Measurement of the Electron-Antineutrino Angular Correlation in Neutron ß Decay.

We report the first result for the electron-antineutrino angular correlation (a coefficient) in free neutron ß decay from the aCORN experiment. aCORN uses a novel method in which the a coefficient is proportional to an asymmetry in proton time of flight for events where the ß electron and recoil proton are detected in delayed coincidence. Data are presented from a 15 month run at the NIST Center for Neutron Research. We obtained a=-0.1090±0.0030(stat)±0.0028(sys), the most precise measurement of the neutron a coefficient reported to date.

Doctor, what are my options? A prospective cohort study of an individualized care plan for patients with gastrointestinal cancer.

BACKGROUND: For cancer patients, information about their disease and its treatment is often delivered within a short time period, potentially leading to patient misunderstanding, which can impede optimal patient care. In this 3-part clinical study, we investigated the utility of an individualized care plan for patients with gastrointestinal (gi) cancer starting a new treatment. METHODS: In part 1, a comprehensive literature search identified items for potential inclusion in the care plan. Those items were formatted into a questionnaire. The questionnaire was then administered to patients as a structured interview. In part 2, health care professionals involved in the care of patients with gi cancer evaluated the resulting care plan for content and relevancy. In part 3, a 20-week prospective cohort study (10 weeks using standard of care, 10 weeks using individualized care plans) was conducted. Outcomes were assessed at baseline and at 2-4 weeks after administration of the care plan. RESULTS: In part 1, a 73-item questionnaire was developed and completed by 20 patients in semi-structured interviews. In part 2, long and short versions of the care plan were created. Most health care professionals preferred the long version. Based on their comments, a final version of the care plan was created. The part 3 study enrolled 104 patients. Overall satisfaction scores were significantly higher in the intervention group at baseline (p = 0.010) and follow-up (p = 0.005). Compared with control patients, the intervention cohort also reported significantly higher overall quality of life (p = 0.044) and fewer symptoms of anxiety (p = 0.048) at follow-up. CONCLUSIONS: Provision of an individualized care plan resulted in improvements in outcome measures at both baseline and follow-up. Future studies are needed to confirm these findings.

Ondansetron rapidly dissolving film for the prophylactic treatment of radiation-induced nausea and vomiting-a pilot study.

INTRODUCTION: The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (rdf) in the prophylaxis of radiation-induced nausea and vomiting (rinv). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient. METHODS: Patients undergoing palliative radiotherapy at risk for rinv were prescribed ondansetron rdf 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting-specific daily diary, the Functional Living Index-Emesis (flie), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C15 Palliative (qlq-C15-pal). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. "Overall control" was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. "Acute phase" was defined as the days during radiation until the first day after radiation; "delayed phase" was defined as days 2-10 after radiation. RESULTS: The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively; during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%; during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and qlq-C15-pal questionnaires. CONCLUSIONS: Ondansetron rdf is effective for the prophylaxis of rinv.

Health system costs for stage-specific breast cancer: a population-based approach.

OBJECTIVE: The objective of the present analysis was to determine the publicly funded health care costs associated with the care of breast cancer (bca) patients by disease stage. METHODS: Incident cases of female invasive bca (2005-2009) were extracted from the Ontario Cancer Registry and linked to administrative datasets from the publicly funded system. The type and use of health care services were stratified by disease stage over the first 2 years after diagnosis. Mean costs and costs by type of clinical resource used in the care of bca patients were compared with costs for a matched control group. The attributable cost for the 2-year time horizon was determined in 2008 Canadian dollars. RESULTS: This cohort study involved 39,655 patients with bca and 190,520 control subjects. The average age in those groups was 61.1 and 60.9 years respectively. Most bca patients were classified as either stage i (34.4%) or stage ii (31.8%). Of the bca cohort, 8% died within the first 2 years after diagnosis. The overall mean cost per bca case from a public payer perspective in the first 2 years after diagnosis was $41,686. Over the 2-year time horizon, the mean cost increased by stage: i, $29,938; ii, $46,893; iii, $65,369; and iv, $66,627. The attributable cost of bca was $31,732. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. CONCLUSIONS: Costs of care increased by stage of bca. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. These data will assist planning and decision-making for the use of limited health care resources.

