Dear Label_Name,

Greetings! I hope you are well.

I am writing on behalf of an international publishing house, Science and Education Publishing, USA (http://www.sciepub.com).

Science and Education Publishing (SciEP) is a multidisciplinary open access publisher of Journals covering the fields of Science, Technology and Medicine. All SciEP publications are subject to high-quality peer review, editorial and production processes and are freely available online.

Welcome to the April, 2013 edition of SciEP newsletter, providing monthly summaries of articles on science & education related topics of interest to scientist and professionals. The mission of our journals is to provide an open access forum for publishing new findings on issues pertinent to scientific and academic field. We also invite you to submit original research papers, review articles, short reports, or case studies are considered for publication in our Multidisciplinary Journals.

American Journal of Public Health Research
DOI: 10.12691/ajphr-1-1-3

The Implementation of a Tele-Homecare System with Service Oriented Architecture and HL7 Message Transmission Standard
Ching-Sung Wang

American Journal of Medical and Biological Research
DOI: 10.12691/ajmbr-1-1-2

The Influence of Ethanol on Pyruvate Kinases Activity in Vivo, in Vitro, in Silico
Lelevich Sergey Vladimirovich, Khrustalev Vladislav Victorovich, Barkovsky Eugene Victorovich, Shedogubova Tatyana Aleksandrovna

American Journal of Medical Sciences and Medicine
DOI: 10.12691/ajmsm-1-1-1

Clinical and Histological Features in Wegener Granulomatosis
Li Cavoli Gioacchino, Passantino Rita, Bono Luisa, Tortorici Calogera, Ferrantelli Angelo, Giammarresi Carlo, Rotolo Ugo

American Journal of Infectious Diseases and Microbiology
DOI: 10.12691/ajidm-1-1-2

The Curse of Lymphatic Filariasis: Would the Continual Use of Diethylcarbamazine Eliminate this Scourge in Papua New Guinea?
Anne Lanham, Lillian Mwanri

We have released issues of some journals on February 2013.
American Journal of Public Health Research
American Journal of Medical Sciences and Medicine
American Journal of Medical and Biological Research
American Journal of Pharmacological Sciences
American Journal of Clinical Medicine Research
American Journal of Nursing Research
American Journal of Cancer Prevention
American Journal of Medicine Studies
American Journal of Infectious Diseases and Microbiology
American Journal of Cardiovascular Disease Research
American Journal of Biomedical Research
American Journal of Mechanical Engineering
American Journal of Microbiological Research
Journal of Preventive Medicine
American Journal of Food and Nutrition
American Journal of Hypertension Research
American Journal of Sports Science and Medicine
Journal of Cancer Research and Treatment
American Journal of Zoological Research
Journal of Biomedical Engineering and Technology
American Journal of Microbiological Research
Biomedical Science and Engineering

We are pleased to announce that submissions are now being accepted for peer review for all the journals across all our subject areas in SciEP.

Please submit your manuscript via our online submission system:
http://www.sciepub.com/author/signin

To unsubscribe from our mailing list, please click on the following link: unsubscribe

I am looking forward to hearing from you.

Kind regards,

David Rain
Email:join@sciepub.com
Science and Education Publishing (http://www.sciepub.com)

Conceptual Model of the Psychosocial Effects of Beryllium Sensitization and Chronic Beryllium Disease

Jeffrey R. Miller*, Gregory C. Petty, Paul C. Erwin, Donna L. Cragle

Oak Ridge Associated Universities, P.O. Box 117, Oak Ridge, TN 37831-0117

Abstract: The objective of this research was to develop a theoretical model that describes the psychosocial effects of beryllium sensitization (BeS) and chronic beryllium disease (CBD). The medical, nursing, health education, and psychological literature was reviewed to identify theories that might support the development of a psychosocial model of BeS and CBD. A proposed model was synthesized based upon elements from multiple academic disciplines. The conceptual model is based on three prominent psychological theories: 1) health, stress, and coping, 2) uncertainty and illness, and 3) psychosocial adjustment to illness. The model hypothesizes that workers who are diagnosed with BeS or CBD experience a great deal of uncertainty that has a detrimental effect on their health quality of life. The focal relationship in this model is between the independent variable uncertainty and the dependent variable health quality of life. It is further hypothesized that the relationship between these two variables is affected by an intermediate variable, the ability to make psychosocial adjustments to disease. Creating this model is a step toward filling a void in our understanding of the natural history of CBD. Once validated it will establish a foundation for future research, interventions and program evaluations and may lead to changes in the psychological, social, financial, and disease management support provided to this population.

Keywords: Beryllium, berylliosis, uncertainty in illness, psychosocial adjustment, stress and coping

Citation: Jeffrey R. Miller, Gregory C. Petty, Paul C. Erwin, Donna L. Cragle, Conceptual Model of the Psychosocial Effects of Beryllium Sensitization and Chronic Beryllium Disease. American Journal of Public Health Research, 6 (2). 72-83. January 2018. doi:10.12691/ajphr-6-2-10

1. Introduction

A research gap exists in the development and testing of theoretical models which might explain the psychosocial aspects of beryllium sensitization (BeS) and chronic beryllium disease (CBD). Such research would help clinicians understand the total experience of their patients and might suggest changes in the types of psychological, social, financial, and disease management support provided to workers with BeS or CBD. The purpose of this research was to develop such a model.

Beryllium is a strong, lightweight metal that is toxic when inhaled into the lungs. People who work in factories where beryllium is processed are sometimes exposed to beryllium particles and may develop an allergic reaction to the metal. In some, this reaction, called BeS, leads to a severe, incurable occupational lung disease known as CBD.

Beryllium is widely used in the aerospace, electronics, biomedical, defense, telecommunications and other industries [1,2,3,4]. The 2010 estimated consumption of beryllium in the U.S. was 320 metric tons and was valued at about $160 million [5]. Beryllium consumption is currently dominated by electronics applications [6]. The estimate for the number of U.S. workers ever exposed to beryllium ranges from 800,000 to 1,000,000 [7,8,9].

Most people who are exposed to beryllium will not experience health effects because there is a strong genetic susceptibility component to sensitization and subsequent disease. However, some develop BeS and some of them go on to develop CBD. Epidemiologic studies have shown that on average, 1-6 percent of exposed workers develop BeS, although the rates can be as high as 19 percent among workers with the highest exposures, such as beryllium machinists [10,11,12,13,14]. Most workers who are going to develop BeS tend to do so early on, but follow-up testing over the years continues to identify workers with BeS-up to 30 percent in one group of workers [15].

The percentage of people with BeS who go on to develop CBD is highly variable, ranging from 10-100 percent in different worker populations [16]. Individuals exposed to the highest levels of airborne beryllium dust are at greatest risk of sensitization, although skin exposure may also be important [17]. Recent research suggests that each year, 6-8 percent of people with BeS will develop CBD [18]. The latency for converting from BeS to CBD is highly variable, ranging from 1-12 years in one longitudinal study [19]. Factors such as particle size, type of beryllium used, amount and duration of exposure to beryllium, occupation, industry, and genetics all play a role in determining why some people develop CBD and others do not [14,16]. Once a person is exposed to beryllium, they carry a lifelong risk of developing beryllium sensitization or CBD, even if the exposure amount was small or their exposure ceases. [16].

The National Research Council (NRC) [20] recognized that the diagnosis of BeS or CBD may be associated with psychosocial stress and/or loss of income and that there was an absence of published data on those phenomena. The NRC further suggested that implementation of a comprehensive beryllium-exposure and disease management program that includes appropriate worker education and counseling, medical-removal, and protection against lost wages can minimize such potential adverse consequences [20].

2. Materials and Methods

The medical, nursing, health education, and psychological literature was reviewed to identify theories that might support the development of a psychosocial model of BeS and CBD. Online searches were conducted to identify publications in the scientific literature and library searches were conducted to identify and obtain other scholarly works. Government publications were obtained from agency websites or through personal requests to contacts in the agencies.

The search was conducted in a sequential manner starting with the medical and epidemiologic literature related to chronic beryllium disease. This was followed by an analysis of the nursing literature related to the psychosocial effects of illness. The psychological literature related to health, stress, and coping was then evaluated. Models from the health education literature were then reviewed to determine how they might be applied to this project.

The literature was synthesized and a figure of the model was developed. Draft versions of the model were shared with subject matter experts from various academic and medical disciplines. Through repeated discussions with experts from multiple disciplines, the proposed model was further refined. The model was shared with key informants who had either BeS or CBD to get their feedback. A research plan was developed to identify how future qualitative and quantitative research projects might be used to validate the proposed model.

3. Results

3.1. The Natural History of CBD

Beryllium induced lung disease can usually be categorized as either an acute or chronic disease process [21]. Acute beryllium disease is of historical significance and was identified in the U.S. in the 1940s [22,23] and is considered an irritative chemical phenomenon related to high exposure levels [24]. With advances in industrial hygiene, acute beryllium disease has been virtually eliminated in the U.S. [21]. Despite these historical improvements in workplace exposure conditions, cases of CBD continue to occur [25].

