Tolerability and effectiveness of palbociclib in older women with metastatic breast cancer.

PURPOSE: Palbociclib has become the standard of care for estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer, but real-world evidence in older women remains scarce. Therefore, we investigated tolerability of palbociclib in older women with metastatic breast cancer. METHODS: Consecutive women aged ≥ 70 with ER+/HER2- metastatic breast cancer, treated with palbociclib in any treatment line in six hospitals, were included. Primary endpoint was grade ≥ 3 palbociclib-related toxicity. Predictors of toxicity were identified using logistic regression models. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier. RESULTS: We included 144 women with a median age of 74 years. Grade 3-4 toxicity occurred in 54% of patients, of which neutropenia (37%) was most common. No neutropenic fever or grade 5 toxicity occurred. Dose reduction during treatment occurred in 50% of patients, 8% discontinued treatment due to toxicity and 3% were hospitalized due to toxicity. Polypharmacy (odds ratio (OR) 2.50; 95% confidence interval (CI) 1.12-5.58) and pretreatment low leukocytes (OR 4.81; 95% CI 1.27-18.21) were associated with grade 3-4 toxicity, while comorbidities were not. In first-line systemic therapy, median PFS was 12 months and median OS 32 months. In second-line, median PFS was 12 months and median OS 31 months. CONCLUSION: Although grade 3-4 toxicity and dose reductions occurred frequently, most were expected and managed by dose reductions, showing that palbociclib is generally well tolerated and thus represents a valuable treatment option in the older population.

Apathy Symptoms, Physical and Cognitive Function, Health-Related Quality of Life, and Mortality in Older Patients With CKD: A Longitudinal Observational Study.

RATIONALE & OBJECTIVE: Apathy reflects diminished motivation, goal-directed behavior, and emotions, as well as less engagement in social interactions. Apathy overlaps with depression and is associated with cognitive decline. In the older individuals with chronic kidney disease (CKD), both depression and cognitive impairments are common, but apathy symptoms have been underreported. We investigated the occurrence of apathy symptoms and their associations with physical and cognitive functioning, health-related quality of life (HRQoL), and mortality in older patients with CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 180 outpatients aged≥65 years with estimated glomerular filtration rate≤20mL/min/1.73m2 from 5 Dutch nephrology centers. EXPOSURE: Apathy symptoms at baseline were considered present when a Geriatric Depression Scale's 3-item apathy subscale score was≥2 points. OUTCOME: Physical and cognitive functioning, HRQoL (assessed in annual geriatric assessments), and 4-year mortality. ANALYTICAL APPROACH: Linear regression for cross-sectional associations, linear regression models for longitudinal associations, and Cox regression models for mortality over 4 years of observation. RESULTS: Apathy symptoms were present in 64 patients (36%; 67% men; median age 75.5 years), of whom 32 (50%) had no depressive symptoms. At baseline, the presence of apathy symptoms was associated with significantly more frailty, more functional dependence, less physical capacity, lower visuoconstructive performance, worse delayed recall, and lower HRQoL scores. The presence of apathy symptoms at baseline was also associated with a higher mortality risk (hazard ratio, 2.3 [95% CI, 1.3-4.2], P=0.005 adjusted for age, sex, and high education level), but not with changes in physical and cognitive functioning or HRQoL during the follow-up period. LIMITATIONS: Risk of selection bias and residual confounding. CONCLUSIONS: Apathy symptoms were highly prevalent and associated with concurrent lower physical and cognitive status, lower HRQoL, and increased mortality. These findings highlight apathy as a potentially important clinical phenotype in older CKD patients. PLAIN-LANGUAGE SUMMARY: We observed that older kidney patients often present apathy symptoms, such as less motivation, fewer goal-directed behaviors, fewer emotions, and less social engagement. Prior research has not extensively described apathy in kidney disease. We investigated the link between apathy symptoms and poor outcomes. We measured physical functioning, cognitive functioning, and quality of life. We learned that one-third of our older kidney patients showed symptoms of apathy, only half of whom had symptoms of depression. Patients with apathy symptoms showed lower quality of life and lower physical and cognitive performance. They also had a higher risk of death. These findings highlight the need for awareness of apathy symptoms in older kidney patients.

Temporal dynamics of depressive symptoms and cognitive decline in the oldest old: dynamic time warp analysis of the Leiden 85-plus study.