Patient engagement in the Continuing Professional Development programs within the department of radiation oncology at the University of Toronto (UTDRO): A qualitative study.

INTRODUCTION: There is little research regarding patient engagement (PE) in Continuing Professional Development (CPD) programs in radiation oncology. This study aims to understand the barriers and enablers to PE in the design and implementation process of CPD programs, and advance PE in these programs moving forward. METHODS: This qualitative study involved 17 semi-structured interviews, with 5 cancer patients and 12 educators, conducted from June 2019 to April 2020. Interview data identified common themes, such as: the current state of PE in CPD programming, and key barriers and recommendations on how to engage patients in meaningful and practical ways. RESULTS: Six themes were identified related to PE: the concept of PE, ethical considerations, barriers, key considerations in planning resources, and the anticipated impact of PE on curriculum planning. CONCLUSION: Both patients and educators emphasized that creating and sustaining meaningful educator-patient relationships and giving patients an active and effective role in CPD planning would improve curriculum content. The University of Toronto Department of Radiation Oncology (UTDRO) should consider building this initiative into its strategic CPD priorities and ensure the appropriate infrastructure is in place.

Dexamethasone for the prophylaxis of radiation-induced pain flare after palliative radiotherapy for symptomatic bone metastases: a phase II study.

AIMS: Pain flare occurs in over one-third of patients receiving palliative radiotherapy for bone metastases. A single dose of dexamethasone can decrease the incidence of pain flare during the first 2 days immediately after radiotherapy. We conducted a phase II prospective study to investigate the prophylactic role of prolonged dexamethasone. MATERIALS AND METHODS: Patients with bone metastases treated with a single 8Gy were prescribed 8mg dexamethasone just before palliative radiotherapy and for 3 consecutive days after treatment. Worst pain score and analgesic consumption data were collected at baseline and daily for 10 days after treatment. Analgesic consumption was converted into a total daily oral morphine equivalent dose in the analysis. Pain flare was defined (a priori) as a two-point increase in worst pain on an 11-point numeric rating scale compared with baseline with no decrease in analgesic intake, or a 25% increase in analgesic intake with no decrease in worst pain score. To distinguish pain flare from progressive disease, we required that the worst pain score and analgesic intake returned to baseline levels after the increase/flare. RESULTS: Forty-one patients were evaluable (32 men, nine women). Their median age was 67 years. The overall incidence of pain flare was 9/41 (22%) within 10 days after the completion of radiotherapy. Most (55%) of these pain flares occurred on day 5. Absence of pain flare was 34/41(83%) and 39/41 (95%) for days 1-5 and 6-10 after the completion of radiotherapy, respectively. CONCLUSION: Dexamethasone is effective in the prophylaxis of radiotherapy-induced pain flare after palliative radiotherapy for bone metastases. Randomised studies are needed to confirm this finding.

The generation of two specific cancer costing algorithms using Ontario administrative databases.

Cancer treatment and management have become increasingly economically burdensome. Consequently, to help with planning health service delivery, it is vital to understand the associated costs. Administrative databases can be used to help understand and generate real-world system-level costs. Using databases to generate costs can take one of two approaches: top-down or bottom-up. Top-down approaches disaggregate the total health care spending from a global health care budget by sector and provider. A bottom-up approach begins with individual-level health care use and its costs, which are then aggregated.

Does the Time of Radiotherapy Affect Treatment Outcomes? A Review of the Literature.