According to Newman, Lloyd, and Daniloff [25] CBD is a systemic disorder that occurs when a sensitized (i.e., allergic) person’s lungs react with beryllium that has been inhaled, producing inflammation in the lungs which leads to the formation of lung granulomas and scarring. They described CBD as a beryllium-specific, cell-mediated immune response gone awry. Based on their review of historical studies Newman, Lloyd & Daniloff [25] concluded that: 1) the disease varies in its clinical presentation, 2) the disease varies in its rate of progression, 3) while removal from exposure may be medically prudent, it is not known to what extent such restrictions will change the natural history for more than a minority of patients, and 4) earlier studies did not systematically review the risk factors for disease progression [25].

The symptoms that cause the patient to seek medical evaluation can include arthralgia, chest pain, cough, or most commonly dyspnea with relatively mild exertion [21]. While some persons with CBD die within a few years of diagnosis in respiratory failure and cor pulmonale, others experience a more insidious downhill course extending over decades [25]. Workers exposed to persistent (i.e., non-soluble) beryllium antigen are at lifelong risk of CBD [16,26].

The diagnosis of CBD is usually preceded by identification of BeS and those workers that become sensitized are at high risk for developing CBD [16]. Conversion from BeS to CBD is highly variable, ranging from 1-12 years in one longitudinal study [18]. The current diagnostic criteria for CBD include all of the following [27,28]:

1. History of or evidence of beryllium exposure

2. Evidence of an immune response to beryllium, that is, positive response in blood or bronchoalveolar lavage lymphocytes exposed to differing levels of beryllium in in vitro cultures (i.e., the beryllium lymphocyte proliferation test (BeLPT)) in two independent tests

3. Symptomatic disease with histological demonstration of noncaseating granulomas on lung biopsy

Current medical management of CBD involves cessation of beryllium exposure and use of immunosuppressive drugs [29,30] but there is limited literature regarding the effect of these interventions on the natural history of CBD. Published mortality rates range from 5.8 to 38% [31].

3.2. Beryllium Sensitization

The development of the BeLPT [11] created a fundamental change in our knowledge of CBD. According to Maier [32], it revolutionized our approach to the diagnosis, screening, and surveillance of beryllium health effects. BeS is not a disease in its own right and has no symptoms, but it is important because it identifies a subgroup of exposed workers who are at risk for developing CBD [20]. A positive BeLPT result differentiates CBD from other lung diseases such as sarcoidosis, chronic obstructive pulmonary disease, and hypersensitivity pneumonitis [20,27,33].

BeLPT results are not always consistent or stable, creating clinical uncertainty [34,35,36,37,38]. Because the test is difficult to perform and results are not always consistent, most physicians and researchers like to require two independent abnormal tests in order to categorize a worker as BeS. Greene and Smith [39] argued that the empirical uncertainty arising from the probabilistic nature of BeLPT screening can be highly unsettling for workers who might expect clear guidance from medical testing. Despite its limitations in test consistency and repeatability, the BeLPT has been an invaluable tool in the identification of workplace risks in population studies and intervention effectiveness [16] and has led to the identification of clinically milder cases [20].

3.3. Lung Cancer

In addition to CBD, workers exposed to beryllium also have significantly elevated risks of lung cancer [40,41,42,43]. The National Toxicology Program [44] listed beryllium as a known carcinogen, as did the International Agency for Research on Cancer [45]. However, beryllium exposure is more commonly associated with CBD than lung cancer and according to the National Institute for Occupational Safety and Health [46], controlling beryllium exposure to prevent CBD should also reduce the risk for lung cancer. The reader is referred to the Agency for Toxic Substances and Disease Registry, Toxicological Profile of Beryllium [47] and Groth [48] for comprehensive reviews of the carcinogenic properties of beryllium.

3.4. Epidemiology of CBD

For the most comprehensive description of the epidemiology of CBD, the reader is referred to the literature review completed by the National Research Council, Committee on Toxicology [2]. This work, along with its companion report [20], were completed for the U.S. Air Force and represent the most current and complete compilation of the beryllium literature.

The population at risk for CBD is workers in industries where beryllium is processed in a manner that creates multiple pathways for inhalation and skin contact with beryllium particles [17]. The range of estimates for the number of U.S. workers exposed to beryllium is 20,000 to 1,000,000 [7,8,9]. Henneberger and others [49] relied on sampling data from the Occupational Safety and Health Administration (OSHA) to estimate that 134,000 U.S. workers were potentially exposed to beryllium. Kreiss, Day, and Schuler [16] believed that the number is far higher because OSHA had not sampled for beryllium in military and nuclear weapons complex workplaces. Other workplaces, such as those recycling electronics equipment, may also be a source of previously unsuspected exposure [20].

The prevalence of BeS and CBD in exposed workers ranges from 1 - 19% and from 0.1 - 7.8%, respectively [14,16]. Table 1 provides prevalence data of BeS and CBD from recent cross-sectional and longitudinal studies conducted in U.S. industry.

Table 1. Prevalence for Beryllium Sensitization and Chronic Beryllium Disease from Selected Epidemiologic Studies

CBD is typically considered only when occupational exposure to beryllium is a certainty; however, CBD has occurred in occupational and environmental settings where exposure was unexpected [21]. Individuals who live near plants that process beryllium may be at greater risk than the general population [53,54]. The general population is exposed to beryllium through inhalation of air and consumption of food and drinking water but people who work in beryllium manufacturing, fabricating, and reclaiming industries are exposed to much higher levels of beryllium than the general population [47].

The nuclear weapons industry has received substantial attention because of worker exposure to beryllium. In fact, beryllium disease was recognized among workers involved in the early development of atomic energy in the World War II era [22,55]. As nuclear weapons proliferated during the Cold War, the number of workers in the U.S. Department of Energy (DOE) nuclear complex grew and the number of workers exposed to beryllium grew proportionately. Beginning in the late 1980s, clusters of CBD were recognized in workers from nuclear weapons plants across the U.S. [11]. A number of additional epidemiologic studies of nuclear workers have been completed over the past two decades helping us to understand the risk of CBD in this population [10,50,56,57,58,59,60,61,62]. These studies and others were chronicled in the DOE regulation (i.e., the Chronic Beryllium Disease Prevention Program) that was promulgated to prevent the continued occurrence of CBD [63].

Among other things, this rule created the DOE Beryllium-Associated Worker Registry for current workers who are exposed to beryllium in their current job, or may have been exposed to beryllium in the past from work conducted at a DOE site [64]. The goal of the registry is to determine the incidence and prevalence of BeS and CBD. The data are analyzed to better understand CBD and to identify those at risk. Another goal is to monitor and evaluate the effectiveness of the Chronic Beryllium Disease Prevention Program. Coupled with the DOE Former Worker Medical Screening Program [65], these surveillance programs provide a mechanism for collecting data about those at risk for BeS and CBD.

3.5. The Psychosocial Aspects of CBD

The National Research Council (NRC) recognized that the diagnosis of CBD or BeS may be associated with psychosocial stress and/or loss of income and that there was an absence of published data on those phenomena [2,20]. The NRC further suggested [20] that implementation of a comprehensive beryllium-exposure and disease management program that includes appropriate worker education and counseling, medical-removal, and protection against lost wages can minimize such potential adverse consequences.

At the 3rd Annual International Conference on Beryllium Disease, Newman [66] made a presentation identifying unanswered questions related to CBD. He argued that there was still much to be learned about the neuro-psychological and social effects of CBD on BeS and CBD patients. He reported that his patients asked how beryllium will affect their employment, finances, insurability, workers compensation, personal well-being, and social lives. Later at the same conference, Cragle [67] encouraged researchers to consider the sensitized/CBD patient as a whole human being and asked, “where are the social scientists?”

In 1999, at the Conference on Beryllium Effects on Worker Health, Henneberger suggested that it was important to survey former employees to estimate the full extent of the problem and to understand the natural history of CBD [68]. In 2008, at the Third International Conference on Beryllium Particulates and Their Detection, McCawley [69] presented the results of a survey of members of the Beryllium Health and Safety Committee to identify the most important topics for future research. In the area of health effects, McCawley reported the second highest priority was to “identify opportunities for therapeutic interventions (pre-CBD) or specific therapies for CBD” and suggested that a research plan needed to be developed to help people with BeS and CBD.

