(Re-) Defining "Successful Aging" as the Endpoint in Clinical Trials? Current Methods, Challenges, and Emerging Solutions.

BACKGROUND AND OBJECTIVES: "Successful aging" as defined in Rowe & Kahn's model aims to include the major domains of aging under a single overarching concept. From here the question arises how "successful aging" itself can be implemented as an endpoint in clinical research in a way that it is compliant to methodological regulatory framework and recommendations as formulated, for example, by the FDA. This article discusses from an applied perspective approaches and examples of how "successful aging" as a multi domain concept can be put into measurement practice. RESEARCH DESIGN AND METHODS: Narrative literature review. RESULTS: Existing methods of merging insights from, e.g., functional, social, and cognitive outcomes, can fail to perform under conditions of extreme heterogeneity, as often present in samples of older adults. In research on rare diseases, the methodological approach of a Multi Domain Responder Index (MDRI) has been proposed to handle heterogeneity. MDRIs may also provide a solution to combine aging outcomes from different domains into a single "successful aging" endpoint. However, strict measurement criteria will need to be fulfilled to find acceptance in decision making and validated meaningful change thresholds are a critical prerequisite. DISCUSSION AND IMPLICATIONS: Gerontology can spearhead methodological approaches of handling multidimensional measurement under heterogeneity by validating a "successful aging" MDRI suitable for use as an endpoint in clinical research.

Successful Aging and Subjective Aging: Toward a Framework to Research a Neglected Connection.

Research related to subjective aging, which describes how individuals perceive, interpret and evaluate their own aging, has substantially grown in the past two decades. Evidence from longitudinal studies shows that subjective aging predicts health, quality of life, and functioning in later life. However, the existing literature on successful aging has mostly neglected the role of subjective aging. This paper proposes an extended framework of successful aging linking subjective aging conceptually and empirically to Rowe and Kahn's (1997) three original key criteria of successful aging (i.e., avoiding disease and disability, maintaining high cognitive and physical function, and engagement with life). A particular focus is placed on subjective aging as an antecedent of successful aging. A review of the empirical subjective aging literature shows that subjective aging concepts consistently predict all three of Rowe and Kahn's criteria of successful aging. Mechanisms underlying these relations are discussed at three levels, namely psychological, behavioral, and physiological pathways. The proposed addition also takes into consideration the interconnections between subjective aging and successful aging throughout the lifespan and across historical time. Finally, we discuss the importance of facilitating successful aging through systematic interventions that support more positive views of aging at the individual and societal level.

Second-line treatment of pediatric patients with relapsed rhabdomyosarcoma adapted to initial risk stratification: Data of the European Soft Tissue Sarcoma Registry (SoTiSaR).

BACKGROUND: Outcome of relapsed disease of localized rhabdomyosarcoma remains poor. An individual treatment approach considering the initial systemic treatment and risk group was included in the Cooperative Weichteilsarkom Studiengruppe (CWS) Guidance. METHODS: Second-line chemotherapy (sCHT) ACCTTIVE based on anthracyclines (adriamycin, carboplatin, cyclophosphamide, topotecan, vincristine, etoposide) was recommended for patients with initial low- (LR), standard- (SR), and high-risk (HR) group after initial treatment without anthracyclines. TECC (topotecan, etoposide, carboplatin, cyclophosphamide) was recommended after initial anthracycline-based regimen in the very high-risk (VHR) group. Data of patients with relapse (n = 68) registered in the European Soft Tissue Sarcoma Registry SoTiSaR (2009-2018) were retrospectively analyzed. RESULTS: Patients of initial LR (n = 2), SR (n = 16), HR (n = 41), and VHR (n = 9) group relapsed. sCHT consisted of ACCTTIVE (n = 36), TECC (n = 12), or other (n = 15). Resection was performed in 40/68 (59%) patients and/or radiotherapy in 47/68 (69%). Initial risk stratification, pattern/time to relapse, and achievement of second complete remission were significant prognostic factors. Microscopically incomplete resection with additional radiotherapy was not inferior to microscopically complete resection (p = .17). The 5-year event-free survival (EFS) and overall survival (OS) were 26% (±12%) and 31% (±14%). The 5-year OS of patients with relapse of SR, HR, and VHR groups was 80% (±21%), 20% (±16%), and 13% (±23%, p = .008), respectively. CONCLUSION: Adapted systemic treatment of relapsed disease considering the initial risk group and initial treatment is reasonable. New treatment options are needed for patients of initial HR and VHR groups.