Circadian rhythm-dependent cell cycle progression produces daily variations in radiosensitivity. This literature review aims to summarise the data on whether radiotherapy outcomes differ depending on administration time. A literature search was conducted on Ovid Medline, Embase, Cochrane Central Register of Controlled Trials and PubMed using key words such as 'radiotherapy', 'circadian rhythm', 'treatment outcome' and 'survival'. Articles evaluating the correlation between radiotherapy time and outcomes in cancer patients were included and relevant information was extracted. Nine studies met the inclusion criteria. Four investigated lung cancer patients undergoing stereotactic radiosurgery for brain metastases, with one study observing improved local control and survival in patients treated in the morning. Another two studies with breast and cervical cancer patients observed that the prevalence of toxicities was higher in afternoon and morning cohorts, respectively. Two studies in head and neck cancer patients found trends indicating morning patients experienced less oral mucositis. Increased toxicities and biochemical failure rates were associated with evening treatment in prostate cancer patients. As inconsistencies in the literature exist regarding the time dependency of radiotherapy outcomes, further investigation is warranted.

The aCORN Backscatter-Suppressed Beta Spectrometer.

Backscatter of electrons from a beta spectrometer, with incomplete energy deposition, can lead to undesirable effects in many types of experiments. We present and discuss the design and operation of a backscatter-suppressed beta spectrometer that was developed as part of a program to measure the electronantineutrino correlation coefficient in neutron beta decay (aCORN). An array of backscatter veto detectors surrounds a plastic scintillator beta energy detector. The spectrometer contains an axial magnetic field gradient, so electrons are efficiently admitted but have a low probability for escaping back through the entrance after backscattering. The design, construction, calibration, and performance of the spectrometer are discussed.

aCORN: An experiment to measure the electron-antineutrino correlation coefficient in free neutron decay.

We describe an apparatus used to measure the electron-antineutrino angular correlation coefficient in free neutron decay. The apparatus employs a novel measurement technique in which the angular correlation is converted into a proton time-of-flight asymmetry that is counted directly, avoiding the need for proton spectroscopy. Details of the method, apparatus, detectors, data acquisition, and data reduction scheme are presented, along with a discussion of the important systematic effects.

Phase I pharmacokinetic study of cyclosporin A combined with doxorubicin.

We performed a phase I trial of cyclosporin A (CsA) in combination with doxorubicin (dox) to determine the maximally tolerated dose (MTD) of the combination in man, to define the quantitative and qualitative toxicities of the combination, and to determine the pharmacokinetics of the two drugs when used together. CsA was administered as a continuous infusion for 6 days, and dox was administered as a single 10-min infusion 24 h after the initiation of CsA. The starting CsA infusion rate was 5 micrograms/kg/min, and the dox starting dose was 30 mg/m2. Courses were administered every 4 weeks with first CsA and then dox being escalated in consecutive cohorts of patients until the MTD was determined. Twenty-three patients and 40 courses were evaluable for toxicity. Pharmacokinetic analysis was performed in 23 patients on the first course for whole blood CsA and plasma dox and doxorubicinol. The MTD of CsA was 6 micrograms/kg/min, and for dox it was 45 mg/m2. Dose-limiting toxicity was neutropenia. Serum creatinine and creatinine clearance did not change over the infusion period. Bilirubin increased from a median of 10 mumol/liter at the initiation of the infusion to a median of 40.4 mumol/liter at the end of the infusion but returned to normal before the next cycle of therapy. Nausea and vomiting were common and marked, whereas thrombocytopenia was mild. Two patients, one with small cell lung cancer and one with breast cancer, had stable disease while receiving treatment for 5 and 6 months, respectively. Mean whole blood steady state concentrations of CsA were 2210 ng/ml during the infusion with total body clearance of 0.177 liter/h/kg. The area under the concentration x time curve (AUC) increased linearly with dose of dox, and total body clearance was independent of dose. The mean total body clearance was 2.46 liters/h/m2, and terminal half-life was 49.6 h. The AUC for dox was greater and clearance was less than has been previously reported at the doses administered in this study. The ratio of AUC for doxorubicinol to AUC for dox was less than expected, suggesting that the metabolism and/or excretion of dox was decreased when administered with CsA. We conclude that dox can be combined with infusioned CsA but at a lower dose than when given alone. This may be due to altered metabolism and/or excretion of dox or increased bone marrow stem cell sensitivity to dox.

