Pharmacology of antineoplastic agents in older cancer patients

Persons over the age of 65 years are the fastest growing segment of the United States population. In the next 30 years it will comprise over 20% of the population. Fifty percent of all cancers occur in this age group and therefore there will be an expected rise in the total cancer burden. Data is becoming available which will better guide the use of chemotherapy in the older patient population. Studies will be presented discussing pharmacokinetic data on a number of chemotherapeutic agents with an emphasis on those which have entered practice over the past few years. Many of these agents seem to have a beneficial therapeutic index, particularly in regard to older patients. There has also been an increasing trend toward the use of oral chemotherapy. Factors that must be considered in choosing chemotherapy include limitations of saturability of absorption, patient compliance and the pharmacokinetic and pharmacodynamic changes which occur in older patients. Interpatient variability and age related changes in drug metabolism are discussed. Careful attention to the physiologic changes with age, and dose adjustments necessary for end organ dysfunction (renal, hepatic) are needed to ensure the safe administration of chemotherapy.     

The impact of immuno-aging on SARS-CoV-2 vaccine development

The SARS-CoV-2 pandemic has almost 56 million confirmed cases resulting in over 1.3 million deaths as of November 2020. This infection has proved more deadly to older adults (those >65 years of age) and those with immunocompromising conditions. The worldwide population aged 65 years and older is increasing, and the total number of aged individuals will outnumber those younger than 65 years by the year 2050. Aging is associated with a decline in immune function and chronic activation of inflammation that contributes to enhanced viral susceptibility and reduced responses to vaccination. Here we briefly review the pathogenicity of the virus, epidemiology and clinical response, and the underlying mechanisms of human aging in improving vaccination. We review current methods to improve vaccination in the older adults using novel vaccine platforms and adjuvant systems. We conclude by summarizing the existing clinical trials for a SARS-CoV-2 vaccine and discussing how to address the unique challenges for vaccine development presented with an aging immune system.

     

Aging with HIV: a practical review

The worldwide elderly population is expected to grow by an additional 694 million people by 2025. By that time, there will be approximately two billion elderly people in the world, most of whom (80%) will be living in developing countries. Based on recent estimates, this population will number over 40 million in 2030 in Brazil and a consequent increase in governmental spending for this population can be expected. Since highly active antiretroviral therapy became available in the mid-1990s, the life expectancy of people living with HIV has increased significantly. Approximately 12 million life years were added to the world between 1996 and 2008 as a consequence of wider access to highly active antiretroviral therapy. In Brazil, the incidence of AIDS among the population aged ≥50 years doubled between 1996 and 2006. The development of antiretroviral therapy has allowed individuals diagnosed at a younger age to live longer, which partially explains the aging tendency associated with the HIV/AIDS epidemic. It is estimated that by 2015, subjects aged ≥50 years will represent 50% of the people living with HIV undergoing clinical treatment. This scenario presents some challenges, including the fact that the diagnosis of HIV tends to be delayed in older patients compared to younger patients because the symptoms of HIV can be confused with those of other common diseases among the elderly and also because healthcare professionals do not consider this population to be at high risk for HIV infection. In regard to the individuals diagnosed with HIV, a further challenge is presented by the morbidity normally associated with aging. Finally, the elderly also exhibit higher susceptibility to the toxic effects and pharmacological interactions of medications. The present article reviews the literature regarding the profile of HIV infection among individuals aged ≥50 years focusing on practical features related to the clinical approach and long-term follow-up of this population.     

Cancer vaccines in old age

The incidence of cancer has increased over the last decade, mainly due to an increase in the elderly population. Vaccine therapy for cancer is less toxic than chemotherapy or radiation and could be, therefore, especially effective in older, more frail cancer patients. However, it has been shown that older individuals do not respond to vaccine therapy as well as younger adults. This has been attributed to T cell unresponsiveness, a phenomenon also observed in cancer patients per se. This review summarizes the current knowledge of T cell unresponsiveness in cancer patients and elderly, the results of cancer vaccination in preclinical models and in clinical trials, and recent data of cancer vaccination at young and old age in preclinical models. Finally, experimental approaches will be proposed how to make cancer vaccines more effective at older age.     

HIV infection in the elderly

In the US, an estimated 1 million people are infected with HIV, although one-third of this population are unaware of their diagnosis. While HIV infection is commonly thought to affect younger adults, there are an increasing number of patients over 50 years of age living with the condition. UNAIDS and WHO estimate that of the 40 million people living with HIV/AIDS in the world, approximately 2.8 million are 50 years and older. With the introduction of highly active antiretroviral therapy (HAART) in the mid-1990s, survival following HIV diagnosis has risen dramatically and HIV infection has evolved from an acute disease process to being managed as a chronic medical condition. As treated HIV-infected patients live longer and the number of new HIV diagnoses in older patients rise, clinicians need to be aware of these trends and become familiar with the management of HIV infection in the older patient. This article is intended for the general clinician, including geriatricians, and will review epidemiologic data and HIV treatment as well as provide a discussion on medical management issues affecting the older HIV-infected patient.     