BACKGROUND: The prevalence of depressive symptoms and cognitive decline increases with age. We investigated their temporal dynamics in individuals aged 85 and older across a 5-year follow-up period. METHODS: Participants were selected from the Leiden 85-plus study and were eligible if at least three follow-up measurements were available (325 of 599 participants). Depressive symptoms were assessed at baseline and at yearly assessments during a follow-up period of up to 5 years, using the 15-item Geriatric Depression Scale (GDS-15). Cognitive decline was measured through various tests, including the Mini Mental State Exam, Stroop test, Letter Digit Coding test and immediate and delayed recall. A novel method, dynamic time warping analysis, was employed to model their temporal dynamics within individuals, in undirected and directed time-lag analyses, to ascertain whether depressive symptoms precede cognitive decline in group-level aggregated results or vice versa. RESULTS: The 325 participants were all 85 years of age at baseline; 68% were female, and 45% received intermediate to higher education. Depressive symptoms and cognitive functioning significantly covaried in time, and directed analyses showed that depressive symptoms preceded most of the constituents of cognitive impairment in the oldest old. Of the GDS-15 symptoms, those with the strongest outstrength, indicating changes in these symptoms preceded subsequent changes in other symptoms, were worthlessness, hopelessness, low happiness, dropping activities/interests, and low satisfaction with life (all P's < 0.01). CONCLUSION: Depressive symptoms preceded cognitive impairment in a population based sample of the oldest old.

Older people's goals of care in relation to frailty status-the COOP-study.

BACKGROUND: Literature relating older people's goals of care to their varying frailty status is scarce. OBJECTIVE: To investigate goals of care in case of acute and/or severe disease in relationship to frailty status among the general older population. METHOD: Older people aged ≥70 in the Netherlands completed a questionnaire. They were divided into three subgroups based on a self-reported Clinical Frailty Scale: fit (CFS 1-3), mildly frail (CFS 4-5) and severely frail (CFS 6-8). Seven goals were graded as unimportant (1-5), somewhat important (6-7) or very important (8-10): extending life, preserving quality of life (QoL), staying independent, relieving symptoms, supporting others, preventing hospital admission and preventing nursing home admission. RESULTS: Of the 1,278 participants (median age 76 years, 63% female), 57% was fit, 32% mildly frail and 12% severely frail. Overall, participants most frequently considered preventing nursing home admission as very important (87%), followed by staying independent (84%) and preserving QoL (83%), and least frequently considered extending life as very important (31%). All frailty subgroups reported similar preferences out of the surveyed goals as the overall study population. However, participants with a higher frailty status attached slightly less importance to each individual goal compared with fit participants (Ptrend-values ≤ 0.037). CONCLUSION: Preferred goals of care are not related to frailty status, while the importance ascribed to individual goals is slightly lower with higher frailty status. Future research should prioritise outcomes related to the shared goals of fit, mildly frail and severely frail older people to improve personalised medicine for older patients.

Current Pyuria Cutoffs Promote Inappropriate Urinary Tract Infection Diagnosis in Older Women.

BACKGROUND: Pre-existing lower urinary tract symptoms (LUTS), cognitive impairment, and the high prevalence of asymptomatic bacteriuria (ASB) complicate the diagnosis of urinary tract infection (UTI) in older women. The presence of pyuria remains the cornerstone of UTI diagnosis. However, >90% of ASB patients have pyuria, prompting unnecessary treatment. We quantified pyuria by automated microscopy and flowcytometry to determine the diagnostic accuracy for UTI and to derive pyuria thresholds for UTI in older women. METHODS: Women ≥65 years with ≥2 new-onset LUTS and 1 uropathogen ≥104 colony-forming units (CFU)/mL were included in the UTI group. Controls were asymptomatic and classified as ASB (1 uropathogen ≥105 CFU/mL), negative culture, or mixed flora. Patients with an indwelling catheter or antimicrobial pretreatment were excluded. Leukocyte medians were compared and sensitivity-specificity pairs were derived from a receiver operating characteristic curve. RESULTS: We included 164 participants. UTI patients had higher median urinary leukocytes compared with control patients (microscopy: 900 vs 26 leukocytes/µL; flowcytometry: 1575 vs 23 leukocytes/µL; P < .001). Area under the curve was 0.93 for both methods. At a cutoff of 264 leukocytes/µL, sensitivity and specificity of microscopy were 88% (positive and negative likelihood ratio: 7.2 and 0.1, respectively). The commonly used cutoff of 10 leukocytes/µL had a poor specificity (36%) and a sensitivity of 100%. CONCLUSIONS: The degree of pyuria can help to distinguish UTI in older women from ASB and asymptomatic controls with pyuria. Current pyuria cutoffs are too low and promote inappropriate UTI diagnosis in older women. Clinical Trials Registration. International Clinical Trials Registry Platform: NL9477 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL9477).

