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OBJECTIVE: Prior studies have reported an association between depression and quality of life (QOL) in Alzheimer's disease (AD), but the effect of self- versus proxy rating of mood and QOL has not been described. DESIGN: In this secondary analysis of data from a cohort study, the authors used a linear mixed-effects model to determine if the association between depression and QOL is affected by whether both measures are assessed by the same member of the patient-caregiver dyad. SETTING: Participants and caregiver informants were recruited from 10 California Alzheimer Disease Centers. PARTICIPANTS: A total of 137 participants with mild-to-moderate Alzheimer's disease and their caregivers. MEASUREMENTS: Self- and proxy-rated scores on both the Geriatric Depression Scale (GDS) and the Quality of Life in Alzheimer's Disease scale (QoL-AD). Multivariable linear mixed-effects models were used to estimate the association between depression and QOL. RESULTS: Results of the multivariable linear mixed-effects models showed a significant association between self-rated QoL-AD and self-rated (B = -0.49, p <0.0001) but not proxy-rated GDS (B = -0.07, p = 0.19) after adjusting for confounders. Likewise, there was a significant association between proxy-rated QoL-AD and proxy-rated GDS (B = -0.48, p <0.0001) but not self-rated GDS (B = 0.05, p = 0.36). CONCLUSION: Depression was associated with QOL in AD over short-term longitudinal follow-up, but the association was not statistically significant if both instruments are not administered to the same member of the patient-caregiver dyad. The choice of self- versus proxy-reported QOL should be intentionally considered in future studies as it may influence reported outcomes.
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Enfermedad de Alzheimer , Humanos , Anciano , Enfermedad de Alzheimer/complicaciones , Calidad de Vida , Depresión/epidemiología , Depresión/complicaciones , Estudios de Cohortes , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , CuidadoresRESUMEN
While a growing body of interprofessional education (IPE) literature demonstrates a positive impact on learner knowledge, there is limited data on its long-term impact on collaborative practice (CP). With the growth of the aging population globally, understanding both the long-term impact on CP and sustainability of community-based geriatric experiential IPE programs are imperative. This study explores the impact of the Interprofessional Geriatric Curriculum (IPGC), a community-based geriatric IPE program, on post-graduate clinical practice among seven health professions. This study utilized a cross-sectional descriptive design, where both qualitative and quantitative data were collected in the same online survey of health professionals' to measure their perceptions of the impact IPGC has had on their respective clinical practice 1-3 years post-graduation. Forty-six per cent of health profession graduates provided clinical care for people 65 years of age or older; 81% worked in interprofessional teams; 80% reported the IPGC experience significantly impacted their practice (N = 137), and all used validated assessment tools taught in the IPGC program in their practice. Eight themes emerged from the list of what health professionals learned from IPGC that they use regularly in their clinical practice: four themes were interprofessional in nature (i.e. teamwork and team-based care, interprofessional communication, roles/responsibilities, and personal/professional) and four themes related to geriatrics (i.e. aging, screening and assessment, medications, and didactic content). This study is one of the first to describe the sustained influence of a community-based IPE program across multiple health professional disciplines on clinical geriatric practice.
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Conducta Cooperativa , Geriatría , Educación Interprofesional , Relaciones Interprofesionales , Humanos , Geriatría/educación , Estudios Transversales , Educación Interprofesional/organización & administración , Grupo de Atención al Paciente/organización & administración , Anciano , Curriculum , Actitud del Personal de Salud , Servicios de Salud Comunitaria/organización & administración , Femenino , MasculinoRESUMEN
This 6-year prospective study describes the impact on student attitudes of an innovative, interprofessional geriatrics curriculum (IPGC) focused on team-based care with older adults in a home-based community setting. Dental, medical, occupational therapy, pharmacy, physical therapy, and physician assistant students were placed into teams each led by faculty members from all of the professions. The curriculum consisted of five, four-hour sessions over one academic year. Teams met with a community-dwelling older adult three times. Students completed the Geriatric Assessment Scale (GAS) before and after the IPGC experience. At the conclusion, improvements in attitudes toward older adults in the GAS and its four domains - social value, medical care, compassion, and societal resources-were observed across a wide spectrum of students. Students with the lowest initial attitudes improved the most, as did the scores of the youngest students. Older students improved more than younger students in the social value domain (i.e., the perceived social value of older adults). Among disciplines, occupational therapy and social work students improved the most in the social value domain. This study demonstrates improvement in attitudes toward older adults from student involvement in IPGC that combines didactic and experiential learning through community partnerships in a home-based setting.