Studies on free radicals,antioxidants, and co-factors

The interplay between free radicals, antioxidants, and co-factors is important in maintaining health, aging and age-related diseases. Free radicals induce oxidative stress, which is balanced by the body’s endogenous antioxidant systems with an input from co-factors, and by the ingestion of exogenous antioxidants. If the generation of free radicals exceeds the protective effects of antioxidants, and some co-factors, this can cause oxidative damage which accumulates during the life cycle, and has been implicated in aging, and age dependent diseases such as cardiovascular disease, cancer, neurodegenerative disorders, and other chronic conditions. The life expectancy of the world population is increasing, and it is estimated that by 2025, 29% of the world population will be aged ≥60 years, and this will lead to an increase in the number of older people acquiring age-related chronic diseases. This will place greater financial burden on health services and high social cost for individuals and society. In order to acheive healthy aging the older people should be encouraged to acquire healthy life styles which should include diets rich in antioxidants. The aim of this review is to highlight the main themes from studies on free radicals, antioxidants and co-factors, and to propose an evidence-based strategy for healthy aging.     

First- and third-person perceptions of images of older people in advertising: an inter-generational evaluation

With the baby boomers increasing in age, the number of older Americans is projected to increase to 82 million by 2050, an increase of 225% from the year 2000. But despite their growing numbers, older individuals continue to face negative attitudes toward them, their way of thinking, and their abilities. These negative attitudes result from the assumption that older people have diminished physical and mental abilities, when in fact, today's older adults are more active and in better physical and mental health than those in any previous generation. This study examines the relationship between first- and third-person perceptions and positive and negative images by determining how older people and younger people perceive each other. More specifically, when older and younger individuals look at positive and negative images of older people in advertisements, what is their perception of the effects those images will have on the other generation? Our findings show that both first- and third-person effects exist and that their perceptions depend on whether the images in the advertisements are positive or negative. The results also indicate that young people rely on the stereotypes they hold of older people when making their perceptions.     

Asthma in Seniors: Part 1. Evidence for Underdiagnosis, Undertreatment, and Increasing Morbidity and Mortality

At least 2 million US citizens over 65 years of age have asthma as a chronic disease, a number that will rapidly increase as the population ages. We used computer-assisted searches to identify epidemiologic studies specific for this age group published in the commonly available medical literature in English between 1988 and 2008. The prevalence of current asthma in individuals aged over 65 years is high (5.3%). Affected patients appear to perceive symptoms of asthma differently than younger patients, often have comorbid conditions with similar symptoms, and present for medical care later and with more fixed airways obstruction. Approximately 50% of deaths from asthma occur in the elderly, and mortality is increasing (10.5/100,000). We found only one longitudinal epidemiologic study that addressed the natural history of asthma in patients aged over 65 years, and that study used historical controls. Asthma in the elderly is a poorly studied, growing chronic disease that is underdiagnosed and undertreated. Present paradigms for diagnosis require modification.     

Early Diagnosis of Alzheimer's Disease: Clinical and Economic Benefits

An estimated four million individuals in the United States have Alzheimer's disease (AD). This number is expected to more than triple by mid-century. Primary care physicians have a key role in evaluating older patients for early signs of dementia and in initiating treatment that can significantly retard its progression over the maximum period of time. That role and its challenges will inevitably grow along with the expected increase in the population aged 65 and older. The tendency for physicians to dismiss memory complaints as normal aging must be replaced by awareness of the need to assess and possibly intervene. Early intervention is the optimal strategy, not only because the patient's level of function will be preserved for a longer period, but also because community-dwelling patients with AD incur less societal cost than those who require long-term institutional placement. Institutionalization contributes heavily to the annual cost of care for AD in the United States, which is estimated to be $100 billion annually.     

Heart failure in the elderly: a U.S. perspective

Heart failure (HF) affects 5 million Americans, of whom three-fourths are over age 65 and half are over age 75.1 HF is currently the leading cause of hospitalization among older adults in the U.S., and it is the most costly medical illness by a factor of almost two.……     

OASIS: A Community-based Model for Successful Aging

OASIS, a national non-profit organization founded in 1982, is dedicated to enriching the lives of people age 50 and older by offering programs that stimulate the intellect, promote healthy and active lifestyles and encourage community service. The OASIS vision is for older adults across the United States to have opportunities to pursue vibrant, healthy, productive and meaningful lives. OASIS seeks to positively impact the older adults’ lives—by partnering with other organizations to share knowledge; offer evidence-based programs; conduct evaluations; and adapt to meet the needs of diverse audiences. Today, nearly 40,000 people participate at any one time in OASIS programs, with more than 6,700 volunteers providing over 488,000 hours of service each year. Approximately 370,000 adults are members of OASIS in 39 cities across the country. This number is expected to increase dramatically with the aging of the United States population. It is estimated that, between the years 2000 and 2030, the number of older adults will grow from 35 million to 72 million.     