Time trends in treatment patterns and survival of older patients with synchronous metastatic colorectal cancer in the Netherlands: A population-based study.

New treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not included in pivotal trials. Therefore, we investigated treatment patterns and overall survival over time in older patients with metastatic colorectal cancer in a population-based study. We identified 22.192 Dutch patients aged ≥70 years diagnosed with synchronous metastatic colorectal cancer between 2005 and 2020 from the Netherlands Cancer Registry. Changes in treatment over time were assessed with logistic regression models. Survival was assessed by Cox proportional hazard ratios (HR). Results showed that chemotherapy use increased between 2005 and 2015, but declined from 2015 onwards, while more patients received best supportive care. Over time, fewer patients underwent primary tumor resection alone. Although survival of both metastatic colon and rectal cancer improved until 2014, survival of colon cancer decreased from 2014 onwards (HR 1.04, 95% confidence interval [CI] 1.01-1.05), which was seen in all age groups. Survival of metastatic rectal cancer patients remained unchanged from 2014 onwards (HR 1.00, 95% CI 0.98-1.03) in all age groups. In conclusion, treatment patterns of Dutch older patients with synchronous metastatic colorectal cancer rapidly changed from 2005 to 2020, with increasing percentages of patients receiving best supportive care. Survival of metastatic colon cancer decreased from 2014 onwards. The implementation of a colorectal cancer screening program and patient selection might explain why only a subset of older patients seem to benefit from the availability of novel treatment options.

PLIS: A metabolomic response monitor to a lifestyle intervention study in older adults.

The response to lifestyle intervention studies is often heterogeneous, especially in older adults. Subtle responses that may represent a health gain for individuals are not always detected by classical health variables, stressing the need for novel biomarkers that detect intermediate changes in metabolic, inflammatory, and immunity-related health. Here, our aim was to develop and validate a molecular multivariate biomarker maximally sensitive to the individual effect of a lifestyle intervention; the Personalized Lifestyle Intervention Status (PLIS). We used 1 H-NMR fasting blood metabolite measurements from before and after the 13-week combined physical and nutritional Growing Old TOgether (GOTO) lifestyle intervention study in combination with a fivefold cross-validation and a bootstrapping method to train a separate PLIS score for men and women. The PLIS scores consisted of 14 and four metabolites for females and males, respectively. Performance of the PLIS score in tracking health gain was illustrated by association of the sex-specific PLIS scores with several classical metabolic health markers, such as BMI, trunk fat%, fasting HDL cholesterol, and fasting insulin, the primary outcome of the GOTO study. We also showed that the baseline PLIS score indicated which participants respond positively to the intervention. Finally, we explored PLIS in an independent physical activity lifestyle intervention study, showing similar, albeit remarkably weaker, associations of PLIS with classical metabolic health markers. To conclude, we found that the sex-specific PLIS score was able to track the individual short-term metabolic health gain of the GOTO lifestyle intervention study. The methodology used to train the PLIS score potentially provides a useful instrument to track personal responses and predict the participant's health benefit in lifestyle interventions similar to the GOTO study.

Delirium in older patients with COVID-19: Prevalence, risk factors and clinical outcomes across the first three waves of the pandemic.

