson: Fifty Years Investigating Hurricanes, Tropical Clouds and Cloud Systems

NASA Technical Reports Server (NTRS)

Tao, W. -K.; Halverson, J.; Adler, R.; Garstang, M.; Houze, R., Jr.; LeMone, M.; Pielke, R., Sr.; Woodley, W.; O'C.Starr, David (Technical Monitor)

2001-01-01

This AMS Meteorological Monographs is dedicated to Dr. Joanne Simpson for her many pioneering research efforts in tropical meteorology during her fifty-year career. Dr. Simpson's major areas of scientific research involved the "hot tower" hypothesis and its role in hurricanes, structure and maintenance of trade winds, air-sea interaction, and observations and the mechanism for hurricanes and waterspouts. She was also a pioneer in cloud modeling with the first one-dimensional model and had the first cumulus model on a computer. She also played a major role in planning and leading observational experiments on convective cloud systems. The launch of the Tropical Rainfall Measuring Mission (TRMM) satellite, a joint U.S.-Japan project, in November of 1997 made it possible for quantitative measurements of tropical rainfall to be obtained on a continuous basis over the entire global tropics. Dr. Simpson was the TRAM Project Scientist from 1986 until its launch in 1997. Her efforts during this crucial period ensured that the mission was both well planned scientifically and well engineered as well as within budget. In this paper, Dr. J. Simpson's nine specific accomplishments during her fifty-year career: (1) hot tower hypothesis, (2) hurricanes, (3) airflow and clouds over heated islands, (4) cloud models, (5) trade winds and their role in cumulus development, (6) air-sea interaction, (7) cloud-cloud interactions and mergers, (8) waterspouts, and (9) TRMM science, will be described and discussed.

Text-Message Abbreviations and Language Skills in High School and University Students

ERIC Educational Resources Information Center

De Jonge, Sarah; Kemp, Nenagh

2012-01-01

This study investigated the use of text-message abbreviations (textisms) in Australian adolescents and young adults, and relations between textism use and literacy abilities. Fifty-two high school students aged 13-15 years, and 53 undergraduates aged 18-24 years, all users of predictive texting, translated conventional English sentences into…

Biophysical and financial impacts of community-based gully rehabilitation in the Birr Watershed, Upper Blue Nile Basin, Ethiopia

USDA-ARS?s Scientific Manuscript database

Although erosion in the Ethiopian highlands has been occurring for thousands of years, rivers sediment concentration has increased two to three fold during the last fifty years, reducing crop and livestock production and the volume of irrigation water stored in reservoirs. Gully erosion in particula...

National and International Associations... 50 Years on

ERIC Educational Resources Information Center

Tuckett, Alan

2010-01-01

Looking back fifty years is a salutary experience. There is a sense that everything changes, and everything stays the same. Whilst people now have a global non-government organisation to support national bodies in the field of adult learning, most of the national members have a fragile financial base, and the International Council for Adult…

Marriage and Fertility in Tianjin, China: Fifty Years of Transition.

ERIC Educational Resources Information Center

Pasternak, Burton

A report of research conducted in Tianjin, People's Republic of China (September 1981-January 1982) describes and analyses changes in family structure, marriage, post-marital residence, and fertility in a neighborhood of factory workers over a 50-year period. Social and economic changes such as delayed marriage, increased access to education, and…

The North Central Association as a Spiritual Force (1946)

ERIC Educational Resources Information Center

Koch, Harlan C.

1975-01-01

Professor Harlan C. Koch of the University of Michigan served as managing editor of the Quarterly for a number of years, and contributed short columns of comment on current issues. The final article of this fifty-years overview of the Quarterly is such a comment of his, written in 1946. (Editor/RK)

50 Years of Testing

NASA Image and Video Library

2016-04-23

A 15-second test of a Saturn V rocket stage on the A-2 Test Stand at Stennis Space Center ushered in the Space Age for south Mississippi. Fifty years later, Stennis has grown into the nation’s largest rocket engine test site, continuing to test rocket engines and stages that power the nation’s space program.

Behavioral and Social Science: Fifty Years of Discovery.

ERIC Educational Resources Information Center

Smelser, Neil J., Ed.; Gerstein, Dean R., Ed.

This commemorative book contains 10 papers that provide a selective sample of behavioral and social science research accomplishments and trends over a 50-year period, and comparisons are made with research presented in the 1933 report, "Recent Social Trends in the United States" (The Ogburn Report). Four chapters in part 1,…

Teaching with Documents: A Cartoonist's View of the Eisenhower Years.

ERIC Educational Resources Information Center

Mueller, Jean West; Schamel, Wynell Burroughs

1990-01-01

Illustrates how to teach U.S. history through the use of original documents such as Charles Nickerson's cartoon, "Images of the Fifties from Disneyland to Suez." States that the original artwork for this cartoon, which portrays the Eisenhower years, is in the Dwight D. Eisenhower Library in Abilene, Kansas. Provides a pretest, teaching…

Academic Self-Perception and Its Relationship to Academic Performance

ERIC Educational Resources Information Center

Stringer, Ronald W.; Heath, Nancy

2008-01-01

One hundred and fifty-five students (average age, 10 years 7 months) were initially tested on reading, arithmetic, and academic self-perception. One year later they were tested again. Initial academic scores accounted for a large proportion of the variance in later academic scores. The children's self-perceptions of academic competence accounted…

Fifty Years Remembered: The First 50 Years of the Tulsa District, U.S. Army Corps of Engineers

DTIC Science & Technology

1989-07-01

life because he cultivated his sense of idealism while embellishing his sense of realism. He artfully combined understanding, empathy , and...its companion smaller civil works projects, would fill a bookshelf and here can be traced only in silhouette. A storyteller might well begin the tale

Geospatial Technology in Geography Education

ERIC Educational Resources Information Center

DeMers, Michael N.

2016-01-01

Depending on how you determine the starting point for the technology driving geographic information systems (GIS) and remote sensing, it is well over fifty years old now. During the first years of its existence in the early 1960s, the new technology benefited relatively few students who attended the handful of college programs that were actually…

Online Instruction, E-Learning, and Student Satisfaction: A Three Year Study

ERIC Educational Resources Information Center

Cole, Michele T.; Shelley, Daniel J.; Swartz, Louis B.

2014-01-01

This article presents the results of a three-year study of graduate and undergraduate students' level of satisfaction with online instruction at one university. The study expands on earlier research into student satisfaction with e-learning. Researchers conducted a series of surveys over eight academic terms. Five hundred and fifty-three students…

The Association between Routinization and Cognitive Resources in Later Life

ERIC Educational Resources Information Center

Tournier, Isabelle; Mathey, Stephanie; Postal, Virginie

2012-01-01

The aim of this study was to investigate the association between routinization of daily life activities and cognitive resources during aging. Routinization could increase excessively during aging and become maladaptative in reducing individual resources. Fifty-two young participants (M = 20.8 years) and 62 older participants (M = 66.9 years)…

34 CFR 600.7 - Conditions of institutional ineligibility.

Code of Federal Regulations, 2012 CFR

2012-07-01

... than fifty percent of its regular enrolled students had neither a high school diploma nor the recognized equivalent of a high school diploma, and the institution does not provide a four-year or two-year... high school and who are available for study in preparation for entering the labor market” under section...

Advancement of knowledge of Brucella over the past 50 years

USDA-ARS?s Scientific Manuscript database

Fifty years ago, bacteria in the genus Brucella were known to cause infertility and reproductive losses. The genus was considered to contain only three species, B. abortus, B. melitensis and B. suis. Since the early 1960’s, at least seven new species have been identified as belonging to the Brucell...

Adult Education Regional Planning

ERIC Educational Resources Information Center

California Community Colleges, Chancellor's Office, 2015

2015-01-01

For more than one hundred and fifty years, until 2008, California was an undisputed national leader in its commitment to adult education. The state's investment in adult learners topped $750 million, a sum greater than the combined total of every other state in the nation. However, for the past several years recession and fiscal crisis have left…

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

PubMed Central

Öztürk, T.; Ağdanlı, D.; Bayturan, Ö.; Çıkrıkcı, C.; Keleş, G.T.

2015-01-01

Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc) prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25) or high-dose (1.2 mg/kg, group H, n=25) rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0), after induction (T1), after rocuronium (just before laryngoscopy; T2), 2 min after intubation (T3), and 5 min after intubation (T4). The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001), and 459 vs 434 ms in group H (P=0.005)]. The incidence of dysrhythmias in group C (28%) and in group H (24%) was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation. PMID:25714880

Bioavailability of sulforaphane from two broccoli sprout beverages: Results of a short term, cross-over clinical trial in Qidong, China

PubMed Central

Egner, Patricia A.; Chen, Jian Guo; Wang, Jin Bing; Wu, Yan; Sun, Yan; Lu, Jian Hua; Zhu, Jian; Zhang, Yong Hui; Chen, Yong Sheng; Friesen, Marlin D.; Jacobson, Lisa P.; Muñoz, Alvaro; Ng, Derek; Qian, Geng Sun; Zhu, Yuan Rong; Chen, Tao Yang; Botting, Nigel P.; Zhang, Qingzhi; Fahey, Jed W.; Talalay, Paul; Groopman, John D; Kensler, Thomas W.

2011-01-01

One of several challenges in design of clinical chemoprevention trials is the selection of the dose, formulation and dose schedule of the intervention agent. Therefore, a cross-over clinical trial was undertaken to compare the bioavailability and tolerability of sulforaphane from two of broccoli sprout-derived beverages: one glucoraphanin-rich (GRR) and the other sulforaphane-rich (SFR). Sulforaphane was generated from glucoraphanin contained in GRR by gut microflora or formed by treatment of GRR with myrosinase from daikon (Raphanus sativus) sprouts to provide SFR. Fifty healthy, eligible participants were requested to refrain from crucifer consumption and randomized into two treatment arms. The study design was as follows: 5-day run-in period, 7-day administration of beverages, 5-day washout period, and 7-day administration of the opposite intervention. Isotope dilution mass spectrometry was used to measure levels of glucoraphanin, sulforaphane and sulforaphane thiol conjugates in urine samples collected daily throughout the study. Bioavailability, as measured by urinary excretion of sulforaphane and its metabolites (in approximately 12 hour collections after dosing), was substantially greater with the SFR (mean = 70%) than with GRR (mean = 5%) beverages. Interindividual variability in excretion was considerably lower with SFR than GRR beverage. Elimination rates were considerably slower with GRR allowing for achievement of steady state dosing as opposed to bolus dosing with SFR. Optimal dosing formulations in future studies should consider blends of sulforaphane and glucoraphanin as SFR and GRR mixtures to achieve peak concentrations for activation of some targets and prolonged inhibition of others implicated in the protective actions of sulforaphane. PMID:21372038

Behavioral and Psychological Predictors of Chemotherapy Adherence in Patients with Advanced Non-Small-Cell Lung Cancer

PubMed Central

Greer, Joseph A.; Pirl, William F.; Park, Elyse R.; Lynch, Thomas J.; Temel, Jennifer S.

2013-01-01

Objective Dose delays and reductions in chemotherapy due to hematologic toxicities are common among patients with advanced non-small-cell lung cancer (NSCLC). However, limited data exist on behavioral or psychological predictors of chemotherapy adherence. The goal of this study was to explore the frequency and clinical predictors of infusion dose delays and reductions in this patient population. Methods Fifty patients newly diagnosed with advanced NSCLC of high performance status (ECOG PS=0-1) completed baseline assessments on quality of life (FACT-L) and mood (HADS) within eight weeks of diagnosis. Participants were followed prospectively for six months. Chemotherapy dosing data came from medical chart review. Results All patients received chemotherapy during the course of the study, beginning with either a platinum-based doublet (74%), an oral epidermal growth factor receptor-tyrosine kinase inhibitor (14%), or a parenteral single agent (12%). Forty percent (N=20) of patients had either a dose delay (38%) and/or reduction (16%) in their scheduled infusions. Fisher’s exact tests showed that patients who experienced neutropenia, smoked at the time of diagnosis, or reported heightened baseline anxiety were significantly more likely to experience dose delays or reductions. There were no associations between chemotherapy adherence and patient demographics, performance status, or quality of life. Conclusion In this sample, over one-third of patients with advanced NSCLC experienced either a dose delay or reduction in prescribed chemotherapy regimens. Behavioral and psychological factors, such as tobacco use and anxiety symptoms, appear to play an important role in chemotherapy adherence, though further study is required to confirm these findings. PMID:19027443

Is a fecal occult blood test a useful tool for judging whether to perform capsule endoscopy in low-dose aspirin users with negative colonoscopy and esophagogastroduodenoscopy?

PubMed

Endo, Hiroki; Kato, Takayuki; Sakai, Eiji; Taniguchi, Leo; Arimoto, Jun; Kawamura, Harunobu; Higurashi, Takuma; Ohkubo, Hidenori; Nonaka, Takashi; Taguri, Masataka; Inamori, Masahiko; Yamanaka, Takeharu; Sakaguchi, Takashi; Hata, Yasuo; Nagase, Hajime; Nakajima, Atsushi

2017-02-01

Aspirin use is reportedly not to be associated with fecal immunochemical occult blood test (FIT) false-positive results for the detection of colorectal cancer. The need for additional small bowel exploration in FIT-positive, low-dose aspirin users with a negative colonoscopy is controversial. The aim of this study was to assess the ability of FIT to judge whether capsule endoscopy (CE) should be performed in low-dose aspirin users with negative colonoscopy and esophagogastroduodenoscopy findings by comparing FIT results with CE findings. A total of 264 consecutive low-dose aspirin users with negative colonoscopy and esophagogastroduodenoscopy who were scheduled to undergo CE at five hospitals in Japan were enrolled. Patients had been offered FIT prior to the CE. The association between the FIT results and the CE findings was then assessed. One hundred and fifty-seven patients were included in the final analysis. Eighty-four patients (53.5 %) had positive FIT results. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of positive FIT results for small bowel ulcers were 0.56, 0.47, 0.30, and 0.73, respectively. Furthermore, the NPV of positive FIT results for severe small bowel injury (Lewis score ≥790) was markedly high (0.90). When the analysis was performed only in low-dose aspirin users with anemia, the sensitivity of the positive FIT results was notably improved (0.72). Small bowel evaluation using CE is not recommended for FIT-negative, low-dose aspirin users. However, small bowel evaluation using CE should be considered in both FIT-positive and anemic low-dose aspirin users.

Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia

PubMed Central

Cortes, Jorge; Talpaz, Moshe; Smith, Hedy P.; Snyder, David S.; Khoury, Jean; Bhalla, Kapil N.; Pinilla-Ibarz, Javier; Larson, Richard; Mitchell, David; Wise, Scott C.; Rutkoski, Thomas J.; Smith, Bryan D.; Flynn, Daniel L.; Kantarjian, Hagop M.; Rosen, Oliver; Van Etten, Richard A.

2017-01-01

A vailable tyrosine kinase inhibitors for chronic myeloid leukemia bind in an adenosine 5′-triphosphate-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first-in-human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. The primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose and recommended Phase 2 dose. Fifty-seven patients received treatment with rebastinib. Sixteen patients were treated using powder-in-capsule preparations at doses from 57 mg to 1200 mg daily, and 41 received tablet preparations at doses of 100 mg to 400 mg daily. Dose-limiting toxicities were dysarthria, muscle weakness, and peripheral neuropathy. The maximum tolerated dose was 150 mg tablets administered twice daily. Rebastinib was rapidly absorbed. Bioavailability was 3- to 4-fold greater with formulated tablets compared to unformulated capsules. Eight complete hematologic responses were achieved in 40 evaluable chronic myeloid leukemia patients, 4 of which had a T315I mutation. None of the 5 patients with acute myeloid leukemia responded. Pharmacodynamic analysis showed inhibition of phosphorylation of substrates of BCR-ABL1 or FLT3 by rebastinib. Although clinical activity was observed, clinical benefit was insufficient to justify continued development in chronic or acute myeloid leukemia. Pharmacodynamic analyses suggest that other kinases inhibited by rebastinib, such as TIE2, may be more relevant targets for the clinical development of rebastinib (clinicaltrials.gov Identifier:00827138). PMID:27927766

Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia.

PubMed

Cortes, Jorge; Talpaz, Moshe; Smith, Hedy P; Snyder, David S; Khoury, Jean; Bhalla, Kapil N; Pinilla-Ibarz, Javier; Larson, Richard; Mitchell, David; Wise, Scott C; Rutkoski, Thomas J; Smith, Bryan D; Flynn, Daniel L; Kantarjian, Hagop M; Rosen, Oliver; Van Etten, Richard A

2017-03-01

A vailable tyrosine kinase inhibitors for chronic myeloid leukemia bind in an adenosine 5'-triphosphate-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first-in-human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. The primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose and recommended Phase 2 dose. Fifty-seven patients received treatment with rebastinib. Sixteen patients were treated using powder-in-capsule preparations at doses from 57 mg to 1200 mg daily, and 41 received tablet preparations at doses of 100 mg to 400 mg daily. Dose-limiting toxicities were dysarthria, muscle weakness, and peripheral neuropathy. The maximum tolerated dose was 150 mg tablets administered twice daily. Rebastinib was rapidly absorbed. Bioavailability was 3- to 4-fold greater with formulated tablets compared to unformulated capsules. Eight complete hematologic responses were achieved in 40 evaluable chronic myeloid leukemia patients, 4 of which had a T315I mutation. None of the 5 patients with acute myeloid leukemia responded. Pharmacodynamic analysis showed inhibition of phosphorylation of substrates of BCR-ABL1 or FLT3 by rebastinib. Although clinical activity was observed, clinical benefit was insufficient to justify continued development in chronic or acute myeloid leukemia. Pharmacodynamic analyses suggest that other kinases inhibited by rebastinib, such as TIE2, may be more relevant targets for the clinical development of rebastinib ( clinicaltrials.gov Identifier:00827138 ). Copyright© Ferrata Storti Foundation.

Hepatitis B virus-related mortality in rheumatoid arthritis patients undergoing long-term low-dose glucocorticoid treatment: A population-based study.

PubMed

Yang, Sheng-Shun; Hung, Chin-Tun; Li, Shu-Fen; Lee, Horng-Mo; Chung, Yueh-Chin; Chen, Hsin-Hua; Chang, Shu-Chuan

2017-09-04

Glucocorticoids (GC) are commonly used in rheumatoid arthritis (RA) patients which bears a risk of hepatitis B virus (HBV) reactivation. The purpose of this study was to investigate the risk of HBV-related mortality under long-term low-dose GCs in Taiwanese RA patients. We retrospectively analyzed 45,423 RA patients using National Health Insurance Research Database from January 1999 to December 2011. Of them, 2204 patients had the diagnosis of HBV and were classified into four groups according to GCs regimens. Outcome comparison by Cox model analysis for liver-related mortality was performed. In this cohort, 90.5% were older than 40. One hundred and five patients had been treated with short-term large-dose GCs (Group A); 862 patients received GCs ≥20 mg/day for ≥3 days or a variable dose but did not meet Group C criteria (Group B); 689 patients were continuously treated with low-dose (<20 mg/day) GCs for ≥3 months for at least one session (Group C); and 548 patients had never been exposed to GCs (Group D). Two hundred and sixty-one patients had been exposed to antiviral agents, which was significantly higher in Group C. Fifty-eight patients (2.63%) died of acute hepatic failure, while no statistically significant difference between each groups (p = 0.074). Groups C and D comparison by two-sample test showed that long-term low-dose GC treatment was not associated with liver-related death after adjusting for malignancy. Long-term low-dose GC treatment was not associated with liver-related mortality in RA with concomitant HBV patients probably due to commonly applied antiviral therapy by rheumatologists. Copyright © 2017. Published by Elsevier B.V.

The Bad Berka dose protocol: comparative results of dosimetry in peptide receptor radionuclide therapy using (177)Lu-DOTATATE, (177)Lu-DOTANOC, and (177)Lu-DOTATOC.

PubMed

Schuchardt, Christiane; Kulkarni, Harshad R; Prasad, Vikas; Zachert, Carolin; Müller, Dirk; Baum, Richard P

2013-01-01

The objective of this study is to analyze the in vivo behavior of the (177)Lu-labeled peptides DOTATATE, DOTANOC, and DOTATOC used for peptide receptor radionuclide therapy (PRRNT) of neuroendocrine tumors (NETs), by measuring organ and tumor kinetics and by performing dosimetric calculations. Two hundred fifty-three patients (group 1) with metastasized NET who underwent PRRNT were examined. Out of these, 185 patients received (177)Lu-DOTATATE, 9 were treated with (177)Lu-DOTANOC, and 59 with (177)Lu-DOTATOC. Additionally, 25 patients receiving, in consecutive PRRNT cycles, DOTATATE followed by DOTATOC (group 2) and 3 patients receiving DOTATATE and DOTANOC (group 3) were analyzed. Dosimetric calculations (according to MIRD scheme) were performed using OLINDA software. In group 1, DOTATOC exhibited the lowest and DOTANOC the highest uptake and therefore mean absorbed dose in normal organs (whole body, kidney, and spleen). In group 2, there was a significant difference between DOTATATE and DOTATOC concerning kinetics and normal organ doses. (177)Lu-DOTATOC had the lowest uptake/dose delivered to normal organs and highest tumor-to-kidney ratio. There were no significant differences between the three peptides concerning tumor kinetics and mean absorbed tumor dose. The study demonstrates a correlation between high affinity of DOTANOC in vitro and high uptake in normal organs/whole body in vivo, resulting in a higher whole-body dose. DOTATOC exhibited the lowest uptake and dose delivered to normal tissues and the best tumor-to-kidney ratio. Due to large interpatient variability, individual dosimetry should be performed for each therapy cycle.

A first in human, safety, pharmacokinetics, and clinical activity phase I study of once weekly administration of the Hsp90 inhibitor ganetespib (STA-9090) in patients with solid malignancies

PubMed Central

2013-01-01

Background This phase I study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics and antitumor activity of ganetespib in patients with solid malignancies. Methods Patients were enrolled in cohorts of escalating ganetespib doses, given as 1 hour IV infusion, once weekly for 3 weeks, followed by a 1-week rest until disease progression or unacceptable toxicity. Endpoints included safety, pharmacokinetic and pharmacodynamic parameters and preliminary clinical activity. Results Fifty-three patients were treated at doses escalating from 7 to 259 mg/m2. The most common adverse events were Grade 1 and 2 diarrhea, fatigue, nausea or vomiting. Dose-limiting toxicities (DLT) observed were: one Grade 3 amylase elevation (150 mg/m2), one Grade 3 diarrhea and one Grade 3 and one Grade 4 asthenia (259 mg/m2). The MTD was 216 mg/m2 and the recommended phase 2 dose was established at 200 mg/m2 given IV at Days 1, 8, and 15 every 4 weeks. There was a linear relationship between dose and exposure. Plasma HSP70 protein levels remained elevated for over a week post treatment. Disease control rate (objective response and stable disease at ≥ 16 weeks) was 24.4%. Conclusions Ganetespib is well tolerated as a weekly infusion for 3 of every 4 weeks cycle. The recommended phase II dose is 200 mg/m2, and is associated with an acceptable tolerability profile. Trial registration NCT00687934 PMID:23530663

Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poorvu, Philip D.; Sadow, Cheryl A.; Townamchai, Kanokpis

2013-04-01

Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneummore » plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy.« less

Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support.