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Geriatría , Visita Domiciliaria , Anciano , Actitud del Personal de Salud , Curriculum , Geriatría/educación , Humanos , Relaciones Interprofesionales , Estudios ProspectivosRESUMEN
Objectives: Our goal is to illuminate cannabis use among persons with dementia (PwD) and their informal caregivers relative to the use of evidence-based as well as other complementary and alternative care practices. Methods: We analyzed focus group (FG) narratives provided by 26 caregivers of PwD and identified five themes concerning the provision of cannabis to PwD and caregivers' self-use. Results: Three of the 26 caregivers provided PwD cannabis and also used themselves, another 3 of the 26 used themselves only, and all but two of the remaining FG participants indicated they would consider providing cannabis to PwD or using for themselves. These caregivers expressed a desire to obtain more empirically-based information about cannabis and to discuss options with their clinical care providers. Conclusions: A small but significant proportion of caregivers are providing cannabis to PwD as a possible treatment for agitation, sleep disturbances and other problematic secondary symptoms and using for themselves as way to relieve stress. Many other caregivers may start using cannabis upon receiving information and guidance from a credible source. Clinical Implications: Notwithstanding the need for more research, clinical gerontologists and other dementia care specialists are being looked upon to provide information and guidance about the benefits and harms of cannabis use among PwD and their caregivers.
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Cannabis , Demencia , Trastornos del Sueño-Vigilia , Cuidadores , Demencia/terapia , Geriatras , HumanosRESUMEN
BACKGROUND: The US population is maturing. As of 2020, over 52 million (16%) people are age 65 or older. With a citizenry that is increasingly "gray," the nation is short of medical providers who specialize in geriatric medical care. For example, the number of geriatrician physicians per 10,000 adults 65 years and older has decreased since 2000, with approximately 5300 in 2018. Nurse practitioners in geriatric medical care numbered 598 in 2018. Considering that the projected needs by 2030 will be over 30,000, the trajectory of geriatricians is becoming increasingly inadequate for the aging population. Physician assistants (PA) are another class of providers that are filling this geriatric medical care role, although little has been published. To address this role of PAs a study was undertaken. METHODS: The National Commission on Certification of Physician Assistants databank provided the number and characteristics of PAs in geriatric medicine and compared them to all other certified PAs. Analyses included descriptive statistics, Chi-Square, and Wilcoxon Rank Sum tests for comparisons between PAs practicing in geriatric medical care vs. all other PA specialties. Where a comparison between PAs in geriatrics and other specialties was made, a P value of .05 or less was considered statistically significant. RESULTS: As of 2018, there were 794 certified PAs, or 0.8% of the certified PA workforce, in geriatric medical care. This cadre has grown significantly since 2013, both in total number (increasing over 373%) and as a percentage of the PA workforce. The median age of certified PAs in geriatrics is 45 years, and 79% are female. Almost half (46%) of PAs in geriatric medicine work in extended care facilities or nursing homes, which differs from PAs in non-geriatric care. Another 8% work in government facilities and 8% in rehabilitation facilities. In 2018, the mean annual income for this PA group was $106,680. CONCLUSIONS: As the American population continues to age, the relative growth of PAs in geriatric medicine makes them a natural part of the solution to the projected physician geriatrician deficit. The role of PAs in geriatric medical care remains to be explored.
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Geriatría , Asistentes Médicos , Anciano , Envejecimiento , Femenino , Humanos , Masculino , Estados Unidos , Recursos HumanosRESUMEN
The development of postoperative confusion in older patients is increasingly being recognized as clinically significant because it is becoming more common as the population ages. Postoperative delirium and postoperative cognitive dysfunction differ in time course of development. Risk factors other than age include certain medications as well as anesthesia (both the type and amount used). Postoperative delirium and postoperative cognitive dysfunction appear to increase a patient's risk for developing dementia. Routine preoperative screening may help to identify patients with preexisting cognitive impairment who are at greatest risk for developing postoperative delirium or postoperative cognitive dysfunction.