3.6. Theoretical Perspectives and Relevant Studies

3.6.1. Stress and Coping Theory

Stress is a term that originated in the disciplines of physics and engineering. Early research on human stress was conducted by scientists in the fields of biology, physiology, and psychology. It was Cannon [70] who coined the enduring term “fight or flight” to describe the human response to stress. Endocrinologist Hans Selye [71] was the father of modern stress research and was the first to publish a paper on the biological syndrome of stress. Over the next twenty years he further explored the concept as it related to disease in man, eventually publishing Stress and Life [72]. In this seminal work, he defined three stages of stress: alarm reaction, stage of resistance, and stage of exhaustion. He described the alarm stage as a generalized call to arms of the defensive forces in the organism. Following this was a stage of biological adaptation of the organs to the stress. After prolonged exposure, the adaptation was eventually lost and the animal entered the stage of exhaustion. At the end of a life under stress, there was a premature aging due to wear and tear. To describe this progression, he used the term general adaptation syndrome [72]. Thus began the study of stress and illness.

While Selye initially focused on biological stress, others turned their attention to the concept of psychological stress. Lazarus [73] considered the field of stress a collective term that included physiological, sociological, and psychological phenomena and their respective concepts. He argued that these diverse terms could be combined in the same study. Lazarus extended the general adaptation syndrome [73] by incorporating the concepts of stress appraisal and coping. He suggested that for a psychosocial situation to be stressful, it must be appraised as such. That is, one must determine whether a situation is potentially threatening, constitutes a harm/loss, is challenging, or is benign. He theorized that this assessment occurred during primary and secondary appraisals. The primary appraisal includes the perception of how stressful the stimulus is and the secondary appraisal estimates whether one has adequate resources to deal with the problem. He defined coping as the strategies one employs for dealing with stress and that when the individual discovers some important motive or value is being threatened, coping activity is mobilized by this threat, by virtue of the cognition that “my life, health, wealth, or cherished social relationships are in danger.” Lazarus [73] referred to these coping modes as direct action, vigilance, and avoidance.

Selye later published a new model [74] that divided stress into eustress and distress. This differentiated stress that enhanced physical or mental functioning (i.e., eustress) and persistent stress that was not resolved through coping and adaptation (i.e., distress). Eustress is positive adaptation to stress and is typified by activities such as exercise to build strength and cardiovascular capacity. Distress results in negative functioning and may lead to anxiety, depression and/or physical ailment. This model more accurately represented both the positive and negative potential associated with stress.

Holroyd and Lazarus [75] explored the linkage between stress, coping, and illness, describing three ways that stress might lead to somatic illness. The first was by the disruption of tissue function from neural and hormonal outpourings (e.g., pounding heart, sweating, trembling, etc.). The second was by engaging in coping activities that were damaging to health (e.g., tobacco use, alcohol consumption, poor diet). The third way that stress might lead to disease is by psychological and/or sociological factors which lead the person to minimize the significance of symptoms or to fail to comply with treatment programs (e.g., avoidance of doctors). They concluded that whether stress led to somatic illness via one of these mechanisms was influenced by a person’s coping methods and skills.

Lazarus and Folkman [76] recognized that people exhibited different coping styles when confronted with stress. They suggested that coping styles are broad, pervasive, encompassing ways of relating to particular types of situations such as ambiguous or clear, imminent or distant, temporary or chronic, evaluative or nonevaluative. They also recognized that coping styles are dynamic and subject to the personality of the individual. These dynamics properties make for a diversity of strategies for those coping with illness. Stress can also have a distinct physiologic effect.

O’Leary [77] reviewed the empirical evidence linking emotional stress to immune function in humans. She reported that chronic stress has been associated with suppression of immune function, and that there is evidence that the immune system may not adapt over time [77]. There is evidence that psychosocial stress influences a variety of immune functions and on several disease processes. This presents some provocative questions about the interaction between psychosocial and physiological stress associated with immune mediated diseases, like CBD.

As the theory of stress and coping evolved and matured, key concepts became more defined. Folkman [78] recognized that the scope of coping had been broadened to include regulation of positive well-being in the face of stress. In addition, research is now being conducted on future-oriented coping, interpersonal coping, and religious and spiritual coping. Models have been developed to explain the concept of stress and coping in society. One such model that explains how stress and coping theory applies to health and well-being is the Transactional Model of Stress and Coping.

3.6.2. Transactional Model of Stress and Coping

Understanding stress and coping is essential to health education, health promotion, and disease prevention [79] and the Transactional Model of Stress and Coping is a framework for evaluating processes of coping with stressful events. Glanz and Schwartz articulated the constructs of the model which is rooted in the cognitive theory of psychological stress and coping developed by Lazarus and Folkman [80]. The theory is transactional in that the person and the environment are viewed as being in a dynamic, mutually reciprocal, bi-directional relationship. Stress is conceptualized as a relationship between the person and the environment that is appraised by the person as taxing or exceeding his or her resources and as endangering well-being [79]. The theory identifies two processes - cognitive appraisal (primary and secondary) and coping strategies (problem, emotion, and meaning-based) as critical mediators of stressful person-environment relationships and their immediate and long-term outcomes including emotional well-being, functional status, and health behaviors [79]. Because stress effects people differently, the ability to cope with stress influences decisions about seeking medical care and social support and whether one believes the advice of professionals. This model serves as the theoretical basis for many health education and disease prevention programs.

3.6.3. Psychosocial Adjustment to Illness Theory

The ability of humans to adjust to threatening events is a derivative of stress and coping theory. Taylor [81] observed that one of the most impressive qualities of the human psyche is its ability to successfully withstand severe personal tragedy. Based on her experience with cancer patients, cardiac patients, rape victims, and other individuals facing life-threatening events [81], she argued that when an individual has experienced a life-threatening event, the readjustment process focused around three themes: 1) a search for meaning in the experience, 2) an attempt to regain mastery over the event in particular and over one’s life more generally, and 3) an effort to enhance one’s self-esteem, to feel good about oneself again despite the personal setback.

How one adjusts to illness has been the subject of much research over the past thirty years [82,83]. Mechanic [84] noted that what interested behavioral scientists was the tremendous variability in response to what was presumably the same illness condition. While one person hardly acknowledged a condition and refused to allow it to alter his life, another with a milder form of the same condition would display profound social and psychological disabilities.

Psychosocial adaptation to chronic illness and disability has been the subject of more research as the prevalence of chronic disease increases in our society. Livneh and Antonak [85] suggested that the prolonged course of treatment, the uncertain prognosis, the constant and intense psychological stress, the gradually increasing interference with the performance of daily activities and life roles, and the associated impact on family and friends all combine to create a profound effect on the lives of persons with chronic illness and disabilities. Cassileth and others [86] compared the psychosocial status of five groups of patients with chronic illness (i.e., arthritis, diabetes, cancer, renal disease, and dermatologic disorders) and found them remarkably adaptive in comparison to patients with depression. They concluded that psychological status was independent of the specific diagnosis for these chronic diseases.

Derogatis was one of the early pioneers in this field and he, along with Abeloff and Melisaratos [87], reported on the psychological coping mechanisms in patients with metastatic breast cancer. They found that, in general, the long-term survivors had higher psychological distress levels than the short-term survivors. They also established that cancer patients whose coping styles facilitated external, conscious expression of negative emotions and psychological distress appeared to survive longer while patients whose coping styles involved suppression or denial of affect or psychological distress had a shorter length of survival. They [87] suggested that psychological interventions could be redesigned to put patients more in touch with their emotions and possibly promote a more successful psychological outcome. This early research led Derogatis to explore the development of psychometric scales that could be used to measure the ability to adjust to illness.

The Global Adjustment to Illness Scale (GAIS) was developed as an instrument to measure the prevalence of psychiatric disorders among cancer patients [88]. In this study the GAIS, along with two other instruments, were administered to a sample of 215 cancer patients. The results of the survey indicated that 47% had a psychiatric diagnosis and that approximately 68% of those diagnoses consisted of adjustment disorders. The authors further suggested that pervasive emotional distress and dysphoria often associated with cancer may not be an inherent part of the neoplastic disease, but rather a separate and potentially treatable condition. This study provided an epidemiologic benchmark for the prevalence of psychiatric disorders among cancer patients and has had far-reaching implications for treatment and therapy. It also motivated Derogatis to further refine his psychometric instrument.

In 1986, Derogatis introduced the interview-based Psychosocial Adjustment to Illness Scale (PAIS) and a self-reporting version (PAIS-SR) to assess the psychological and social adjustment of medical patients, or members of their immediate families, to the patient’s illness. The PAIS and PAIS-SR were developed to reflect seven principal domains [89], all of which had been shown to have a high relevancy for adjustment to medical illness. The seven domains include:

1. health care orientation

2. vocational empowerment

3. domestic environment

4. sexual relationships

5. extended family relationships

6. social environment

7. psychological distress

The instruments were tested for factor structure, reliability, and validity and a library of six normative groups was developed (lung cancer patients, renal dialysis patients, acute burn patients, hypertensive patients, cardiac bypass patients, and heterogeneous cancer patients). Later, other researchers [90,91] conducted additional factor structure analyses on the PAIS-SR.