PubMed

Elias, A D; Wheeler, C; Ayash, L J; Schwartz, G; Ibrahim, J; Mills, L; McCauley, M; Coleman, N; Warren, D; Schnipper, L; Antman, K H; Teicher, B A; Frei, E

1998-06-01

Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain, predominantly in stocking glove distribution, occurring between day -3 and day 0, and a sensory peripheral neuropathy with similar distribution peaking around day +60. The maximal achievable dose of etanidazole (16 g/m2 dose level) resulted in a mean serum level of 38 micrograms/ml (25-55 micrograms/ml). Etanidazole significantly enhanced host toxicity of high-dose ICE. Effective modulatory doses of etanidazole could not be given with acceptable toxicity using this schedule.

The First-Year Urban High School Teacher: Holding the Torch, Lighting the Fire

ERIC Educational Resources Information Center

Weinberg, Paul J.; Weinberg, Carl

2008-01-01

The book tracks co-author Paul Weinberg during his first year of teaching as he is introduced to the daily tribulations of an urban Los Angeles high school. Paul's father Carl Weinberg, who fifty years earlier himself began his career in education an urban secondary school teacher, shares his experiences side-by-side with those of his son.…

From Secret Garden to Crowded Marketplace: Fifty Years of ASE and the Science Curriculum

ERIC Educational Resources Information Center

Hollins, Martin

2013-01-01

This article charts some of the most notable ways in which the science curriculum has changed over the past 50 years and identifies the influence of members of the Association for Science Education (ASE) in both projects and policy developments. The world is different from that of 50 years ago but there are continuing issues about the teaching,…

Abuse potential assessment of propofol by its subjective effects after sedation.

PubMed

Tezcan, Aysu Hayriye; Ornek, Dilsen Hatice; Ozlu, Onur; Baydar, Mustafa; Yavuz, Nurcan; Ozaslan, Nihal Gokbulut; Dilek, Kevser; Keske, Aylin

2014-01-01

In this study, we examined the euphoric effect of propofol and its high satisfaction ratio regarding its liability to be abused, particularly in painless procedures, such as colonoscopy. Fifty subjects aged between 18 and 65 years who fulfilled the criteria for ASA 1-2 and were prepared for colonoscopy were enrolled into this study. For intravenous sedation induction, 2 mg/kg propofol was used, and additional injections were administered according to BIS values. After colonoscopy, the subjects were taken to a recovery room and observed for 30 minutes. Patients were interviewed with the modified Brice questionnare regarding the incidence and the content of dreams. A 5-point Likert scale was used to classify their dreams, and the content of the dreams was also recorded. To assess the subjective effects of propofol, the patients were asked to use the Hall and Van der Castle emotion scale; their biological states were also assessed. The patients' feelings regarding propofol were each rated as absent or present. We used the Morphine-Benzedrine Group scale to measure the euphoric effects of propofol. At the end of the study, subjects scored their satisfaction on a five-point scale. There were no statistically significant differences in sex age, weight, propofol dose, or satisfaction ratio (p>0.05) in the groups, although male patients received a higher dose of propofol and had higher satisfaction ratio. Patients reported no residual after-effects. The incidence of dreaming was 42%. There was no statistically significant difference in dreaming between the sexes, but male patients had a higher dreaming ratio. Dreamers received higher propofol doses and had a higher satisfaction ratio (p>0.05). All dreamers reported happy dreams regarding daily life, and their mean MBG score was 10.5. There was no correlation between MBG scores and propofol doses (r= -0.044, p= 0.761). We conclude that propofol functions as a reward; that patients enjoy its acute effects; and that no residual after-effects should arise. We suggest that propofol may carry potential for abuse, and further abuse liability testing is indicated.

Abuse potential assessment of propofol by its subjective effects after sedation

PubMed Central

Tezcan, Aysu Hayriye; Ornek, Dilsen Hatice; Ozlu, Onur; Baydar, Mustafa; Yavuz, Nurcan; Ozaslan, Nihal Gokbulut; Dilek, Kevser; Keske, Aylin

2014-01-01

Objective: In this study, we examined the euphoric effect of propofol and its high satisfaction ratio regarding its liability to be abused, particularly in painless procedures, such as colonoscopy. Methods: Fifty subjects aged between 18 and 65 years who fulfilled the criteria for ASA 1-2 and were prepared for colonoscopy were enrolled into this study. For intravenous sedation induction, 2 mg/kg propofol was used, and additional injections were administered according to BIS values. After colonoscopy, the subjects were taken to a recovery room and observed for 30 minutes. Patients were interviewed with the modified Brice questionnare regarding the incidence and the content of dreams. A 5-point Likert scale was used to classify their dreams, and the content of the dreams was also recorded. To assess the subjective effects of propofol, the patients were asked to use the Hall and Van der Castle emotion scale; their biological states were also assessed. The patients’ feelings regarding propofol were each rated as absent or present. We used the Morphine-Benzedrine Group scale to measure the euphoric effects of propofol. At the end of the study, subjects scored their satisfaction on a five-point scale. Results: There were no statistically significant differences in sex age, weight, propofol dose, or satisfaction ratio (p>0.05) in the groups, although male patients received a higher dose of propofol and had higher satisfaction ratio. Patients reported no residual after-effects. The incidence of dreaming was 42%. There was no statistically significant difference in dreaming between the sexes, but male patients had a higher dreaming ratio. Dreamers received higher propofol doses and had a higher satisfaction ratio (p>0.05). All dreamers reported happy dreams regarding daily life, and their mean MBG score was 10.5. There was no correlation between MBG scores and propofol doses (r= -0.044, p= 0.761). Conclusions: We conclude that propofol functions as a reward; that patients enjoy its acute effects; and that no residual after-effects should arise. We suggest that propofol may carry potential for abuse, and further abuse liability testing is indicated. PMID:25674117

Fifty Years of Institutional Rehabilitation Outcomes: Inventory and Implications.

ERIC Educational Resources Information Center

Gibson, David; Fields, Donald L.

1983-01-01

Temporal variability within the record was more easily attributed to the adequacy of past accountability research and to public policy than to program effects, socioeconomic climate, or changing receiver group attitudes. (Author/SEW)

Physiological growth hormone replacement and rate of recurrence of craniopharyngioma: the Genentech National Cooperative Growth Study.

PubMed

Smith, Timothy R; Cote, David J; Jane, John A; Laws, Edward R

2016-10-01

OBJECTIVE The object of this study was to establish recurrence rates in patients with craniopharyngioma postoperatively treated with recombinant human growth hormone (rhGH) as a basis for determining the risk of rhGH therapy in the development of recurrent tumor. METHODS The study included 739 pediatric patients with craniopharyngioma who were naïve to GH upon entering the Genentech National Cooperative Growth Study (NCGS) for treatment. Reoperation for tumor recurrence was documented as an adverse event. Cox proportional-hazards regression models were developed for time to recurrence, using age as the outcome and enrollment date as the predictor. Patients without recurrence were treated as censored. Multivariate logistic regression was used to examine the incidence of recurrence with adjustment for the amount of time at risk. RESULTS Fifty recurrences in these 739 surgically treated patients were recorded. The overall craniopharyngioma recurrence rate in the NCGS was 6.8%, with a median follow-up time of 4.3 years (range 0.7-6.4 years.). Age at the time of study enrollment was statistically significant according to both Cox (p = 0.0032) and logistic (p < 0.001) models, with patients under 9 years of age more likely to suffer recurrence (30 patients [11.8%], 0.025 recurrences/yr of observation, p = 0.0097) than those ages 9-13 years (17 patients [6.0%], 0.17 recurrences/yr of observation) and children older than 13 years (3 patients [1.5%], 0.005 recurrences/yr of observation). CONCLUSIONS Physiological doses of GH do not appear to increase the recurrence rate of craniopharyngioma after surgery in children, but long-term follow-up of GH-treated patients is required to establish a true natural history in the GH treatment era.

Heart rate variability (HRV) analysis in radio and TV broadcasting stations workers.

PubMed

Bortkiewicz, Alicja; Gadzicka, Elżbieta; Szymczak, Wiesław; Zmyślony, Marek

2012-09-01

The aim of the study was to assess the mechanism of cardiovascular impairments in workers exposed to UHF-VHF radio frequency electromagnetic fields (EMF). Heart rate variability (HRV) was analysed using 512 normal heart beats registered at rest. The analysis concerned time-domain (STD R-R) and frequency-domain (VLF, LF, HF) parameters of HRV. Fifty nine workers (group I) with low-level and 12 workers (group II) with high-level exposure were examined. The mean age of the subjects was 47 ± 9 years and 41 ± 14 years, and mean exposure duration 19.1 ± 8.8 years and 13 ± 4 years, in groups I and II, respectively. The groups were divided according to: E(max), E(dose), E(mean) for frequencies UHF, VHF and UHF+VHF: The control group consisted of 42 non-exposed subjects, aged 49 ± 8 years. Statistical analysis comprised one-way analysis of variance, covariance analysis and logistic regression models. In the exposed groups, the heart rate was higher than in the control one. Standard deviation of R-R intervals (STD R-R) was found to be significantly (p = 0.0285) lower in group I (42.5 ± 24.7 ms) compared to the control group (62.9 ± 53.5 ms). The risk of lowered STD R-R was significantly increased (OR = 2.37, p = 0.023) in group II. Both exposed groups presented significantly higher VLF and LF values than the control group (p = 0.005 and p = 0.0025, respectively). The EMF-exposed groups were characterised by the dominance of the sympathetic system (LF/HF 1.3 ± 0.35). The results indicate that exposure to radiofrequency EMF may affect the neurovegetative regulation.

A phase 2 study of the safety, tolerability, and pharmacodynamics of FBS0701, a novel oral iron chelator, in transfusional iron overload

PubMed Central

Neufeld, Ellis J.; Galanello, Renzo; Viprakasit, Vip; Aydinok, Yesim; Piga, Antonio; Harmatz, Paul; Forni, Gian Luca; Shah, Farrukh T.; Grace, Rachael F.; Porter, John B.; Wood, John C.; Peppe, Jennifer; Jones, Amber

2012-01-01

This was a 24-week, multicenter phase- 2 study designed to assess safety, tolerability, and pharmacodynamics of FBS0701, a novel oral chelator, in adults with transfusional iron overload. Fifty-one patients, stratified by transfusional iron intake, were randomized to FBS0701 at either 14.5 or 29 mg/kg/d (16 and 32 mg/kg/d salt form). FBS0701 was generally well tolerated at both doses. Forty-nine patients (96%) completed the study. There were no drug-related serious adverse events. No adverse events (AEs) showed dose-dependency in frequency or severity. Treatment-related nausea, vomiting, abdominal pain, and diarrhea were each noted in < 5% of patients. Mean serum creatinine did not change significantly from Baseline or between dose groups. Transaminases wer increased in 8 (16%), three of whom acquired HCV on-study from a single blood bank while five had an abnormal baseline ALT. The 24 week mean change in liver iron concentration (ΔLIC) at 14.5 mg/kg/d was +3.1 mg/g (dw); 29% achieved a decrease in LIC. Mean ΔLIC at 29 mg/kg/d was −0.3 mg/g (dw); 44% achieved a decrease in LIC (P < .03 for ΔLIC between doses). The safety and tolerability profile at therapeutic doses compare favorably to other oral chelators. This trial was registered at www.clinicaltrials.gov as NCT01186419. PMID:22251482

Root biomass response to foliar application of imazapyr for two imidazolinone tolerant alleles of sunflower (Helianthus annuus L.)

PubMed Central

Sala, Carlos A.; Bulos, Mariano; Altieri, Emiliano; Ramos, María Laura

2012-01-01

Imisun and CLPlus are two imidazolinone tolerance traits in sunflower (Helianthus annuus L.) determined by the expression of two alleles at the locus Ahasl1. Both traits differed in their tolerance level to imazapyr —a type of imidazolinone herbicide— when aboveground biomass is considered, but the concomitant herbicide effect over the root system has not been reported. The objective of this work was to quantify the root biomass response to increased doses of imazapyr in susceptible (ahasl1/ahasl1), Imisun (Ahasl1-1/Ahasl1-1) and CLPlus (Ahasl1-3/Ahasl1-3) homozygous sunflower genotypes. These materials were sprayed at the V2–V4 stage with increased doses of imazapyr (from 0 to 480 g active ingredient ha−1) and 14 days after treatment root biomass of each plant was assessed. Genotype at the Ahasl1 locus, dose of imazapyr and their interaction significantly contributed (P < 0.001) to explain the reduction in root biomass accumulation after herbicide application. Estimated dose of imazapyr required to reduce root biomass accumulation by fifty percent (GR50) differed statistically for the three genotypes under study (P < 0.001). CLPlus genotypes showed the highest values of GR50, 300 times higher on average than the susceptible genotypes, and almost 8 times higher than Imisun materials, demonstrating that both alleles differ in their root biomass response to foliar application of increased doses of imazapyr. PMID:23226083

An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.

PubMed

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.

Nitrates for stable angina: a systematic review and meta-analysis of randomized clinical trials.

PubMed

Wei, Jiafu; Wu, Taixiang; Yang, Qing; Chen, Mao; Ni, Juan; Huang, Dejia

2011-01-07

To assess the effect (harms and benefits) of nitrates for stable angina. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Randomized controlled trials with both parallel and crossover design were included. The following outcome measures were evaluated: number of angina attacks weekly and nitroglycerin consumption, quality of life, total exercise duration, time to onset of angina and time to 1 mm ST depression. Fifty-one trials with 3595 patients meeting inclusion criteria were analyzed. Both intermittent and continuous regimens of nitrates lengthened exercise duration significantly by 31 and 53 s respectively. The number of angina attacks was significantly reduced by 2.89 episodes weekly for continuous administration and 1.5 episodes weekly for intermittent administration. With intermittent administration, increased dose provided with 21 s more length of exercise duration. With continuous administration, exercise duration was pronged more in low-dose group. Quality of life was not improved by continuous application of GTN patches and was similar between continuous and intermittent groups. In addition, 51.6% patients receiving nitrates complained with headache. Long-term administration of nitrates was beneficial for angina prophylaxis and improved exercise performance but might be ineffective for improving quality of life. With continuous regimen, low-dose nitrates were more effective than high-dose ones for improving exercise performance. By contrast, with intermittent regimen, high-dose nitrates were more effective. In addition, intermittent administration could bring zero-hour effect. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Adjunctive levetiracetam treatment in pediatric Lennox-Gastaut syndrome.

PubMed

Kim, Hyo Jeong; Kim, Shin Hye; Kang, Hoon-Chul; Lee, Joon Soo; Chung, Hee Jung; Kim, Heung Dong

2014-10-01

Our aim was to investigate the efficacy and tolerability of levetiracetam as an add-on treatment in pediatric patients with Lennox-Gastaut syndrome. The study was an open-label, multicenter, observational clinical trial of levetiracetam as an add-on treatment in Lennox-Gastaut syndrome. Fifty-five patients aged 1.1-18.6 years (mean, 10.0 years) were enrolled. The study included a 4-8-week titration period and an 8-week maintenance period. The maintenance dose of levetiracetam was 20-80 mg/kg/day, according to its effectiveness and tolerability. The primary end point was reduction in seizure frequency, and related variables were also evaluated. Among 55 patents, 51 patients (92.7%) completed the study. Thirty-two patients (58.2%) experienced a more than 50% reduction in seizure frequency, and 15 patients (27.3%) became seizure free. A reduction in seizure frequency of more than 50% was observed in 21 of 36 patients (58.3%) with convulsive seizures, 7 of 12 patients (58.3%) with drop attacks, 2 of 4 patients (50.0%) with myoclonic seizures, and 2 of 3 patients (66.7%) with epileptic spasms. Overall, 34.5% of patients reported adverse events. None of the adverse events were life threatening, and the most common adverse event was hyperactivity (12.7%). This study suggests that levetiracetam is a safe and effective treatment in pediatric patients with Lennox-Gastaut syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

Survey of management of neonatal haemolytic jaundice in Australasia.

PubMed

Malhotra, Atul; Carse, Elizabeth

2010-05-01

Haemolytic jaundice is an important entity in neonatal clinical practice. Because of the decrease in rhesus isoimmunisation since the advent of anti-D immunoglobulin and improved antenatal management strategies, its management in the neonatal period has become less intensive and exchange transfusions rarely performed. We planned to review the practice of Australasian perinatal units in light of recent advances and recommendations. An electronic survey was sent to the directors of all 25 tertiary-level perinatal units across Australasia. The questionnaire comprised 20 questions dealing with the management of haemolytic jaundice. Twenty out of the 25 neonatal units responded. Most were aware of the recent American Academy of Pediatrics guidelines, but only eight (40%) based their practice on it. Fifty per cent of neonatal units had written protocols to manage such infants, but almost all had written guidelines for performing exchange transfusions. Seven (35%) units started prophylactic phototherapy; however, the criteria used for early exchange were variable, most related to cord haemoglobin or rate of rise of bilirubin. Few units used high-dose intravenous immunoglobulin in haemolytic jaundice. Average exchange rates (based on the last 2 years) were 3.5/year (0-10). Variable practice was noted across the Australasian units. Written protocols form the backbone of management of jaundice in such babies. The use of intravenous immunoglobulin is minimal, and the information available on its use needs to be critically appraised.

Multi-Institutional Assessment of Adverse Health Outcomes Among North American Testicular Cancer Survivors After Modern Cisplatin-Based Chemotherapy

PubMed Central

Fung, Chunkit; Sesso, Howard D.; Williams, Annalynn M.; Kerns, Sarah L.; Monahan, Patrick; Abu Zaid, Mohammad; Feldman, Darren R.; Hamilton, Robert J.; Vaughn, David J.; Beard, Clair J.; Kollmannsberger, Christian K.; Cook, Ryan; Althouse, Sandra; Ardeshir-Rouhani-Fard, Shirin; Lipshultz, Steve E.; Fossa, Sophie D.; Travis, Lois B.

2017-01-01

Purpose To provide new information on adverse health outcomes (AHOs) in testicular cancer survivors (TCSs) after four cycles of etoposide and cisplatin (EPX4) or three or four cycles of bleomycin, etoposide, cisplatin (BEPX3/BEPX4). Methods Nine hundred fifty-two TCSs > 1 year postchemotherapy underwent physical examination and completed a questionnaire. Multinomial logistic regression estimated AHOs odds ratios (ORs) in relation to age, cumulative cisplatin and/or bleomycin dose, time since chemotherapy, sociodemographic factors, and health behaviors. Results Median age at evaluation was 37 years; median time since chemotherapy was 4.3 years. Chemotherapy consisted largely of BEPX3 (38.2%), EPX4 (30.9%), and BEPX4 (17.9%). None, one to two, three to four, or five or more AHOs were reported by 20.4%, 42.0%, 25.1%, and 12.5% of TCSs, respectively. Median number after EPX4 or BEPX3 was two (range, zero to nine and zero to 11, respectively; P > .05) and two (range, zero to 10) after BEPX4. When comparing individual AHOs for EPX4 versus BEPX3, Raynaud phenomenon (11.6% v 21.4%; P < .01), peripheral neuropathy (29.2% v 21.4%; P = .02), and obesity (25.5% v 33.0%; P = .04) differed. Larger cumulative bleomycin doses (OR, 1.44 per 90,000 IU) were significantly associated with five or more AHOs. Increasing age was a significant risk factor for one to two, three to four, or five or more AHOs versus zero AHOs (OR, 1.22, 1.50, and 1.87 per 5 years, respectively; P < .01); vigorous physical activity was protective (OR, 0.62, 0.51, and 0.41, respectively; P < .05). Significant risk factors for three to four and five or more AHOs included current (OR, 3.05 and 3.73) or former (OR, 1.61 and 1.76) smoking (P < .05). Self-reported health was excellent/very good in 59.9% of TCSs but decreased as AHOs increased (P < .001). Conclusion Numbers of AHOs after EPX4 or BEPX3 appear similar, with median follow-up of 4.3 years. A healthy lifestyle was associated with reduced number of AHOs. PMID:28240972

Adolescent booster with hepatitis B virus vaccines decreases HBV infection in high-risk adults.

PubMed

Wang, Yuting; Chen, Taoyang; Lu, Ling-Ling; Wang, Minjie; Wang, Dongmei; Yao, Hongyu; Fan, Chunsun; Qi, Jun; Zhang, Yawei; Qu, Chunfeng

2017-02-15

Neutralizing antibodies (anti-HBs) after immunization with hepatitis B virus (HBV) vaccines against HBV surface antigen (HBsAg) wane after 10-15years. We analyzed the effect of an adolescent booster given to vaccination-protected children born to mothers with different HBsAg-carrying status against HBV infection in their mature adulthood. A total of 9793 individuals, who were HBsAg-negative at childhood (baseline) and donated blood samples, both during childhood and adulthood, from the vaccination group in "Qidong Hepatitis B Intervention Study", were enrolled. Among them 7414 received a one-dose, 10μg-recombinant HBV vaccine booster at 10-14years of age. At endpoint (23-28years of age), we determined the HBV serological markers and quantified their serum HBV-DNA in each of the chronic HBV-infected adults. Fifty-seven adults were identified as chronic HBV infection, indicated by HBsAg(+)&anti-HBc(+) for more than 6months. The individuals who were born to HBsAg-positive mothers (high-risk adults) had significantly increased risk of developing chronic HBV infections in adulthood compared with those who were born to HBsAg-negative mothers; the adjusted odds ratio (OR) was 12.56, 95%CI:7.14-22.08. The seronegative status of anti-HBs at 10-11years of age significantly increased the risk of HBV infections among the high-risk adults. When HBsAg(-)&anti-HBc(+) children who were born to HBsAg-positive mothers 70% of them remained as the status and 10% of them developed HBsAg(+)&anti-HBc(+). While when they were born to HBsAg-negative mothers 1.05% HBsAg(-)&anti-HBc(+) children developed HBsAg(+)&anti-HBc(+) and 24.74% of them remained as the status in 12-18years. One dose of adolescent booster showed significant protection on high-risk adults from chronic HBV infection; P for trend was 0.015. Maternal HBsAg-positive status was an independent risk factor for vaccination-protected children to develop HBV breakthrough infection in adulthood. Adolescent boosters might be appropriate for high-risk individuals who were born to HBsAg-positive mothers when their serum anti-HBs<10mIU/ml. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis.