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Anestesia/efectos adversos , Trastornos del Conocimiento/inducido químicamente , Confusión/etiología , Delirio/inducido químicamente , Complicaciones Posoperatorias/etiología , Procedimientos Quirúrgicos Operativos/efectos adversos , Factores de Edad , Anciano , Anciano de 80 o más Años , Trastornos del Conocimiento/prevención & control , Confusión/prevención & control , Delirio/prevención & control , Evaluación Geriátrica , Humanos , Complicaciones Posoperatorias/prevención & control , Factores de RiesgoRESUMEN
Our study assesses changes in students' knowledge and attitudes after participation in an interprofessional, team-based, geriatric home training program. Second-year medical, physician assistant, occupational therapy, social work, and physical therapy students; third-year pharmacy students; and fourth-year dental students were led by interprofessional faculty teams. Student participants were assessed before and after the curriculum using an interprofessional attitudes learning scale. Significant differences and positive data trends were noted at year-end. Our study suggests that early implementation, assessment, and standardization of years of student training is needed for optimal interprofessional geriatric learning. Additionally, alternative student assessment tools should be considered for future studies.
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Educación Profesional/organización & administración , Geriatría/educación , Conocimientos, Actitudes y Práctica en Salud , Servicios de Atención de Salud a Domicilio , Relaciones Interprofesionales , Grupo de Atención al Paciente , Anciano , Curriculum , Educación Profesional/normas , Femenino , Humanos , Masculino , Estudiantes del Área de la Salud , Encuestas y CuestionariosRESUMEN
ABSTRACT: The international growth of the physician assistant/associate (PA) profession provides opportunities for global exchange that PA faculty and clinicians should seek out and cultivate. Physician assistant/associate programs can benefit from the experiences and expertise of faculty educators from different backgrounds and countries. The Fulbright International Scholars Program is a well-established and recognized organization dedicated to supporting international exchange in higher education. This study describes the experience of an American PA who received a Fulbright Specialist Program award that provided the opportunity to collaborate with a Dutch PA program on improvement of their geriatric medicine didactic curriculum.
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Curriculum , Geriatría , Asistentes Médicos , Asistentes Médicos/educación , Humanos , Geriatría/educación , Intercambio Educacional Internacional , Estados Unidos , Países BajosRESUMEN
Primary care practitioners (PCPs) are the first point of contact for most patients with suspected dementia and have identified a need for more training and support around dementia diagnosis and care. This qualitative study examined the Alzheimer's Disease-Extension for Community Healthcare Outcomes (AD-ECHO) program. AD-ECHO was designed to strengthen PCP capacity in dementia through bimonthly virtual meetings with a team of dementia experts. We conducted 24 hr of direct observations at AD-ECHO sessions and interviewed 14 participants about their experiences participating. Using thematic analysis, we found that participants valued the supportive learning environment and resources; knowledge gained empowered them to take more action around dementia; they identified ways of disseminating knowledge gained into their practice settings, and many desired ongoing AD-ECHO engagement. However, most identified time as a barrier to participation. AD-ECHO has the potential to strengthen the primary care workforce's knowledge and confidence around dementia care.
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Importance: Although the barriers to dementia care in primary care are well characterized, primary care practitioner (PCP) perspectives could be used to support the design of values-aligned dementia care pathways that strengthen the role of primary care. Objective: To describe PCP perspectives on their role in dementia diagnosis and care. Design, Setting, and Participation: In this qualitative study, interviews were conducted with 39 PCPs (medical doctors, nurse practitioners, and doctors of osteopathic medicine) in California between March 2020 and November 2022. Results were analyzed using thematic analysis. Main Outcomes and Measures: Overarching themes associated with PCP roles in dementia care. Results: Interviews were conducted with 39 PCPs (25 [64.1%] were female; 16 [41%] were Asian). The majority (36 PCPs [92.3%]) reported that more than half of their patients were insured via MediCal, the California Medicaid program serving low-income individuals. Six themes were identified that convey PCPs' perspectives on their role in dementia care. These themes focused on (1) their role as first point of contact and in the diagnostic workup; (2) the importance of long-term, trusting relationships with patients; (3) the value of understanding patients' life contexts; (4) their work to involve and educate families; (5) their activities around coordinating dementia care; and (6) how the care they want to provide may be limited by systems-level constraints. Conclusions and Relevance: In this qualitative study of PCP perspectives on their role in dementia care, there was alignment between PCP perspectives about the core values of primary care and their work diagnosing and providing care for people living with dementia. The study also identified a mismatch between these values and the health systems infrastructure for dementia care in their practice environment.