OBJECTIVES: Delirium is a serious condition, which poses treatment challenges during hospitalisation for COVID-19. Improvements in testing, vaccination and treatment might have changed patient characteristics and outcomes through the pandemic. We evaluated whether the prevalence and risk factors for delirium, and the association of delirium with in-hospital mortality changed through the pandemic. METHODS: This study was part of the COVID-OLD study in 19 Dutch hospitals including patients ≥70 years in the first (spring 2020), second (autumn 2020) and third wave (autumn 2021). Multivariable logistic regression models were used to study risk factors for delirium, and in-hospital mortality. Differences in effect sizes between waves were studied by including interaction terms between wave and risk factor in logistic regression models. RESULTS: 1540, 884 and 370 patients were included in the first, second and third wave, respectively. Prevalence of delirium in the third wave (12.7%) was significantly lower compared to the first (22.5%) and second wave (23.5%). In multivariable-adjusted analyses, pre-existing memory problems was a consistent risk factor for delirium across waves. Previous delirium was a risk factor for delirium in the first wave (OR 4.02), but not in the second (OR 1.61) and third wave (OR 2.59, p-value interaction-term 0.028). In multivariable-adjusted analyses, delirium was not associated with in-hospital mortality in all waves. CONCLUSION: Delirium prevalence declined in the third wave, which might be the result of vaccination and improved treatment strategies. Risk factors for delirium remained consistent across waves, although some attenuation was seen in the second wave.

Weight loss, visit-to-visit body weight variability and cognitive function in older individuals.

OBJECTIVE: to investigate the association between variability and loss of body weight with subsequent cognitive performance and activities of daily living in older individuals. DESIGN: cross-sectional cohort study. SETTING: PROspective Study of Pravastatin in the Elderly at Risk, multicentre trial with participants from Scotland, Ireland and the Netherlands. SUBJECTS: 4,309 participants without severe cognitive dysfunction (mean age 75.1 years, standard deviation (SD) = 3.3), at higher risk for cardiovascular disease (CVD). METHODS: body weight was measured every 3 months for 2.5 years. Weight loss was defined as an average slope across all weight measurements and as ≥5% decrease in baseline body weight during follow-up. Visit-to-visit variability was defined as the SD of weight measurements (kg) between visits. Four tests of cognitive function were examined: Stroop test, letter-digit coding test (LDCT), immediate and delayed picture-word learning tests. Two measures of daily living activities: Barthel Index (BI) and instrumental activities of daily living (IADL). All tests were examined at month 30. RESULTS: both larger body weight variability and loss of ≥5% of baseline weight were independently associated with worse scores on all cognitive tests, but minimally with BI and IADL. Compared with participants with stable weight, participants with significant weight loss performed 5.83 seconds (95% CI 3.74; 7.92) slower on the Stroop test, coded 1.72 digits less (95% CI -2.21; -1.13) on the LDCT and remembered 0.71 pictures less (95% CI -0.93; -0.48) on the delayed picture-word learning test. CONCLUSION: in older people at higher risk for CVD, weight loss and variability are independent risk-factors for worse cognitive function.

Temporal changes in characteristics and external validity of randomized controlled trials in older people from 2012 to 2019.

BACKGROUND: Older individuals are often underrepresented in clinical trials. In 2012 only 7% of RCT's specifically studied older people and their geriatric characteristics were poorly reported. The aim of this review was to investigate temporal changes in characteristics and external validity of randomized controlled trials in older people from 2012 to 2019. METHODS: PubMed was searched for randomized clinical trials (RCTs) published in 2019. Firstly, the proportion of RCTs specially designed for older people were determined by the following criteria: a reported mean age of ≥ 70 years or a lower age cutoff of ≥ 55. Secondly, the trials with a majority of older people, defined by a reported mean age of ≥ 60 years, were screened for reporting of geriatric assessments. Both parts were compared with identical reviews performed in 2012. RESULTS: From a 10% random sample, 1446 RCTs were included in this systematic review. First, 8% of trials were specifically designed for older people in 2019 compared to 7% in 2012. Secondly, 25% of the trials included a majority of older people in 2019, compared to 22% in 2012. Thirdly, in 52% of these trials in 2019 one or more of the geriatric assessments were reported compared to 34% in 2012. CONCLUSIONS: Although in 2019 the proportion of published RCTs specifically designed for older people remains low, more characteristics on geriatric assessments were reported compared to 2012. Continued efforts should be paid to increase both the number and the validity of trials for older people.

