Frailty and long-term mortality of older breast cancer patients: CALGB 369901 (Alliance).

PURPOSE: Breast cancer patients aged 65+ ("older") vary in frailty status. We tested whether a deficits accumulation frailty index predicted long-term mortality. METHODS: Older patients (n = 1280) with non-metastatic, invasive breast cancer were recruited from 78 Alliance sites from 2004 to 2011, with follow-up to 2015. Frailty categories (robust, pre-frail, and frail) were based on 35 baseline illness and function items. Cox proportional hazards and competing risk models were used to calculate all-cause and breast cancer-specific mortality for up to 7 years, respectively. Potential covariates included demographic, psychosocial, and clinical factors, diagnosis year, and care setting. RESULTS: Patients were 65-91 years old. Most (76.6%) were robust; 18.3% were pre-frail, and 5.1% frail. Robust patients tended to receive more chemotherapy ± hormonal therapy (vs. hormonal) than pre-frail or frail patients (45% vs. 37 and 36%, p = 0.06), and had the highest adherence to hormonal therapy. The adjusted hazard ratios for all-cause mortality (n = 209 deaths) were 1.7 (95% CI 1.2-2.4) and 2.4 (95% CI 1.5-4.0) for pre-frail and frail versus robust women, respectively, with an absolute mortality difference of 23.5%. The adjusted hazard of breast cancer death (n-99) was 3.1 (95% CI 1.6-5.8) times higher for frail versus robust patients (absolute difference of 14%). Treatment differences did not account for the relationships between frailty and mortality. CONCLUSIONS: Most older breast cancer patients are robust and could consider chemotherapy where otherwise indicated. Patients who are frail or pre-frail have elevated long-term all-cause and breast cancer mortality. Frailty indices could be useful for treatment decision-making and care planning with older patients.

Electron paramagnetic resonance radiation dose assessment in fingernails of the victim exposed to high dose as result of an accident.

In this paper, we report results of radiation dose measurements in fingernails of a worker who sustained a radiation injury to his right thumb while using 130 kVp X-ray for nondestructive testing. Clinically estimated absorbed dose was about 20-25 Gy. Electron paramagnetic resonance (EPR) dose assessment was independently carried out by two laboratories, the Naval Dosimetry Center (NDC) and French Institut de Radioprotection et de Sûreté Nucléaire (IRSN). The laboratories used different equipments and protocols to estimate doses in the same fingernail samples. NDC used an X-band transportable EPR spectrometer, e-scan produced by Bruker BioSpin, and a universal dose calibration curve. In contrast, IRSN used a more sensitive Q-band stationary spectrometer (EMXplus) with a new approach for the dose assessment (dose saturation method), derived by additional dose irradiation to known doses. The protocol used by NDC is significantly faster than that used by IRSN, nondestructive, and could be done in field conditions, but it is probably less accurate and requires more sample for the measurements. The IRSN protocol, on the other hand, potentially is more accurate and requires very small amount of sample but requires more time and labor. In both EPR laboratories, the intense radiation-induced signal was measured in the accidentally irradiated fingernails and the resulting dose assessments were different. The dose on the fingernails from the right thumb was estimated as 14 ± 3 Gy at NDC and as 19 ± 6 Gy at IRSN. Both EPR dose assessments are given in terms of tissue kerma. This paper discusses the experience gained by using EPR for dose assessment in fingernails with a stationary spectrometer versus a portable one, the reasons for the observed discrepancies in dose, and potential advantages and disadvantages of each approach for EPR measurements in fingernails.

Local Dose Coefficients for Radionuclide Contamination in Wounds.