Exploring biomarkers in routine diagnostics for the risk stratification of older patients in the Chest Pain Unit: a prospective cohort study.

OBJECTIVES: This study aims to estimate the association of the often, in daily clinical practice, used biological age-related biomarkers high-sensitivity troponin-T (hs-TnT), C reactive protein (CRP) and haemoglobin (Hb) with all-cause mortality for the purpose of older patient's risk stratification in the emergency department (ED). DESIGN: Exploratory, prospective cohort study with a follow-up at 2.5 years after recruitment started. For the predictors, data from the hospital files including the routinely applied biological age-related biomarkers hs-TnT, CRP and Hb were supplemented by a questionnaire. SETTING: A cardiological ED, Chest Pain Unit, University Hospital Heidelberg, Germany. PARTICIPANTS: N=256 cardiological ED patients with a minimum age of 70 years and the capability to informed consent. PRIMARY OUTCOME MEASURES: The primary outcome of this study was all-cause mortality which was assessed by requesting registry office information. RESULTS: Among N=256 patients 63 died over the follow-up period. Positive results in each of the three biomarkers alone as well as the combination were associated with increased all-cause mortality at follow-up. The number of positive age-related biomarkers appeared to be strongly indicative of the risk of mortality, even when controlled for major confounders (age, sex, body mass index, creatinine clearance and comorbidity). CONCLUSIONS: In older ED patients, biomarkers explicitly related to biological ageing processes such as hs-TnT, CRP and Hb were to a certain degree independently of each other as well as combined associated with an increased risk of all-cause mortality. Thus, they may have the potential to be used to supplement the general risk stratification of older patients in the ED. Validation of the results in a large dataset is needed.

Congenital spindle cell rhabdomyosarcoma: An international cooperative analysis.

BACKGROUND: Spindle cell rhabdomyosarcoma (RMS) is a rare variant of RMS accounting for up to 10% of cases in infants. In older children and adults, spindle cell RMS is associated with MYOD1 mutations and a poor prognosis. In infants, it is associated with recurring fusions involving NCOA2 and VGLL2. Reports in the literature suggest a favorable prognosis for this subset, however, little is known about treatment and outcome data of infants with spindle cell RMS. METHODS: Characteristics, treatment, and outcome of an international cohort of 40 patients aged ≤ 12 months with spindle cell RMS treated from 1997 to 2018 were evaluated. RESULTS: Localized disease (LD) was diagnosed in 39 patients. The median age at diagnosis was 2.5 months (range 0-12 months). Expert pathologic review confirmed the diagnosis of spindle cell RMS in all patients. Among 26 tumors that had molecular evaluation, 13 had rearrangements of NCOA and/or VGLL. Multimodal treatment of infants with LD included conventional (age adjusted) chemotherapy (n = 37), resection (n = 31) and radiotherapy (RT) (n = 5, brachytherapy in 3). Complete remission was achieved in 37/39 patients. Progressive disease occurred in two infants, relapsed disease in three. Microscopically complete surgical resection was associated with five-year event-free survival (EFS) and overall survival (OS) of 100%. Two patients with tumors ≤ 5 cm were treated with microscopically complete resection only and were alive 1 and 4.2 years after diagnosis. The 5-year EFS and OS for infants with LD were 86% (±11; CI 95%) and 91% (±9; CI 95%), respectively. One patient had metastatic disease (NCOA fusion positive) with primary tumor in head and neck and brain metastases. This patient died despite chemotherapy and delayed resection of the primary tumor due to respiratory failure secondary to cytomegalovirus infection 1.2 years after diagnosis. CONCLUSION: Infants with spindle cell RMS have an excellent prognosis. Multimodal treatment including microscopically complete resection of the tumor is strongly recommended.