Deficits in Geriatric Assessment Associate With Disease Activity and Burden in Older Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: We aimed to perform geriatric assessment in older patients with inflammatory bowel disease (IBD) to evaluate which IBD characteristics associate with deficits in geriatric assessment and the impact of deficits on disease burden (health-related quality of life). METHODS: A prospective multicenter cohort study including 405 consecutive outpatient patients with IBD aged ≥65 years. Somatic domain (comorbidity, polypharmacy, malnutrition), impairments in (instrumental) activities of daily living, physical capacity (handgrip strength, gait speed), and mental (depressive symptoms, cognitive impairment) and social domain (life-partner) were assessed. Deficits in geriatric assessment were defined as ≥2 abnormal domains; 2-3 moderate deficits and 4-5 severe deficits. Clinical (Harvey Bradshaw Index >4/partial Mayo Score >2) and biochemical (C-reactive protein ≥10 mg/L and/or fecal calprotectin ≥250 µg/g) disease activity and disease burden (short Inflammatory Bowel Disease Questionnaire) were assessed. RESULTS: Somatic domain (51.6%) and activities of daily living (43.0%) were most frequently impaired. A total of 160 (39.5%) patients had moderate deficits in their geriatric assessment; 32 (7.9%) severe. Clinical and biochemical disease activity associated with deficits (clinical: adjusted odds ratio, 2.191; 95% confidence interval, 1.284-3.743; P = .004; biochemical: adjusted odds ratio, 3.358; 95% confidence interval, 1.936-5.825; P < .001). Deficits in geriatric assessment independently associate with lower health-related quality of life. CONCLUSION: Deficits in geriatric assessment are highly prevalent in older patients with IBD. Patients with active disease are more prone to deficits, and deficits associate with lower health-related quality of life, indicating higher disease burden. Prospective data validating impact of frailty and geriatric assessment on outcomes are warranted to further improve treatment strategies.

Thyroid antibodies and levothyroxine effects in subclinical hypothyroidism: A pooled analysis of two randomized controlled trials.

BACKGROUND: Antithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed whether older adults with subclinical hypothyroidism (SHypo) caused by autoimmune thyroid disease derive more benefits from levothyroxine treatment (LT4). OBJECTIVE: To determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies. METHODS: We pooled individual participant data from two RCTs, Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism and IEMO 80+. Participants with persistent SHypo were randomly assigned to receive LT4 or placebo. We compared the effects of LT4 versus placebo in participants with and without anti-thyroid peroxidase (TPO) at baseline. The two primary outcomes were 1-year change in Hypothyroid Symptoms and Tiredness scores on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire. RESULTS: Among 660 participants (54% women) ≥65 years, 188 (28.5%) had positive anti-TPO. LT4 versus placebo on Hypothyroid Symptoms lead to an adjusted between-group difference of -2.07 (95% confidence interval: -6.04 to 1.90) for positive antibodies versus 0.89 (-1.76 to 3.54) for negative antibodies (p for interaction = 0.31). Similarly, there was no treatment effect modification by baseline antibody status for Tiredness scores-adjusted between-group difference 1.75 (-3.60 to 7.09) for positive antibodies versus 1.14 (-1.90 to 4.19) for negative antibodies (p for interaction = 0.98). Positive anti-TPO were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment. CONCLUSIONS: Among older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4.

Timing of objectively-collected physical activity in relation to body weight and metabolic health in sedentary older people: a cross-sectional and prospective analysis.

BACKGROUND: Little is known about the impact of timing as opposed to frequency and intensity of daily physical activity on metabolic health. Therefore, we assessed the association between accelerometery-based daily timing of physical activity and measures of metabolic health in sedentary older people. METHODS: Hourly mean physical activity derived from wrist-worn accelerometers over a 6-day period was collected at baseline and after 3 months in sedentary participants from the Active and Healthy Ageing study. A principal component analysis (PCA) was performed to reduce the number of dimensions (e.g. define periods instead of separate hours) of hourly physical activity at baseline and change during follow-up. Cross-sectionally, a multivariable-adjusted linear regression analysis was used to associate the principal components, particularly correlated with increased physical activity in data-driven periods during the day, with body mass index (BMI), fasting glucose and insulin, HbA1c and the homeostatic model assessment for insulin resistance (HOMA-IR). For the longitudinal analyses, we calculated the hourly changes in physical activity and change in metabolic health after follow-up. RESULTS: We included 207 individuals (61.4% male, mean age: 64.8 [SD 2.9], mean BMI: 28.9 [4.7]). Higher physical activity in the early morning was associated with lower fasting glucose (-2.22%, 95% CI: -4.19, -0.40), fasting insulin (-13.54%, 95%CI: -23.49, -4.39), and HOMA-IR (-16.07%, 95%CI: -27.63, -5.65). Higher physical activity in the late afternoon to evening was associated with lower BMI (-2.84%, 95% CI: -4.92, -0.70). Higher physical activity at night was associated with higher BMI (2.86%, 95% CI: 0.90, 4.78), fasting glucose (2.57%, 95% CI: 0.70, 4.30), and HbA1c (2.37%, 95% CI: 1.00, 3.82). Similar results were present in the prospective analysis. CONCLUSION: Specific physical activity timing patterns were associated with more beneficial metabolic health, suggesting particular time-dependent physical activity interventions might maximise health benefits.