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Demencia , Médicos de Atención Primaria , Atención Primaria de Salud , Femenino , Humanos , Masculino , Demencia/diagnóstico , Demencia/terapia , Personal de Salud , Estados Unidos , Rol del MédicoRESUMEN
OBJECTIVE: The Spanish English Neuropsychological Assessment Scale (SENAS) is a cognitive battery with English and Spanish versions for use with persons for whom either language is predominant. Few studies have examined its utility outside the normative sample. The current study examined SENAS performance in samples of older adult Latines and Latines with or at risk for autosomal dominant Alzheimer's disease (ADAD) mutations. METHOD: The SENAS was administered to 202 older adults from the Los Angeles Latino Eye Study (LALES) and 29 adults with (carriers) or without (non-carriers) mutations causing ADAD. We examined associations between SENAS, age, education, and language (LALES) and between SENAS, estimated years from familial age of dementia diagnosis, education, language, and acculturation (ADAD). Partial correlations were used to examine differences in correlational strength between estimated years from familial age of dementia diagnosis and SENAS scores among ADAD carriers compared to chronological age and SENAS in the LALES sample. Exploratory t-tests were performed to examine SENAS performance differences between ADAD carriers and non-carriers. RESULTS: In an older adult sample (LALES), increased age correlated with worse verbal delayed recall; English fluency and higher education correlated with better naming and visuospatial subtest performance. Among ADAD carriers, verbal and nonverbal delayed recall and object naming subtest performance worsened as they approached their familial age of dementia diagnosis. English fluency and higher U.S.-acculturation were related to better SENAS performance among carriers and non-carriers. Tests of verbal delayed recall and object naming best distinguished ADAD carriers from their familial non-carrier counterparts. CONCLUSIONS: Verbal delayed recall and object naming measures appear to be most sensitive to age-related changes in older adult samples and mutation-related changes in distinguishing ADAD carriers from non-carriers. Future research should examine the sensitivity of SENAS in other samples, such as larger samples of symptomatic ADAD carriers and other AD subtypes.
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Enfermedad de Alzheimer , Humanos , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Lenguaje , Mutación , Hispánicos o Latinos/psicología , Pruebas NeuropsicológicasRESUMEN
Training health professional students to work with older adults will improve future workforce capacity to meet growing needs. Additionally, older adults may benefit from health education and interactions with health professional students. We analyzed survey responses from older adults who had participated in an interprofessional health student education program regarding their experiences. Qualitative data were summed and averaged, and quantitative survey data were analyzed with Fisher's Exact Test. At least 60% of participants reported receiving information for health needs or making changes to physical activity, dental care, or diet. The most significant differences in lifestyle modifications were noted among racial and ethnic minorities and among speakers of different primary languages. 64% of the qualitative responses reflected positive affirmation of the program. Our data suggest that interactions with health students are meaningful experiences for older adults, are associated with healthy habit changes, and reflect demographic differences in response to health education.