While Derogatis [89] noted that there were more than two dozen instruments available to assess psychiatric patients, he developed this instrument because there was a dearth of tools for measuring the psychosocial status of non-psychiatric patients. Others [92,93,94,95] began using the instrument to describe the psychosocial illness experience for patients with cancer and occasionally for other conditions like kidney disease [96,97] chronic lung disease [98], burns [99], and multiple sclerosis [100]. The PAIS and PAIS-SR were tools that helped fill the void in this field of research.

Folkman and Greer [101] provided an appraisal and coping framework that has helped tie adjustment to illness theory to the empirical data generated by research tools like the PAIS. They suggested a model therapeutic program aimed at improving the psychological well-being of patients facing serious illness. Since the 1990s, psychosocial interventions have become increasingly more relevant as evidenced by the meta analysis that Rehse and Pukrop [102] conducted on 37 controlled outcome studies. It is now widely recognized [103] that understanding the process by which most individuals adjust to illness offers important insights to enhance the efficacy of interventions that facilitate psychological adjustment. Helping individuals adjust to their illness has become a priority, especially for those with chronic diseases.

3.6.4. Uncertainty and Illness Theory

The uncertainty and illness theory is another attempt to explain the human illness experience. Spawned from stress and coping theory, uncertainty and illness has been of particular interest to clinicians and researchers trying to understand the challenges of patients coping with chronic illness.

According to Brashers [104] uncertainty exists when details of situations are ambiguous, complex, unpredictable, or probabilistic; when information is unavailable or inconsistent; and when people feel insecure in their own state of knowledge or the state of knowledge in general. Babrow, Hines, and Kasch [105] further postulated that because uncertainty is multilayered, interconnected, and temporal, people experience multiple sources of uncertainty at once, that manipulating one type of uncertainty can impact (e.g., increase or decrease) uncertainties of other types, and that experiences of uncertainty are ongoing and changing features of life.

After an exhaustive search of the psychological literature, Norton [106] concluded that no matter the source, when an event is judged to be uncertain, it will contain one or more of the following eight dimensions: 1) multiple meanings; 2) vagueness; 3) probability; 4) unstructured; 5) lack of information; 6) ambiguity; 7) inconsistencies and contradictions; and 8) unclear. This provided a framework for the concept of uncertainty that has been used in research across multiple disciplines.

Babrow, Kasch, and Ford [107] identified uncertainty as a central part of the experience of illness. They described multiple sources of variation within the concept of uncertainty including, complexity, qualities of information, probability, structure of information and lay epistemology. For example, clarity (e.g., the use of medical jargon), accuracy (e.g., laboratory analytical methods), and ambiguity (e.g., different interpretations of results) are all qualities of information that can vary greatly. They attempted to reconcile sources of variation in conceptions of uncertainty and synthesize more specific conceptions of uncertainty in illness. Recognizing what contributes to uncertainty in illness and how it can be managed remains a daunting assignment. One of the pioneers in this effort was Merle Mishel.

Mishel [108] investigated the role of uncertainty as a significant variable influencing patients’ experiences in illness, treatment, and hospitalization. She proposed a model of perceived uncertainty in illness and developed an instrument (i.e., the Mishel Uncertainty in Illness Scale – MUIS) for measuring uncertainty in symptomatology, diagnosis, treatment, relationship with caregivers, and planning for the future. She continued to refine the structure of the model [109,110,111] and the MUIS was applied to a variety of populations [112,113]. In 1988 she published a seminal paper [114] on uncertainty in illness. In this paper she defined uncertainty as the inability to determine the meaning of illness-related events and stated the fundamental belief that uncertainty concerning what will happen, what the consequences of an event are, and what the event means, are important to a person with any illness. Furthermore, she argued that managing the uncertainty associated with an illness and its treatment may be an essential task in adaptation. She encouraged further research applying the model and MUIS in different patient populations and varied settings.

While the model had been previously applied to acute illnesses or those in a downward illness trajectory, little had been done to understand uncertainty in chronic diseases. Mishel [114] reconceptualized the uncertainty in illness theory to address the experience of living with continual, constant uncertainty in either a chronic illness or in an illness with a treatable acute phase and possible eventual recurrence. This was based in part on the qualitative observation that the longer chronically ill subjects lived with continual uncertainty, the more positively they evaluated the uncertainty. This supported the argument that uncertainty can be a positive experience but was contrary to the cultural value that uncertainty is an aversive experience and, except in an extreme situation, is definitely not preferable to certainty.

Drawing on chaos theory, Michel [115] postulated that uncertainty surrounding a chronic illness or life-threatening condition qualified as a sufficient fluctuation to threaten the preexisting organization of the person. Michel viewed uncertainty in illness as:

“A fluctuation that begins in only one part of the human system and, according to chaos theory, can either regress and cause no particular disruption or spread to the whole system. As uncertain disease related factors, like severity of the illness, success of treatment, impact of illness on one’s life, and ability to pursue life’s dreams and ambitions, are introduced into the person’s life the uncertainty competes with the person’s previous mode of functioning. As the concentration of the uncertainty expands, it can exceed the person’s level of tolerance, causing the personal system to become unstable. The uncertainty that early in the illness was the source of fluctuation, later in the illness becomes the foundation on which the person constructs a new sense of order.” [[115], p. 259]

Thus, she postulated [115] that uncertainty is used by individuals to reformulate their view of life and that this new view of life allows one to view uncertainty as an opportunity rather than a danger or threat. Mishel [115] encouraged health care providers to adopt a probabilistic rather than a mechanistic paradigm. That is, accept uncertainty as a natural, inherent part of reality that is not determinable with precision and abandon the view that uncertainty is the enemy and must be eliminated.

Uncertainty and illness theory has matured over thirty years and become a cornerstone for understanding the psychosocial effects of chronic disease. In studies examining the adjustment to uncertainty in illness [115], the most common conclusion is that high uncertainty is related to high emotional distress, anxiety, depression, and fatigue. This progression has been supported by the work of others beside Mishel who have conducted research to clarify the concepts within the theory [108,116,117,118,119,120,121,122,123], understand how nursing interventions can be used to manage uncertainty [124], to illuminate processes of coping with uncertainty [125,126], and to conceptualize how adaptation to uncertainty effects health-related quality of life [127]. One chronic disease to which uncertainty and illness theory has been successfully applied is prostate cancer.

3.6.5. Psychosocial Effects of Prostate Cancer

According to the American Cancer Society [128], prostate cancer is the second most commonly diagnosed cancer among men in the U.S. and the second most common cause of cancer death among men. In 2010, an estimated 217,730 new cases of prostate cancer were diagnosed in the U.S. [128]. Changes in the incidence of prostate cancer over the past 20 years reflect the widespread use of the prostate specific antigen (PSA) screening tool [128]. According to Tombal [129], the PSA has led to a dramatic increase in the number of patients diagnosed with prostate cancer, a significant number of them being non-clinically significant. The diagnosis of prostate cancer has well-described psychosocial difficulties [130] that vary across stages of disease and types of treatment. Some men, who are asymptomatic and have low-risk, early stage cancer, are eligible for active surveillance which offers a means to monitor the cancer while delaying treatment [130,131]. This is in contrast to watchful waiting which is a conservative management strategy for men who are more likely to die from co-morbidities [131,132]. The result of this phenomenon is that there are now a large number of men living with localized prostate cancer and the uncertainty that it bestows.

Germino, Mishel and others [133] began applying uncertainty of illness theory to prostate cancer soon after the PSA-stimulated diagnosis boom. Since then, studies [134] have shown that prostate cancer is a disease fraught with uncertainty that often makes adjustment to the illness difficult. To gain a richer understanding of uncertainty in men undergoing watchful waiting or active surveillance, qualitative and quantitative studies [132,135,136,137,138] were conducted by number of researchers. Collectively, this body of knowledge has established a foundation from which researchers [139,140,141] can design and conduct randomized clinical trials to evaluate the efficacy of psychosocial interventions. Those experiments and a number of others were recently summarized [142] in the literature. With evidence on the efficacy of interventions in hand, researchers [143,144] are now reporting the results of longitudinal studies to measure the change in quality of life among prostate cancer patients and their partners.

4. Discussion

The example of prostate cancer suggests a possible path forward for the study of the psychosocial effects of CBD. In this example, researchers recognized that prostate cancer was unique from other types of cancers and studied both the physical and psychological aspects of the natural history of the disease. They conducted qualitative studies to gain an initial understanding of the psychosocial problems confronting patients and their partners. Then they developed a theory base (i.e., uncertainty of illness) and conducted quantitative studies to refine a model that accurately described the psychosocial component of prostate cancer. Following this, theory-based interventions were developed, implemented, and evaluated. Finally, longitudinal studies were conducted to determine the long-term effect of the intervention in the study population. Executing a similar systematic approach should be the goal for researchers and clinicians studying the psychosocial effects of BeS and CBD.