Survival of patients who opt for dialysis versus conservative care: a systematic review and meta-analysis.

BACKGROUND: Non-dialytic conservative care (CC) has been proposed as a treatment option for patients with kidney failure. This systematic review and meta-analysis aims at comparing survival outcomes between dialysis and CC in studies where patients made an explicit treatment choice. METHODS: Five databases were systematically searched from origin through 25 February 2021 for studies comparing survival outcomes among patients choosing dialysis versus CC. Adjusted and unadjusted survival rates were extracted and meta-analysis performed where applicable. Risk of bias analysis was performed according to the Cochrane Risk Of Bias In Non-randomized Studies of Interventions. RESULTS: A total of 22 cohort studies were included covering 21 344 patients. Most studies were prone to selection bias and confounding. Patients opting for dialysis were generally younger and had fewer comorbid conditions, fewer functional impairments and less frailty than patients who chose CC. The unadjusted median survival from treatment decision or an estimated glomerular filtration rate <15 mL/min/1.73 m2 ranged from 20 and 67 months for dialysis and 6 and 31 months for CC. Meta-analysis of 12 studies that provided adjusted hazard ratios (HRs) for mortality showed a pooled adjusted HR of 0.47 (95% confidence interval 0.39-0.57) for patients choosing dialysis compared with CC. In subgroups of patients with older age or severe comorbidities, the reduction of mortality risk remained statistically significant, although analyses were unadjusted. CONCLUSIONS: Patients opting for dialysis have an overall lower mortality risk compared with patients opting for CC. However, a high risk of bias and heterogeneous reporting preclude definitive conclusions and results cannot be translated to an individual level.

Geriatric assessment and treatment outcomes in a Dutch cohort of older patients with potentially curable esophageal cancer.

BACKGROUND: Patients with potentially curable esophageal cancer can be treated with neo-adjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy with curative intent. For frail older patients choosing the appropriate oncological treatment can be difficult, and data on geriatric deficits as determinants of treatment outcomes are not yet available. OBJECTIVES: To describe the prevalence of geriatric deficits and to study their association with treatment discontinuation and mortality in older patients with potentially curable esophageal cancer. MATERIAL AND METHODS: A cohort study was conducted in a Dutch tertiary care hospital including patients aged ≥70 years with primary stage I-IVA esophageal cancer. Geriatric screening and assessment data were collected. Outcomes were treatment discontinuation and one year all-cause mortality. RESULTS: In total, 138 patients with curable esophageal cancer were included. Mean age was 76.1 years (standard deviation 4.7), 54% had clinical stage III and 24% stage IVA disease. Most patients received neo-adjuvant chemoradiotherapy and surgery (41%), 32% definitive chemoradiotherapy and 22% palliative radiotherapy. Overall, one year all-cause mortality was 36%. Geriatric screening and assessment was performed in 94 out of 138 patients, of which 60% was malnourished, 20% dependent in Instrumental Activities of Daily Living (IADL) and 52% was frail. Malnutrition was associated with higher mortality risk (Hazard Ratio, 3.2; 95% Confidence Interval, 1.3-7.7)) independent of age, sex and tumor stage. Seventy-six out of 94 patients were treated with chemoradiotherapy, of which 23% discontinued treatment. Patients with IADL dependency and Charlson Comorbidity Index ≥1 discontinued treatment more often. CONCLUSION: All-cause mortality within one year was high, irrespective of treatment modality. Treatment discontinuation rate was high, especially in patients treated with definitive chemoradiotherapy. Geriatric assessment associates with outcomes in older patients with esophageal cancer and may inform treatment decisions and optimization in future patients, but more research is needed to establish its predictive value. Trial registration: The study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22-10-2019.