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BACKGROUND: Frequent review and update of guidelines are necessary for them to remain current and useful for clinical practices. This second revision of the postdiagnostic management of Alzheimer's disease (AD) guideline by the California Workgroup was prompted by significant advances in knowledge about appropriate care management, including pharmacologic and nonpharmacologic approaches to treatment of the disease, accompanying behavioral problems, and functional decline. The focus remains explicitly on primary care, where the majority of it occurs for those with AD and other dementias. METHODS: In all, 40 experts in dementia care were recruited from a variety of disciplines across California. Four workgroups were created that reviewed recent research findings from a total of 569 publications since 2002. The revised Guideline incorporates 305 new references, including 11 state and federal laws, in addition to 78 references from the previous version. RESULTS: The Guideline is divided into four sections that address postdiagnostic management: (1) assessment, (2) treatment, (3) patient and family education and support, and (4) legal considerations associated with AD. Significant revisions and changes in each area and the underlying research to support the recommendations are presented in this article. New topics related to early stage and end-of-life were identified and recommendations were developed for these specific populations. CONCLUSIONS: The Guideline recommendations provide a framework to inform and improve medical care for AD by primary health care providers.
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Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/terapia , Apoyo Social , Enfermedad de Alzheimer/psicología , California , Humanos , Atención Primaria de Salud/legislación & jurisprudencia , Atención Primaria de Salud/normasRESUMEN
BACKGROUND/OBJECTIVES: While it is well-known that caregiving can have adverse effects on the physical and mental health of informal caregivers and their families, caregivers of those with early-onset Alzheimer's Disease (EOAD) may have distinct needs. Little is written about the experiences of Latino caregivers of family members with EOAD, especially inherited forms. This study's objective was to explore the experiences and needs of Latino caregivers of persons with EOAD. METHODS: Five focus group discussions (FGDs) were conducted among 27 informal caregivers of Latinos with EOAD who were recruited through an AD clinic in Los Angeles. RESULTS: The stress of caregiving was compounded by other pressures and worries, such as taking care of young children, providing financially for family, caregivers' own co-morbidities, and contemplating their own risk of inheriting EOAD. Resources for monolingual Spanish speakers were scarce. Participants had two primary unmet needs: information and support services. Participants lacked information about how to provide appropriate care, which heightened fears. Difficulty in obtaining a diagnosis from physicians who were uninformed about EOAD was also common. Recommended topics for informational campaigns included how-to videos on caring for a loved one but also topics related to self-care for caregivers. CONCLUSIONS: Our results underscore the need to tailor programs for caregivers of family members with EOAD. Educational campaigns could help to dispel myths and misconceptions, reduce stigma associated with EOAD, and encourage more people to seek timely care. Additional psychosocial support, such as support groups, could build solidarity and self-efficacy. Better access to dual-language information and support could encourage early help-seeking but also improve caregivers' quality of life as they manage long-term caregiving responsibilities.
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Enfermedad de Alzheimer/enfermería , Cuidadores/psicología , Hispánicos o Latinos/estadística & datos numéricos , Grupos de Autoayuda , Adulto , Ansiedad/psicología , Femenino , Grupos Focales , Humanos , Los Angeles , Masculino , Calidad de Vida/psicologíaRESUMEN
This study describes and provides qualitative analysis of an innovative, inter-professional (IP) geriatrics curriculum focused on team-based care with healthy older adults in a home-based community setting. The curriculum consisted of five, four-hour didactic and experiential sessions over one academic year. Dental, medical, occupational therapy, pharmacy, physical therapy, and physician assistant students were placed into teams led by IP faculty from each health professional school. Teams met with a community-dwelling older adult three times. At the program's conclusion, students responded to the reflective question "What is the most important learning experience you expect to take away from the geriatric inter-professional training? A qualitative analysis of student responses revealed four common themes from all five professions aligning with curricular goals: (1) health professional roles/scope of practice, (2) geriatric care and health outcomes, (3) team communication/collaboration, and (4) advocating for one's own profession. As sites for institutional clinical training become scarcer for health professions' trainees, this study offers both a novel, IP, geriatrics curriculum with didactic/experiential learning through community partnerships in a home-based setting and a reflective evaluation.
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Atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions (aFTLD-U) is an uncommon cause of frontotemporal dementia characterized by fused in sarcoma-positive inclusions. It is classified as a subtype of frontotemporal lobar degeneration with FUS pathology. Cases with aFTLD-U pathology typically display an early onset of symptoms and severe psychobehavioral changes in the absence of significant aphasia, cognitive-intellectual dysfunction or motor features. This phenotype is regarded as being sufficiently unusual and consistent as to allow antemortem diagnosis with a high degree of accuracy. In this report, we describe 2 cases with aFTLD-U pathology that broaden the associated phenotype to include later age of onset, milder behavioral abnormalities and early memory and language impairment.