There are psychological theories described in the literature that help us understand stress, coping, and chronic illness. We know that the stress of chronic diseases, like CBD, affects people differently. Fortunately, humans have a remarkable ability to adapt to stress when faced with chronic disease. The Transactional Model of Stress and Coping was developed to help us understand the inter-relatedness of stress and coping concepts to health and well-being. This model is commonly used by health professionals who are developing interventions to help people cope with stress. There are valid and reliable instruments, like the MUIS and PAIS, which help us measure the psychosocial effects of stress and chronic disease. These instruments have been used in a variety of studies of chronic illnesses, like prostate cancer, but never to study individuals with CBD.

4.1. Conceptual Model

The conceptual model is based on three prominent psychological theories: 1) health, stress, and coping, 2) uncertainty and illness, and 3) psychosocial adjustment to illness. The model supports the hypothesis that workers who are diagnosed with BeS or CBD experience a great deal of uncertainty and that has a detrimental effect on their health status. The focal relationship in this model is between the independent variable uncertainty (i.e., the characteristic being observed) and the dependent variable health status (i.e., the outcome of interest). It is suspected that the relationship between these two variables may be partially mediated by an intermediate variable, the ability to make psychosocial adjustments to disease. Figure 1 illustrates the conceptual model.

Figure 1. A conceptual model of the psychosocial effects of chronic beryllium disease

As depicted in Figure 1 there are five antecedents (i.e., preceding events) that influence the independent variable: 1) host (genetic) susceptibility to beryllium disease, 2) exposure to beryllium in the workplace, 3) sensitization (allergy) to beryllium, 4) symptoms of CBD, and 5) diagnosis of CBD. Exposure to beryllium in the workplace is the most critical antecedent. Exposure is necessary but not sufficient when acting alone (i.e., one cannot get CBD if he/she is never exposed to beryllium, but exposure does not guarantee that disease will occur). Exposure must be combined with host susceptibility, sensitization, symptoms of disease, and/or diagnosis of CBD to create a necessary and sufficient combination of factors to activate the model.

There are at least six potential confounding variables to be considered: 1) age, 2) education level, 3) socioeconomic status, 4) vocation, 5) marital status, and 6) history of involvement with the healthcare system. These variables may distort the truth because they may be associated with both uncertainty and health status. For example, individuals with a higher socioeconomic status may have less uncertainty (e.g., a more predictable life) because they own their home and have sufficient income so they do not live paycheck-to-paycheck. They also may have greater access to healthcare or seek and comply with medical recommendations better, which translates to regular physical exams and screenings that help prevent the development of chronic diseases (i.e., greater physical functioning).

In the model, uncertainty is proposed as an independent variable that influences health status. This proposition is based on the research conducted by Mishel [108] to determine how uncertainty influences patients’ experiences in illness, treatment, and hospitalization. She developed a model of perceived uncertainty in illness and developed an instrument (i.e., the Mishel Uncertainty in Illness Scale – MUIS) for measuring uncertainty in symptoms, diagnosis, treatment, relationship with caregivers, and planning for the future. The MUIS has six primary domains: 1) ambiguity, 2) inconsistency, 3) vagueness, 4) unpredictability, 5) lack of information, and 6) unfamiliarity. In studies examining the adjustment to uncertainty in illness [115], the most common conclusion was that high uncertainty was related to high emotional distress, anxiety, depression, and fatigue.

A proposed intermediate variable is psychosocial adjustment to illness. This proposition is based on the research conducted by Derogatis [89]. He introduced the Psychosocial Adjustment to Illness Scale (PAIS) to assess the psychological and social adjustment of medical patients, or members of their immediate families, to the patient’s illness. The PAIS was developed to reflect seven principal domains [89], all of which had been shown to have a high relevancy for adjustment to medical illness: 1) health care orientation, 2) vocational empowerment, 3) domestic environment, 4) sexual relationships, 5) extended family relationships, 6) social environment, and 7) psychological distress. An example of the mediating role this variable may play is illustrated as follows. The lag period between when a person becomes sensitized and develops symptoms of CBD is difficult to predict and may range from months to decades. This subclinical period may be tempered by the individual’s healthcare orientation (e.g., their general approach to taking care of their health). That is, someone who is very attentive to their health needs and exhibits healthy behaviors, such as regular exercising and maintaining a proportional weight, may postpone the onset of CBD symptoms.

In the model, the outcome of interest is health quality of life. This includes both the physical and mental domains. The Rand Corporation developed an instrument (SF-36v2, Quality Metric Incorporated) that measures eight health concepts: 1) vitality, 2) physical functioning, 3) bodily pain, 4) general health perceptions, 5) physical role functioning, 6) emotional role functioning, 7) social role functioning, and 8) mental health. This is a valid and reliable scale that is widely used to measure health quality of life among sick and well populations. Based on anecdotal reports, a hypothetical example has been constructed to illustrate how this model functions.

4.2. Example

A skilled machinist applied for a job at a metal machining and fabrication shop where various aircraft parts were manufactured from beryllium and other metals. Whether he was genetically susceptible to beryllium was unknown. Prior to his employment, he was given a pre-employment physical examination and screened for beryllium sensitization using the BeLPT. The BeLPT was normal, he was declared fit for duty, and hired.

He worked in the factory for 5 years and was promoted to journeyman machinist. Each year he had the BeLPT and the result was normal. Industrial hygiene samples were occasionally collected in the factory and 90% of the results showed that airborne beryllium concentrations were less than the limit of detection of 0.05 micrograms per cubic meter of air (μg/m³) and all of the results were less than 0.1 μg/m³. This was 20 times less than the Occupational Safety and Health Administration (OSHA) standard so management believed the exposure levels were safe. Several breathing zone samples were collected from various machinists but none were ever collected directly from the breathing zone of this Worker.

During the Worker’s annual physical at the start of his sixth year, his BeLPT result was abnormal. The plant nurse told him not to worry as false positives were common with this test and that they always had to do a second BeLPT to confirm the first result. She drew blood for a second BeLPT and sent it to the laboratory for analysis. The results, received six-weeks later, were reported as “borderline.” The plant nurse told the Worker that a third test was needed because a borderline test was neither positive nor negative. They repeated the test and waited six more weeks for results. This result was also abnormal. The Company Doctor told the Worker that he was sensitized to beryllium. The Worker had no symptoms and his pulmonary function tests were normal. The Doctor told him he could not say with certainty if or when he might develop CBD. He said some people went for 10-15 years and never developed symptoms and others developed symptoms within a few months; everybody was different. In the meantime, it was prudent that he no longer work with beryllium.

The Worker’s supervisor told him that he would not be able to come back to his machinist position because it was company policy that a sensitized worker could not work around beryllium and they did not have any machinists positions where he would not be potentially exposed to beryllium. He said he could transfer to the grounds maintenance, however, if he chose to do that he would have to work at a 50% pay reduction.

The Worker went home and told his wife that he would have to take a 50% pay reduction and work on the grounds crew if he wanted to stay at the factory. She was concerned about that but was mostly worried about what would happen if he developed CBD. The Worker wondered if he was going to have to change careers. He had always been a machinist and did not know what else he could do and make an equivalent salary. He wondered if he could make an insurance claim for disability or workers compensation because he was sensitized to beryllium.

In this example, the reader may have recognized two of the antecedents (i.e., exposure and sensitization) along with several sources of uncertainty. Ambiguity was represented by the alternating normal and abnormal BeLPT results. Vagueness was represented by the industrial hygiene sampling results that were reported as less than the limit of detection. Unpredictability was present when the Doctor described the natural history of CBD. Lack of information was present when the Worker wondered about whether he was eligible for a workers compensation or disability insurance claim. Unfamiliarity was present when the Worker wondered about what other trade he could learn.

The effect of this uncertainty may be mediated (i.e., modified) by the Worker’s individual situation and life experiences. For example, his wife had a job in the healthcare field that paid well and mediated some of the healthcare and financial uncertainty. He had two friends from the factory that also had become sensitized to beryllium and they had joined a local CBD support group. This may have mediated the social functioning. His brother owned a construction business and he talked to him about working for him, helping to mediate the vocational uncertainty. This hypothetical example is a composite of actual scenarios and demonstrates the potential for uncertainty with BeS and CBD.

Creating this model is a step toward filling a void in our understanding of the natural history of CBD. Once validated, it will establish a foundation for future research and program evaluations and may lead to changes in the psychological, social, financial, and disease management support provided to this population.

Acknowledgements

This research was supported by a grant from University of Tennessee, Department of Public Health.

Statement of Competing Interests

The authors have no competing interests.

Authors Declaration

This paper does not breach the copy right of other persons and has not been published or submitted for publication to any other journal or book.

