Testing Quantum Electrodynamics with Exotic Atoms.

Precision study of few-electron, high-Z ions is a privileged field for probing high-field, bound-state quantum electrodynamics (BSQED). However, the accuracy of such tests is plagued by nuclear uncertainties, which are often larger than the BSQED effects under investigation. We propose an alternative method with exotic atoms and show that transitions may be found between circular Rydberg states where nuclear contributions are vanishing while BSQED effects remain large. When probed with newly available quantum sensing detectors, these systems offer gains in sensitivity of 1 to 2 orders of magnitude, while the mean electric field largely exceeds the Schwinger limit.

Satisfaction with end-of-life care: a longitudinal study of patients and their family caregivers in the last months of life.

To determine whether and how ratings of satisfaction with end-of-life (EOL) care change over time and across settings, we administered a satisfaction questionnaire to patients 55 years and older with advanced medical disease and their family caregivers (FCGs). We re-interviewed approximately every two months for a maximum of four visits. Overall, 97 patients and 68 FCGs completed a baseline interview; 57 and 40 completed two interviews, 35 and 22 completed three, and 15 and 10 completed four. Patient satisfaction increased over time and in three of the six questionnaire domains, but this was largely confounded with the location of interview. Satisfaction scores were greater among patients whose baseline interviews occurred at home. FCGs reported increased satisfaction over time; members of the subgroup that cared for patients who died during the study were less satisfied in the spirituality domain during bereavement than prior to their relative's death. Satisfaction with care tends to vary based on location of interview and may vary across time with respect to certain aspects of EOL care.

5-hydroxytryptamine-3 receptor antagonist with or without short-course dexamethasone in the prophylaxis of radiation induced emesis: a placebo-controlled randomized trial of the National Cancer Institute of Canada Clinical Trials Group (SC19).

PURPOSE: To evaluate the effectiveness of prophylactic dexamethasone for the control of radiation induced emesis (RIE) when added to ondansetron during days 1 to 5 of fractionated radiotherapy. The study had two hypotheses: ondansetron and dexamethasone could provide superior control of RIE over ondansetron alone during the prophylactic period and; the combination could provide sustained control of RIE during subsequent fractions of radiotherapy. PATIENTS AND METHODS: Between May 2001 to Jan 2004, 211 patients receiving radiotherapy (> or = 15 fractions) to the upper abdomen were randomly assigned to receive ondansetron 8 mg bid with either dexamethasone 4 mg daily or placebo during fractions 1 to 5. Rescue antiemetics were provided. RESULTS: During the prophylactic period there was a trend for improved complete control of nausea in the dexamethasone arm (50% v 38%; P = .06) while complete and partial control of emesis, average nausea score, and use of rescue medications were similar in the two groups. During the overall study period patients receiving dexamethasone had better complete control of emesis (23% v 12%; P = .02) and a lower average nausea score (0.28 v 0.39; P = .03); there was a trend towards less use of rescue medications with dexamethasone (70% v 80%; P = .09); other outcomes were similar on the two arms. Quality of life analysis showed a significant difference in appetite. CONCLUSION: The addition of dexamethasone to ondansetron as prophylaxis provides a modest improvement in protection against RIE during moderately emetogenic fractionated radiotherapy. It is a potentially useful addition to 5-hydroxytryptamine-3 receptor antagonists in this setting.

Randomized trial comparing cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer: update of National Cancer Institute of Canada Clinical Trials Group Trial MA5.

PURPOSE: Certain anthracycline-containing adjuvant chemotherapy regimens are associated with improved relapse-free survival (RFS) and overall survival (OS) compared with the classic regimen of cyclophosphamide, methotrexate, and fluorouracil in women with early-stage breast cancer. PATIENTS AND METHODS: Between 1989 and 1993, 710 pre- and perimenopausal women with axillary node-positive breast cancer were randomly assigned to either cyclophosphamide 75 mg/m(2) orally days 1 through 14, epirubicin 60 mg/m(2) intravenously days 1 and 8, and fluorouracil 500 mg/m(2) intravenously days 1 and 8 (CEF) or CMF (cyclophosphamide 100 mg/m(2) orally days 1 through 14, methotrexate 40 mg/m(2) intravenously days 1 and 8, and fluorouracil 600 mg/m(2) intravenously days 1 and 8). On the basis of follow-up to May 1997 (median follow-up time, 59 months), there was a statistically significant improvement in RFS and OS for CEF compared with CMF. RESULTS: The trial results are now updated, with a median follow-up of 10 years for live patients. The 10-year RFS is 52% for patients who received CEF compared with 45% for CMF patients (hazard ratio [HR] for CMF v CEF = 1.31; stratified log-rank, P = .007). The 10-year OS for patients who received CEF and CMF are 62% and 58%, respectively (HR for CMF v CEF = 1.18; stratified log-rank, P = .085). The rates of acute leukemia have not changed since the original report, whereas the rates of congestive heart failure are slightly higher but acceptable (four patients [1.1%] in the CEF group v one patient [0.3%] in the CMF group). CONCLUSION: The previously demonstrated benefit of CEF compared with CMF adjuvant chemotherapy is maintained with longer follow-up in the MA5 trial.

Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG).

BACKGROUND: Gemcitabine has been shown to have activity as a single agent in lymphoma and, when combined with cisplatin, is effective therapy for a number of solid tumors. The authors wished to determine the response rate and toxicity of gemcitabine, dexamethasone, and cisplatin for recurrent or refractory non-Hodgkin lymphoma (NHL). METHODS: Patients with recurrent or refractory diffuse large B-cell NHL or variants (REAL classification), measurable disease, and one previous chemotherapy regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m(2) intravenously (i.v.) on Days 1 and 8, dexamethasone 40 mg orally on Days 1-4, and cisplatin 75 mg/m(2) i.v. on Day 1 (GDP), every 21 days as an outpatient. The primary end point was a response after two cycles. Patients could then proceed to stem cell transplantation (SCT) or receive up to six treatment cycles. RESULTS: Fifty-one eligible patients were evaluable for toxicity and response. The median age of the patients was 57 years (range, 18-84 years) and most had diffuse large-cell lymphoma. After 2 cycles, there were 8 complete responses (CR; 16%) and 17 partial responses (PR; 33%). There was an overall response rate (RR) of 49% (95% confidence interval = 37-63%). The RR afer completion of all protocol chemotherapy (including those who received > 2 cycles of GDP) was 53% (11 CR, 16 PR). Grade 3 and 4 neutropenia occurred in 33% and 39% of patients, respectively. Grade 3 and 4 thrombocytopenia occurred in 24% and 4% of patients, respectively. Seven patients (14%) experienced febrile neutropenia. Of the 35 patients < 66 years, 22 (63%) proceeded to SCT. CONCLUSIONS: GDP is an active regimen in B-cell NHL and can be administered with acceptable toxicity to outpatients. A Phase III trial comparing GDP with standard cisplatin-based chemotherapy is now ongoing through the National Cancer Institute of Canada Clinical Trials Group.

Night vision disturbances after corneal refractive surgery.

A certain percentage of patients complain of "glare" at night after undergoing a refractive surgical procedure. When patients speak of glare they are, technically, describing a decrease in quality of vision secondary to glare disability, decreased contrast sensitivity, and image degradations, or more succinctly, "night vision disturbances." The definitions, differences, and methods of measurement of such vision disturbances after refractive surgery are described in our article. In most cases of corneal refractive surgery, there is a significant increase in vision disturbances immediately following the procedure. The majority of patients improve between 6 months to 1 year post-surgery. The relation between pupil size and the optical clear zone are most important in minimizing these disturbances in RK. In PRK and LASIK, pupil size and the ablation diameter size and location are the major factors involved. Treatment options for disabling glare are also discussed. With the exponential increase of patients having refractive surgery, the increase of patients complaining of scotopic or mesopic vision disturbances may become a major public health issue in the near future. Currently, however, there are no gold-standard clinical tests available to measure glare disability, contrast sensitivity, or image degradations. Standardization is essential for objective measurement and follow-up to further our understanding of the effects of these surgeries on the optical system and thus, hopefully, allow for modification of our techniques to decrease or eliminate post-refractive vision disturbances.

Factors affecting workload of cancer clinical trials: results of a multicenter study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Increasingly, cancer treatment centers need to be able to estimate specific costs and resources associated with clinical trials. Because the time requirements of trial coordination and data collection are not well known, the Clinical Research Associates (CRA) Committee of the National Cancer Institute of Canada Clinical Trials Group carried out a multicenter study to measure trials' task times and evaluate the effects of certain factors. METHODS: A data collection instrument was designed and validated before its implementation in the study. Eighty-three CRAs from 24 cancer treatment institutions across Canada collected timing observations of 41 tasks (156 subtasks). Information from all stages of trials activity (protocol management, eligibility and entry, treatment, and follow-up and final stage) was obtained, from initial negotiations to follow-up after study closure. RESULTS: After controlling for stage, phase and sponsor were found to be significant independent factors. Analysis within the stages showed similar patterns. New drug inclusion as a factor was confounded with phase. Industry-sponsored studies had significantly higher overall mean times than did local and cooperative group studies. Early-phase studies required more time than did phase III trials. External sponsorship of any kind increased CRA time more than that necessary for locally coordinated studies, except during the protocol management stage. The burden of a phase I study increased to greater than average once underway and accruing patients. CONCLUSION: Our data demonstrated that sponsor and study phase are important factors to be taken into consideration when estimating clinical trial costs and resource use.