Mark S. Lachs

Predicting Chemotherapy Toxicity in Older Adults With Cancer: A Prospective Multicenter Study

PURPOSE Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity. PATIENTS AND METHODS Patients age ≥ 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P < .001). CONCLUSION A risk stratification schema can establish the risk of chemotherapy toxicity in older adults. Geriatric assessment variables independently predicted the risk of toxicity.

Caregiver Burden: A Clinical Review

IMPORTANCE Caregiver burden may result from providing care for patients with chronic illness. It can occur in any of the 43.5 million individuals providing support to midlife and older adults. Caregiver burden is frequently overlooked by clinicians. OBJECTIVES To outline the epidemiology of caregiver burden; to provide strategies to diagnose, assess, and intervene for caregiver burden in clinical practice; and to evaluate evidence on interventions intended to avert or mitigate caregiver burden and related caregiver distress. EVIDENCE Cohort studies examining the relation between demographic and social risk factors and adverse outcomes of caregiver burden were reviewed. Review of recent meta-analyses to summarize the effectiveness of caregiver burden interventions were identified by searching Ovid MEDLINE, AgeLine, and the Cochrane Library. RESULTS Risk factors for caregiver burden include female sex, low educational attainment, residence with the care recipient, higher number of hours spent caregiving, depression, social isolation, financial stress, and lack of choice in being a caregiver. Practical assessment strategies for caregiver burden exist to evaluate caregivers, their care recipients, and the care recipients overall caregiving needs. A variety of psychosocial and pharmacological interventions have shown mild to modest efficacy in mitigating caregiver burden and associated manifestations of caregiver distress in high-quality meta-analyses. Psychosocial interventions include support groups or psychoeducational interventions for caregivers of dementia patients (effect size, 0.09-0.23). Pharmacologic interventions include use of anticholinergics or antipsychotic medications for dementia or dementia-related behaviors in the care recipient (effect size, 0.18-0.27). Many studies showed improvements in caregiver burden-associated symptoms (eg, mood, coping, self-efficacy) even when caregiver burden itself was minimally improved. CONCLUSIONS AND RELEVANCE Physicians have a responsibility to recognize caregiver burden. Caregiver assessment and intervention should be tailored to the individual circumstances and contexts in which caregiver burden occurs.

Spectrum Bias in the Evaluation of Diagnostic Tests: Lessons from the Rapid Dipstick Test for Urinary Tract Infection

OBJECTIVE To determine if the leukocyte esterase and bacterial nitrite rapid dipstick test for urinary tract infection (UTI) is susceptible to spectrum bias (when a diagnostic test has different sensitivities or specificities in patients with different clinical manifestations of the disease for which the test is intended). DESIGN Cross-sectional study. PATIENTS A total of 366 consecutive adult patients in whom clinicians performed urinalysis to diagnose or exclude UTI. SETTING An urban emergency department and walk-in clinic. MEASUREMENTS After the patient encounter, but before dipstick test or culture was done, clinicians recorded the signs and symptoms that were the basis for suspecting UTI and for performing a urinalysis and an estimate of the probability of UTI based on the clinical evaluation. For all patients who received urinalysis, dipstick tests and culture were done in the clinical microbiology laboratory by medical technologists blinded to clinical evaluation. Sensitivity for the dipstick was calculated using a positive result in either leukocyte esterase or bacterial nitrite, or both, as the criterion for a positive dipstick, and greater than 10(5) CFU/mL for a positive culture. RESULTS In the 107 patients with a high (greater than 50%) prior probability of UTI, who had many characteristic UTI symptoms, the sensitivity of the test was excellent (0.92; 95% CI, 0.82 to 0.98). In the 259 patients with a low (less than or equal to 50%) prior probability of UTI, the sensitivity of the test was poor (0.56; CI, 0.03 to 0.79). CONCLUSIONS The leukocyte esterase and bacterial nitrite dipstick test for UTI is susceptible to spectrum bias, which may be responsible for differences in the tests sensitivity reported in previous studies. As a more general principle, diagnostic tests may have different sensitivities or specificities in different parts of the clinical spectrum of the disease they purport to identify or exclude, but studies evaluating such tests rarely report sensitivity and specificity in subgroups defined by clinical symptoms. When diagnostic tests are evaluated, information about symptoms in the patients recruited for study should be included, and analyses should be done within appropriate clinical subgroups so that clinicians may decide if reported sensitivities and specificities are applicable to their patients.