References

[1]   | Jaskula B. 2010. 2008 Minerals Yearbook, Beryllium (Advance Release): U.S. Department of the Interior, U.S. Geological Survey.
[2]   | Council NR. 2007. Health effects of beryllium exposure: A literature review Washington, DC: National Research Council of the National Academies, Committee on Toxicology, Committee on Beryllium Alloy Exposures.
[3]   | Rossman MD, Preuss OP, Powers MB, editors. 1991. Beryllium: Biomedical and environmental issues. Baltimore, MD: Williams & Wilkins.
[4]   | Kolanz ME. 2001. Introduction to beryllium: Uses, regulatory history, and disease. App Occ Env Heal 16: 559-567.
[5]   | Jaskula B. 2011. U.S. Geological Survey, Mineral Commodity Summaries. In: Interior USDo editor. p 28-29.
[6]   | Kelly TD, Matos GR. 2011. U.S. Geological Survey, historical statistics for mineral and material commodities in the United States: U.S. Geological Survey data series 140.
[7]   | Cullen MR, Cherniack MG, Kominsky JR. 1986. Chronic beryllium disease in the United States. Seminars in Respiratory Critical Care Medicine 7: 203-209.
[8]   | Infante PF, Newman LS. 2004. Beryllium exposure and chronic beryllium disease. Lancet 363: 415-416.
[9]   | Samuel G, Maier LA. 2008. Immunology of chronic beryllium disease. Current Opinion in Allergy and Clinical Immunology 8: 126-134 110.1097/ACI.1090b1013e3282f1824a1094.
[10]   | Kreiss K, Mroz MM, Zhen BG, Martyny JW, Newman LS. 1993. Epidemiology of beryllium sensitization and disease in nuclear workers. Am Rev Resp Dis 148: 985-991.
[11]   | Kreiss K, Newman LS, Mroz MM, Campbell PA. 1989. Screening blood test identifies subclinical beryllium disease. J Occ Env Med 31: 603-608.
[12]   | Kreiss K, Mroz MM, Zhen B, Wiedemann H, Barna B. 1997. Risks of beryllium disease related to work processes at a metal, alloy, and oxide production plant. Occ Env Med 54: 605-612.
[13]   | Kreiss K, Mroz MM, Newman LS, Martyny J, Zhen B. 1996. Machining risk of beryllium disease and sensitization with median exposures below 2 μg/m3. Am J Ind Med 30: 16-25.
[14]   | Maier LA. 2002. Genetic and exposure risks for chronic beryllium disease. Clinics in Chest Medicine 23: 827-839.
[15]   | Schuler CR, Kitt MM, Henneberger PK, Deubner DC, Kreiss K. 2008. Cumulative sensitization and disease in a beryllium oxide ceramics worker cohort. J Occ Env Med 50: 1343-1350.
[16]   | Kreiss K, Day GA, Schuler CR. 2007. Beryllium: A modern industrial hazard. Ann Rev Pub Heal 28: 259-277.
[17]   | Day GA, Dufresne A, Stefaniak AB, Schuler CR, Stanton ML, Miller WE, Kent MS, Deubner DC, Kreiss K, Hoover MD. 2006. Exposure pathway assessment at a copper–beryllium alloy facility. Ann Occ Hyg 51: 67-80.
[18]   | Newman LS, Mroz MM, Balkissoon R, Maier LA. 2005a. Beryllium sensitization progresses to chronic beryllium disease - A longitudinal study of disease risk. Am J Resp Crit Care Med 171: 54-60.
[19]   | Newman LS, Mroz MM, Balkissoon R, Maier LA. 2005b. Screening for chronic beryllium disease. Am J Resp Crit Care Med 172: 1230-1231.
[20]   | Council NR. 2008. Managing health effects of beryllium exposure Washington, DC: National Research Council of the National Academies, Committee on Toxicology, Committee on Beryllium Alloy Exposures.
[21]   | Middleton DC. 1998. Chronic beryllium disease: Uncommon disease, less common diagnosis. Env Heal Perspectives 106: 765-767.
[22]   | Van Orsdstrand HS, Hughes R, DeNardi JM, Carmody MG. 1945. Beryllium poisoning. JAMA 129: 1084-1090.
[23]   | Hardy HL, Tabershaw IR. 1946. Delayed chemicial pneumonitis occurring in workers exposed to beryllium compounds. Journal of Industrial Hygiene Toxicology 28: 197-211.
[24]   | Cummings K, Stefaniak A, Abbas V, Kreiss K. 2009. A reconsideration of acute beryllium disease Research Triangle Park, NC: US Department of Health and Human Services. 7 p.
[25]   | Newman LS, Lloyd J, Daniloff E. 1996. The natural history of beryllium sensitization and chronic beryllium disease. Env Heal Perspectives 104: 937-943.
[26]   | Eisenbud M, Lisson J. 1983. Epidemiological aspects of beryllium-induced nonmalignant lung disease: A 30-year update. J Occ Env Med 25: 196-202.
[27]   | Müller-Quernheim J, Gaede KI, Fireman E, Zissel G. 2006. Diagnoses of chronic beryllium disease within cohorts of sarcoidosis patients. European Respiratory Journal 27: 1190-1195.
[28]   | Maier LA, Raynolds MV, Young DA, Barker EA, Newman LS. 1999. Angiotensin-1 converting enzyme polymorphisms in chronic beryllium disease. Am J Resp Crit Care Med 159: 1342-1350.
[29]   | Sood A. 2009. Current treatment of chronic beryllium disease. J Occ Env Hyg 6: 762-765.
[30]   | Sood A, Beckett WS, Cullen MR. 2004. Variable response to long-term corticosteroid therapy in chronic beryllium disease. Chest 126: 2000-2007.
[31]   | Newman LS. 1996. Immunology, genetics, and epidemiology of beryllium disease. Chest 109: S40-S43.
[32]   | Maier LA. 2001. Beryllium health effects in the era of the beryllium lymphocyte proliferation test. App Occ Env Heal 16: 514-520.
[33]   | Newman LS. 1995. Beryllium disease and sarcoidosis: Clinical and laboratory links. Sarcoidosis 12: 7-19.
[34]   | Deubner DD, Goodman M, Iannuzzi J. 2001. Variability, predictive value, and uses of the beryllium blood lymphocyte proliferation test (BLPT): Preliminary analysis of the ongoing workforce survey. App Occ Env Heal 16: 521-526.
[35]   | Stange AW, Furman FJ, Hilmas DE. 2004. The beryllium lymphocyte proliferation test: Relevant issues in beryllium health surveillance. Am J Ind Med 46: 453-462.
[36]   | Mroz MM, Kreiss K, Lezotte DC, Campbell PA, Newman LS. 1991. Reexamination of the blood lymphocyte-transformation test in the diagnosis of chronic beryllium disease. Journal of Allergy and Clinical Immunology 88: 54-60.
[37]   | Middleton DC, Mayer AS, Lewin MD, Mroz MM, Maier LA. 2011. Interpreting borderline belpt results. Am J Ind Med 54: 205-209.
[38]   | Middleton DC, Lewin MD, Kowalski PJ, Cox SS, Kleinbaum D. 2006. The BeLPT: Algorithms and implications. Am J Ind Med 49: 36-44.
[39]   | Greene M, Smith SM. 2008. Consenting to uncertainty: challenges for informed consent to disease screening-a case study. Theoretical Medicine and Bioethics 29: 371-386.
[40]   | Ward EM, Okun A, Ruder A, Fingerhut M, Steenland K. 1992. A mortality study of workers at seven beryllium processing plants. Am J Ind Med 22: 885-904.
[41]   | Steenland K, Ward EM. 1991. Lung Cancer incidence among patients with beryllium disease: A cohort mortality study. J Nat Cancer Inst 83: 1380-1385.
[42]   | Sanderson WT, Ward EM, Steenland K, Petersen MR. 2001. Lung cancer case–control study of beryllium workers*. Am J Ind Med 39: 133-144.
[43]   | Schubauer-Berigan MK, Couch JR, Petersen MR, Carreón T, Jin Y, Deddens JA. 2010. Cohort mortality study of workers at seven beryllium processing plants: update and associations with cumulative and maximum exposure. Occ Env Med.
[44]   | Program NT. 2009. Report on Carcinogens, Beryllium (CAS No. 7440-41-7) and beryllium compounds. 11th ed. Washington, DC: U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program
[45]   | Cancer IAfRo. 1993. Monographs on the Evaluation of Carcinogenic Risks to Humans: Beryllium, Cadmium, Mercury, and Exposures in the Glass Manufacturing Industry International Agency for Research on Cancer.
[46]   | Health NIfOSa. 2011. Preventing sensitization and disease from beryllium exposure: Department of Health and Human Services, Centers for Disease Control and Prevention
[47]   | Registry AfTSaD. 2002. Toxicological profile for beryllium Atlanta, GA: U.S. Department of Health and human Services, Public Health Service
[48]   | Groth DH. 1980. Carcinogenicity of beryllium: Review of the literature. Env Res 21: 56-62.
[49]   | Henneberger PK, Goe SK, Miller WE, Doney B, Groce DW. 2004. Industries in the United States with airborne beryllium exposure and estimates of the number of current workers potentially exposed. J Occ Env Hyg 1: 648-659.