Effects of a Home-Based Physical Training and Activity Promotion Program in Community-Dwelling Older Persons with Cognitive Impairment after Discharge from Rehabilitation: A Randomized Controlled Trial.

BACKGROUND: Older people with cognitive impairment (CI) are at high risk for mobility limitations and adverse outcomes after discharge from geriatric rehabilitation settings. The aim was to estimate the effects of a specifically designed home-based physical training and activity promotion program on physical capacity, different aspects of physical activity (PA), and psychosocial status. METHODS: Patients with mild to moderate CI (Mini-Mental State Examination [MMSE]: 17-26 points) discharged home after rehabilitation were included in this randomized, double-blind, placebo-controlled trial with a 12-week intervention and 12-week follow-up period. The intervention group performed a CI-specific, autonomous, home-based strength, balance, and walking training supported by tailored motivational strategies to foster training adherence and promote PA. The control group participated in an unspecific motor placebo activity. Primary outcomes were physical capacity (Short Physical Performance Battery [SPPB]) and PA (sensor-based activity time). RESULTS: Among 118 randomized participants (82.3 ± 6.0 years) with CI (MMSE: 23.3 ± 2.4) and high levels of multimorbidity, those participants undergoing home-based training demonstrated superior outcomes to the control group in SPPB (mean difference between groups 1.9 points; 95% CI: 1.0-2.8; p < .001), with persistent benefits over the follow-up (1.3 points; 95% CI: 0.4-2.2; p < .001). There were no differences in PA across any time points. Among secondary outcomes, fear of falling and activity avoidance behavior were reduced in the intervention group at all time points, life-space mobility improved short-term. CONCLUSIONS: The results demonstrate clinically important benefits of an individually tailored autonomous physical training and activity promotion program on physical capacity and secondary outcomes in different domains in a vulnerable, multimorbid population. CLINICAL TRIAL REGISTRATION: ISRCTN82378327.

Experience of Time and Subjective Age When Facing a Limited Lifetime: The Case of Older Adults with Advanced Cancer.

OBJECTIVES: We addressed two questions: (1) Does advanced cancer in later life affect a person's awareness of time and their subjective age? (2) Are awareness of time and subjective age associated with distress, perceived quality of life, and depression? METHODS: We assessed patients suffering terminal cancer (OAC, n = 91) and older adults free of any life-threatening disease (OA, n = 89), all subjects being aged 50 years or older. RESULTS: Older adults with advanced cancer perceived time more strongly as being a finite resource and felt significantly older than OA controls. Feeling younger was meaningfully related with better quality of life and less distress. In the OA group, feeling younger was also associated to reduced depression. Perceiving time as a finite resource was related to higher quality of life in the OA group. DISCUSSION: Major indicators of an older person's awareness of time and subjective aging differ between those being confronted with advanced cancer versus controls.

Awareness of age-related change in very different cultural-political contexts: A cross-cultural examination of aging in Burkina Faso and Germany.

Combining recent developments in research on personal views on aging (VoA) and a cross-country comparative approach, this study examined awareness of age-related change (AARC) in samples from rural Burkina Faso and Germany. The aims of this study were (1) to examine for an assumed proportional shift in the relationship between gains/losses toward more losses as predicted by life span psychology; (2) to estimate the association between AARC dimensions and subjective age; and (3) to examine the association between health variables and AARC. A cross-sectional method involving a large, representative sample from rural Burkina Faso that included participants aged 40 and older (N = 3,028) and a smaller convenience sample of German respondents aged 50 years and older (N = 541) were used to address these questions. A proportional shift toward more AARC-losses was more clearly observable in the sample from Burkina Faso as compared to the German reference. In both samples, subjective age was consistently more strongly related to AARC-losses than to AARC-gains. Within the sample from Burkina Faso, differential associations of AARC-gains and AARC-losses to health variables could be shown. In conclusion, the findings support key tenets of life span psychology including that age-related gains occur even late in life and that a shift toward more losses occurs with increasing age. Also, feeling subjectively younger may indeed be more strongly guided by lowered negative aging experiences than by increased positive ones.