PubMed

Wang, Yongjun; Parker, Claire E; Bhanji, Tania; Feagan, Brian G; MacDonald, John K

2016-04-21

Oral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs in doses of at least 2 g/day, were more effective than placebo but no more effective than SASP for inducing remission in ulcerative colitis. This updated review includes more recent studies and evaluates the efficacy and safety of 5-ASA preparations used for the treatment of mild to moderately active ulcerative colitis. The primary objectives were to assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for induction of remission in active ulcerative colitis. A secondary objective of this systematic review was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. A computer-assisted literature search for relevant studies (inception to July 9, 2015) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies. Studies were accepted for analysis if they were randomized controlled clinical trials of parallel design, with a minimum treatment duration of four weeks. Studies of oral 5-ASA therapy for treatment of patients with active ulcerative colitis compared with placebo, SASP or other formulations of 5-ASA were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA (two or three times daily) and 5-ASA dose ranging studies were also considered for inclusion. The outcomes of interest were the failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, endoscopic improvement, adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. SASP-controlled trials were subgrouped by 5-ASA/SASP mass ratios. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol, Claversal, Salofalk and Pentasa). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention-to-treat basis. Fifty-three studies (8548 patients) were included. The majority of included studies were rated as low risk of bias. 5-ASA was significantly superior to placebo with regard to all measured outcome variables. Seventy-one per cent of 5-ASA patients failed to enter clinical remission compared to 83% of placebo patients (RR 0.86, 95% CI 0.82 to 0.89). A dose-response trend for 5-ASA was also observed. No statistically significant differences in efficacy were found between 5-ASA and SASP. Fifty-four per cent of 5-ASA patients failed to enter remission compared to 58% of SASP patients (RR 0.90, 95% CI 0.77 to 1.04). No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Forty-five per cent of once daily patients failed to enter clinical remission compared to 48% of conventionally dosed patients (RR 0.94, 95% CI 0.83 to 1.07). Eight per cent of patients dosed once daily failed to adhere to their medication regimen compared to 6% of conventionally dosed patients (RR 1.36, 95% CI 0.64 to 2.86). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Fifty per cent of patients in the 5-ASA group failed to enter remission compared to 52% of patients in the 5-ASA comparator group (RR 0.94, 95% CI 0.86 to 1.02). A pooled analysis of 3 studies (n = 1459 patients) studies found no statistically significant difference in clinical improvement between Asacol 4.8 g/day and 2.4 g/day used for the treatment of moderately active ulcerative colitis. Thirty-seven per cent of patients in the 4.8 g/day group failed to improve clinically compared to 41% of patients in the 2.4 g/day group (RR 0.89; 95% CI 0.78 to 1.01). Subgroup analysis indicated that patients with moderate disease may benefit from the higher dose of 4.8 g/day. One study compared (n = 123 patients) Pentasa 4 g/day to 2.25 g/day in patients with moderate disease. Twenty-five per cent of patients in the 4 g/day group failed to improve clinically compared to 57% of patients in the 2.25 g/day group (RR 0.44; 95% CI 0.27 to 0.71). A pooled analysis of two studies comparing MMX mesalamine 4.8 g/day to 2.4 g/day found no statistically significant difference in efficacy (RR 1.03, 95% CI 0.82 to 1.29). There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulation and 5-ASA dose ranging (high dose versus low dose) studies. Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache and worsening ulcerative colitis. SASP was not as well tolerated as 5-ASA. Twenty-nine percent of SASP patients experienced an adverse event compared to 15% of 5-ASA patients (RR 0.48, 95% CI 0.37 to 0.63). 5-ASA was superior to placebo and no more effective than SASP. Considering their relative costs, a clinical advantage to using oral 5-ASA in place of SASP appears unlikely. 5-ASA dosed once daily appears to be as efficacious and safe as conventionally dosed 5-ASA. Adherence does not appear to be enhanced by once daily dosing in the clinical trial setting. It is unknown if once daily dosing of 5-ASA improves adherence in a community-based setting. There do not appear to be any differences in efficacy or safety among the various 5-ASA formulations. A daily dosage of 2.4 g appears to be a safe and effective induction therapy for patients with mild to moderately active ulcerative colitis. Patients with moderate disease may benefit from an initial dose of 4.8 g/day.

Locally acting ACE-083 increases muscle volume in healthy volunteers.

PubMed

Glasser, Chad E; Gartner, Michael R; Wilson, Dawn; Miller, Barry; Sherman, Matthew L; Attie, Kenneth M

2018-02-27

ACE-083 is a locally acting follistatin-based therapeutic that binds myostatin and other muscle regulators and has been shown to increase muscle mass and force in neuromuscular disease mouse models. This first-in-human study examined these effects. In this phase 1, randomized, double-blind, placebo-controlled, dose-ranging study in healthy postmenopausal women, ACE-083 (50-200 mg) or placebo was administered unilaterally into rectus femoris (RF) or tibialis anterior (TA) muscles as 1 or 2 doses 3 weeks apart. Fifty-eight postmenopausal women were enrolled, 42 ACE-083 and 16 placebo. No serious adverse events (AE), dose-limiting toxicities, or discontinuations resulting from AEs occurred. Maximum (mean ± SD) increases in RF and TA muscle volume were 14.5% ± 4.5% and 8.9% ± 4.7%, respectively. No significant changes in mean muscle strength were observed. ACE-083 was well tolerated and resulted in significant targeted muscle growth. ACE-083 may have the potential to increase muscle mass in a wide range of neuromuscular disorders. Muscle Nerve, 2018. © 2018 The Authors Muscle & Nerve Published by Wiley Periodicals, Inc.

Adaptive Statistical Iterative Reconstruction-V Versus Adaptive Statistical Iterative Reconstruction: Impact on Dose Reduction and Image Quality in Body Computed Tomography.

PubMed

Gatti, Marco; Marchisio, Filippo; Fronda, Marco; Rampado, Osvaldo; Faletti, Riccardo; Bergamasco, Laura; Ropolo, Roberto; Fonio, Paolo

The aim of this study was to evaluate the impact on dose reduction and image quality of the new iterative reconstruction technique: adaptive statistical iterative reconstruction (ASIR-V). Fifty consecutive oncologic patients acted as case controls undergoing during their follow-up a computed tomography scan both with ASIR and ASIR-V. Each study was analyzed in a double-blinded fashion by 2 radiologists. Both quantitative and qualitative analyses of image quality were conducted. Computed tomography scanner radiation output was 38% (29%-45%) lower (P < 0.0001) for the ASIR-V examinations than for the ASIR ones. The quantitative image noise was significantly lower (P < 0.0001) for ASIR-V. Adaptive statistical iterative reconstruction-V had a higher performance for the subjective image noise (P = 0.01 for 5 mm and P = 0.009 for 1.25 mm), the other parameters (image sharpness, diagnostic acceptability, and overall image quality) being similar (P > 0.05). Adaptive statistical iterative reconstruction-V is a new iterative reconstruction technique that has the potential to provide image quality equal to or greater than ASIR, with a dose reduction around 40%.

Tissue distribution and serum kinetics of T101 monoclonal antibody during passive anti-cancer therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shawler, D.L.; Beauregard, J.; Halpern, S.E.

We have administered fifty-six 24 hr infusions of the anti-human T-cell monoclonal antibody T101 to 10 patients with cutaneous T-cell lymphoma (CTCL) and 6 patients with chronic lymphocytic leukemia (CLL) in doses of 10, 50, 100, 150, and 500 mg. The larger doses of T101 resulted in higher, more persistent serum T101 concentrations, and CTCL patients generally developed higher serum T101 levels than CLL patients given equivalent doses. The presence of host anti-mIgG antibodies prior to infusion was associated with decreased serum concentrations of T101. Treatments that demonstrated measurable serum T101 levels were also associated with in vivo T101 bindingmore » and cytodestruction of circulating target cells. Immunofluorescence analysis of bone marrow and lymph node biopsies in CLL, and skin biopsies in CTCL, suggested that T101 had reached extravascular tumor sites. Infusion of /sup 111/In-conjugated T101 showed uptake in the liver, spleen, lymph nodes, and (in CTCL) skin infiltrates. Our data demonstrate the tissue distribution of T101 and suggest that immunoconjugates of T101 with toxins, drugs, or radioisotopes may result in better therapeutic responses.« less

Diagnostic reference levels in low- and middle-income countries: early "ALARAm" bells?

PubMed

Meyer, Steven; Groenewald, Willem A; Pitcher, Richard D

2017-04-01

Background In 1996 the International Commission on Radiological Protection (ICRP) introduced diagnostic reference levels (DRLs) as a quality assurance tool for radiation dose optimization. While many countries have published DRLs, available data are largely from high-income countries. There is arguably a greater need for DRLs in low- and middle-income-countries (LMICs), where imaging equipment may be older and trained imaging technicians are scarce. To date, there has been no critical analysis of the published work on DRLs in LMICs. Such work is important to evaluate data deficiencies and stimulate future quality assurance initiatives. Purpose To review the published work on DRLs in LMICs and to critically analyze the comprehensiveness of available data. Material and Methods Medline, Scopus, and Web of Science database searches were conducted for English-language articles published between 1996 and 2015 documenting DRLs for diagnostic imaging in LMICs. Retrieved articles were analyzed and classified by geographical region, country of origin, contributing author, year of publication, imaging modality, body part, and patient age. Results Fifty-three articles reported DRLs for 28 of 135 LMICs (21%), reflecting data from 26/104 (25%) middle-income countries and 2/31 (6%) low-income countries. General radiography (n = 26, 49%) and computerized tomography (n = 17, 32%) data were most commonly reported. Pediatric DRLs (n = 14, 26%) constituted approximately one-quarter of published work. Conclusion Published DRL data are deficient in the majority of LMICs, with the paucity most striking in low-income countries. DRL initiatives are required in LMICs to enhance dose optimization.

Treatment of Acute Abnormal Uterine Bleeding in Adolescents: What Are Providers Doing in Various Specialties?

PubMed

Huguelet, Patricia S; Buyers, Eliza M; Lange-Liss, Jill H; Scott, Stephen M

2016-06-01

The purpose of this study was to assess whether variability exists in the management of acute abnormal uterine bleeding (AUB) in adolescents between pediatric Emergency Department (ED) physicians, pediatric gynecologists, and adolescent medicine specialists. Retrospective chart review. Tertiary care medical center ED. We included girls aged 9-22 years who presented from July 2008 to June 2014 with the complaint of acute AUB. Patients were identified using the International Classification of Diseases, ninth revision codes for heavy menstrual bleeding, AUB, and irregular menses. Exclusion criteria included pregnancy and current use of hormonal therapy. One hundred fifty patients were included. Among those evaluated, 61% (n = 92) were prescribed hormonal medication to stop their bleeding by providers from the ED, Adolescent Medicine, or Pediatric Gynecology. ED physicians prescribed mostly single-dose and multidose taper combined oral contraceptive pills (85%; n = 24), compared with Adolescent Medicine (54%, n = 7), and Gynecology (28%, n = 13). Pediatric gynecologists were more likely than ED physicians to treat patients with norethindrone acetate, either alone or in combination with a single dose combined oral contraceptive pill (61%, n = 33 vs 7%, n = 2; P < .001). Variations in treatment strategies for adolescents who present with acute AUB exist among pediatric specialties, which reflects a lack of standardized care for adolescents. Prospective evaluation of the shortest interval to cessation of bleeding, side effects, and patient satisfaction are valuable next steps. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections.

PubMed

Wright, Karen D; Panetta, John C; Onar-Thomas, Arzu; Reddick, Wilburn E; Patay, Zoltan; Qaddoumi, Ibrahim; Broniscer, Alberto; Robinson, Giles; Boop, Frederick A; Klimo, Paul; Ward, Deborah; Gajjar, Amar; Stewart, Clinton F

2015-01-01

High-dose methotrexate (HD-MTX) has been used to treat children with central nervous system tumors. Accumulation of MTX within pleural, peritoneal, or cardiac effusions has led to delayed excretion and increased risk of systemic toxicity. This retrospective study analyzed the association of intracranial post-resection fluid collections with MTX plasma disposition in infants and young children with brain tumors. Brain MRI findings were analyzed for postoperative intracranial fluid collections in 75 pediatric patients treated with HD-MTX and for whom serial MTX plasma concentrations (MTX) were collected. Delayed plasma excretion was defined as (MTX) ≥1 μM at 42 hours (h). Leucovorin was administered at 42 h and then every 6 h until (MTX) <0.1 μM. Population and individual MTX pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling. Fifty-eight patients had intracranial fluid collections present. Population average (inter-individual variation) MTX clearance was 96.0 ml/min/m² (41.1 CV %) and increased with age. Of the patients with intracranial fluid collections, 24 had delayed excretion; only 2 of the 17 without fluid collections (P < 0.04) had delayed excretion. Eleven patients had grade 3 or 4 toxicities attributed to HD-MTX. No significant difference was observed in intracranial fluid collection, total leucovorin dosing, or hydration fluids between those with and without toxicity. Although an intracranial fluid collection is associated with delayed MTX excretion, HD-MTX can be safely administered with monitoring of infants and young children with intracranial fluid collections. Infants younger than 1 year may need additional monitoring to avoid toxicity.

AIR insulin capsules of different dose strengths may be combined to yield equivalent pharmacokinetics and glucodynamics.

PubMed

de la Peña, Amparo; Seger, Mary; Rave, Klaus; Heinemann, Lutz; Silverman, Bernard; Muchmore, Douglas B

2009-09-01

In order to assess pharmacokinetic (PK) and glucodynamic (GD) attributes relevant to the end user of an inhaled insulin, this study examined the exposure and GD effect of doses of AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) by combining capsules of different strengths in healthy subjects. Fifty-nine healthy, nonsmoking, male or female subjects with normal pulmonary function were enrolled in an open-label, randomized, crossover study. Subjects underwent up to five euglycemic glucose clamp procedures, separated by 5-18 days. The five AIR insulin treatments tested included one 6 unit-equivalent (U-eq) capsule containing 2.6 mg of insulin, three 2 U-eq (0.9 mg) capsules (2.7 mg total), one 10 U-eq (3.9 mg) capsule, one 6 U-eq capsule plus two 2 U-eq capsules (4.4 mg total), and two 10 U-eq capsules (7.8 mg total). Samples for PK and GD assessments were taken up to 10 h post-dose. Based on both PK (area under the curve from time 0 to time of return to baseline and maximum concentration) and GD (total amount of glucose infused and maximum glucose infusion rate) responses, administration of a 6 U-eq capsule was equivalent to three 2 U-eq capsules; 90% confidence intervals for the ratios were contained within the interval (0.8, 1.25). Similarly, both overall exposure and glucodynamic response after administration of a 10 U-eq capsule were comparable to the 6 U-eq plus two 2 U-eq capsule combination. AIR insulin exhibited PK dose proportionality and dose-dependent increases in GD responses over the 2.6-7.8 mg dose range. AIR insulin exhibited dose strength interchangeability and dose proportionality after single-dose administration in healthy subjects.

[The role of CYP2E1 in the protection of garlic oil's from n-hexane-induced neurotoxicity].

PubMed

Bi, Ye; Chen, Jing-jing; Li, Yang; Fu, Qiang-qiang; Zeng, Tao; Xie, Ke-qin

2011-11-01

To study the role of CYP2E1 in the protective effects and mechanism of garlic oil (GO) on the peripheral nerve injuries induced by n-hexane. Fifty male Wistar rats were randomly divided into five groups (n = 10): the control, the GO (80 mg/kg) control, the n-hexane (2000 mg/kg) model, the low dose GO (40 mg/kg) plus n-hexane, and the high dose GO (80 mg/kg) plus n-hexane groups. All rats were treated by intragastric administration 6 times a week for 10 weeks. The gait scores were determined every two weeks for monitoring the peripheral neurotrosis. All rats were sacrificed in 10 weeks, the activities and expression levels of hepatic CYP2E1 and 2, 5-HD in serum were examined. As compared with control group, the content and activity of hepatic CYP2E1 in GO control group reduced by 83.1% and 48.3% respectively (P < 0.01), the content and activity of hepatic CYP2E1 in model group increased by 112.5% and 72.2% respectively (P < 0.01). As compared with model group, the contents of hepatic CYP2E1 in low dose and high dose GO groups reduced by 32.9% and 39.1% respectively, the activities of hepatic CYP2E1 in low dose and high dose GO groups reduced by 27.4% and 44.5% respectively (P < 0.01); the contents of serum 2,5-HD in low dose and high dose GO groups reduced by 47.7% and 78.7% respectively (P < 0.01). The gait scores in model, low dose and high dose GO groups were significantly lower than that in control group, but the gait scores in low dose and high dose GO groups were significantly lower than that in model group (P < 0.05). Garlic oil can effectively reduce the peripheral neurotrosis induced by n-hexane due to the decreased content and activity of hepatic CYP2E1, resulting in the reduced formation of 2, 5-HD from n-hexane.

Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant

PubMed Central

Hawwa, Ahmed F; McKiernan, Patrick J; Shields, Michael; Millership, Jeff S; Collier, Paul S; McElnay, James C

2009-01-01

AIMS The aim of this study was to investigate the influence of genetic polymorphisms in ABCB1 on the incidence of nephrotoxicity and tacrolimus dosage-requirements in paediatric patients following liver transplantation. METHODS Fifty-one paediatric liver transplant recipients receiving tacrolimus were genotyped for ABCB1 C1236>T, G2677>T and C3435>T polymorphisms. Dose-adjusted tacrolimus trough concentrations and estimated glomerular filtration rates (EGFR) indicative of renal toxicity were determined and correlated with the corresponding genotypes. RESULTS The present study revealed a higher incidence of the ABCB1 variant-alleles examined among patients with renal dysfunction (≥30% reduction in EGFR) at 6 months post-transplantation (1236T allele: 63.3% vs 37.5% in controls, P= 0.019; 2677T allele: 63.3% vs. 35.9%, p = 0.012; 3435T allele: 60% vs. 39.1%, P= 0.057). Carriers of the G2677->T variant allele also had a significant reduction (%) in EGFR at 12 months post-transplant (mean difference = 22.6%; P= 0.031). Haplotype analysis showed a significant association between T-T-T haplotypes and an increased incidence of nephrotoxicity at 6 months post-transplantation (haplotype-frequency = 52.9% in nephrotoxic patients vs 29.4% in controls; P= 0.029). Furthermore, G2677->T and C3435->T polymorphisms and T-T-T haplotypes were significantly correlated with higher tacrolimus dose-adjusted pre-dose concentrations at various time points examined long after drug initiation. CONCLUSIONS These findings suggest that ABCB1 polymorphisms in the native intestine significantly influence tacrolimus dosage-requirement in the stable phase after transplantation. In addition, ABCB1 polymorphisms in paediatric liver transplant recipients may predispose them to nephrotoxicity over the first year post-transplantation. Genotyping future transplant recipients for ABCB1 polymorphisms, therefore, could have the potential to individualize better tacrolimus immunosuppressive therapy and enhance drug safety. PMID:19740399

High-dose sublingual immunotherapy in patients with uncontrolled allergic rhinitis sensitized to pollen: a real-life clinical study.

PubMed

Irani, Carla; Saleh, Roula Abi; Jammal, Mouin; Haddad, Fady

2014-10-01

High-dose pollen sublingual immunotherapy (SLIT) is indicated in patients with moderate to severe allergic rhinitis (AR), especially those who are unable to control their disease with pharmacotherapy. We explore the use of high-dose SLIT in patients with severe AR and sensitized to pollen, in real-life clinical practice. We also analyzed the effect on asthma. This was a prospective observational study conducted at the Allergy outpatient clinic at Hotel Dieu de France Hospital (HDF), Beirut, Lebanon. The cohort, composed of 118 patients between 7 and 55 years old, was regularly evaluated at inclusion, at 12 months, and at 36 months. Fifty-five percent of AR patients had associated controlled asthma. Patients received a standardized pollen extract (Staloral 300IR). The pollen combination was 1 to 3 pollens, the most commonly used were Parietaria judaica, Cupressaceae, 5 grasses, and Oleaceae. In a previous study, those were the main allergenic pollens correlated to AR in the same population. Global assessment of the effect of SLIT was measured using a rhinitis total symptom score (RTSS), a rhinitis medication consumption score (RMCS), a global asthma score (ASS), and an asthma medication consumption score (AMCS). Using a t test we found that the average scores at inclusion, 12 months, and 36 months, respectively, were as follows: RTSS: 31.32, 16.39 (p < 0.041), and 13.35 (p < 0.041); RMCS: 6.96, 1.96 (p < 0.0162), and 1.61 (p < 0.0162); ASS: 4.62, 1.96 (p < 0.0005), and 1.33 (p < 0.0005); and AMCS: 2.35, 0.78 (p < 0.0005), and 0.7 (p < 0.0005). Our study showed favorable results of SLIT to aeroallergens in patients with uncontrolled AR. The effect is also applicable to the subgroup of patients suffering from concomitant, controlled asthma. © 2014 ARS-AAOA, LLC.

Prognostic value of high-dose dobutamine stress magnetic resonance imaging in 1,493 consecutive patients: assessment of myocardial wall motion and perfusion.

PubMed

Korosoglou, Grigorios; Elhmidi, Yacine; Steen, Henning; Schellberg, Dieter; Riedle, Nina; Ahrens, Johannes; Lehrke, Stephanie; Merten, Constanze; Lossnitzer, Dirk; Radeleff, Jannis; Zugck, Christian; Giannitsis, Evangelos; Katus, Hugo A

2010-10-05

This study sought to determine the prognostic value of wall motion and perfusion assessment during high-dose dobutamine stress (DS) cardiac magnetic resonance imaging (MRI) in a large patient cohort. DS-MRI offers the possibility to integrate myocardial perfusion and wall motion analysis in a single examination for the detection of coronary artery disease (CAD). A total of 1,493 consecutive patients with suspected or known CAD underwent DS-MRI, using a standard protocol in a 1.5-T magnetic resonance scanner. Wall motion and perfusion were assessed at baseline and during stress, and outcome data including cardiac death, nonfatal myocardial infarction ("hard events"), and "late" revascularization performed >90 days after the MR scans were collected during a 2 ± 1 year follow-up period. Fifty-three hard events, including 14 cardiac deaths and 39 nonfatal infarctions, occurred during the follow-up period, whereas 85 patients underwent "late" revascularization. Using multivariable regression analysis, an abnormal result for wall motion or perfusion during stress yielded the strongest independent prognostic value for both hard events and late revascularization, clearly surpassing that of clinical and baseline magnetic resonance parameters (for wall motion: adjusted hazard ratio [HR] of 5.9 [95% confidence interval (CI): 2.5 to 13.6] for hard events and of 3.1 [95% CI: 1.7 to 5.6] for late revascularization, and for perfusion: adjusted HR of 5.4 [95% CI: 2.3 to 12.9] for hard events and of 6.2 [95% CI: 3.3 to 11.3] for late revascularization, p < 0.001 for all). DS-MRI can accurately identify patients who are at increased risk for cardiac death and myocardial infarction, separating them from those with normal findings, who have very low risk for future cardiac events. (Prognostic Value of High Dose Dobutamine Stress Magnetic Resonance Imaging; NCT00837005). Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Anesthesia maintenance with 'induction dose only' sevoflurane during pediatric ophthalmic examination: comparison with standard low-flow technique through a randomized controlled trial.