[50]   | Stange AW, Hilmas DE, Furman FJ, Gatliffe TR. 2001. Beryllium sensitization and chronic beryllium disease at a former nuclear weapons facility. App Occ Env Heal 16: 405-417.
[51]   | Newman LS, Mroz MM, Maier LA, Daniloff EM, Balkissoon R. 2001. Efficacy of serial medical surveillance for chronic beryllium disease in a beryllium machining plant. J Occ Env Med 43: 231-237.
[52]   | Henneberger PK, Cumro D, Deubner DD, Kent MS, McCawley M, Kreiss K. 2001. Beryllium sensitization and disease among long-term and short-term workers in a beryllium ceramics plant. International Archives of Occupational and Environmental Health 74: 167-176.
[53]   | Maier LA, Martyny JW, Liang J, Rossman MD. 2008. Recent chronic beryllium disease in residents surrounding a beryllium facility. AM J Resp Crit Care Med 177: 1012-1017.
[54]   | Eisenbud M, Wanta RC, Dustan C, Steadman LT, Harris WB, Wolf BS. 1949. Non-occupational berylliosis. J Ind Hyg Tox 31: 282-294.
[55]   | Hardy HL. 1955. Epidemiology, clinical character, and treatment of beryllium poisoning. AMA Archives Industrial Health 11: 273-279.
[56]   | Stange AW, Furman FJ, Hilmas DE. 1996a. Rocky Flats beryllium health surveillance Research Triangle Park, NC: U.S. Department of Health and Human Services. 6 p.
[57]   | Stange AW, Hilmas DE, Furman FJ. 1996b. Possible health risks from low level exposure to beryllium. Toxicology 111: 213-224.
[58]   | Sackett HM, Maier LA, Silveira LJ, Mroz MM, Ogden LG, Murphy JR, Newman LS. 2004. Beryllium medical surveillance at a former nuclear weapons facility during cleanup operations. J Occ Env Med 46: 953-961.
[59]   | Welch L, Ringen K, Bingham E, Dement J, Takaro T, McGowan W, Chen A, Quinn P. 2004. Screening for beryllium disease among construction trade workers at Department of Energy nuclear sites. Am J Ind Med 46: 207-218.
[60]   | Rodrigues EG, McClean MD, Weinberg J, Pepper LD. 2008. Beryllium sensitization and lung function among former workers at the Nevada Test Site. Am J Ind Med 51: 512-523.
[61]   | Arjomandi M, Seward J, Gotway MB, Nishimura S, Fulton GP, Thundiyil J, King TEJ, Harber P, Balmes JR. 2010. Low prevalence of chronic beryllium disease among workers at a nuclear weapons research and development facility. J Occ Env Med 52: 647-652 610.1097/JOM.1090b1013e3181e36439.
[62]   | Mikulski MA, Leonard SA, Sanderson WT, Hartley PG, Sprince NL, Fuortes LJ. 2011. Risk of beryllium sensitization in a low-exposed former nuclear weapons cohort from the cold war era. Am J Ind Med 54: 194-204.
[63]   | Energy Do. 1999. Chronic beryllium disease prevention program: final rule Washington DC: Federal Register. p 64:68854-68914.
[64]   | Energy Do. 2011a. Beryllium-Associated Worker Registry Summary, October 2010: Department of Energy.
[65]   | Energy Do. 2011b. Former Worker Medical Screening Program, 2010 Annual Report: Department of Energy.
[66]   | Newman LS. 2007. Unanswered questions from patients, workers, (and their doctors). The 3rd Annual International Conference on Beryllium Disease Philadelphia, PA.
[67]   | Cragle DL. 2007. Beryllium health effects: Research directions from the persepctive of an occupational epidmeiologist. The 3rd Annual International Conference on Beryllium Disease Philadelphia, PA.
[68]   | Henneberger PK, Kreiss K. 1999. Current NIOSH epidemiologic research on beryllium sensitization and disease. Beryllium: Effect on Worker health Washington, DC.
[69]   | McCawley M. 2008. Beryllium research needs. Third International Symposium on Beryllium Particulates and Their Detection Albuquerque, NM.
[70]   | Cannon WB. 1929. Bodily changes in pain, hunger, fear and rage: An account of recent research into the function of emotional excitement. 2nd ed. New York, NY: Appleton-Century-Crofts,.
[71]   | Selye H. 1936. A syndrome produced by diverse nocuous agents. Nature 138.
[72]   | Selye H. 1956. The Stress of Life New York, NY: McGraw-Hill Book Company.
[73]   | Lazarus RS. 1966. Psychological stress and the coping process New York, NY: McGraw-Hill Book Company, Inc.
[74]   | Selye H. 1975. Confusion and controversy in the stress field. Journal of Human Stress 1: 37-44.
[75]   | Holroyd KA, Lazarus RS. 1982. Stress, coping and somatic adaptation. In: Goldberger LEaB, S. editor. Handbook of Stress: Theoretical and Clinical Aspects New York, NY: Free Press. p pp. 21-35.
[76]   | Lazarus RS, Folkman S. 1991. Stress and coping: An anthology. In: Monat A, Lazarus RS editors. The Concept of Coping. 3rd ed. New York, NY: Columbia University Press. p 189-206.
[77]   | O'Leary A. 1990. Stress, emotion, and human immune function. Psychological Bulletin 108: 363-382.
[78]   | Folkman S, editor 2011. The Oxford handbook of stress, health, and coping. New York, NY: Oxford University Press.
[79]   | Glanz K, Rimer BK, Viswanath K, editors. 2008. Health behavior and health education: Theory, research, and practice. San Francisco: Jossey-Bass.
[80]   | Lazarus RS, Folkman S. 1984. Stress, appraisal, and coping New York, NY: Springer.
[81]   | Taylor SE. 1983. Adjustment to threatening events. The American Psychologist 38: 1161.
[82]   | Kalman TP, Wilson PG, Kalman CM. 1983. Psychiatric morbidity in long-term renal transplant recipients and patients undergoing hemodialysis. The Journal of the American Medical Association 250: 55-58.
[83]   | Zyzanski SJ, Stanton BA, Jenkins CD, Klein MD. 1981. Medical and psychosocial outcomes in survivors of major heart surgery. J Psychosomatic Res 25: 213-221.
[84]   | Mechanic D. 1978. Medical sociology. 2nd ed. New York, NY: The Free Press.
[85]   | Livneh H, Antonak RF. 1997. Psychosical adaptation to chronic illness and disability Gaithersburg, MD: Aspen Publishers, Inc.
[86]   | Cassileth BR, Lusk EJ, Strouse TB, Miller DS, Brown LL, Cross PA, Tenaglia AN. 1984. Psychosocial status in chronic illness. A comparative analysis of six diagnostic groups. New England J Med 311: 506-511.
[87]   | Derogatis LR, Abeloff MD, Melisaratos N. 1979. Psychological coping mechanisms and survival time in metastatic breast cancer. The Journal of the American Medical Association 242: 1504-1508.
[88]   | Derogatis LR, Morrow GR, Fetting J, Penman D, Piasetsky S, Schmale AM, Henrichs M, Carnicke CLM. 1983. The prevalence of psychiatric disorders among cancer patients. The Journal of the American Medical Association 249: 751-757.
[89]   | Derogatis LR. 1986. The psychosocial adjustment to illness scale (PAIS). J Psychosomatic Res 30: 77-91.
[90]   | Merluzzi TV, Martinez-Sanchez MA. 1997. Factor structure of the psychosocial adjustment to illness scale (self-report) for persons with cancer. Psychological Assessment 9: 269-276.
[91]   | Rodrigue JR, Kanasky WF, Jackson SI, Perri MG. 2000. The psychosocial adjustment to iIllness scale--self-seport: Factor structure and item stability. Psychological Assessment 12: 409-413.
[92]   | Cain EN, Kohorn EI, Quinlan DM, Latimer K, Schwartz PE. 1986. Psychosocial benefits of a cancer support group. Cancer 57: 183-189.
[93]   | Jenkins PL, Linington A, Whittaker JA. 1991. A retrospective study of psychosocial morbidity in bone marrow transplant recipients. Psychosomatics 32: 65-71.
[94]   | Northouse L, Mood DW, Templin T, Mellon S, George T. 2000. Couples' patterns of adjustment to colon cancer. Social Science & Medicine 50: 271-284.
[95]   | Greer S, Moorey S, Baruch JD, Watson M, Robertson BM, Mason A, Rowden L, Law MG, Bliss JM. 1992. Adjuvant psychological therapy for patients with cancer: a prospective randomised trial. British Med J 304: 675-680.
[96]   | Soskolne V, De-Nour AK. 1989. The psychosocial adjustment of patients and spouses to dialysis treatment. Social Science & Medicine 29: 497-502.
[97]   | De-Nour AK. 1982. Psychological adjustment to illness scale (PAIS): A study of chronic hemodialysis patients. J Psychosomatic Res 26: 11-22.