ABSTRACT: When a radiation accident has occurred that leads to radioactive material being imparted to a wound, this is treated as an internal contamination scenario. It is common for the material to transport throughout the body based upon biokinetics of the material in the body. While standard internal dosimetry approaches can be used to estimate committed effective dose from the insult, some material may get fixed for longer periods of time at the wound location, even after medical procedures such as decontamination and debridement have been applied. In this case, the radioactive material becomes a local dose contributor. This research was to generate local dose coefficients for radionuclide-contaminated wounds to supplement committed effective dose coefficients. These dose coefficients can be used to calculate activity limits at the wound site that could lead to a clinically significant dose. This is useful for emergency response to assist in decisions on medical treatment, including decorporation therapy. Wound models were created for injections, lacerations, abrasions, and burns, and the MCNP radiation transport code was used to simulate the dose to tissue considering 38 radionuclides. Biokinetic models accounted for biological removal of the radionuclides from the wound site. It was found that radionuclides that are not retained well at the wound site are likely of little concern locally, but for highly retained radionuclides, estimated local doses may require further investigation by medical and health physics personnel.

Innovative legal approaches to address obesity.

CONTEXT: The law is a powerful public health tool with considerable potential to address the obesity issue. Scientific advances, gaps in the current regulatory environment, and new ways of conceptualizing rights and responsibilities offer a foundation for legal innovation. METHODS: This article connects developments in public health and nutrition with legal advances to define promising avenues for preventing obesity through the application of the law. FINDINGS: Two sets of approaches are defined: (1) direct application of the law to factors known to contribute to obesity and (2) original and innovative legal solutions that address the weak regulatory stance of government and the ineffectiveness of existing policies used to control obesity. Specific legal strategies are discussed for limiting children's food marketing, confronting the potential addictive properties of food, compelling industry speech, increasing government speech, regulating conduct, using tort litigation, applying nuisance law as a litigation strategy, and considering performance-based regulation as an alternative to typical regulatory actions. Finally, preemption is an overriding issue and can play both a facilitative and a hindering role in obesity policy. CONCLUSIONS: Legal solutions are immediately available to the government to address obesity and should be considered at the federal, state, and local levels. New and innovative legal solutions represent opportunities to take the law in creative directions and to link legal, nutrition, and public health communities in constructive ways.

Performance-based regulation: enterprise responsibility for reducing death, injury, and disease caused by consumer products.

This article offers a bold new idea for confronting the staggering level of death, injury, and disease caused by five consumer products: cigarettes, alcohol, guns, junk food, and motor vehicles. Business leaders try to frame these negative outcomes as "collateral damage" that is someone else's problem. That framing not only is morally objectionable but also overlooks the possibility that, with proper prodding, industry could substantially lessen these public health disasters. I seek to reframe the public perception of who is responsible and propose to deploy a promising approach called "performance-based regulation" to combat the problem. Performance-based regulation would impose on manufacturers a legal obligation to reduce the negative social costs of their products. Rather than involving them in litigation or forcing them to operate differently (as "command-and-control" regimes do), performance-based regulation allows the firms to determine how best to decrease bad public health consequences. Like other public health strategies, performance-based regulation focuses on those who are far more likely than individual consumers to achieve real gains. Analogous to a tax on causing harm that exceeds a threshold level, performance-based regulation seeks to harness private initiative in pursuit of the public good.

Using performance-based regulation to reduce childhood obesity.

BACKGROUND: Worldwide, the public health community has recognized the growing problem of childhood obesity. But, unlike tobacco control policy, there is little evidence about what public policies would work to substantially reduce childhood obesity. Public health leaders currently tend to support traditional "command and control" schemes that order private enterprises and governments to stop or start doing specific things that, is it hoped, will yield lower childhood obesity rates. These include measures such as 1) taking sweetened beverages out of schools, 2) posting calorie counts on fast-food menu boards, 3) labeling foods with a "red light" if they contain high levels of fat or sugar, 4) limiting the density of fast food restaurants in any neighborhood, 5) requiring chain restaurants to offer "healthy" alternatives, and 6) eliminating junk food ads on television shows aimed at children. Some advocates propose other regulatory interventions such as 1) influencing the relative prices of healthy and unhealthy foods through taxes and/or subsidies and 2) suing private industry for money damages as a way of blaming childhood obesity on certain practices of the food industry (such as its marketing, product composition, or portion size decisions). The food industry generally seeks to deflect blame for childhood obesity onto others, such as parents and schools.