PubMed

Datta, Priyankar K; Sinha, Renu; Ray, Bikash Ranjan; Jambunathan, Venkateswaran; Kundu, Riddhi

2017-02-01

Sevoflurane is preferred for pediatric day care procedures. However, financial and environmental costs remain major limitations. Induction dose of sevoflurane could itself be sufficient for maintaining anesthesia with low fresh gas flow during short noninvasive procedures. Fifty children, aged 1-5 years, scheduled for ophthalmic examination under anesthesia, were randomized into two groups. All children were induced with 8% sevoflurane in O 2 : N 2 O (40 : 60). In the Group S, anesthesia was maintained with 2% sevoflurane at 1 l·min -1 fresh gas flow [O 2 : N 2 O = 50 : 50]. In Group L, the sevoflurane vaporizer was turned off and fresh gas flow was reduced to 0.5 l·min -1 [O 2 : N 2 O = 50 : 50]. HR, BP, MAC, BIS, total sevoflurane consumption, ocular deviation, body movement, time to laryngeal mask airway removal (T WO ), and airway complications were compared between the groups. Rescue propofol bolus was used, if needed. Median duration of examination was 14 min (IQR = 9-17) in Group S and 15 min (IQR = 10-17) in Group L. Sevoflurane consumption was lower in the Group L (7 ml) compared to Group S (9 ml) [median difference = 2 ml, P < 0.001, 95% CI = 0.96-3.04]. T WO was lower in Group L (86 s) compared to Group S (131 s) [median difference = 45 s, P = 0.002, 95% CI = 19.85-70.15]. There was no difference in hemodynamic parameters, incidence of ocular deviation, movement or airway complications, and need for rescue propofol. Induction dose of sevoflurane is, in itself, adequate for maintaining anesthesia for short noninvasive ophthalmic examinations lasting approximately 15 min. This method significantly reduces sevoflurane consumption and cost. © 2016 John Wiley & Sons Ltd.

Feasibility of high-pitch spiral dual-source CT angiography in children with complex congenital heart disease compared to retrospective-gated spiral acquisition.

PubMed

Li, T; Zhao, S; Liu, J; Yang, L; Huang, Z; Li, J; Luo, C; Li, X

2017-10-01

To investigate the use of second-generation dual-source high-pitch computed tomography in obtaining confident diagnostic image quality using a low radiation dose in young patients with congenital heart disease (CHD). From July 2014 to June 2016, 50 consecutive children <4 years with complex CHD underwent electrocardiography (ECG)-triggered dual-source computed tomography (CT). The patients were assigned randomly to two groups: high-pitch (pitch 3.4) spiral dual-source CT acquisition (group A) and retrospectively spiral dual-source CT acquisition (group B). The image quality, diagnostic accuracy, coronary artery origin, course demonstration, and radiation exposure were compared between the two groups. Fifty examinations were performed (group A, 25; group B, 25). There were no significant differences in image quality, diagnostic accuracy, coronary artery origin, and course demonstration between the two groups. The image quality scores were 1.3±0.4 in group A and 1.1±0.3 in group B (p=0.2). The diagnostic accuracy was 100% in both groups. The coronary arteries were traceable in 80% in group A and 84% in group B (p=0.7). A single coronary artery was identified in one case in group A and the left anterior descending (LAD) branch originated from the right coronary artery (RCA) in one case in group B. There were significant differences in the effective doses between the two groups (0.40±0.20 mSv in group A and 2.7±1.0 mSv in group B, p<0.05). Intra-cardiac and extra-cardiac malformation, coronary artery origin, and course malformation can be visualised clearly using a high-pitch ECG-triggered dual-source CT with a low radiation dose and good image quality in patients with CHD. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Six-Year-Olds' Learning of Novel Words through Addressed and Overheard Speech

ERIC Educational Resources Information Center

Boderé, Anneleen; Jaspaert, Koen

2017-01-01

Recent research indicates that infants can learn novel words equally well through addressed speech as through overhearing two adult experimenters. The current study examined to which extent six-year-old children learn from overhearing opportunities in regular kindergarten classroom practices. Fifty-three children (M age = 5;6) were exposed to a…

Sugar maple provenance study: West Virginia outplanting - 10-year results

Treesearch

G. W. Wendel; W. J. Gabriel

1980-01-01

After 10 years, survival of sugar maple (Acer saccharum Marsh.) provenances outplanted in West Virginia did not differ significantly. Total height, height growth and dbh measurements were significantly different among provenances. Fifty percent of the trees had major forks below 9.0 feet. Thirty-eight percent of the trees had no forks but 71 percent...

50 Years after Sputnik, America Sees Itself in Another Science Race

ERIC Educational Resources Information Center

Brainard, Jeffrey

2007-01-01

Fifty years ago this month, the Soviet Union launched the world's first artificial satellite, Sputnik 1, an event that transformed American higher education. Americans felt threatened by the "red moon" overhead and communist know-how, and Congress supported a flurry of federal spending that helped to greatly expand the number of American research…

Australian Children with Special Health Care Needs: Social-Emotional and Learning Competencies in the Early Years

ERIC Educational Resources Information Center

Whiteford, Chrystal; Walker, Sue; Berthelsen, Donna

2013-01-01

This study examined the relationship between special health care needs and social-emotional and learning competence in the early years, reporting on two waves of data from the Kindergarten Cohort of "Growing up in Australia: The Longitudinal Study of Australian Children" (LSAC). Six hundred and fifty children were identified through the…

Spatiotemporal Analysis of High-Speed Videolaryngoscopic Imaging of Organic Pathologies in Males

ERIC Educational Resources Information Center

Bohr, Christopher; Kräck, Angelika; Dubrovskiy Denis; Eysholdt, Ulrich; Svec, Jan; Psychogios, Georgios; Ziethe, Anke; Döllinger, Michael

2014-01-01

Purpose: The aim of this study was to identify parameters that would differentiate healthy from pathological organic-based vocal fold vibrations to emphasize clinical usefulness of high-speed imaging. Method: Fifty-five men (M age = 36 years, SD = 20 years) were examined and separated into 4 groups: 1 healthy (26 individuals) and 3 pathological…

Collaborative Problem Solving Skills of 15-Year-Olds: Results from PISA 2015. Data Point. NCES 2017-249

ERIC Educational Resources Information Center

National Center for Education Statistics, 2017

2017-01-01

The Program for International Student Assessment (PISA) is a global education study of 15-year-old students' reading, mathematics, and science literacy and, in 2015, two optional components: financial literacy and collaborative problem solving. Fifty-one education systems administered the collaborative problem solving assessment, including 32 of…

The Kitty Genovese Story in Introductory Psychology Textbooks: Fifty Years Later

ERIC Educational Resources Information Center

Griggs, Richard A.

2015-01-01

Given the many inaccuracies in the original "New York Times" 38-witnesses version of the Kitty Genovese story, this study examined the accuracy of this story in current introductory psychology textbooks, 50 years later. Recent studies have shown that there is no evidence for the following three key features of the original story: (1)…

Cognitive Developmental Levels of Preschool Children in Relation to Peer Relationships

ERIC Educational Resources Information Center

Ogelman, Hülya Gülay; Seçer, Zarife; Önder, Alev

2015-01-01

The purpose of the study is to investigate the cognitive developmental levels of five- to six-year-old preschool children with regard to their peer relationships. The relational survey method was used in the study. One hundred and fifty one children aged five- to six-years-old participated in the study. The Child Behaviour Scale, Peer…

Managing Bipolar Youths in a Psychiatric Inpatient Emergency Service

ERIC Educational Resources Information Center

Masi, Gabriele; Mucci, Maria; Pias, Paola; Muratori, Filippo

2011-01-01

Among the youths referred to our Psychiatric Inpatient Emergency Service, we focused on bipolar disorder (BD), to explore predictive elements for the outcome. Fifty-one patients (30 males, 21 females, age range 8-18 years, mean age 14.2 plus or minus 3.1 years) received a diagnosis of BD, according to historical information, prolonged…

Implementing principles of the integrated control concept 50 years later – current challenges in IPM for arthropod pests

USDA-ARS?s Scientific Manuscript database

Pest management theory and concepts developed fifty years ago as part of the integrated control concept remain at the foundation of IPM today. Implementation of integrated control and subsequently IPM has always been faced with the challenge of carrying out their principles in a rigorous, disciplin...

Semiconducting Metal Oxide Based Sensors for Selective Gas Pollutant Detection

PubMed Central

Kanan, Sofian M.; El-Kadri, Oussama M.; Abu-Yousef, Imad A.; Kanan, Marsha C.

2009-01-01

A review of some papers published in the last fifty years that focus on the semiconducting metal oxide (SMO) based sensors for the selective and sensitive detection of various environmental pollutants is presented. PMID:22408500

Big Bang Day: The Making of CERN (Episode 1)

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2009-10-06

A two-part history of the CERN project. Quentin Cooper explores the fifty-year history of CERN, the European particle physics laboratory in Switzerland. The institution was created to bring scientists together after WW2 .......

Big Bang Day: The Making of CERN (Episode 1)

ScienceCinema

None

2017-12-09

A two-part history of the CERN project. Quentin Cooper explores the fifty-year history of CERN, the European particle physics laboratory in Switzerland. The institution was created to bring scientists together after WW2 .......

Effect of Age on Cost-Effectiveness of Unicompartmental Knee Arthroplasty Compared with Total Knee Arthroplasty in the U.S.

PubMed Central

Ghomrawi, Hassan M.; Eggman, Ashley A.; Pearle, Andrew D.

2015-01-01

Background: Trade-offs between upfront benefits and later risk of revision of unicompartmental knee arthroplasty compared with those of total knee arthroplasty are poorly understood. The purpose of our study was to compare the cost-effectiveness of unicompartmental knee arthroplasty with that of total knee arthroplasty across the age spectrum of patients undergoing knee replacement. Methods: Using a Markov decision analytic model, we compared unicompartmental knee arthroplasty with total knee arthroplasty with regard to lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) from a societal perspective for patients undergoing surgery at forty-five, fifty-five, sixty-five, seventy-five, or eighty-five years of age. Transition probabilities were estimated from the literature; survival, from the Swedish Knee Arthroplasty Register; and costs, from the literature and the Healthcare Cost and Utilization Project (HCUP) database. Costs and QALYs were discounted at 3.0% annually. We conducted sensitivity analyses to test the robustness of model estimates and threshold analyses. Results: For patients sixty-five years of age and older, unicompartmental knee arthroplasty dominated total knee arthroplasty, with lower lifetime costs and higher QALYs. Unicompartmental knee arthroplasty was no longer cost-effective at a $100,000/QALY threshold when total knee arthroplasty rehabilitation costs were reduced by two-thirds or more for these older patients. Lifetime societal savings from utilizing unicompartmental knee arthroplasty in all older patients (sixty-five or older) in 2015 and 2020 were $56 to $336 million and $84 to $544 million, respectively. In the forty-five and fifty-five-year-old age cohorts, total knee arthroplasty had an ICER of $30,300/QALY and $63,000/QALY, respectively. Unicompartmental knee arthroplasty became cost-effective when its twenty-year revision rate dropped from 27.8% to 25.7% for the forty-five-year age group and from 27.9% to 26.7% for the fifty-five-year age group. Conclusions: Unicompartmental knee arthroplasty is an economically attractive alternative in patients sixty-five years of age or older, and modest improvements in implant survivorship could make it a cost-effective alternative in younger patients. PMID:25740030

Utilisation Pattern of Nonspecific Nonsteroidal Anti-Inflammatory Drugs and COX-2 Inhibitors in a Local Health Service Unit in Northeast Italy.

PubMed

Chiroli, S; Chinellato, A; Didoni, G; Mazzi, S; Lucioni, C

2003-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed widely in Italy. They include nonspecific NSAIDs (NS-NSAIDs) and the newly marketed cyclo-oxygenase (COX)-2 specific inhibitors (COXIBs) celecoxib and rofecoxib. The objective of this study was to describe the prescribing patterns for NS-NSAIDs and COXIBs in a local Italian area, analysing an administrative database. We extracted from the database information on subjects who had received at least one reimbursed prescription of an NSAID during the period between 1 January 2001 and 31 December 2001, including age, sex, patient identification code, Anatomical Therapeutic Chemical (ATC) classification system code, strength, formulation, number of packs prescribed, prescription date, and prescription of gastroprotective agents (GPAs) on the same day as the prescription of the NSAID. On the basis of the type of NSAID received, we divided the patients into five cohorts: oral NS-NSAIDs only during the observed year, injectable NS-NSAIDs only, celecoxib only, rofecoxib only, and a combination. For descriptive purposes, we defined three age groups: <40 years, 40-64 years, and >64 years. The duration of exposure to NSAID therapy was calculated using the most commonly prescribed dose for the different drugs. Subjects receiving >/=30 doses per year were defined as "regular users". Analyses included mean age, mean duration of exposure, percentage of regular users, and percentage of GPAs co-prescribed in the different cohorts. NSAIDs were prescribed to 62 059 subjects from a resident population of 365 321 inhabitants; 43.8% received oral NS-NSAIDs only, 22.6% injectable NS-NSAIDs only, 7.2% celecoxib only, 5.2% rofecoxib only, and 22% different regimens of different types of NSAIDs. The mean duration of treatment increased with age in all cohorts; the mean age was 56 years in the NS-NSAID cohort, 61 years in the celecoxib cohort, and 62 years in the rofecoxib cohort (p = 0.01, COXIBs vs NS-NSAIDs). The mean duration of therapy was 11.4 days/year for injectable NS-NSAIDs, 43.8 days/year for rofecoxib, 50.5 days/year for oral NS-NSAIDs, and 53.7 days/year for celecoxib. Fifty-four percent of subjects in the oral NS-NSAID cohort were regular users versus 64% in the rofecoxib and 70% in the celecoxib groups (p = 0.001, COXIBs vs NS-NSAIDs). Co-prescription with GPAs was 9.5% for NS-NSAIDs, 8.4% for rofecoxib, and 7.7% for celecoxib. Analysis of an administrative database in Italy showed a trend suggesting that COXIBs are prescribed to an older population and for a longer period of time than NS-NSAIDs, and that their use is less frequently associated with GPAs.

HYDration and Bicarbonate to Prevent Acute Renal Injury After Endovascular Aneurysm Repair With Suprarenal Fixation: Pilot/Feasibility Randomised Controlled Study (HYDRA Pilot Trial).

PubMed

Saratzis, Athanasios; Chiocchia, Virginia; Jiffry, Ahmad; Hassanali, Neelam; Singh, Surjeet; Imray, Christopher H; Bown, Matthew J; Mahmood, Asif

2018-05-01

Up to 25% of patients undergoing elective endovascular aneurysm repair (EVAR) develop acute kidney injury (AKI), which is associated with short and long-term morbidity and mortality. There is no high quality randomised evidence regarding prevention of EVAR related AKI. A novel AKI prevention strategy for EVAR was devised, based on best evidence and an expert consensus group. This included a bolus of high dose sodium bicarbonate (NaHCO 3 ) immediately before EVAR (1 mL/kg of 8.4% NaHCO 3 ) and standardised crystalloid based hydration pre- and post-EVAR. A pilot/feasibility randomised controlled trial (RCT) was performed in two centres to assess the safety of the intervention, potential impact on AKI prevention, and feasibility of a national RCT; the primary end point was the proportion of eligible patients recruited into the study. AKI was defined using "Kidney Disease Improving Global Outcomes" and "Acute Kidney Injury Network" criteria based on National Institute for Health and Clinical Excellence AKI recommendations, using serum creatinine and hourly urine output. Fifty-eight patients (84% of those screened; median age 75 years [range 57-89 years], 10% female) were randomised to receive the standardised intravenous hydration with (intervention) or without (control) NaHCO 3 . Groups were comparable in terms of AKI risk factors; 56 of 58 participants had a device with suprarenal fixation. Overall, 33% of patients in the control arm developed AKI versus 7% in the intervention arm (as treated analysis). None of the patients receiving NaHCO 3 developed a serious intervention related adverse event; five patients did not attend their 30 day follow-up. Bolus high dose NaHCO 3 and hydration is a promising EVAR related AKI prevention method. This trial has confirmed the feasibility of delivering a definitive large RCT to confirm the efficacy of this novel intervention, in preventing EVAR related AKI. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The Effect of Different Carbapenem Antibiotics (Ertapenem, Imipenem/Cilastatin, and Meropenem) on Serum Valproic Acid Concentrations.

PubMed

Wu, Chien-Chih; Pai, Tsung-Yu; Hsiao, Fei-Yuan; Shen, Li-Jiuan; Wu, Fe-Lin Lin

2016-10-01

Carbapenem antibiotics (CBPMs) may significantly reduce the serum concentration of valproic acid (VPA), but the extent of this effect among various CBPMs is unknown. This study compared the extent and onset of the interactions among ertapenem, imipenem/cilastatin, and meropenem. A 5-year retrospective study was performed. Hospitalized patients over 18 years old who received VPA and a CBPM concurrently were enrolled via the pharmacy computer system. Patients who lacked VPA serum concentration measurements before or during CBPMs' use, had concurrent medication(s) that might interfere with VPA metabolism, or had a history of liver cirrhosis were excluded. Total VPA serum concentrations before and during CBPMs' use and after its discontinuation were recorded, and differences among various CBPMs were analyzed. Fifty-two patients were included in this analysis. Irrespective of the route of administration, VPA serum concentrations were subtherapeutic in 90% of the subjects during CBPMs' use. There was a significant decrease (P < 0.001) in VPA serum concentrations during the use of CBPMs: 72% ± 17%, 42% ± 22%, and 67% ± 19% in the ertapenem (N = 9), imipenem/cilastatin (N = 17), and meropenem (N = 26) groups, respectively. The effect of ertapenem and meropenem on VPA was significantly more expressed than that of imipenem/cilastatin (P < 0.005). The onset of this drug interaction occurred within 24 hours of CBPMs' administration, and VPA serum concentrations returned to 90% of baseline within 7 days of CBPMs' discontinuation along with a 20% increase in VPA dose. Increasing VPA dose during the use of ertapenem or meropenem did not result in elevating VPA serum concentrations to therapeutic levels during the combined therapy period. CBPMs reduced VPA serum concentration within 24 hours of administration by approximately 60%. Ertapenem and meropenem had a greater effect on VPA serum concentration than imipenem/cilastatin. Because of the dramatic reduction of VPA serum concentration during CBPMs' use, concomitant use of VPA and CBPMs should be avoided.

Outcomes of stereotactic body radiotherapy (SBRT) treatment of multiple synchronous and recurrent lung nodules.

PubMed

Owen, Dawn; Olivier, Kenneth R; Mayo, Charles S; Miller, Robert C; Nelson, Kathryn; Bauer, Heather; Brown, Paul D; Park, Sean S; Ma, Daniel J; Garces, Yolanda I

2015-02-18

Stereotactic body radiotherapy (SBRT) is evolving into a standard of care for unresectable lung nodules. Local control has been shown to be in excess of 90% at 3 years. However, some patients present with synchronous lung nodules in the ipsilateral or contralateral lobe or metasynchronous disease. In these cases, patients may receive multiple courses of lung SBRT or a single course for synchronous nodules. The toxicity of such treatment is currently unknown. Between 2006 and 2012, 63 subjects with 128 metasynchronous and synchronous lung nodules were treated at the Mayo Clinic with SBRT. Demographic patient data and dosimetric data regarding SBRT treatments were collected. Acute toxicity (defined as toxicity < 90 days) and late toxicity (defined as toxicity > = 90 days) were reported and graded as per standardized CTCAE 4.0 criteria. Local control, progression free survival and overall survival were also described. The median age of patients treated was 73 years. Sixty five percent were primary or recurrent lung cancers with the remainder metastatic lung nodules of varying histologies. Of 63 patients, 18 had prior high dose external beam radiation to the mediastinum or chest. Dose and fractionation varied but the most common prescriptions were 48 Gy/4 fractions, 54 Gy/3 fractions, and 50 Gy/5 fractions. Only 6 patients demonstrated local recurrence. With a median follow up of 12.6 months, median SBRT specific overall survival and progression free survival were 35.7 months and 10.7 months respectively. Fifty one percent (32/63 patients) experienced acute toxicity, predominantly grade 1 and 2 fatigue. One patient developed acute grade 3 radiation pneumonitis at 75 days. Forty six percent (29/63 patients) developed late effects. Most were grade 1 dyspnea. There was one patient with grade 5 pneumonitis. Multiple courses of SBRT and SBRT delivery after external beam radiotherapy appear to be feasible and safe. Most toxicity was grade 1 and 2 but the risk was approximately 50% for both acute and late effects.

Megathrust earthquakes and sea-level change: A tribute to George Plafker

USGS Publications Warehouse

Freymueller, Jeffrey T.

2015-01-01

For numerous scientific disciplines that contribute to the understanding of megathrust earthquakes, 2014 was an anniversary year of two great, >Mw9, earthquakes; fifty years since the March 27 1964 earthquake in Alaska and ten years since the December 26 2004 Aceh-Andaman earthquake and attendant tsunami. 2014 was also the final year of International Geoscience Programme (IGCP) Project 588 “Preparing for Coastal Change”, which was the latest in the 25 year history of IGCP coastal change research.

The Cognitive Processes Underlying Event-Based Prospective Memory in School-Age Children and Young Adults: A Formal Model-Based Study

ERIC Educational Resources Information Center

Smith, Rebekah E.; Bayen, Ute J.; Martin, Claudia

2010-01-01

Fifty children 7 years of age (29 girls, 21 boys), 53 children 10 years of age (29 girls, 24 boys), and 36 young adults (19 women, 17 men) performed a computerized event-based prospective memory task. All 3 groups differed significantly in prospective memory performance, with adults showing the best performance and with 7-year-olds showing the…

A randomized double-blind trial of two low dose combined oral contraceptives.

PubMed

Bounds, W; Vessey, M; Wiggins, P

1979-04-01

Fifty-five women using Loestrin-20 (20 microgram ethinyl oestradiol and 1 mg norethisterone acetate) as an oral contraceptive have been compared with a like number using Microgynon-30 (30 microgram ethinyl oestradiol and 150 microgram levonorgestrel) in a randomized, double-blind trial. Despite the small sample size, the main finding in the trial is clear-cut; Loestrin-20 provides poor cycle control and is thus less acceptable as an oral contraceptive than Microgynon-30. Although there is also a suggestion that Loestrin-20 may be less effective than Microgynon-30, the difference in the accidental pregnancy rates is not statistically significant.