Role for dual individualization with cefmenoxime.

Cefmenoxime concentration/effect relationships were retrospectively explored for gram-negative bacteria isolated from 14 critical care patients treated for nosocomial pneumonia. The effects of cefmenoxime concentrations on in vitro growth kinetics of 21 isolated pathogens were studied using the Abbott MS-2 Research System, from which a dynamic response concentration was derived. Serum pharmacokinetic profiles were obtained in each patient. These data were used to calculate the in vivo total area under the curve over dynamic response concentration and the time that cefmenoxime concentrations exceeded the dynamic response concentration for each bacteria. The same determinations were made in 18 patients prospectively treated, except that dosage was optimized on the basis of previous mathematical relations to achieve bacterial eradication in four days. This method of dosage optimization is termed dual individualization. Serial cultures of infected tissues were evaluated to determine the number of days to the eradication of bacteria, and the pharmacokinetic and pharmacodynamic variables were used to describe the bacteriologic response of the original pathogen isolated in pretreatment culture. Bacterial eradication rates could be described from cefmenoxime pharmacokinetics in the patient and from the relation between concentration and bacterial inhibition. Patients who were prospectively treated using these retrospectively derived relationships had a predictable day of bacterial eradication. This, in turn, was associated with a shorter duration of treatment (p less than 0.05). The success of prospective dual individualization is encouraging and suggests that more precise optimization of antibiotic dosage can yield a predictable rate of bacterial eradication from the infection site.

Capitation reimbursement for pediatric primary care.

A feasibility analysis of capitation reimbursement for a primarily Medicaid population in The Johns Hopkins Pediatric Primary Care Clinic was conducted. The utilization of all inpatient and outpatient care of 2,261 patients was monitored for a 6-month period. As a result, per capita rates based on charges were determined for each group of patients according to type of insurance. Blue Cross and private insurance patients had capitation rates three times that of the Medicaid patients and over ten times that of self-pay patients This variation in utilization was attributed to the selection of enrollees, the morbidity of the population, and the varying services covered by payor group. Administrative issues regarding establishing a pediatric health maintenance organization are also discussed. Close supervision of house staff in treating patients, including admissions, length of stay, and specialty referral is of utmost importance in containing costs in this clinic setting.

Twenty-five years of residents: what and where are they now.

To evaluate the effectiveness of our program in meeting the subsequent career needs of our graduates and to describe their professional experiences as a microcosm of pediatrics, a survey was completed of the 419 pediatricians who had completed the Harriet Lane Residency Program at The Johns Hopkins Hospital between 1960 and 1984. Overall, the 326 respondents found the program to have been effective in the areas they deemed appropriate to be taught in residency years. In decreasing order, the chief resident, fellow house officers, and full-time faculty were rated to have had the greatest teaching effectiveness. The women respondents were less likely to be married (76% vs 89%), had fewer children on average (1.2 vs 2.31), missed more work, and were more likely to enter postresidency training (89% vs 78%) than the men. Of all respondents, 73% reported being certain of their career goals during residency and 77% of those reported a reasonable similarity with current positions. More than 93% reported being satisfied with their current careers, and 87% would still choose pediatrics. They are generally well reimbursed financially, with academician salaries matching those of private practitioners 10 years after completing residency and surpassing them, slightly, thereafter. This information provides much food for thought in preparing tomorrow's pediatricians.

Preparedness of practicing pediatricians to manage emergencies.