Feeling Younger in Rural Burkina Faso: Exploring the Role of Subjective Age in the Light of Previous Research From High-Income Countries.

OBJECTIVES: Previous research on subjective age (SA), that is, how young or old a person feels relative to their chronological age, has shown that older adults tend to feel younger than they are (by about 15%-20%), but the extent of this effect depends, in part, on their health. However, as most of the studies have been conducted in Western countries, it is unclear how well these results generalize to culturally different samples. Objectives, therefore, were to examine SA in middle-aged and older adults from a very low-income setting in rural Burkina Faso, to examine associations between SA and health/quality of life-related measures, and to compare findings with Western studies. METHODS: Representative, cross-sectional sample of N = 3,028 adults (≥40 years, recruited in 2018) from north-western Burkina Faso. Data included questionnaires on depression (Patient Health Questionnaire-9) and quality of life (World Health Organization Quality of Life scale, including subjective health) as well as performance-based and objective health-related measures (Community Screening Instrument for Dementia as cognitive screening, walking speed). RESULTS: Respondents felt on average 3% younger (SD = 0.13) than their chronological age, with 48% (95% confidence interval: 0.46-0.50) feeling younger-27 percentage points lower than seen in representative Western studies. Lower depression, better walking speed, cognition, and quality of life were all associated with younger SA. DISCUSSION: Middle-aged and older adults in Nouna felt less young than similar age groups in Western studies. One of the reasons may be that youthfulness is less of a value outside Western cultures. As in Western studies, parts of the variation in SA can be explained by health parameters.

Health and Subjective Views on Aging: Longitudinal Findings From the ActiFE Ulm Study.

OBJECTIVES: Previous research supports that subjective views on aging (VoA), such as older subjective age (SA) and negative attitudes toward own aging (ATOA), go along with negative outcomes. A differentiated treatment of health and disease as antecedents of VoA is largely lacking. Therefore, our objective was to estimate the relationship between generally framed physical, affective, and cognitive health as well as specific diseases and VoA, operationalized both as SA and ATOA. METHODS: Data were drawn from the ActiFE Ulm study for which a representative sample of community-dwelling older people (65-90 years) was recruited at baseline. Follow-ups were conducted 7.7 years (median) after recruitment (N = 526). Health- and disease-related data at baseline, based on established assessment procedures for epidemiological studies, were regressed on VoA (1-item SA indicator, 5-item ATOA scale) measures at follow-up. RESULTS: Reported severity of affective health problems such as depression was the strongest general risk factor for both older SA and negative ATOA. Also, some but not all major diseases considered were associated with VoA. Notably, back pain predicted negative ATOA, while cancer was associated with older SA. Rheumatism was linked with more negative ATOA along with higher SA. Throughout analyses, explained variance in ATOA was considerably higher than in SA. DISCUSSION: Affective health problems, such as depression, should be regarded as a major correlate of subjective aging views. Interestingly, diseases do not have to be life-threatening to be associated with older SA or negative ATOA.

Increasing Life-Space Mobility in Community-Dwelling Older Persons With Cognitive Impairment Following Rehabilitation: A Randomized Controlled Trial.