Aspirin, lysine, mifepristone and doxycycline combined can effectively and safely prevent and treat cancer metastasis: prevent seeds from gemmating on soil

PubMed Central

Xu, Huo; Ma, Ji; Zhu, Yewei; Lu, Yusheng; Wang, Jichuang; Zhang, Ting; Li, Tao; Xie, Jingjing; Xu, Bo; Xie, Fangwei; Gao, Yu; Shao, Jingwei; Tu, Xiaohuang; Jia, Lee

2015-01-01

Recent scientific advances have increased our understanding of the cancer metastatic complexities and provided further impetus for new combination therapies to prevent cancer metastasis. Here, we demonstrated that a combination (HAMPT) of aspirin, lysine, mifepristone and doxycycline can effectively and safely prevent cancer metastasis. The pharmaceutically-formulated HAMPT inhibited adhesion of cancer cells to either endothelial cells or extracellular matrix via down-regulating cell adhesion molecules ICAM-1 and α4-integrin. HAMPT inhibited the cloak effect by activated platelets on cancer cells, thereby interfering adhesion and invasion of cancer cells to the underlying stroma. At the effective concentration, HAMPT induced cancer cells into dormancy with minor inhibition on cell viability. Four-day pretreatment followed by 30-day oral administration of HAMPT (33.5-134 mg/kg) to the mice inoculated with cancer cells produced significant inhibition on cancer metastasis dose-dependently without marked side effects. Fifty-day rat toxicity study with HAMPT at doses (335-1340 mg/kg) 20-fold higher than its therapeutic dose produced no significant toxicity. Interestingly, the acute toxic death could not be reached at the maximum administrable dose (5 g/kg). This proof-of-concept study provides the first conceptual evidence that cancer metastasis can be controlled by using affordable old drugs to restrain circulating tumor cells from gemmating on the metastatic soil without the need for cytotoxicity. PMID:26459390

Poor Immune Responses to a Birth Dose of Diphtheria, Tetanus, and Acellular Pertussis Vaccine

PubMed Central

Halasa, Natasha B.; O’Shea, Alice; Shi, Jian R.; Lafleur, Bonnie J.; Edwards, Kathryn M.

2013-01-01

Objectives To evaluate the safety and immunogenicity of an additional birth dose of diphtheria, tetanus, and acellular pertussis vaccine (DTaP). Study design Fifty infants between 2 to 14 days of age were randomly assigned to receive either DTaP and hepatitis B vaccines (experimental) or hepatitis B alone (control) at birth. At 2, 4, 6, and 17 months of age, DTaP and routine vaccines were administered to both groups. Safety data were collected after each dose, and sera were obtained at birth, 6, 7, 17, and 18 months. Immune responses to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae were measured by enzyme-linked immunosorbent assay; responses to other vaccines were assessed. Results No differences were seen between the 2 groups in either local or systemic reactions; all vaccines were well tolerated. Compared with the control group, infants in the experimental group demonstrated significantly lower geometric mean antibody concentrations for pertussis toxin and pertactin 6, 7, and 18 months, for fimbrae at 6, 7, 17, and 18 months, and for FHA at 18 months, and lower geometric mean antibody concentrations for diphtheria at 7 months. Immune responses to all other vaccine antigens were comparable. Conclusion Administration of an additional dose of DTaP at birth was safe but was associated with a significantly lower response to diphtheria and 3 of 4 pertussis antigens compared with controls. PMID:18534242

Evaluation of fleroxacin (RO 23-6240) as single-oral-dose therapy of culture-proven chancroid in Nairobi, Kenya.

PubMed Central

MacDonald, K S; Cameron, D W; D'Costa, L; Ndinya-Achola, J O; Plummer, F A; Ronald, A R

1989-01-01

Chancroid is gaining importance as a sexually transmitted disease because of its association with transmission of human immunodeficiency virus type 1 (HIV-1). Effective, simply administered therapy for chancroid is necessary. Fleroxacin is effective against Haemophilus ducreyi in vitro. We performed an initial randomized clinical trial to assess the efficacy of fleroxacin for treatment of chancroid in Nairobi, Kenya. Fifty-three men with culture-positive chancroid were randomly assigned to receive either 200 mg (group 1) or 400 mg (group 2) of fleroxacin as a single oral dose. Groups 1 and 2 were similar with regard to severity of disease, bubo formation, and HIV-1 status. A satisfactory clinical response to therapy was noted in 23 of 26 patients (88%) in group 1 and 18 of 23 patients (78%) in group 2. Bacteriological failure occurred in 1 of 26 evaluable patients (4%) in group 1 and 4 of 23 evaluable patients (17%) in group 2. Two of 37 HIV-1-seronegative men (5%) and 3 of 11 HIV-1-infected men (27%) were bacteriological failures. Fleroxacin, 200 or 400 mg as a single oral dose, is efficacious therapy for microbiologically proven chancroid in patients who do not have concurrent HIV-1 infection. Among HIV-1-infected men, a single dose of 200 or 400 mg of fleroxacin is inadequate therapy for chancroid. PMID:2502065

High acceptability of HIV pre-exposure prophylaxis but challenges in adherence and use: qualitative insights from a phase I trial of intermittent and daily PrEP in at-risk populations in Kenya.

PubMed

Van der Elst, Elisabeth Maria; Mbogua, Judie; Operario, Don; Mutua, Gaudensia; Kuo, Caroline; Mugo, Peter; Kanungi, Jennifer; Singh, Sagri; Haberer, Jessica; Priddy, Frances; Sanders, Eduard Joachim

2013-07-01

This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.

A Phase II Study of Intensity Modulated Radiation Therapy to the Pelvis for Postoperative Patients With Endometrial Carcinoma: Radiation Therapy Oncology Group Trial 0418

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jhingran, Anuja, E-mail: ajhingra@mdanderson.org; Winter, Kathryn; Portelance, Lorraine

2012-09-01

Purpose: To determine the feasibility of pelvic intensity modulated radiation therapy (IMRT) for patients with endometrial cancer in a multi-institutional setting and to determine whether this treatment is associated with fewer short-term bowel adverse events than standard radiation therapy. Methods: Patients with adenocarcinoma of the endometrium treated with pelvic radiation therapy alone were eligible. Guidelines for target definition and delineation, dose prescription, and dose-volume constraints for the targets and critical normal structures were detailed in the study protocol and a web-based atlas. Results: Fifty-eight patients were accrued by 25 institutions; 43 were eligible for analysis. Forty-two patients (98%) had anmore » acceptable IMRT plan; 1 had an unacceptable variation from the prescribed dose to the nodal planning target volume. The proportions of cases in which doses to critical normal structures exceeded protocol criteria were as follows: bladder, 67%; rectum, 76%; bowel, 17%; and femoral heads, 33%. Twelve patients (28%) developed grade {>=}2 short-term bowel adverse events. Conclusions: Pelvic IMRT for endometrial cancer is feasible across multiple institutions with use of a detailed protocol and centralized quality assurance (QA). For future trials, contouring of vaginal and nodal tissue will need continued monitoring with good QA and better definitions will be needed for organs at risk.« less

Comparison of the Predictive Validity of Three Questionnaires Measuring Psychological Defenses.

DTIC Science & Technology

1980-05-01

and a mean of 11.2 years (+ 1.20 S.D.) of education . Fifty-four participants had less than 12 years of schooling, 41 had 12 years of schooling, and...major behavioral adjustment probleros. VYears of education " was also used as a measure of behavioral adjustment, as completion of high school may...ofdefenstve-dtMermnce-betwen-theTF, US,-and MC groups using analysis of . variance procedures.,- Years -of, education " was related -to defenses

[Neoadjuvant Chemotherapy Using S-1 for Pancreatic Cancer - Mid-Term Results].

PubMed

Homma, Yuki; Honda, Goro; Sakamoto, Katsunori; Kurata, Masanao; Honjo, Masahiko; Hirata, Yoshihiro; Shinya, Satoshi

2016-10-01

Although surgical resection is the only curative strategy for pancreatic cancer, the prognosis of patients with pancreatic cancer remains poor. Recently, neoadjuvant treatment has been frequently employed as a promising treatment. Here, the mid-term results of neoadjuvant chemoradiotherapy(NACRT)using S-1, which has been performed in our hospital since 2008, are reported. Seventy-nine patients with resectable or borderline resectable pancreatic ductal adenocarcinoma, who had been intended to undergo NACRT treatment using S-1, were enrolled. The NACRT comprised radiotherapy( 1.8 Gy×28 days)and full-dose twice-daily oral S-1 given on the same days as the radiotherapy. The results of the NACRT and pancreatectomy and the patients' prognoses were evaluated. Fifty-five patients(69.6%)underwent pancreatectomy, with no case of mortality. The curative resection rate was 94.5%. Postoperative adjuvant chemotherapy was administered in 46 patients(83.6%). The 3-year survival rates of all 79 patients and 55 pancreatectomy patients were 40.1% and 50.4%, respectively. NACRT using S-1 was found to be feasible, and good mid-term outcomes were obtained. However, analysis of the long-term outcomes and comparisons with other novel anti-cancer drugs are still required.

Trampoline-related injuries.

PubMed

Larson, B J; Davis, J W

1995-08-01

Two hundred and seventeen patients who had sustained an injury during the recreational use of a trampoline were managed in the emergency room of Logan Regional Hospital in Logan, Utah, from January 1991 through December 1992. We retrospectively reviewed the charts and radiographs of these patients to categorize the injuries. Additional details regarding the injuries of seventy-two patients (33 per cent) were obtained by means of a telephone interview with use of a questionnaire. The injuries occurred from February through November, with the peak incidence in July. The patients were eighteen months to forty-five years old (average, ten years old); ninety-four patients (43 per cent) were five to nine years old. Eighty-four patients (39 per cent) sustained a fracture; fifty-four (25 per cent), a sprain or strain; forty-five (21 per cent), a laceration; and thirty-four (16 per cent), a contusion. Fifty-seven injuries (26 per cent) involved the elbow or forearm; forty-six (21 per cent), the head or neck; forty (18 per cent), the ankle or foot; thirty-three (15 per cent), the knee or leg; nineteen (9 per cent), the trunk or back; thirteen (6 per cent), the shoulder or arm; and nine (4 per cent), the wrist or hand. Thirteen patients (6 per cent) had a back injury, but none of them had a permanent neurological deficit. One patient who had an ocular injury was transferred to a tertiary care center. One hundred and fifty-six patients (72 per cent) were evaluated radiographically, fifteen (7 per cent) were admitted to the hospital, and thirteen (6 per cent) had an operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer

PubMed Central

Pötter, Richard; Georg, Petra; Dimopoulos, Johannes C.A.; Grimm, Magdalena; Berger, Daniel; Nesvacil, Nicole; Georg, Dietmar; Schmid, Maximilian P.; Reinthaller, Alexander; Sturdza, Alina; Kirisits, Christian

2011-01-01

Background To analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy (EBRT) ± chemotherapy (ChT). Methods Treatment schedule was EBRT with 45–50.4 Gy ± concomitant cisplatin chemotherapy plus 4 × 7 Gy High Dose Rate (HDR) brachytherapy. Patients were treated in the “protocol period” (2001–2008) with the prospective application of the High Risk CTV concept (D90) and dose volume constraints for organs at risk including biological modelling. Dose volume adaptation was performed with the aim of dose escalation in large tumours (prescribed D90 > 85 Gy), often with inserting additional interstitial needles. Dose volume constraints (D2cc) were 70–75 Gy for rectum and sigmoid and 90 Gy for bladder. Late morbidity was prospectively scored, using LENT/SOMA Score. Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis. Findings One hundred and fifty-six consecutive patients (median age 58 years) with cervix cancer FIGO stages IB–IVA were treated with definitive radiotherapy in curative intent. Histology was squamous cell cancer in 134 patients (86%), tumour size was >5 cm in 103 patients (66%), lymph node involvement in 75 patients (48%). Median follow-up was 42 months for all patients. Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 (44%) patients. Total prescribed mean dose (D90) was 93 ± 13 Gy, D2cc 86 ± 17 Gy for bladder, 65 ± 9 Gy for rectum and 64 ± 9 Gy for sigmoid. Complete remission was achieved in 151/156 patients (97%). Overall local control at 3 years was 95%; 98% for tumours 2–5 cm, and 92% for tumours >5 cm (p = 0.04), 100% for IB, 96% for IIB, 86% for IIIB. Cancer specific survival at 3 years was overall 74%, 83% for tumours 2–5 cm, 70% for tumours >5 cm, 83% for IB, 84% for IIB, 52% for IIIB. Overall survival at 3 years was in total 68%, 72% for tumours 2–5 cm, 65% for tumours >5 cm, 74% for IB, 78% for IIB, 45% for IIIB. In regard to late morbidity in total 188 grade 1 + 2 and 11 grade 3 + 4 late events were observed in 143 patients. G1 + 2/G3 + 4 events for bladder were n = 32/3, for rectum n = 14/5, for bowel (including sigmoid) n = 3/0, for vagina n = 128/2, respectively. Interpretation 3D conformal radiotherapy ± chemotherapy plus image (MRI) guided adaptive intracavitary brachytherapy including needle insertion in advanced disease results in local control rates of 95–100% at 3 years in limited/favourable (IB/IIB) and 85–90% in large/poor response (IIB/III/IV) cervix cancer patients associated with a moderate rate of treatment related morbidity. Compared to the historical Vienna series there is relative reduction in pelvic recurrence by 65–70% and reduction in major morbidity. The local control improvement seems to have impact on CSS and OS. Prospective clinical multi-centre studies are mandatory to evaluate these challenging mono-institutional findings. PMID:21821305

Long-term follow-up in toxic solitary autonomous thyroid nodules treated with radioactive iodine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huysmans, D.A.; Corstens, F.H.; Kloppenborg, P.W.

1991-01-01

The long-term effects of radioiodine treatment on thyroid function in patients with a toxic solitary autonomous thyroid nodule were evaluated. Fifty-two patients received a therapeutic dose of 20 mCi of iodine-131 ({sup 131}I). Duration of follow-up was 10 +/- 4 yr. Follow-up data included a biochemical evaluation of thyroid function. The failure rate (recurrent hyperthyroidism) was 2%. The incidence of hypothyroidism was 6% and was not related to the dose per gram of nodular tissue. Oral administration of 20 mCi of radioiodine is a simple and highly effective method for the treatment of patients with a toxic autonomous thyroid nodule.more » The risk of development of hypothyroidism is low if extranodular uptake of {sup 131}I is prevented. This can be achieved by not treating euthyroid patients, by no longer using injections of exogenous thyroid stimulating hormone in the diagnostic work-up of the patients and by always performing radioiodine imaging shortly before treatment.« less

Symptomatic Radiation Pneumonitis After Accelerated Partial Breast Irradiation Using Three-dimensional Conformal Radiotherapy.

PubMed

Shikama, Naoto; Kumazaki, Y U; Miyazawa, Kazunari; Miyaura, Kazunori; Kato, Shingo; Nakamura, Naoki; Kawamori, Jiro; Shimizuguchi, Takuya; Saito, Naoko; Saeki, Toshiaki

2016-05-01

To examine the relationship between symptomatic radiation pneumonitis and lung dose-volume parameters for patients receiving accelerated partial breast irradiation (APBI) using three dimensional-conformal radiotherapy (3D-CRT). The prescribed radiation dose was 30 Gy in 5 fractions over 10 days. Toxicity was graded according to the Common Terminology Criteria for Adverse Events (version 4.0). Fifty-five patients were enrolled from August 2010 to October 2013 and the median follow-up time was 30 months (range=18-46 months). Three patients (5%) developed grade 2 symptomatic radiation pneumonitis after 3D-CRT APBI. Among 16 patients with ILV10Gy (% ipsilateral lung receiving ≥10 Gy) of 10% or higher, three patients (19%) developed symptomatic radiation pneumonitis. This trend was not observed in any of the patients with ILV10Gy less than 10% (p=0.005). High ILV10Gy might be associated with symptomatic radiation pneumonitis after 3D-CRT APBI. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The Mark of a Dying Star

NASA Image and Video Library

2006-01-19

Six hundred and fifty light-years away in the constellation Aquarius, a dead star about the size of Earth, is refusing to fade away peacefully. NASA Hubble and Spitzer Space Telescopes have captured the complex structure of the Helix nebula.

National child safety seat distribution program evaluation

DOT National Transportation Integrated Search

1999-03-01

The National Child Safety Seat Distribution Program (NCSS) was a multi-year, multi-phase program intended to distribute $8 million in child safety seats to low-income and special needs children in all fifty states. Non-profit organizations that recei...

Humans to Mars: Fifty Years of Mission Planning, 1950-2000

NASA Technical Reports Server (NTRS)

Portree, David S. F.

2001-01-01

Contents of this document include: On the Grand Scale; Earliest NASA Concepts; EMPIRE and After; A Hostile Environment; Apogee; Viking and the Resources of Mars; The Case for Mars; Challengers; Space Exploration Initiative; and Design Reference Mission.

Antimicrobial use: Alternatives

USDA-ARS?s Scientific Manuscript database

For over fifty years, antimicrobials have been used in food animal production to maintain animal health and to increase productivity. The resulting increase in antimicrobial resistance among enteric bacteria has created two principal concerns: 1) the prevalence of drug-resistant pathogens leaves th...

A NICHE FOR ISOTOPIC ECOLOGY

EPA Science Inventory

Fifty years ago, GE Hutchinson defined the ecological niche as a hypervolume in n-dimensional space with environmental variables as axes. Ecologists have recently developed renewed interest in the concept, and technological advances now allow us to use stable isotope analyses to ...

A Comprehensive Lifestyle Peer Group-Based Intervention on Cardiovascular Risk Factors: The Randomized Controlled Fifty-Fifty Program.

PubMed

Gómez-Pardo, Emilia; Fernández-Alvira, Juan Miguel; Vilanova, Marta; Haro, Domingo; Martínez, Ramona; Carvajal, Isabel; Carral, Vanesa; Rodríguez, Carla; de Miguel, Mercedes; Bodega, Patricia; Santos-Beneit, Gloria; Peñalvo, Jose Luis; Marina, Iñaki; Pérez-Farinós, Napoleón; Dal Re, Marian; Villar, Carmen; Robledo, Teresa; Vedanthan, Rajesh; Bansilal, Sameer; Fuster, Valentin

2016-02-09

Cardiovascular diseases stem from modifiable risk factors. Peer support is a proven strategy for many chronic illnesses. Randomized trials assessing the efficacy of this strategy for global cardiovascular risk factor modification are lacking. This study assessed the hypothesis that a peer group strategy would help improve healthy behaviors in individuals with cardiovascular risk factors. A total of 543 adults 25 to 50 years of age with at least 1 risk factor were recruited; risk factors included hypertension (20%), overweight (82%), smoking (31%), and physical inactivity (81%). Subjects were randomized 1:1 to a peer group-based intervention group (IG) or a self-management control group (CG) for 12 months. Peer-elected leaders moderated monthly meetings involving role-play, brainstorming, and activities to address emotions, diet, and exercise. The primary outcome was mean change in a composite score related to blood pressure, exercise, weight, alimentation, and tobacco (Fuster-BEWAT score, 0 to 15). Multilevel models with municipality as a cluster variable were applied to assess differences between groups. Participants' mean age was 42 ± 6 years, 71% were female, and they had a mean baseline Fuster-BEWAT score of 8.42 ± 2.35. After 1 year, the mean scores were significantly higher in the IG (n = 277) than in the CG (n = 266) (IG mean score: 8.84; 95% confidence interval (CI): 8.37 to 9.32; CG mean score: 8.17; 95% CI: 7.55 to 8.79; p = 0.02). The increase in the overall score was significantly larger in the IG compared with the CG (difference: 0.75; 95% CI: 0.32 to 1.18; p = 0.02). The mean improvement in the individual components was uniformly greater in the IG, with a significant difference for the tobacco component. The peer group intervention had beneficial effects on cardiovascular risk factors, with significant improvements in the overall score and specifically on tobacco cessation. A follow-up assessment will be performed 1 year after the final assessment reported here to determine long-term sustainability of the improvements associated with peer group intervention. (Peer-Group-Based Intervention Program [Fifty-Fifty]; NCT02367963). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

First results of a phase I/II dose escalation trial in non-small cell lung cancer using three-dimensional conformal radiotherapy.

PubMed

Belderbos, José S A; De Jaeger, Katrien; Heemsbergen, Wilma D; Seppenwoolde, Yvette; Baas, Paul; Boersma, Liesbeth J; Lebesque, Joos V

2003-02-01

To evaluate the feasibility of dose escalation in non-small cell lung cancer (NSCLC) using three-dimensional conformal radiation therapy. The main eligibility criteria of the trial were: pathologically proven inoperable NSCLC, ECOG performance status or=grade 3 (SWOG), grade 3 early and grade 2 late esophageal toxicity or any other (RTOG) grade 3 or 4 complications). Fifty-five patients were included. Tumor stage was I/II in 47%, IIIA in 33% and IIIB in 20%. The majority of the patients received a dose of 74.3 Gy (n=17) or 81.0 Gy (n=23). Radiation pneumonitis occurred in seven patients: four patients developed a grade 2, two patients grade 3 and one patient a grade 4. Esophageal toxicity was mild. In 50 patients tumor response at 3 months follow-up was evaluable. In six patients a complete response was recorded, in 38 a partial response, five patients had stable disease and one patient experienced progressive disease. Only one patient developed an isolated failure in an uninvolved nodal area. So far the radiation dose was safely escalated to 87.8 Gy in group 1 (lowest rMLD), 81.0 Gy in groups 2 and 3 and 74.3 Gy in group 4. Three-dimensional conformal radiotherapy enables significant dose escalation in NSCLC. The maximum tolerable dose has not yet been reached in any risk group.

Medical students' perspective about role-plays as a teaching strategy in community medicine.

PubMed

Manzoor, Iram; Mukhtar, Fatima; Hashmi, Noreen Rahat

2012-04-01

To assess the students' perspective about role-plays conducted as a teaching methodology in community medicine. A quasi-experimental study. Department of Community Medicine at Fatima Memorial College of Medicine and Dentistry from July to November 2010. A probability technique of simple random sampling was used to collect 63 students from the third and fourth year MBBS who were randomly distributed in five sub-groups. They were variously ascribed the roles of obsceners, participants and helpers. A questionnaire was distributed to collect student's responses. The data was analyzed on SPSS version 17 to compare the responses. Chi-square test was applied and p-value was fixed at < 0.05 as significant. Sixty-three students were selected as participants of this study in which 46 belonged to the fourth year MBBS class (73%) and 17 were third year MBBS students (27%). There were 13 male (20.6%) and 50 female (79.4%) students. Role-plays were identified as most effective method of teaching (n = 25, 37.9%) followed by lectures (n = 17, 25.8%, p = 0.054). Fifty-two students (78.5%) admitted that role-plays improved their knowledge of the subject, 55 (84.6%) said that it will help them in their clinical performance. Fifty-nine participants (89.4%) found role-plays interesting and 49 (74.2%) wanted to incorporate role-plays as a part of curriculum. Fifty-six of the participants (88.9%) agreed that role-plays improved their communication skills. Twenty-one participants (31.8%) believed that it helped them in making acquaintance with the local situation. Forty-six students (76.7%) identified role-plays as a feasible way of andragogy (p = 0.005) and 48 (76.2%) said that it provoked critical thinking about the subject (p = 0.038). Fifty-four students (85.7%) admitted that their attention span was better in role-plays as compared to lectures (p = 0.047). Role-plays were well accepted by the students as an effective teaching methodology and can be incorporated as a part of teaching strategies in Community Medicine.