[98]   | Stubbing D, Haalboom P, Barr P. 1998. Comparison of the psychosocial adjustment to iIllness scale-self report and clinical judgment in patients with chronic lung disease. Journal of Cardiopulmonary Rehabilitation and Prevention 18: 32-36.
[99]   | Browne G, Byrne C, Brown B, Pennock M, Streiner D, Roberts R, Eyles P, Truscott D, Dabbs R. 1985. Psychosocial adjustment of burn survivors. Burns 12: 28-35.
[100]   | Pakenham KI. 1999. Adjustment to multiple sclerosis: Application of a stress and coping model. Health Psychology 18: 383-392.
[101]   | Folkman S, Greer S. 2000. Promoting psychological well-being in the face of serious illness: When theory, research and practice inform each other. Psycho-Oncology 9: 11-19.
[102]   | Rehse B, Pukrop R. 2003. Effects of psychosocial interventions on quality of life in adult cancer patients: Meta analysis of 37 published controlled outcome studies. Patient Education and Counseling 50: 179-186.
[103]   | Sharpe L, Curran L. 2006. Understanding the process of adjustment to illness. Social Science & Medicine 62: 1153-1166.
[104]   | Brashers DE. 2001. Communication and uncertainty management. Journal of Communication 51: 477-497.
[105]   | Babrow AS, Hines SC, Kasch CR, editors. 2000. Managing uncertainty in illness Explanation: An application of problematic integration theory. Hillsdale, NJ: Erlbaum.
[106]   | Norton RW. 1975. Measurement of ambiguity tolerance. Journal of Personality Assessment 39: 607.
[107]   | Babrow A, Kasch C, Ford L. 1998. The many meanings of uncertainty in illness: Toward a systematic accounting. Health Communication 10: 1-23.
[108]   | Mishel MH. 1981. The measurement of uncertainty in illness. Nursing Research 30: 258-263.
[109]   | Mishel MH. 1983. Adjusting the fit: development of uncertainty scales for specific clinical populations. West J Nurs Res 5: 355-370.
[110]   | Mishel MH. 1984. Perceived uncertainty and stress in illness. Research Nursing Health 7: 163-171.
[111]   | Mishel MH, Braden CJ. 1988. Finding meaning: Antecedents of uncertainty in illness. Nursing Research 37: 98-103.
[112]   | Mishel MH, Hostetter T, King B, Graham V. 1984. Predictors of psychosocial adjustment in patients newly diagnosed with gynecological cancer. Cancer Nursing 7: 291-300.
[113]   | Mishel MH, Murdaugh CL. 1987. Family adjustment to heart transplantation: Redesigning the dream. Nursing Research 36: 332-338.
[114]   | Mishel MH. 1988. Uncertainty in illness. J Nur Schol 20: 225-232.
[115]   | Mishel MH. 1990. Reconceptualization of the uncertainty in illness theory. J Nur Schol 22: 256-262.
[116]   | Christman NJ, McConnell EA, Pfeiffer C, Webster KK, Schmitt M, Ries J. 1988. Uncertainty, coping, and distress following myocardial infarction: Transition from hospital to home. Research in Nursing & Health 11: 71-82.
[117]   | Mishel MH. 1997. Uncertainty in acute illness. Ann Rev Nursing Res 15: 57-80.
[118]   | Mishel MH, Padilla GV, Grant MM, Sorenson DS. 1991. Uncertainty in illness theory: A replication of the mediating effects of mastery and coping. Nursing Research 40: 236-240.
[119]   | Webster KK, Christman NJ, Mishel MH. 1988. Perceived uncertainty and coping post myocardial Infarction. W J Nurs Res 10: 384-400.
[120]   | White RE, Frasure-Smith N. 1995. Uncertainty and psychologic stress after coronary angioplasty and coronary bypass surgery. Heart & Lung: The Journal of Acute and Critical Care 24: 19-27.
[121]   | Johnson LM, Zautra AJ, Davis MC. 2006. The role of illness uncertainty on coping with fibromyalgia symptoms. Health Psychology 25: 696-703.
[122]   | Bailey D, Barroso J, Muir A, Sloane R, Richmond Ji, McHutchison J, Patel K, Landerman L, Mishel M. 2010. Patients with chronic hepatitis C undergoing watchful waiting: Exploring trajectories of illness uncertainty and fatigue. Research in Nursing & Health 33: 465-473.
[123]   | Sammarco A, Konecny L. 2008. Quality of life, social support, and uncertainty among latina breast cancer survivors. Oncology Nursing Forum 35: 844-849.
[124]   | McCormick KM. 2002. A concept analysis of uncertainty in iIllness. J Nur Schol 34: 127-131.
[125]   | Neville KL. 2003. Uncertainty in illness: an integrative review. Orthopaedic Nursing 22: 206-214.
[126]   | Cohen MH. 1993. The unknown and the unknowable-managing sustained uncertainty. W J Nurs Res 15: 77-96.
[127]   | Babrow AS, Kline KN. 2000. From "reducing" to "coping with" uncertainty: Reconceptualizing the central challenge in breast self-exams. Social Science & Medicine 51: 1805-1816.
[128]   | Society AC. 2010. Cancer Facts & Figures. Special Section: Prostate Cancer Atlanta, GA: American Cancer Society p23-36.
[129]   | Tombal B. 2006. Over- and underdiagnosis of prostate cancer: The dangers. European Urology Supplements 5: 511-513.
[130]   | Eton DT, Lepore SJ. 2002. Prostate cancer and health-related quality of life: A review of the literature. Psycho-Oncology 11: 307-326.
[131]   | Warlick CA, Allaf ME, Carter HB. 2006. Expectant treatment with curative intent in the prostate-specific antigen era: Triggers for definitive therapy. Urologic Oncology: Seminars and Original Investigations 24: 51-57.
[132]   | Oliffe JL, Davison BJ, Pickles T, Mroz L. 2009. The self-management of uncertainty among men undertaking active surveillance for low-risk prostate cancer. Qualitative Health Research 19: 432-443.
[133]   | Germino BB, Mishel MH, Belyea M, Harris L, Ware A, Mohler J. 1998. Uncertainty in prostate cancer. Ethnic and family patterns. Cancer Practice 6: 107-113.
[134]   | Shaha M, Cox CL, Talman K, Kelly D. 2008. Uncertainty in breast, prostate, and colorectal cancer: implications for supportive care. J Nur Schol 40: 60-67.
[135]   | Wallace M. 2003. Uncertainty and quality of life of older men who undergo watchful waiting for prostate cancer. Oncol Nurs Forum 30: 303-309.
[136]   | Bailey DE, Jr., Wallace M, Mishel MH. 2007. Watching, waiting and uncertainty in prostate cancer. Journal Clinical Nursing 16: 734-741.
[137]   | Kazer MW, Bailey DE, Colberg J, Kelly WK, Carroll P. 2011. The needs for men undergoing active surveillance (AS) for prostate cancer: Results of a focus group study. Journal of Clinical Nursing 20: 581-586.
[138]   | Bailey Jr D, Wallace M, Latini D, Hegarty J, Carroll P, Klein E, Albertsen P. 2011. Measuring illness uncertainty in men undergoing active surveillance for prostate cancer. App Nurs Res In Press, Corrected Proof.
[139]   | Mishel MH, Belyea M, Germino BB, Stewart JL, Bailey DE, Robertson C, Mohler J. 2002. Helping patients with localized prostate carcinoma manage uncertainty and treatment side effects. Cancer 94: 1854-1866.
[140]   | Steginga SK, Turner E, Donovan J. 2008. The decision-related psychosocial concerns of men with localised prostate cancer: Targets for intervention and research. World Journal of Urology 26: 469-474.
[141]   | Mishel MH, Germino BB, Lin L, Pruthi RS, Wallen EM, Crandell J, Blyler D. 2009. Managing uncertainty about treatment decision making in early stage prostate cancer: A randomized clinical trial. Patient Education and Counseling 77: 349-359.
[142]   | Chambers S, Pinnock C, Lepore S, Hughes S, O'Connell D. 2011. A systematic review of psychosocial interventions for men with prostate cancer and their partners. Patient Education and Counseling.
[143]   | Kershaw TS, Mood DW, Newth G, Ronis DL, Sanda MG, Vaishampayan U, Northouse LL. 2008. Longitudinal analysis of a model to predict quality of life in prostate cancer patients and their spouses. Ann Behavorial Med 36: 117-128.
[144]   | Song L, Northouse LL, Braun TM, Zhang LN, Cimprich B, Ronis DL, Mood DW. 2010. Assessing longitudinal quality of life in prostate cancer patients and their spouses: a multilevel modeling approach. Quality of Life Research 20: 371-381.