Vascular disease and apathy symptoms in the very old: A cross-sectional and longitudinal meta-analysis of individual participant data.

OBJECTIVES: Previous findings suggest a vascular foundation underlying apathy, but transdiagnostic and prospective evidence on vascular apathy is scarce. This study examines the association between vascular disease and the presence and development of apathy symptoms in the very old. METHODS: Four cohorts of the Towards Understanding Longitudinal International older People Studies (TULIPS)-consortium were included in a two-staged, individual participant data meta-analysis using generalized linear mixed models. Vascular disease was defined as a history of any clinical atherosclerotic pathology (angina pectoris, myocardial infarction, intermittent claudication, transient ischemic attack, stroke or related surgeries) and was related to apathy symptoms as repeatedly measured by the Geriatric Depression Scale (GDS-3A ≥2) over a maximum of 5 years. RESULTS: Of all 1868 participants (median age 85 years old), 53.9% had vascular disease and 44.3% experienced apathy symptoms. Participants with vascular disease had a 76% higher risk of apathy symptoms at baseline (odds ratio (OR) 1.76, 95% confidence interval (CI) 1.32-2.35), irrespective of depressive symptoms and only partially explained by stroke. Conversely, there was no association of vascular disease with the occurrence of apathy symptoms longitudinally, both in those with apathy at baseline (OR 1.00, 95% CI 0.84-1.20) and without (OR 0.96, 95% CI 0.84-1.09). CONCLUSIONS: Vascular disease in the very old is associated with apathy symptoms cross-sectionally, but not proven longitudinally, independent of depressive symptoms. These findings query a vascular cause underlying apathy symptoms. However, the consistency of our cross-sectional findings in direction and magnitude across the TULIPS-consortium do emphasize international relevance of the interplay of vascular factors and apathy in advanced age, which meaning needs further unravelling.

Delirium in older COVID-19 patients: Evaluating risk factors and outcomes.

OBJECTIVES: A high incidence of delirium has been reported in older patients with Coronavirus disease 2019 (COVID-19). We aimed to identify determinants of delirium, including the Clinical Frailty Scale, in hospitalized older patients with COVID-19. Furthermore, we aimed to study the association of delirium independent of frailty with in-hospital outcomes in older COVID-19 patients. METHODS: This study was performed within the framework of the multi-center COVID-OLD cohort study and included patients aged ≥60 years who were admitted to the general ward because of COVID-19 in the Netherlands between February and May 2020. Data were collected on demographics, co-morbidity, disease severity, and geriatric parameters. Prevalence of delirium during hospital admission was recorded based on delirium screening using the Delirium Observation Screening Scale (DOSS) which was scored three times daily. A DOSS score ≥3 was followed by a delirium assessment by the ward physician In-hospital outcomes included length of stay, discharge destination, and mortality. RESULTS: A total of 412 patients were included (median age 76, 58% male). Delirium was present in 82 patients. In multivariable analysis, previous episode of delirium (Odds ratio [OR] 8.9 [95% CI 2.3-33.6] p = 0.001), and pre-existent memory problems (OR 7.6 [95% CI 3.1-22.5] p < 0.001) were associated with increased delirium risk. Clinical Frailty Scale was associated with increased delirium risk (OR 1.63 [95%CI 1.40-1.90] p < 0.001) in univariable analysis, but not in multivariable analysis. Patients who developed delirium had a shorter symptom duration and lower levels of C-reactive protein upon presentation, whereas vital parameters did not differ. Patients who developed a delirium had a longer hospital stay and were more often discharged to a nursing home. Delirium was associated with mortality (OR 2.84 [95% CI1.71-4.72] p < 0.001), but not in multivariable analyses. CONCLUSIONS: A previous delirium and pre-existent memory problems were associated with delirium risk in COVID-19. Delirium was not an independent predictor of mortality after adjustment for frailty.

Geriatric emergency medicine-a model for frailty friendly healthcare.