Quantification of incidental mediastinal and hilar irradiation delivered during definitive stereotactic body radiation therapy for peripheral non-small cell lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, Kate L.; Gomez, Jorge; Nazareth, Daryl P.

2012-07-01

To determine the amount of incidental radiation dose received by the mediastinal and hilar nodes for patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Fifty consecutive patients with NSCLC, treated using an SBRT technique, were identified. Of these patients, 38 had a prescription dose of 60 Gy in 20-Gy fractions and were eligible for analysis. For each patient, ipsilateral upper (level 2) and lower (level 4) paratracheal, and hilar (level 10) nodal regions were contoured on the planning computed tomography (CT) images. Using the clinical treatment plan, dose and volume calculations were performed retrospectivelymore » for each nodal region. SBRT to upper lobe tumors resulted in an average total ipsilateral mean dose of between 5.2 and 7.8 Gy for the most proximal paratracheal nodal stations (2R and 4R for right upper lobe lesions, 2L and 4L for left upper lobe lesions). SBRT to lower lobe tumors resulted in an average total ipsilateral mean dose of between 15.6 and 21.5 Gy for the most proximal hilar nodal stations (10R for right lower lobe lesions, 10 l for left lower lobe lesions). Doses to more distal nodes were substantially lower than 5 Gy. The often substantial incidental irradiation, delivered during SBRT for peripheral NSCLC of the lower lobes to the most proximal hilar lymph nodes may be therapeutic for low-volume, subclinical nodal disease. Treatment of peripheral upper lobe lung tumors delivers less incidental irradiation to the paratracheal lymph nodes with lower likelihood of therapeutic benefit.« less

Effects of Gamma Irradiation on Bacterial Microflora Associated with Human Amniotic Membrane

PubMed Central

Binte Atique, Fahmida; Ahmed, Kazi Tahsin; Asaduzzaman, S. M.; Hasan, Kazi Nadim

2013-01-01

Human amniotic membrane is considered a promising allograft material for the treatment of ocular surface reconstruction, burns, and other skin defects. In order to avoid the transmission of any diseases, grafts should be perfectly sterile. Twenty-five amniotic sacs were collected to determine the microbiological quality of human amniotic membrane, to analyze the radiation sensitivity pattern of the microorganism, and to detect the radiation decimal reduction dose (D10) values. All the samples were found to be contaminated, and the bioburden was ranged from 3.4 × 102 to 1.2 × 105 cfu/g. Initially, a total fifty bacterial isolates were characterized according to their cultural, morphological, and biochemical characteristics and then tested for the radiation sensitivity in an incremental series of radiation doses from 1 to 10 KGy. The results depict gradual decline in bioburden with incline of radiation doses. Staphylococcus spp. were the most frequently isolated bacterial contaminant in tissue samples (44%). The D10 values of the bacterial isolates were ranged from 0.6 to 1.27 KGy. Streptococcus spp. were found to be the highest radioresistant strain with the radiation sterilization dose (RSD) of 11.4 KGy for a bioburden level of 1000. To compare the differences, D10 values were also calculated by graphical evaluations of the data with two of the representative isolates of each bacterial species which showed no significant variations. Findings of this study indicate that lower radiation dose is quite satisfactory for the sterilization of amniotic membrane grafts. Therefore, these findings would be helpful to predict the efficacy of radiation doses for the processing of amniotic membrane for various purposes. PMID:24063009

Minimal percentage of dose received by 90% of the urethra (%UD90) is the most significant predictor of PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer.

PubMed

Tanaka, Nobumichi; Asakawa, Isao; Fujimoto, Kiyohide; Anai, Satoshi; Hirayama, Akihide; Hasegawa, Masatoshi; Konishi, Noboru; Hirao, Yoshihiko

2012-09-14

To clarify the significant clinicopathological and postdosimetric parameters to predict PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer. We studied 200 consecutive patients who received LDR-brachytherapy between July 2004 and November 2008. Of them, 137 patients did not receive neoadjuvant or adjuvant androgen deprivation therapy. One hundred and forty-two patients were treated with LDR-brachytherapy alone, and 58 were treated with LDR-brachytherapy in combination with external beam radiation therapy. The cut-off value of PSA bounce was 0.1 ng/mL. The incidence, time, height, and duration of PSA bounce were investigated. Clinicopathological and postdosimetric parameters were evaluated to elucidate independent factors to predict PSA bounce in hormone-naïve patients who underwent LDR-brachytherapy alone. Fifty patients (25%) showed PSA bounce and 10 patients (5%) showed PSA failure. The median time, height, and duration of PSA bounce were 17 months, 0.29 ng/mL, and 7.0 months, respectively. In 103 hormone-naïve patients treated with LDR-brachytherapy alone, and univariate Cox proportional regression hazard model indicated that age and minimal percentage of the dose received by 30% and 90% of the urethra were independent predictors of PSA bounce. With a multivariate Cox proportional regression hazard model, minimal percentage of the dose received by 90% of the urethra was the most significant parameter of PSA bounce. Minimal percentage of the dose received by 90% of the urethra was the most significant predictor of PSA bounce in hormone-naïve patients treated with LDR-brachytherapy alone.

Unenhanced 320-row multidetector computed tomography of the brain in children: comparison of image quality and radiation dose among wide-volume, one-shot volume, and helical scan modes.

PubMed

Jeon, Sun Kyung; Choi, Young Hun; Cheon, Jung-Eun; Kim, Woo Sun; Cho, Yeon Jin; Ha, Ji Young; Lee, Seung Hyun; Hyun, Hyejin; Kim, In-One

2018-04-01

The 320-row multidetector computed tomography (CT) scanner has multiple scan modes, including volumetric modes. To compare the image quality and radiation dose of 320-row CT in three acquisition modes - helical, one-shot volume, and wide-volume scan - at pediatric brain imaging. Fifty-seven children underwent unenhanced brain CT using one of three scan modes (helical scan, n=21; one-shot volume scan, n=17; wide-volume scan, n=19). For qualitative analysis, two reviewers evaluated overall image quality and image noise using a 5-point grading system. For quantitative analysis, signal-to-noise ratio, image noise and posterior fossa artifact index were calculated. To measure the radiation dose, adjusted CT dose index per unit volume (CTDI adj ) and dose length product (DLP) were compared. Qualitatively, the wide-volume scan showed significantly less image noise than the helical scan (P=0.009), and less streak artifact than the one-shot volume scan (P=0.001). The helical mode showed significantly lower signal-to-noise ratio, with a higher image noise level compared with the one-shot volume and wide-volume modes (all P<0.05). The CTDI adj and DLP were significantly lower in the one-shot volume and wide-volume modes compared with those in the helical scan mode (all P<0.05). For pediatric unenhanced brain CT, both the wide-volume and one-shot volume scans reduced radiation dose compared to the helical scan mode, while the wide-volume scan mode showed fewer streak artifacts in the skull vertex and posterior fossa than the one-shot volume scan.

Radiation dose to patients and image quality evaluation from coronary 256-slice computed tomographic angiography

NASA Astrophysics Data System (ADS)

Chen, Liang-Kuang; Wu, Tung-Hsin; Yang, Ching-Ching; Tsai, Chia-Jung; Lee, Jason J. S.

2010-07-01

The aim of this study is to assess radiation dose and the corresponding image quality from suggested CT protocols which depends on different mean heart rate and high heart rate variability by using 256-slice CT. Fifty consecutive patients referred for a cardiac CT examination were included in this study. All coronary computed tomographic angiography (CCTA) examinations were performed on a 256-slice CT scanner with one of five different protocols: retrospective ECG-gating (RGH) with full dose exposure in all R-R intervals (protocol A), RGH of 30-80% pulsing window with tube current modulation (B), RGH of 78±5% pulsing window with tube current modulation (C), prospective ECG-triggering (PGT) of 78% R-R interval with 5% padding window (D) and PGT of 78% R-R interval without padding window (E). Radiation dose parameters and image quality scoring were determined and compared. In this study, no significant differences were found in comparison on image quality of the five different protocols. Protocol A obtained the highest radiation dose comparing with those of protocols B, C, D and E by a factor of 1.6, 2.4, 2.5 and 4.3, respectively ( p<0.001), which were ranged between 2.7 and 11.8 mSv. The PGT could significantly reduce radiation dose delivered to patients, as compared to the RGH. However, the use of PGT has limitations and is only good in assessing cases with lower mean heart rate and stable heart rate variability. With higher mean heart rate and high heart rate variability circumstances, the RGH within 30-80% of R-R interval pulsing window is suggested as a feasible technique for assessing diagnostic performance.

Necrosis and Apoptosis in Hepatocellular Carcinoma Following Low-Dose Versus High-Dose Preoperative Chemoembolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu Wei, E-mail: dr-lw@163.com; Li Yanhao, E-mail: liyanhao@fimmu.com; He Xiaofeng

Our purpose was to study necrosis and apoptosis of hepatocellular carcinoma (HCC) cells after preoperative transcatheter arterial chemoembolization (TACE) with use of low-dose and high-dose anticancer drugs in HCCs. Fifty-four patients with advanced but surgically resectable HCC were studied. Thirty-four patients who elected to undergo preoperative superselective TACE were randomized to low- and high-dose TACE. Patients in group A (n = 16) received low-dose anticancer drugs: 2 mg mitomycin C (MMC), 10 mg epirubicin (EPI), and 100 mg carboplatin (CBP). Patients in group B (n = 18) were given high doses of anticancer drugs (10 mg MMC, 40 mg EPI,more » and 300 mg CBP). Hepatic resection was subsequently performed. Group C comprised 20 patients who underwent resection without TACE. In all patients the necrosis rates and apoptosis index of tumor cells were evaluated by pathologic examinations and terminal deoxynucleotidyl transferase-mediated nick-end labeling assay. There was no significant difference between group A and group B in tumor response (p > 0.05) after TACE. Necrosis rates in groups A, B, and C were 88.4 {+-} 11.1%, 87.1 {+-} 12.5%, and 7.3 {+-} 3.5%, respectively. There was no significant difference between group A and group B (p > 0.05), while statistical difference was found between group A and group C (p < 0.001) and between group B and group C (p < 0.001). Apoptosis indexes in the three groups were 11.0 {+-} 4.0%, 10.7 {+-} 3.9%, and 5.6 {+-} 2.6%, respectively. Statistical difference exhibited between group A and group C (p < 0.001) and group B versus group C (p < 0.001). No significant difference was observed between group A and group B (p > 0.05). In conclusion, superselective TACE with low- and high-dose chemotherapeutic agents induced similar degrees of cellular apoptosis and necrosis.« less

A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer.

PubMed

Masters, G A; Mauer, A M; Hoffman, P C; Wyka, D; Samuels, B L; Krauss, S A; Watson, S; Golomb, H; Vokes, E E

1998-06-01

We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.

Long-Acting C-Terminal Peptide-Modified hGH (MOD-4023): Results of a Safety and Dose-Finding Study in GHD Children.

PubMed

Zelinska, Nataliya; Iotova, Violeta; Skorodok, Julia; Malievsky, Oleg; Peterkova, Valentina; Samsonova, Lubov; Rosenfeld, Ron G; Zadik, Zvi; Jaron-Mendelson, Michal; Koren, Ronit; Amitzi, Leanne; Raduk, Dmitri; Hershkovitz, Oren; Hart, Gili

2017-05-01

Daily injections are required for growth hormone (GH) replacement therapy, which may cause low compliance as a result of inconvenience and distress in patients. C-terminal peptide-modified human GH (MOD-4023) is developed for once-a-week dosing regimen in GH-deficient (GHD) adults and children. The present trial was a safety and dose-finding study for weekly MOD-4023 in GHD children. A multicenter, open-label, randomized, controlled phase 2 study in children with GHD, evaluating the safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy of three different weekly MOD-4023 doses, compared with daily recombinant human GH (r-hGH). The trial was conducted in 14 endocrinology centers in Europe. Fifty-three prepubertal children with GHD completed 12 months of treatment with either MOD-4023 (N = 42) or r-hGH (N = 11). C-terminal peptide-modified hGH (MOD-4023) was administered weekly at a dose of either 0.25, 0.48, or 0.66 mg/kg/wk and compared with daily hGH at a dose of 0.24 mg/kg/wk. MOD-4023 showed an estimated half-life approximately fivefold to 10-fold longer when compared with daily r-hGH. Insulin-like growth factor (IGF)-I and IGF-binding peptide 3 showed a dose-dependent increase during MOD-4023 treatment. IGF-I standard deviation score for MOD-4023 did not exceed +2. All MOD-4023 cohorts demonstrated adequate catch-up growth. The 0.66 mg/kg/wk dose demonstrated efficacy closest to daily r-hGH. No serious adverse events were observed during MOD-4023 treatment, and its tolerability was consistent with known properties of r-hGH. This study confirms the long-acting properties of MOD-4023 and shows a promising safety and tolerability profile. This provides support for initiation of a phase 3 study in GHD children using a single weekly injection of MOD-4023. Copyright © 2017 by the Endocrine Society

A Phase I Dose-Escalation Study of Danusertib (PHA-739358) Administered as a 24-hour Infusion With and Without G-CSF in a 14-day Cycle in Patients with Advanced Solid Tumors

PubMed Central

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

Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral, Small-Molecule Mitogen-Activated Protein Kinase Kinase 1/2 Inhibitor AZD6244 (ARRY-142886) in Patients With Advanced Cancers

PubMed Central

Adjei, Alex A.; Cohen, Roger B.; Franklin, Wilbur; Morris, Clive; Wilson, David; Molina, Julian R.; Hanson, Lorelei J.; Gore, Lia; Chow, Laura; Leong, Stephen; Maloney, Lara; Gordon, Gilad; Simmons, Heidi; Marlow, Allison; Litwiler, Kevin; Brown, Suzy; Poch, Gregory; Kane, Katie; Haney, Jerry; Eckhardt, S. Gail

2009-01-01

Purpose To assess the tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of the mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancer. Patients and Methods In part A, patients received escalating doses to determine the maximum-tolerated dose (MTD). In both parts, blood samples were collected to assess PK and PD parameters. In part B, patients were stratified by cancer type (melanoma v other) and randomly assigned to receive the MTD or 50% MTD. Biopsies were collected to determine inhibition of ERK phosphorylation, Ki-67 expression, and BRAF, KRAS, and NRAS mutations. Results Fifty-seven patients were enrolled. MTD in part A was 200 mg bid, but this dose was discontinued in part B because of toxicity. The 50% MTD (100 mg bid) was well tolerated. Rash was the most frequent and dose-limiting toxicity. Most other adverse events were grade 1 or 2. The PKs were less than dose proportional, with a median half-life of approximately 8 hours and inhibition of ERK phosphorylation in peripheral-blood mononuclear cells at all dose levels. Paired tumor biopsies demonstrated reduced ERK phosphorylation (geometric mean, 79%). Five of 20 patients demonstrated ≥ 50% inhibition of Ki-67 expression, and RAF or RAS mutations were detected in 10 of 26 assessable tumor samples. Nine patients had stable disease (SD) for ≥ 5 months, including two patients with SD for 19 (thyroid cancer) and 22 (uveal melanoma plus renal cancer) 28-day cycles. Conclusion AZD6244 was well tolerated with target inhibition demonstrated at the recommended phase II dose. PK analyses supported twice-daily dosing. Prolonged SD was seen in a variety of advanced cancers. Phase II studies are ongoing. PMID:18390968

Maternal Sensitivity and Children's Behavior Problems: Examining the Moderating Role of Infant Sleep Duration

ERIC Educational Resources Information Center

Bordeleau, Stephanie; Bernier, Annie; Carrier, Julie

2012-01-01

The current study aimed to examine infant sleep duration as a moderator of the relations between maternal sensitivity and child externalizing and internalizing symptoms, in a prospective longitudinal design. Fifty-five Caucasian infants (33 girls) took part in 2 assessments, at 1 and 4 years. Maternal sensitivity was rated at 1 year, based on…

Does Federal Financial Aid Policy Influence the Institutional Aid Policies of Four-Year Colleges and Universities? An Exploratory Analysis

ERIC Educational Resources Information Center

Hossler, Don; Kwon, Jihye

2015-01-01

There is a dearth of empirical work that examines the relationships between federal financial aid policy and institutional financial aid priorities and expenditures. This study uses Resource Dependency Theory to explore whether changes the amount of financial aid awarded by colleges and universities during the last fifty years are best explained…

78 FR 62430 - Department of Defense (DoD)-Defense Industrial Base (DIB) Voluntary Cyber Security and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

... National Defense Authorization Act for Fiscal Year 2013. Comments DoD published an interim final rule on May 11, 2012 (77 FR 27615). Fifty comments from twelve respondents were received and reviewed by the... year. Public Law 96-354, ``Regulatory Flexibility Act'' (5 U.S.C. 601) It has been certified that 32...

Pathways of Sleep, Affect, and Stress Constellations during the First Year of College: Transition Difficulties of Emerging Adults

ERIC Educational Resources Information Center

Ari, Lilac Lev; Shulman, Shmuel

2012-01-01

One hundred and fifty Israeli first-year college students were assessed twice: during the first semester following the commencement of their undergraduate studies and toward the end of the second semester. At each semester, participants completed web-based daily diaries for seven consecutive days assessing daily sleep, affective mood, stress, and…

So They Want Us to Learn French: Promoting and Opposing Bilingualism in English-Speaking Canada

ERIC Educational Resources Information Center

Hayday, Matthew

2015-01-01

Since the 1960s, bilingualism has become a defining aspect of Canadian identity. And yet, fifty years after the Royal Commission on Bilingualism and Biculturalism was formed and with over forty years of federal government funding and supports for second-language education, relatively few English Canadians speak or choose to speak French. What…

The State of the South 2004. Fifty Years after Brown v. Board of Education

ERIC Educational Resources Information Center

Greene, Alison; Guillory, Ferrel; Lipsitz, Joan; Rubin,Sarah

2004-01-01

State of the South 2004 is the fifth edition in North Carolina Manpower Development Corporation MDC's State of the South series, which examines the region's economic and demographic landscape and how Southerners are faring within it. This edition considers the region through the lens of public education, 50 years after the Supreme Court?s Brown…

'Suddenly the First Fifty Years of My Life Made Sense': Experiences of Older People with Autism

ERIC Educational Resources Information Center

Hickey, Aoife; Crabtree, Jason; Stott, Joshua

2018-01-01

Research on the experience of growing older with autism is very limited. In this study, 13 people with autism aged over 50 years participated in semi-structured interviews about their experiences of diagnosis, social support and getting older. Interviews were analysed using thematic analysis. Three overarching themes were generated: difference,…

Enrollment Management Strategies at Four-Year Open Enrollment Institutions of Higher Education

ERIC Educational Resources Information Center

Santoro, Dana S.

2017-01-01

Enrollment management plans have been researched and documented for the last fifty years and literature verifies that the use of these plans has only become more relevant in the 21st century. Strategies and activities for managing enrollment have been defined and shared for most types of institutions, however, there is limited research on the best…

Measuring site index in the central hardwood region

Treesearch

Robert A. McQuilkin

1989-01-01

Site index is the average height of dominant and codominant trees growing in well-stocked, even-aged stands at a given age called ?index age.? Fifty years is the most commonly used index age in upland hardwoods. Sometimes 25 or 30 years are used for short-rotation bottomland hardwoods. Site index is widely used to indicate site quality because it correlates well with...

Learning about a Level Physics Students' Understandings of Particle Physics Using Concept Mapping

ERIC Educational Resources Information Center

Gourlay, H.

2017-01-01

This paper describes a small-scale piece of research using concept mapping to elicit A level students' understandings of particle physics. Fifty-nine year 12 (16- and 17 year-old) students from two London schools participated. The exercise took place during school physics lessons. Students were instructed how to make a concept map and were…

Interdisciplinary Education and Critical Thinking in Religion and History: The Delivery of Two "Content-Based" Linked Courses

ERIC Educational Resources Information Center

McDougall, Roseanne; LaMonica, Jeffrey

2007-01-01

Primary sources in religion and history enable first year university students to connect "content-based" linked courses in the core curriculum. Fifty-four first year university students in three separate pairs of courses worked in teams to present oral critical reports on texts related to the Reformation, the Enlightenment, and the…

Fostering the Memoir Writing Skills as a Creative Non-Fiction Genre Using a WebQuest Model

ERIC Educational Resources Information Center

Al-Sayed, Rania Kamal Muhammad; Abdel-Haq, Eman Muhammad; El-Deeb, Mervat Abou-Bakr; Ali, Mahsoub Abdel-Sadeq

2016-01-01

The present study aimed at developing the memoir writing skills as a creative non-fiction genre of second year distinguished governmental language preparatory school pupils using the a WebQuest model. Fifty participants from second year at Hassan Abu-Bakr Distinguished Governmental Language School at Al-Qanater Al-Khairia(Qalubia Governorate) were…

Future Trends in San Diego: Population, Income, Employment, Post College Wages and Enrollment.

ERIC Educational Resources Information Center

Barnes, Randy; Armstrong, William B.; Bersentes, Gina; Turingan, Maria

This report contains forecasted data for San Diego through the year 2015 and examines changes that have taken place over the past fifty years. Historically, San Diego population growth rates have been relatively high compared with the rest of the nation. Between 1998 and 2015, the population will not only become larger, it will become more…

"It Is through Others That We Become Ourselves": A Study of Vygotskian Play in Russian and Irish Schools

ERIC Educational Resources Information Center

Murphy, Colette; Doherty, Andrea; Kerr, Karen

2016-01-01

Fifty years after publishing his seminal work on play and its role in child development, Vygotskian theory is still highly influential in education, and particularly in early years. This paper presents two examples of full integration of Vygotskian principles into schools in two very different settings. Both report improvements in learning and in…

A Century of Women's Basketball. From Frailty to Final Four.

ERIC Educational Resources Information Center

Hult, Joan S., Ed.; Trekell, Marianna, Ed.

This book consists of writings which focus on the role of physical educators in the growth, development, and evolution of competitive basketball. It is divided into two parts, "The Early Years of Basketball--l890s-l930s" and "The Second Fifty Years of Basketball--1940s-1980s." Part I contains 3 sections which place basketball…

Fifty Years Later: A Chance to Get ESEA Back on Track

ERIC Educational Resources Information Center

Bishop, Joseph P.; Jackson, John H.