Falls and Physical Performance Deficits in Older Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy

OBJECTIVES Men experience a decrease in lean muscle mass and strength during the first year of androgen deprivation therapy (ADT). The prevalence of falls and physical and functional impairment in this population have not been well described. METHODS A total of 50 men aged 70 years and older (median 78) receiving ADT for systemic prostate cancer (80% biochemical recurrence) underwent functional and physical assessments. The functional assessments included Katzs Activities of Daily Living (ADLs) and Lawtons Instrumental Activities of Daily Living (IADLs). Patients completed the Vulnerable Elders Survey-13, a short screening tool of self-perceived functional and physical performance ability. Physical performance was assessed using the Short Physical Performance Battery. The history of falls was recorded. Of the 50 patients, 40 underwent follow-up assessment with the same instruments 3 months after the initial assessment. RESULTS Of the 50 men, 24% had impairment in the ADLs, 42% had impairment in the IADLs, 56% had abnormal Short Physical Performance Battery findings, and 22% reported falls within the previous 3 months. Within the Short Physical Performance Battery, deficits occurred within all subcomponents (balance, walking, and chair stands). On univariate analysis, age, deficits in ADLs and IADLs, and abnormal cognitive and functional screen findings were associated with an increased risk of abnormal physical performance. ADL deficits, the use of an assistive device, and abnormal functional screen findings were associated with an increased risk of falling. CONCLUSIONS The results of our study have shown that older men with prostate cancer receiving long-term ADT exhibit significant functional and physical impairment and are at risk of falls that is greater than that for similar-aged cohorts. Careful assessment of the functional and physical deficits in older patients receiving ADT is warranted.

A prospective community-based pilot study of risk factors for the investigation of elder mistreatment.

Purpose: To identify risk factors for the investigation of elder abuse, neglect, self‐neglect, exploitation, and abandonment in a population‐based observational cohort of community living elders.

Identifying Vulnerable Older Adults with Cancer: Integrating Geriatric Assessment into Oncology Practice

OBJECTIVES: To integrate the principles of geriatric assessment into the care of older patients with cancer in order to identify vulnerable older adults and develop interventions to optimize cancer treatment.

Older Adults: An 11-Year Longitudinal Study of Adult Protective Service Use

BACKGROUND Little is known about the epidemiology of adult protective services agency (APS) utilization, the state entities charged with assessment and advocacy for disenfranchised older adults. OBJECTIVE To determine the prevalence of utilization by older adults and risk factors for APS. METHODS A longitudinal study using the New Haven Established Population for Epidemiologic Studies in the Elderly population, a cohort of 2812 community-dwelling adults who were older than 65 years in 1982. The main outcome measure was referral to the state ombudsman on aging for protective services. RESULTS Over the 11-year follow-up period, 209 cohort members (7.4%) were referred to the ombudsman 302 times as protective service cases for a community prevalence of 6.4% after adjusting for the sampling strategy of the cohort. Self-neglect was the most common indication for referral (73% of the cases). While in bivariate analyses a variety of baseline sociodemographic features, functional impairments, medical conditions, and social network factors were associated with APS use, in multivariable analysis only sociodemographic variables remained independent risk factors including low income (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.8 to 3.9), nonwhite race (OR, 2.2; 95% CI, 1.3 to 3.7), and age older than 75 years at cohort inception (OR, 1.9; 95% CI, 1.1 to 3.0). CONCLUSIONS Prevalence of APS use by older adults is substantial, and sociodemographic features were the most compelling risk factors in our cohort. As the population ages, the number of older adults at risk for abuse, neglect, self-neglect, exploitation, and abandonment will increase; physicians will need to become familiar with APS referral pathways and mandatory reporting laws in their states.