To determine pediatrician preparedness to manage emergencies, a nationally representative random sample of 1000 non-hospital-based pediatricians was surveyed about (1) types of emergencies encountered and methods of transport to an emergency facility, (2) availability and use of equipment and medications in the office, and (3) determinants of pediatrician confidence in managing emergencies. The proportion of pediatricians who had encountered specific emergencies ranged from 86% for meningitis to 22% for cardiopulmonary arrest. The majority transported acutely ill children to an emergency department by ambulance. Availability of individual pieces of equipment and medications in offices ranged from 97% for epinephrine 1:1000 to 11% for bone marrow needles for intraosseous access. Combination of equipment available to manage particular emergencies ranged from 61% for severe dehydration to 11% for cardiopulmonary arrest. The equipment available in a pediatrician's office was significantly related to the type of primary work setting. Pediatrician confidence in managing the initial stabilization of emergencies ranged from 58% for seizures to 25% for epiglottitis. Confidence was related significantly to year residency was completed, Advanced Cardiac or Advanced Pediatric Life Support training, work setting, and the availability of equipment in the office. Continuing education regarding initial office management of and equipment for common emergencies should improve the pediatrician's confidence and competence in this area.

Health services use by children enrolled in a hospital-based primary care clinic: a longitudinal perspective.

The use of a hospital-based primary care clinic for health maintenance and illness care and use of the emergency room were monitored for 3 years for 293 children who had been enrolled in the clinic as infants. Infrequent users of one facet of care were infrequent users of other facets of care, and they remained so for all 3 years. The same trends were noted for frequent users. Children who used the clinic for health maintenance infrequently were more likely to have registered in the clinic after 2 months of age and to demonstrate consistently infrequent use throughout the 3 years. Children who used the clinic for illness care infrequently were more likely to have at least two siblings and to demonstrate consistently infrequent use. Children who used the emergency room infrequently were likely to have been consistently infrequent users for emergencies and illness throughout the 3 years. Conversely, those who used the clinic frequently for health maintenance were more likely to have registered before 1 month of age, to have multiple chronic conditions, and to demonstrate consistently frequent use for maintenance throughout the 3 years. Frequent users for illness care were more likely to have none or one sibling, multiple chronic conditions, and to demonstrate consistently frequent use for illnesses. Finally, children who used the emergency room frequently were likely to have multiple chronic conditions and to demonstrate sustained frequent use throughout the 3 years. These results suggest that patterns of use are established as early as the first year of life.

Independent parental administration of prednisone in acute asthma: a double-blind, placebo-controlled, crossover study.

OBJECTIVE: To determine the effectiveness of a single dose of prednisone administered by a parent to a child early in an asthma attack. DESIGN: A randomized, double-blind, placebo-controlled, crossover study with children enrolled for 12 months (6 months prednisone, 6 months placebo). SETTING: A primary-care clinic and emergency department of an inner-city teaching hospital from March 1992 through May 1993. CHILDREN: Children 2 to 14 years of age enrolled in this clinic who had made two or more outpatient (emergency department or primary-care clinic) visits for acute asthma in the preceding year. SELECTION: There were 204 eligible children, of whom 86 were contacted and enrolled; of these, 78 (91%) completed the study. INTERVENTION: Capsules containing prednisone (2 mg/kg up to 60 mg) or placebo. Parents were instructed to give their child one capsule for an asthma attack that had not improved after a dose of the child's regular acute asthma medicine. MEASUREMENTS: Parents were interviewed every 3 months. Computerized patient records and chart reviews were used to verify parent reports. Outcome measures were the numbers of outpatient visits and hospitalizations for treatment of acute asthma. RESULTS: Neither the total number of attacks nor the number for which medicine was used differed significantly by arm of study. There was a larger number of attacks resulting in outpatient visits when children were in the group that received prednisone (1.1 +/- 0.59 versus 0.59 +/- 0.86). This trend was less pronounced but persisted when limited to attacks for which the medicine was given (0.58 +/- 0.99 versus 0.35 +/- 0.55). Neither the number of attacks resulting in admission nor the number of hospital days differed significantly by arm of study. CONCLUSIONS: A single dose of prednisone available for use at home early in an asthma attack was associated with an increase in outpatient visits made for acute asthma. When prednisone was given for an attack, there was no reduction in outpatient visits. This intervention can not be recommended for children with asthma. These results should be confirmed in other pediatric populations.