Rapid Response, Dose Assessment, and Clinical Management of a Plutonium-contaminated Puncture Wound.

Internalization of radionuclides occurs not only by inhalation, ingestion, parenteral injection (i.e., administration of radioactive material for a medical purpose), and direct transdermal absorption, but also by contaminated wounds. In June 2010, a glove-box operator at the U.S. Department of Energy's Savannah River Site sustained a puncture wound while venting canisters containing legacy materials contaminated with Pu. To indicate the canisters had been vented, a flag was inserted into the vent hole. The shaft of the flag penetrated the protective gloves worn by the operator. Initial monitoring performed with a zinc-sulfide alpha detector indicated 300 dpm at the wound site. After being cleared by radiological controls personnel, the patient was taken to the site medical facility where decontamination was attempted and diethylenetriaminepentaacetic acid (DTPA) was administered intravenously within 1.5 h of the incident. The patient was then taken to the Savannah River Site In Vivo Counting Facility where the wound was counted with a Canberra GL 2820 high-purity germanium detector, capable of quantifying contamination by detecting low-energy x rays and gamma rays. In addition to the classic 13, 17, and 20 keV photons associated with Pu, the low-yield (0.04%) 43.5 keV peak was also detected. This indicated a level of wound contamination orders of magnitude above the initial estimate of 300 dpm detected with handheld instrumentation. Trace quantities of Am were also identified via the 59.5 keV peak. A 24 h urine sample collection was begun on day 1 and continued at varying intervals for over a year. The patient underwent a punch biopsy at 3 h postincident (14,000 dpm removed) and excisional biopsies on days 1 and 9 (removal of an additional 3,200 dpm and 3,800 dpm, respectively). The initial post-DTPA urine sample analysis report indicated excretion in excess of 24,000 dpm Pu. Wound mapping was performed in an effort to determine migration from the wound site and indicated minimum local migration. In vivo counts were performed on the liver, axillary lymph nodes, supratrochlear lymph nodes, and skeleton to assess uptake and did not indicate measurable activity. Seventy-one total doses of DTPA were administered at varying frequencies for 317 d post intake. After allowing 100 d for removal of DTPA from the body, five 24 h urine samples were collected and analyzed for dose assessment by using the wound model described in National Council on Radiation Protection and Measurements Report No. 156. The total effective dose averted via physical removal of the contaminant and DTPA administration exceeded 1 Sv, demonstrating that rapid recognition of incident magnitude and prompt medical intervention are critical for dose aversion.

Fighting childhood obesity through performance-based regulation of the food industry.

That childhood obesity is an alarming public health problem is clear and widely appreciated. What is altogether unclear is what our society should do about it. Some people think the solution lies in using tort law to sue McDonald's, Coca-Cola, and other corporations. We reject that notion. Others believe that government should order specific changes in the behavior of food companies and school officials--and yet, there is little reason for confidence that these "command and control" strategies will make a difference. Instead, we propose "performance-based regulation" of the food industry. This is analogous to the approach our country is now taking with respect to elementary and secondary education (most prominently in the No Child Left Behind legislation). Schools are not told how to achieve better educational results, but better outcomes are demanded of them. This strategy has also been used in the environmental context to reduce harmful power plant emissions, and it has been briefly proposed as a way of regulating cigarette companies. In this Article, we propose that large firms selling food and drink that is high in sugar or fat will be assigned the responsibility of reducing obesity rates in a specific pool of children. A firm's share of the overall responsibility will be based on its share of the "bad' food market, and the children assigned to it will be organized by geographically proximate schools where obesity rates are currently above the plan's nationwide target rate of 8 percent (the actual childhood obesity rate today is approximately 16 percent). Firms that fail to achieve their goals will be subject to serious financial penalties.