Where is Malaysia in the midst of the Asian epidemic of diabetes mellitus?

Population studies all over the world have clearly showed that the prevalence of Type 2 diabetes mellitus (DM) is escalating at phenomenal scale and very likely we are heading towards epidemic proportions. In 1985, the estimated population of diabetic individuals in the world was 30 million but by 1995 this figure soared to 135 million. Based on current trends, epidemiologists predict that the population of diabetic individuals will swell up to a staggering 300 million by the year 2025. Almost half of that will be in the Asia Oceania region alone. Dr Hilary King of WHO pointed out that there will be a projected rise of about 42% in developed countries whereas the developing countries will see an escalation to the magnitude of 170% (H. King, R.E. Aubert, W.H. Herman, Global burden of diabetes, 1995-2025: prevalence, numerical estimates and projections, Diabetes Care 21 (1998) 1414-1431; WHO Health Report 1997, WHO Switzerland). There will be a 3-fold rise of the disease in Asia and much of these will be seen in China (40 million) and India (55 million) by virtue of the massive population of these countries. Nevertheless, the other rapidly developing Asian nations like Singapore, Malaysia, Thailand and those making up Indochina will experience the surge. At the same time the prevalence and incidence of diabetes complications will also increase. Based on recent WHO prediction (WHO Newsletter, The global burden of diabetes 1995-2025. World Diabetes 3 (1997) 5-6), it is estimated that by the year 2000 the following figures will be seen:Diabetes complications are major causes of premature death all over the world and most of these are avoidable. DCCT and UKPDS are landmark studies showing strong evidence that major complications can be drastically reduced by maintaining to near normoglycaemic control.     

The Evolution of Living Kidney Donation and Transplantation in Older Adults

Kidney transplantation is a good option for adults aged 65 and older with end‐stage renal disease because it has been shown to reduce morbidity and mortality, improve quality of life, and is more cost‐effective than other renal replacement options. However, older age has been a deterrent to access to the deceased donor waiting list, and individuals aged 65 and older have a lower probability of being referred to and listed for transplantation compared to younger adults. Because the deceased organ supply is limited, living donor kidney transplantation offers an effective alternative for older adults facing long waiting times for cadaveric organs. This article describes the evolution of living kidney donation and transplantation in older adults over 15 years using the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients database. Between 1997 and 2011, 28,034 kidney transplantations were performed in adults aged 65 and older. Living‐donor and cadaveric kidney transplantation increased in older adults over the 15‐year period. Offspring are the most common living donors in this age group, followed by unrelated donors (e.g., friends), whereas the most common donors in younger transplant recipients are spouses, siblings, and parents. The number of living kidney donors aged 65 and older is slowly increasing, although the total number of transplants in this age group remains low. The expansion of living‐donor kidney transplantation in the aging population may offer a solution for organ shortage and thereby improve the quality of life of older adults. More research is needed to understand the older donor–recipient relationship and barriers to transplantation in this population.     

Effect of Therapeutic Ionizing Radiation on Implantable Electronic Devices: Systematic Review and Practical Guidance

Cardiac implantable electronic devices (CIEDs) have been in use for over 50 years and their therapeutic value is undisputable. With the rapidly aging population, it is estimated that the number of CIEDs will grow dramatically over the next 2 decades. Given these predictions, the topic of management of concomitant conditions associated with older age becomes more relevant than ever. In particular, the number of patients with an implanted CIED diagnosed with cancer is expected to rise by about 70%, from 14 million in 2012 to 22 million within the next 2 decades. Treatment of most of these tumors and tumor metastases requires radiation therapy. However, the necessary high doses of radiation can potentially interact with the function, longevity, and integrity of the CIEDs and/or cause harm to the patient. The impact of an absence of clear therapeutic guidelines for oncology patients with CIEDs who should undergo radiation therapy is vast; and due to the fear of possible complications related to device failure, many of these patients may not be treated adequately to their needs, which can strongly affect their prognosis. This article summarizes the available data on the management of patients with CIEDs undergoing radiotherapy. It systematically presents possible causes and consequences of direct and scattered radiation on CIEDs, highlights possible complications that may occur during this kind of treatment, and provides practical guidance for this challenging real life clinical setting.     