As the world's population continues to age over the decades ahead, medical educators and researchers in every adult medical and surgical specialty will need to 'geriatricise' their clinical science. Many have already engaged with geriatrics. Here we describe the progress that has been made and the opportunities ahead in the field of Geriatric Emergency Medicine (GEM), a field that has taken large steps in integrating holistic care. Future opportunities exist in the three domains of evidence-based medicine: including patient preferences and needs, generating scientific evidence, and improving physician knowledge and expertise. Implementation requires new innovations also in the organisation of care. Similar strategies may be useful in other fields of medicine, in making holistic care the standard for older people.

Characteristics and outcomes of older patients hospitalised for COVID-19 in the first and second wave of the pandemic in The Netherlands: the COVID-OLD study.

BACKGROUND: as the coronavirus disease of 2019 (COVID-19) pandemic progressed diagnostics and treatment changed. OBJECTIVE: to investigate differences in characteristics, disease presentation and outcomes of older hospitalised COVID-19 patients between the first and second pandemic wave in The Netherlands. METHODS: this was a multicentre retrospective cohort study in 16 hospitals in The Netherlands including patients aged ≥ 70 years, hospitalised for COVID-19 in Spring 2020 (first wave) and Autumn 2020 (second wave). Data included Charlson comorbidity index (CCI), disease severity and Clinical Frailty Scale (CFS). Main outcome was in-hospital mortality. RESULTS: a total of 1,376 patients in the first wave (median age 78 years, 60% male) and 946 patients in the second wave (median age 79 years, 61% male) were included. There was no relevant difference in presence of comorbidity (median CCI 2) or frailty (median CFS 4). Patients in the second wave were admitted earlier in the disease course (median 6 versus 7 symptomatic days; P < 0.001). In-hospital mortality was lower in the second wave (38.1% first wave versus 27.0% second wave; P < 0.001). Mortality risk was 40% lower in the second wave compared with the first wave (95% confidence interval: 28-51%) after adjustment for differences in patient characteristics, comorbidity, symptomatic days until admission, disease severity and frailty. CONCLUSIONS: compared with older patients hospitalised in the first COVID-19 wave, patients in the second wave had lower in-hospital mortality, independent of risk factors for mortality.The better prognosis likely reflects earlier diagnosis, the effect of improvement in treatment and is relevant for future guidelines and treatment decisions.

Assessment of the appropriateness of cardiovascular preventive medication in older people: using the RAND/UCLA Appropriateness Method.

BACKGROUND: In clinical practice and science, there is debate for which older adults the benefits of cardiovascular preventive medications (CPM) still outweigh the risks in older age. Therefore, we aimed to assess how various clinical characteristics influence the judgement of appropriateness of CPM in older adults. METHOD: We assessed the appropriateness of CPM for adults ≥75 years with regard to clinical characteristics (cardiovascular variables, complexity of health problems, age, side effects and life expectancy) using the RAND/ University of California at Los Angeles Appropriateness Method. A multidisciplinary panel, including 11 medical professionals and 3 older representatives of the target population, received an up-to-date overview of the literature. Using 9-point Likert scales (1 = extremely inappropriate; 9 = extremely appropriate), they assessed the appropriateness of starting and stopping cholesterol lowering medication, antihypertensives and platelet aggregation inhibitors, for various theoretical clinical scenarios. There were two rating rounds, with one face-to-face discussion in between. The overall appropriateness judgments were based on the median panel ratings of the second round and level of disagreement. RESULTS: The panelists emphasized the importance of the individual context of the patient for appropriateness of CPM. They judged that in general, a history of atherosclerotic cardiovascular disease strongly adds to the appropriateness of CPM, while increasing complexity of health problems, presence of hindering or severe side effects, and life expectancy < 1 year all contribute to the inappropriateness of CPM. Age had only minor influence on the appropriateness judgments. The appropriateness judgments were different for the three types of CPM. The literature, time-to-benefit, remaining life expectancy, number needed to treat, and quality of life, were major themes in the panel discussions. The considerations to stop CPM were different from the considerations not to start CPM. CONCLUSION: Next to the patients' individual context, which was considered decisive in the final decision to start or stop CPM, there were general trends of how clinical characteristics influenced the appropriateness, according to the multidisciplinary panel. The decision to stop, and not start CPM, appeared to be two distinct concepts. Results of this study may be used in efforts to support clinical decision making about CPM in older adults.