2015-01-01

Looking at the evolution of the Elementary and Secondary Education Act (ESEA) over the last 50 years, this paper argues that many of the racial, social, and economic inequities of 1965 that President Johnson was hoping to address have only been accelerated. It's not only time for a modern rethink on educational equity, but also a much broader set…

Serving the Nation for Fifty Years: 1952 - 2002 Lawrence Livermore National Laboratory [LLNL], Fifty Years of Accomplishments

DOE R&D Accomplishments Database

2002-01-01

For 50 years, Lawrence Livermore National Laboratory has been making history and making a difference. The outstanding efforts by a dedicated work force have led to many remarkable accomplishments. Creative individuals and interdisciplinary teams at the Laboratory have sought breakthrough advances to strengthen national security and to help meet other enduring national needs. The Laboratory's rich history includes many interwoven stories -- from the first nuclear test failure to accomplishments meeting today's challenges. Many stories are tied to Livermore's national security mission, which has evolved to include ensuring the safety, security, and reliability of the nation's nuclear weapons without conducting nuclear tests and preventing the proliferation and use of weapons of mass destruction. Throughout its history and in its wide range of research activities, Livermore has achieved breakthroughs in applied and basic science, remarkable feats of engineering, and extraordinary advances in experimental and computational capabilities. From the many stories to tell, one has been selected for each year of the Laboratory's history. Together, these stories give a sense of the Laboratory -- its lasting focus on important missions, dedication to scientific and technical excellence, and drive to made the world more secure and a better place to live.

The utility of mock oral examinations in preparation for the American Board of Surgery certifying examination.

PubMed

Higgins, Rana M; Deal, Rebecca A; Rinewalt, Daniel; Hollinger, Edward F; Janssen, Imke; Poirier, Jennifer; Austin, Delores; Rendina, Megan; Francescatti, Amanda; Myers, Jonathan A; Millikan, Keith W; Luu, Minh B

2016-02-01

Determine the utility of mock oral examinations in preparation for the American Board of Surgery certifying examination (ABS CE). Between 2002 and 2012, blinded data were collected on 63 general surgery residents: 4th and 5th-year mock oral examination scores, first-time pass rates on ABS CE, and an online survey. Fifty-seven residents took the 4th-year mock oral examination: 30 (52.6%) passed and 27 (47.4%) failed, with first-time ABS CE pass rates 93.3% and 81.5% (P = .238). Fifty-nine residents took the 5th-year mock oral examination: 28 (47.5%) passed and 31 (52.5%) failed, with first-time ABS CE pass rates 82.1% and 93.5% (P = .240). Thirty-eight responded to the online survey, 77.1% ranked mock oral examinations as very or extremely helpful with ABS CE preparation. Although mock oral examinations and ABS CE passing rates do not directly correlate, residents perceive the mock oral examinations to be helpful. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationship among chelator adherence, change in chelators, and quality of life in thalassemia.

PubMed

Trachtenberg, Felicia L; Gerstenberger, Eric; Xu, Yan; Mednick, Lauren; Sobota, Amy; Ware, Hannah; Thompson, Alexis A; Neufeld, Ellis J; Yamashita, Robert

2014-10-01

Thalassemia, a chronic blood disease, necessitates life-long adherence to blood transfusions and chelation therapy to reduce iron overload. We examine stability of health-related quality of life (HRQOL) in thalassemia and adherence to chelation therapy over time, especially after changes in chelator choice. Thalassemia Longitudinal Cohort participants in the USA, UK, and Canada completed the SF-36v2 (ages 14+) and the PF-28 CHQ (parents of children <14 years). Chelation adherence was defined as self-reported percent of doses administered in the last 4 weeks. Two hundred and fifty-eight adults/adolescents (mean 29.7 years) and 133 children (mean 8.5 years) completed a mean of 2.8-years follow-up. Children made few chelator changes, whereas a mean of 2.2 changes was observed among the 37% of adults/adolescents who made chelator changes, mainly due to patient preference or medical necessity. Physical HRQOL improved among those with lower iron burden (better health status) at baseline who made a single change in chelator, but declined among participants with multiple changes and/or high iron burden (worse health status). Mental health improved among participants with lower iron burden, but iron overload was negatively associated with social functioning. Adherence did not significantly change over follow-up except for an increase after a change from deferoxamine (DFO) infusion to oral deferasirox (p = 0.03). Predictors of lower adherence for adults/adolescents at follow-up included side effects, smoking, younger age, problems preparing DFO, increased number of days per week DFO prescribed, and lower physical quality of life . Strategies to balance medical needs with family, work, and personal life may assist in adherence.

Feasibility of Elective Nodal Irradiation (ENI) and Involved Field Irradiation (IFI) in Radiotherapy for the Elderly Patients (Aged ≥ 70 Years) with Esophageal Squamous Cell Cancer: A Retrospective Analysis from a Single Institute.

PubMed

Jing, Wang; Zhu, Hui; Guo, Hongbo; Zhang, Yan; Shi, Fang; Han, Anqin; Li, Minghuan; Kong, Li; Yu, Jinming

2015-01-01

We conducted a retrospective analysis to assess the feasibility of involved field irradiation (IFI) in elderly patients with esophageal squamous cell cancer (ESCC). We performed a retrospective review of the records of elderly patients (≥ 70 years) with unresectable ESCC and no distant metastases who received treatment with radiotherapy between January 2009 and March 2013. According to the irradiation volume, patients were allocated into either the elective nodal irradiation (ENI) group or the IFI group. Overall survival (OS), progression-free survival (PFS) and treatment-related toxicities were compared between the two groups. A total of 137 patients were enrolled. Fifty-four patients (39.4%) were allocated to the ENI group and 83 patients (60.6%) to the IFI group, the median doses in the two groups were 60 Gy and 59.4 Gy, respectively. For the entire group, the median survival time (MST) and PFS were 16 months and 12 months, respectively. The median PFS and 3-year PFS rate in the ENI group were 13 months and 20.6%, compared to 11 months and 21.0% in the IFI groups (p = 0.61). The MST and 3-year OS rate in the ENI and IFI groups were 17 months and 26.4% and 15.5 months and 21.7%, respectively (p = 0.25). The rate of grade ≥ 3 acute irradiation esophagitis in the ENI group was significantly higher than that in the IFI group (18.5% vs. 6.0%; p = 0.027). Other grade ≥ 3 treatment-related toxicities did not significantly differ between the two groups. IFI resulted in decreased irradiation toxicities without sacrificing OS in elderly patients with ESCC.

Pediatric investigation plans for specific immunotherapy: Questionable contributions to childhood health.

PubMed

Rose, Klaus; Kopp, Matthias Volkmar

2015-12-01

Allergen-specific immunotherapy (SIT) is the only disease-modifying treatment for children, adolescents, and adults with allergic diseases. The EU has a combined system of national and EU-wide marketing authorization for all medicines. Germany introduced a new therapy allergen ordinance in 2008. Allergen products manufacturers had to apply for marketing authorization application for the major allergen groups (grass group, birch group, mites group, bee/wasp venom). Due to the EU pediatric regulation, in force since 2007, manufacturers had also to submit a pediatric investigation plan (PIP) for each allergen product. We investigated the allergic rhinoconjunctivitis (ARC) standard PIP, developed jointly by the European Medicines Agency (EMA) and the German Paul Ehrlich Institut (PEI). We analyzed the 118 EMA PIP decisions, looked for SIT trials in children in www.clinicaltrials.gov, and further analyzed EMA/EU justifications. The PIPs request a 1-year dose-finding study in adults, a 5-year placebo-controlled (PC) efficacy & safety (E&S) study in adults, and a 5-year PC E&S study in children. Fifty-eight PIP development programs will have to be performed until 2031. But children benefit even more from SIT for ARC than adults. There is no convincing medical/scientific justification for PC E&S studies in children in the relevant EMA documents. The PIP requirement to withhold effective treatment to thousands of children in the placebo group over a 5-year period raises profound concerns. The EMA justifications are formalistic and lack scientific foundation. A critical academic review of the ARC PIPs and the entire PIP system is urgently needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fifty Years of Silent Service: A Peek Inside the CIA Library.

ERIC Educational Resources Information Center

Newlen, Robert R.

1998-01-01

Describes the CIA (Central Intelligence Agency) library. Highlights include security measures, a day in the life of two CIA librarians, sample reference questions, collection development, the Historical Intelligence Collection, the CIA Web site, and library modernization. (JAK)

Fifty years of obstetrics and gynaecology.

PubMed

Drife, James O

2016-10-01

The term 'obstetrics and gynaecology' now feels like an outmoded name for women's health care. Since the 1960s the specialty has been transformed by social change, technical innovation and medical subspecialization, although the core values of good clinical practice remain unchanged.

The Auto

ERIC Educational Resources Information Center

Novick, Sheldon

1976-01-01

The basic automobile design has persisted for fifty years with innovations only in production and marketing. Complex interrelationships among steel, oil, rubber, road building, and automobile industries perpetuate the "modern Model T's." Efforts to alter design to meet safety and environmental standards face tremendous resistance from a…

Fifty Years of Scholarship in Media Ethics

ERIC Educational Resources Information Center

Christians, Clifford G.

1977-01-01

Describes changing attitudes toward the role of mass media ethics, as reflected in the literature. Available from: Journal of Communication, The Annenberg School of Communications, University of Pennsylvania, 3620 Walnut Street, Philadelphia, PA 19104, $15.00 yr; $4.00 sc. (KS)

Reirradiation of tumors in cats and dogs.

PubMed

Turrel, J M; Théon, A P

1988-08-15

Fifty-one cats and dogs with tumor recurrence after irradiation were treated with a second course of radiotherapy, using either teletherapy or brachytherapy. Eighty-six percent of the tumors had partial or complete response at 2 months after reirradiation. Tumor response was significantly (P = 0.041) affected when the interval between the 2 courses of irradiation was greater than 5 months. The estimated local tumor control rate was 38% at 1 year after reirradiation. Of all the factors examined, complete response at 2 months, reirradiation field size less than or equal to 10 cm2, and reirradiation dose greater than 40 gray emerged as predictors of local tumor control. The estimated overall survival rate was 47% at 2 years. Tumor location had a significant (P = 0.001) influence on overall survival; animals with cutaneous tumors had the longest survival times, and those with oral tumors had the shortest survival times. The other significant (P = 0.001) factor affecting overall survival time was the field size of the reirradiated site. Estimated survival time after reirradiation was 41% at 1 year. Favorable prognostic indicators were complete response at 2 months and location of tumor; animals with skin tumors had a favorable prognosis. The acute effects of reirradiation on normal tissues were acceptable, but 12% of the animals had severe delayed complications. Significant risk of complications after reirradiation was associated with squamous cell carcinoma (P = 0.015) and reirradiated field size greater than 30 cm2 (P = 0.056). When the interval between irradiations was greater than 5 months, the risk of complications was significantly (P = 0.022) lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Retrospective analysis of detomidine infusion for standing chemical restraint in 51 horses.

PubMed

Wilson, D V; Bohart, G V; Evans, A T; Robertson, S; Rondenay, Y

2002-01-01

To assess the effectiveness of a detomidine infusion technique to provide standing chemical restraint in the horse. Retrospective study. Fifty-one adult horses aged 9.5 ± 6.9 years (range 1-23 years) and weighing 575 ± 290.3 kg. Records of horses presented to our clinic over a 3-year period in which a detomidine infusion was used to provide standing chemical restraint were reviewed. Information relating to the types of procedure performed, duration of infusion, drug dosages and adjunct drugs administered was retrieved. Detomidine was administered as an initial bolus loading dose (mean ± SD) of 7.5 ± 1.87 μg kg -1 . The initial infusion rate was 0.6 μg kg -1 minute -1 , and this was halved every 15 minutes. The duration of the infusion ranged from 20 to 135 minutes. Twenty horses received additional detomidine or butorphanol during the procedure. All horses undergoing surgery received local anesthesia or epidural analgesia in addition to the detomidine infusion. A wide variety of procedures were performed in these horses. Detomidine administered by infusion provides prolonged periods of chemical restraint in standing horses. Supplemental sedatives or analgesics may be needed in horses undergoing surgery. An effective method that provides prolonged periods of chemical restraint in standing horses is described. The infusion alone did not provide sufficient analgesia for surgery and a significant proportion of animals required supplemental sedatives and analgesics. Copyright © 2002 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Image-guided radiation therapy for liver tumors: gastrointestinal histology matters.

PubMed

Katsoulakis, Evangelia; Riaz, Nadeem; Cannon, Donald M; Goodman, Karyn; Spratt, Daniel E; Lovelock, Michael; Yamada, Yoshiya

2014-12-01

To describe the safety and efficacy of single-fraction and hypofractionated image-guided radiotherapy techniques for the treatment of large liver tumors. Forty-six patients, with 50 tumors (10 primary liver tumors, 40 liver metastases) from March 2004 to March 2011 were reviewed. The maximal tumor diameter ranged from 1.2 to 11.3 cm (median, 4.2 cm). Eighty-seven percent of patients received prior systemic chemotherapy. Fifty-nine percent had prior invasive local therapy including surgery, ablation, or embolization. Twenty-five lesions were treated with hypofractionated therapy (24 to 30 Gy in 3 to 5 fractions), whereas 19 received a single fraction (18 or 24 Gy). Local control (LC) was calculated using competing risk analysis. Overall survival was calculated by the Kaplan-Meier method. Median follow-up for all patients was 29.8 months (range, 3 to 46 mo). The median survival was 15.4 months. The 1- and 2-year LC rates were 78% and 75%, respectively. Dose and tumor size had no significant effect on tumor progression. The local progression at 1 and 2 years was 29% and 32% for gastrointestinal (GI) histologies versus 0% for non-GI histologies (P=0.02). Tumor volumes larger than 112 cm correlated with decreased survival (P=0.05). Three patients developed late grade 3 GI stricture or ulceration. Image-guided radiotherapy for liver tumors achieves good rates of LC with minimal toxicity at 1 and 2 years even in patients with large or recurrent disease that has been heavily pretreated. GI histology demonstrated decreased LC rates. Further management strategies should be considered in these patients.

Mathematics Intervention for Prevention of Neurocognitive Deficits in Childhood Leukemia

PubMed Central

Moore (Ki), Ida M.; Hockenberry, Marilyn J.; Anhalt, Cynthia; McCarthy, Kathy; Krull, Kevin R.

2011-01-01

Background Despite evidence that CNS treatment is associated with cognitive and academic impairment, interventions to prevent or mitigate these problems are limited. The purpose was to determine if early intervention can prevent declines in mathematics abilities. Procedures Fifty-seven children with ALL were enrolled and randomized to a Mathematics Intervention or Standard Care. Subjects completed neurocognitive assessments prior to the intervention, post intervention, and one year later. Parents received written results and recommendations for use with their school. The Mathematics Intervention was based on Multiple Representation Theory and delivered individually over one year. Results Thirty-two of 57 subjects completed the study and were included in data analyses. These 32 subjects completed all neurocognitive assessments and, for those in the intervention group, 40–50 hours of the mathematics intervention. There were no group differences on relevant demographic variables; risk stratification; number of intrathecal methotrexate injections or high dose systemic methotrexate. Significant improvements in calculation and applied mathematics from baseline to post-intervention (p = 0.003 and 0.002, respectively) and in visual working memory from baseline to one year follow-up (p = 0.02) were observed in the Intervention but not the Standard Care group. Results from repeated measures ANOVA demonstrated significant between group differences for applied mathematics (F[2, 29] 12.47, p<0.001) and visual working memory (F[2 29]= 5.53, p=0.009). Conclusions The Mathematics Intervention improved mathematics abilities and visual working memory compared to standard care. Future studies are needed to translate the Mathematics Intervention into a “virtual” delivery method more readily available to parents and children. PMID:21938763

Mathematics intervention for prevention of neurocognitive deficits in childhood leukemia.

PubMed

Moore, Ida M; Hockenberry, Marilyn J; Anhalt, Cynthia; McCarthy, Kathy; Krull, Kevin R

2012-08-01

Despite evidence that CNS treatment is associated with cognitive and academic impairment, interventions to prevent or mitigate these problems are limited. The purpose was to determine if early intervention can prevent declines in mathematics abilities. Fifty-seven children with ALL were enrolled and randomized to a Mathematics Intervention or Standard Care. Subjects completed neurocognitive assessments prior to the intervention, post-intervention, and 1 year later. Parents received written results and recommendations for use with their school. The Mathematics Intervention was based on Multiple Representation Theory and delivered individually over 1 year. Thirty-two of 57 subjects completed the study and were included in data analyses. These 32 subjects completed all neurocognitive assessments and, for those in the Intervention Group, 40-50 hours of the Mathematics Intervention. There were no group differences on relevant demographic variables; risk stratification; number of intrathecal methotrexate injections; or high dose systemic methotrexate. Significant improvements in calculation and applied mathematics from Baseline to Post-Intervention (P = 0.003 and 0.002, respectively) and in visual working memory from Baseline to 1 year Follow-up (P = 0.02) were observed in the Intervention but not the Standard Care Group. Results from repeated measures ANOVA demonstrated significant between group differences for applied mathematics [F(2,29) = 12.47, P < 0.001] and visual working memory [F(2,29) = 5.53, P = 0.009]. The Mathematics Intervention improved mathematics abilities and visual working memory compared to standard care. Future studies are needed to translate the Mathematics Intervention into a "virtual" delivery method more readily available to parents and children. Copyright © 2011 Wiley Periodicals, Inc.

The Journal of The Experimental Analysis of Behavior at Fifty

PubMed Central

Laties, Victor G

2008-01-01

The Journal of the Experimental Analysis of Behavior was founded in 1958 by a group of male psychologists, mainly from the northeastern USA and connected with either Harvard or Columbia. Fifty years later about 20% of both editors and authors reside outside this country and almost the same proportion is made up of women. Other changes in the journal include having its own website for more than a decade and now publishing online as well as on paper. A recent connection with PubMed Central of the National Library of Medicine has made possible the completely free electronic presentation of the entire archive of about 3,800 articles. PMID:18338677

Is low-dose amitriptyline effective in the management of chronic low back pain? Study protocol for a randomised controlled trial.

PubMed

Urquhart, Donna M; Wluka, Anita E; Sim, Malcolm R; van Tulder, Maurits; Forbes, Andrew; Gibson, Stephen J; Arnold, Carolyn; Fong, Chris; Anthony, Shane N; Cicuttini, Flavia M

2016-10-22

Low back pain is a major clinical and public health problem, with limited evidence-based treatments. Low-dose antidepressants are commonly used to treat pain in chronic low back pain. However, their efficacy is unproven. The aim of this pragmatic, double-blind, randomised, placebo-controlled trial is to determine whether low-dose amitriptyline (an antidepressant) is more effective than placebo in reducing pain in individuals with chronic low back pain. One hundred and fifty individuals with chronic low back pain will be recruited through hospital and private medical and allied health clinics, advertising in local media and posting of flyers in community locations. They will be randomly allocated to receive either low-dose amitriptyline (25 mg) or an active placebo (benztropine mesylate, 1 mg) for 6 months. The primary outcome measure of pain intensity will be assessed at baseline, 3 and 6 months using validated questionnaires. Secondary measures of self-reported low back disability, work absence and hindrance in the performance of paid/unpaid work will also be examined. Intention-to-treat analyses will be performed. This pragmatic, double-blind, randomised, placebo-controlled trial will provide evidence regarding the effectiveness of low-dose antidepressants compared with placebo in reducing pain, disability, work absenteeism and hindrance in work performance in individuals with chronic low back pain. This trial has major public health and clinical importance as it has the potential to provide an effective approach to the management of chronic low back pain. Australian New Zealand Clinical Trials Registry: ACTRN12612000131853 ; registered on 30 January 2012.

Skin-sparing Helical Tomotherapy vs 3D-conformal Radiotherapy for Adjuvant Breast Radiotherapy: In Vivo Skin Dosimetry Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Capelle, Lisa; Warkentin, Heather; MacKenzie, Marc

Purpose: We investigated whether treatment-planning system (TPS)-calculated dose accurately reflects skin dose received for patients receiving adjuvant breast radiotherapy (RT) with standard three-dimensional conformal RT (3D-CRT) or skin-sparing helical tomotherapy (HT). Methods and Materials: Fifty patients enrolled in a randomized controlled trial investigating acute skin toxicity from adjuvant breast RT with 3D-CRT compared to skin-sparing HT, where a 5-mm strip of ipsilateral breast skin was spared. Thermoluminescent dosimetry or optically stimulated luminescence measurements were made in multiple locations and were compared to TPS-calculated doses. Skin dosimetric parameters and acute skin toxicity were recorded in these patients. Results: With HT theremore » was a significant correlation between calculated and measured dose in the medial and lateral ipsilateral breast (r = 0.67, P<.001; r = 0.44, P=.03, respectively) and the medial and central contralateral breast (r = 0.73, P<.001; r = 0.88, P<.001, respectively). With 3D-CRT there was a significant correlation in the medial and lateral ipsilateral breast (r = 0.45, P=.03; r = 0.68, P<.001, respectively); the medial and central contralateral breast (r = 0.62, P=.001; r = 0.86, P<.001, respectively); and the mid neck (r = 0.42, P=.04, respectively). On average, HT-calculated dose overestimated the measured dose by 14%; 3D-CRT underestimated the dose by 0.4%. There was a borderline association between highest measured skin dose and moist desquamation (P=.05). Skin-sparing HT had greater skin homogeneity (homogeneity index of 1.39 vs 1.65, respectively; P=.005) than 3D-CRT plans. HT plans had a lower skin{sub V50} (1.4% vs 5.9%, respectively; P=.001) but higher skin{sub V40} and skin{sub V30} (71.7% vs 64.0%, P=.02; and 99.0% vs 93.8%, P=.001, respectively) than 3D-CRT plans. Conclusion: The 3D-CRT TPS more accurately reflected skin dose than the HT TPS, which tended to overestimate dose received by 14% in patients receiving adjuvant breast RT.« less

Reduction of Intimal Hyperplasia with Re-188-labeled Stents in a Rabbit Model at 7 and 26 Weeks: An Experimental Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tepe, Gunnar, E-mail: gunnar.tepe@med.uni-tuebingen.de; Dietrich, Tobias; Grafen, Franziska

2005-06-15

The aim of this study was to analyze the feasibility of {sup 188}Re-labeled stents to reduce neointimal formation in a rabbit atherosclerosis model and to test the long-term effects at 7 and 26 weeks. Fifty-nine male New Zealand White rabbits were fed a 0.5% cholesterol diet for 4 weeks before balloon angioplasty and insertion of Palmaz stents in the infrarenal aorta. The animals were sacrificed 7 and 26 weeks after stent implantation. Control stents were compared with {sup 188}Re stents: (dose 1) 11.3 {+-} 1.8 MBq; (dose 2) 37.3 {+-} 4.2 MBq, and (dose 3) 80.1 {+-} 7.8 MBq. Eachmore » activity group consisted of a short-term (7 weeks) and a long-term group (26 weeks), resulting in a total of eight study groups. No thrombotic occlusion was observed. The neointimal formation in the control group was 2.11 [95% confidence interval (CI): 0.68-6.52] mm{sup 2} at 7 weeks and 2.10 (0.62-7.11) at 26 weeks. In the treatment groups, neointima reduction was detectable at 7 weeks [dose 1: 0.33 (0.09-1.22) mm{sup 2}; dose 2: 0.17 (0.05-0.57) mm{sup 2}; dose 3: 0.03 (0.01-0.13) mm{sup 2}]. After 26 weeks, a catch-up of neointimal formation in the radioactive groups was most obvious in the low-dose group [dose 1: 0.80 (0.28-2.29) mm{sup 2}; dose 2: 0.18([0.06-0.52) mm{sup 2}; dose 3: 0.50 (0.17-1.42) mm{sup 2}]. Compared to the long-term control group, neointimal reduction was still >60%. No induction of neointimal formation was observed at the edges of the stents. Radiation resulted in delayed re-endothelialization. {sup 188}Re stents were capable to reduce intimal hyperplasia and did not cause thrombosis. The edge effect, which was the major limitation of {sup 32}P stents, was not observed in {sup 188}Re stents.« less

Screening and evaluation of anticancer agents.