Subspecialization within pediatric practice: a broader spectrum.

This study was undertaken to describe subspecialty characteristics and practices of the population of pediatricians given the ongoing controversy regarding a projected manpower oversupply of general pediatricians. A questionnaire was mailed to a national random sample of 1620 United States physicians listed in the American Medical Association's Physician Masterfile as being in office-based pediatric practice. The final response rate was 63%. Seventy percent of respondents designated their practices as "general pediatrics" versus 17% as "general pediatrics with a specific subspecialty interest" and 13% as "subspecialty practice." The general pediatricians with a specific subspecialty interest were intermediate in the proportion that had some training in a pediatric fellowship program (general pediatricians with a specific subspecialty interest, 63% versus general pediatricians, 14%, P < .0001, and pediatricians with a subspecialty practice, 92%, P < .0001) and that were certified in a pediatric subspecialty by the American Board of Pediatrics (general pediatricians with a specific subspecialty interest 16% versus general pediatricians, 2%, P < .0001, and pediatricians with a subspecialty practice, 62%, P < .0001). They were also intermediate in the proportion involved in various academic pursuits. Their practices, however, more closely resembled general pediatricians than pediatricians with a subspecialty practice in their location, setting, associates, and commitment to primary care. They were more likely than general pediatricians to utilize or provide specialized tests or procedures. A large percentage of pediatricians incorporate subspecialty elements into their general pediatric practices. Models of current and projected pediatric manpower supply need to be reassessed in light of this form of practice.

Cost-effectiveness of erythromycin versus mupirocin for the treatment of impetigo in children.

A new topical antibiotic, mupirocin, has been found to be as effective as erythromycin for the treatment of impetigo, but concerns about its expense have been raised. This controlled clinical trial sought to compare the cost-effectiveness of erythromycin (E) and mupirocin (M). Ninety-three children, aged 3 months to 16 years, were randomly assigned to receive 10 days of oral erythromycin (n = 46) or topical mupirocin (n = 47). Costs and effects were measured through structured interviews. Cost per case differed significantly by group (E = $56.85; M = $62.30; P less than .05) due chiefly to extra visits and medication changes needed by those treated with mupirocin. Erythromycin and mupirocin were equally effective. The likelihood of side effects (E = 43%, M = 22%) approached significance (P less than .07); those treated with erythromycin were willing to pay more for a different medicine to avoid the side effects experienced (P less than .05). Working parents and school-age children were more likely to alter their daily activities when the patient was taking erythromycin (P less than .04). Compliance and parental satisfaction did not differ by treatment group; however, parents of children treated with erythromycin were more likely to prefer the alternate drug regimen. It is concluded that the type of medication prescribed can be based on parental preference because the increased cost of mupirocin is offset by increased side effects and number of schooldays and workdays lost with erythromycin.

Substance abuse education in pediatrics.

Historically, physicians have received little formal education related to alcohol or other drug abuse and dependence. A survey of all pediatric programs in the United States was conducted to assess the current status of alcohol/drug education in pediatrics. At the medical student and residency training levels, only 44% and 40% of programs, respectively, required any formal instruction, and only 27% and 34%, respectively, offered an elective for medical students or residents. Although most respondents endorsed the inclusion of both required and elective alcohol and drug education in the curriculum, few programs that did not include it already had a future plan for it. Major impediments identified were curriculum time constraints (86% medical student level, 68% resident level) and the lack of a qualified instructor (55% medical student level, 50% resident level). The survey results suggest a strong need for development of faculty and structured alcohol and drug abuse educational plans specific to pediatrics.