“Failure To Thrive” in Older Adults

It is a scenario familiar to physicians who provide primary care to older adults. A once functionally independent patient is no longer flourishing in the community. Sometimes the office visit is patient initiated, but more often a family member, frustrated by a decline that might escape the notice of more casual observers, serves as the impetus for consultation. The physician also may become frustrated when a traditional history and physical examination fail to elicit telltale signs or symptoms leading to well-traveled algorithms of differential diagnosis. Discrete temporal landmarks as to the onset of symptoms are unelicitable. The examinations may show little other than the stigmata of malnutrition. Psychomotor retardation may be present, but it is unclear whether this represents a dementing syndrome, depression, or simply an appropriate response to the overall situation. Out of exasperation, the family may insist on hospitalization. Alternatively, the patient and family may present to the emergency department and become the dreaded social admission, whereupon an often poorly tolerated search for cancer and other occult illness begins, usually without satisfying diagnostic resolution. Subsequently, pressure from the family is replaced by pressure from insurers to hasten discharge, bringing pragmatic social issues such as patient safety, nursing home placement, and decision-making capacity to the fore. We became interested in this topic after encountering many older patients who had received a diagnosis of failure to thrive. Reviewing the medical literature, we discovered that failure to thrive is a complex construct derived from many overlapping bodies of literature. It also possesses a complicated medical etymology that will be of interest to physicians and medical sociologists. In this paper, we review the origins of failure to thrive as a diagnostic construct and propose a rational approach to the problem based on the limited medical literature. Finally, we suggest important areas for research into this understudied problem. Review of the Literature: An Intellectual Tension A review of the complicated failure to thrive literature shows many synonyms and colloquialisms familiar to physicians [1-5] (Table 1). Pediatricians use the term failure to thrive when their patients fail to achieve height, weight, or behavioral milestones as determined from large populations that have generated normative data [6]. Braun [7] was the first to provide a justification for exporting the concept to geriatrics: The clinical picture or symptom complex in the elderly failure-to-thrive person presents as a mirror image of the infant failure-to-thrive. The older person loses weight, declines in physical and cognitive function, and often exhibits signs of hopelessness and helplessness. Table 1. Synonyms Encountered in Reviewing the Medical Literature on Failure to Thrive in Older Adults* The verbs lose and decline in the above statement underscore the primary intellectual obstacle to a tidy transposition of the term failure to thrive from infant to octogenarian: The pediatrician uses the term to describe the patient who has not attained functional status; the geriatrician uses it for the patient who has not maintained functional status. The distinction is crucial because it forces the internist to reconfront a central challenge of geriatric medicinedistinguishing disease states prevalent in older adults from normal aging (for example, distinguishing dementing illness from physiologic changes in the aging brain [8]). If we were to take a cue from our pediatric colleagues and construct nomograms with activities of daily living dependence rather than height or weight as the measure of scrutiny, we would discover that the prevalence of at least one impairment increases with each decade of life and approaches 40% in nonagenarians [9]. If some degree of impairment is a normative milestone, it is certainly not a desirable one; should we express surprise or acceptance when our patients reach it? Given the pervasive ageism in our society, in which older adults are often denied optimal care [10], geriatricians teach that it is a mistake to reflexively ascribe decline to old age and accept it as inevitable. It is with these same noble ideals that failure to thrive was first described by Hodkinson [11] in 1973: Illness [in the elderly] often presents as insidious and progressive physical deterioration, for which the paediatric term failure to thrive is appropriate. Typically the patients decline comprises deteriorating social competence, weight loss, loss of appetite, increasing frailty, and diminishing initiative, concentration, and drive. This general failure of the old person is all too often accepted as due to old age or senility or is regarded as a dementing process and the physical basis is overlooked. There are many diagnostic possibilities. Seeking occult and treatable illnesses as the basis for decline resonates with modern geriatric practice. In contrast, Isaacs and colleagues [1] reported on the functional status of residents of Glasgow toward the end of life: a high proportion of all deaths in old age were preceded by a period of pre-death during which the patient was unable to care for himself in consequence of loss of mobility, incontinence, or mental abnormality It seems that many of those who survive into old age enter a phase of pre-death in which they outlive the vigour of their bodies and the wisdom of their brains. The juxtaposition of these two papers from the early 1970s emphasizes the balance between the thorough medical evaluations typical of the geriatrician and failure to thrive as a prelude to natural death. Could the symptom complex described as failure to thrive sometimes be simply the manifestations of pre-death? It has been proposed that in the absence of disease, very elderly patients will eventually undergo a process of progressive functional decline, apathy, and loss of willingness to eat and drink that culminates in death [12]. Clearly, in such a situation, an aggressive diagnostic approach would not only be futile but could contribute to suffering. But which is the more appropriate vantage point from which to approach such patients? No published work addresses this question directly. Two systematic studies [13, 14], both retrospective and done in inpatient settings, have examined how failure to thrive is used as a diagnosis in adults. These studies show that the term is applied to a heterogeneous, incapacitated group of patients who are no longer able to function independently. Comorbid conditions, functional impairment, anorexia, depression, and dementia are prevalent. In the larger study [13], 45% of patients were incontinent, 35% were fallers, and 9.8% had decubiti. All of these problems are familiar geriatric syndromes in their own right. Although 13% to 15% of patients died during hospitalization and more than 30% were discharged to nursing homes, neither study addressed the extent and cost of the diagnostic procedures done with the hope of finding something curable. Despite the heterogeneity of the patients studied (and the subsequent admonition [13] that the diagnosis failure to thrive should perhaps be abandoned), several subsequent review articles in the medical [2, 15, 16] and nursing [17-19] literature have conceptually approached failure to thrive as a clinically meaningful diagnosis. It has had its own International Classification of Diseases, Ninth Revision (ICD-9) code since 1979 and is used increasingly in the geriatric population as well as in patients positive for the human immunodeficiency virus (HIV). A recent evaluation of a geriatric inpatient unit showed that failure to thrive was a common admitting diagnosis, alongside more tangible entities, such as diabetes and gastrointestinal bleeding [20]. Unlike diabetes and gastrointestinal bleeding, however, the symptom complex inconsistently described as failure to thrive does not conform to any accepted model of disease (such as that of the New York Heart Association), in which a fully specified disease must include a clear definition of its cause, anatomy, pathophysiology, and functional effect [21]. Alternatively, one might conceptualize failure to thrive as a geriatric syndrome (such as falling and immobility) that may be defined as a cluster of symptoms, conditions, and disabilities resulting in a variety of physiologic changes, pathologic conditions, comorbid conditions, and environmental challenges [22]. With this approach, the National Institute on Aging in 1991 described failure to thrive as a syndrome of weight loss, decreased appetite and poor nutrition, and inactivity, often accompanied by dehydration, depressive symptoms, impaired immune function, and low cholesterol [22]. A Rational Approach to Management Abandoning Failure To Thrive as a Disease Construct How, then, should one proceed when confronted with a patient who, by anyones definition, is failing? Ironically, we believe that the rather disorderly literature on failure to thriveby the very nature of its disorganizationsays something about the conceptual framework required to care for these patients. In our view, the label failure to thrive promotes an intellectual lazinessaccompanied by a certain resignation, passivity, or fatalismthat needs to be balanced by a considered and thoughtful deconstructionist approach, wherein the areas of impairment would be carefully identified, quantified, and, most importantly, scrutinized for potential interactions. We therefore advocate the abandonment of the term failure to thrive and the adoption of a more measurement-oriented approach with particular attention to four major contributor domains that recur in this literature and are known to be morbid and mortal entities in older adults: impaired physical functioning, malnutrition, depression, and dementia (Figure 1). Figure 1. Evaluation of the older adult who is failing in the c