PubMed

Zee-Cheng, R K; Cheng, C C

1988-02-01

The screening and evaluation procedures for the development of anticancer agents indicated that the entire process is a rather difficult task. This is particularly true in choosing screening models and criteria for activity. If the criteria were set too low, then some clinically false-positive results may be faced; and if the criteria were set too high, some agents could be missed which might be effective against certain types of human cancer. Presently, active compounds are selected by prescreening and screening against transplanted mouse tumors and human tumor xenografts as well as by the in vitro systems. Xenografts of human tumor in athymic nude animals represent metabolic characteristics of human malignant disease which appear to be of value in the preclinical screening. Human tumor cloning assays have gained increased attention as a promising in vitro test system for the screening as well as for the prediction of patient responses. Application of chemosensitivity tests in the prediction of the responses of individuals to chemotherapy, especially in the identification of drug resistant tumors are, in general, quite reliable. Human tumor xenografts, human tumor cloning assays and chemosensitivity tests may be regarded as the major impetus in screening during the past decade. After promising agents are selected from the screening procedures, before the filing of an investigational new drug application, the preclinical toxicology and pharmacology should be completed. Information on the nature of toxicity, dose-response effects, and dose schedule are necessary for predicting the effects of the drug in man. The new drugs then go through three phases of clinical trials to assure safety, effectiveness, and reliability of the drugs. During the past fifteen years eight-three antineoplastic drugs were evaluated clinically under the NCI sponsorship and twenty-four are active in at least one disease. Among these active drugs, eleven possess novel clinical structure, the remaining thirteen are analogues of known active compounds already in clinical trials. After an investigational anticancer drug is approved by the U.S. Food and Drug Administration it becomes a commercial product on the market and the benefits can be shared by the general public. The time required for evaluation and development from the first discovery of activity to final FDA approval for fifty-two therapeutic drugs are tabled. The average interval is 8.8 years, but in the 1950s the average was only 2.8 years, in the 1960s, 6.5 years; in the 1970s, 13.9 years; and in the 1980s, 16.0 years. This reflects the increasing stricter requirements for an antineoplastic drug to be officially recognize

Diversity and abundance of phosphonate biosynthetic genes in nature

USDA-ARS?s Scientific Manuscript database

Phosphonates, molecules containing direct C-P bonds, comprise a structurally diverse class of natural products with interesting and useful biological properties. Although their synthesis in protozoa was discovered more than fifty years ago, the extent and diversity of phosphonate production in natur...

A Survey of Pediatric CT Protocols and Radiation Doses in South Korean Hospitals to Optimize the Radiation Dose for Pediatric CT Scanning

PubMed Central

Hwang, Jae-Yeon; Do, Kyung-Hyun; Yang, Dong Hyun; Cho, Young Ah; Yoon, Hye-Kyung; Lee, Jin Seong; Koo, Hyun Jung

2015-01-01

Abstract Children are at greater risk of radiation exposure than adults because the rapidly dividing cells of children tend to be more radiosensitive and they have a longer expected life time in which to develop potential radiation injury. Some studies have surveyed computed tomography (CT) radiation doses and several studies have established diagnostic reference levels according to patient age or body size; however, no survey of CT radiation doses with a large number of patients has yet been carried out in South Korea. The aim of the present study was to investigate the radiation dose in pediatric CT examinations performed throughout South Korea. From 512 CT (222 brain CT, 105 chest CT, and 185 abdominopelvic CT) scans that were referred to our tertiary hospital, a dose report sheet was available for retrospective analysis of CT scan protocols and dose, including the volumetric CT dose index (CTDIvol), dose-length product (DLP), effective dose, and size-specific dose estimates (SSDE). At 55.2%, multiphase CT was the most frequently performed protocol for abdominopelvic CT. Tube current modulation was applied most often in abdominopelvic CT and chest CT, accounting for 70.1% and 62.7%, respectively. Regarding the CT dose, the interquartile ranges of the CTDIvol were 11.1 to 22.5 (newborns), 16.6 to 39.1 (≤1 year), 14.6 to 41.7 (2–5 years), 23.5 to 44.1 (6–10 years), and 31.4 to 55.3 (≤15 years) for brain CT; 1.3 to 5.7 (≤1 year), 3.9 to 6.8 (2–5 years), 3.9 to 9.3 (6–10 years), and 7.7 to 13.8 (≤15 years) for chest CT; and 4.0 to 7.5 (≤1 year), 4.2 to 8.9 (2–5 years), 5.7 to 12.4 (6–10 years), and 7.6 to 16.6 (≤15 years) for abdominopelvic CT. The SSDE and CTDIvol were well correlated for patients <5 years old, whereas the CTDIvol was lower in patients ≥6 years old. Our study describes the various parameters and dosimetry metrics of pediatric CT in South Korea. The CTDIvol, DLP, and effective dose were generally lower than in German and UK surveys, except in certain age groups. PMID:26683922

Evaluating the Role of Writing in the First and Second Year University Foreign Language Curriculum

ERIC Educational Resources Information Center

Hubert, Michael D.

2014-01-01

Approaches to foreign language (FL) instruction have changed a great deal in the past fifty years, the most fundamental change being the shift from a focus solely on language form to a focus on communicative competence (CC). Although most FL instructors now appear to focus on CC in the teaching of speaking, they do not necessarily apply CC to…

Relationships between Perceptual-Motor Skills and Postural Balance in Nine Years Old Boys

ERIC Educational Resources Information Center

Atilgan, Oya Erkut

2012-01-01

The aim of this study is to investigate relationship between static-dynamic balance performance and two-hand coordination, reaction time, anthropometric measurements and leg strength. Fifty voluntary male children (age: 9.29 plus or minus 1.11 years, height: 138.86 plus or minus 7.86 cm, weight: 35.20 plus or minus 9.2 kg) who did not exercise…

Alcohol and Cannabis: Young People Talking about How Parents Respond to Their Use of These Two Drugs

ERIC Educational Resources Information Center

Highet, Gill

2005-01-01

In recent years, there has been increasing concern over rising levels of alcohol and cannabis use among young people. This paper reports findings from a qualitative investigation of young people's cannabis-related beliefs and behaviour. Fifty-nine boys and girls aged 13 to 15 years were interviewed, mostly in self-selected friendship pairs, in six…

C. H. McCloy Lecture: Fifty Years of Advancements in Fitness and Activity Research

ERIC Educational Resources Information Center

Corbin, Charles B.

2012-01-01

Over the past 50 years progress in fitness and activity research has been influenced by social events, technical innovations, and changes in the field of physical education and kinesiology. The conventional wisdom of the 1950s yielded to a new wisdom based on research evidence. The author's research, as well as the research of others, from 1960 to…

Fifty years of wilderness science: An international perspective

Treesearch

Steve Carver; Steve McCool; Zdenka Krenova; Mark Fisher; Stephen Woodley

2014-01-01

The 50th Anniversary of the U.S. Wilderness Act is a cause for celebration, not least of which is the scientific use recognized in Section 4(b) of the act. This year also marks the 20th anniversary of publication of the International Journal of Wilderness (IJW). IJW plays a unique role in wilderness stewardship, science, and advocacy, providing a forum for presentation...

Employment among Spinal Cord Injured Patients Living in Turkey: A Cross-Sectional Study

ERIC Educational Resources Information Center

Gunduz, Berrin; Erhan, Belgin; Bardak, Ayse Nur

2010-01-01

The aim of this study was to determine the rate of employment and to establish the factors affecting vocational status in spinal cord injured patients living in Turkey. One hundred and fifty-two traumatic spinal cord injured patients older than 18 years with injury duration of at least 1 year and living in the community were included in the study;…

Survey of the States: Economic and Personal Finance Education in Our Nation's Schools in 2004. A Report Card

ERIC Educational Resources Information Center

National Council on Economic Education (NJ1), 2005

2005-01-01

This is the fourth biennial survey on the state of economic and personal finance education in the fifty states conducted by the National Council on Economic Education (NCEE). NCEE conducts these surveys to gauge how the state standards, their implementation, and state testing change from year to year. Since the last survey, published April 2003,…

Black, White, Greek...Like Who?: Howard University Student Perceptions of a White Fraternity on Campus

ERIC Educational Resources Information Center

Hughey, Matthew W.

2006-01-01

On March 2, 1867, the Historically Black College or University (HBCU) Howard University (HU) was founded in Washington, D. C. Almost exactly one year later, the all white fraternity of Pi Kappa Alpha was founded at the University of Virginia. Over 100 years later, on February 18 2006, fifty-five HU students became charter members of Pi Kappa Alpha…

A model immunization programme to control Japanese encephalitis in Viet Nam.

PubMed

Yen, Nguyen Thu; Liu, Wei; Hanh, Hoang Duc; Chang, Na Yoon; Duong, Tran Nhu; Gibbons, Robert V; Marks, Florian; Thu, Nghiem Anh; Hong, Nguyen Minh; Park, Jin Kyung; Tuan, Pham Anh; Nisalak, Ananda; Clemens, John D; Xu, Zhi-Yi

2015-03-01

In Viet Nam, an inactivated, mouse brain-derived vaccine for Japanese encephalitis (JE) has been given exclusively to ≤ 5 years old children in 3 paediatric doses since 1997. However, JE incidence remained high, especially among children aged 5-9 years. We conducted a model JE immunization programme to assess the feasibility and impact of JE vaccine administered to 1-9 year(s) children in 3 standard-dose regimen: paediatric doses for children aged <3 years and adult doses for those aged ≥ 3 years. Of the targeted children, 96.2% were immunized with ≥ 2 doses of the vaccine. Compared to the national immunization programme, JE incidence rate declined sharply in districts with the model programme (11.32 to 0.87 per 100,000 in pre-versus post-vaccination period). The rate of reduction was most significant in the 5-9 years age-group. We recommend a policy change to include 5-9 years old children in the catch-up immunization campaign and administer a 4th dose to those aged 5-9 years, who had received 3 doses of the vaccine during the first 2-3 years of life.

A Model Immunization Programme to Control Japanese Encephalitis in Viet Nam

PubMed Central

Yen, Nguyen Thu; Hanh, Hoang Duc; Chang, Na Yoon; Duong, Tran Nhu; Gibbons, Robert V.; Marks, Florian; Thu, Nghiem Anh; Hong, Nguyen Minh; Park, Jin Kyung; Tuan, Pham Anh; Nisalak, Ananda; Clemens, John D.; Xu, Zhi-yi

2015-01-01

ABSTRACT In Viet Nam, an inactivated, mouse brain-derived vaccine for Japanese encephalitis (JE) has been given exclusively to ≤5 years old children in 3 paediatric doses since 1997. However, JE incidence remained high, especially among children aged 5-9 years. We conducted a model JE immunization programme to assess the feasibility and impact of JE vaccine administered to 1-9 year(s) children in 3 standard-dose regimen: paediatric doses for children aged <3 years and adult doses for those aged ≥3 years. Of the targeted children, 96.2% were immunized with ≥2 doses of the vaccine. Compared to the national immunization programme, JE incidence rate declined sharply in districts with the model programme (11.32 to 0.87 per 100,000 in pre-versus post-vaccination period). The rate of reduction was most significant in the 5-9 years age-group. We recommend a policy change to include 5-9 years old children in the catch-up immunization campaign and administer a 4th dose to those aged 5-9 years, who had received 3 doses of the vaccine during the first 2-3 years of life. PMID:25995736

Opening-wedge high tibial osteotomy with a locked low-profile plate: surgical technique.

PubMed

Kolb, Werner; Guhlmann, Hanno; Windisch, Christoph; Koller, Heiko; Grützner, Paul; Kolb, Klaus

2010-09-01

High tibial osteotomy has been recognized as a beneficial treatment for osteoarthritis of the medial compartment of the knee. The purpose of this prospective study was to assess the short-term results of opening-wedge high tibial osteotomies with locked plate fixation. From September 2002 to November 2005, fifty-one consecutive medial opening-wedge high tibial osteotomies were performed. The mean age of the patients at the time of the index operation was forty-nine years. The preoperative and postoperative factors analyzed included the grade of arthritis of the tibiofemoral compartment (the Ahlbäck radiographic grade), the anatomic tibiofemoral angle, patellar height, the Hospital for Special Surgery rating system score, and the Lysholm and Gillquist knee score. Postoperatively, one superficial wound infection occurred. Fifty of the fifty-one osteotomies healed after an average period of 12.9 weeks (range, eight to sixteen weeks) without bone grafts. A nonunion developed in a sixty-two-year-old patient who was a cigarette smoker. The average postoperative tibiofemoral angle was 9° of valgus. Forty-nine patients were followed for a mean of fifty-two months. The average score on the Hospital for Special Surgery rating system was 86 points at the time of the most recent follow-up. The rating was excellent in twenty-eight patients (57%), good in twelve (24%), fair in four (8%), and poor in five (10%). The average score on the Lysholm and Gillquist knee-scoring scale was 83 points. According to these scores, the outcome was excellent in nine patients (18%), good in thirty-one (63%), fair in three (6%), and poor in six (12%). Four knees failed after an average of thirty-six months. Our results suggest that an opening-wedge high tibial osteotomy with locked plate fixation allows a correct valgus angle to be achieved with good short-term results.

Spermatogenetic disorders in adult rats exposed to tributyltin chloride during puberty.

PubMed

Yu, Wook Joon; Lee, Beom Jun; Nam, Sang Yoon; Kim, Young Chul; Lee, Yong Soon; Yun, Young Won

2003-12-01

Adverse effects of tributyltin (TBT) chloride were investigated on the reproductive system in male adult rats as exposed during puberty. Fifty Sprague-Dawley rats at the age of 35 days were assigned to five different groups: negative control receiving vehicle, methyltestosterone (10 mg/kg B.W.), and TBT chloride treatments (5, 10, and 20 mg/kg B.W.). Animals were treated by oral gavage for ten consecutive days and sacrificed at 5 weeks after final treatment. The treatment of TBT chloride at the high dose of 20 mg/kg B.W. significantly decreased homogenization-resistant testicular sperm counts (p<0.05). The TBT chloride treatment at the doses of 10 and 20 mg/kg B.W. also significantly decreased caudal epididymal sperm counts (p<0.01). Some of motion kinematic parameters (motility, mean angular displacement, lateral head displacement, and dance) of sperms retrieved from vasa deference were significantly decreased in rats treated with the TBT chloride at the dose of 20 mg/kg B.W. (p<0.05). These results provide a further evidence that an exposure to TBT chloride during pubertal period in male rats produces spermatogenic disorders characterized by decreasing testicular and epididymal sperm counts and some motion parameters of sperms in the vasa deference.

The relationship of thyroid cancer with radiation exposure from nuclear weapon testing in the Marshall Islands.

PubMed

Takahashi, Tatsuya; Schoemaker, Minouk J; Trott, Klaus R; Simon, Steven L; Fujimori, Keisei; Nakashima, Noriaki; Fukao, Akira; Saito, Hiroshi

2003-03-01

The US nuclear weapons testing program in the Pacific conducted between 1946 and 1958 resulted in radiation exposure in the Marshall Islands. The potentially widespread radiation exposure from radio-iodines of fallout has raised concerns about the risk of thyroid cancer in the Marshallese population. The most serious exposures and its health hazards resulted from the hydrogen-thermonuclear bomb test, the Castle BRAVO, on March 1, 1954. Between 1993 and 1997, we screened 3,709 Marshallese for thyroid disease who were born before the BRAVO test. It was 60% of the entire population at risk and who were still alive at the time of our examinations. We diagnosed 30 thyroid cancers and found 27 other study participants who had been operated for thyroid cancer before our screening in this group. Fifty-seven Marshallese born before 1954 (1.5%) had thyroid cancer or had been operated for thyroid cancer. Nearly all (92%) of these cancers were papillary carcinoma. We derived estimates of individual thyroid dose proxy from the BRAVO test in 1954 on the basis of published age-specific doses estimated on Utirik atoll and 137Cs deposition levels on the atolls where the participants came from. There was suggestive evidence that the prevalence of thyroid cancer increased with category of estimated dose to the thyroid.

Addition of Ceftriaxone and Amikacin to a Ciprofloxacin plus Metronidazole Regimen for Preventing Infectious Complications of Transrectal Ultrasound-Guided Prostate Biopsy: A Randomized Controlled Trial

PubMed Central

Izadpanahi, Mohammad-Hossein; Majidi, Seyed Mahmood; Khorrami, Mohammad-Hatef; Mohammadi-Sichani, Mehrdad

2017-01-01

Background. The objective of this study was to evaluate the efficacy of adding single doses of ceftriaxone and amikacin to a ciprofloxacin plus metronidazole regimen on the reduction of infectious complications following transrectal ultrasound-guided prostate biopsy (TRUS Bx). Materials and Methods. Four hundred and fifty patients who were candidates for TRUS Bx were divided into two groups of 225 each. The control group received ciprofloxacin 500 mg orally every 12 hours together with metronidazole 500 mg orally every 8 hours from the day prior to the procedure until the fifth postoperative day. In the second group, single doses of ceftriaxone 1 g by intravenous infusion and amikacin 5 mg/kg intramuscularly were administered 30–60 minutes before TRUS Bx in addition to the oral antimicrobials described for group 1. The incidence of infection was compared between the groups. Results. The incidence of infectious complications in the intervention group was significantly lower than that in the control group (4.6% versus 0.9%, p = 0.017). Conclusion. The addition of single doses of intramuscular amikacin and intravenously infused ceftriaxone to our prophylactic regimen of ciprofloxacin plus metronidazole resulted in a statistically significant reduction of infectious complications following TRUS Bx. PMID:28167960

Addition of Ceftriaxone and Amikacin to a Ciprofloxacin plus Metronidazole Regimen for Preventing Infectious Complications of Transrectal Ultrasound-Guided Prostate Biopsy: A Randomized Controlled Trial.

PubMed

Izadpanahi, Mohammad-Hossein; Nouri-Mahdavi, Kia; Majidi, Seyed Mahmood; Khorrami, Mohammad-Hatef; Alizadeh, Farshid; Mohammadi-Sichani, Mehrdad

2017-01-01

Background. The objective of this study was to evaluate the efficacy of adding single doses of ceftriaxone and amikacin to a ciprofloxacin plus metronidazole regimen on the reduction of infectious complications following transrectal ultrasound-guided prostate biopsy (TRUS Bx). Materials and Methods. Four hundred and fifty patients who were candidates for TRUS Bx were divided into two groups of 225 each. The control group received ciprofloxacin 500 mg orally every 12 hours together with metronidazole 500 mg orally every 8 hours from the day prior to the procedure until the fifth postoperative day. In the second group, single doses of ceftriaxone 1 g by intravenous infusion and amikacin 5 mg/kg intramuscularly were administered 30-60 minutes before TRUS Bx in addition to the oral antimicrobials described for group 1. The incidence of infection was compared between the groups. Results. The incidence of infectious complications in the intervention group was significantly lower than that in the control group (4.6% versus 0.9%, p = 0.017). Conclusion. The addition of single doses of intramuscular amikacin and intravenously infused ceftriaxone to our prophylactic regimen of ciprofloxacin plus metronidazole resulted in a statistically significant reduction of infectious complications following TRUS Bx.

Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

PubMed

Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

2013-03-01

Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

[Study on effect of Jiangtang decoction on AGEs-RAGE and oxidative stress in KK-Ay mice].

PubMed

Hong, Jin-Ni; Li, Wei-Wei; Fu, Hong; Wang, Xue-Mei

2017-07-01

To elucidate the efficacy of Jiangtang decoction(JTD) on AGEs-RAGE and oxidative stress in type 2 diabetic model KK-Ay mice. Fifty KK-Ay mice were randomly divided into 5 groups as follows： model group, metformin group, low-dose, medium-dose and high-dose of JTD group, with 10 C57BL/6J as normal group. All groups are orally administrated with equal distilled water, 250 mg•kg⁻¹ metformin hydrochloride, 2, 4,8 g•kg⁻¹ JTD, equal distilled water respectively, once per day for 12 weeks. Alanine aminotransferase(ALT), creatinine(CREA), urea nitrogen(BUN),advanced glycation end products(AGEs) and receptor of glycation end products(RAGE) in blood or urine were measured during the experiments. Furthermore, on the day of the sacrifice, kidney was collected, and electronic microscopy and immunohistochemistry were performed to evaluate the protective renal effect of JTD. In addition, the levels of AGEs, RAGE, Cata-lase(CAT) and superoxide dismutase(SOD) were assessed by Western blot, Real-time PCR or ELISA to analyze the efficacy of JTD. This study demonstrated that JTD might protect kidney of KK-Ay by down-regulating the expression of AGEs, RAGE and oxidative stress. Copyright© by the Chinese Pharmaceutical Association.

A preliminary study comparing methadone and buprenorphine in patients with chronic pain and coexistent opioid addiction.

PubMed

Neumann, Anne M; Blondell, Richard D; Jaanimägi, Urmo; Giambrone, Amanda K; Homish, Gregory G; Lozano, Jacqueline R; Kowalik, Urszula; Azadfard, Mohammadreza

2013-01-01

Patients with opioid addiction who receive prescription opioids for treatment of nonmalignant chronic pain present a therapeutic challenge. Fifty-four participants with chronic pain and opioid addiction were randomized to receive methadone or buprenorphine/naloxone. At the 6-month follow-up examination, 26 (48.1%) participants who remained in the study noted a 12.75% reduction in pain (P = 0.043), and no participants in the methadone group compared to 5 in the buprenorphine group reported illicit opioid use (P = 0.039). Other differences between the two conditions were not found. Long-term, low-dose methadone or buprenorphine/naloxone treatment produced analgesia in participants with chronic pain and opioid addiction.