A New Cytogenetic Biodosimetry Image Repository for the Dicentric Assay.

The BioDoseNet was founded by the World Health Organization as a global network of biodosimetry laboratories for building biodosimetry laboratory capacities in countries. The newly established BioDoseNet image repository is a databank of ~25 000 electronically captured images of metaphases from the dicentric assay, which have been previously analysed by international experts. The detailed scoring results and dose estimations have, in most cases, already been published. The compilation of these images into one image repository provides a valuable tool for training and research purposes in biological dosimetry. No special software is needed to view and score the image galleries. For those new to the dicentric assay, the BioDoseNet Image Repository provides an introduction to and training for the dicentric assay. It is an excellent instrument for intra-laboratory training purposes or inter-comparisons between laboratories, as recommended by the International Organization for Standardisation standards. In the event of a radiation accident, the repository can also increase the surge capacity and reduce the turnaround time for dose estimations. Finally, it provides a mechanism for the discussion of scoring discrepancies in difficult cases.

Ionizing radiation injuries and illnesses.

Although the spectrum of information related to diagnosis and management of radiation injuries and illnesses is vast and as radiation contamination incidents are rare, most emergency practitioners have had little to no practical experience with such cases. Exposures to ionizing radiation and internal contamination with radioactive materials can cause significant tissue damage and conditions. Emergency practitioners unaware of ionizing radiation as the cause of a condition may miss the diagnosis of radiation-induced injury or illness. This article reviews the pertinent terms, physics, radiobiology, and medical management of radiation injuries and illnesses that may confront the emergency practitioner.

Management of ionizing radiation injuries and illnesses, part 2: nontherapeutic radiologic/nuclear incidents.

In the second of 5 articles on the management of injuries and illnesses caused by ionizing radiation, the authors discuss nontherapeutic radiologic/nuclear incidents: use of a radiologic exposure device, use of a radiologic dispersal device, nuclear power plant safety failure, and detonation of an improvised nuclear device. The present article focuses on how such incidents--whether involving deliberate or accidental methods of radiation exposure--produce casualties and how physicians need to understand the pathologic process of injuries caused by these incidents. To identify the diagnoses associated with nontherapeutic exposure in time to improve morbidity and mortality, physicians must maintain a high index of suspicion when faced with a specific constellation of symptoms. In some scenarios, the sheer number of uninjured, unaffected persons who might present to health care institutions or professionals may be overwhelming. Public health and safety issues may seriously disrupt the ability to respond to and recover from a radiologic and nuclear incident, especially a nuclear detonation.

Management of ionizing radiation injuries and illnesses, part 1: physics, radiation protection, and radiation instrumentation.

Ionizing radiation injuries and illnesses are exceedingly rare; therefore, most physicians have never managed such conditions. When confronted with a possible radiation injury or illness, most physicians must seek specialty consultation. Protection of responders, health care workers, and patients is an absolute priority for the delivery of medical care. Management of ionizing radiation injuries and illnesses, as well as radiation protection, requires a basic understanding of physics. Also, to provide a greater measure of safety when working with radioactive materials, instrumentation for detection and identification of radiation is needed. Because any health care professional could face a radiation emergency, it is imperative that all institutions have emergency response plans in place before an incident occurs. The present article is an introduction to basic physics, ionizing radiation, radiation protection, and radiation instrumentation, and it provides a basis for management of the consequences of a radiologic or nuclear incident.

Management of ionizing radiation injuries and illnesses, Part 3: Radiobiology and health effects of ionizing radiation.

Ionizing radiation exposure can induce profound changes in intracellular components, potentially leading to diverse health effects in exposed individuals. Any cellular component can be damaged by radiation, but some components affect cellular viability more profoundly than others. The ionization caused by radiation lasts longer than the initial inciting incident, continuing as 1 ionization incident causes another. In some cases, damage to DNA can lead to cellular death at mitosis. In other cases, activation of the genetic machinery can lead to a genetic cascade potentially leading to mutations or cell death by apoptosis. In the third of 5 articles on the management of injuries and illnesses caused by ionizing radiation, the authors provide a clinically relevant overview of the pathophysiologic process associated with potential exposure to ionizing radiation.