Distress in Older Patients With Cancer

PURPOSE To determine the predictors of distress in older patients with cancer. PATIENTS AND METHODS Patients age >or= 65 years with a solid tumor or lymphoma completed a questionnaire that addressed these geriatric assessment domains: functional status, comorbidity, psychological state, nutritional status, and social support. Patients self-rated their level of distress on a scale of zero to 10 using a validated screening tool called the Distress Thermometer. The relationship between distress and geriatric assessment scores was examined. RESULTS The geriatric assessment questionnaire was completed by 245 patients (mean age, 76 years; standard deviation [SD], 7 years; range, 65 to 95 years) with cancer (36% stage IV; 71% female). Of these, 87% also completed the Distress Thermometer, with 41% (n = 87) reporting a distress score of >or= 4 on a scale of zero to 10 (mean score, 3; SD, 3; range, zero to 10). Bivariate analyses demonstrated an association between higher distress (>or= 4) and poorer physical function, increased comorbid medical conditions, poor eyesight, inability to complete the questionnaire alone, and requiring more time to complete the questionnaire. In a multivariate regression model based on the significant bivariate findings, poorer physical function (increased need for assistance with instrumental activities of daily living [P = .015] and lower physical function score on the Medical Outcomes Survey [P = .018]) correlated significantly with a higher distress score. CONCLUSION Significant distress was identified in 41% of older patients with cancer. Poorer physical function was the best predictor of distress. Further studies are needed to determine whether interventions that improve or assist with physical functioning can help to decrease distress in older adults with cancer.

Resident-to-Resident Aggression in Long-Term Care Facilities: Insights from Focus Groups of Nursing Home Residents and Staff

OBJECTIVES: To more fully characterize the spectrum of resident‐to‐resident aggression (RRA).