BACKGROUND: Community-dwelling older persons with cognitive impairment (CI) following discharge from geriatric rehabilitation are at high risk of losing life-space mobility (LSM). Interventions to improve their LSM are, however, still lacking. The aim of this study was to evaluate the effects of a CI-specific, home-based physical training and activity promotion program on LSM. METHODS: Older persons with mild-to-moderate CI (Mini-Mental State Examination: 17-26 points) discharged home from rehabilitation were included in this double-blinded, randomized, placebo-controlled trial with a 12-week intervention period and 12-week follow-up period. The intervention group received a CI-specific, home-based strength, balance, and walking training supported by tailored motivational strategies. The control group received a placebo activity. LSM was evaluated by the Life-Space Assessment in Persons with Cognitive Impairment, including a composite score for LSM and 3 subscores for maximal, equipment-assisted, and independent life space. Mixed-model repeated-measures analyses were used. RESULTS: One hundred eighteen participants (82.3 ± 6.0 years) with CI (Mini-Mental State Examination: 23.3 ± 2.4) were randomized. After the intervention, the home-based training program resulted in a significant benefit in the Life-Space Assessment in Persons with Cognitive Impairment composite scores (b = 8.15; 95% confidence interval: 2.89-13.41; p = .003) and independent life-space subscores (b = 0.39; 95% confidence interval: 0.00-0.78; p = .048) in the intervention group (n = 63) compared to control group (n = 55). Other subscores and follow-up results were not significantly different. CONCLUSIONS: The home-based training program improved LSM and independent life space significantly in this vulnerable population. Effects were not sustained over the follow-up. The program may represent a model for improved transition from rehabilitation to the community to prevent high risk of LSM restriction.

Nurses' emotional tone toward older inpatients: Do cognitive impairment and acute hospital setting matter?

The emotional tone of nurses' voice toward residents has been characterized as overly controlling and less person-centered. However, it is unclear whether this critical imbalance also applies to acutely ill older patients, who represent a major subgroup in acute hospitals. We therefore examined nurses' emotional tone in this setting, contrasting care interactions with severely cognitively impaired (CI) versus cognitively unimpaired older patients. Furthermore, we included a general versus a geriatric acute hospital to examine the role of different hospital environments. A mixed-methods design combining audio-recordings with standardized interviews was used. Audio-recorded clips of care interactions between 34 registered nurses (M age = 38.9 years, SD = 12.3 years) and 92 patients (M age = 83.4 years, SD = 6.1 years; 50% with CI) were evaluated by 12 naïve raters (M age = 32.8 years, SD = 9.3 years). Based on their impressions of the vocal qualities, raters judged nurses' emotional tone by an established procedure which allows to differentiate between a person-centered and a controlling tone (Cronbach's α = .98 for both subscales). Overall, findings revealed that nurses used rather person-centered tones. However, nurses' tone was rated as more controlling for CI patients and in the geriatric hospital. When controlling for patients' functional status, both effects lost significance. To our knowledge, this is the first study that examined nurses' emotional tone in the acute hospital setting. Findings suggest that overall functional status of older patients may play a more important role for emotional tone in care interactions than CI and setting differences.

Hospital Staff's Attitudes Toward and Knowledge About Dementia Before and After a Two-Day Dementia Training Program.

BACKGROUND: The outcomes of hospitalized People with Dementia (PwD) are likely to be negative due to, among other key causes, negative staff attitudes and limited staff knowledge regarding dementia. Targeted interventions have been shown to positively change the attitudes of the hospital staff while also increasing their overall knowledge of dementia. However, training effects are often short-lived and frequently long-term effects are not examined in studies. OBJECTIVE: To examine whether attending a dementia training program changes the attitudes of hospital staff toward PwD and/or increases their knowledge levels about dementia, and whether or not these changes are stable. METHODS: The training program lasted two days and N = 60 attending hospital staff members agreed to participate in the study. Data were assessed with questionnaires prior to the training, 3 months, and 6 months after the training. German versions of the Dementia Attitude Scale (DAS-D) and the Knowledge in Dementia (KIDE) scale were used. Additionally, data about perception of PwD and confidence in dealing with challenging behavior were collected and analyzed. RESULTS: After the training program, participants showed a significantly better attitude toward PwD as measured by DAS-D. These time-effects occurred in both DAS-D subscales ("dementia knowledge" and "social comfort"). Although a positive trend could be seen in the KIDE scale, no statistically significant increase occurred over time. CONCLUSION: Specialist training programs seem to be promising in positively changing attitudes toward and increasing knowledge about PwD with long-term effects. Further research should address the effects of attitude change in patient care.