Role of dicentric analysis in an overarching biodosimetry strategy for use following a nuclear detonation in an urban environment.

In the moments immediately following a nuclear detonation, casualties with a variety of injuries including trauma, burns, radiation exposure, and combined injuries would require immediate assistance. Accurate and timely radiation dose assessments, based on patient history and laboratory testing, are absolutely critical to support adequately the triage and treatment of those affected. This capability is also essential for ensuring the proper allocation of scarce resources and will support longitudinal evaluation of radiation-exposed individuals and populations. To maximize saving lives, casualties must be systematically triaged to determine what medical interventions are needed, the nature of those interventions, and who requires intervention immediately. In the National Strategy for Improving the Response and Recovery for an Improvised Nuclear Device (IND) Attack, the U.S. Department of Homeland Security recognized laboratory capacity for radiation biodosimetry as having a significant gap for performing mass radiation dose assessment. The anticipated demand for radiation biodosimetry exceeds its supply, and this gap is partly linked to the limited number and analytical complexity of laboratory methods for determining radiation doses within patients. The dicentric assay is a key component of a cytogenetic biodosimetry response asset, as it has the necessary sensitivity and specificity for assessing medically significant radiation doses. To address these shortfalls, the authors have developed a multimodal strategy to expand dicentric assay capacity. This strategy includes the development of an internet-based cytogenetics network that would address immediately the labor intensive burden of the dicentric chromosome assay by increasing the number of skilled personnel to conduct the analysis. An additional option that will require more time includes improving surge capabilities by combining resources available within the country's 150 clinical cytogenetics laboratories. Key to this intermediate term effort is the fact that geneticists and technicians may be experts in matters related to identifying chromosomal abnormalities related to genetic disorders, but they are not familiar with dosimetry for which training and retraining will be required. Finally, long-term options are presented to improve capacity focus on ways to automate parts of the dicentric chromosome assay method.

Rapid internal dose magnitude estimation in emergency situations using annual limits on intake (ALI) comparisons.

It is crucial to integrate health physics into the medical management of radiation illness or injury. The key to early medical management is not necessarily radiation dose calculation and assignment, but radiation dose magnitude estimation. The magnitude of the dose can be used to predict potential biological consequences and the corresponding need for medical intervention. It is, therefore, imperative that physicians and health physicists have the necessary tools to help guide this decision making process. All internal radiation doses should be assigned using proper dosimetry techniques, but the formal internal dosimetry process often takes time that may delay treatment, thus reducing the efficacy of some medical countermeasures. Magnitudes of inhalation or ingestion intakes or intakes associated with contaminated wounds can be estimated by applying simple rules of thumb to sample results or direct measurements and comparing the outcome to known limits for a projection of dose magnitude. Although a United States regulatory unit, the annual limit on intake (ALI) is based on committed dose, and can therefore be used as a comparison point. For example, internal dose magnitudes associated with contaminated wounds can be estimated by comparing a direct wound measurement taken soon after the injury to the product of the ingestion ALI and the associated f1 value (the fractional uptake from the small intestine to the blood). International Commission on Radiation Protection Publication 96, as well as other resources, recommends treatment based on ALI determination. Often, treatment decisions have to be made with limited information. However, one can still perform dose magnitude estimations in order to help effectively guide the need for medical treatment by properly assessing the situation and appropriately applying basic rules of thumb.

A balanced tobacco control policy.

By raising the price of cigarettes through tobacco taxes, policymakers might only be delaying some smokers' initiation of smoking rather than permanently preventing them from smoking. This is one of several reasons for adopting a balanced tobacco control policy that relies only in part on cigarette taxation.