Perioperative care of the geriatric patient for noncardiac surgery

Adults age 65 and over are the fastest growing segment of the population in the United States and around the world. As the size of this population expands, the number of older adults referred for surgical procedures will continue to increase. Due to the physiologic changes of aging and the increased frequency of comorbidities, older adults are at increased risk for adverse outcomes, and perioperative care is inherently more complex than in younger individuals. In this review, we discuss the physiologic changes of aging relevant to the surgical patient, comprehensive preoperative assessment, and postoperative management of common complications in older adults in order to promote optimal clinical outcomes both perioperatively and long-term.     

Incorporating geriatrics into the respiratory care curriculum

The absolute number of adults over the age of 65 years is increasing nationwide and worldwide. Older adults today are more independent and self-sufficient than persons of that age were a generation ago. An increased incidence of acute and chronic disease results in relative morbidity but less mortality in those aged 65 years and older. The decision to incorporate or infuse education in geriatrics into existing respiratory care classes is not difficult. Implementation may be a little more challenging, but gradually adding geriatric components to courses over time is a perfectly reasonable way to introduce students to their future patient population. Fortunately, a growing number of elderly individuals desire to treat pathology rather than accept it as an inevitable consequence of aging.For these reasons, respiratory therapists have been brought into the realm of geriatric medicine, more by default than by organizational planning. The most passionate converts to the important role of geriatrics are physicians, nurses, and therapists who have recently attempted to shepherd their own aging parents through a health care system. If that experience that leads to these conversions could be measured and communicated, the world at large might be convinced of the value of education in geriatrics.     

Health and Health Care System for Older Persons

Thailand has now reached a new demographic turning point with the advent of an ageing society. Improvements in the health care system and technology advancement over recent decades mean that Thais can now enjoy better health in old age than previously. Life expectancy at birth for the Thai population has been increasing steadily, and there has been an improvement among older persons in all aspects of health behaviors. Even though the majority of Thai elderly are sufficiently healthy to take care of themselves, there are an increasing number of elderly people who have difficulty with essential daily activities, leading to problems with disability and dependency. Non communicable diseases such as hypertension, diabetes mellitus, dyslipidemia, osteoarthritis, cardio-cerebrovascular diseases and tumor are some of the major health problems confronting older Thais. Due a higher incidence of illness and chronic conditions as compared to young people, the elderly typically require different types of care and health services. As Thailand becomes an ageing society, health services and proper care systems specifically for the elderly group need to be prepared and well established. Given the far greater likelihood of chronic conditions and disabilities among older persons compared to the rest of population, pressures on long-term care facilities and services will increase enormously. The issue of ageing should be given a high priority in both local and national government agendas. All sectors should be involved in adjusting care systems and programs to accommodate the rapid growth of older persons and the relative balance of age groups within the population. It will be crucial for the health sectors to provide services oriented towards geriatric and long-term care issues.     

Hematopoietic growth factors in the older cancer patient

Aging is associated with a progressive decline in the functional reserve of multiple organ systems, which may lead to enhanced susceptibility to stress such as that caused by cancer chemotherapy. Myelodepression is the most common and the most commonly fatal complication of antineoplastic drug therapy and may represent a serious hindrance to the management of cancer in older individuals. This is already a common and pervasive problem and promises to become more so. Currently 60% of all neoplasms occur in persons aged 65 years and older, and this percentage is expected to increase as the population ages. This well-known phenomenon, sometimes referred to as squaring or the age pyramid, is caused by the combination of an increasing life expectancy and a decreasing birth rate. This article explores the use of hematopoietic growth factors in the older cancer patient after reviewing the influence of age on hemopoiesis and chemotherapy-related complications. The issue is examined in terms of effectiveness and cost. An outline of the assessment of the older cancer patient is provided at the end of the chapter as a frame of reference for clinical decisions.     

Treatment of cancer in old age, shortcomings and challenges.

The burden of cancer in old age is increasing as a result from both the expanding number of older persons in the population and the high and still increasing cancer incidence in this group. The goal of this article is to outline the shortcomings and challenges of the management of cancer in the elderly. Several factors contribute to the complexity of this management, such as the enormous heterogeneity in this population, increased co-morbidity, reduced functional status, increased frailty and different treatment goals from those in younger patients. Other problems include the lack of data on the efficacy and toxicity of cancer treatment in this age group, the lack of awareness of life-expectancy and the lack of an easy applicable and validated frailty scale. Improvement of the quality of oncological care in this age group could be achieved by initiation of clinical trials specifically directed at the elderly, in which a frailty scale is implemented. The results of these trials may lead to more evidence-based decision making in cancer treatment in the elderly.