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Encéfalo/patología , Degeneración Lobar Frontotemporal/genética , Degeneración Lobar Frontotemporal/patología , Fenotipo , Proteína FUS de Unión a ARN/genética , Anciano , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: To compare the rates of depression in Alzheimer Disease (AD) determined using National Institute of Mental Health (NIMH) provisional criteria for depression in AD (NIMH-dAD) to those determined using other established depression assessment tools. DESIGN: Descriptive longitudinal cohort study. SETTING: The Alzheimer's Disease Research Centers of California. PARTICIPANTS: A cohort of 101 patients meeting NINDS-ADRDA criteria for possible/probable AD, intentionally selected to increase the frequency of depression at baseline. MEASUREMENTS: Depression was diagnosed at baseline and after 3 months using NIMH-dAD criteria and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I Disorders. Depressive symptoms also were assessed with the Cornell Scale for Depression in Dementia (CSDD), the Geriatric Depression Scale (GDS), and the Neuropsychiatric Inventory Questionnaire. RESULTS: The baseline frequency of depression using NIMH-dAD criteria (44%) was higher than that obtained using DSM-IV criteria for major depression (14%; Z = -5.50, df = 101, p <0.001) and major or minor depression (36%; Z = -2.86, df = 101, p = 0.021) or using established cut-offs for the CSDD (30%; Z = -2.86, df = 101, p = 0.004) or GDS (33%; Z = -2.04, df = 101, p = 0.041). The NIMH-dAD criteria correctly identified all patients meeting DSM-IV criteria for major depression, and correlated well with DSM-IV criteria for major or minor depression (kappa = 0.753, p <0.001), exhibiting 94% sensitivity and 85% specificity. The higher rates of depression found with NIMH-dAD criteria derived primarily from its less stringent requirements for the frequency and duration of symptoms. Remission rates at 3 months were similar across instruments. CONCLUSIONS: The NIMH-dAD criteria identify a greater proportion of AD patients as depressed than several other established tools.
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Enfermedad de Alzheimer/diagnóstico , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo/diagnóstico , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/psicología , Estudios de Cohortes , Comorbilidad , Estudios Transversales , Trastorno Depresivo/epidemiología , Trastorno Depresivo/psicología , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/psicología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estudios Longitudinales , Masculino , Escala del Estado Mental/estadística & datos numéricos , Pruebas Neuropsicológicas/estadística & datos numéricos , Determinación de la Personalidad/estadística & datos numéricos , Psicometría/estadística & datos numéricos , Reproducibilidad de los ResultadosRESUMEN
Chloroquine (CQ) is an antimalarial drug and late-stage inhibitor of autophagy currently FDA-approved for use in the treatment of rheumatoid arthritis and other autoimmune diseases. Based primarily on its ability to inhibit autophagy, CQ and its derivative, hydroxychloroquine, are currently being investigated as primary or adjuvant therapy in multiple clinical trials for cancer treatment. Oncogenic RAS has previously been shown to regulate autophagic flux, and cancers with high incidence of RAS mutations, such as pancreatic cancer, have been described in the literature as being particularly susceptible to CQ treatment, leading to the hypothesis that oncogenic RAS makes cancer cells dependent on autophagy. This autophagy "addiction" suggests that the mutation status of RAS in tumors could identify patients who would be more likely to benefit from CQ therapy. Here we show that RAS mutation status itself is unlikely to be beneficial in such a patient selection because oncogenic RAS does not always promote autophagy addiction. Moreover, oncogenic RAS can have opposite effects on both autophagic flux and CQ sensitivity in different cells. Finally, for any given cell type, the positive or negative effect of oncogenic RAS on autophagy does not necessarily predict whether RAS will promote or inhibit CQ-mediated toxicity. Thus, although our results confirm that different tumor cell lines display marked differences in how they respond to autophagy inhibition, these differences can occur irrespective of RAS mutation status and, in different contexts, can either promote or reduce chloroquine sensitivity of tumor cells.